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Childhood Diseases
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PDF generated at: Mon, 06 Dec 2010 19:34:04 UTC
Contents
Articles
Measles
1
Diphtheria
9
Mumps
14
Pertussis
19
Impetigo
25
Herpes zoster
28
Herpes labialis
39
Rubella
43
Hepatitis A
48
Hepatitis B
54
Hepatitis C
65
Hepatitis D
79
Hepatitis E
81
Hepatitis F virus
84
Tuberculosis
85
Chickenpox
107
Scabies
114
Streptococcal pharyngitis
122
Erythema infectiosum
128
Conjunctivitis
131
References
Article Sources and Contributors
136
Image Sources, Licenses and Contributors
141
Article Licenses
License
143
Measles
1
Measles
Measles
Classification and external resources
[1]
ICD-10
B 05.
ICD-9
055
DiseasesDB
7890
MedlinePlus
001569
eMedicine
derm/259
MeSH
D008457
[2]
[3]
[4]
[5]
emerg/389
[6]
ped/1388
[7]
[8]
Measles virus
Measles virus
Virus classification
Group:
Group V ((-)ssRNA)
Order:
Mononegavirales
Family:
Paramyxoviridae
Genus:
Morbillivirus
Type species
Measles virus
Measles, also known as Rubeola, is an infection of the respiratory system caused by a virus, specifically a
paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped,
single-stranded, negative-sense RNA viruses. Symptoms include fever, cough, runny nose, red eyes and a
generalized, maculopapular, erythematous rash.
Measles
2
Measles (sometimes known as English Measles) is spread through respiration (contact with fluids from an infected
person's nose and mouth, either directly or through aerosol transmission), and is highly contagious—90% of people
without immunity sharing living space with an infected person will catch it. The infection has an average incubation
period of 14 days (range 6–19 days) and infectivity lasts from 2–4 days prior, until 2–5 days following the onset of
the rash (i.e. 4–9 days infectivity in total).[9]
An alternative name for measles in English-speaking countries is rubeola, which is sometimes confused with rubella
(German measles); the diseases are unrelated.[10] [11]
Signs and symptoms
The classical symptoms of measles include four day fevers, the three
Cs—cough, coryza (runny nose) and conjunctivitis (red eyes). The
fever may reach up to 40 °C (104 °F). Koplik's spots seen inside the
mouth are pathognomonic (diagnostic) for measles but are not often
seen, even in real cases of measles, because they are transient and may
disappear within a day of arising.
This patient presented on the third pre-eruptive
day with “Koplik spots” indicative of the
beginning onset of measles.
The characteristic measles rash is classically described as a
generalized, maculopapular, erythematous rash that begins several days
after the fever starts. It starts on the head before spreading to cover
most of the body, often causing itching. The rash is said to "stain",
changing colour from red to dark brown, before disappearing.
Complications
Complications with measles are relatively common, ranging from relatively mild and less serious diarrhea, to
pneumonia and encephalitis (subacute sclerosing panencephalitis), corneal ulceration leading to corneal scarring.[12]
Complications are usually more severe amongst adults who catch the virus.
The fatality rate from measles for otherwise healthy people in developed countries is 3 deaths per thousand cases, or
0.3%.[13] In underdeveloped nations with high rates of malnutrition and poor healthcare, fatality rates have been as
high as 28%.[13] In immunocompromised patients (e.g. people with AIDS) the fatality rate is approximately 30%.[14]
Cause
Patients with the measles should be placed on respiratory precautions.[15]
Humans are the only known natural host of measles, although the virus can infect some non-human primate species.
Diagnosis
Clinical diagnosis of measles requires a history of fever of at least three days together with at least one of the three
C's (cough, coryza, conjunctivitis). Observation of Koplik's spots is also diagnostic of measles.
Alternatively, laboratory diagnosis of measles can be done with confirmation of positive measles IgM antibodies or
isolation of measles virus RNA from respiratory specimens. In children, where phlebotomy is inappropriate, saliva
can be collected for salivary measles specific IgA test. Positive contact with other patients known to have measles
adds strong epidemiological evidence to the diagnosis. The contact with any infected person in any way, including
semen through sex, saliva, or mucus can cause infection.
Measles
Prevention
In developed countries, most children are immunized against measles by the age of 18 months, generally as part of a
three-part MMR vaccine (measles, mumps, and rubella). The vaccination is generally not given earlier than this
because children younger than 18 months usually retain anti-measles immunoglobulins (antibodies) transmitted from
the mother during pregnancy. A second dose is usually given to children between the ages of four and five, in order
to increase rates of immunity. Vaccination rates have been high enough to make measles relatively uncommon. Even
a single case in a college dormitory or similar setting is often met with a local vaccination program, in case any of
the people exposed are not already immune.
In developing countries where measles is highly endemic, the WHO recommend that two doses of vaccine be given
at six months and at nine months of age. The vaccine should be given whether the child is HIV-infected or not.[16]
The vaccine is less effective in HIV-infected infants, but the risk of adverse reactions is low. Measles vaccination
programs are often used to deliver other child health interventions as well, such as bed nets to protect against
malaria, de-worming medicine and vitamin A supplements, and so contribute to the reduction of child deaths from
other causes.[17]
Unvaccinated populations are at risk for the disease. After vaccination rates dropped in northern Nigeria in the early
2000s due to religious and political objections, the number of cases rose significantly, and hundreds of children
died.[18]
In 1998 the MMR vaccine controversy in the United Kingdom regarding a potential link between the combined
MMR vaccine (vaccinating children from mumps, measles and rubella) and autism prompted a reemergence of the
"measles party", where parents deliberately expose their child to measles in the hope of building up the child's
immunity without an injection. This practice poses many health risks to the child, and has been discouraged by the
public health authorities.[19] Scientific evidence provides no support for the hypothesis that MMR plays a role in
causing autism.[20] In 2009, The Sunday Times reported that Wakefield had manipulated patient data and misreported
results in his 1998 paper, creating the appearance of a link with autism.[21] The Lancet fully retracted the 1998 paper
on 2 February 2010.[22] In January 2010, another study of Polish children found that vaccination with the measles,
mumps, and rubella vaccine was not a risk factor for development of autistic disorder, in fact the vaccinated patients
had a slightly reduced risk of autistic disorder, although the mechanism of action behind that is unknown, and this
result may have been coincidental.[23]
The autism related MMR study in Britain caused use of the vaccine to plunge, and measles cases came back: 2007
saw 971 cases in England and Wales, the biggest rise in occurrence in measles cases since records began in 1995.[24]
A 2005 measles outbreak in Indiana was attributed to children whose parents refused vaccination.[25]
Treatment
There is no specific treatment for measles. Most patients with uncomplicated measles will recover with rest and
supportive treatment. It is, however, important to seek medical advice if the patient becomes more unwell, as they
may be developing complications.
Some patients will develop pneumonia as a sequel to the measles. Other complications include ear infections,
bronchitis, and encephalitis. Acute measles encephalitis has a mortality rate of 15%. While there is no specific
treatment for measles encephalitis, antibiotics are required for bacterial pneumonia, sinusitis, and bronchitis that can
follow measles.
All other treatment is symptomatic, with ibuprofen, or acetaminophen (also called paracetamol) to reduce fever and
pain and, if required, a fast-acting bronchodilator for cough. Note that young children should never be given aspirin
without medical advice, due to the risk of inducing a disease known as Reye's syndrome.
The use of Vitamin A in treatment has been investigated. A systematic review of trials into its use found no
significant reduction in overall mortality, but that it did reduce mortality in children aged under 2 years.[26] [27] [28]
3
Measles
Prognosis
While the vast majority of patients survive measles, complications occur fairly frequently and may include
bronchitis, pneumonia, otitis media, hemorrhagic complications, acute disseminated encephalomyelitis, acute
measles encephalitis, subacute sclerosing panencephalitis (sspe), blindness, deafness, and death. Statistically out of
1000 measles cases, 2-3 patients die, and 5-105 suffer complications. In patients who do not develop complications,
the prognosis is generally excellent. However, although most patients survive, it is still important to get vaccinated,
as up to 15 percent of measles patients experience complications, some fairly mild, others (such as subacute
sclerosing panencephalitis) typically fatal. Also, even if the patient is not concerned about death or sequela from the
measles, the person may spread the disease to an immunocompromised patient, for whom the risk of death is much
higher, due to complications such as giant cell pneumonia. Acute measles encephalitis is another serious risk of
measles virus infection. It typically occurs 2 days to one week after the breakout of the measles exanthem, and
begins with very high fever, severe headache, convulsions, and altered mentation. Patient may become comatose,
and death or brain injury may occur.[29]
Epidemiology
According to the World Health Organization (WHO), measles is a leading cause of vaccine-preventable childhood
mortality. Worldwide, the fatality rate has been significantly reduced by a vaccination campaign led by partners in
the Measles Initiative: the American Red Cross, the United States Centers for Disease Control and Prevention
(CDC), the United Nations Foundation, UNICEF and the World Health Organization (WHO). Globally, measles fell
60% from an estimated 873,000 deaths in 1999 to 345,000 in 2005.[17] Estimates for 2008 indicate deaths fell further
to 164,000 globally, with 77% of the remaining measles deaths in 2008 occurring within the South-East Asian
region.[30]
Five out of six WHO regions have set goals to eliminate measles, and at the 63rd World Health Assembly in May
2010, delegates agreed a global target of a 95% reduction in measles mortality by 2015 from the level seen in 2000,
as well as to move towards eventual eradication. However, no specific global target date for eradication has yet been
agreed as of May 2010.[31] [32]
Evolution
The measles virus evolved from the then widespread rinderpest virus most probably between the 11th and 12th
centuries.[33] The earliest likely origin is within the 7th century: for this earlier origin there is some linguistic
evidence.[34] [35] The current epidemic strain evolved at the beginning of the 20th century - most probably between
1908 and 1943[36]
History and culture
History
The Antonine Plague, 165-180 AD, also known as the Plague of Galen, who described it, was probably smallpox or
measles. Disease killed as much as one-third of the population in some areas, and decimated the Roman army.[37]
The first scientific description of measles and its distinction from smallpox and chickenpox is credited to the Persian
physician, Muhammad ibn Zakariya ar-Razi (860-932), known to the West as "Rhazes", who published a book
entitled The Book of Smallpox and Measles (in Arabic: Kitab fi al-jadari wa-al-hasbah).[38]
Measles is an endemic disease, meaning that it has been continually present in a community, and many people
develop resistance. In populations that have not been exposed to measles, exposure to a new disease can be
devastating. In 1529, a measles outbreak in Cuba killed two-thirds of the natives who had previously survived
smallpox. Two years later measles was responsible for the deaths of half the population of Honduras, and had
4
Measles
ravaged Mexico, Central America, and the Inca civilization.[39]
In roughly the last 150 years, measles has been estimated to have killed about 200 million people worldwide.[40]
During the 1850s, measles killed a fifth of Hawaii's people.[41] In 1875, measles killed over 40,000 Fijians,
approximately one-third of the population.[42] In the 19th century, the disease decimated the Andamanese
population.[43] In 1954, the virus causing the disease was isolated from an 11-year old boy from the United States,
David Edmonston, and adapted and propagated on chick embryo tissue culture.[44] To date, 21 strains of the measles
virus have been identified.[45] While at Merck, Maurice Hilleman developed the first successful vaccine.[46] Licensed
vaccines to prevent the disease became available in 1963.
Recent outbreaks
Since the beginning of September, 2009, Johannesburg, a city in Gauteng, South Africa reported about 48 cases of
measles. Soon after the outbreak, the Government ordered that all children be vaccinated. Vaccination programs
were then initiated in all schools and parents of young children were advised to have them vaccinated.[47] Many
people were not willing to have the vaccination done, as it is believed to be unsafe and ineffective. The Health
Department assured the public that their program was indeed safe. Speculation arose as to whether or not new
needles were being used.[48] By mid-October there were at least 940 recorded cases, and 4 deaths.[49]
On February 19, 2009, 505 measles cases were reported in twelve provinces in the North of Vietnam, with Hanoi
accounting for 160 cases.[50] A high rate of complications including meningitis & encephalitis has worried health
workers[51] and the U.S. CDC recommended that all travelers be immune to measles.[52]
On The 1st of April 2009, an outbreak has happened in two schools in North Wales. Ysgol John Bright and Ysgol
Ffordd Dyffryn in Wales have had the outbreak and are making sure every pupil has had the Measles vaccine.
In 2007, a large measles outbreak in Japan caused a number of universities and other institutions to close in an
attempt to contain the disease.[53] [54]
Approximately 1000 cases of the disease were reported in Israel between August 2007 and May 2008 (in sharp
contrast to just some dozen cases the year before). Many children in ultra-Orthodox Jewish communities were
affected due to low vaccination coverage.[55] [56] As of 2008 the disease is endemic in the United Kingdom, with
1,217 cases diagnosed in 2008, [57] and epidemics have been reported in Austria, Italy and Switzerland.[58]
In March 2010, Philippines declared an epidemic about the continuously rising cases of measles.
The Americas
Indigenous measles were declared to have been eliminated in North, Central, and South America; the last endemic
case in the region was reported on November 12, 2002, with only Northern Argentina and rural Canada, particularly
in the provinces of Ontario, Quebec, and Alberta having minor endemic status.[59] Outbreaks are still occurring,
however, following importations of measles viruses from other world regions. In June 2006, an outbreak in Boston
resulted after a resident became infected in India,[60] and in October 2007, a Michigan girl who had been vaccinated
contracted the disease in Sweden.[61]
Between January 1 and April 25, 2008, a total of 64 confirmed measles cases were preliminarily reported in the
United States to the Centers for Disease Control and Prevention,[62] [63] the most reported by this date for any year
since 2001. Of the 64 cases, 54 were associated with importation of measles from other countries into the United
States, and 63 of the 64 patients were unvaccinated or had unknown or undocumented vaccination status.[64]
By July 9, 2008, a total of 127 cases were reported in 15 states (including 22 in Arizona),[65] making it the largest
U.S. outbreak since 1997 (when 138 cases were reported).[66] Most of the cases were acquired outside of the United
States and afflicted individuals who had not been vaccinated.
By July 30, 2008, the number of cases had grown to 131. Of these, about half involved children whose parents
rejected vaccination. The 131 cases occurred in 7 different outbreaks. There were no deaths, and 15 hospitalizations.
5
Measles
6
11 of the cases had received at least one dose of the measles vaccine. 122 of the cases involved children who were
unvaccinated or whose vaccination status was unknown. Some of these were under the age of one year old and
below the age when vaccination is recommended, but in 63 cases the vaccinations had been refused for religious or
philosophical reasons.
Additional images
Intra oral rash of measles
Measles in African Child
This
European
child shows a
classic day-4
rash with
measles.
Histopathology of measles
pneumonia. Giant cell
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7
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External links
• WHO.int (http://www.who.int/vaccine_research/diseases/measles/en/) - 'Initiative for Vaccine Research
(IVR): Measles', World Health Organization (WHO)
• Measles FAQ (http://www.cdc.gov/vaccines/vpd-vac/measles/faqs-dis-vac-risks.htm) from Centers for
Disease Control and Prevention in the United States
• Case of an adult male with measles (facial photo) (http://news.bbc.co.uk/1/hi/health/7385020.stm)
• Clinical pictures of measles (http://www.skinsight.com/child/rubeolaMeasles.htm)
• Virus Pathogen Database and Analysis Resource (ViPR): Paramyxoviridae (http://www.viprbrc.org/brc/home.
do?decorator=paramyxo)
8
Diphtheria
9
Diphtheria
Diphtheria
Diphtheria causes a characteristic swollen neck, sometimes referred to as “bull neck”.
[1]
ICD-10
A 36.
ICD-9
032
DiseasesDB
3122
MedlinePlus
001608
eMedicine
emerg/138
MeSH
D004165
[2]
[3]
[4]
[5]
med/459
[6]
oph/674
[7]
ped/596
[8]
[9]
Diphtheria (Greek διφθέρα (diphthera) "pair of leather scrolls") is an upper respiratory tract illness caused by
Corynebacterium diphtheriae, a facultative anaerobic Gram-positive bacterium.[10] [11] It is characterized by sore
throat, low fever, and an adherent membrane (a pseudomembrane) on the tonsils, pharynx, and/or nasal cavity.[12] A
milder form of diphtheria can be restricted to the skin. Uncommon consequences include myocarditis (about 20% of
cases) [13] and peripheral neuropathy (about 10% of cases).[14]
Diphtheria is a contagious disease spread by direct physical contact or breathing the aerosolized secretions of
infected individuals. Historically quite common, diphtheria has largely been eradicated in industrialized nations
through widespread vaccination. In the United States for example, there were 52 reported cases of diphtheria
between 1980 and 2000; between 2000 and 2007 there were only three cases[15] as the DPT
(Diphtheria–Pertussis–Tetanus) vaccine is recommended for all school-age children. Boosters of the vaccine are
recommended for adults since the benefits of the vaccine decrease with age without constant re-exposure; they are
particularly recommended for those traveling to areas where the disease has not been eradicated.
Diphtheria
Mechanism
Diphtheria toxin consists of a single protein or polypeptide. The
protein is broken down (Proteolysis) to yield two fragments (A and B),
which are held together by a disulfide bond. Fragment A prevents the
host cells from undergoing protein synthesis. Fragment B is a
recognition subunit (the host cell basically allows it to enter). Fragment
B gains access to the host cell by binding to the plasma membrane at
specific sites called the EGF-like domain of Heparin-binding EGF-like
growth factor (HB-EGF). The HB-EGF then takes in the fragments
through receptor-mediated endocytosis. The low pH of the endosome
A diphtheria skin lesion on the leg.
(sac which transports the HB-EGF and bound fragments A and B)
induces fragment B to begin producing pores and catalyses the release of a catalytic fragment A into the cytosol or
intracellular fluid. The toxin catalyses the ADP-ribosylation of (and inactivates) the elongation factor eEF-2. This
elongation factor is a protein that is essential to protein synthesis; by inactivating it, the translation portion of protein
synthesis is inhibited. The toxin enters the host cell and is hydrolysed by a trypsin-like protease to produce a toxic
fragment. The toxin then transfers an ADP-ribose from NAD+ to a diphthamide residue (a modified Histidine amino
acid) found within the EF-2 protein. EF-2 is needed for the moving of tRNA from the A-site to the P-site of the
ribosome during translation. The ADP-ribosylation is reversible when by giving high doses of nicotinamide (or
vitamin B3), one of the reaction's products. Diphtheria toxin is produced by C. diphtheriae only when it is infected
with a bacteriophage. The bacteriophage integrates a gene into the bacteria that causes the toxin to be produced. [16]
Diagnosis
The current definition of diphtheria used by the Centers for Disease Control and Prevention (CDC) is based on both
laboratory and clinical criteria.
Laboratory criteria
• Isolation of Corynebacterium diphtheriae from a clinical specimen, or
• Histopathologic diagnosis of diphtheria
Clinical criteria
• Upper respiratory tract illness with sore throat
• Low-grade fever (>103°F is rare)
• An adherent pseudomembrane of the tonsil(s), pharynx, and/or nose.
Case classification
• Probable: a clinically compatible case that is not laboratory-confirmed and is not epidemiologically linked to a
laboratory-confirmed case
• Confirmed: a clinically compatible case that is either laboratory-confirmed or epidemiologically linked to a
laboratory-confirmed case
Empirical treatment should generally be started in a patient in whom suspicion of diphtheria is high.
10
Diphtheria
Treatment
The disease may remain manageable, but in more severe cases lymph nodes in the neck may swell, and breathing
and swallowing will be more difficult. People in this stage should seek immediate medical attention, as obstruction
in the throat may require intubation or a tracheotomy. Abnormal cardiac rhythms can occur early in the course of the
illness or weeks later, and can lead to heart failure. Diphtheria can also cause paralysis in the eye, neck, throat, or
respiratory muscles. Patients with severe cases will be put in a hospital intensive care unit (ICU) and be given a
diphtheria anti-toxin. Since antitoxin does not neutralize toxin that is already bound to tissues, delaying its
administration is associated with an increase in mortality risk. Therefore, the decision to administer diphtheria
antitoxin is based on clinical diagnosis, and should not await laboratory confirmation.[15]
Antibiotics have not been demonstrated to affect healing of local infection in diphtheria patients treated with
antitoxin. Antibiotics are used in patients or carriers to eradicate C. diphtheriae and prevent its transmission to
others. The CDC recommends[17] either:
• Erythromycin (orally or by injection) for 14 days (40 mg/kg per day with a maximum of 2 g/d), or
• Procaine penicillin G given intramuscularly for 14 days (300,000 U/d for patients weighing <10 kg and 600,000
U/d for those weighing >10 kg). Patients with allergies to penicillin G or erythromycin can use rifampin or
clindamycin.
In cases that progress beyond a throat infection, diphtheria toxin spreads through the bloodstream and can lead to
potentially life-threatening complications that affect other organs of the body, such as the heart and kidneys. The
toxin can cause damage to the heart that affects its ability to pump blood or the kidneys' ability to clear wastes. It can
also cause nerve damage, eventually leading to paralysis. 40% to 50% of those left untreated can die.
Epidemiology
Diphtheria is a serious disease, with fatality rates between 5% and
10%. In children under 5 years and adults over 40 years, the fatality
rate may be as much as 20%.[15] Outbreaks, though very rare, still
occur worldwide, even in developed nations such as Germany and
Canada. After the breakup of the former Soviet Union in the late
1980s, vaccination rates in its constituent countries fell so low that
Diphtheria cases reported to the World Health
there was an explosion of diphtheria cases. In 1991 there were 2,000
Organization between 1997 and 2006 (see
cases of diphtheria in the USSR. By 1998, according to Red Cross
description for legend).
estimates, there were as many as 200,000 cases in the Commonwealth
of Independent States, with 5,000 deaths.[18] This was so great an increase that diphtheria was cited in the Guinness
Book of World Records as "most resurgent disease".
History
In 1878, Queen Victoria's daughter Princess Alice and her family became infected with it, causing two deaths,
Princess Marie of Hesse and by Rhine and Princess Alice herself.
In the 1920s there were an estimated 100,000 to 200,000 cases of diphtheria per year in the United States, causing
13,000 to 15,000 deaths per year.[15] Children represented a large majority of these cases and fatalities. One of the
most famous outbreaks of diphtheria was in Nome, Alaska; the 1925 serum run to Nome to deliver diphtheria
antitoxin is now celebrated by the "Great Race of Mercy".
One of the first effective treatments for diphtheria was discovered in the 1880s by U.S. physician Joseph O'Dwyer
(1841–1898). O'Dwyer developed tubes that were inserted into the throat, and prevented victims from suffocating
due to the membrane sheath that grows over and obstructs airways. In 1884 Friedrich Loeffler discovered the
11
Diphtheria
causative organism (Corynebacterium diphtheriae). In the 1890s, the German physician Emil von Behring developed
an antitoxin that did not kill the bacterium, but neutralized the toxic poisons that the bacterium releases into the
body. Von Behring discovered that animal blood has antitoxins in it and so he took the blood, removed the clotting
agents and injected it into human patients. Von Behring was awarded the first Nobel Prize in Medicine for his role in
the discovery, and development of a serum therapy for diphtheria. (Americans William H. Park and Anna Wessels
Williams; and Pasteur Institute scientists Emile Roux and Auguste Chaillou also independently developed diphtheria
antitoxin in the 1890s.) The first successful vaccine for diphtheria was developed in 1913 by Behring. However,
antibiotics against diphtheria were not available until the discovery and development of sulfa drugs.
The Schick test, invented between 1910 and 1911, is a test used to determine whether or not a person is susceptible
to diphtheria. It was named after its inventor, Béla Schick (1877–1967), a Hungarian-born American pediatrician. A
massive five-year campaign was coordinated by Dr. Schick. As a part of the campaign, 85 million pieces of literature
were distributed by the Metropolitan Life Insurance Company with an appeal to parents to "Save your child from
diphtheria." A vaccine was developed in the next decade, and deaths began declining in earnest in 1924.[19]
In early May 2010, a case of diphtheria was diagnosed in Port-au-Prince, Haiti after the devastating 2010 Haiti
earthquake. The 15 year old male patient died while workers searched for anti-toxin.[20]
References
[1] http:/ / apps. who. int/ classifications/ apps/ icd/ icd10online/ ?ga36. htm+ a36
[5] http:/ / www. emedicine. com/ emerg/ topic138. htm
[6] http:/ / www. emedicine. com/ med/ topic459. htm#
[7] http:/ / www. emedicine. com/ oph/ topic674. htm#
[10] Office of Laboratory Security, Public Health Agency of Canada Corynebacterium diphtheriae (http:/ / www. phac-aspc. gc. ca/ msds-ftss/
msds42e. html) Material Safety Data Sheet. January 2000.
[11] Corynebacterium diphtheriae only produces diphtheria toxin when lysogenized by beta phage
[12] Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 299–302. ISBN 0838585299.
[13] Havaldar, PV; Sankpal MN, Doddannavar RP. (2000). "Diphtheritic myocarditis: clinical and laboratory parameters of prognosis and fatal
outcome.". Ann Trop Paediatr. 20 (3): 209–15.. PMID 11064774.
[14] Solders, G; Nennesmo I, Persson A. (1989). "Diphtheritic neuropathy, an analysis based on muscle and nerve biopsy and repeated
neurophysiological and autonomic function tests." (http:/ / www. pubmedcentral. nih. gov/ articlerender. fcgi?tool=pmcentrez&
artid=1031936). J Neurol Neurosurg Psychiatry 52 (7): 876–80.. doi:10.1136/jnnp.52.7.876. PMID 2549201. PMC 1031936.
[15] Atkinson W, Hamborsky J, McIntyre L, Wolfe S, eds. (2007). Diphtheria. in: Epidemiology and Prevention of Vaccine-Preventable
Diseases (The Pink Book) (http:/ / www. cdc. gov/ vaccines/ pubs/ pinkbook/ downloads/ dip. pdf) (10 ed.). Washington DC: Public Health
Foundation. pp. 59–70. .
[16] "Diphtheria Mechanism." The Medical News. Web. 07 Oct. 2010. <http://www.news-medical.net/health/Diphtheria-Mechanism.aspx>.
[17] The first version of this article was adapted from the CDC document "Diphtheria - 1995 Case Definition" at http:/ / www. cdc. gov/ epo/
dphsi/ casedef/ diphtheria_current. htm. As a work of an agency of the U.S. Government without any other copyright notice it should be
available as a public domain resource.
[18] "Diphtheria in the Former Soviet Union: Reemergence of a Pandemic Disease" (http:/ / www. cdc. gov/ ncidod/ eid/ vol4no4/ vitek. htm).
CDC, Emerging Infectious Diseases. 1998-10-01. .
[19] "United States mortality rate from measles, scarlet fever, typhoid, whooping cough, and diphtheria from 1900–1965" (http:/ / web. archive.
org/ web/ 20080508025250/ http:/ / www. healthsentinel. com/ graphs. php?id=14& event=graphs_print_list_item). HealthSentinel.com.
Archived from the original (http:/ / www. healthsentinel. com/ graphs. php?id=14& event=graphs_print_list_item) on 2008-05-08. . Retrieved
2008-06-30.
[20] "CNN's Anderson Cooper talks with Sean Penn and Dr. Sanjay Gupta about the threat of diptheria in Haiti." (http:/ / www. cnn. com/ video/
#/ video/ world/ 2010/ 05/ 07/ ac. penn. gupta. haiti. med. supply. cnn). CNN.com. . Retrieved 2010-05-09.
12
Diphtheria
Further reading
• Holmes RK, "Diphtheria and other corynebacterial infections". In Harrison's Principles of Internal Medicine, 16th
Ed. (2005).
• "Antitoxin dars 1735 and 1740." The William and Mary Quarterly, 3rd Ser., Vol 6, No 2. p. 338.
• Shulman ST, "The History of Pediatric Infectious Diseases" (http://scholar.google.com/scholar?hl=en&lr=&
safe=off&q=cache:FVEy_eca3ToJ:binf.gmu.edu/rkadoi/sysbio/PediatricInfectious.pdf+diphtheria+history+
1735+and+1740), Pediatric Research. Vol. 55, No. 1 (2004).
13
Mumps
14
Mumps
Mumps
Child with mumps.
ICD-10
B 26.
ICD-9
072
DiseasesDB
8449
[1]
[2]
[3]
MedlinePlus 001557 [4]
eMedicine
emerg/324
MeSH
D009107
[5]
emerg/391
[6]
ped/1503
[7]
[8]
Mumps and epidemic parotitis is a viral disease of the human species, caused by the mumps virus. Before the
development of vaccination and the introduction of a vaccine, it was a common childhood disease worldwide, and is
still a significant threat to health in the third world.[9]
Painful swelling of the salivary glands (classically the parotid gland) is the most typical presentation.[10] Painful
testicular swelling (orchitis) and rash may also occur. The symptoms are generally not severe in children. In teenage
males and men, complications such as infertility or subfertility are more common, although still rare in absolute
terms.[11] [12] [13] The disease is generally self-limited, running its course before receding, with no specific treatment
apart from controlling the symptoms with painkillers.
Signs and symptoms
The more common symptoms of mumps are:
• Parotid inflammation (or parotitis) in 60–70% of infections and 95% of patients with symptoms.[10] Parotitis
causes swelling and local pain, particularly when chewing. It can occur on one side (unilateral) but is more
common on both sides (bilateral) in about 90% of cases.[14]
• Fever
• Headache
• Orchitis, referring to painful inflammation of the testicle.[15] Males past puberty who develop mumps have a 30
percent risk of orchitis.[16]
Other symptoms of mumps can include dry mouth, sore face and/or ears and occasionally in more serious cases, loss
of voice. In addition, up to 20% of persons infected with the mumps virus do not show symptoms, so it is possible to
Mumps
be infected and spread the virus without knowing it.[17]
Prodrome
Fever and headache are prodromal symptoms of mumps, together with malaise and anorexia.
Cause
Mumps is a contagious disease that is spread from person-to-person through contact with respiratory secretions such
as saliva from an infected person. When an infected person coughs or sneezes, the droplets aerosolize and can enter
the eyes, nose, or mouth of another person. Mumps can also be spread by sharing food and drinks. The virus can also
survive on surfaces and then be spread after contact in a similar manner. A person infected with mumps is
contagious from approximately 6 days before the onset of symptoms until about 9 days after symptoms start.[18] [19]
The incubation period (time until symptoms begin) can be from 14–25 days but is more typically 16–18 days.[20]
Diagnosis
A physical examination confirms the presence of the swollen glands. Usually the disease is diagnosed on clinical
grounds and no confirmatory laboratory testing is needed. If there is uncertainty about the diagnosis, a test of saliva,
or blood may be carried out; a newer diagnostic confirmation, using real-time nested polymerase chain reaction
(PCR) technology, has also been developed.[21] An estimated 20%-30% of cases are asymptomatic.[22] As with any
inflammation of the salivary glands, serum amylase is often elevated.[23] [24]
Prevention
The most common preventative measure against mumps is immunization with a mumps vaccine, invented by
Maurice Hilleman at Merck.[25] The vaccine may be given separately or as part of the MMR immunization vaccine
which also protects against measles and rubella. In the US, MMR is now being supplanted by MMRV, which adds
protection against chickenpox. The WHO (World Health Organization) recommends the use of mumps vaccines in
all countries with well-functioning childhood vaccination programmes. In the United Kingdom it is routinely given
to children at age 15 months. The American Academy of Pediatrics recommends the routine administration of MMR
vaccine at ages 12–15 months and at 4–6 years.[26] In some locations, the vaccine is given again between 4 to 6
years of age, or between 11 and 12 years of age if not previously given. The efficacy of the vaccine depends on the
strain of the vaccine, but is usually around 80%.[27] ,[28] The Jeryl Lynn strain is most commonly used in developed
countries but has been shown to have reduced efficacy in epidemic situations. The Leningrad-Zagreb strain
commonly used in developing countries appears to have superior efficacy in epidemic situations.[29]
Due to the outbreaks within college and university settings, many governments have established vaccination
programs to prevent large-scale outbreaks. In Canada, provincial governments and the Public Health Agency of
Canada have all participated in awareness campaigns to encourage students ranging from grade 1 to college and
university to get vaccinated.[30]
Some anti-vaccine activists protest against the administration of a vaccine against mumps, claiming that the
attenuated vaccine strain is harmful, and/or that the wild disease is beneficial. There is very little evidence to support
the claim that the wild disease is beneficial, or that the MMR vaccine is harmful. Claims have been made that the
MMR vaccine is linked to autism and inflammatory bowel disease, including one study by Andrew Wakefield (paper
retracted in 2010) that indicated a link between gastrointestinal disease, autism, and the MMR vaccine. However, all
further studies since that time have indicated no link between vaccination with the MMR and autism or bowel
disease. Furthermore, there is scant evidence to suggest that autism is linked to bowel disease, though several poorly
designed studies have indicated a weak link between the two disorders. Since the dangers of the disease are well
known, while the dangers of the vaccine are quite minimal, most doctors recommend vaccination.
15
Mumps
The WHO, the American Academy of Pediatrics, the Advisory Committee on Immunization Practices of the Centers
for Disease Control and Prevention, the American Academy of Family Physicians, the British Medical Association
and the Royal Pharmaceutical Society of Great Britain currently recommend routine vaccination of children against
mumps. The British Medical Association and Royal Pharmaceutical Society of Great Britain had previously
recommended against general mumps vaccination, changing that recommendation in 1987. In 1988 it became United
Kingdom government policy to introduce mass child mumps vaccination programmes with the MMR vaccine, and
MMR vaccine is now routinely administered in the UK.
Before the introduction of the mumps vaccine, the mumps virus was the leading cause of viral meningoencephalitis
in the United States. However, encephalitis occurs rarely (less than 2 per 100,000).[31] In one of the largest studies in
the literature, the most common symptoms of mumps meningoencephalitis were found to be fever (97%), vomiting
(94%) and headache (88.8%).[32] The mumps vaccine was introduced into the United States in December 1967: since
its introduction there has been a steady decrease in the incidence of mumps and mumps virus infection. There were
151,209 cases of mumps reported in 1968. Since 2001, the case average was only 265 per year, excluding an
outbreak of >6000 cases in 2006 attributed largely to university contagion in young adults.[33] [34]
Treatment
There is no specific treatment for mumps. Symptoms may be relieved by the application of intermittent ice or heat to
the affected neck/testicular area and by acetaminophen/paracetamol (Tylenol) for pain relief. Aspirin is not used due
to a hypothetical link with Reye's syndrome. Warm salt water gargles, soft foods, and extra fluids may also help
relieve symptoms.
Patients are advised to avoid fruit juice or any acidic foods, since these stimulate the salivary glands, which can be
painful.
Prognosis
Death is very unusual. The disease is self-limiting, and general outcome is good, even if other organs are involved.
Known complications of mumps include:
• Infection of other organ systems
• Mumps viral infections in adolescent and adult males carry an up to 30% risk that the testes may become infected
(orchitis or epididymitis), which can be quite painful; about half of these infections result in testicular atrophy,
and in rare cases sterility can follow.[35]
• Spontaneous abortion in about 27% of cases during the first trimester of pregnancy.[35]
• Mild forms of meningitis in up to 10% of cases[35] (40% of cases occur without parotid swelling)
• Oophoritis (inflammation of ovaries) in about 5% of adolescent and adult females,[35] but fertility is rarely
affected.
• Pancreatitis in about 4% of cases, manifesting as abdominal pain and vomiting
• Encephalitis (very rare, and fatal in about 1% of the cases when it occurs)[35]
• Profound (91 dB or more) but rare sensorineural hearing loss, uni- or bilateral. Acute unilateral deafness occurs in
about 0.005% of cases.[35]
After the illness, life-long immunity to mumps generally occurs; reinfection is possible but tends to be mild and
atypical.[35]
16
Mumps
References
[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
http:/ / apps. who. int/ classifications/ apps/ icd/ icd10online/ ?gb25. htm+ b26
http:/ / www. icd9data. com/ getICD9Code. ashx?icd9=072
http:/ / www. diseasesdatabase. com/ ddb8449. htm
http:/ / www. nlm. nih. gov/ medlineplus/ ency/ article/ 001557. htm
http:/ / www. emedicine. com/ emerg/ topic324. htm
http:/ / www. emedicine. com/ emerg/ topic391. htm#
http:/ / www. emedicine. com/ ped/ topic1503. htm#
http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2010/ MB_cgi?field=uid& term=D009107
Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, Isselbacher KJ, Eds. (2004). Harrison's Principles of Internal
Medicine (16th ed.). McGraw-Hill Professional. ISBN 0-07-140235-7.
[10] Hviid A, Rubin S, Mühlemann K (March 2008). "Mumps". The Lancet 371 (9616): 932–44. doi:10.1016/S0140-6736(08)60419-5.
PMID 18342688.
[11] Preveden T, Jovanovic J, Ristic D (1996). "[Fertility in men after mumps infection without manifestations of orchitis]". Med Pregl 49 (3-4):
99–102. PMID 8692089.
[12] Shakhov EV, Krupin VN (1990). "[The clinico-statistical characteristics of the testicular generative function in male subfertility following
mumps]". Urol Nefrol (Mosk) (2): 46–50. PMID 2368216.
[13] Tsvetkov D (1990). "[Spermatological disorders in patients with postmumps orchitis]". Akush Ginekol (Sofiia) 29 (6): 46–9. PMID 2100952.
[14] Bedford H (2005). "Mumps: current outbreaks and vaccination recommendations". Nurs Times 101 (39): 53–4, 56. PMID 16218124.
[15] Manson AL (1990). "Mumps orchitis". Urology 36 (4): 355–8. doi:10.1016/0090-4295(90)80248-L. PMID 2219620.
[16] (http:/ / www. uchc. edu/ ocomm/ features/ stories/ stories06/ feature_mumps. html)
[17] Mumps (http:/ / www. health. gov. on. ca/ cs/ mumps/ english/ faq/ ), FAQ For Young Adults, Ministry of Health and Long-Term Care,
Ontario.ca
[18] Symptoms of mumps (http:/ / www. nhs. uk/ Conditions/ Mumps/ Pages/ Symptoms. aspx?url=Pages/ What-is-it. aspx)
[19] Letter:Compliance with Exclusion Requirements to Prevent Mumps Transmission (http:/ / www. cdc. gov/ eid/ content/ 13/ 10/ 1617. htm),
By Stephanie M. Borchardt, Preethi Rao, and Mark S. Dworkin, Volume 13, Number 10–October 2007
[20] Conly J, Johnston B (January 2007). "Is mumps making a comeback?" (http:/ / www. pubmedcentral. nih. gov/ articlerender.
fcgi?tool=pmcentrez& artid=2542890). Can J Infect Dis Med Microbiol 18 (1): 7–9. PMID 18923686. PMC 2542890.
[21] Krause CH, Eastick K, Ogilvie MM (November 2006). "Real-time PCR for mumps diagnosis on clinical specimens--comparison with
results of conventional methods of virus detection and nested PCR". J. Clin. Virol. 37 (3): 184–9. doi:10.1016/j.jcv.2006.07.009.
PMID 16971175.
[22] Centers for Disease Control and Prevention (CDC) (April 2006). "Mumps epidemic--Iowa, 2006" (http:/ / www. cdc. gov/ mmwr/ preview/
mmwrhtml/ mm5513a3. htm). MMWR Morb. Mortal. Wkly. Rep. (Centers for Disease Control and Prevention (CDC)) 55 (13): 366–8.
PMID 16601665. . Retrieved 2009-11-13.
[23] Amylase: The Test (http:/ / www. labtestsonline. org. uk/ understanding/ analytes/ amylase/ test. html), Lab Tests Online UK
[24] Skrha J, Stĕpán J, Sixtová E (October 1979). "Amylase isoenzymes in mumps". Eur. J. Pediatr. 132 (2): 99–105. doi:10.1007/BF00447376.
PMID 499265.
[25] Offit PA (2007). Vaccinated: One Man's Quest to Defeat the World's Deadliest Diseases. Washington, DC: Smithsonian.
ISBN 0-06-122796-X.
[26] (http:/ / www. cispimmunize. org/ IZSchedule. pdf)PDF
[27] Schlegel M, Osterwalder JJ, Galeazzi RL, Vernazza PL (1999). "Comparative efficacy of three mumps vaccines during disease outbreak in
Eastern Switzerland: cohort study" (http:/ / bmj. com/ cgi/ pmidlookup?view=long& pmid=10435956). BMJ 319 (7206): 352.
PMID 10435956. PMC 32261. .
[28] "Summary" (http:/ / www. who. int/ vaccines/ en/ mumps. shtml#summary). WHO: Mumps vaccine. . Retrieved 2006-04-18.
[29] Peltola H, Kulkarni PS, Kapre SV, Paunio M, Jadhav SS, Dhere RM (August 2007). "Mumps outbreaks in Canada and the United States:
time for new thinking on mumps vaccines". Clin. Infect. Dis. 45 (4): 459–66. doi:10.1086/520028. PMID 17638194.
[30] Table 2: Provincial and Territorial recommendations for mumps-containing immunization, 2007 (http:/ / www. phac-aspc. gc. ca/
mumps-oreillons/ prof-eng. php#t2), Information on Outbreaks of Mumps In Canada - Information for Health Professionals, Public Health
Agency Canada
[31] Atkinson W, Humiston S, Wolfe C, Nelson R (Editors). (2006). Epidemiology and Prevention of Vaccine-Preventable Diseases (9th ed.).
Centers for Disease Control and prevention. Fulltext (http:/ / www. cdc. gov/ nip/ publications/ pink/ def_pink_full. htm).
[32] Kanra G, Isik P, Kara A, Cengiz AB, Secmeer G, Ceyhan M (2004). "Complementary findings in clinical and epidemiologic features of
mumps and mumps meningoencephalitis in children without mumps vaccination". Pediatr Int 46 (6): 663–8.
doi:10.1111/j.1442-200x.2004.01968.x. PMID 15660864.
[33] McNabb SJ, Jajosky RA, Hall-Baker PA, et al. (March 2008). "Summary of notifiable diseases--United States, 2006" (http:/ / www. cdc.
gov/ mmwr/ preview/ mmwrhtml/ mm5553a1. htm). MMWR Morb. Mortal. Wkly. Rep. 55 (53): 1–92. PMID 18354375. . Retrieved
2009-11-13.
17
Mumps
[34] 2006 mumps outbreak occurred despite high vaccination rate - Los Angeles Times (http:/ / www. latimes. com/ features/ health/
la-he-mumps14apr14,1,547450. story)
[35] Senanayake SN (2008). "Mumps: a resurgent disease with protean manifestations" (http:/ / www. mja. com. au/ public/ issues/
189_08_201008/ sen10220_fm. html). Med J Aust 189 (8): 456–9. PMID 18928441. .
External links
• Original version based on the National Library of Medicine's Medline Plus (http://www.nlm.nih.gov/
medlineplus/ency/article/001557.htm) website. Update Date: 08/15/01. Update date included for
cross-reference against newer versions.
• NHS.uk (http://www.nhsdirect.nhs.uk/articles/article.aspx?articleId=255) – Encyclopedia – 'NHS Direct
Online Health Encyclopaedia: Mumps', National Health Service (UK)
• WHO.int (http://www.who.int/immunization/topics/mumps/en/index.html) – "Immunization, Vaccines and
Biologicals: Mumps vaccine", World Health Organisation
• MicrobiologyBytes: Paramyxoviruses (http://www.microbiologybytes.com/virology/Paramyxoviruses.html)"
• nih.gov (http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=Nucleotide&dopt=GenBank&val=7592770)
– "NIH database entry: complete genome of Miyahara strain of Mumps"
• cdc.gov (http://www.cdc.gov/vaccines/vpd-vac/mumps/default.htm) – Collection of information from the
CDC concerning mumps
• ontario.ca (http://www.ontario.ca/mumps) – Ontario Mumps Catch-Up Vaccination Campaign targeted at
Students
• TWU.ca (http://www.twu.ca/life/wellness/bulletin-boards/mumps-outbreak.html), SFU.ca (http://news.
students.sfu.ca/2008/09/15/mumps-outbreak/) – Information from 2008 Mumps Outbreak in British
Columbia
• GNB.ca (http://www.gnb.ca/cnb/news/he/2007e0881he.htm) – New Brunswick Vaccination Campaign
• gov.pe.ca (http://www.gov.pe.ca/news/getrelease.php3?number=5308) – P.E.I. Vaccination Campaign
• gov.yk.ca (http://www.hss.gov.yk.ca/news/2006/id_51/) – Yukon Vaccination Campaign
• Public Health Agency of Canada (http://www.phac-aspc.gc.ca/mumps-oreillons/prof-eng.php#t2) – Public
Health Agency of Canada Vaccination Campaigns
• Virus Pathogen Database and Analysis Resource (ViPR): Paramyxoviridae (http://www.viprbrc.org/brc/home.
do?decorator=paramyxo)
18
Pertussis
19
Pertussis
Pertussis
A young boy coughing due to pertussis.
[1]
ICD-10
A 37.
ICD-9
033
DiseasesDB
1523
MedlinePlus
001561
eMedicine
emerg/394
MeSH
D014917
[2]
[3]
[4]
[5]
ped/1778
[6]
[7]
Pertussis, also known as whooping cough (pronounced /ˈhuːpɪŋ kɒf/), is a highly contagious disease caused by the
bacterium Bordetella pertussis. It is known to last for a duration of approximately 6 weeks before subsiding. The
disease derives its name from the "whoop" sound made from the inspiration of air after a cough. A similar, milder
disease is caused by B. parapertussis.[8] Although many medical sources describe the whoop as "high-pitched", this
is generally the case with infected babies and children only, not adults.[9]
Signs and symptoms
The classic symptoms of pertussis is a paroxysmal cough, inspiratory whoop, and post coughing vomiting.[10] The
cough from pertussis has been documented to cause subconjunctival hemorrhages, rib fractures, urinary
incontinence, hernias, post cough syncope, and vertebral artery dissection.[10]
The incubation period is typically seven to ten days, in infants or young children, after which there is usually mild
respiratory symptoms, mild coughing, sneezing, or runny nose. This is known as the catarrhal stage. After one to two
weeks, the coughing classically develops into uncontrollable fits, each with five to ten forceful coughs, followed by a
high-pitched "whoop" sound in younger children, or a gasping sound in older children, as the patient struggles to
breathe in afterwards (paroxysmal stage). Fits can occur on their own or can be triggered by yawning, stretching,
laughing, eating or yelling; they usually occur in groups, with multiple episodes every hour around the clock. This
Pertussis
stage lasts two to eight weeks, or sometimes longer. A gradual transition then occurs to the convalescent stage,
which usually lasts one to two weeks. This stage is marked by a decrease in paroxysms of coughing, both in
frequency and severity, and a cessation of vomiting. Common complications of the disease include pneumonia,
encephalopathy, earache, or seizures. Infection in newborns is particularly severe.
Diagnosis
Methods used in laboratory diagnosis include culturing of nasopharyngeal swabs on Bordet-Gengou medium,
polymerase chain reaction (PCR), direct immunofluorescence (DFA), and serological methods. The bacteria can be
recovered from the patient only during the first three weeks of illness, rendering culturing and DFA useless after this
period, although PCR may have some limited usefulness for an additional three weeks. For most adults and
adolescents, who often do not seek medical care until several weeks into their illness, serology is often used to
determine whether antibody against pertussis toxin or another component of B. pertussis is present at high levels in
the blood of the patient. By this stage they have been contagious for some weeks. Because of this, adults, who are
not in great danger from pertussis, are increasingly being encouraged to be vaccinated.
Vaccine
Pertussis vaccines are highly effective, strongly recommended, and save many lives each year. The duration of
protection is between 5 to 10 years, which covers childhood, the time of greatest exposure and greatest risk.[11] [10]
The immunizations are given in combination with tetanus, diphtheria, polio and haemophilus influenzae type B
immunizations, at ages 2, 4, and 6 months, and a single later booster at 3 to 4 years of age.
The short-term effectiveness of the vaccines and the presence of B. pertussis infection in adults and adolescents who
may transmit the bacteria to infants have caused many in the medical field to call for booster immunizations at later
ages. Although Canada, France, the U.S. and Germany now have approved booster shots for adolescents, adults, or
both, other countries adhere to the tradition of discontinuing pertussis vaccination after the age of seven, from
concerns that there are side effects associated with the first available "whole-cell" pertussis immunizations that
tended to increase with age. The whole-cell vaccine is still used in poor countries, because it is cheaper than the
newer and safer acellular formulation.
Infection with pertussis induces natural immunity, but not lasting protective immunity – a second attack is
possible.[12]
Whereas the immunity from infection or vaccination lasts only a few years, the discontinuation of booster
vaccination in older persons caused the emergence of a large pool of older persons lacking immunity, followed by an
increase of adult-onset pertussis that accelerated beginning in about 2004.[13] This burgeoning outbreak is predicted
to increasingly infect adults and adolescents with debilitating cases, but poses even more serious public health
dangers to newborns. As adolescent and adult cases surge, newborns are again at risk of exposure to pertussis
circulating in adolescents or adults in the community before the infants' vaccinations can be completed.
The decision to resume vaccinating teens and adults reflects in part that the newer acellular vaccine, known as DTaP,
has greatly reduced the incidence of adverse effects observed with the earlier "whole-cell" pertussis vaccine. An
acellular vaccine preparation for adults and adolescents has been approved in Canada, Europe, and the United States.
In the U.S., the Food and Drug Administration has authorized both the use of the vaccines Boostrix
(GlaxoSmithKline) for 10-18 year olds in May 2005, with an expanded indication to age 64 in December 2008, and
Adacel (Sanofi Pasteur) for 11-64 year olds in August 2005.[14] These vaccines are recommended for all teens and
adults within the indicated age ranges, except for those with a history of adverse reaction to the whole-cell pertussis
vaccines. The most serious side-effects of traditional "whole-cell" pertussis immunizations were neurological: and
included seizures and hypotonic episodes.
20
Pertussis
Controversy
Much of the controversy surrounding the DPT vaccine in the 1970s and 1980s related to the question of whether the
whole-cell pertussis component caused permanent brain injury in rare cases. Although it was well-established that
the pertussis component of the DPT vaccine accounted for most of the minor local and systemic side effects in many
vaccinated infants, several published studies failed to show a causal relationship between administration of the DPT
vaccine and permanent brain injury. However, criticism of these studies and well-publicized anecdotal reports of
DPT-induced permanent disability and death gave rise to anti-DPT movements.[15] In addition, a number of children
suffered allergic and adverse reactions to the pertussis vaccination, including severe seizures. Despite this, doctors
recommended the vaccine due to the overwhelming public health benefit.
By the late 1970s, publicity about adverse reactions and deaths following pertussis vaccination caused the
immunization rate to fall in several countries, including Great Britain, Sweden, and Japan. In many cases, a dramatic
increase in the incidence of pertussis followed.[16] Unscientific claims about the vaccine forced suppliers of the
vaccines preventing whooping cough out of the market.[17] These developments led Yuji Sato to introduce a safer
acellular version of the pertussis vaccine for Japan in 1981. Nevertheless, other countries continued to use the
whole-cell DTP formulation.
In the United States, low profit margins and an increase in vaccine-related lawsuits led many manufacturers to stop
producing the DTP vaccine by the early 1980s. In 1982, the television documentary "DTP: Vaccine Roulette"
depicted the lives of children whose severe disabilities were blamed on the DTP vaccine. The negative publicity
generated by the documentary led to a tremendous increase in the number of lawsuits filed against vaccine
manufacturers.[18] By 1985, manufacturers of vaccine had difficulty obtaining liability insurance. The price of the
DTP vaccine skyrocketed, leading to shortages around the country. Only one manufacturer of the DTP vaccine
remained in the U.S. by the end of 1985. To avert a vaccine crisis, Congress in 1986 passed the National Childhood
Vaccine Injury Act (NCVIA), which established a federal no-fault system to compensate victims of injury caused by
mandated vaccines.[19] The majority of claims that have been filed through the NCVIA have been related to injuries
allegedly caused by the whole-cell DTP vaccine. The acellular pertussis vaccine was approved in the United States
in 1992 for use in the combination DTaP vaccine. Research has shown the acellular vaccine to be safer, with fewer
reports of adverse effects.[20] Although the whole-cell DTP vaccine is no longer used in the United States, it is still
purchased by the World Health Organization and distributed to developing nations because of its much reduced cost
compared to the acellular DTaP vaccine.
There is newly emerging evidence that some strains of the bacteria that cause pertussis have become resistant to the
acellular version of the vaccine which is leading to a rise in the incidence of whooping cough in the wealthy
countries that use it[21] .
Treatment
Antibiotics
Treatment with an effective antibiotic (erythromycin or azithromycin) shortens the infectious period but does not
generally alter the outcome of the infection; however, when treatment is initiated during the catarrhal stage,
symptoms may be less severe. Three macrolides (erythromycin, azithromycin and clarithromycin) are used in the
U.S. for treatment of pertussis; trimethoprim-sulfamethoxazole is generally used when a macrolide is ineffective or
is contraindicated. Close contacts who receive appropriate antibiotics (chemoprophylaxis) during the 7–21 day
incubation period may be protected from developing symptomatic disease. Close contacts are defined as anyone
coming into contact with the respiratory secretions of an infected person in the 21 days before or after the infected
person's cough began. There is no known antitoxin.
21
Pertussis
Cough
Effective treatments of the cough associated with this condition have not yet been developed.[22] Herbal treatments
and vitamin C in the form of sodium ascorbate have been said to greatly decrease the severity of the cough caused by
pertussis, but scant scientific studies have been performed to investigate this claim. [23] .
Prognosis
Most healthy older children and adults will have a full recovery from pertussis, however those with comorbid
conditions can have a higher risk of morbidity and mortality. Pertussis is fatal in an estimated one in 100 infants
under 6 months, and fatal in one in 200 infants aged 2 to 12 months. Infants under one are also more likely to
develop complications (eg pneumonia (20%), encephalopathy, seizures (1%), failure to thrive, and death (0.2%)).
Pertussis can cause severe paroxysm-induced cerebral hypoxia and apnea. Reported fatalities from pertussis in
infants have increased substantially over the past 20 years. [24]
Epidemiology
Worldwide whooping cough affects 48.5 million people yearly resulting in nearly 295,000 deaths.[22] This is despite
generally high coverage with the DTP and DTaP vaccines, pertussis is one of the leading causes of
vaccine-preventable deaths world-wide. Ninety percent of all cases occur in developing countries.
Before vaccines, an average of 157 cases per 100,000 persons were reported in the U.S., with peaks reported every
two to five years; more than 93% of reported cases occurred in children under 10 years of age. The actual incidence
was likely much higher. After vaccinations were introduced in the 1940s, incidence fell dramatically to less than 1
per 100,000 by 1970. Incidence rates have increased somewhat since 1980.
Pertussis is the only vaccine-preventable disease that is associated with increasing deaths in the U.S. The number of
deaths increased from 4 in 1996 to 17 in 2001, almost all of which were infants under one year.[25] In Canada, the
number of pertussis infections has varied between 2,000 to 10,000 reported cases each year over the last 10 years.[26]
Australia reports an average of 10,000 cases a year, but the number of cases has increased in recent years.[27] In 2010
ten infants in California died and health authorities declared an epidemic.[28] Doctors had been misdiagnosing the
infants' condition despite having seen infants on multiple visits.[29]
History
B. pertussis was isolated in pure culture in 1906 by Jules Colneal and Octave Gengou, who also developed the first
serology and vaccine. The complete B. pertussis genome of 9,086,186 base pairs was sequenced in 2004.
Efforts to develop an inactivated whole-cell pertussis vaccine began soon after B. pertussis was grown in pure
culture in 1906. In the 1920s Dr. Louis W. Sauer developed a vaccine for whooping cough at Evanston Hospital
(Evanston, IL). In 1925, the Danish physician Thorvald Madsen was the first to test a whole-cell pertussis vaccine on
a wide scale.[30] He used the vaccine to control outbreaks in the Faroe Islands in the North Sea. In 1942, the
American scientist Pearl Kendrick combined the whole-cell pertussis vaccine with diphtheria and tetanus toxoids to
generate the first DTP combination vaccine. To minimize the frequent side effects caused by the pertussis
component of the vaccine, the Japanese scientist Yuji Sato developed an acellular pertussis vaccine consisting of
purified haemagglutinins (HAs: filamentous strep throat and leucocytosis-promoting-factor HA), which are secreted
by B. pertussis into the culture medium. Sato's acellular pertussis vaccine was used in Japan since the autumn of
1981.[31] Later versions of the acellular pertussis vaccine used in other countries consisted of additional defined
components of B. pertussis and were often part of the DTaP combination vaccine.
22
Pertussis
References
[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
http:/ / apps. who. int/ classifications/ apps/ icd/ icd10online/ ?ga30. htm+ a37
Finger H, von Koenig CHW (1996). Bordetella–Clinical Manifestations. In: Barron's Medical Microbiology (Barron S et al., eds.) (http:/ /
www. ncbi. nlm. nih. gov/ books/ bv. fcgi?rid=mmed. section. 1694) (4th ed.). Univ of Texas Medical Branch. ISBN 0-9631172-1-1. .
[9] Symptoms and Sounds (http:/ / www. whoopingcough. net/ symptoms. htm) from WhoopingCough.net
[10] Cornia PB, Hersh AL, Lipsky BA, Newman TB, Gonzales R (August 2010). "Does this coughing adolescent or adult patient have
pertussis?". JAMA 304 (8): 890–6. doi:10.1001/jama.2010.1181. PMID 20736473.
[11] Versteegh FGA, Schellekens JFP, Fleer A, Roord JJ. (2005). "Pertussis: a concise historical review including diagnosis, incidence, clinical
manifestations and the role of treatment and vaccination in management." (http:/ / www. revmedmicrobiol. com/ pt/ re/ revmedmicrob/
abstract. 00013542-200508000-00001. htm). Rev Med Microbiol 16 (3): 79–89. .
[12] Disease Control Priorities Project. (2006). Vaccine-Preventable Diseases (Table 20.1, page 390 (http:/ / files. dcp2. org/ pdf/ expressbooks/
vaccine. pdf)). International Bank for Reconstruction and Development, World Bank. Washington DC (www.worldbank.org).
[13] Kate Murphy. (2005). Enduring and Painful, Pertussis Leaps Back. New York Times (22 February 2005).
[14] "Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed, ADACEL, Aventis Pasteur Ltd" (http:/ / web.
archive. org/ web/ 20070216224327/ http:/ / www. fda. gov/ Cber/ products/ tdapave061005. htm). Archived from the original (http:/ / www.
fda. gov/ Cber/ products/ tdapave061005. htm) on 2007-02-16. . Retrieved 2006-05-01.
[15] Geier D, Geier M (2002). "The true story of pertussis vaccination: a sordid legacy?". Journal of the history of medicine and allied sciences
57 (3): 249–84. doi:10.1093/jhmas/57.3.249. PMID 12211972.
[16] Gangarosa EJ, Galazka AM, Wolfe CR, Phillips LM, Gangarosa RE, Miller E, Chen RT (1998). "Impact of anti-vaccine movements on
pertussis control: the untold story". Lancet 351 (9099): 356–61. doi:10.1016/S0140-6736(97)04334-1. PMID 9652634.
[17] http:/ / www. overlawyered. com/ articles/ huber/ junksci. html
[18] Evans G (2006). "Update on vaccine liability in the United States: presentation at the National Vaccine Program Office Workshop on
strengthening the supply of routinely recommended vaccines in the United States, 12 February 2002". Clin. Infect. Dis. 42 Suppl 3: S130–7.
doi:10.1086/499592. PMID 16447135.
[19] Smith MH (1988). "National Childhood Vaccine Injury Compensation Act". Pediatrics 82 (2): 264–9. PMID 3399300.
[20] Pichichero ME, Rennels MB, Edwards KM, et al. (June 2005). "Combined tetanus, diphtheria, and 5-component pertussis vaccine for use in
adolescents and adults". JAMA 293 (24): 3003–11. doi:10.1001/jama.293.24.3003. PMID 15933223.
[21] http:/ / www. newscientist. com/ blogs/ shortsharpscience/ 2010/ 02/ whooping-cough-evolves-to-esca. html
[22] Bettiol S, Thompson MJ, Roberts NW, Perera R, Heneghan CJ, Harnden A (2010). "Symptomatic treatment of the cough in whooping
cough". Cochrane Database Syst Rev (1): CD003257. doi:10.1002/14651858.CD003257.pub3. PMID 20091541.
[23] http:/ / www. ncbi. nlm. nih. gov/ pmc/ articles/ PMC2210412/ pdf/ brmedj04218-0015. pdf
[24] Guinto-Ocampo, Hazel; Bryon K McNeil, Stephen C Aronoff (Apr 27, 2010). "Pertussis: Follow-up" (http:/ / emedicine. medscape. com/
article/ 967268-followup). emedicine (WebMD). . Retrieved Sep 29, 2010.
[25] Gregory DS (2006). "Pertussis: a disease affecting all ages" (http:/ / www. aafp. org/ afp/ 20060801/ 420. html). Am Fam Physician 74 (3):
420–6. PMID 16913160. .
[26] http:/ / chealth. canoe. ca/ channel_condition_info_details. asp?disease_id=217& channel_id=2026& relation_id=18305& rot=4
[27] Lavelle P (January 20, 2009). "A bad year for whooping cough" (http:/ / www. abc. net. au/ health/ thepulse/ stories/ 2009/ 01/ 20/ 2469770.
htm). Australian Broadcasting Corporation. .
[28] Miriam Falco (October 20, 2010). "Ten infants dead in California whooping cough outbreak" (http:/ / us. cnn. com/ 2010/ HEALTH/ 10/ 20/
california. whooping. cough/ index. html). CNN. . Retrieved 2010-10-21. "Whooping cough, also known as pertussis, has claimed the 10th
victim in California, in what health officials are calling the worst outbreak in 60 years."
[29] Rong-Gong Lin II (September 7, 2010). "Diagnoses lagged in baby deaths" (http:/ / articles. latimes. com/ 2010/ sep/ 07/ local/
la-me-whooping-cough-20100907). Los Angeles Times. . Retrieved 2010-09-08.
[30] Baker JP, Katz SL (2004). "Childhood vaccine development: an overview". Pediatr. Res. 55 (2): 347–56.
doi:10.1203/01.PDR.0000106317.36875.6A. PMID 14630981.
[31] Sato Y, Kimura M, Fukumi H (1984). "Development of a pertussis component vaccine in Japan". Lancet 1 (8369): 122–6.
doi:10.1016/S0140-6736(84)90061-8. PMID 6140441.
23
Pertussis
External links
• Pertussis at Todar's Online Textbook of Bacteriology (http://textbookofbacteriology.net/pertussis.html)
• Versteegh FGA, Schellekens JFP, Fleer A, Roord JJ. Pertussis: a concise historical review including diagnosis,
incidence, clinical manifestations and the role of treatment and vaccination in management. Rev Med Microbiol
|2005;16(3)79–89 (http://www.sepeap.es/revisiones/archivos/9902.pdf)
• Pertussis: new insights in diagnosis, incidence and clinical manifestations, F.G.A. Versteegh, Thesis, 2005 (http:/
/hdl.handle.net/1871/10211)
• Symptoms and Sounds (http://www.whoopingcough.net/symptoms.htm)
• Versteegh FGA, Schellekens JFP, Fleer A, Roord JJ. Pertussis: a concise historical review including diagnosis,
incidence, clinical manifestations and the role of treatment and vaccination in management. Rev Med Microbiol
|2005;16(3)79–89 (http://www.sepeap.es/revisiones/archivos/9902.pdf)
24
Impetigo
25
Impetigo
Impetigo
Impetigo Skin Lesions
ICD-10
L 01.
ICD-9
684
DiseasesDB
6753
[1]
[2]
[3]
eMedicine
derm/195
MeSH
D007169
[5]
emerg/283
[6]
med/1163
[7]
ped/1172
[8]
[9]
Impetigo English pronunciation: /ɪmpɨˈtaɪɡoʊ/ is a highly contagious bacterial skin infection most common among
pre-school children.[10] People who play close contact sports such as rugby, American football and wrestling are also
susceptible, regardless of age. Impetigo is not as common in adults. The name derives from the Latin impetere
("assail"). It is also known as school sores.[11]
Impetigo
Classification
Bullous impetigo
Bullous impetigo primarily affects infants and children younger than 2 years. It causes painless, fluid-filled blisters
— usually on the trunk, arms and legs. The skin around the blister is usually red and itchy but not sore. The blisters,
which break and scab over with a yellow-colored crust, may be large or small, and may last longer than sores from
other types of impetigo.
Ecthyma
Ecthyma is a more serious form of impetigo in which the infection penetrates deeper into the skin's second layer, the
dermis. Signs and symptoms include:
•
•
•
•
•
Painful fluid- or pus-filled sores that turn into deep ulcers, usually on the legs and feet
A hard, thick, gray-yellow crust covering the sores
Swollen lymph glands in the affected area
Little holes the size of pinheads to the size of pennies appear after crust recedes
Scars that remain after the ulcers heal
Causes
It is primarily caused by Staphylococcus aureus, and sometimes by Streptococcus pyogenes.[12] According to the
American Academy of Family Physicians, both bullous and nonbullous are primarily caused by Staphylococcus
aureus, with Streptococcus also commonly being involved in the nonbullous form."[13]
Transmission
The infection is spread by direct contact with lesions or with nasal carriers. The incubation period is 1–3 days. Dried
streptococci in the air are not infectious to intact skin. Scratching may spread the lesions.
Diagnosis
Impetigo generally appears as honey-colored scabs formed from dried serum, and is often found on the arms, legs, or
face.[12]
Prevention
Good hygiene practices can help prevent impetigo from spreading. Those who are infected should use soap and
water to clean their skin and take baths or showers regularly. Non-infected members of the household should pay
special attention to areas of the skin that have been injured, such as cuts, scrapes, insect bites, areas of eczema, and
rashes. These areas should be kept clean and covered to prevent infection. In addition, anyone with impetigo should
cover the impetigo sores with gauze and tape. All members of the household should wash their hands thoroughly
with soap on a regular basis. It is also a good idea for everyone to keep their fingernails cut short to make hand
washing more effective. Contact with the infected person and his or her belongings should be avoided, and the
infected person should use separate towels for bathing and hand washing. If necessary, paper towels can be used in
place of cloth towels for hand drying. The infected person's bed linens, towels, and clothing should be separated
from those of other family members, as well. Whilst suffering from impetigo, it is best to stay indoors for a few days
to stop any bacteria from getting into the blisters and making the infections worse. When a person has impetigo, it is
common for them to get it a second time in the space of 6–9 months. This usually occurs in people aged 12–16.
26
Impetigo
Treatment
For generations, the disease was treated with an application of the antiseptic gentian violet.[14] Today, topical or oral
antibiotics are usually prescribed. Treatment may involve washing with soap and water and letting the impetigo dry
in the air. Mild cases may be treated with bactericidal ointment, such as fusidic acid, mupirocin, chloramphenicol or
neosporin, which in some countries may be available over-the-counter. More severe cases require oral antibiotics,
such as dicloxacillin, flucloxacillin or erythromycin. Alternatively amoxicillin combined with clavulanate potassium,
cephalosporins (1st generation) and many others may also be used as an antibiotic treatment.
Hydrogen peroxide is an alternative to topical antibiotics in the treatment of Impetigo. In a cream formulation
hydrogen peroxide 1% is stabilized, thereby avoiding fast degradation with the result of prolonged antimicrobial
effect and effective treatment. Hydrogen peroxide has been shown to be as effective as antibiotics in the treatment of
Impetigo Contagiosa.
See also
• List of cutaneous conditions
use calamiol
References
Notes
[1] http:/ / apps. who. int/ classifications/ apps/ icd/ icd10online/ ?gl00. htm+ l01
[5] http:/ / www. emedicine. com/ derm/ topic195. htm
[7] http:/ / www. emedicine. com/ med/ topic1163. htm#
[10] NHS Impetigo (http:/ / www. nhs. uk/ conditions/ Impetigo/ Pages/ Introduction. aspx)
[11] Impetigo - school sores - Better Health Channel (http:/ / www. betterhealth. vic. gov. au/ bhcv2/ bhcarticles. nsf/ pages/
Impetigo_or_school_sores?OpenDocument)
[12] Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; & Mitchell, Richard N. (2007). Robbins Basic Pathology (8th ed.). Saunders Elsevier. pp.
843 ISBN 978-1-4160-2973-1
[13] Stulberg DL, Penrod MA, Blatny RA (2002). "Common bacterial skin infections." (http:/ / www. aafp. org/ afp/ 20020701/ 119. html).
American Family Physician 66 (1): 119–24. PMID 12126026. .
[14] http:/ / www. bmj. com/ cgi/ content/ full/ 329/ 7472/ 979
External links
• Impetigo Pictures (http://www.staph-infection-pictures.com/impetigo-pictures.php) - Pictures of Impetigo
caused by Staph Infections and MRSA.
• NIH/Medline (http://www.nlm.nih.gov/medlineplus/impetigo.html)
• Photo (University of Iowa) (http://tray.dermatology.uiowa.edu/Impetigo004.htm)
• Dermnet NZ (http://www.dermnetnz.org/bacterial/impetigo.html)
• Merck Manual (professional) (http://www.merck.com/mmpe/sec10/ch119/ch119i.html)
27
Herpes zoster
28
Herpes zoster
Herpes zoster
Herpes zoster blisters on the neck and shoulder
[1]
ICD-10
B 02.
ICD-9
053
DiseasesDB
29119
[2]
[3]
eMedicine
med/1007
[5]
derm/180
[6]
emerg/823
[7]
oph/257
[8]
ped/996
[9]
Herpes zoster (or simply zoster), commonly known as shingles and also known as zona, is a viral disease
characterized by a painful skin rash with blisters in a limited area on one side of the body, often in a stripe. The
initial infection with varicella zoster virus (VZV) causes the acute (short-lived) illness chickenpox which generally
occurs in children and young people. Once an episode of chickenpox has resolved, the virus is not eliminated from
the body but can go on to cause shingles—an illness with very different symptoms—often many years after the
initial infection.
Varicella zoster virus can become latent in the nerve cell bodies and less frequently in non-neuronal satellite cells of
dorsal root, cranial nerve or autonomic ganglion,[10] without causing any symptoms.[11] Years or decades after a
chickenpox infection, the virus may break out of nerve cell bodies and travel down nerve axons to cause viral
infection of the skin in the region of the nerve. The virus may spread from one or more ganglia along nerves of an
affected segment and infect the corresponding dermatome (an area of skin supplied by one spinal nerve) causing a
painful rash.[12] [13] Although the rash usually heals within two to four weeks, some sufferers experience residual
nerve pain for months or years, a condition called postherpetic neuralgia. Exactly how the virus remains latent in the
body, and subsequently re-activates is not understood.[10]
Throughout the world the incidence rate of herpes zoster every year ranges from 1.2 to 3.4 cases per 1,000 healthy
individuals, increasing to 3.9–11.8 per year per 1,000 individuals among those older than 65 years.[14] [15] [16]
Antiviral drug treatment can reduce the severity and duration of herpes zoster if a seven- to ten-day course of these
drugs is started within 72 hours of the appearance of the characteristic rash.[14] [17]
Herpes zoster
29
Name
The family name of all the herpesviridae is derived from the Greek word herpein ("to creep"), referring to the latent,
recurring infections typical of this group of viruses. Zoster comes from Greek zōstēr, meaning "belt" or "girdle",
after the characteristic belt-like dermatomal rash.[18] The name shingles represents Latin cingulus, a variant of Latin
cingulum meaning "girdle".
Despite the similarity of name, herpes zoster is not the same disease as herpes simplex, although both the varicella
zoster virus and herpes simplex virus belong to the same viral subfamily (Alphaherpesvirinae).
Signs and symptoms
The earliest symptoms of herpes zoster, which include headache, fever, and malaise, are nonspecific, and may result
in an incorrect diagnosis.[14] [19] These symptoms are commonly followed by sensations of burning pain, itching,
hyperesthesia (oversensitivity), or paresthesia ("pins and needles": tingling, pricking, or numbness).[20] The pain may
be mild to extreme in the affected dermatome, with sensations that are often described as stinging, tingling, aching,
numbing or throbbing, and can be interspersed with quick stabs of agonizing pain.[21] Herpes zoster in children is
often painless.
In most cases after 1–2 days, but sometimes as long as 3 weeks, the initial phase is followed by the appearance of the
characteristic skin rash. The pain and rash most commonly occurs on the torso, but can appear on the face, eyes or
other parts of the body. At first the rash appears similar to the first appearance of hives; however, unlike hives,
herpes zoster causes skin changes limited to a dermatome, normally resulting in a stripe or belt-like pattern that is
limited to one side of the body and does not cross the midline.[20] Zoster sine herpete ("herpes without zoster")
describes a patient who has all of the symptoms of herpes zoster except this characteristic rash.[22]
Later the rash becomes vesicular, forming small blisters filled with a serous exudate, as the fever and general malaise
continue. The painful vesicles eventually become cloudy or darkened as they fill with blood, crust over within seven
to ten days; usually the crusts fall off and the skin heals, but sometimes, after severe blistering, scarring and
discolored skin remain.[20]
Development of the shingles rash
Day 1
Day 2
Day 5
Day 6
Herpes zoster may have additional symptoms, depending on the dermatome involved. Herpes zoster ophthalmicus
involves the orbit of the eye and occurs in approximately 10–25% of cases. It is caused by the virus reactivating in
the ophthalmic division of the trigeminal nerve. In a few patients, symptoms may include conjunctivitis, keratitis,
uveitis, and optic nerve palsies that can sometimes cause chronic ocular inflammation, loss of vision, and debilitating
pain.[23] Herpes zoster oticus, also known as Ramsay Hunt syndrome type II, involves the ear. It is thought to result
from the virus spreading from the facial nerve to the vestibulocochlear nerve. Symptoms include hearing loss and
vertigo (rotational dizziness).[10]
Herpes zoster
30
Pathophysiology
The causative agent for herpes zoster is varicella zoster virus (VZV), a
double-stranded DNA virus related to the Herpes simplex virus group.
Most people are infected with this virus as children, and suffer from an
episode of chickenpox. The immune system eventually eliminates the
virus from most locations, but it remains dormant (or latent) in the
ganglia adjacent to the spinal cord (called the dorsal root ganglion) or
the ganglion semilunare (ganglion Gasseri) in the base of the skull.[24]
Repeated attacks of herpes zoster are rare,[20] and it is extremely rare
for patients to suffer more than three recurrences.[24]
Herpes zoster occurs only in people who have had chickenpox, and
although it can occur at any age, the majority of sufferers are more
Progression of herpes zoster. A cluster of small
than 50 years old.[25] The disease results from the virus reactivating in
bumps
(1) turns into blisters (2). The blisters fill
a single sensory ganglion.[13] In contrast to Herpes simplex virus, the
with lymph, break open (3), crust over (4), and
latency of VZV is poorly understood. The virus has not been recovered
finally disappear. Postherpetic neuralgia can
sometimes occur due to nerve damage (5),
from human nerve cells by cell culture and the location and structure of
the viral DNA is not known. Virus-specific proteins continue to be
made by the infected cells during the latent period, so true latency, as opposed to a chronic low-level infection, has
not been proven.[11] [26] Although VZV has been detected in autopsies of nervous tissue,[27] there are no methods to
find dormant virus in the ganglia in living people.
Unless the immune system is compromised, it suppresses reactivation of the virus and prevents herpes zoster. Why
this suppression sometimes fails is poorly understood,[15] but herpes zoster is more likely to occur in people whose
immune system is impaired due to aging, immunosuppressive therapy, psychological stress, or other factors.[28]
Upon reactivation, the virus replicates in the nerve cells, and virions are shed from the cells and carried down the
axons to the area of skin served by that ganglion. In the skin, the virus causes local inflammation and blisters. The
short- and long-term pain caused by herpes zoster comes from the widespread growth of the virus in the infected
nerves, which causes inflammation.[29]
The symptoms of herpes zoster cannot be transmitted to another person.[30] However, during the blister phase, direct
contact with the rash can spread VZV to a person who has no immunity to the virus. This newly-infected individual
may then develop chickenpox, but will not immediately develop shingles. Until the rash has developed crusts, a
person is extremely contagious. A person is also not infectious before blisters appear, or during postherpetic
neuralgia (pain after the rash is gone). The person is no longer contagious after the rash has disappeared.[20]
Diagnosis
If the rash has appeared, identifying this disease (making a differential
diagnosis) only requires a visual examination, since very few diseases
produce a rash in a dermatomal pattern (see map). However, herpes
simplex virus (HSV) can occasionally produce a rash in such a pattern.
The Tsanck smear is helpful for diagnosing acute infection with a
herpes virus, but does not distinguish between HSV and VZV.[31]
When the rash is absent (early or late in the disease, or in the case of
zoster sine herpete), herpes zoster can be difficult to diagnose.[32]
Apart from the rash, most symptoms can occur also in other conditions.
Herpes zoster on the chest
Herpes zoster
31
Laboratory tests are available to diagnose herpes zoster. The most popular test detects VZV-specific IgM antibody in
blood; this only appears during chickenpox or herpes zoster and not while the virus is dormant.[33] In larger
laboratories, lymph collected from a blister is tested by the polymerase chain reaction for VZV DNA, or examined
with an electron microscope for virus particles.[34]
In a recent study, samples of lesions on the skin, eyes, and lung from 182 patients with presumed herpes simplex or
herpes zoster were tested with real-time PCR or with viral culture. In this comparison, viral culture detected VZV
with only a 14.3% sensitivity, although the test was highly specific (specificity=100%). By comparison, real-time
PCR resulted in 100% sensitivity and specificity. Overall testing for herpes simplex and herpes zoster using PCR
showed a 60.4% improvement over viral culture.[35]
Prevention
A live vaccine for VZV exists, marketed as Zostavax.[36] In a 2005 study of 38,000 older adults it prevented half the
cases of herpes zoster and reduced the number of cases of postherpetic neuralgia by two-thirds.[37] A 2007 study
found that the zoster vaccine is likely to be cost-effective in the U.S., projecting an annual savings of $82 to $103
million in healthcare costs with cost-effectiveness ratios ranging from $16,229 to $27,609 per quality-adjusted life
year gained.[38] In October 2007 the vaccine was officially recommended in the U.S. for healthy adults aged 60 and
over.[36] [39] As of October 2008, a controlled study is underway to evaluate the effectiveness on those aged
50–59.[40] Adults also receive an immune boost from contact with children infected with varicella (chicken pox), a
boosting method that prevents about a quarter of herpes zoster cases among unvaccinated adults, but which is
becoming less common in the U.S. now that children are routinely vaccinated against varicella.[17] [41]
In the United Kingdom and other parts of Europe, population-based immunization is not practised. The rationale is
that until the entire population could be immunized adults who have previously contracted VZV would instead
derive benefit from occasional exposure to VZV (from children), which serves as a booster to their immunity to the
virus, and may reduce the risk of shingles later on in life.[42] The UK Health Protection Agency states that, while the
vaccine is licensed in the UK, there are no plans to introduce it into the routine childhood immunization scheme,
although it may be offered to healthcare workers who have no immunity to VZV.[43]
A 2006 study of 243 cases and 483 matched controls found that fresh fruit is associated with a reduced risk of
developing shingles: people who consumed less than one serving of fruit a day had a risk three times as great as
those who consumed more than three servings, after adjusting for other factors such as total energy intake. For those
aged 60 or more, vitamins and vegetable intake had a similar association.[44]
Treatment
The aims of treatment are to limit the severity and duration of pain,
shorten the duration of a shingles episode, and reduce complications.
Symptomatic treatment is often needed for the complication of
postherpetic neuralgia.[45] However, a study on untreated herpes zoster
shows that pain once the rash has cleared (post herpetic neuralgia) is
very rare in people under 50 and wears off in time; in older people the
pain wore off more slowly, but even in people over 70, 85% were pain
free one year after their shingles outbreak.[46]
Herpes zoster on lower back
Analgesics
Herpes zoster
People with mild to moderate pain can be treated with over-the-counter analgesics. Topical lotions containing
calamine can be used on the rash or blisters and may be soothing. Occasionally, severe pain may require an opioid
medication, such as morphine. Once the lesions have crusted over, capsaicin cream (Zostrix) can be used. Topical
lidocaine and nerve blocks may also reduce pain.[47] Administering gabapentin along with antivirals may offer relief
of postherpetic neuralgia.[45]
Antivirals
Antiviral drugs inhibit VZV replication and reduce the severity and duration of herpes zoster with minimal side
effects, but do not reliably prevent postherpetic neuralgia. Of these drugs, acyclovir has been the standard treatment,
but the new drugs valaciclovir and famciclovir demonstrate similar or superior efficacy and good safety and
tolerability.[45] The drugs are used both as prophylaxis (for example in AIDS patients) and as therapy during the
acute phase. Antiviral treatment is recommended for all immunocompetent individuals with herpes zoster over 50
years old, preferably given within 72 hours of the appearance of the rash.[48] Complications in immunocompromised
individuals with herpes zoster may be reduced with intravenous acyclovir. In people who are at a high risk for
repeated attacks of shingles, five daily oral doses of acyclovir are usually effective.[10]
Steroids
Orally administered corticosteroids are frequently used in treatment of the infection, despite clinical trials of this
treatment being unconvincing. Nevertheless, one trial studying immunocompetent patients older than 50 years of age
with localized herpes zoster, suggested that administration of prednisone with aciclovir improved healing time and
quality of life.[49] Upon one-month evaluation, aciclovir with prednisone increased the likelihood of crusting and
healing of lesions by about twofold, when compared to placebo. This trial also evaluated the effects of this drug
combination on quality of life at one month, showing that patients had less pain, and were more likely to stop the use
of analgesic agents, return to usual activities and have uninterrupted sleep. However, when comparing cessation of
herpes zoster-associated pain or post herpetic neuralgia, there was no difference between aciclovir plus prednisone
and simply aciclovir alone. Because of the risks of corticosteroid treatment, it is recommended that this combination
of drugs only be used in people more than 50 years of age, due to their greater risk of postherpetic neuralgia.[49]
Herpes zoster ophthalmicus
Treatment for herpes zoster ophthalmicus is similar to standard
treatment for herpes zoster at other sites. A recent trial comparing
aciclovir with its prodrug, valaciclovir, demonstrated similar efficacies
in treating this form of the disease.[50] The significant advantage of
valciclovir over aciclovir is its dosing of only 3 times/day (compared
with aciclovir's 5 times/day dosing), which could make it more
convenient for patients and improve adherence with therapy.[51]
Prognosis
The rash and pain usually subside within three to five weeks, but about
Herpes zoster ophthalmicus
one in five patients develops a painful condition called postherpetic
neuralgia, which is often difficult to manage. In some patients, herpes
zoster can reactivate presenting as zoster sine herpete: pain radiating along the path of a single spinal nerve (a
dermatomal distribution), but without an accompanying rash. This condition may involve complications that affect
several levels of the nervous system and cause multiple cranial neuropathies, polyneuritis, myelitis, or aseptic
meningitis. Other serious effects that may occur in some cases include partial facial paralysis (usually temporary),
32
Herpes zoster
ear damage, or encephalitis.[10] During pregnancy, first infections with VZV, causing chickenpox, may lead to
infection of the fetus and complications in the newborn, but chronic infection or reactivation in shingles are not
associated with fetal infection.[52] [53]
There is a slightly increased risk of developing cancer after a herpes zoster infection. However, the mechanism is
unclear and mortality from cancer did not appear to increase as a direct result of the presence of the virus.[54] Instead,
the increased risk may result from the immune suppression that allows the reactivation of the virus.[55]
Although herpes zoster typically resolves within 2 weeks, certain complications may arise:
• Secondary bacterial infection
• Motor involvement - incl. weakness especially in "motor herpes zoster"
• Eye involvement - trigeminal nerve involvement (as seen in herpes ophthalmicus) should be treated early and
aggressively as it may lead to blindness. Involvement of the tip of the nose in the zoster rash is a strong predictor
of herpes ophthalmicus.[56]
• Postherpetic neuralgia - a condition of chronic pain following herpes zoster
Epidemiology
Varicella zoster virus has a high level of infectivity and is prevalent
worldwide,[57] and has a very stable prevalence from generation to
generation.[58] VZV is a benign disease in a healthy child in developed
countries. However, varicella can be lethal to individuals who are
infected later in life or who have low immunity. The number of people
in this high-risk group has increased, due to the HIV epidemic and the
increase in immunosuppressive therapies.[59] Infections of varicella in
institutions such as hospitals are also a significant problem, especially
in hospitals that care for these high-risk populations.[60]
In general, herpes zoster has no seasonal incidence and does not occur
in epidemics.[28] In temperate zones chickenpox is a disease of
Electron micrograph of Varicella zoster virus.
children, with most cases occurring during the winter and spring, most
Approx. 150,000-fold magnification.
likely due to school contact; there is no evidence for regular epidemics.
In the tropics chickenpox typically occurs among older people.[61]
Incidence is highest in people who are over age 55, as well as in immunocompromised patients regardless of age
group, and in individuals undergoing psychological stress. Non-whites may be at lower risk; it is unclear whether the
risk is increased in females. Other potential risk factors include mechanical trauma, genetic susceptibility, and
exposure to immunotoxins.[28]
The incidence rate of herpes zoster ranges from 1.2 to 3.4 per 1,000 person-years among healthy individuals,
increasing to 3.9–11.8 per 1,000 person‐years among those older than 65 years.[14] Similar incidence rates have been
observed worldwide.[14] [16] Herpes zoster develops in an estimated 500,000 Americans each year.[62] Multiple
studies and surveillance data, at least when viewed superficially, demonstrate no consistent trends in incidence in the
U.S. since the chickenpox vaccination program began in 1995.[63] However, upon closer inspection, the two studies
that showed no increase in shingles incidence were conducted among populations where varicella vaccination was
not as yet widespread in the community.[64] [65] A recent study by Patel et al. concluded that since the introduction of
the chickenpox vaccine, hospitalization costs for complications of shingles have increased by more than $700
million annually for those over 60 years.[66] Another study by Yih et al. reported that as varicella vaccine coverage in
children increased, the incidence of varicella decreased and the occurrence of shinges among adults increased
90%.[67] The results of a further study by Yawn et al. showed a 28% increase in shingles incidence from 1996 to
2001.[68] Additionally, there was a statistically significant increase in adult shingles cases reported to the Antelope
33
Herpes zoster
Valley Varicella Active Surviellance Project (VASP) from 2000 to 2003. The 56.1% increase from 237 cases in
2000 to 370 cases in 2002 yields a rate ratio of 1.4 (95% C.I. 1.2–1.7). Increases in cases of shingles reported to
VASP occurred in every age category (except 70+) from 2000 to 2001. VASP also reported verified cases of
shingles among adults aged 50 years and older increased 27.5% from 2006 to 2007. (Annual Summary, 2001, 2002,
2003, 2006, 2007 Antelope Valley Varicella Active Surveillance Project, Los Angeles County Department of Health
Services; Centers for Disease Control and Prevention (CDC) Cooperative Agreement No. U66/CCU911165-10;
Mascola L, et al.) It is likely that incidence rate will change in the future, due to the aging of the population, changes
in therapy for malignant and autoimmune diseases, and changes in chickenpox vaccination rates; a wide adoption of
zoster vaccination could dramatically reduce the incidence rate.[14]
In one study, it was estimated that 26% of patients who contract herpes zoster eventually present with complications.
Postherpetic neuralgia arises in approximately 20% of patients.[69] A study of 1994 California data found
hospitalization rates of 2.1 per 100,000 person-years, rising to 9.3 per 100,000 person-years for ages 60 and up.[70]
An earlier Connecticut study found a higher hospitalization rate; the difference may be due to the prevalence of HIV
in the earlier study, or to the introduction of antivirals in California before 1994.[71]
A 2008 study revealed that people with close relatives who have had shingles are twice as likely to develop it
themselves. The study speculates that there are genetic factors in who is more susceptible to VZV.[72]
History
Herpes zoster has a long recorded history, although historical accounts fail to distinguish the blistering caused by
VZV and those caused by smallpox,[25] ergotism, and erysipelas. It was only in the late eighteenth century that
William Heberden established a way to differentiate between herpes zoster and smallpox,[73] and only in the late
nineteenth century that herpes zoster was differentiated from erysipelas. In 1831, Richard Bright hypothesized that
the disease arose from the dorsal root ganglion, and this was confirmed in an 1861 paper by Felix von
Bärunsprung.[74]
The first indications that chickenpox and herpes zoster were caused by the same virus were noticed at the beginning
of the 20th century. Physicians began to report that cases of herpes zoster were often followed by chickenpox in the
younger people who lived with the shingles patients. The idea of an association between the two diseases gained
strength when it was shown that lymph from a sufferer of herpes zoster could induce chickenpox in young
volunteers. This was finally proved by the first isolation of the virus in cell cultures, by the Nobel laureate Thomas
Huckle Weller, in 1953.[75]
Until the 1940s, the disease was considered benign, and serious complications were thought to be very rare.[76]
However, by 1942, it was recognized that herpes zoster was a more serious disease in adults than in children, and
that it increased in frequency with advancing age. Further studies during the 1950s on immunosuppressed
individuals showed that the disease was not as benign as once thought, and the search for various therapeutic and
preventive measures began.[60] By the mid-1960s, several studies identified the gradual reduction in cellular
immunity in old age, observing that in a cohort of 1,000 people who lived to the age of 85, approximately 500 (i.e.,
50%) would have at least one attack of herpes zoster, and 10 (i.e., 1%) would have at least two attacks.[77]
In historical shingles studies, shingles incidence generally increased with age. However, in his 1965 paper, Dr.
Hope-Simpson was first to suggest, “The peculiar age distribution of zoster may in part reflect the frequency with
which the different age groups encounter cases of varicella and because of the ensuing boost to their antibody
protection have their attacks of zoster postponed.” Lending support to this hypothesis that contact with children with
chickenpox boosts adult cell-mediated immunity to help postpone or suppress shingles, is the study by Thomas et al.
which reported that adults in households with children, had lower rates of shingles than households without
children.[78] Also, the study by Terada et al. indicated that pediatricians reflected incidence rates from 1/2 to 1/8 that
of the general population their age.[79]
34
Herpes zoster
See also
• Disseminated herpes zoster
• Inflammatory skin lesions following zoster infection
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assay for the diagnosis of herpes simplex and varicella-zoster virus infections". J Clin Virol. 30 (1): 39–44. doi:10.1016/j.jcv.2003.08.006.
PMID 15072752.
[36] Harpaz R, Ortega-Sanchez IR, Seward JF (June 6, 2008). "Prevention of herpes zoster: recommendations of the Advisory Committee on
Immunization Practices (ACIP)" (http:/ / www. cdc. gov/ mmwr/ preview/ mmwrhtml/ rr5705a1. htm). MMWR Recomm Rep 57 (RR-5):
1–30; quiz CE2–4. PMID 18528318. . Retrieved 2010-01-04.
[37] Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD et al. (2005). "A vaccine to prevent herpes zoster and postherpetic
neuralgia in older adults". N. Engl. J. Med. 253 (22): 2271–84. doi:10.1056/NEJMoa051016. PMID 15930418.
[38] Pellissier JM, Brisson M, Levin MJ (2007). "Evaluation of the cost-effectiveness in the United States of a vaccine to prevent herpes zoster
and postherpetic neuralgia in older adults". Vaccine 25 (49): 8326–37. doi:10.1016/j.vaccine.2007.09.066. PMID 17980938.
[39] Advisory Committee on Immunization Practices (20 November 2007). "Recommended adult immunization schedule: United States, October
2007 – September 2008" (http:/ / www. annals. org/ cgi/ content/ full/ 147/ 10/ 725). Ann Intern Med 147 (10): 725–9. PMID 17947396. .
[40] A Phase IIIClinical Trial to Evaluate the Efficacy, Immunogenicity, Safety, and Tolerability of Zostavax in Subjects 50 – 59 Years of Age;
Protocol no. V211-022-00; Sponsor Marck & Co Inc.
[41] Brisson M, Gay N, Edmunds W, Andrews N (2002). "Exposure to varicella boosts immunity to herpes-zoster: implications for mass
vaccination against chickenpox". Vaccine 20 (19–20): 2500–7. doi:10.1016/S0264-410X(02)00180-9. PMID 12057605.
[42] NHS Direct (2008-02-07). "Why isn’t the chickenpox vaccine available in the UK?" (http:/ / web. archive. org/ web/ 20080423095454/ http:/
/ www. nhsdirect. nhs. uk/ articles/ article. aspx?articleId=1032). Archived from the original (http:/ / www. nhsdirect. nhs. uk/ articles/ article.
aspx?articleId=1032) on 2008-04-23. . Retrieved 2008-03-22.
[43] Health Protection Agency (2006-05-11). "Chickenpox / Varicella — General Information" (http:/ / www. hpa. org. uk/ infections/ topics_az/
chickenpox/ gen_info. htm). . Retrieved 2008-03-22.
[44] Thomas SL, Wheeler JG, Hall AJ (2006). "Micronutrient intake and the risk of herpes zoster: a case-control study" (http:/ / ije.
oxfordjournals. org/ cgi/ content/ full/ 35/ 2/ 307). Int J Epidemiol 35 (2): 307–14. doi:10.1093/ije/dyi270. PMID 16330478. .
[45] Tyring SK (2007). "Management of herpes zoster and postherpetic neuralgia". J Am Acad Dermatol 57 (6 Suppl): S136–42.
doi:10.1016/j.jaad.2007.09.016. PMID 18021865.
[46] Sigurdur Helgason et al (2000). "Prevalence of postherpetic neuralgia after a single episode of herpes zoster: prospective study with long
term follow up" (http:/ / www. bmj. com/ cgi/ content/ full/ 321/ 7264/ 794) (PDF). British Medical Journal 321 (7264): 794–6.
doi:10.1136/bmj.321.7264.794. PMID 11009518. PMC 27491. .
[47] Baron R (2004). "Post-herpetic neuralgia case study: optimizing pain control". Eur. J. Neurol 11 Suppl 1: 3–11.
doi:10.1111/j.1471-0552.2004.00794.x. PMID 15061819.
[48] Breuer J, Whitley R (2007). "Varicella zoster virus: natural history and current therapies of varicella and herpes zoster" (http:/ / www. ihmf.
org/ journal/ download/ 2 - Herpes 14. 2 suppl Breuer. pdf) (PDF). Herpes 14 (Suppl 2): 25–9. PMID 17939892. .
[49] Whitley RJ, Weiss H, Gnann JW, Tyring S, Mertz GJ, Pappas PG, Schleupner CJ, Hayden F, Wolf J, Soong SJ (1996). "Acyclovir with and
without prednisone for the treatment of herpes zoster. A randomized, placebo-controlled trial. The National Institute of Allergy and Infectious
Diseases Collaborative Antiviral Study Group". Ann. Intern. Med. 125 (5): 376–83. PMID 8702088.
[50] Colin J, Prisant O, Cochener B, Lescale O, Rolland B, Hoang-Xuan T (2000). "Comparison of the Efficacy and Safety of Valaciclovir and
Acyclovir for the Treatment of Herpes zoster Ophthalmicus". Ophthalmology 107 (8): 1507–11. doi:10.1016/S0161-6420(00)00222-0.
PMID 10919899.
[51] Osterberg L, Blaschke T (2005). "Adherence to medication". N. Engl. J. Med. 353 (5): 487–97. doi:10.1056/NEJMra050100.
PMID 16079372.
[52] Paryani SG, Arvin AM (1986). "Intrauterine infection with varicella-zoster virus after maternal varicella". N. Engl. J. Med. 314 (24):
1542–6. doi:10.1056/NEJM198606123142403. PMID 3012334.
[53] Enders G, Miller E, Cradock-Watson J, Bolley I, Ridehalgh M (1994). "Consequences of varicella and herpes zoster in pregnancy:
prospective study of 1739 cases". Lancet 343 (8912): 1548–51. doi:10.1016/S0140-6736(94)92943-2. PMID 7802767.
[54] Sørensen HT, Olsen JH, Jepsen P, Johnsen SP, Schønheyder HC, Mellemkjaer L (2004). "The risk and prognosis of cancer after
hospitalisation for herpes zoster: a population-based follow-up study" (http:/ / www. pubmedcentral. nih. gov/ articlerender.
fcgi?tool=pmcentrez& artid=2409892). Br. J. Cancer 91 (7): 1275–9. doi:10.1038/sj.bjc.6602120. PMID 15328522. PMC 2409892.
[55] Ragozzino MW, Melton LJ, Kurland LT, Chu CP, Perry HO (1982). "Risk of cancer after herpes zoster: a population-based study". N. Engl.
J. Med. 307 (7): 393–7. doi:10.1056/NEJM198208123070701. PMID 6979711.
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[56] "Herpes Zoster Ophthalmicus" (http:/ / www. merck. com/ mmpe/ sec09/ ch102/ ch102e. html). Merck Manual (Merk.com). October 2008. .
Retrieved June 2010.
[57] Apisarnthanarak A, Kitphati R, Tawatsupha P, Thongphubeth K, Apisarnthanarak P, Mundy LM (2007). "Outbreak of varicella-zoster virus
infection among Thai healthcare workers". Infect Control Hosp Epidemiol 28 (4): 430–4. doi:10.1086/512639. PMID 17385149.
[58] Abendroth A, Arvin AM (2001). "Immune evasion as a pathogenic mechanism of varicella zoster virus". Semin. Immunol. 13 (1): 27–39.
doi:10.1006/smim.2001.0293. PMID 11289797.
[59] Strangfeld A, Listing J; Herzer, P.; , et al (2009). "Risk of herpes zoster in patients with rheumatoid arthritis treated With anti–TNF-α
agents". J Am Med Assoc 301 (7): 737–744. doi:10.1001/jama.2009.146. PMID 19224750.
[60] Weller TH (1997). "Varicella-herpes zoster virus". In Evans AS, Kaslow RA. Viral Infections of Humans: Epidemiology and Control.
Plenum Press. pp. 865–92. ISBN 978-0306448553.
[61] Wharton M (1996). "The epidemiology of varicella-zoster virus infections". Infect Dis Clin North Am 10 (3): 571–81.
doi:10.1016/S0891-5520(05)70313-5. PMID 8856352.
[62] Insinga RP; Itzler, RF; Pellissier, JM; Saddier, P; Nikas, AA (2005). "The incidence of herpes zoster in a United States administrative
database" (http:/ / www. pubmedcentral. nih. gov/ articlerender. fcgi?tool=pmcentrez& artid=1490195). J Gen Intern Med 20 (6): 748–753.
doi:10.1111/j.1525-1497.2005.0150.x. PMID 16050886. PMC 1490195.
[63] Marin M, Güris D, Chaves SS, Schmid S, Seward JF (June 22, 2007). "Prevention of varicella: recommendations of the Advisory
Committee on Immunization Practices (ACIP)" (http:/ / www. cdc. gov/ mmwr/ preview/ mmwrhtml/ rr5604a1. htm). MMWR Recomm Rep
56 (RR-4): 1–40. PMID 17585291. .
[64] Jumaan AO, Yu O, Jackson LA, Bohlke K, Galil K, Seward JF (2005). "Incidence of herpes zoster, before and after
varicella-vaccination-associated decreases in the incidence of varicella, 1992–2002". J Infect Dis. 191 (12): 2002–2007. doi:10.1086/430325.
PMID 15897984.
[65] Whitley RJ (2005). "Changing dynamics of varicella-zoster virus infections in the 21st century: the impact of vaccination". J Infect Dis. 191
(12): 1999–2001. doi:10.1086/430328. PMID 15897983.
[66] Patel MS, Gebremariam A, Davis MM (2008). "Herpes zoster-related hospitalizations and expenditures before and after introduction of the
varicella vaccine in the United States". Control Hosp. Epidemiol. 29 (12): 1157–1163. doi:10.1086/591975. PMID 18999945.
[67] Yih WK, Brooks DR, Lett SM, Jumaan AO, Zhang Z. Clements KM, Seward JF (2005). "The incidence of varicella and herpes zoster in
Massachusetts as measured by the Behavioral Risk Factor Surveillance System (BRFSS) during a period of increasing varicella vaccine
coverage, 1998–2003" (http:/ / www. pubmedcentral. nih. gov/ articlerender. fcgi?tool=pmcentrez& artid=1177968). BMC Public Health 5:
68–68. doi:10.1186/1471-2458-5-68. PMID 15960856. PMC 1177968.
[68] Yawn BP, Saddier P, Wollan PC, St Sauver JL, Kurland MJ, Sy LS (2007). "A Population-Based Study of the Incidence and Complication
Rates of Herpes Zoster Before Zoster Vaccine Introduction". Mayo Clin Proc. 82 (11): 1341–1349. doi:10.4065/82.11.1341. PMID 17976353.
[69] Volpi A (2007). "Severe complications of herpes zoster" (http:/ / www. ihmf. org/ journal/ download/ 4 - Herpes 14. 2 suppl Volpi. pdf)
(PDF). Herpes 14 (Suppl 2): 35A–9A. PMID 17939894. .
[70] Coplan P, Black S, Rojas C (2001). "Incidence and hospitalization rates of varicella and herpes zoster before varicella vaccine introduction:
a baseline assessment of the shifting epidemiology of varicella disease". Pediatr Infect Dis J 20 (7): 641–5.
doi:10.1097/00006454-200107000-00002. PMID 11465834.
[71] Weaver BA (1 March 2007). "The burden of herpes zoster and postherpetic neuralgia in the United States" (http:/ / www. jaoa. org/ cgi/
content/ full/ 107/ suppl_1/ S2). J Am Osteopath Assoc 107 (3 Suppl): S2–7. PMID 17488884. .
[72] Hicks LD, Cook-Norris RH, Mendoza N, Madkan V, Arora A, Tyring SK (May 2008). "Family history as a risk factor for herpes zoster: a
case-control study". Arch Dermatol 144 (5): 603–8. doi:10.1001/archderm.144.5.603. PMID 18490586.
[73] Weller TH (2000). "Chapter 1. Historical perspective". In Arvin AM, Gershon AA. Varicella-Zoster Virus: Virology and Clinical
Management. Cambridge University Press. ISBN 0521660246.
[74] Oaklander AL (October 1999). "The pathology of shingles: Head and Campbell's 1900 monograph". Arch. Neurol. 56 (10): 1292–4.
doi:10.1001/archneur.56.10.1292. PMID 10520948.
[75] Weller TH (1953). "Serial propagation in vitro of agents producing inclusion bodies derived from varicella and herpes zoster". Proc. Soc.
Exp. Biol. Med. 83 (2): 340–6. PMID 13064265.
[76] Holt LE, McIntosh R (1936). Holt's Diseases of Infancy and Childhood. D Appleton Century Company. pp. 931–3.
[77] Hope-Simpson RE (1965). "The nature of herpes zoster; a long-term study and a new hypothesis" (http:/ / www. pubmedcentral. nih. gov/
articlerender. fcgi?tool=pmcentrez& artid=1898279). Proc R Soc Med 58: 9–20. PMID 14267505. PMC 1898279.
[78] Thomas SL, Wheeler JG, Hall AJ (2002). "Contacts with varicella or with children and protection against herpes zoster in adults: a
case-control study". Lancet 360 (9334): 678–682. doi:10.1016/S0140-6736(02)09837-9. PMID 12241874.
[79] Terada K, Hiraga Y, Kawano S, Kataoka N (1995). "Incidence of herpes zoster in pediatricians and history of reexposure to varicella-zoster
virus in patients with herpes zoster". Kansenshogaku Zasshi 69 (8): 908–912. PMID 7594784.
37
Herpes zoster
External links
• NINDS Shingles Information Page (http://www.ninds.nih.gov/disorders/shingles/shingles.htm), National
Institute of Neurological Disorders and Stroke
• Herpes zoster (http://www.dmoz.org/Health/Conditions_and_Diseases/Infectious_Diseases/Viral/Herpes/
Herpes_Zoster//) at the Open Directory Project
• Links to pictures of Shingles (Hardin MD) (http://www.lib.uiowa.edu/hardin/md/shingles.html) University
of Iowa
• Facts About The Cornea and Corneal Disease: Herpes Zoster (Shingles) (http://www.nei.nih.gov/health/
cornealdisease/index.asp#f), National Eye Institute
38
Herpes labialis
39
Herpes labialis
Herpes labialis
Herpes labialis of the lower lip. Note the blisters in a group marked by an arrow.
[1]
ICD-10
B 00.1
ICD-9
054.9
MeSH
D006560
[2]
[3]
Herpes labialis or "orolabial herpes" [4] :368 is an infection of the lip by herpes simplex virus. An outbreak typically
causes small blisters or sores on or around the mouth commonly known as cold sores or fever blisters. The sores
typically heal within 2–3 weeks, but the herpes virus remains dormant in the facial nerves, following orofacial
infection, periodically reactivating (in symptomatic people) to create sores in the same area of the mouth or face at
the site of the original infection.
80% of adults in the United States are carriers of the virus that causes cold sores, and more than 50 million adults in
the U.S. develop symptomatic episodes every year.[5] Cold sore has a rate of frequency that varies from rare episodes
to 12 or more recurrences per year. Most sufferers experience one to three attacks annually. The frequency and
severity of outbreaks generally decreases over time.[6]
The virus is transmitted from cold sores and also when there are no symptoms, as it can make copies of itself on the
skin in the absence of a blister. This phenomenon is called "asymptomatic shedding". 80%–90% of adults under age
50 with HSV-1 caught it from someone close to them.[7]
Definitions
In medical contexts, "labia" is a general term for "lip"; "herpes labialis" does not refer to the labia of the genitals,
though the etymology is the same. When the viral infection affects both face and mouth, the broader term "orofacial
herpes" is used to describe the condition, whereas the term "herpetic stomatitis" is used to specifically describe
infection of the mouth; "stomatitis" is derived from the Greek word stoma that means "mouth".
Signs and symptoms
Herpes infections often show no symptoms;[8] when symptoms do appear they typically resolve within two weeks.[9]
The main symptom of oral infection is inflammation of the mucosa of the cheek and gums—known as acute herpetic
gingivostomatitis -- which occurs within 5–10 days of infection. Other symptoms may also develop, including
headache, nausea, dizziness and painful ulcers—sometimes confused with canker sores—fever, and sore throat.[9]
Herpes labialis
Primary HSV infection in adolescents frequently manifests as severe pharyngitis with lesions developing on the
cheek and gums. Some individuals develop difficulty in swallowing (dysphagia) and swollen lymph nodes
(lymphadenopathy).[9] Primary HSV infections in adults often results in pharyngitis similar to that observed in
glandular fever (infectious mononucleosis), but gingivostomatitis is less likely.
Recurrent oral infection is more common with HSV-1 infections than with HSV-2. Symptoms typically progress in a
series of eight stages:
1. Latent (weeks to months incident-free): The remission period; After initial infection, the viruses move to sensory
nerve ganglia (Trigeminal ganglion),[10] where they reside as life-long, latent viruses. Asymptomatic shedding of
contagious virus cells can occur during this stage.
2. Prodromal (day 0-1): Symptoms often precede a recurrence. Symptoms typically begin with tingling (itching) and
reddening of the skin around the infected site. This stage can last from a few days to a few hours preceding the
physical manifestation of an infection and is the best time to start treatment.
3. Inflammation (day 1): Virus begins reproducing and infecting cells at the end of the nerve. The healthy cells react
to the invasion with swelling and redness displayed as symptoms of infection.
4. Pre-sore (day 2-3): This stage is defined by the appearance of tiny, hard, inflamed papules and vesicles that may
itch and are painfully sensitive to touch. In time, these fluid-filled blisters form a cluster on the lip (labial) tissue,
the area between the lip and skin (vermilion border), and can occur on the nose, chin, and cheeks.
5. Open lesion (day 4): This is the most painful and contagious of the stages. All the tiny vesicles break open and
merge to create one big, open, weeping ulcer. Fluids are slowly discharged from blood vessels and inflamed
tissue. This watery discharge is teeming with active viral particles and is highly contagious. Depending on the
severity, one may develop a fever and swollen lymph glands under the jaw.[11]
6. Crusting (day 5-8): A honey/golden crust starts to form from the syrupy exudate. This yellowish or brown crust
or scab is not made of active virus but from blood serum containing useful proteins such as albumin and
globulins. This appears as the healing process begins and should not be scraped or picked at. The sore is still
painful at this stage, but, more painful, however, is the constant cracking of the scab as one moves or stretches
their lips, as in smiling or eating. Virus filled fluid will still ooze out of the sore through any cracks.
7. Healing (day 9-14): New skin begins to form underneath the scab as the virus retreats into latency. A series of
scabs will form over the sore (Called Meier Complex), each one smaller than the last. During this phase irritation,
itching, and some pain are common.
8. Post-scab (2–14 days): A reddish area may linger at the site of viral infection as the destroyed cells are
regenerated. Virus shedding can still occur during this stage.[12]
The recurrent infection is thus often called herpes simplex labialis. Rare reinfections occur inside the mouth
(intraoral HSV stomatitis) affecting the gums, alveolar ridge, hard palate, and the back of the tongue, possibly
accompanied by herpes labialis.[9]
Causes
Herpes labialis infection occurs when the herpes simplex virus comes into contact with oral mucosal tissue or
abraded skin of the mouth. Infection by the type 1 strain of herpes simplex virus (HSV-1) is most common; however,
cases of oral infection by the type 2 strain are increasing.[9]
Cold sores are the result of the virus's reactivating in the body. Once HSV-1 has entered the body, it never leaves.
The virus moves from the mouth to quietly reside (“remain latent”) in the central nervous system. In approximately
one-third of people, the virus can “wake up” or reactivate to cause disease. When reactivation occurs, the virus
travels down the nerves to the skin where it may cause blisters (cold sores) around the lips, in the mouth or, in about
10% of cases, on the nose, chin, or cheeks. Cold sore outbreaks may be influenced by stress, menstruation, sunlight,
sunburn, fever, or local skin trauma. Surgical procedures such as dental or neural surgery, lip tattooing, or
dermabrasion are also common triggers. HSV-1 can in rare cases be transmitted to newborn babies by family
40
Herpes labialis
members or hospital staff who have cold sores; this can cause a severe disease called Neonatal herpes simplex.
People can transfer the virus from their cold sores to other areas of the body, such as the eye, skin, or fingers; this is
called “autoinoculation." Eye infection, in the form of conjunctivitis or keratitis, can happen when the eyes are
rubbed after touching the lesion. Finger infection (herpetic whitlow) can occur when a child with cold sores or
primary HSV-1 infection sucks his/her fingers.
Treatment
Docosanol, a saturated fatty alcohol, is a safe and effective FDA approved treatment for herpes labialis in adults with
properly functioning immune systems that is comparable in effectiveness to prescription antiviral agents applied
topically; due to its mechanism of action, there is little risk of drug resistance.[13] The duration of symptoms can be
reduced by a small amount if a antiviral, anaesthetic or non-treatment cream (such as zinc oxide or zinc sulfate) is
applied promptly.[8] Effective antiviral medications include acyclovir[14] and penciclovir, and these can speed
healing by as much as 10%.[15] Famciclovir or valaciclovir, taken in pill form, can be effective using a single day,
high-dose application and is more cost effective and convenient than the traditional treatment of lower doses for 5–7
days.[16]
Lysine has been suggested as a treatment for herpes labialis based on in vitro studies, but the evidence is equivocal in
humans.[17]
Prevention
Avoiding touching an active outbreak site, washing hands frequently while the outbreak is occurring, not sharing
items that come in contact with the mouth, and not coming into contact with others by avoiding kissing, oral sex,
contact sports can reduce the likelihood of the infection being spread to others.[6]
Because the onset of an infection is difficult to predict, last a short period of time and heal rapidly, it is difficult to
conduct research on cold sores. Though famciclovir improves lesion healing time, it is not effecitve in preventing
lesions; valaciclovir and a mixture of acyclovir and hydrocortisone are similarly useful in treating outbreaks but may
also help prevent them.[15]
References
[1]
[2]
[3]
[4]
http:/ / www. icd9data. com/ getICD9Code. ashx?icd9=054. 9
James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier.
ISBN 0-7216-2921-0.
[5] FDA Approves Non-Prescription Cold Sore Topical Treatment Docosonal 10% (http:/ / www. pslgroup. com/ dg/ 1dadee. htm)
[6] http:/ / www. uhs. wisc. edu/ display_story. jsp?id=674& cat_id=38
[7] http:/ / www. herpesguide. ca/ articles/ facts_cold_sores. html
[8] Opstelten W, Neven AK, Eekhof J (December 2008). "Treatment and prevention of herpes labialis" (http:/ / www. cfp. ca/ cgi/ content/ full/
54/ 12/ 1683). Can Fam Physician 54 (12): 1683–7. PMID 19074705. PMC 2602638. .
[9] Bruce AJ, Rogers RS (2004). "Oral manifestations of sexually transmitted diseases". Clin. Dermatol. 22 (6): 520–7.
doi:10.1016/j.clindermatol.2004.07.005. PMID 15596324.
[10] http:/ / www. cfp. ca/ cgi/ content/ full/ 54/ 12/ 1683
[11] http:/ / www. aafp. org/ afp/ 20000315/ 1697. html
[12] http:/ / dentalresource. org/ topic52herpes. htm
[13] Treister, N. S.; Woo, S. B. (2010). "Topicaln-docosanol for management of recurrent herpes labialis". Expert Opinion on Pharmacotherapy
11 (5): 853. doi:10.1517/14656561003691847. PMID 20210688.
[14] Raborn GW, Chan KS, Grace M (January 2004). "Treatment modalities and medication recommended by health care professionals for
treating recurrent herpes labialis" (http:/ / jada. ada. org/ cgi/ pmidlookup?view=long& pmid=14959874). J Am Dent Assoc 135 (1): 48–54.
PMID 14959874. .
41
Herpes labialis
[15] Harmenberg, J.; Öberg, B.; Spruance, S. (2010). "Prevention of Ulcerative Lesions by Episodic Treatment of Recurrent Herpes Labialis: A
Literature Review". Acta Dermato Venereologica 90 (2): 122. doi:10.2340/00015555-0806. PMID 20169294.
[16] Gilbert, SC (2007). "Management and prevention of recurrent herpes labialis in immunocompetent patients". Herpes : the journal of the
IHMF 14 (3): 56–61. PMID 18371287.
[17] Robb-Nicholson, C (2007-01-03). "Does lysine prevent cold sores?" (http:/ / harvardpartnersinternational. staywellsolutionsonline. com/
HealthNewsLetters/ 69,W0307e). Harvard Health Newsletters. Harvard Women's Health Watch. . Retrieved 2010-08-31.
42
Rubella
43
Rubella
Rubella
[1]
ICD-10
B 06.
ICD-9
056
DiseasesDB
11719
[2]
[3]
eMedicine
emerg/388
MeSH
D012409
[5]
peds/2025
[6]
derm/259
[7]
[8]
Rubella, commonly known as German measles, is a disease caused by the rubella virus. The name "rubella" is
derived from the Latin, meaning little red. Rubella is also known as German measles because the disease was first
described by German physicians in the mid-eighteenth century. This disease is often mild and attacks often pass
unnoticed. The disease can last one to three days. Children recover more quickly than adults. Infection of the mother
by Rubella virus during pregnancy can be serious; if the mother is infected within the first 20 weeks of pregnancy,
the child may be born with congenital rubella syndrome (CRS), which entails a range of serious incurable illnesses.
Spontaneous abortion occurs in up to 20% of cases.[9]
Rubella is a common childhood infection usually with minimal systemic upset although transient arthropathy may
occur in adults. Serious complications are very rare. Apart from the effects of transplacental infection on the
developing fetus, rubella is a relatively trivial infection.
Acquired (i.e. not congenital) rubella is transmitted via airborne droplet emission from the upper respiratory tract of
active cases. The virus may also be present in the urine, feces and on the skin. There is no carrier state: the reservoir
exists entirely in active human cases. The disease has an incubation period of 2 to 3 weeks.[10]
In most people the virus is rapidly eliminated. However, it may persist for some months post partum in infants
surviving the CRS. These children are a significant source of infection to other infants and, more importantly, to
pregnant female contacts.
Rubella
The name rubella is sometimes confused with rubeola, an alternative name for measles in English-speaking
countries; the diseases are unrelated.[11] [12] In some other European languages, rubella and rubeola are synonyms,
and rubeola is not an alternative name for measles.[13]
Signs and symptoms
After an incubation period of 14–21 days, German measles causes symptoms that are similar to the flu. The primary
symptom of rubella virus infection is the appearance of a rash (exanthem) on the face which spreads to the trunk and
limbs and usually fades after three days (that is why it is often referred to as three-day measles). The facial rash
usually clears as it spreads to other parts of the body. Other symptoms include low grade fever, swollen glands (sub
occipital & posterior cervical lymphadenopathy), joint pains, headache and conjunctivitis.[14] The swollen glands or
lymph nodes can persist for up to a week and the fever rarely rises above 38 oC (100.4 oF). The rash of German
measles is typically pink or light red. The rash causes itching and often lasts for about three days. The rash
disappears after a few days with no staining or peeling of the skin. When the rash clears up, the patient may notice
that his skin sheds in very small flakes wherever the rash covered it. Forchheimer's sign occurs in 20% of cases, and
is characterized by small, red papules on the area of the soft palate.
Rubella can affect anyone of any age and is generally a mild disease, rare in infants or those over the age of 40. The
older the person is the more severe the symptoms are likely to be. Up to two-thirds of older girls or women
experience joint pain or arthritic type symptoms with rubella. The virus is contracted through the respiratory tract
and has an incubation period of 2 to 3 weeks. During this incubation period, the patient is contagious typically for
about one week before he develops a rash and for about one week thereafter.
Congenital rubella syndrome
Rubella can cause congenital rubella syndrome in the newly born. The syndrome (CRS) follows intrauterine
infection by Rubella virus and comprises cardiac, cerebral, ophthalmic and auditory defects.[15] It may also cause
prematurity, low birth weight, and neonatal thrombocytopenia, anaemia and hepatitis. The risk of major defects or
organogenesis is highest for infection in the first trimester. CRS is the main reason a vaccine for rubella was
developed. Many mothers who contract rubella within the first critical trimester either have a miscarriage or a still
born baby. If the baby survives the infection, it can be born with severe heart disorders (PDA being the most
common), blindness, deafness, or other life threatening organ disorders. The skin manifestations are called
"blueberry muffin lesions." [16]
Cause
The disease is caused by Rubella virus, a togavirus that is enveloped and has a single-stranded RNA genome.[17] The
virus is transmitted by the respiratory route and replicates in the nasopharynx and lymph nodes. The virus is found in
the blood 5 to 7 days after infection and spreads throughout the body. The virus has teratogenic properties and is
capable of crossing the placenta and infecting the fetus where it stops cells from developing or destroys them.[14]
Increased susceptibility to infection might be inherited as there is some indication that HLA-A1 or factors
surrounding A1 on extended haplotypes are involved in virus infection or non-resolution of the disease.[18] [19]
44
Rubella
Diagnosis
Rubella virus specific IgM antibodies are present in people recently infected by Rubella virus but these antibodies
can persist for over a year and a positive test result needs to be interpreted with caution.[20] The presence of these
antibodies along with, or a short time after, the characteristic rash confirms the diagnosis.[21]
Prevention
Rubella infections are prevented by active immunisation programs using live, disabled virus vaccines. Two live
attenuated virus vaccines, RA 27/3 and Cendehill strains, were effective in the prevention of adult disease. However
their use in prepubertile females did not produce a significant fall in the overall incidence rate of CRS in the UK.
Reductions were only achieved by immunisation of all children.
The vaccine is now usually given as part of the MMR vaccine. The WHO recommends the first dose is given at 12 to
18 months of age with a second dose at 36 months. Pregnant women are usually tested for immunity to rubella early
on. Women found to be susceptible are not vaccinated until after the baby is born because the vaccine contains live
virus.[22]
The immunisation program has been quite successful. Cuba declared the disease eliminated in the 1990s, and in 2004
the Centers for Disease Control and Prevention announced that both the congenital and acquired forms of rubella had
been eliminated from the United States.[23] [24]
Treatment
There is no specific treatment for Rubella; however, management is a matter of responding to symptoms to diminish
discomfort. Treatment of newly born babies is focused on management of the complications. Congenital heart
defects and cataracts can be corrected by direct surgery.[25] Management for ocular CRS is similar to that for
age-related macular degeneration, including counseling, regular monitoring, and the provision of low vision devices,
if required.[26]
Prognosis
Rubella infection of children and adults is usually mild, self-limiting and often asymptomatic. The prognosis in
children born with CRS is poor.[27]
Epidemiology
Rubella is a disease that occurs worldwide. The virus tends to peak during the spring in countries with temperate
climates. Before the vaccine to rubella was introduced in 1969, widespread outbreaks usually occurred every 6–9
years in the United States and 3–5 years in Europe, mostly affecting children in the 5-9 year old age group.[28] Since
the introduction of vaccine, occurrences have become rare in those countries with high uptake rates.
Vaccination has interrupted the transmission of rubella in the Americas: no endemic case has been observed since
February 2009.[29] Since the virus can always be reintroduced from other continents, the population still need to
remain vaccinated to keep the western hemisphere free of rubella. During the epidemic in the US between
1962-1965, Rubella virus infections during pregnancy were estimated to have caused 30,000 still births and 20,000
children to be born impaired or disabled as a result of CRS.[30] [31] Universal immunisation producing a high level of
herd immunity is important in the control of epidemics of rubella.[32]
In the UK, there remains a large population of men susceptible to rubella who have not been vaccinated. Outbreaks
of rubella occurred amongst many young men in the UK in 1993 and in 1996 the infection was transmitted to
pregnant women, many of whom were immigrants and were susceptible. Outbreaks still arise, usually in developing
countries where the vaccine is not as accessible.[33]
45
Rubella
History
Rubella was first described in the mid-eighteenth century. Friedrich Hoffmann made the first clinical description of
rubella in 1740,[34] which was confirmed by de Bergen in 1752 and Orlow in 1758.[35]
In 1814, George de Maton first suggested that it be considered a disease distinct from both measles and scarlet fever.
All these physicians were German, and the disease was known as Rötheln (from the German name Röteln), hence the
common name of "German measles".[36] Henry Veale, an English Royal Artillery surgeon, described an outbreak in
India. He coined the name "rubella" (from the Latin, meaning "little red") in 1866.[34] [37] [38] [39]
It was formally recognised as an individual entity in 1881, at the International Congress of Medicine in London.[40]
In 1914, Alfred Fabian Hess theorised that rubella was caused by a virus, based on work with monkeys.[41] In 1938,
Hiro and Tosaka confirmed this by passing the disease to children using filtered nasal washings from acute cases.[38]
In 1940, there was a widespread epidemic of rubella in Australia. Subsequently, ophthalmologist Norman McAllister
Gregg found 78 cases of congenital cataracts in infants and 68 of them were born to mothers who had caught rubella
in early pregnancy.[37] [38] Gregg published an account, Congenital Cataract Following German Measles in the
Mother, in 1941. He described a variety of problems now known as congenital rubella syndrome (CRS) and noticed
that the earlier the mother was infected, the worse the damage was. The virus was isolated in tissue culture in 1962
by two separate groups led by physicians Parkman and Weller.[37] [39]
There was a pandemic of rubella between 1962 and 1965, starting in Europe and spreading to the United States.[39]
In the years 1964-65, the United States had an estimated 12.5 million rubella cases. This led to 11,000 miscarriages
or therapeutic abortions and 20,000 cases of congenital rubella syndrome. Of these, 2,100 died as neonates, 12,000
were deaf, 3,580 were blind and 1,800 were mentally retarded. In New York alone, CRS affected 1% of all births [42]
In 1969 a live attenuated virus vaccine was licensed.[38] In the early 1970s, a triple vaccine containing attenuated
measles, mumps and rubella (MMR) viruses was introduced.[39]
References
[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
http:/ / www. emedicine. com/ peds/ topic2025. htm#
http:/ / www. emedicine. com/ derm/ topic259. htm#
Siegel M, Fuerst HT, Guinee VF (1971). "Rubella epidemicity and embryopathy. Results of a long-term prospective study". Am. J. Dis.
Child. 121 (6): 469–73. PMID 5581012.
[10] Richardson M, Elliman D, Maguire H, Simpson J, Nicoll A (2001). "Evidence base of incubation periods, periods of infectiousness and
exclusion policies for the control of communicable diseases in schools and preschools" (http:/ / meta. wkhealth. com/ pt/ pt-core/
template-journal/ lwwgateway/ media/ landingpage. htm?issn=0891-3668& volume=20& issue=4& spage=380). Pediatr. Infect. Dis. J. 20 (4):
380–91. doi:10.1097/00006454-200104000-00004. PMID 11332662. .
[11] Merriam-webster:Rubeola (http:/ / www. merriam-webster. com/ dictionary/ rubeola) Accessed 2009-09-20.
[12] T. E. C. Jr. Letters to the editor (http:/ / pediatrics. aappublications. org/ cgi/ content/ abstract/ 49/ 1/ 150-a) Pediatrics Vol. 49 No. 1 January
1972, pp. 150-151.
[13] Webster's Online Dictionary: German measles (http:/ / www. websters-online-dictionary. org/ Ge/ German_measles. html) Accessed
2009-09-20
[14] Edlich RF, Winters KL, Long WB, Gubler KD (2005). "Rubella and congenital rubella (German measles)". J Long Term Eff Med Implants
15 (3): 319–28. doi:10.1615/JLongTermEffMedImplants.v15.i3.80. PMID 16022642.
[15] Atreya CD, Mohan KV, Kulkarni S (2004). "Rubella virus and birth defects: molecular insights into the viral teratogenesis at the cellular
level". Birth Defects Res. Part a Clin. Mol. Teratol. 70 (7): 431–7. doi:10.1002/bdra.20045. PMID 15259032.
[16] De Santis M, Cavaliere AF, Straface G, Caruso A (2006). "Rubella infection in pregnancy" (http:/ / linkinghub. elsevier. com/ retrieve/ pii/
S0890-6238(05)00073-0). Reprod. Toxicol. 21 (4): 390–8. doi:10.1016/j.reprotox.2005.01.014. PMID 16580940. .
[17] Frey TK (1994). "Molecular biology of rubella virus". Adv. Virus Res. 44: 69–160. doi:10.1016/S0065-3527(08)60328-0. PMID 7817880.
46
Rubella
[18] Forrest JM, Turnbull FM, Sholler GF, et al. (2002). "Gregg's congenital rubella patients 60 years later" (http:/ / www. mja. com. au/ public/
issues/ 177_11_021202/ for10634_fm. html). Med. J. Aust. 177 (11-12): 664–7. PMID 12463994. .
[19] Honeyman MC, Dorman DC, Menser MA, Forrest JM, Guinan JJ, Clark P (February 1975). "HL-A antigens in congenital rubella and the
role of antigens 1 and 8 in the epidemiology of natural rubella". Tissue Antigens 5 (1): 12–8. doi:10.1111/j.1399-0039.1975.tb00520.x.
PMID 1138435.
[20] Best JM (2007). "Rubella" (http:/ / linkinghub. elsevier. com/ retrieve/ pii/ S1744-165X(07)00018-2). Semin Fetal Neonatal Med 12 (3):
182–92. doi:10.1016/j.siny.2007.01.017. PMID 17337363. .
[21] Stegmann BJ, Carey JC (2002). "TORCH Infections. Toxoplasmosis, Other (syphilis, varicella-zoster, parvovirus B19), Rubella,
Cytomegalovirus (CMV), and Herpes infections". Curr Women's Health Rep 2 (4): 253–8. PMID 12150751.
[22] Watson JC, Hadler SC, Dykewicz CA, Reef S, Phillips L (1998). "Measles, mumps, and rubella--vaccine use and strategies for elimination
of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization
Practices (ACIP)". MMWR Recomm Rep 47 (RR-8): 1–57. PMID 9639369.
[23] Dayan GH, Castillo-Solórzano C, Nava M, et al. (2006). "Efforts at rubella elimination in the United States: the impact of hemispheric
rubella control". Clin. Infect. Dis. 43 Suppl 3: S158–63. doi:10.1086/505949. PMID 16998776.
[24] Centers for Disease Control and Prevention (CDC) (2005). "Elimination of rubella and congenital rubella syndrome--United States,
1969-2004" (http:/ / www. cdc. gov/ mmwr/ preview/ mmwrhtml/ mm5411a5. htm). MMWR Morb. Mortal. Wkly. Rep. 54 (11): 279–82.
PMID 15788995. .
[25] Khandekar R, Sudhan A, Jain BK, Shrivastav K, Sachan R (2007). "Pediatric cataract and surgery outcomes in Central India: a hospital
based study" (http:/ / www. indianjmedsci. org/ article.
asp?issn=0019-5359;year=2007;volume=61;issue=1;spage=15;epage=22;aulast=Khandekar). Indian J Med Sci 61 (1): 15–22.
doi:10.4103/0019-5359.29593. PMID 17197734. .
[26] Weisinger HS, Pesudovs K (2002). "Optical complications in congenital rubella syndrome". Optometry 73 (7): 418–24. PMID 12365660.
[27] Freij BJ, South MA, Sever JL (1988). "Maternal rubella and the congenital rubella syndrome". Clin Perinatol 15 (2): 247–57.
PMID 3288422.
[28] Reef SE, Frey TK, Theall K, et al. (2002). "The changing epidemiology of rubella in the 1990s: on the verge of elimination and new
challenges for control and prevention" (http:/ / jama. ama-assn. org/ cgi/ pmidlookup?view=long& pmid=11798368). JAMA 287 (4): 464–72.
doi:10.1001/jama.287.4.464. PMID 11798368. .
[29] (http:/ / new. paho. org/ hq/ index. php?option=com_docman& task=cat_view& gid=2010& Itemid=673) Accessed 2010-04-10.
[30] Plotkin SA (2001). "Rubella eradication" (http:/ / linkinghub. elsevier. com/ retrieve/ pii/ S0264410X01000731). Vaccine 19 (25-26):
3311–9. doi:10.1016/S0264-410X(01)00073-1. PMID 11348695. .
[31] Cooper, L.Z. Congenital Rubella in the United States. 1975 In: Krugman, S Gershon, A (eds), Symposium on Infections Of the Fetus and
Newborn Infant. New York, Alan R. Liss Inc.,p.1.
[32] Danovaro-Holliday MC, LeBaron CW, Allensworth C, et al. (2000). "A large rubella outbreak with spread from the workplace to the
community" (http:/ / jama. ama-assn. org/ cgi/ pmidlookup?view=long& pmid=11105178). JAMA 284 (21): 2733–9.
doi:10.1001/jama.284.21.2733. PMID 11105178. .
[33] Reef S (2006). "Rubella mass campaigns". Curr. Top. Microbiol. Immunol. 304: 221–9. doi:10.1007/3-540-36583-4_12. PMID 16989272.
[34] Ackerknecht, Erwin Heinz (1982). A short history of medicine. Baltimore: Johns Hopkins University Press. pp. 129. ISBN 0-8018-2726-4.
[35] Wesselhoeft C (1949). "Rubella and congenital deformities". N. Engl. J. Med. 240 (7): 258–61. doi:10.1056/NEJM194902172400706.
PMID 18109609.
[36] Best, J.M., Cooray, S., Banatvala J.E. Rubella in Topley and Wilson's Microbiology and Microbial Infections, Vol. 2, Virology, Chapter 45,
p.960-92, ISBN 0 340 88562 9, 2005
[37] Lee JY, Bowden DS (2000). "Rubella virus replication and links to teratogenicity" (http:/ / cmr. asm. org/ cgi/ content/ full/ 13/ 4/ 571).
Clin. Microbiol. Rev. 13 (4): 571–87. doi:10.1128/CMR.13.4.571-587.2000. PMID 11023958. PMC 88950. .
[38] Atkinson W, Hamborsky J, McIntyre L, Wolfe S, eds. (2007). "Chapter 12. Rubella" (http:/ / www. cdc. gov/ vaccines/ pubs/ pinkbook/
downloads/ rubella. pdf). Epidemiology and Prevention of Vaccine-Preventable Diseases. 10th ed. (http:/ / www. cdc. gov/ vaccines/ pubs/
pinkbook/ pink-chapters. htm). Centers for Disease Control and Prevention. . Retrieved 2007-07-03.
[39] "Chapter 11 - Rubella" (http:/ / www. moh. govt. nz/ moh. nsf/ pagesmh/ 4617/ $File/ 2006-11rubella. pdf). Immunisation Handbook 2006
(http:/ / www. moh. govt. nz/ moh. nsf/ indexmh/ immunisation-handbook-2006). Ministry of Health, Wellington, NZ.. April 2006.
ISBN 0-478-29926-5. . Retrieved 2007-07-03.
[40] Smith, J. L. Contributions to the study of Rötheln. Trans. Int. Med. Congr. Phil. 4,14. 1881
[41] Hess, Alfred Fabian (1914). "German measles (rubella): an experimental study". The Archives of Internal Medicine (Chicago) 13: 913–916.
as cited by Enersen, Ole Daniel. "Alfred Fabian Hess" (http:/ / www. whonamedit. com/ doctor. cfm/ 2283. html). WhoNamedIt. . Retrieved
2007-07-03.
[42] J.B. Hanshaw, J.A. Dudgeon, and W.C. Marshall. Viral diseases of the fetus and newborn. W.B. Saunders Co., Philadelphia, 1985
47
Rubella
48
External links
• Rubella (http://www.virology-online.com/viruses/Rubella.htm) at Wong's Virology.
• Immunization Action Coalition: Rubella (http://www.immunize.org/rubella/index.htm)
• DermNet viral/rubella (http://dermnetnz.org/viral/rubella.html)
Hepatitis A
Hepatitis A
[1]
ICD-10
B 15.
ICD-9
070.1
DiseasesDB
5757
[2]
[3]
eMedicine
med/991
MeSH
D006506
[5]
ped/977
[6]
[7]
Hepatitis A
Electron micrograph of hepatitis A
virions.
Group:
Group IV ((+)ssRNA)
Family:
Picornaviridae
Genus:
Hepatovirus
Species:
Hepatitis A virus
Hepatitis A (formerly known as infectious hepatitis) is an acute infectious disease of the liver caused by the hepatitis
A virus (HAV),[8] which is transmitted person-to-person by ingestion of contaminated food or water or through
direct contact with an infectious person. Tens of millions of individuals worldwide are estimated to become infected
with HAV each year.[9] The time between infection and the appearance of the symptoms, (the incubation period), is
between two and six weeks and the average incubation period is 28 days.[10]
In developing countries, and in regions with poor hygiene standards, the incidence of infection with this virus is
high[11] and the illness is usually contracted in early childhood. As incomes rise and access to clean water increases,
the incidence of HAV decreases.[12] Hepatitis A infection causes no clinical signs and symptoms in over 90% of
infected children and since the infection confers lifelong immunity, the disease is of no special significance to those
Hepatitis A
infected early in life. In Europe, the United States and other industrialized countries, on the other hand, the infection
is contracted primarily by susceptible young adults, most of whom are infected with the virus during trips to
countries with a high incidence of the disease[10] or through contact with infectious persons.
HAV infection produces a self-limited disease that does not result in chronic infection or chronic liver disease.
However, 10%–15% of patients might experience a relapse of symptoms during the 6 months after acute illness.
Acute liver failure from Hepatitis A is rare (overall case-fatality rate: 0.5%). The risk for symptomatic infection is
directly related to age, with >80% of adults having symptoms compatible with acute viral hepatitis and the majority
of children having either asymptomatic or unrecognized infection.[13] Antibody produced in response to HAV
infection persists for life and confers protection against reinfection. The disease can be prevented by vaccination, and
hepatitis A vaccine has been proven effective in controlling outbreaks worldwide.[10]
Signs and symptoms
Early symptoms of hepatitis A infection can be mistaken for influenza, but some sufferers, especially children,
exhibit no symptoms at all. Symptoms typically appear 2 to 6 weeks, (the incubation period), after the initial
infection.[14]
Symptoms can return over the following 2–6 months and include:[15]
•
•
•
•
•
•
•
•
•
•
•
•
•
Fatigue
Fever
Abdominal pain
Nausea
Diarrhea
Appetite loss
Depression
Jaundice, a yellowing of the skin or whites of the eyes
Sharp pains in the right-upper quadrant of the abdomen
Weight loss
Itching
Bile is removed from blood stream and excreted in urine, giving it a dark amber colour
Feces tend to be light in colour due to lack of bilirubin in bile
Pathogenesis
Following ingestion, HAV enters the bloodstream through the epithelium of the oropharynx or intestine.[16] The
blood carries the virus to its target, the liver, where it multiplies within hepatocytes and Kupffer cells (liver
macrophages). Virions are secreted into the bile and released in stool. HAV is excreted in large quantities
approximately 11 days prior to appearance of symptoms or anti-HAV IgM antibodies in the blood. The incubation
period is 15–50 days and mortality is less than 0.5%. Within the liver hepatocytes the RNA genome is released from
the protein coat and is translated by the cell's own ribosomes. Unlike other members of the Picornaviruses this virus
requires an intact eukaryote initiating factor 4G (eIF4G) for the initiation of translation.[17] The requirement for this
factor results in an inability to shut down host protein synthesis unlike other picornaviruses. The virus must then
inefficiently compete for the cellular translational machinery which may explain its poor growth in cell culture.
Presumably for this reason the virus has strategically adopted a naturally highly deoptimized codon usage with
respect to that of its cellular host. Precisely how this stategy works is not quite clear yet.
There is no apparent virus-mediated cytotoxicity presumably because of the virus' own requirement for an intact
eIF4G and liver pathology is likely immune-mediated.
49
Hepatitis A
50
Diagnosis
Although HAV is excreted in the feces towards the end of the
incubation period, specific diagnosis is made by the detection of
HAV-specific IgM antibodies in the blood.[18] IgM antibody is only
present in the blood following an acute hepatitis A infection. It is
detectable from one to two weeks after the initial infection and persists
for up to 14 weeks. The presence of IgG antibody in the blood means
that the acute stage of the illness is past and the person is immune to
further infection. IgG antibody to HAV is also found in the blood
following vaccination and tests for immunity to the virus are based on
the detection of this antibody.[18]
Serum IgG, IgM and ALT following Hepatitis A
virus infection
During the acute stage of the infection, the liver enzyme alanine
transferase (ALT) is present in the blood at levels much higher than is
normal. The enzyme comes from the liver cells that have been damaged by the virus.[19]
Hepatitis A virus is present in the blood, (viremia), and feces of infected people up to two weeks before clinical
illness develops.[19]
Prevention
Hepatitis A can be prevented by vaccination, good hygiene and sanitation.[8] [20]
The vaccine protects against HAV in more than 95% of cases for longer than 20 years. It contains inactivated
hepatitis A virus providing active immunity against a future infection.[21] [22] The vaccine was first phased in 1996
for children in high-risk areas, and in 1999 it was spread to areas with elevating levels of infection.[23]
The vaccine is given by injection. An initial dose provides protection starting two to four weeks after vaccination;
the second booster dose, given six to twelve months later, provides protection for over twenty years.[21] [23]
Treatment
There is no specific treatment for hepatitis A. Sufferers are advised to rest, avoid fatty foods and alcohol (these may
be poorly tolerated for some additional months during the recovery phase and cause minor relapses), eat a
well-balanced diet, and stay hydrated.
Pharmacotherapeutic goals are to reduce the morbidity and prevent complications involved in infection. The therapy
is given by the agents like
• 1. Analgesics-to reduce the abdominal pain; usually Acetaminophen is given. Acetaminophen also acts as an
antipyretic, to reduce the fever
• 2. Antiemetics-to supress vomiting and nausea; usually Metoclopramide is given
• 3. Immune globulins usually BayGam 15-18% IG is given through intramuscular route
Hepatitis A
Prognosis
The United States Centers for Disease Control and Prevention (CDC) in 1991 reported a low mortality rate for
hepatitis A of 4 deaths per 1000 cases for the general population but a higher rate of 17.5 per 1000 in those aged 50
and over. The risk of death from acute liver failure following HAV infection increases with age and when the person
has underlying chronic liver disease.
Young children who are infected with hepatitis A typically have a milder form of the disease, usually lasting from
1–3 weeks, whereas adults tend to experience a much more severe form of the disease.[24]
Epidemiology
Prevalence
Antibodies to HAV (anti-HAV) in the blood are a marker of past or current infection. High-income regions (Western
Europe, Australia, New Zealand, Canada, the United States, Japan, the Republic of Korea, and Singapore) have very
low HAV endemicity levels and a high proportion of susceptible adults, low-income regions (sub-Saharan Africa
and parts of South Asia) have high endemicity levels and almost no susceptible adolescents and adults, and most
middle-income regions have a mix of intermediate and low endemicity levels. Anti-HAV prevalence suggest that
middle-income regions in Asia, Latin America, Eastern Europe, and the Middle East currently have an intermediate
or low level of endemicity. The countries in these regions may have an increasing burden of disease from hepatitis
A.[25]
There were 30,000 cases of Hepatitis A reported to the CDC in the U.S. in 1997. The agency estimates that there
were as many as 270,000 cases each year from 1980 through 2000.[26]
Transmission
The virus spreads by the fecal-oral route and infections often occur in conditions of poor sanitation and
overcrowding. Hepatitis A can be transmitted by the parenteral route but very rarely by blood and blood products.
Food-borne outbreaks are not uncommon,[24] and ingestion of shellfish cultivated in polluted water is associated with
a high risk of infection.[27] Approximately 40% of all acute viral hepatitis is caused by HAV.[16] Infected individuals
are infectious prior to onset of symptoms, roughly 10 days following infection. The virus is resistant to detergent,
acid (pH 1), solvents (e.g., ether, chloroform), drying, and temperatures up to 60oC. It can survive for months in
fresh and salt water. Common-source (e.g., water, restaurant) outbreaks are typical. Infection is common in children
in developing countries, reaching 100% incidence, but following infection there is life-long immunity. HAV can be
inactivated by: chlorine treatment (drinking water), formalin (0.35%, 37oC, 72 hours), peracetic acid (2%, 4 hours),
beta-propiolactone (0.25%, 1 hour), and UV radiation (2 μW/cm2/min).
Cases
The most widespread hepatitis A outbreak in the United States afflicted at least 640 people (killing four) in
north-eastern Ohio and south-western Pennsylvania in late 2003. The outbreak was blamed on tainted green onions
at a restaurant in Monaca, Pennsylvania.[28] In 1988, 300,000 people in Shanghai, China were infected with HAV
after eating clams from a contaminated river.[16]
Virology
The Hepatitis virus (HAV) is a Picornavirus; it is non-enveloped and contains a single-stranded RNA packaged in a
protein shell.[29] There is only one serotype of the virus, but multiple genotypes exist.[30] Codon use within the
genome is biased and unusually distinct from its host. It also has a poor internal ribosome entry site[31] In the region
that codes for the HAV capsid there are highly conserved clusters of rare codons that restrict antigenic variability.[32]
51
Hepatitis A
See also
•
•
•
•
•
•
•
•
Hepatitis B
Hepatitis B in China
Hepatitis C
Hepatitis D
Hepatitis E
Hepatitis F
Hepatitis G
Maurice Hilleman
References
[1]
[2]
[3]
[4]
[5]
[6]
[7]
http:/ / www. emedicine. com/ med/ topic991. htm
[8] Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 541–4. ISBN 0838585299.
[9] Wasley A, Fiore A, Bell BP (2006). "Hepatitis A in the era of vaccination". Epidemiol Rev 28: 101–11. doi:10.1093/epirev/mxj012.
PMID 16775039.
[10] Connor BA (2005). "Hepatitis A vaccine in the last-minute traveler" (http:/ / linkinghub. elsevier. com/ retrieve/ pii/
S0002-9343(05)00611-X). Am. J. Med. 118 Suppl 10A: 58S–62S. doi:10.1016/j.amjmed.2005.07.018. PMID 16271543. .
[11] Steffen R (October 2005). "Changing travel-related global epidemiology of hepatitis A" (http:/ / linkinghub. elsevier. com/ retrieve/ pii/
S0002-9343(05)00609-1). Am. J. Med. 118 Suppl 10A: 46S–49S. doi:10.1016/j.amjmed.2005.07.016. PMID 16271541. . Retrieved
2008-12-20.
[12] Jacobsen KH, Koopman JS (2005). "The effects of socioeconomic development on worldwide hepatitis A virus seroprevalence patterns". Int
J Epidemiol 34 (3): 600–9. doi:10.1093/ije/dyi062. PMID 15831565.
[13] Ciocca M. (2000). "Clinical course and consequences of hepatitis A infection.". Vaccine 18: 71–4. doi:10.1016/S0264-410X(99)00470-3.
PMID 10683554.
[14] "Hepatitis A Symptoms" (http:/ / www. emedicinehealth. com/ hepatitis_a/ page3_em. htm#Hepatitis A Symptoms). eMedicineHealth.
2007-05-17. . Retrieved 2007-05-18.
[15] "Hepatitis A : Fact Sheet" (http:/ / www. cdc. gov/ Ncidod/ diseases/ hepatitis/ a/ fact. htm). Center for Disease Control. 2007-08-09. .
[16] Murray, P. R., Rosenthal, K. S. & Pfaller, M. A. (2005) Medical Microbiology 5th ed., Elsevier Mosby.
[17] Aragonès L, Guix S, Ribes E, Bosch A, Pintó RM (2010) Fine-tuning translation kinetics selection as the driving force of codon usage bias
in the hepatitis a virus capsid. PLoS Pathog. 6(3):e1000797
[18] Stapleton JT (1995). "Host immune response to hepatitis A virus". J. Infect. Dis. 171 Suppl 1: S9–14. PMID 7876654.
[19] Musana KA, Yale SH, Abdulkarim AS (2004). "Tests of liver injury" (http:/ / www. clinmedres. org/ cgi/ pmidlookup?view=long&
pmid=15931347). Clin Med Res 2 (2): 129–31. doi:10.3121/cmr.2.2.129. PMID 15931347. PMC 1069083. .
[20] http:/ / www. nhs. uk/ Conditions/ Hepatitis-A/ Pages/ Prevention. aspx?url=Pages/ What-is-it. aspx
[21] "Avaxim" (http:/ / www. netdoctor. co. uk/ medicines/ 100003051. html). NetDoctor.co.uk. . Retrieved 2007-03-12.
[22] Hammitt, LL; Bulkow, L; Hennessy, TW; Zanis, C; Snowball, M; Williams, JL; Bell, BP; Mcmahon, BJ (2008). "Persistence of antibody to
Hepatitis A virus 10 years after vaccination among children and adults". J Infect Dis 198 (12): 1776–1782. doi:10.1086/593335.
PMID 18976095.
[23] "Hepatitis A Vaccine: What you need to know" (http:/ / www. cdc. gov/ vaccines/ pubs/ vis/ downloads/ vis-hep-a. pdf). Vaccine
Information Statement. CDC. 2006-03-21. . Retrieved 2007-03-12.
[24] Brundage SC, Fitzpatrick AN (June 2006). "Hepatitis A". American Family Physician 73 (12): 2162–8. PMID 16848078.
[25] Jacobsen K, Wiersma S (2010). "Hepatitis A virus seroprevalence by age and world region, 1990 and 2005". Vaccine 28 (41): 6653–6657.
doi:10.1016/j.vaccine.2010.08.037. PMID 20723630.
[26] Index | CDC Viral Hepatitis (http:/ / www. cdc. gov/ Ncidod/ diseases/ hepatitis/ a/ global_hepA_epi. pdf)
[27] Lees D (2000). "Viruses and bivalve shellfish" (http:/ / linkinghub. elsevier. com/ retrieve/ pii/ S0168-1605(00)00248-8). Int. J. Food
Microbiol. 59 (1–2): 81–116. doi:10.1016/S0168-1605(00)00248-8. PMID 10946842. .
[28] Hepatitis A Outbreak Associated with Green Onions at a Restaurant – Monaca, Pennsylvania, 2003 (http:/ / www. cdc. gov/ mmwR/
preview/ mmwrhtml/ mm5247a5. htm)
52
Hepatitis A
[29] Cristina J, Costa-Mattioli M (August 2007). "Genetic variability and molecular evolution of hepatitis A virus". Virus Res. 127 (2): 151–7.
doi:10.1016/j.virusres.2007.01.005. PMID 17328982.
[30] Costa-Mattioli M, Di Napoli A, Ferré V, Billaudel S, Perez-Bercoff R, Cristina J (December 2003). "Genetic variability of hepatitis A virus"
(http:/ / vir. sgmjournals. org/ cgi/ pmidlookup?view=long& pmid=14645901). J. Gen. Virol. 84 (Pt 12): 3191–201.
doi:10.1099/vir.0.19532-0. PMID 14645901. .
[31] Whetter LE, Day SP, Elroystein O, Brown EA, Lemon SM (1994) Low efficiency of the 5' nontranslated region of hepatitis A virus RNA in
directing cap-independent translation in permissive monkey kidney cells. J Virol 68: 5253–5263
[32] Aragones L, Bosch A, Pinto RM (2008) Hepatitis A virus mutant spectra under the selective pressure of monoclonal antibodies: Codon
usage constraints limit capsid variability. J Virol 82: 1688–1700
External links
•
•
•
•
CDC's hepatitis A links (http://www.cdc.gov/ncidod/diseases/hepatitis/a/index.htm)
CDC's hepatitis A Fact Sheet (http://www.cdc.gov/ncidod/diseases/hepatitis/a/fact.htm)
MeSH Hepatitis+A (http://www.nlm.nih.gov/cgi/mesh/2009/MB_cgi?mode=&term=Hepatitis+A)
MeSH Hepatitis+A+virus (http://www.nlm.nih.gov/cgi/mesh/2009/MB_cgi?mode=&term=Hepatitis+A+
virus)
• Virus Pathogen Database and Analysis Resource (ViPR): Picornaviridae (http://www.viprbrc.org/brc/home.
do?decorator=picorna)
53
Hepatitis B
54
Hepatitis B
Hepatitis B
Electron micrograph of Hepatitis B virus
[1]
ICD-10
B 16. ,
[2]
[3]
B 18.0 -B 18.1
ICD-9
070.2
OMIM
610424
DiseasesDB
5765
MedlinePlus
000279
eMedicine
med/992
MeSH
D006509
[4]
- 070.3
[5]
[6]
[7]
[8]
[9]
ped/978
[10]
[11]
Hepatitis B is an infectious illness caused by hepatitis B virus (HBV) which infects the liver of hominoidea,
including humans, and causes an inflammation called hepatitis. Originally known as "serum hepatitis",[12] the
disease has caused epidemics in parts of Asia and Africa, and it is endemic in China.[13] About a third of the world's
population, more than 2 billion people, have been infected with the hepatitis B virus.[14] This includes 350 million
chronic carriers of the virus.[15] Transmission of hepatitis B virus results from exposure to infectious blood or body
fluids.[14]
The acute illness causes liver inflammation, vomiting, jaundice and rarely, death. Chronic hepatitis B may eventually
cause liver cirrhosis and liver cancer—a fatal disease with very poor response to current chemotherapy.[16] The
infection is preventable by vaccination.[17]
Hepatitis B virus is an hepadnavirus—hepa from hepatotrophic and dna because it is a DNA virus[18] —and it has a
circular genome composed of partially double-stranded DNA. The viruses replicate through an RNA intermediate
form by reverse transcription, and in this respect they are similar to retroviruses.[19] Although replication takes place
in the liver, the virus spreads to the blood where virus-specific proteins and their corresponding antibodies are found
in infected people. Blood tests for these proteins and antibodies are used to diagnose the infection.[20]
Hepatitis B
Signs and symptoms
Acute infection with hepatitis B virus is associated with acute viral hepatitis – an illness that begins with general
ill-health, loss of appetite, nausea, vomiting, body aches, mild fever, dark urine, and then progresses to development
of jaundice. It has been noted that itchy skin has been an indication as a possible symptom of all hepatitis virus types.
The illness lasts for a few weeks and then gradually improves in most affected people. A few patients may have
more severe liver disease (fulminant hepatic failure), and may die as a result of it. The infection may be entirely
asymptomatic and may go unrecognized.
Chronic infection with hepatitis B virus may be either asymptomatic or may be associated with a chronic
inflammation of the liver (chronic hepatitis), leading to cirrhosis over a period of several years. This type of infection
dramatically increases the incidence of hepatocellular carcinoma (liver cancer). Chronic carriers are encouraged to
avoid consuming alcohol as it increases their risk for cirrhosis and liver cancer. Hepatitis B virus has been linked to
the development of Membranous glomerulonephritis (MGN).[21]
Mechanisms
Pathogenesis
The hepatitis B virus primarily interferes with the functions of the liver
by replicating in liver cells, known as hepatocytes.
The receptor is not yet known, though there is evidence that the
receptor in the closely related duck hepatitis B virus is
carboxypeptidase D.[22] [23] HBV virions (DANE particle) bind to the
host cell via the preS domain of the viral surface antigen and are
subsequently internalized by endocytosis. PreS and IgA receptors are
accused of this interaction. HBV-preS specific receptors are primarily
expressed on hepatocytes; however, viral DNA and proteins have also
been detected in extrahepatic sites, suggesting that cellular receptors
for HBV may also exist on extrahepatic cells.
During HBV infection, the host immune response causes both
hepatocellular damage and viral clearance. Although the innate
Cirrhosis of the liver and liver cancer may ensue
immune response does not play a significant role in these processes,
from Hepatitis B.
the adaptive immune response, particularly virus-specific cytotoxic T
lymphocytes (CTLs), contributes to most of the liver injury associated
with HBV infection. CTLs eliminate HBV infection by killing infected cells and producing antiviral cytokines,
which are then used to purge HBV from viable hepatocytes.[24] Although liver damage is initiated and mediated by
the CTLs, antigen-nonspecific inflammatory cells can worsen CTL-induced immunopathology, and platelets
activated at the site of infection may facilitate the accumulation of CTLs in the liver.[25]
Transmission
Transmission of hepatitis B virus results from exposure to infectious blood or body fluids containing blood. Possible
forms of transmission include sexual contact, blood transfusions, re-use of contaminated needles & syringes, and
vertical transmission from mother to child during childbirth. Without intervention, a mother who is positive for
HBsAg confers a 20% risk of passing the infection to her offspring at the time of birth. This risk is as high as 90% if
the mother is also positive for HBeAg. HBV can be transmitted between family members within households,
possibly by contact of nonintact skin or mucous membrane with secretions or saliva containing HBV.[26] [27]
However, at least 30% of reported hepatitis B among adults cannot be associated with an identifiable risk factor.[28]
55
Hepatitis B
56
Virology
Structure
Hepatitis B virus (HBV) is a member of the Hepadnavirus family.[18]
The virus particle, (virion) consists of an outer lipid envelope and an
icosahedral nucleocapsid core composed of protein. The nucleocapsid
encloses the viral DNA and a DNA polymerase that has reverse
transcriptase activity.[19] The outer envelope contains embedded
proteins which are involved in viral binding of, and entry into,
susceptible cells. The virus is one of the smallest enveloped animal
viruses, with a virion diameter of 42 nm, but pleomorphic forms exist,
including filamentous and spherical bodies lacking a core. These
particles are not infectious and are composed of the lipid and protein
that forms part of the surface of the virion, which is called the surface
antigen (HBsAg), and is produced in excess during the life cycle of the virus.[29]
Hepatitis B virus replication.
Genome
The genome of HBV is made of circular DNA, but it is unusual because the DNA is not fully double-stranded. One
end of the full length strand is linked to the viral DNA polymerase. The genome is 3020–3320 nucleotides long (for
the full-length strand) and 1700–2800 nucleotides long (for the short length-strand).[30] The negative-sense,
(non-coding), is complementary to the viral mRNA. The viral DNA is found in the nucleus soon after infection of
the cell. The partially double-stranded DNA is rendered fully double-stranded by completion of the (+) sense strand
and removal of a protein molecule from the (-) sense strand and a short sequence of RNA from the (+) sense strand.
Non-coding bases are removed from the ends of the (-) sense strand and the ends are rejoined. There are four known
genes encoded by the genome, called C, X, P, and S. The core protein is coded for by gene C (HBcAg), and its start
codon is preceded by an upstream in-frame AUG start codon from which the pre-core protein is produced. HBeAg is
produced by proteolytic processing of the pre-core protein. The DNA polymerase is encoded by gene P. Gene S is
the gene that codes for the surface antigen (HBsAg). The HBsAg gene is one long open reading frame but contains
three in frame "start" (ATG) codons that divide the gene into three sections, pre-S1, pre-S2, and S. Because of the
multiple start codons, polypeptides of three different sizes called large, middle, and small (pre-S1 + pre-S2 + S,
pre-S2 + S, or S) are produced.[31] The function of the protein coded for by gene X is not fully understood but it is
associated with the development of liver cancer. It stimulates genes that promote cell growth and inactivates growth
regulating molecules.[32]
Replication
The life cycle of hepatitis B virus is complex. Hepatitis B is one of a few known non-retroviral viruses which use
reverse transcription as a part of its replication process. The virus gains entry into the cell by binding to an unknown
receptor on the surface of the cell and enters it by endocytosis. Because the virus multiplies via RNA made by a host
enzyme, the viral genomic DNA has to be transferred to the cell nucleus by host proteins called chaperones. The
partially double stranded viral DNA is then made fully double stranded and transformed into covalently closed
circular DNA (cccDNA) that serves as a template for transcription of four viral mRNAs. The largest mRNA, (which
is longer than the viral genome), is used to make the new copies of the genome and to make the capsid core protein
and the viral DNA polymerase. These four viral transcripts undergo additional processing and go on to form progeny
virions which are released from the cell or returned to the nucleus and re-cycled to produce even more copies.[31] [33]
The long mRNA is then transported back to the cytoplasm where the virion P protein synthesizes DNA via its
reverse transcriptase activity.
Hepatitis B
Serotypes and genotypes
The virus is divided into four major serotypes (adr, adw, ayr, ayw) based on antigenic epitopes presented on its
envelope proteins, and into eight genotypes (A-H) according to overall nucleotide sequence variation of the genome.
The genotypes have a distinct geographical distribution and are used in tracing the evolution and transmission of the
virus. Differences between genotypes affect the disease severity, course and likelihood of complications, and
response to treatment and possibly vaccination.[34] [35]
Genotypes differ by at least 8% of their sequence and were first reported in 1988 when six were initially described
(A-F).[36] Two further types have since been described (G and H).[37] Most genotypes are now divided into
subgenotypes with distinct properties.[38]
Genotype A is most commonly found in the Americas, Africa, India and Western Europe. Genotype B is most
commonly found in Asia and the United States. Genotype B1 dominates in Japan, B2 in China and Vietnam while
B3 confined to Indonesia. B4 is confined to Vietnam. All these strains specify the serotype ayw1. B5 is most
common in the Philippines. Genotype C is most common in Asia and the United States. Subgenotype C1 is common
in Japan, Korea and China. C2 is common in China, South-East Asia and Bangladesh and C3 in Oceania. All these
strains specify the serotype adrq. C4 specifying ayw3 is found in Aborigines from Australia.[39] Genotype D is most
commonly found in Southern Europe, India and the United States and has been divided into 8 subtypes (D1-D8). In
Turkey genotype D is also the most common type. A pattern of defined geographical distribution is less evident with
D1-D4 where these subgenotypes are widely spread within Europe, Africa and Asia. This may be due to their
divergence having occurred before than of genotypes B and C. D4 appears to be the oldest split and is still the
dominating subgenotype of D in Oceania. Type E is most commonly found in West and Southern Africa. Type F is
most commonly found in Central and South America and has been divided into two subgroups (F1 and F2).
Genotype G has an insertion of 36 nucleotides in the core gene and is found in France and the United States.[40] Type
H is most commonly found in Central and South America and California in United States. Africa has five genotypes
(A-E). Of these the predominant genotypes are A in Kenya, B and D in Egypt, D in Tunisia, A-D in South Africa
and E in Nigeria.[39] Genotype H is probably split off from genotype F within the New World.[41]
Diagnosis
Hepatitis B viral antigens and antibodies detectable in the blood following acute infection.
Hepatitis B viral antigens and antibodies detectable in the blood of a chronically infected person.
57
Hepatitis B
The tests, called assays, for detection of hepatitis B virus infection
involve serum or blood tests that detect either viral antigens (proteins
produced by the virus) or antibodies produced by the host.
Interpretation of these assays is complex.[20]
The hepatitis B surface antigen (HBsAg) is most frequently used to
screen for the presence of this infection. It is the first detectable viral
antigen to appear during infection. However, early in an infection, this
antigen may not be present and it may be undetectable later in the
Ground glass hepatocytes as seen in a chronic
infection as it is being cleared by the host. The infectious virion
hepatitis B. Liver biopsy. H&E stain.
contains an inner "core particle" enclosing viral genome. The
icosahedral core particle is made of 180 or 240 copies of core protein,
alternatively known as hepatitis B core antigen, or HBcAg. During this 'window' in which the host remains infected
but is successfully clearing the virus, IgM antibodies to the hepatitis B core antigen (anti-HBc IgM) may be the only
serological evidence of disease.
Shortly after the appearance of the HBsAg, another antigen named as the hepatitis B e antigen (HBeAg) will appear.
Traditionally, the presence of HBeAg in a host's serum is associated with much higher rates of viral replication and
enhanced infectivity; however, variants of the hepatitis B virus do not produce the 'e' antigen, so this rule does not
always hold true. During the natural course of an infection, the HBeAg may be cleared, and antibodies to the 'e'
antigen (anti-HBe) will arise immediately afterwards. This conversion is usually associated with a dramatic decline
in viral replication.
If the host is able to clear the infection, eventually the HBsAg will become undetectable and will be followed by IgG
antibodies to the hepatitis B surface antigen and core antigen, (anti-HBs and anti HBc IgG).[18] The time between the
removal of the HBsAg and the appearance of anti-HBs is called the window period. A person negative for HBsAg
but positive for anti-HBs has either cleared an infection or has been vaccinated previously.
Individuals who remain HBsAg positive for at least six months are considered to be hepatitis B carriers.[42] Carriers
of the virus may have chronic hepatitis B, which would be reflected by elevated serum alanine aminotransferase
levels and inflammation of the liver, as revealed by biopsy. Carriers who have seroconverted to HBeAg negative
status, particularly those who acquired the infection as adults, have very little viral multiplication and hence may be
at little risk of long-term complications or of transmitting infection to others.[43]
PCR tests have been developed to detect and measure the amount of HBV DNA, called the viral load, in clinical
specimens. These tests are used to assess a person's infection status and to monitor treatment.[44] Individuals with
high viral loads, characteristically have ground glass hepatocytes on biopsy.
58
Hepatitis B
59
Prevention
Several vaccines have been developed by Maurice Hilleman for the
prevention of hepatitis B virus infection. These rely on the use of one
of the viral envelope proteins (hepatitis B surface antigen or HBsAg).
The vaccine was originally prepared from plasma obtained from
patients who had long-standing hepatitis B virus infection. However,
currently, it is made using a synthetic recombinant DNA technology
that does not contain blood products. One cannot be infected with
hepatitis B from this vaccine.[45]
Following vaccination, hepatitis B surface antigen may be detected in
serum for several days; this is known as vaccine antigenaemia.[46] The
vaccine is administered in either two-, three-, or four-dose schedules
into infants and adults, which provides protection for 85–90% of
individuals.[47] Protection has been observed to last 12 years in
individuals who show adequate initial response to the primary course
of vaccinations, and that immunity is predicted to last at least 25 years.[48]
HBsAg
Unlike hepatitis A, hepatitis B does not generally spread through water and food. Instead, it is transmitted through
body fluids; prevention is thus the avoidance of such transmission: unprotected sexual contact, blood transfusions,
re-use of contaminated needles and syringes, and vertical transmission during child birth. Infants may be vaccinated
at birth.[49]
Shi, et al showed that besides the WHO recommended joint immunoprophylaxis starting from the newborn, multiple
injections of small doses of hepatitis B immune globulin (HBIg, 200–400 IU per month),[50] [51] or oral lamivudine
(100 mg per day) in HBV carrier mothers with a high degree of infectiousness (>106 copies/ml) in late pregnancy
(the last three months of pregnancy),[52] [53] effectively and safely prevent HBV intrauterine transmission, which
provide new insight into prevention of HBV at the earliest stage.
Treatment
Acute hepatitis B infection does not usually require treatment because most adults clear the infection
spontaneously.[54] Early antiviral treatment may only be required in fewer than 1% of patients, whose infection takes
a very aggressive course (fulminant hepatitis) or who are immunocompromised. On the other hand, treatment of
chronic infection may be necessary to reduce the risk of cirrhosis and liver cancer. Chronically infected individuals
with persistently elevated serum alanine aminotransferase, a marker of liver damage, and HBV DNA levels are
candidates for therapy.[55]
Although none of the available drugs can clear the infection, they can stop the virus from replicating, thus
minimizing liver damage. Currently, there are seven medications licensed for treatment of hepatitis B infection in the
United States. These include antiviral drugs lamivudine (Epivir), adefovir (Hepsera), tenofovir (Viread), telbivudine
(Tyzeka) and entecavir (Baraclude) and the two immune system modulators interferon alpha-2a and PEGylated
interferon alpha-2a (Pegasys). The use of interferon, which requires injections daily or thrice weekly, has been
supplanted by long-acting PEGylated interferon, which is injected only once weekly.[] However, some individuals
are much more likely to respond than others and this might be because of the genotype of the infecting virus or the
patient's heredity. The treatment reduces viral replication in the liver, thereby reducing the viral load (the amount of
virus particles as measured in the blood).[56]
Infants born to mothers known to carry hepatitis B can be treated with antibodies to the hepatitis B virus (HBIg).
When given with the vaccine within twelve hours of birth, the risk of acquiring hepatitis B is reduced 90%.[57] This
treatment allows a mother to safely breastfeed her child.
Hepatitis B
Response to treatment differs between the genotypes. Interferon treatment may produce an e antigen seroconversion
rate of 37% in genotype A but only a 6% seroconversion in type D. Genotype B has similar seroconversion rates to
type A while type C seroconverts only in 15% of cases. Sustained e antigen loss after treatment is ~45% in types A
and B but only 25–30% in types C and D.[58]
In July 2005, researchers identified an association between a host-derived DNA-binding protein and the amount of
HBV replication in the liver. Controlling the level of production of this protein could be used to treat hepatitis B.[59]
Prognosis
Hepatitis B virus infection may either be acute (self-limiting) or chronic (long-standing). Persons with self-limiting
infection clear the infection spontaneously within weeks to months.
Children are less likely than adults to clear the infection. More than 95% of people who become infected as adults or
older children will stage a full recovery and develop protective immunity to the virus. However, this drops to 30%
for younger children, and only 5% of newborns that acquire the infection from their mother at birth will clear the
infection.[60] This population has a 40% lifetime risk of death from cirrhosis or hepatocellular carcinoma.[61] Of
those infected between the age of one to six, 70% will clear the infection.[62]
Hepatitis D (HDV) can only occur with a concomitant hepatitis B infection, because HDV uses the HBV surface
antigen to form a capsid.[63] Co-infection with hepatitis D increases the risk of liver cirrhosis and liver cancer.[64]
Polyarteritis nodosa is more common in people with hepatitis B infection.
Reactivation
Hepatitis B virus DNA persists in the body after infection and in some people the disease recurs.[65] Although rare,
reactivation is seen most often in people with impaired immunity.[66] HBV goes through cycles of replication and
non-replication. Approximately 50% of patients experience acute reactivation. Male patients with baseline ALT of
200 UL/L are three times more likely to develop a reactivation than patients with lower levels. Patients who undergo
chemotherapy are at risk for HBV reactivation. The current view is that immunosuppressive drugs favor increased
HBV replication while inhibiting cytotoxic T cell function in the liver.[67]
Epidemiology
As of 2004, there are an estimated 350 million HBV infected individuals worldwide. National and regional
prevalence ranges from over 10% in Asia to under 0.5% in the United States and northern Europe. Routes of
infection include vertical transmission (such as through childbirth), early life horizontal transmission (bites, lesions,
and sanitary habits), and adult horizontal transmission (sexual contact, intravenous drug use).[68] The primary
method of transmission reflects the prevalence of chronic HBV infection in a given area. In low prevalence areas
such as the continental United States and Western Europe, injection drug abuse and unprotected sex are the primary
methods, although other factors may also be important.[69] In moderate prevalence areas, which include Eastern
Europe, Russia, and Japan, where 2–7% of the population is chronically infected, the disease is predominantly
spread among children. In high prevalence areas such as China and South East Asia, transmission during childbirth is
most common, although in other areas of high endemicity such as Africa, transmission during childhood is a
significant factor.[70] The prevalence of chronic HBV infection in areas of high endemicity is at least 8%.
60
Hepatitis B
History
The earliest record of an epidemic caused by hepatitis B virus was made by Lurman in 1885.[71] An outbreak of
smallpox occurred in Bremen in 1883 and 1,289 shipyard employees were vaccinated with lymph from other people.
After several weeks, and up to eight months later, 191 of the vaccinated workers became ill with jaundice and were
diagnosed as suffering from serum hepatitis. Other employees who had been inoculated with different batches of
lymph remained healthy. Lurman's paper, now regarded as a classical example of an epidemiological study, proved
that contaminated lymph was the source of the outbreak. Later, numerous similar outbreaks were reported following
the introduction, in 1909, of hypodermic needles that were used, and more importantly reused, for administering
Salvarsan for the treatment of syphilis. The virus was not discovered until 1965 when Baruch Blumberg, then
working at the National Institutes of Health (NIH), discovered the Australia antigen (later known to be hepatitis B
surface antigen, or HBsAg) in the blood of Australian aboriginal people.[72] Although a virus had been suspected
since the research published by MacCallum in 1947,[73] D.S. Dane and others discovered the virus particle in 1970
by electron microscopy.[74] By the early 1980s the genome of the virus had been sequenced,[75] and the first vaccines
were being tested.[76]
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61
Hepatitis B
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cytotoxic T lymphocyte-induced liver damage" (http:/ / www. nature. com/ nm/ journal/ v11/ n11/ abs/ nm1317. html) (Free full text). Nature
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[28] Shapiro, CN (1993). "Epidemiology of hepatitis B". The Pediatric infectious disease journal 12 (5): 433–7.
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[29] Howard, C. R. (1986). "The Biology of Hepadnaviruses". Journal of General Virology 67: 1215. doi:10.1099/0022-1317-67-7-1215.
PMID 3014045.
[30] Kay, A.; Zoulim, F. (2007). "Hepatitis B virus genetic variability and evolution". Virus research 127 (2): 164–176.
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[31] Beck, J; Nassal (2007). "Hepatitis B virus replication". World journal of gastroenterology : WJG 13 (1): 48–64. PMID 17206754.
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activation of c-Myc in human hepatocarcinoma cell line, HepG2
[33] Bruss, V (2007). "Hepatitis B virus morphogenesis". World journal of gastroenterology : WJG 13 (1): 65–73. PMID 17206755.
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[35] Magnius, LO; Norder (1995). "Subtypes, genotypes and molecular epidemiology of the hepatitis B virus as reflected by sequence variability
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[37] Shibayama T, Masuda G, Ajisawa A, Hiruma K, Tsuda F, Nishizawa T, Takahashi M, Okamoto H (May 2005). "Characterization of seven
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[39] Kurbanov F, Tanaka Y, Mizokami M (January 2010). "Geographical and genetic diversity of the human hepatitis B virus". Hepatology
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[40] Stuyver L, De Gendt S, Van Geyt C, Zoulim F, Fried M, Schinazi RF, Rossau R (2000) A new genotype of hepatitis B virus: complete
genome and phylogenetic relatedness. J Gen Virol 81:67–74
[41] Arauz-Ruiz, Norder PH, Robertson BH, Magnius LO (2002) Genotype H: A new Amerindian genotype of hepatitis B virus revealed in
Central America. J Gen Virol 2002, 83:2059–2073
[42] Lok, A.; Mcmahon, B. (2007). "Chronic hepatitis B". Hepatology (Baltimore, Md.) 45 (2): 507–539. doi:10.1002/hep.21513.
PMID 17256718.
[43] Chu, C.; Liaw, Y. (2007). "Predictive factors for reactivation of hepatitis B following hepatitis B e antigen seroconversion in chronic
hepatitis B". Gastroenterology 133 (5): 1458–1465. doi:10.1053/j.gastro.2007.08.039. PMID 17935720.
[44] Zoulim, F. (2006). "New nucleic acid diagnostic tests in viral hepatitis". Seminars in liver disease 26 (4): 309–317.
doi:10.1055/s-2006-951602. PMID 17051445.
[45] "Hepatitis B Vaccine" (http:/ / www. hepb. org/ professionals/ hepatitis_b_vaccine. htm). Doylestown, Pennsylvania: Hepatitis B
Foundation. 2009-01-31. . Retrieved 2010-03-13.
[46] Martín-Ancel, A.; Casas, M.; Bonet, B. (2004). "Implications of postvaccination hepatitis B surface antigenemia in the management of
exposures to body fluids". Infection control and hospital epidemiology : the official journal of the Society of Hospital Epidemiologists of
America 25 (7): 611–613. doi:10.1086/502449. PMID 15301037.
[47] Joint Committee on Vaccination and Immunisation (2006). "Chapter 18 Hepatitis B" (http:/ / www. dh. gov. uk/ en/ Publichealth/
Healthprotection/ Immunisation/ Greenbook/ DH_4097254?IdcService=GET_FILE& dID=152019& Rendition=Web) (PDF). Immunisation
Against Infectious Disease 2006 ("The Green Book") (3rd edition (Chapter 18 revised 10 October 2007) ed.). Edinburgh: Stationery Office.
pp. 468. ISBN 0113225288. .
[48] Vandamme, P.; Van Herck, K. (2007). "A review of the long-term protection after hepatitis a and B vaccination". Travel Medicine and
Infectious Disease 5 (2): 79–84. doi:10.1016/j.tmaid.2006.04.004. PMID 17298912.
[49] O'Connor, John (2008-10-03). "Hepatitis B Prevention – The Body" (http:/ / www. thebody. com/ content/ art17089. html). Body Health
Resources Corporation. . Retrieved 2009-01-30.
[50] Shi Z, Li X, Ma L, Yang Y (July 2010). "Hepatitis B immunoglobulin injection in pregnancy to interrupt hepatitis B virus mother-to-child
transmission-a meta-analysis". International Journal of Infectious Diseases : IJID : Official Publication of the International Society for
Infectious Diseases 14 (7): e622–34. doi:10.1016/j.ijid.2009.09.008. PMID 20106694.
[51] Li XM, Shi MF, Yang YB, Shi ZJ, Hou HY, Shen HM, Teng BQ (November 2004). "Effect of hepatitis B immunoglobulin on interruption
of HBV intrauterine infection". World J Gastroenterol 10 (21): 3215–7. PMID 15457579.
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[52] Li XM, Yang YB, Hou HY, Shi ZJ, Shen HM, Teng BQ, Li AM, Shi MF, Zou L (July 2003). "Interruption of HBV intrauterine
transmission: a clinical study". World J Gastroenterol 9 (7): 1501–3. PMID 12854150.
[53] Shi Z, Yang Y, Ma L, Li X, Schreiber A (July 2010). "Lamivudine in late pregnancy to interrupt in utero transmission of hepatitis B virus: a
systematic review and meta-analysis". Obstet Gynecol 116 (1): 147–59. doi:10.1097/AOG.0b013e3181e45951. PMID 20567182.
[54] Hollinger FB, Lau DT. Hepatitis B: the pathway to recovery through treatment (http:/ / journals. elsevierhealth. com/ retrieve/ pii/
S0889-8553(06)00102-6). Gastroenterology Clinics of North America. 2006;35(4):895–931. doi:10.1016/j.gtc.2006.10.002 (http:/ / dx. doi.
org/ 10. 1016/ j. gtc. 2006. 10. 002). PMID 17129820.
[55] Lai CL, Yuen MF. The natural history and treatment of chronic hepatitis B: a critical evaluation of standard treatment criteria and end
points. Annals of Internal Medicine. 2007;147(1):58–61. PMID 17606962.
[56] Pramoolsinsup C. Management of viral hepatitis B (http:/ / www3. interscience. wiley. com/ resolve/ openurl?genre=article&
sid=nlm:pubmed& issn=0815-9319& date=2002& volume=17& issue=& spage=S125). Journal of Gastroenterology and Hepatology.
2002;17 Suppl:S125–45. PMID 12000599.
[57] Libbus MK, Phillips LM. Public health management of perinatal hepatitis B virus (http:/ / www3. interscience. wiley. com/ resolve/
openurl?genre=article& sid=nlm:pubmed& issn=0737-1209& date=2009& volume=26& issue=4& spage=353). Public Health Nursing
(Boston, Mass.). 2009;26(4):353–61. doi:10.1111/j.1525-1446.2009.00790.x (http:/ / dx. doi. org/ 10. 1111/ j. 1525-1446. 2009. 00790. x).
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[58] Cao GW. Clinical relevance and public health significance of hepatitis B virus genomic variations (http:/ / www. wjgnet. com/ 1007-9327/
15/ 5761. asp). World Journal of Gastroenterology : WJG. 2009;15(46):5761–9. PMID 19998495. PMC 2791267 (http:/ / www. ncbi. nlm.
nih. gov/ pmc/ articles/ PMC2791267/ ).
[59] Ng, F.; Chan, M.; Chan, H.; Cheng, C.; Leung, H.; Chen, N.; Ren, C. (Jul 2005). "Host heterogeneous ribonucleoprotein K (hnRNP K) as a
potential target to suppress hepatitis B virus replication" (http:/ / dx. plos. org/ 10. 1371/ journal. pmed. 0020163) (Free full text). PLoS
medicine 2 (7): e163. doi:10.1371/journal.pmed.0020163. ISSN 1549-1277. PMID 16033304. PMC 1181871. . Lay summary (http:/ / www.
surgery. usc. edu/ divisions/ hep/ livernewsletter-reactivationofhepatitisb. html) – Agency for Science, Technology and Research
(2005-07-26).
[60] Bell, S J; Nguyen, T (2009). "The management of hepatitis B" (http:/ / www. australianprescriber. com/ magazine/ 32/ 4/ 99/ 104/ ) (Free
full text). Aust Prescr 23 (4): 99–104. .
[61] Dienstag, J. L. (2008). "Hepatitis B virus infection" (http:/ / content. nejm. org/ cgi/ content/ short/ 359/ 14/ 1486) (Free full text). The New
England journal of medicine 359 (14): 1486–1500. doi:10.1056/NEJMra0801644. PMID 18832247. .
[62] Kerkar, N. (2005). "Hepatitis B in children: complexities in management". Pediatric transplantation 9 (5): 685–691.
doi:10.1111/j.1399-3046.2005.00393.x. PMID 16176431.
[63] Taylor, J. (2006). "Hepatitis delta virus". Virology 344 (1): 71–76. doi:10.1016/j.virol.2005.09.033. PMID 16364738.
[64] Oliveri, F; Brunetto; Actis; Bonino (1991). "Pathobiology of chronic hepatitis virus infection and hepatocellular carcinoma (HCC)". The
Italian journal of gastroenterology 23 (8): 498–502. PMID 1661197.
[65] Vierling, J. (2007). "The immunology of hepatitis B". Clinics in liver disease 11 (4): 727–759, vii-759. doi:10.1016/j.cld.2007.08.001.
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[66] Katz, L.; Fraser, A.; Gafter-Gvili, A.; Leibovici, L.; Tur-Kaspa, R. (2008). "Lamivudine prevents reactivation of hepatitis B and reduces
mortality in immunosuppressed patients: systematic review and meta-analysis" (http:/ / www. blackwell-synergy. com/
openurl?genre=article& sid=nlm:pubmed& issn=1352-0504& date=2008& volume=15& issue=2& spage=89) (Free full text). Journal of viral
hepatitis 15 (2): 89–102. doi:10.1111/j.1365-2893.2007.00902.x. PMID 18184191. .
[67] Bonacini, Maurizio, MD. "Hepatitis B Reactivation" (http:/ / www. surgery. usc. edu/ divisions/ hep/
livernewsletter-reactivationofhepatitisb. html). University of Southern California Department of Surgery. . Retrieved 2009-01-24.
[68] Custer; Sullivan, SD; Hazlet, TK; Iloeje, U; Veenstra, DL; Kowdley, KV (2004). "Global epidemiology of hepatitis B virus". Journal of
clinical gastroenterology 38 (10 Suppl 3): S158–68. doi:10.1097/00004836-200411003-00008. PMID 15602165.
[69] Redd, J.; Baumbach, J.; Kohn, W.; Nainan, O.; Khristova, M.; Williams, I. (2007). "Patient-to-patient transmission of hepatitis B virus
associated with oral surgery" (http:/ / www. osap. org/ associations/ 4930/ files/ HBV patient transmission rept. jid. pdf) (PDF). The Journal of
infectious diseases 195 (9): 1311–1314. doi:10.1086/513435. PMID 17397000. .
[70] Alter, M. (2003). "Epidemiology and prevention of hepatitis B". Seminars in liver disease 23 (1): 39–46. doi:10.1055/s-2003-37583.
PMID 12616449.
[71] Lurman A. (1885) Eine icterus epidemic. (In German). Berl Klin Woschenschr 22:20–3.
[72] Alter, HJ; Blumberg (1966). "Further studies on a "new" human isoprecipitin system (Australia antigen)". Blood 27 (3): 297–309.
PMID 5930797.
[73] MacCallum, F.O., Homologous serum hepatitis. Lancet 2, 691, (1947)
[74] Dane, D. (1970). "Virus-Like Particles in Serum of Patients with Australia-Antigen-Associated Hepatitis". The Lancet 295: 695–698.
doi:10.1016/S0140-6736(70)90926-8.
[75] Galibert, F.; Mandart, E.; Fitoussi, F.; Tiollais, P.; Charnay, P. (1979). "Nucleotide sequence of the hepatitis B virus genome (subtype ayw)
cloned in E. Coli". Nature 281 (5733): 646. doi:10.1038/281646a0. PMID 399327.
[76] "Hepatitis B vaccine". Lancet 2 (8206): 1229–30. 1980.
63
Hepatitis B
External links
• CDC webpage on Hepatitis B (http://www.cdc.gov/hepatitis/B/)
• NIH collection of links to relevant articles on Hepatitis B (http://www.nlm.nih.gov/medlineplus/hepatitisb.
html)
64
Hepatitis C
65
Hepatitis C
Hepatitis C
Electron micrograph of hepatitis C virus purified from cell culture. The scale = 50 nanometers
[1]
ICD-10
B 17.1
ICD-9
070.70
OMIM
609532
DiseasesDB
5783
MedlinePlus
000284
eMedicine
med/993
MeSH
D006526
, B 18.2
[3]
, 070.4
[2]
[4]
, 070.5
[5]
[6]
[7]
[8]
[9]
ped/979
[10]
[11]
Hepatitis C is an infectious disease affecting the liver, caused by the hepatitis C virus (HCV).[12] The infection is
often asymptomatic, but once established, chronic infection can progress to scarring of the liver (fibrosis), and
advanced scarring (cirrhosis) which is generally apparent after many years. In some cases, those with cirrhosis will
go on to develop liver failure or other complications of cirrhosis, including liver cancer[12] or life threatening
esophageal varices and gastric varices.
The hepatitis C virus is spread by blood-to-blood contact. Most people have few, if any symptoms after the initial
infection, yet the virus persists in the liver in about 85% of those infected. Persistent infection can be treated with
medication, peginterferon and ribavirin being the standard-of-care therapy. 51% are cured overall. Those who
develop cirrhosis or liver cancer may require a liver transplant, and the virus universally recurs after transplantation.
An estimated 270-300 million people worldwide are infected with hepatitis C. Hepatitis C is only known to cause
disease in humans. No vaccine against hepatitis C is currently available. The existence of hepatitis C (originally
"non-A non-B hepatitis") was postulated in the 1970s and proven in 1989.[13] It is one of five known hepatitis
viruses: A, B, C, D, and E.
Hepatitis C
Signs and symptoms
Acute
Acute hepatitis C refers to the first 6 months after infection with HCV. Between 60% and 70% of people infected
develop no symptoms during the acute phase. In the minority of patients who experience acute phase symptoms, they
are generally mild and nonspecific, and rarely lead to a specific diagnosis of hepatitis C. Symptoms of acute hepatitis
C infection include decreased appetite, fatigue, abdominal pain, jaundice, itching, and flu-like symptoms. Hep C
genotypes 2A and 3A have the highest cure rates, at 81% and 74% respectively.
The hepatitis C virus is usually detectable in the blood by PCR within one to three weeks after infection, and
antibodies to the virus are generally detectable within three to 15 weeks. Spontaneous viral clearance rates are highly
variable; between 10 and 60%[14] of persons infected with HCV clear the virus from their bodies during the acute
phase, as shown by normalization of the liver enzymes alanine transaminase (ALT) and aspartate transaminase
(AST), and plasma HCV-RNA clearance (this is known as spontaneous viral clearance). However, persistent
infections are common[15] and most patients develop chronic hepatitis C, i.e., infection lasting more than 6
months.[16] [17] [18]
Previous practice was to not treat acute infections to see if the person would spontaneously clear; recent studies have
shown that treatment during the acute phase of genotype 1 infections has a greater than 90% success rate, with half
the treatment time required for chronic infections.[19]
Chronic
Chronic hepatitis C is defined as infection with the hepatitis C virus persisting for more than six months. Clinically,
it is often asymptomatic, and it is mostly discovered accidentally (e.g. usual checkup).
The natural course of chronic hepatitis C varies considerably from one person to another. Although almost all people
infected with HCV have evidence of inflammation on liver biopsy, the rate of progression of liver scarring (fibrosis)
shows significant variability among individuals. Accurate estimates of the risk over time are difficult to establish
because of the limited time that tests for this virus have been available.
Recent data suggest that among untreated patients, roughly one-third progress to liver cirrhosis in less than 20 years.
Another third progress to cirrhosis within 30 years. The remainder of patients appear to progress so slowly that they
are unlikely to develop cirrhosis within their lifetimes. In contrast, the NIH consensus guidelines state the risk of
progression to cirrhosis over a 20-year period is 3-20 percent.[20]
Factors that have been reported to influence the rate of HCV disease progression include age (increasing age
associated with more rapid progression), gender (males have more rapid disease progression than females), alcohol
consumption (associated with an increased rate of disease progression), HIV coinfection (associated with a markedly
increased rate of disease progression), and fatty liver (the presence of fat in liver cells has been associated with an
increased rate of disease progression).
Symptoms specifically suggestive of liver disease are typically absent until substantial scarring of the liver has
occurred. However, hepatitis C is a systemic disease and patients may experience a wide spectrum of clinical
manifestations ranging from an absence of symptoms to a more symptomatic illness prior to the development of
advanced liver disease. Generalized signs and symptoms associated with chronic hepatitis C include fatigue, flu-like
symptoms, joint pains, itching, sleep disturbances, appetite changes, nausea, and depression.
Once chronic hepatitis C has progressed to cirrhosis, signs and symptoms may appear that are generally caused by
either decreased liver function or increased pressure in the liver circulation, a condition known as portal
hypertension. Possible signs and symptoms of liver cirrhosis include ascites (accumulation of fluid in the abdomen),
bruising and bleeding tendency, varices (enlarged veins, especially in the stomach and esophagus), jaundice, and a
syndrome of cognitive impairment known as hepatic encephalopathy. Hepatic encephalopathy is due to the
66
Hepatitis C
accumulation of ammonia and other substances normally cleared by a healthy liver.
Liver enzyme tests show variable elevation of ALT and AST. Periodically, they might show normal results. Usually
prothrombin and albumin results are normal, but may become abnormal, once cirrhosis has developed. The levels of
elevation of liver tests do not correlate well with the amount of liver injury on biopsy. Viral genotype and viral load
also do not correlate with the amount of liver injury. Liver biopsy is the best test to determine the amount of scarring
and inflammation. Radiographic studies, such as ultrasound or CT scan, do not always show liver injury until it is
fairly advanced. However, noninvasive tests (blood sample) are coming, with FibroTest[21] and ActiTest,
respectively estimating liver fibrosis and necrotic inflammation. These tests are validated[22] and recommended in
Europe (FDA procedures initiated in USA).
Chronic hepatitis C, more than other forms of hepatitis, can be associated with extrahepatic manifestations associated
with the presence of HCV, such as porphyria cutanea tarda, cryoglobulinemia (a form of small-vessel vasculitis)[23]
and glomerulonephritis (inflammation of the kidney), specifically membranoproliferative glomerulonephritis
(MPGN).[24] Hepatitis C is also rarely associated with sicca syndrome (an autoimmune disorder), thrombocytopenia,
lichen planus, diabetes mellitus and with B-cell lymphoproliferative disorders.[25]
Virology
The hepatitis C virus is a small (50 nm in size), enveloped, single-stranded, positive sense RNA virus. It is the only
known member of the hepacivirus genus in the family Flaviviridae. There are six major genotypes of the hepatitis C
virus, which are indicated numerically (e.g., genotype 1, genotype 2, etc.).
The hepatitis C virus is transmitted by blood-to-blood contact. In developed countries, it is estimated that 90% of
persons with chronic HCV infection were infected through transfusion of unscreened blood or blood products or via
injecting drug use or sexual exposure. In developing countries, the primary sources of HCV infection are unsterilized
injection equipment and infusion of inadequately screened blood and blood products. There has not been a
documented transfusion-related case of hepatitis C in the United States for over a decade, as the blood supply is
vigorously screened with both EIA and PCR technologies.
Although injection drug use is the most common route of HCV infection, any practice, activity, or situation that
involves blood-to-blood exposure can potentially be a source of HCV infection. The virus may be sexually
transmitted, although this is rare, and usually only occurs when an STD that causes open sores and bleeding is also
present and makes blood contact more likely.[26]
Transmission
Sexual activities and practices were initially identified as potential sources of exposure to the hepatitis C virus. More
recent studies question this route of transmission.[27] Currently, heterosexual vaginal intercourse is thought to be a
rare means of transmission of hepatitis C infection. The following are the currently known modes of transmission.
There may be other, as yet unknown, means of transmission.
Injection drug use
Those who currently use or have used drug injection as their delivery route for drugs are at increased risk for getting
hepatitis C because they may be sharing needles or other drug paraphernalia (includes cookers, cotton, spoons,
water, etc.), which may be contaminated with HCV-infected blood. An estimated 60% to 80% of intravenous
recreational drug users in the United States have been infected with HCV.[28] Harm reduction strategies are
encouraged in many countries to reduce the spread of hepatitis C, through education, provision of clean needles and
syringes, and safer injecting techniques. For reasons that are not clear, transmission by this route currently appears to
be declining in the USA.
67
Hepatitis C
The VA Testimony before the Subcommittee on Benefits Committee on Veterans’ Affairs, U.S. House of
Representatives, April 13, 2000, Gary A. Roselle, M. D., Program Director for Infectious Diseases, Veterans Health
Administration, Department of Veterans Affairs, state, "One in 10 US Veterans are infected with HCV", a rate five
times greater than the 1.8% infection rate of the general population."
A study conducted in 1999, by the Veterans Health Administration (VHA), and involving 26,000 veterans shows that
up to 10% of all veterans in the VHA system tested positive for hepatitis C.
Of the total number of persons who were hepatitis C antibody positive, and reported an era of service, 62.7% were
noted to be from the Vietnam. The second most frequent group is listed as post-Vietnam at 18.2%, followed by 4.8%
Korean conflict, 4.3% post-Korean conflict, 4.2% from WWII, and 2.7% Persian Gulf era veterans.
Blood products
Blood transfusion, blood products, or organ transplantation prior to implementation of HCV screening (in the U.S.,
this would refer to procedures prior to 1992) are all risk factors for hepatitis C.
A cDNA clone from the hepatitis C virus genome was first isolated in 1989[29] and reliable tests to screen for the
virus were not available until 1992. Therefore, those who received blood or blood products prior to the
implementation of screening the blood supply for HCV may have been exposed to the virus. Blood products include
clotting factors (taken by hemophiliacs), immunoglobulin, Rhogam, platelets, and plasma. In 2001, the Centers for
Disease Control and Prevention reported the risk of HCV infection from a unit of transfused blood in the United
States is less than one per million transfused units.
Iatrogenic medical or dental exposure
People can be exposed to HCV via inadequately or improperly sterilized medical or dental equipment. Equipment
that may harbor contaminated blood if improperly sterilized includes needles or syringes, hemodialysis equipment,
oral hygiene instruments, jet air guns, etc. Scrupulous use of appropriate sterilization techniques and proper disposal
of used equipment can reduce the risk of iatrogenic exposure to HCV to virtually zero. Limitations in the
implementation and enforcement of stringent standard precautions in public and private medical and dental facilities
is known to be the primary cause of the spread of HCV in Egypt, the country with highest rate of infection in the
world.[30]
Blood exposure
Occupation
Medical and dental personnel, first responders (e.g., firefighters, paramedics, emergency medical technicians, law
enforcement officers), and military combat personnel can be exposed to HCV through accidental exposure to blood
through needle sticks or blood spatter to the eyes or open wounds. Universal precautions to protect against such
accidental exposures significantly reduce the risk of exposure to HCV.
Recreation
Contact sports and other activities, such as "slam dancing" that may result in accidental blood-to-blood exposure are
potential sources of exposure to HCV.[31]
Sexual exposure
Sexual transmission of HCV is considered to be rare. Studies show the risk of sexual transmission in heterosexual,
monogamous relationships is extremely rare or even nil.[32] [33] The CDC does not recommend the use of condoms
between long-term monogamous discordant couples (where one partner is positive and the other is negative).[34]
However, because of the high prevalence of hepatitis C, this small risk may translate into a nontrivial number of
cases transmitted by sexual routes. Vaginal penetrative sex is believed to have a lower risk of transmission than
68
Hepatitis C
sexual practices that involve higher levels of trauma to anogenital mucosa (anal penetrative sex, fisting, or use of sex
toys).[35]
Body piercings and tattoos
Tattooing dyes, ink pots, stylets, and piercing implements can transmit HCV-infected blood from one person to
another if proper sterilization techniques are not followed. Tattoos or piercings performed either before the mid
1980s, "underground," or nonprofessionally are of particular concern, since sterile techniques in such settings may
have been insufficient to prevent disease; sharing unsterilized tattooing equipment (for example, in the prison
system)[36] has an obvious increased risk of acquiring HCV. Indeed, it is this method of transmission that caused
Pamela Anderson to officially state :"I contracted hepatitis C while sharing a tattoo needle with my ex-husband
Tommy Lee. Tommy has the disease and never disclosed it to me during our marriage."[37] The U.S. Centers for
Disease Control and Prevention's position on this subject states that, "Whenever tattoos or body piercings are
performed in informal settings or with nonsterile instruments, transmission of hepatitis C and other infectious
diseases is possible." Despite these risks, it is rare for tattoos in an approved facility to be directly associated with
HCV infection [38]
Shared personal care items
Personal care items such as razors, toothbrushes, cuticle scissors, and other manicuring or pedicuring equipment can
easily be contaminated with blood. Sharing such items can potentially lead to exposure to HCV.[39] Appropriate
caution should be taken regarding any medical condition which results in bleeding, such as canker sores, cold sores,
and immediately after flossing.
HCV is not spread through casual contact, such as hugging, kissing, or sharing eating or cooking utensils.[40]
Vertical transmission
Vertical transmission refers to the transmission of a communicable disease from an infected mother to her child
during the birth process. Mother-to-child transmission of hepatitis C has been well described, but occurs relatively
infrequently. Transmission occurs only among women who are HCV RNA positive at the time of delivery; the risk
of transmission in this setting is approximately 6 out of 100. Among women who are both HCV and HIV positive at
the time of delivery, the risk of transmitting HCV is increased to approximately 25 out of 100.
The risk of vertical transmission of HCV does not appear to be associated with method of delivery or breastfeeding.
Diagnosis
The diagnosis of hepatitis C is rarely made during the acute phase of the disease, because the majority of people
infected experience no symptoms during this phase. Those who do experience acute phase symptoms are rarely ill
enough to seek medical attention. The diagnosis of chronic phase hepatitis C is also challenging due to the absence
or lack of specificity of symptoms until advanced liver disease develops, which may not occur until decades into the
disease.
Chronic hepatitis C may be suspected on the basis of the medical history (particularly if there is any history of IV
drug abuse or inhaled substance usage such as cocaine), a history of piercings or tattoos, unexplained symptoms, or
abnormal liver enzymes or liver function tests found during routine blood testing. Occasionally, hepatitis C is
diagnosed as a result of targeted screening, such as blood donation (blood donors are screened for numerous
blood-borne diseases including hepatitis C) or contact tracing.
Hepatitis C testing begins with serological blood tests used to detect antibodies to HCV. Anti-HCV antibodies can be
detected in 80% of patients within 15 weeks after exposure, in >90% within 5 months after exposure, and in >97%
by 6 months after exposure. Overall, HCV antibody tests have a strong positive predictive value for exposure to the
hepatitis C virus, but may miss patients who have not yet developed antibodies (seroconversion), or have an
69
Hepatitis C
insufficient level of antibodies to detect. Immunocompromised individuals infected with HCV may never develop
antibodies to the virus and therefore, never test positive using HCV antibody screening. Because of this possibility,
RNA testing (see nucleic acid testing methods below) should be considered when antibody testing is negative but
suspicion of hepatitis C is high (e.g. because of elevated transaminases in someone with risk factors for hepatitis C).
However, liver function tests alone are not useful in predicting the severity of infection and normal results do not
exclude the possibility of liver disease.[41]
Anti-HCV antibodies indicate exposure to the virus, but cannot determine if ongoing infection is present. All persons
with positive anti-HCV antibody tests must undergo additional testing for the presence of the hepatitis C virus itself
to determine whether current infection is present. The presence of the virus is tested for using molecular nucleic acid
testing methods, such as polymerase chain reaction (PCR), transcription mediated amplification (TMA), or branched
DNA (b-DNA). All HCV nucleic acid molecular tests have the capacity to detect not only whether the virus is
present, but also to measure the amount of virus present in the blood (the HCV viral load). The HCV viral load is an
important factor in determining the probability of response to interferon-based therapy, but does not indicate disease
severity nor the likelihood of disease progression.
In people with confirmed HCV infection, genotype testing is generally recommended. HCV genotype testing is used
to determine the required length and potential response to interferon-based therapy.
Prevention
According to Centers for Disease Control, hepatitis C virus is spread by exposure to large quantities of blood, either
through the skin or by injection:[42]
• Injection drug use (currently the most common means of HCV transmission in the United States)
• Receipt of donated blood, blood products, and organs (once a common means of transmission, but now rare in the
United States since blood screening became available in 1992)
• Needle stick injuries in healthcare settings
• Birth to an HCV-infected mother
HCV can also be spread infrequently through
• Sex with an HCV-infected person (an inefficient means of transmission)
• Sharing personal items contaminated with infectious blood, such as razors or toothbrushes (also inefficient
vectors of transmission)
• Other healthcare procedures that involve invasive procedures, such as injections (usually recognized in the
context of outbreaks)
• Sharing drug products via insufflation
Strategies such as the provision of new needles and syringes, and education about safer drug injection procedures,
greatly decrease the risk of hepatitis C spreading between injecting drug users.
No vaccine protects against contracting hepatitis C, or helps to treat it. Vaccines are under development and some
have shown encouraging results.[43]
70
Hepatitis C
Treatment
The hepatitis C virus induces chronic infection in 50%-80% of infected persons. Approximately 50% of these do not
respond to therapy. There is a very small chance of clearing the virus spontaneously in chronic HCV carriers (0.5%
to 0.74% per year).[44] [45] However, the majority of patients with chronic hepatitis C will not clear it without
treatment.
Medications (interferon and ribavirin)
Current treatment is a combination of pegylated interferon-alpha-2a or pegylated interferon-alpha-2b (brand names
Pegasys or PEG-Intron) and the antiviral drug ribavirin for a period of 24 or 48 weeks, depending on hepatitis C
virus genotype. In a large multicenter randomized control study among genotype 2 or 3 infected patients
(NORDymanIC),[46] patients achieving HCV RNA below 1000 IU/mL by day 7 who were treated for 12 weeks
demonstrated similar cure rates as those treated for 24 weeks.[47] [48]
Pegylated interferon-alpha-2a plus ribavirin may increase sustained virological response among patients with chronic
hepatitis C as compared to pegylated interferon-alpha-2b plus ribavirin according to a systematic review of
randomized controlled trials .[49] The relative benefit increase was 14.6%. For patients at similar risk to those in this
study (41.0% had sustained virological response when not treated with pegylated interferon alpha 2a plus ribavirin),
this leads to an absolute benefit increase of 6%. About 16.7 patients must be treated for one to benefit (number
needed to treat = 16.7; click here [50] to adjust these results for patients at higher or lower risk of sustained
virological response). However, this study's results may be biased due to uncertain temporality of association,
selective dose response.
Treatment is generally recommended for patients with proven hepatitis C virus infection and persistently abnormal
liver function tests.
Treatment during the acute infection phase has much higher success rates (greater than 90%) with a shorter duration
of treatment; however, this must be balanced against the 15-40% chance of spontaneous clearance without treatment
(see Acute Hepatitis C section above).
Those with low initial viral loads respond much better to treatment than those with higher viral loads (greater than
400,000 IU/mL). Current combination therapy is usually supervised by physicians in the fields of gastroenterology,
hepatology or infectious disease.
The treatment may be physically demanding, particularly for those with a prior history of drug or alcohol abuse. It
can qualify for temporary disability in some cases. A substantial proportion of patients will experience a panoply of
side effects ranging from a 'flu-like' syndrome (the most common, experienced for a few days after the weekly
injection of interferon) to severe adverse events including anemia, cardiovascular events and psychiatric problems
such as suicide or suicidal ideation. The latter are exacerbated by the general physiological stress experienced by the
patient.
Cure rates by genotype
Responses can vary by genotype. Approximately 80% of hepatitis C patients in the United States have genotype 1,
and genotype 4 is more common in the Middle East and Africa.
71
Hepatitis C
72
Description
Genotype
2 and 3
Sustained cure rates (sustained viral response) of 75% or better are seen in people with HCV genotypes 2 and 3 with 24 weeks of
[51]
treatment.
Patients achieving HCV RNA below 1000 IU/mL by day 7 (i.e. just prior to the second dose of pegylated interferon)
[47]
may be treated for as little as 12 weeks with retained sustained cure rates.
1
Sustained response is about 50% in patients with HCV genotype 1 given 48 weeks of treatment. In patients with HCV genotype 1, if
treatment with pegylated interferon + ribavirin does not produce a 2-log viral load reduction or complete clearance of RNA (termed
"early virological response") after 12 weeks the chance of treatment success is less than 1%.
4
Sustained response is about 65% in those with genotype 4 given 48 weeks of treatment.
6
The evidence for treatment in genotype 6 disease is currently sparse, and the evidence that exists is for 48 weeks of treatment at the
[52]
same doses as are used for genotype 1 disease.
Physicians considering shorter durations of treatment (e.g., 24 weeks) should do so
within the context of a clinical trial.
Early virological response is typically not tested in non-genotype 1 patients, as the chances of attaining it are greater
than 90%. The mechanism of cure is not entirely clear, because some patients who have a sustained virological
response still appear to have actively replicating virus in their liver and peripheral blood mononuclear cells.[53]
Special factors affecting patients
Host factors
For genotype 1 hepatitis C treated with pegylated interferon-alpha-2a or pegylated interferon-alpha-2b combined
with ribavirin, it has been shown that genetic polymorphisms near the human IL28B gene, encoding interferon
lambda 3, are associated with significant differences in response to the treatment. This finding, originally reported in
Nature,[54] showed that genotype 1 hepatitis C patients carrying certain genetic variant alleles near the IL28B gene
are more possibly to achieve sustained virological response after the treatment than others. A later report from
Nature [55] demonstrated the same genetic variants are also associated with the natural clearance of the genotype 1
hepatitis C virus.
Similarly, baseline pretreatment plasma levels of IP-10 (also known as CXCL10) are elevated in patients chronically
infected with hepatitis C virus (HCV) of genotypes 1 or 4 who do not achieve a sustained viral response (SVR) after
completion of antiviral therapy.[56] [57] IP-10 in plasma is mirrored by intrahepatic IP-10 mRNA, and both strikingly
predict the first days of elimination of HCV RNA (“first phase decline”) during interferon/ribavirin therapy for all
HCV genotypes.[58]
Viral factors
The basis for the differential response to treatment between viral genotypes is still being worked out. Mutations in
the core arginine70glutamine (R70Q) and in the nonstructural protein 5A within its interferon sensitivity determining
region have been associated with responsiveness at weeks 12 and 4 respectively.[59]
Depression during therapy
In the study by Leutscher et al., evaluating 325 chronically infected genotype 2 or 3 patients, it was observed that (1)
depressive symptoms among patients undergoing HCV therapy are commonly overlooked by routine clinical
interviews, (2) the emergence of depression compromises the outcome of HCV therapy, and (3) the major depression
inventory (MDI) scale may be useful in identifying patients at risk for treatment-induced depression.[60]
Hepatitis C
Pregnancy and breastfeeding
If a woman who is pregnant has risk factors for hepatitis C, she should be tested for antibodies against HCV. About
4% infants born to HCV-infected women become infected. While there is no preventative treatment, there is a high
probability of the babies ridding themselves the HCV in the first 12 months.
In a mother who also has HIV, the rate of transmission can be as high as 19%. There are currently no data to
determine whether antiviral therapy reduces perinatal transmission. Ribavirin and interferons are contraindicated
during pregnancy. However, avoiding fetal scalp monitoring and prolonged labor after rupture of membranes may
reduce the risk of transmission to the infant.
HCV antibodies from the mother may persist in infants until 15 months of age. If an early diagnosis is desired,
testing for HCV RNA can be performed between the ages of 2 and 6 months, with a repeat test done independent of
the first test result. If a later diagnosis is preferred, an anti-HCV test can performed after 15 months of age. Most
infants infected with HCV at the time of birth have no symptoms and do well during childhood. There is no evidence
that breast-feeding spreads HCV. To be cautious, an infected mother should avoid breastfeeding if her nipples are
cracked and bleeding.[61]
Additional recommendations and alternative therapies
Current guidelines strongly recommend that hepatitis C patients be vaccinated for hepatitis A and B if they have not
yet been exposed to these viruses, as infection with a second virus could worsen their liver disease.
Alcoholic beverage consumption accelerates HCV associated fibrosis and cirrhosis, and makes liver cancer more
likely; insulin resistance and metabolic syndrome may similarly worsen the hepatic prognosis. There is also evidence
that smoking increases the fibrosis (scarring) rate.
Several alternative therapies aim to maintain liver functionality, rather than treat the virus itself, thereby slowing the
course of the disease to retain quality of life. As an example, extract of Silybum marianum and Sho-saiko-to are sold
for their HCV related effects; the first is said to provide some generic help to hepatic functions, and the second
claims to aid in liver health and provide some antiviral effects.[62] There has never been any verifiable histologic or
virologic benefit demonstrated with any of the alternative therapies.
Epidemiology
It is estimated that hepatitis C has infected nearly 200 million people
worldwide, and infects 3-4 million more people per year.[63] [64] There
are about 35,000 to 185,000 new cases a year in the United States. It is
currently a leading cause of cirrhosis, a common cause of
hepatocellular carcinoma, and as a result of these conditions it is the
leading reason for liver transplantation in the United States.
Prevalence of hepatitis C worldwide (1999,
Coinfection with HIV is common, and rates among HIV positive
WHO)
populations are higher. Annual deaths from HCV in the United States
range from 10,000 to 20,000; expectations are that this mortality rate will increase, as those who were infected by
transfusion before HCV testing become apparent. A survey conducted in California showed a prevalence of up to
34% among prison inmates;[65] 82% of subjects diagnosed with hepatitis C have previously been in jail,[66] and
transmission while in prison is well described.[67]
Prevalence is higher in some countries in Africa and Asia.[68] Egypt has the highest seroprevalence for HCV, up to
20% in some areas. There is a hypothesis that the high prevalence is linked to a now-discontinued mass-treatment
campaign for schistosomiasis, which is endemic in that country.[69] Regardless of how the epidemic started, a high
rate of HCV transmission continues in Egypt, both iatrogenically and within the community and household.
73
Hepatitis C
Coinfection with HIV
Approximately 350,000 people (35% of patients) in the USA infected with HIV are coinfected with the hepatitis C
virus, mainly because both viruses are blood-borne and are present in similar populations. HCV is the leading cause
of chronic liver disease in the USA. It has been demonstrated in clinical studies that HIV infection causes a more
rapid progression of chronic hepatitis C to cirrhosis and liver failure. This is not to say treatment is not an option for
those living with coinfection.
In a study involving 21 HIV coinfected patients (DICO),[70] pretreatment baseline plasma levels of IP-10 predicted
the reduction of HCV RNA during the first days of interferon/ribavirin therapy (“first phase decline”) for HCV
genotypes 1-3,[71] as is also the case in HCV monoinfected patients.[56] [57] [58] Pretreatment IP-10 levels below 150
pg/mL are predictive of a favorable response, and may thus be useful in encouraging these otherwise
difficult-to-treat patients to initiate therapy.[71]
History
In the mid 1970s, Harvey J. Alter, Chief of the Infectious Disease Section in the Department of Transfusion
Medicine at the National Institutes of Health, and his research team demonstrated how most posttransfusion hepatitis
cases were not due to hepatitis A or B viruses. Despite this discovery, international research efforts to identify the
virus, initially called non-A, non-B hepatitis (NANBH), failed for the next decade. In 1987, Michael Houghton,
Qui-Lim Choo, and George Kuo at Chiron Corporation, collaborating with Dr. D.W. Bradley from CDC, used a
novel molecular cloning approach to identify the unknown organism and develop a diagnostic test.[72] In 1988, the
virus was confirmed by Alter by verifying its presence in a panel of NANBH specimens. In April 1989, the
discovery of the virus, renamed hepatitis C virus (HCV), was published in two articles in the journal Science.[73] [74]
The discovery led to significant improvements in diagnosis and improved antiviral treatment.[72]
Chiron filed for several patents on the virus and its diagnosis.[75] A competing patent application by the CDC was
dropped in 1990 after Chiron paid $1.9 million to the CDC and $337,500 to Bradley. In 1994, Bradley sued Chiron,
seeking to invalidate the patent, have himself included as a coinventor, and receive damages and royalty income. He
dropped the suit in 1998 after losing before an appeals court.[76] [77]
In 2000, Drs. Alter and Houghton were honored with the Lasker Award for Clinical Medical Research for
"pioneering work leading to the discovery of the virus that causes hepatitis C and the development of screening
methods that reduced the risk of blood transfusion-associated hepatitis in the U.S. from 30% in 1970 to virtually zero
in 2000."[78]
In 2004, Chiron held 100 patents in 20 countries related to hepatitis C, and had successfully sued many companies
for infringement. Scientists and competitors have complained the company hinders the fight against hepatitis C by
demanding too much money for its technology.[76]
Research
The drug viramidine, which is a prodrug of ribavirin that has better targeting for the liver, and therefore may be more
effective against hepatitis C for a given tolerated dose, is in phase III experimental trials against hepatitis C. It will
be used in conjunction with interferons, in the same manner as ribavirin. However, this drug is not expected to be
active against ribavirin-resistant strains, and the use of the drug against infections which have already failed
ribavirin/interferon treatment, is unproven.
There are new drugs under development, like the protease inhibitors (including telaprevir/VX 950), entry inhibitors
(such as SP 30 and ITX 5061)[79] [80] [81] and polymerase inhibitors (such as RG7128, PSI-7977 and NM 283), but
development of some of these is still in the early phase. VX 950, also known as Telaprevir[82] is currently in Phase
III trials. [83] [84] One protease inhibitor, BILN 2061, had to be discontinued due to safety problems early in the
clinical testing. Some more modern new drugs that provide some support in treating HCV are albuferon[85] and
74
Hepatitis C
Zadaxin.[86] Antisense phosphorothioate oligos have been targeted to hepatitis C.[87] Antisense Morpholino oligos
have shown promise in preclinical studies[88] however, they were found to cause a limited viral load reduction.[89]
Some studies have shown that HCV viral replication is dependent upon the host factor miR-122. As a result,
pharmaceutical companies are developing potential HCV drugs that target miR-122. HCV therapies that target this
host factor necessary for viral replication, rather than the virus itself, are promising, as they show little to no
potential for viral resistance. [90] One such drug is miravirsen, developed by Santaris Pharma a/s, a locked nucleic
acid based miR-122 antagonist in Phase II clinical trials as of late 2010. [91]
Immunoglobulins against the hepatitis C virus exist, and newer types are under development. Thus far, their roles
have been unclear, as they have not been shown to help in clearing chronic infection or in the prevention of infection
with acute exposures (e.g. needle sticks). They do have a limited role in transplant patients.
In addition to the standard treatment with interferon and ribavirin, some studies have shown higher success rates
when the antiviral drug amantadine (Symmetrel) is added to the regimen. Sometimes called "triple therapy", it
involves the addition of 100 mg of amantadine twice a day. Studies indicate this may be especially helpful for
"nonresponders" - patients who have not been successful in previous treatments using interferon and ribavirin
only.[92] Currently, amantadine is not approved for treatment of hepatitis C, and studies are ongoing to determine
when it is most likely to benefit the patient and when it is a risk due to their liver deterioration.
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Journal of Infectious Diseases 194 (7): 895–903. doi:10.1086/507307. PMID 16960776.
[57] Lagging M, Romero AI, Westin J, et al. (December 2006). "IP-10 predicts viral response and therapeutic outcome in difficult-to-treat
patients with HCV genotype 1 infection". Hepatology 44 (6): 1617–25. doi:10.1002/hep.21407. PMID 17133471.
[58] Askarieh G, Alsiö A, Pugnale P, et al. (May 2010). "Systemic and intrahepatic interferon-gamma-inducible protein 10 kDa predicts the
first-phase decline in hepatitis C virus RNA and overall viral response to therapy in chronic hepatitis C". Hepatology 51 (5): 1523–30.
doi:10.1002/hep.23509. PMID 20186843.
[59] Enomoto, Nobuyuki; Maekawa, Shinya (2010). "HCV Genetic Elements Determining the Early Response to Peginterferon and Ribavirin
Therapy". Intervirology 53 (1): 66. doi:10.1159/000252787. PMID 20068344.
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C". Hepatology 52 (2): 430–5. doi:10.1002/hep.23699. PMID 20683942.
[61] Mast EE (2004). "Mother-to-infant hepatitis C virus transmission and breastfeeding". Advances in Experimental Medicine and Biology 554:
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[62] NCCAM. Hepatitis C and Complementary and Alternative Medicine: 2003 Update (http:/ / nccam. nih. gov/ health/ hepatitisc/ ). May 2004.
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[63] Hepatitis C (http:/ / www. who. int/ vaccine_research/ diseases/ hepatitis_c/ en/ ), WHO
[64] Hepatitis C Infection (http:/ / www. drugabuse. gov/ HepatitisAlert/ HepatitisAlert. html), The National Institute on Drug Abuse (NIDA)
[65] Ruiz JD, Molitor F, Plagenhoef JA (November 2002). "Trends in hepatitis C and HIV infection among inmates entering prisons in
California, 1994 versus 1999". AIDS 16 (16): 2236–8. doi:10.1097/00002030-200211080-00023. PMID 12409752.
[66] Campbell JV, Hagan H, Latka MH, et al. (February 2006). "High prevalence of alcohol use among hepatitis C virus antibody positive
injection drug users in three US cities" (http:/ / www. pubmedcentral. nih. gov/ articlerender. fcgi?tool=pmcentrez& artid=2196223). Drug
and Alcohol Dependence 81 (3): 259–65. doi:10.1016/j.drugalcdep.2005.07.005. PMID 16129567. PMC 2196223.
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[68] Chapter 4 - Hepatitis, Viral, Type C - Yellow Book (http:/ / wwwn. cdc. gov/ travel/ yellowBookCh4-HepC. aspx), CDC Health Information
for International Travel 2008
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virus in Egypt". Lancet 355 (9207): 887–91. doi:10.1016/S0140-6736(99)06527-7. PMID 10752705.
[70] Falconer K, Sandberg JK, Reichard O, Alaeus A (2009). "HCV/HIV coinfection at a large HIV outpatient clinic in Sweden: feasibility and
results of hepatitis C treatment". Scandinavian Journal of Infectious Diseases 41 (11-12): 881–5. doi:10.3109/00365540903214272.
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[71] Falconer K, Askarieh G, Weis N, Hellstrand K, Alaeus A, Lagging M (July 2010). "IP-10 predicts the first phase decline of HCV RNA and
overall viral response to therapy in patients co-infected with chronic hepatitis C virus infection and HIV". Scandinavian Journal of Infectious
Diseases: 100707060350094. doi:10.3109/00365548.2010.498019. PMID 20608766.
[72] Boyer, JL (2001). Liver cirrhosis and its development: proceedings of the Falk Symposium 115. Springer. pp. 344 (http:/ / books. google.
ca/ books?id=n5P696E7T0wC& pg=PA344#v=onepage& q& f=false). ISBN 9780792387602.
[73] Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M (April 1989). "Isolation of a cDNA clone derived from a blood-borne
non-A, non-B viral hepatitis genome". Science 244 (4902): 359–62. doi:10.1126/science.2523562. PMID 2523562.
[74] Kuo G, Choo QL, Alter HJ, et al. (April 1989). "An assay for circulating antibodies to a major etiologic virus of human non-A, non-B
hepatitis". Science 244 (4902): 362–4. doi:10.1126/science.2496467. PMID 2496467.
[75] Houghton, M., Q.-L. Choo, and G. Kuo. NANBV Diagnostics and Vaccines. European Patent No. EP-0-3 18-216-A1. European Patent
Office (filed 18 November 1988, published 31 May 1989).
[76] Paul Elias. " "Hepatitis Drug-Maker Complaints Reviewed" (http:/ / www. hcvadvocate. org/ news/ newsRev/ 2004/ NewsRev-37. html#15),
The Associated Press, 27 February 2004
[77] Daniel W. Bradley v. Chiron Corporation, 136 F. 3d 1317 (U.S. Court of Appeals for the Federal Circuit, 1998)
[78] 2000 Winners Albert Lasker Award for Clinical Medical Research (http:/ / web. archive. org/ web/ 20080225184627/ http:/ / www.
laskerfoundation. org/ awards/ library/ 2000clinical. shtml), The Lasker Foundation. Retrieved 20 February 2008.
[79] "SP-30: A Novel Treatment for Hepatitis C" (http:/ / www. samaritanpharma. com/ aids_hiv_program_sp-10T1. asp). . Retrieved 2 March
2010.
[80] "ITX-5061" (http:/ / www. itherx. com/ hepatitis. html). . Retrieved 2 March 2010.
77
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[81] "iTherX Pharmaceuticals Announces Phase 2a Proof-of-concept Trial of First Hepatitis C Virus Entry Inhibitor" (http:/ / www.
hivandhepatitis. com/ hep_c/ news/ 2009/ 021309_a. html). . Retrieved 2 March 2010.
[82] "Telaprevir" (http:/ / www. vrtx. com/ current-projects/ drug-candidates/ telaprevir-VX-950. html). Vrtx.com. . Retrieved 2010-08-27.
[83] Hinrichsen H, Benhamou Y, Wedemeyer H, et al. (November 2004). "Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine
protease inhibitor, in hepatitis C genotype 1 patients". Gastroenterology 127 (5): 1347–55. doi:10.1053/j.gastro.2004.08.002.
PMID 15521004.
[84] Lamarre D, Anderson PC, Bailey M, et al. (November 2003). "An NS3 protease inhibitor with antiviral effects in humans infected with
hepatitis C virus". Nature 426 (6963): 186–9. doi:10.1038/nature02099. PMID 14578911.
[85] "Human Genome Sciences Announces Completion of Enrollment in Phase 2b Monthly-Dosing Trial of Albuferon" (http:/ / sev. prnewswire.
com/ health-care-hospitals/ 20090619/ PH3522819062009-1. html). PR Newswire. 19 June 2009. . Retrieved 13 July 2009. "Trial conducted
by Novartis evaluating safety and efficacy of Albuferon administered every four weeks in combination with ribavirin in patients with
genotypes 2 and 3 hepatitis C"
[86] Poo, Jorge L.; Francisco Sánchez Ávila; David Kershenobich; Xochitl García Samper; Rocío Torres-Ibarra; Julieta Góngora; Carlos Cano;
Miguel Parada;1 Misael Uribe (2008). "Efficacy of triple therapy with thymalfasin, peginterferon α-2a, and ribavirin for the treatment of
hispanic chronic HCV nonresponders" (http:/ / www. medigraphic. com/ pdfs/ hepato/ ah-2008/ ah084j. pdf) (PDF). Annals of Hepatology. .
Retrieved 20 July 2009. "More recently, thymalfasin (thymosin alpha 1, Tα1, ZADAXIN, SciClone Pharmaceuticals, Inc., CA, USA) has
shown efficacy in the treatment of chronic HCV infection."
[87] Zhang H, Hanecak R, Brown-Driver V, et al. (February 1999). "Antisense oligonucleotide inhibition of hepatitis C virus (HCV) gene
expression in livers of mice infected with an HCV-vaccinia virus recombinant" (http:/ / aac. asm. org/ cgi/ pmidlookup?view=long&
pmid=9925530). Antimicrobial Agents and Chemotherapy 43 (2): 347–53. PMID 9925530. PMC 89075. .
[88] McCaffrey AP, Meuse L, Karimi M, Contag CH, Kay MA (August 2003). "A potent and specific morpholino antisense inhibitor of hepatitis
C translation in mice". Hepatology 38 (2): 503–8. doi:10.1053/jhep.2003.50330. PMID 12883495.
[89] "Study of AVI-4065 in Healthy Volunteers and Chronic Active HCV Patients - Full Text View" (http:/ / clinicaltrials. gov/ ct/ show/
NCT00229749?order=1). ClinicalTrials.gov. . Retrieved 2010-08-27.
[90] Elmén, Joacim et al. 2008. "LNA-mediated microRNA silencing in non-human primates.” (http:/ / www. nature. com/ nature/ journal/ v452/
n7189/ full/ nature06783. html) Nature 452: 896-899.
[91] Franciscus, Alan. "Hepatitis C Treatments in Current Development," (http:/ / www. hcvadvocate. org/ hepatitis/ hepC/ HCVDrugs. html)
HCV Advocate (2010): 1-22.
[92] Maynard M, Pradat P, Bailly F, et al. (March 2006). "Amantadine triple therapy for non-responder hepatitis C patients. Clues for
controversies (ANRS HC 03 BITRI)". Journal of Hepatology 44 (3): 484–90. doi:10.1016/j.jhep.2005.11.038. PMID 16426697.
External links
Information and resources
• CDC's Hepatitis C Fact Sheet (http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm)
• Hepatitis C (http://www.dmoz.org/Health/Conditions_and_Diseases/Digestive_Disorders/Liver/Hepatitis/
Hepatitis_C/) at the Open Directory Project
• "What I need to know about Hepatitis C" (http://digestive.niddk.nih.gov/ddiseases/pubs/hepc_ez/). National
Digestive Diseases Information Clearinghouse. May 2004. Retrieved 2008-09-28.
• Virus Pathogen Database and Analysis Resource (ViPR): Flaviviridae (http://www.viprbrc.org/brc/home.
do?decorator=flavi)
Organizations and programs
•
•
•
•
•
National Hepatitis C Program (http://www.hepatitis.va.gov/) U.S. Department of Veterans Affairs
Hepatitis C (http://www.liverfoundation.org/abouttheliver/info/hepatitisc/) American Liver Foundation
Hepatitis Australia (http://www.hepatitisaustralia.com/) Hepatitis Australia
Hepatitis C (http://www.hepc.nhs.uk/) homepage of the UK National Health Service
National CIHR Research Training Program in Hepatitis C (http://www.ncrtp-hepc.ca/) Training program for
student researchers funded by the Canadian Institutes of Health Research.
78
Hepatitis D
79
Hepatitis D
Hepatitis D
Group:
Group V ((-)ssRNA)
Order:
Unassigned
Family: Unassigned
Genus:
Deltavirus
Species: Hepatitis delta virus
Hepatitis D
[1]
ICD-10
B 17.0
ICD-9
070.31
MeSH
D003699
, B 18.0
[2]
[2]
[3]
Hepatitis D, also referred to as Hepatitis D virus (HDV) and classified as Hepatitis delta virus, is a disease caused
by a small circular enveloped RNA virus. It is one of seven known hepatitis viruses: A, B, C, D , E, F,G. HDV is
considered to be a subviral satellite because it can propagate only in the presence of the Hepatitis B virus (HBV).[4]
Transmission of HDV can occur either via simultaneous infection with HBV (coinfection) or via infection of an
individual previously infected with HBV (superinfection).
Both superinfection and coinfection with HDV results in more severe complications compared to infection with
HBV alone. These complications include a greater likelihood of experiencing liver failure in acute infections and a
rapid progression to liver cirrhosis, with an increased chance of developing liver cancer in chronic infections.[5] In
combination with hepatitis B virus, hepatitis D has the highest mortality rate of all the hepatitis infections of 20%.
Virology
Genome
The HDV genome exists as an enveloped negative sense, single-stranded, closed circular RNA. Because of a
nucleotide sequence that is 70% self-complementary, the HDV genome forms a partially double stranded RNA
structure that is described as rod-like.[6] With a genome of approximately 1700 nucleotides, HDV is the smallest
"virus" known to infect animals.
It has been proposed that HDV may have originated from a class of plant viruses called viroids.[7] Evidence in
support of this hypothesis stems from the fact that both HDV and viroids exist as single-stranded, closed circular
RNAs that have rod-like structures. Likewise, both HDV and viroids contain RNA sequences that can assume
catalytically active structures called ribozymes. During viral replication, these catalytic RNAs are required in order
to produce unit length copies of the genome from longer RNA concatamers. Finally, neither HDV nor viroids encode
their own polymerase. Instead, replication of HDV and viroids requires a host polymerase that can utilize RNA as a
template.[8] RNA polymerase II has been implicated as the polymerase responsible for the replication of HDV.[9] [10]
Normally RNA polymerase II utilizes DNA as a template and produces mRNA. Consequently, if HDV indeed
utilizes RNA polymerase II during replication, it would be the only known pathogen capable of using a
DNA-dependent polymerase as an RNA-dependent polymerase.
Hepatitis D
Delta antigens
A significant difference between viroids and HDV is that, while viroids produce no proteins, HDV produces two
proteins called the small and large delta antigens (HDAg-S and HDAg-L, respectively). These two proteins are
produced from a single open reading frame. They are identical for 195 amino acids and differ only by the presence of
an additional 19 amino acids at the C-terminus of HDAg-L. Despite having 90% identical sequences, these two
proteins play diverging roles during the course of an infection. HDAg-S is produced in the early stages of an
infection and is required for viral replication. HDAg-L, in contrast, is produced during the later stages of an
infection, acts as an inhibitor of viral replication, and is required for assembly of viral particles.[11]
Transmission
HDV is rare in most developed countries, and is mostly associated with intravenous drug use. However, HDV is
much more common in the immediate Mediterranean region, sub-Saharan Africa, the Middle East, and the northern
part of South America.[12] In all, about 20 million people may be infected with HDV.[13]
References
[4] Makino S, Chang MF, Shieh CK, et al. (1987). "Molecular cloning and sequencing of a human hepatitis delta (delta) virus RNA". Nature 329
(6137): 343–6. doi:10.1038/329343a0. PMID 3627276.
[5] Fattovich G, Giustina G, Christensen E, et al. (March 2000). "Influence of hepatitis delta virus infection on morbidity and mortality in
compensated cirrhosis type B. The European Concerted Action on Viral Hepatitis (Eurohep)" (http:/ / gut. bmj. com/ cgi/
pmidlookup?view=long& pmid=10673308). Gut 46 (3): 420–6. doi:10.1136/gut.46.3.420. PMID 10673308. PMC 1727859. .
[6] Saldanha JA, Thomas HC, Monjardino JP (July 1990). "Cloning and sequencing of RNA of hepatitis delta virus isolated from human serum"
(http:/ / vir. sgmjournals. org/ cgi/ pmidlookup?view=long& pmid=2374010). J. Gen. Virol. 71 ( Pt 7): 1603–6.
doi:10.1099/0022-1317-71-7-1603. PMID 2374010. .
[7] Elena SF, Dopazo J, Flores R, Diener TO, Moya A (July 1991). "Phylogeny of viroids, viroidlike satellite RNAs, and the viroidlike domain of
hepatitis delta virus RNA" (http:/ / www. pnas. org/ cgi/ pmidlookup?view=long& pmid=1712103). Proc. Natl. Acad. Sci. U.S.A. 88 (13):
5631–4. doi:10.1073/pnas.88.13.5631. PMID 1712103. PMC 51931. .
[8] Taylor JM (April 2003). "Replication of human hepatitis delta virus: recent developments". Trends Microbiol. 11 (4): 185–90.
doi:10.1016/S0966-842X(03)00045-3. PMID 12706997.
[9] Lehmann E, Brueckner F, Cramer P (November 2007). "Molecular basis of RNA-dependent RNA polymerase II activity". Nature 450 (7168):
445–9. doi:10.1038/nature06290. PMID 18004386.
[10] Filipovska J, Konarska MM (January 2000). "Specific HDV RNA-templated transcription by pol II in vitro" (http:/ / www. rnajournal. org/
cgi/ pmidlookup?view=long& pmid=10668797). RNA 6 (1): 41–54. doi:10.1017/S1355838200991167. PMID 10668797. PMC 1369892. .
[11] Sato S, Cornillez-Ty C, Lazinski DW (August 2004). "By inhibiting replication, the large hepatitis delta antigen can indirectly regulate
amber/W editing and its own expression" (http:/ / jvi. asm. org/ cgi/ pmidlookup?view=long& pmid=15254184). J. Virol. 78 (15): 8120–34.
doi:10.1128/JVI.78.15.8120-8134.2004. PMID 15254184. PMC 446097. .
[12] Radjef N, Gordien E, Ivaniushina V, et al. (March 2004). "Molecular phylogenetic analyses indicate a wide and ancient radiation of African
hepatitis delta virus, suggesting a deltavirus genus of at least seven major clades" (http:/ / jvi. asm. org/ cgi/ pmidlookup?view=long&
pmid=14963156). J. Virol. 78 (5): 2537–44. doi:10.1128/JVI.78.5.2537-2544.2004. PMID 14963156. PMC 369207. .
[13] Taylor JM (January 2006). "Hepatitis delta virus". Virology 344 (1): 71–6. doi:10.1016/j.virol.2005.09.033. PMID 16364738.
External links
• World Health Organization Fact sheet on Hepatitis D (http://www.who.int/csr/disease/hepatitis/
whocdscsrncs20011/en/index.html)
• Viralzone: Deltavirus (http://www.expasy.org/viralzone/all_by_species/175.html)
80
Hepatitis E
81
Hepatitis E
Hepatitis E
Hepatitis E virus
[1]
ICD-10
B 17.2
ICD-9
070.4
DiseasesDB
5794
eMedicine
med/995
MeSH
D016751
[4]
[2]
[3]
[4]
Hepatitis E is a viral hepatitis (liver inflammation) caused by infection with a virus called hepatitis E virus (HEV).
HEV is a positive-sense single-stranded RNA icosahedral virus with a 7.5 kilobase genome. HEV has a fecal-oral
transmission route. It is one of five known hepatitis viruses: A, B, C, D, and E. Infection with this virus was first
documented in 1955 during an outbreak in New Delhi, India.[5]
Molecular biology
Although it was originally classified in the Caliciviridae family, the virus has since been classified into the genus
Hepevirus, but was not assigned to a viral family. The virus itself is a small non-enveloped particle.
The genome is approximately 7200 bases in length, is a polyadenylated single-strand RNA molecule that contains
three discontinuous and partially overlapping open reading frames (ORFs) along with 5' and 3' cis-acting elements,
which have important roles in HEV replication and transcription. ORF1 encode a methyltransferase, protease,
helicase and replicase; ORF2 encode the capsid protein and ORF3 encodes a protein of undefined function. A
three-dimensional, atomic-resolution structure of the capsid protein in the context of a virus-like particle has been
described.[6] An in vitro culture system is not yet available.
As of 2009 there are approximately 1,600 sequences of both human and animal isolates of HEV available in
open-access sequence databases.
Hepatitis E
Epidemiology
The incidence of hepatitis E is highest in juveniles and adults between the ages of 15 and 40. Though children often
contract this infection as well, they less frequently become symptomatic. Mortality rates are generally low, for
Hepatitis E is a “self-limiting” disease, in that it usually goes away by itself and the patient recovers. However,
during the duration of the infection (usually several weeks), the disease severely impairs a person’s ability to work,
care for family members, and obtain food. Hepatitis E occasionally develops into an acute severe liver disease, and is
fatal in about 2% of all cases. Clinically, it is comparable to hepatitis A, but in pregnant women the disease is more
often severe and is associated with a clinical syndrome called fulminant hepatic failure. Pregnant women, especially
those in the third trimester, suffer an elevated mortality rate from the disease of around 20%.
Although there is one serotype of this virus, four distinct genotypes have been reported. Genotypes 1 and 2 are
restricted to humans and often associated with large outbreaks and epidemics in developing countries with poor
sanitation conditions. Genotypes 3 and 4 infect humans, pigs and other animal species and have been responsible for
sporadic cases of hepatitis E in both developing and industrialized countries.
Patterns
Hepatitis E is prevalent in most developing countries, and common in any country with a hot climate. It is
widespread in Southeast Asia, northern and central Africa, India, and Central America. It is spread mainly through
fecal contamination of water supplies or food; person-to-person transmission is uncommon. Outbreaks of epidemic
Hepatitis E most commonly occur after heavy rainfalls and monsoons because of their disruption of water supplies.
Major outbreaks have occurred in New Delhi, India (30,000 cases in 1955-1956), Burma (20,000 cases in
1976-1977), Kashmir, India (52,000 cases in 1978), Kanpur, India (79,000 cases in 1991), and China (100,000 cases
between 1986 and 1988).
Animals as a reservoir
Domestic animals have been reported as a reservoir for the hepatitis E virus, with some surveys showing infection
rates exceeding 95% among domestic pigs.[7] Transmission after consumption of wild boar meat and uncooked deer
meat has been reported as well.[8] The rate of transmission to humans by this route and the public health importance
of this are however still unclear.[9]
A number of other small mammals have been identified as potential reservoirs: the lesser bandicoot rat (Bandicota
bengalensis), the black rat (Rattus rattus brunneusculus) and the Asian house shrew (Suncus murinus).[10] A new
virus designated rat hepatitis E virus has been isolated.[11]
An avian virus has been described that is associated with Hepatitis-Splenomegaly syndrome in chickens. This virus
is genetically and antigenically related to mammalian HEV and probably represents a new genus in the family.
Replicative virus has been found in the small intestine, lymph nodes, colon as well as the liver of experimentally
infected pigs.
Recent outbreaks
In 2004, there were two major outbreaks, both of them in sub-Saharan Africa. There was an outbreak in Chad in
which, as of September 27, were 1,442 reported cases and 46 deaths. The second was in Sudan with, as of September
28, 6,861 cases and 87 deaths. Increasingly, hepatitis E is being seen in developed nations with reports of cases in
the UK, US and Japan. The disease is thought to be a zoonosis in that animals are thought to be the source. Both deer
and pigs have been implicated.
82
Hepatitis E
Prevention
Improving sanitation is the most important measure, which consists of proper treatment and disposal of human
waste, higher standards for public water supplies, improved personal hygiene procedures and sanitary food
preparation. Thus, prevention strategies of this disease are similar to those of many others that plague developing
nations, and they require large-scale international financing of water supply and water treatment projects. A vaccine
based on recombinant viral proteins has been developed and recently tested in a high-risk population (military
personnel of a developing country).[12] The vaccine appeared to be effective and safe, but further studies are needed
to assess the long-term protection and the cost-effectiveness of hepatitis E vaccination.
References
[1]
[2]
[3]
[4]
[5]
Gupta DN, Smetana HF (1957). "The histopathology of viral hepatitis as seen in the Delhi epidemic (1955-56)". Indian J. Med. Res. 45
(Suppl.): 101–13. PMID 13438544.
[6] Guu TS, Liu Z, Ye Q, et al. (August 2009). "Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and
receptor binding" (http:/ / www. pubmedcentral. nih. gov/ articlerender. fcgi?tool=pmcentrez& artid=2722310). Proc. Natl. Acad. Sci. U.S.A.
106 (31): 12992–7. doi:10.1073/pnas.0904848106. PMID 19622744. PMC 2722310.
[7] Satou K, Nishiura H (2007). "Transmission Dynamics of Hepatitis E Among Swine: Potential Impact upon Human Infection" (http:/ / www.
biomedcentral. com/ 1746-6148/ 3/ 9). BMC Vet. Res. 3: 9. doi:10.1186/1746-6148-3-9. PMID 17493260. PMC 1885244. .
[8] Li TC, Chijiwa K, Sera N, et al. (2005). "Hepatitis E Virus Transmission from Wild Boar Meat" (http:/ / www. cdc. gov/ ncidod/ EID/
vol11no12/ 05-1041. htm). Emerging Infect. Dis. 11 (12): 1958–60. PMID 16485490. .
[9] Kuniholm MH & Nelson KE (2008). "Of Organ Meats and Hepatitis E Virus: One Part of a Larger Puzzle Is Solved". J Infect Dis 198 (12):
1727–1728. doi:10.1086/593212. PMID 18983247.
[10] RatBehavior.org (http:/ / www. ratbehavior. org/ WildRatDisease. htm)
[11] Johne, R.; Plenge-Bönig, A.; Hess M.; Ulrich, R. G.; Reetz, J.; Schielke, A. (2009) "Detection of a Novel Hepatitis E-like Virus in Faeces of
Wild Rats Using a Nested Broad-spectrum RT-PCR". J. Gen. Virol.
[12] Shrestha MP, Scott RM, Joshi DM, et al. (2007). "Safety and efficacy of a recombinant hepatitis E vaccine". N. Engl. J. Med. 356 (9):
895–903. doi:10.1056/NEJMoa061847. PMID 17329696.
External links
• WHO hepatitis E factsheet (http://www.who.int/mediacentre/factsheets/fs280/en/)
• Virus Pathogen Database and Analysis Resource (ViPR): Hepeviridae (http://www.viprbrc.org/brc/home.
do?decorator=hepe)
• The Night My Liver Started Running My Life (New York Times, October 18, 2010) (http://www.nytimes.com/
2010/10/19/health/views/19case.html)
83
Hepatitis F virus
Hepatitis F virus
Hepatitis F is a hypothetical virus linked to hepatitis. Several hepatitis F candidates emerged in the 1990s; none of
these reports have been substantiated.[1] [2] [3]
In 1994, Deka et al. reported that novel viral particles had been discovered in the stool of post-transfusion,
non-hepatitis A, non-hepatitis B, non-hepatitis C, non-hepatitis E patients.[4] Injection of these particles into the
bloodstream of Indian rhesus monkeys caused hepatitis, and the virus was named hepatitis F or Toga virus. Further
investigations failed to confirm the existence of the virus, and it was delisted as a cause for infectious hepatitis.[3] [5]
A subsequently-discovered virus thought to cause hepatitis was named Hepatitis G virus, though its role in hepatitis
has not been confirmed and it is now considered synonymous with GB virus C and is an "orphan virus" with no
causal links to any human disease.[6]
References
[1] Uchida, T. (1993). "Genetic Variations of the Hepatitis B Virus and Their Clinical Relevance". Microbiol. Immunol. 37 (6): 425–39.
PMID 7694049.
[2] Fagan, E. A. (1994). "Acute Liver Failure of Unknown Pathogenesis: The Hidden Agenda". Hepatology 19 (5): 1307–12.
doi:10.1002/hep.1840190532. PMID 8175156.
[3] Bowden, S. (2001). "New Hepatitis Viruses: Contenders and Pretenders". J Gastroenterol. Hepatol. 16 (2): 124–31.
doi:10.1046/j.1440-1746.2001.02405.x. PMID 11207890.
[4] Deka N, Sharma MD, Mukerjee R (1994). "Isolation of the Novel Agent from Human Stool Samples That Is Associated with Sporadic
Non-A, Non-B Hepatitis" (http:/ / www. pubmedcentral. nih. gov/ articlerender. fcgi?tool=pmcentrez& artid=237242). J. Virol. 68 (12):
7810–5. PMID 7966570. PMC 237242.
[5] Kelly, D.; Skidmore, S. (2002). "Hepatitis C-Z: Recent Advances" (http:/ / www. pubmedcentral. nih. gov/ articlerender.
fcgi?tool=pmcentrez& artid=1751087). Arch. Dis. Child. 86 (5): 339–43. doi:10.1136/adc.86.5.339. PMID 11970925. PMC 1751087.
[6] Lefrère J. J.; Laperche, S.; Roudot-Thoraval, F. (April 2008). "Hepatitis G Virus: A Suitable Marker of in vivo Efficacy for Pathogen
Inactivation". Vox Sang 95 (1): 76. doi:10.1111/j.1423-0410.2008.01050.x. PMID 18393946.
84
Tuberculosis
85
Tuberculosis
Tuberculosis
Chest X-ray of a patient with far-advanced tuberculosis
[1]
ICD-10
A 15.
ICD-9
010
OMIM
607948
DiseasesDB
8515
–A 19.
[3]
– 018
[2]
[4]
[5]
[6]
MedlinePlus 000077 [7] 000624 [8]
eMedicine
med/2324
MeSH
D014376
[9]
emerg/618
[10]
radio/411
[11]
[12]
Tuberculosis or TB (short for tubercles bacillus) is a common and often deadly infectious disease caused by various
strains of mycobacteria, usually Mycobacterium tuberculosis in humans.[13] Tuberculosis usually attacks the lungs
but can also affect other parts of the body. It is spread through the air when people who have the disease cough,
sneeze, or spit.[14] Most infections in humans result in an asymptomatic, latent infection, and about one in ten latent
infections eventually progresses to active disease, which, if left untreated, kills more than 50% of its victims.
The classic symptoms are a chronic cough with blood-tinged sputum, fever, night sweats, and weight loss (the last
giving rise to the formerly prevalent colloquial term "consumption"). Infection of other organs causes a wide range
of symptoms. Diagnosis relies on radiology (commonly chest X-rays), a tuberculin skin test, blood tests, as well as
microscopic examination and microbiological culture of bodily fluids. Treatment is difficult and requires long
courses of multiple antibiotics. Contacts are also screened and treated if necessary. Antibiotic resistance is a growing
problem in (extensively) multi-drug-resistant tuberculosis. Prevention relies on screening programs and vaccination,
usually with Bacillus Calmette-Guérin vaccine.
One third of the world's population is thought to be infected with M. tuberculosis,[15] [16] and new infections occur at
a rate of about one per second.[17] The proportion of people who become sick with tuberculosis each year is stable or
falling worldwide but, because of population growth, the absolute number of new cases is still increasing.[17] In 2007
there were an estimated 13.7 million chronic active cases, 9.3 million new cases, and 1.8 million deaths, mostly in
developing countries.[18] In addition, more people in the developed world are contracting tuberculosis because their
immune systems are compromised by immunosuppressive drugs, substance abuse, or AIDS. The distribution of
tuberculosis is not uniform across the globe; about 80% of the population in many Asian and African countries test
Tuberculosis
86
positive in tuberculin tests, while only 5-10% of the US population test positive.[13]
Classification
The current clinical classification system for tuberculosis (TB) is based on the pathogenesis of the disease.
Classification System for TB
Class
Type
Description
0
No TB exposure
Not infected
No history of exposure
Negative reaction to tuberculin skin test
1
TB exposure
History of exposure
No evidence of infection Negative reaction to tuberculin skin test
Ghon complex
2
TB infection
No disease
Positive reaction to tuberculin skin test
Negative bacteriologic studies (if done)
Fibrocaseous cavitary lesion (usually in upper lobe of lungs)
3
TB, clinically active
M. tuberculosis cultured (if done)
Clinical, bacteriologic, or radiographic evidence of current disease
4
TB
Not clinically active
History of episode(s) of TB
or
Abnormal but stable radiographic findings
Positive reaction to the tuberculin skin test
Negative bacteriologic studies (if done)
and
No clinical or radiographic evidence of current disease
5
TB suspect
Diagnosis pending
TB disease should be ruled in or out within 3 months
Signs and symptoms
When the disease becomes active, 75% of the cases are pulmonary TB,
that is, TB in the lungs. Symptoms include chest pain, coughing up
blood, and a productive, prolonged cough for more than three weeks.
Systemic symptoms include fever, chills, night sweats, appetite loss,
weight loss, pallor, and often a tendency to fatigue very easily.[17]
In the other 25% of active cases, the infection moves from the lungs,
causing other kinds of TB, collectively denoted extrapulmonary
tuberculosis.[19] This occurs more commonly in immunosuppressed
persons and young children. Extrapulmonary infection sites include the
pleura in tuberculosis pleurisy, the central nervous system in
meningitis, the lymphatic system in scrofula of the neck, the
genitourinary system in urogenital tuberculosis, and bones and joints in
Pott's disease of the spine. An especially serious form is disseminated
TB, more commonly known as miliary tuberculosis. Extrapulmonary
TB may co-exist with pulmonary TB as well.[20]
Scanning electron micrograph of Mycobacterium
tuberculosis
Tuberculosis
Causes
The primary cause of TB, Mycobacterium tuberculosis, is a small
aerobic non-motile bacillus. High lipid content of this pathogen
accounts for many of its unique clinical characteristics.[21] It divides
every 16 to 20 hours, an extremely slow rate compared with other
bacteria, which usually divide in less than an hour.[22] (For example,
one of the fastest-growing bacteria is a strain of E. coli that can divide
roughly every 20 minutes.) Since MTB has a cell wall but lacks a
Phylogenetic tree of the genus Mycobacterium.
phospholipid outer membrane, it is classified as a Gram-positive
bacterium. However, if a Gram stain is performed, MTB either stains
very weakly Gram-positive or does not retain dye due to the high lipid & mycolic acid content of its cell wall.[23]
MTB can withstand weak disinfectants and survive in a dry state for weeks. In nature, the bacterium can grow only
within the cells of a host organism, but M. tuberculosis can be cultured in vitro.[24]
Using histological stains on expectorate samples from phlegm (also called sputum), scientists can identify MTB
under a regular microscope. Since MTB retains certain stains after being treated with acidic solution, it is classified
as an acid-fast bacillus (AFB).[13] [23] The most common acid-fast staining technique, the Ziehl-Neelsen stain, dyes
AFBs a bright red that stands out clearly against a blue background. Other ways to visualize AFBs include an
auramine-rhodamine stain and fluorescent microscopy.
The M. tuberculosis complex includes four other TB-causing mycobacteria: M. bovis, M. africanum, M. canetti and
M. microti.[25] M. africanum is not widespread, but in parts of Africa it is a significant cause of tuberculosis.[26] [27]
M. bovis was once a common cause of tuberculosis, but the introduction of pasteurized milk has largely eliminated
this as a public health problem in developed countries.[13] [28] M. canetti is rare and seems to be limited to Africa,
although a few cases have been seen in African emigrants.[29] M. microti is mostly seen in immunodeficient people,
although it is possible that the prevalence of this pathogen has been underestimated.[30]
Other known pathogenic mycobacteria include Mycobacterium leprae, Mycobacterium avium and M. kansasii. The
last two are part of the nontuberculous mycobacteria (NTM) group. Nontuberculous mycobacteria cause neither TB
nor leprosy, but they do cause pulmonary diseases resembling TB.[31]
Risk factors
Persons with silicosis have an approximately 30-fold greater risk for developing TB.[32] Silica particles irritate the
respiratory system, causing immunogenic responses such as phagocytosis, which, as a consequence, results in high
lymphatic vessel deposits.[33] It is this interference and blockage of macrophage function that increases the risk of
tuberculosis.[34] Persons with chronic renal failure and also on hemodialysis have an increased risk: 10—25 times
greater than the general population. Persons with diabetes mellitus have a risk for developing active TB that is two to
four times greater than persons without diabetes mellitus, and this risk is likely greater in persons with
insulin-dependent or poorly controlled diabetes. Other clinical conditions that have been associated with active TB
include gastrectomy with attendant weight loss and malabsorption, jejunoileal bypass, renal and cardiac
transplantation, carcinoma of the head or neck, and other neoplasms (e.g., lung cancer, lymphoma, and leukemia).[35]
Given that silicosis greatly increases the risk of tuberculosis, more research about the effect of various indoor or
outdoor air pollutants on the disease would be necessary. Some possible indoor source of silica includes paint,
concrete and Portland cement. Crystalline silica is found in concrete, masonry, sandstone, rock, paint, and other
abrasives. The cutting, breaking, crushing, drilling, grinding, or abrasive blasting of these materials may produce fine
silica dust. It can also be in soil, mortar, plaster, and shingles. When you wear dusty clothing at home or in your car,
you may be carrying silica dust that your family will breathe.[36]
87
Tuberculosis
Low body weight is associated with risk of tuberculosis as well. A body mass index (BMI) below 18.5 increases the
risk by 2—3 times. On the other hand, an increase in body weight lowers the risk.[37] [38] Patients with diabetes
mellitus are at increased risk of contracting tuberculosis,[39] and they have a poorer response to treatment, possibly
due to poorer drug absorption[40]
Other conditions that increase risk include IV drug abuse; recent TB infection or a history of inadequately treated
TB; chest X-ray suggestive of previous TB, showing fibrotic lesions and nodules; prolonged corticosteroid therapy
and other immunosuppressive therapy; Immunocompromised patients (30-40% of AIDS patients in the world also
have TB) hematologic and reticuloendothelial diseases, such as leukemia and Hodgkin's disease; end-stage kidney
disease; intestinal bypass; chronic malabsorption syndromes; vitamin D deficiency;[41] and low body weight.[13] [20]
Twin studies in the 1940s showed that susceptibility to TB was heritable. If one of a pair of twins got TB, then the
other was more likely to get TB if he was identical than if he was not.[42] These findings were more recently
confirmed by a series of studies in South Africa.[43] [44] [45] Specific gene polymorphisms in IL12B have been linked
to tuberculosis susceptibility.[46]
Some drugs, including rheumatoid arthritis drugs that work by blocking tumor necrosis factor-alpha (an
inflammation-causing cytokine), raise the risk of activating a latent infection due to the importance of this cytokine
in the immune defense against TB.[47]
Mechanism
Transmission
When people suffering from active pulmonary TB cough, sneeze, speak, or spit, they expel infectious aerosol
droplets 0.5 to 5 µm in diameter. A single sneeze can release up to 40,000 droplets.[48] Each one of these droplets
may transmit the disease, since the infectious dose of tuberculosis is very low and inhaling less than ten bacteria may
cause an infection.[49] [50]
People with prolonged, frequent, or intense contact are at particularly high risk of becoming infected, with an
estimated 22% infection rate. A person with active but untreated tuberculosis can infect 10–15 other people per
year.[17] Others at risk include people in areas where TB is common, people who inject drugs using unsanitary
needles, residents and employees of high-risk congregate settings, medically under-served and low-income
populations, high-risk racial or ethnic minority populations, children exposed to adults in high-risk categories,
patients immunocompromised by conditions such as HIV/AIDS, people who take immunosuppressant drugs, and
health care workers serving these high-risk clients.[51]
Transmission can only occur from people with active — not latent — TB.[13] The probability of transmission from
one person to another depends upon the number of infectious droplets expelled by a carrier, the effectiveness of
ventilation, the duration of exposure, and the virulence of the M. tuberculosis strain.[20] The chain of transmission
can, therefore, be broken by isolating patients with active disease and starting effective anti-tuberculous therapy.
After two weeks of such treatment, people with non-resistant active TB generally cease to be contagious. If someone
does become infected, then it will take at least 21 days, or three to four weeks, before the newly infected person can
transmit the disease to others.[52] TB can also be transmitted by eating meat infected with TB. Mycobacterium bovis
causes TB in cattle. (See details below.)
88
Tuberculosis
Pathogenesis
About 90% of those infected with Mycobacterium tuberculosis have asymptomatic, latent TB infection (sometimes
called LTBI), with only a 10% lifetime chance that a latent infection will progress to TB disease.[13] However, if
untreated, the death rate for these active TB cases is more than 50%.[53]
TB infection begins when the mycobacteria reach the pulmonary alveoli, where they invade and replicate within the
endosomes of alveolar macrophages.[13] [54] The primary site of infection in the lungs is called the Ghon focus, and
is generally located in either the upper part of the lower lobe, or the lower part of the upper lobe.[13] Bacteria are
picked up by dendritic cells, which do not allow replication, although these cells can transport the bacilli to local
(mediastinal) lymph nodes. Further spread is through the bloodstream to other tissues and organs where secondary
TB lesions can develop in other parts of the lung (particularly the apex of the upper lobes), peripheral lymph nodes,
kidneys, brain, and bone.[13] [55] All parts of the body can be affected by the disease, though it rarely affects the
heart, skeletal muscles, pancreas and thyroid.[56]
Tuberculosis is classified as one of the granulomatous inflammatory conditions. Macrophages, T lymphocytes, B
lymphocytes and fibroblasts are among the cells that aggregate to form a granuloma, with lymphocytes surrounding
the infected macrophages. The granuloma functions not only to prevent dissemination of the mycobacteria, but also
provides a local environment for communication of cells of the immune system. Within the granuloma, T
lymphocytes secrete cytokines such as interferon gamma, which activates macrophages to destroy the bacteria with
which they are infected.[57] Cytotoxic T cells can also directly kill infected cells, by secreting perforin and
granulysin.[54]
Importantly, bacteria are not always eliminated within the granuloma, but can become dormant, resulting in a latent
infection.[13] Another feature of the granulomas of human tuberculosis is the development of abnormal cell death,
also called necrosis, in the center of tubercles. To the naked eye this has the texture of soft white cheese and was
termed caseous necrosis.[58]
If TB bacteria gain entry to the bloodstream from an area of damaged tissue they spread through the body and set up
many foci of infection, all appearing as tiny white tubercles in the tissues. This severe form of TB disease is most
common in infants and the elderly and is called miliary tuberculosis. Patients with this disseminated TB have a
fatality rate near 100% if untreated. However, If treated early, the fatality rate is reduced to near 10%.[59]
In many patients the infection waxes and wanes. Tissue destruction and necrosis are balanced by healing and
fibrosis.[58] Affected tissue is replaced by scarring and cavities filled with cheese-like white necrotic material.
During active disease, some of these cavities are joined to the air passages bronchi and this material can be coughed
up. It contains living bacteria and can therefore pass on infection. Treatment with appropriate antibiotics kills
bacteria and allows healing to take place. Upon cure, affected areas are eventually replaced by scar tissue.[58]
If untreated, infection with Mycobacterium tuberculosis can become lobar pneumonia.[60]
Diagnosis
Tuberculosis is diagnosed definitively by identifying the causative organism (Mycobacterium tuberculosis) in a
clinical sample (for example, sputum or pus). When this is not possible, a probable - although sometimes
inconclusive[14] - diagnosis may be made using imaging (X-rays or scans) and/or a tuberculin skin test (Mantoux
test).
The main problem with tuberculosis diagnosis is the difficulty in culturing this slow-growing organism in the
laboratory (it may take 4 to 12 weeks for blood or sputum culture). A complete medical evaluation for TB must
include a medical history, a physical examination, a chest X-ray, microbiological smears, and cultures. It may also
include a tuberculin skin test, a serological test. The interpretation of the tuberculin skin test depends upon the
person's risk factors for infection and progression to TB disease, such as exposure to other cases of TB or
immunosuppression.[20]
89
Tuberculosis
90
Currently, latent infection is diagnosed in a non-immunized person by a tuberculin skin test, which yields a delayed
hypersensitivity type response to an extract made from M. tuberculosis.[13] Those immunized for TB or with
past-cleared infection will respond with delayed hypersensitivity parallel to those currently in a state of infection, so
the test must be used with caution, particularly with regard to persons from countries where TB immunization is
common.[61] Tuberculin tests have the disadvantage of producing false negatives, especially when the patient is
co-morbid with sarcoidosis, Hodgkins lymphoma, malnutrition, or most notably active tuberculosis disease.[13] The
newer interferon release assays (IGRAs) overcome many of these problems. IGRAs are in vitro blood tests that are
more specific than the skin test. IGRAs detect the release of interferon gamma in response to mycobacterial proteins
such as ESAT-6.[62] These are not affected by immunization or environmental mycobacteria, so generate fewer false
positive results.[63] There is also evidence that the T-SPOT.TB IGRA is more sensitive than the skin test.[64]
New TB tests are being developed that offer the hope of cheap, fast and more accurate TB testing. These include
polymerase chain reaction assays for the detection of bacterial DNA. The development of a rapid and inexpensive
diagnostic test would be particularly valuable in the developing world.[65]
Prevention
TB prevention and control takes two parallel
approaches. In the first, people with TB and
their contacts are identified and then treated.
Identification of infections often involves
testing high-risk groups for TB. In the
second approach, children are vaccinated to
protect them from TB. No vaccine is
available that provides reliable protection
for adults. However, in tropical areas where
the levels of other species of mycobacteria
are high, exposure to nontuberculous
mycobacteria gives some protection against
TB.[66]
Map showing the 22 high-burden countries (HBC) that according to WHO account
for 80% of all new TB cases arising each year. The Global Plan is especially aimed
at these countries.
The World Health Organization (WHO) declared TB a global health emergency in 1993, and the Stop TB
Partnership developed a Global Plan to Stop Tuberculosis that aims to save 14 million lives between 2006 and
2015.[67] Since humans are the only host of Mycobacterium tuberculosis, eradication would be possible. This goal
would be helped greatly by an effective vaccine.[68]
Vaccines
Many countries use Bacillus Calmette-Guérin (BCG) vaccine as part of their TB control programmes, especially for
infants. According to the WHO, this is the most often used vaccine worldwide, with 85% of infants in 172 countries
immunized in 1993.[69] This was the first vaccine for TB and developed at the Pasteur Institute in France between
1905 and 1921.[70] However, mass vaccination with BCG did not start until after World War II.[71] The protective
efficacy of BCG for preventing serious forms of TB (e.g. meningitis) in children is greater than 80%; its protective
efficacy for preventing pulmonary TB in adolescents and adults is variable, ranging from 0 to 80%.[72]
In South Africa, the country with the highest prevalence of TB, BCG is given to all children under age three.[73]
However, BCG is less effective in areas where mycobacteria are less prevalent; therefore BCG is not given to the
entire population in these countries. In the USA, for example, BCG vaccine is not recommended except for people
who meet specific criteria:[20]
Tuberculosis
91
• Infants or children with negative skin test results who are continually exposed to untreated or ineffectively treated
patients or will be continually exposed to multidrug-resistant TB.
• Healthcare workers considered on an individual basis in settings in which a high percentage of MDR-TB patients
has been found, transmission of MDR-TB is likely, and TB control precautions have been implemented and were
not successful.
BCG provides some protection against severe forms of pediatric TB, but has been shown to be unreliable against
adult pulmonary TB, which accounts for most of the disease burden worldwide. Currently, there are more cases of
TB on the planet than at any other time in history and most agree there is an urgent need for a newer, more effective
vaccine that would prevent all forms of TB—including drug resistant strains—in all age groups and among people
with HIV.[74]
Several new vaccines to prevent TB infection are being developed. The first recombinant tuberculosis vaccine
rBCG30, entered clinical trials in the United States in 2004, sponsored by the National Institute of Allergy and
Infectious Diseases (NIAID).[75] A 2005 study showed that a DNA TB vaccine given with conventional
chemotherapy can accelerate the disappearance of bacteria as well as protect against re-infection in mice; it may take
four to five years to be available in humans.[76] A very promising TB vaccine, MVA85A, is currently in phase II
trials in South Africa by a group led by Oxford University,[77] and is based on a genetically modified vaccinia virus.
Many other strategies are also being used to develop novel vaccines,[78] including both subunit vaccines (fusion
molecules composed of two recombinant proteins delivered in an adjuvant) such as Hybrid-1, HyVac4 or M72, and
recombinant adenoviruses such as Ad35.[79] [80] [81] [82] Some of these vaccines can be effectively administered
without needles, making them preferable for areas where HIV is very common.[83] All of these vaccines have been
successfully tested in humans and are now in extended testing in TB-endemic regions. To encourage further
discovery, researchers and policymakers are promoting new economic models of vaccine development including
prizes, tax incentives and advance market commitments.[84] [85]
Screening
Mantoux tuberculin skin tests are often used for routine screening of
high risk individuals.[86]
Interferon-γ release assays are blood tests used in the diagnosis of
some infectious diseases. There are currently two interferon-γ release
assays available for the diagnosis of tuberculosis:
• QuantiFERON-TB Gold (licensed in US, Europe and Japan); and
• T-SPOT.TB, a form of ELISPOT (licensed in Europe).
Chest photofluorography has been used in the past for mass screening
for tuberculosis.
Mantoux tuberculin skin test
Treatment
Treatment for TB uses antibiotics to kill the bacteria. Effective TB treatment is difficult, due to the unusual structure
and chemical composition of the mycobacterial cell wall, which makes many antibiotics ineffective and hinders the
entry of drugs.[87] [88] [89] [90] The two antibiotics most commonly used are rifampicin and isoniazid. However,
instead of the short course of antibiotics typically used to cure other bacterial infections, TB requires much longer
periods of treatment (around 6 to 24 months) to entirely eliminate mycobacteria from the body.[20] Latent TB
treatment usually uses a single antibiotic, while active TB disease is best treated with combinations of several
antibiotics, to reduce the risk of the bacteria developing antibiotic resistance.[91] People with latent infections are
treated to prevent them from progressing to active TB disease later in life.
Tuberculosis
92
Drug-resistant tuberculosis is transmitted in the same way as regular TB. Primary resistance occurs in persons
infected with a resistant strain of TB. A patient with fully susceptible TB develops secondary resistance (acquired
resistance) during TB therapy because of inadequate treatment, not taking the prescribed regimen appropriately, or
using low-quality medication.[91] Drug-resistant TB is a public health issue in many developing countries, as
treatment is longer and requires more expensive drugs. Multi-drug-resistant tuberculosis (MDR-TB) is defined as
resistance to the two most effective first-line TB drugs: rifampicin and isoniazid. Extensively drug-resistant TB
(XDR-TB) is also resistant to three or more of the six classes of second-line drugs.[92]
The DOTS (Directly Observed Treatment Short-course) strategy of tuberculosis treatment recommended by WHO
was based on clinical trials done in the 1970s by Tuberculosis Research Centre, Chennai, India. The country in
which a person with TB lives can determine what treatment they receive. This is because multidrug-resistant
tuberculosis is resistant to most first-line medications, the use of second-line antituberculosis medications is
necessary to cure the patient. However, the price of these medications is high; thus poor people in the developing
world have no or limited access to these treatments.[93]
Recurrence
Studies utilizing DNA fingerprinting of M. tuberculosis strains have shown that reinfection contributes more
substantially to recurrent TB than previously thought,[94] with between 12% and 77% of cases attributable to
reinfection (instead of reactivation).[95]
Prognosis
Progression from TB infection to TB disease occurs when the TB bacilli overcome the immune system defenses and
begin to multiply. In primary TB disease—1–5% of cases—this occurs soon after infection.[13] However, in the
majority of cases, a latent infection occurs that has no obvious symptoms.[13] These dormant bacilli can produce
tuberculosis in 2–23% of these latent cases, often many years after infection.[96] The risk of reactivation increases
with immunosuppression, such as that caused by infection with HIV. In patients co-infected with M. tuberculosis and
HIV, the risk of reactivation increases to 10% per year.[13] [53]
Epidemiology
Roughly a third of the world's population has been infected with M.
tuberculosis, and new infections occur at a rate of one per second.[17]
However, not all infections with M. tuberculosis cause TB disease and
many infections are asymptomatic.[98] In 2007, an estimated 13.7
million people had active TB disease, with 9.3 million new cases and
1.8 million deaths; the annual incidence rate varied from 363 per
100,000 in Africa to 32 per 100,000 in the Americas.[18] Tuberculosis
is the world's greatest infectious killer of women of reproductive age
and the leading cause of death among people with HIV/AIDS.[99]
Annual number of new reported TB cases. Data
[97]
from WHO.
The rise in HIV infections and the neglect of TB control programs
have enabled a resurgence of tuberculosis.[100] The emergence of drug-resistant strains has also contributed to this
new epidemic with, from 2000 to 2004, 20% of TB cases being resistant to standard treatments and 2% resistant to
second-line drugs.[92] The rate at which new TB cases occur varies widely, even in neighboring countries, apparently
because of differences in health care systems.[101]
In 2007, the country with the highest estimated incidence rate of TB was Swaziland, with 1200 cases per 100,000
people. India had the largest total incidence, with an estimated 2.0 million new cases.[18] The Philippines ranks
fourth in the world for the number of cases of tuberculosis and has the highest number of cases per head in Southeast
Tuberculosis
Asia. Almost two thirds of Filipinos have tuberculosis, and up to an additional five million people are infected
yearly.[102] In developed countries, tuberculosis is less common and is mainly an urban disease. In the United
Kingdom, the national average was 15 per 100,000 in 2007, and the highest incidence rates in Western Europe were
30 per 100,000 in Portugal and Spain. These rates compared with 98 per 100,000 in China and 48 per 100,000 in
Brazil. In the United States, the overall tuberculosis case rate was 4 per 100,000 persons in 2007.[18] In Canada
tuberculosis is still endemic in some rural areas.[103]
The incidence of TB varies with age. In Africa, TB primarily affects adolescents and young adults.[104] However, in
countries where TB has gone from high to low incidence, such as the United States, TB is mainly a disease of older
people, or of the immunocompromised.[13] [105]
There are a number of known factors that make people more susceptible to TB infection: worldwide the most
important of these is HIV. Co-infection with HIV is a particular problem in Sub-Saharan Africa, due to the high
incidence of HIV in these countries.[106] [107] Smoking more than 20 cigarettes a day also increases the risk of TB by
two to four times.[108] [109] Diabetes mellitus is also an important risk factor that is growing in importance in
developing countries.[110] Other disease states that increase the risk of developing tuberculosis are Hodgkin
lymphoma, end-stage renal disease, chronic lung disease, malnutrition, and alcoholism.[13]
Diet may also modulate risk. For example, among immigrants in London from the Indian subcontinent, vegetarian
Hindu Asians were found to have an 8.5 fold increased risk of tuberculosis, compared to Muslims who ate meat and
fish daily.[111] Although a causal link is not proved by this data,[112] this increased risk could be caused by
micronutrient deficiencies: possibly iron, vitamin B12 or vitamin D.[111] Further studies have provided more
evidence of a link between vitamin D deficiency and an increased risk of contracting tuberculosis.[113] [114] Globally,
the severe malnutrition common in parts of the developing world causes a large increase in the risk of developing
active tuberculosis, due to its damaging effects on the immune system.[115] [116] Along with overcrowding, poor
nutrition may contribute to the strong link observed between tuberculosis and poverty.[117] [118]
Prisoners, especially in poor countries, are particularly vulnerable to infectious diseases such as HIV/AIDS and TB.
Prisons provide a conditions that allow TB to spread rapidly, due to overcrowding, poor nutrition and a lack of health
services. Since the early 1990s, TB outbreaks have been reported in prisons in many countries in Eastern Europe.
The prevalence of TB in prisons is much higher than among the general population – in some countries as much as
40 times higher.[119] [120]
History
Tuberculosis has been present in humans since antiquity. The earliest unambiguous detection of Mycobacterium
tuberculosis is in the remains of bison dated 18,000 years before the present.[121] Whether tuberculosis originated in
cattle and then transferred to humans, or diverged from a common ancestor infecting a different species, is currently
unclear.[122] However, it is clear that M. tuberculosis is not directly descended from M. bovis, which seems to have
evolved relatively recently.[123]
93
Tuberculosis
94
Tubercular decay has been found in the spines of
Egyptian mummies. Pictured: Egyptian mummy
in the British Museum
Skeletal remains from a Neolithic Settlement in the Eastern
Mediterranean show prehistoric humans (7000 BC) had TB,[124] and
tubercular decay has been found in the spines of mummies from
3000–2400 BC.[125] Phthisis is a Greek term for tuberculosis; around
460 BC, Hippocrates identified phthisis as the most widespread disease
of the times involving coughing up blood and fever, which was almost
always fatal.[126] In South America, the earliest evidence of
tuberculosis is associated with the Paracas-Caverna culture (circa 750
BC to circa 100 AD).[127] [128]
Other names
In the past, tuberculosis has been called consumption, because it seemed to consume people from within, with a
bloody cough, fever, pallor, and long relentless wasting. Other names included phthisis (Greek for consumption) and
phthisis pulmonalis; scrofula (in adults), affecting the lymphatic system and resulting in swollen neck glands; tabes
mesenterica, TB of the abdomen and lupus vulgaris, TB of the skin; wasting disease; white plague, because sufferers
appear markedly pale; king's evil, because it was believed that a king's touch would heal scrofula; and Pott's disease,
or gibbus of the spine and joints.[129] [130]
Miliary tuberculosis—now commonly known as disseminated TB—occurs when
the infection invades the circulatory system, resulting in millet-like seeding of
TB bacilli in the lungs as seen on an X-ray.[129] [131] TB is also called Koch's
disease, after the scientist Robert Koch.[132]
Folklore
Before the Industrial Revolution, tuberculosis may sometimes have been
regarded as vampirism. When one member of a family died from it, the other
members that were infected would lose their health slowly. People believed that
this was caused by the original victim draining the life from the other family
members. Furthermore, people who had TB exhibited symptoms similar to what
people considered to be vampire traits. People with TB often have symptoms
Dr. Robert Koch discovered the
tuberculosis bacillus.
such as red, swollen eyes (which also creates a sensitivity to bright light), pale
skin, extremely low body heat, a weak heart and coughing blood, suggesting the
idea that the only way for the afflicted to replenish this loss of blood was by sucking blood.[133] Another folk belief
told that the affected individual was being forced, nightly, to attend fairy revels, so that the victim wasted away
owing to lack of rest; this belief was most common when a strong connection was seen between the fairies and the
dead.[134] Similarly, but less commonly, it was attributed to the victims being "hagridden"—being transformed into
horses by witches (hags) to travel to their nightly meetings, again resulting in a lack of rest.[134]
TB was romanticized in the nineteenth century. Many people believed TB produced feelings of euphoria referred to
as Spes phthisica ("hope of the consumptive"). It was believed that TB sufferers who were artists had bursts of
creativity as the disease progressed. It was also believed that TB sufferers acquired a final burst of energy just before
they died that made women more beautiful and men more creative.[135] In the early 20th century, some believed TB
to be caused by masturbation.[136]
Tuberculosis
Study and treatment
The study of tuberculosis, sometimes known as phthisiatry, dates back to The Canon of Medicine written by Ibn Sina
(Avicenna) in the 1020s. He was the first physician to identify pulmonary tuberculosis as a contagious disease, the
first to recognise the association with diabetes, and the first to suggest that it could spread through contact with soil
and water.[137] [138] He developed the method of quarantine in order to limit the spread of tuberculosis.[139] In
ancient times, treatments focused on sufferers' diets. Pliny the Elder described several methods in his Natural
History: "wolf's liver taken in thin wine, the lard of a sow that has been fed upon grass, or the flesh of a she-ass taken
in broth".[140]
Although it was established that the pulmonary form was associated with "tubercles" by Dr Richard Morton in
1689,[141] [142] due to the variety of its symptoms, TB was not identified as a single disease until the 1820s and was
not named "tuberculosis" until 1839 by J. L. Schönlein.[143] During the years 1838 – 1845, Dr. John Croghan, the
owner of Mammoth Cave, brought a number of tuberculosis sufferers into the cave in the hope of curing the disease
with the constant temperature and purity of the cave air; they died within a year.[144] The first TB sanatorium opened
in 1854 in Görbersdorf, Germany (today Sokołowsko, Poland) by Hermann Brehmer.[145]
The bacillus causing tuberculosis, Mycobacterium tuberculosis, was identified and described on 24 March 1882 by
Robert Koch. He received the Nobel Prize in physiology or medicine in 1905 for this discovery.[146] Koch did not
believe that bovine (cattle) and human tuberculosis were similar, which delayed the recognition of infected milk as a
source of infection. Later, this source was eliminated by the pasteurization process. Koch announced a glycerine
extract of the tubercle bacilli as a remedy for tuberculosis in 1890, calling it "tuberculin". It was not effective, but
was later adapted as a test for pre-symptomatic tuberculosis.[147]
The first genuine success in immunizing against tuberculosis was developed from attenuated bovine-strain
tuberculosis by Albert Calmette and Camille Guérin in 1906. It was called "BCG" (Bacillus of Calmette and Guérin).
The BCG vaccine was first used on humans in 1921 in France,[70] but it was not until after World War II that BCG
received widespread acceptance in the USA, Great Britain, and Germany.[71]
Tuberculosis, or "consumption" as it was commonly known, caused the most widespread public concern in the 19th
and early 20th centuries as an endemic disease of the urban poor.[148] In 1815, one in four deaths in England was of
consumption; by 1918 one in six deaths in France were still caused by TB. In the 20th century, tuberculosis killed an
estimated 100 million people.[149] After the establishment in the 1880s that the disease was contagious, TB was
made a notifiable disease in Britain; there were campaigns to stop spitting in public places, and the infected poor
were pressured to enter sanatoria that resembled prisons; the sanatoria for the middle and upper classes offered
excellent care and constant medical attention.[145] Whatever the purported benefits of the fresh air and labor in the
sanatoria, even under the best conditions, 50% of those who entered were dead within five years (1916).[145]
95
Tuberculosis
The promotion of Christmas Seals began in Denmark during 1904 as a way to
raise money for tuberculosis programs. It expanded to the United States and
Canada in 1907 – 1908 to help the National Tuberculosis Association (later
called the American Lung Association).
In the United States, concern about the spread of tuberculosis played a role in the
movement to prohibit public spitting except into spittoons.
In Europe, deaths from TB fell from 500 out of 100,000 in 1850 to 50 out of
100,000 by 1950. Improvements in public health were reducing tuberculosis even
before the arrival of antibiotics. The disease remained such a significant threat to
public health, that when the Medical Research Council was formed in Britain in
1913, its initial focus was tuberculosis research.[150]
It was not until 1946 with the development of the antibiotic streptomycin that
effective treatment and cure became possible. Prior to the introduction of this
Public health campaigns tried to halt
drug, the only treatment besides sanatoria were surgical interventions, including
the spread of TB
bronchoscopy and suction as well as the pneumothorax or plombage
technique — collapsing an infected lung to "rest" it and allow lesions to heal — a technique that was of little benefit
and was mostly discontinued by the 1950s.[151] The emergence of multidrug-resistant TB has again introduced
surgery as part of the treatment for these infections. Here, surgical removal of chest cavities will reduce the number
of bacteria in the lungs, as well as increasing the exposure of the remaining bacteria to drugs in the bloodstream. It is
therefore thought to increase the effectiveness of the chemotherapy.[152]
Hopes that the disease could be completely eliminated have been dashed since the rise of drug-resistant strains in the
1980s. For example, tuberculosis cases in Britain, numbering around 117,000 in 1913, had fallen to around 5,000 in
1987, but cases rose again, reaching 6,300 in 2000 and 7,600 cases in 2005.[153] Due to the elimination of public
health facilities in New York and the emergence of HIV, there was a resurgence of TB in the late 1980s.[154] The
number of patients failing to complete their course of drugs is high. New York had to cope with more than 20,000
TB patients with multidrug-resistant strains (resistant to, at least, both Rifampin and Isoniazid).
The resurgence of tuberculosis resulted in the declaration of a global health emergency by the World Health
Organization (WHO) in 1993.[155] Every year, nearly half a million new cases of multidrug-resistant tuberculosis
(MDR-TB) are estimated to occur worldwide.[156]
Evolution
Tuberculosis has co-evolved with humans for many thousands of years, and perhaps for several million years.[157]
The oldest known human remains showing signs of tuberculosis infection are 9,000 years old.[158] During this
evolution, M. tuberculosis has lost numerous coding and non-coding regions in its genome, losses that can be used to
distinguish between strains of the bacteria. The implication is that M. tuberculosis strains differ geographically, so
their genetic differences can be used to track the origins and movement of each strain.[159]
A new species has recently been discovered for the first time in 20 years.[160] [161]
96
Tuberculosis
Society and culture
Through its affecting important historical figures, tuberculosis has influenced particularly European history, and
become a theme in art – mostly literature, music, and film.
Public health
Tuberculosis is one of the three primary diseases of poverty along with AIDS and malaria.[162] The Global Fund to
Fight AIDS, Tuberculosis and Malaria was started in 2002 to raise finances to address these infectious diseases.
Globalization has led to increased opportunities for disease spread. A tuberculosis scare occurred in 2007 when
Andrew Speaker flew on a transatlantic flight infected with multi-drug-resistant tuberculosis.[163]
In the United States, the National Center for HIV, STD, and TB Prevention, as part of the Centers for Disease
Control and Prevention (CDC), is responsible for public health surveillance and prevention research.
Research
The Mycobacterium Tuberculosis Structural Genomics Consortium is a global consortium of scientists conducting
research regarding the diagnosis and treatment of tuberculosis. They are attempting to determine the 3-dimensional
structures of proteins from M. Tuberculosis.
In other animals
Tuberculosis can be carried by mammals; domesticated species, such as cats and dogs, are generally free of
tuberculosis, but wild animals may be carriers.
Mycobacterium bovis causes TB in cattle. An effort to eradicate bovine tuberculosis from the cattle and deer herds of
New Zealand is underway. It has been found that herd infection is more likely in areas where infected natural
reservoir such as Australian brush-tailed possums come into contact with domestic livestock at farm/bush
borders.[164] Controlling the vectors through possum eradication and monitoring the level of disease in livestock
herds through regular surveillance are seen as a "two-pronged" approach to ridding New Zealand of the disease.
In Ireland and the United Kingdom, badgers have been identified as one vector species for the transmission of bovine
tuberculosis. As a result, governments have come under pressure from some quarters, primarily dairy farmers, to
mount an active campaign of eradication of badgers in certain areas with the purpose of reducing the incidence of
bovine TB. The effectiveness of culling on the incidence of TB in cattle is a contentious issue, with proponents and
opponents citing their own studies to support their position.[165] [166] [167] For instance, a study by an Independent
Study Group on badger culling reported on 18 June 2007 that it was unlikely to be effective and would only make a
“modest difference” to the spread of TB and that "badger culling cannot meaningfully contribute to the future control
of cattle TB"; in contrast, another report concluded that this policy would have a significant impact.[168] On 4 July
2008, the UK government decided against a proposed random culling policy.[169]
97
Tuberculosis
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[169] "Farmers' anger on cull rejection" (http:/ / news. bbc. co. uk/ 2/ hi/ uk_news/ england/ 7489413. stm). BBC News. 4 July 2008. . Retrieved
4 July 2008.
Further reading
• Blumberg HM, Leonard MK, Jasmer RM (2005). "Update on the treatment of tuberculosis and latent tuberculosis
infection". JAMA 293 (22): 2776–84. doi:10.1001/jama.293.22.2776. PMID 15941808.
• Dormandy, Thomas (2000). The White Death. New York: New York University Press. ISBN 0814719279.
• Joint Tuberculosis Committee of the British Thoracic Society (2000). "Control and prevention of tuberculosis in
the United Kingdom: code of practice 2000" (http://thorax.bmjjournals.com/cgi/content/abstract/55/11/
887). Thorax 55 (11): 887–901. doi:10.1136/thorax.55.11.887. PMID 11050256. PMC 1745632.
• Kidder, Tracy (2004). Mountains Beyond Mountains. New York: Random House Trade Paperbacks.
ISBN 0812973011. A nonfiction account of treating TB in Haiti, Peru, Russia, and elsewhere.
• Lawlor, Clark (2007). Consumption and Literature. Basingstoke: Palgrave Macmillan. ISBN 0230020038.
• Nemery B, Yew WW, Albert R, et al. (2005). "Tuberculosis, nontuberculous lung infection, pleural disorders,
pulmonary function, respiratory muscles, occupational lung disease, pulmonary infections, and social issues in
AJRCCM in 2004". Am. J. Respir. Crit. Care Med. 171 (6): 554–62. doi:10.1164/rccm.2412009.
PMID 15753485.
• Overlock, Melvin G. (January 1912). " Driving Tuberculosis Out Of Industry: The Overlock Agreement That
Protects 2,000,000 Workers (http://books.google.com/books?id=Vv--PfedzLAC&pg=PA294)". The World's
Work: A History of Our Time XXIII: 268–187.
104
Tuberculosis
• Ryan, Frank (1993). The Forgotten Plague: How the Battle Against Tuberculosis Was Won — and Lost. Boston,
MA: Little, Brown and Company. ISBN 0-316-76380-2.. First published in the United Kingdom as Tuberculosis:
The Greatest Story Never Told.
• Walton D, Farmer P (2000). "MSJAMA: the new white plague". JAMA 284 (21): 2789.
doi:10.1001/jama.284.21.2789. PMID 11105192.
External links
• General information, public health websites and epidemiology
• Special Issue of Future Medicinal Chemistry on TB drug development (http://www.future-science.com/toc/
fmc/2/8)
• World Health Organization (WHO) - Tuberculosis (http://www.who.int/tb/en/)
• Tuberculosis (http://www.dmoz.org/Health/Conditions_and_Diseases/Infectious_Diseases/Mycobacterial/
Tuberculosis//) at the Open Directory Project
• The Stop TB Partnership (http://www.stoptb.org/) - established in 2000 with the goal of eliminating
tuberculosis as a public health problem
• KNCV Tuberculosis Foundation (http://www.kncvtbc.nl/Site/Professional.aspx?language=en-GB) committed to reducing tuberculosis in the Netherlands and worldwide, in around forty countries. It does so by
means of policy development, technical assistance, advisory services, training programs, capacity building, as
well as epidemiological and operational research.
• Tuberculosis in Europe (http://ecdc.europa.eu/en/Health_topics/tuberculosis) factsheet from European
Centre for Disease Prevention and Control, agency of European Union
• Central Asia Health Review (CAHR). High Prevalence of Multi-Drug-Resistant Tuberculosis in Uzbekistan
(http://www.cahr.info/index_files/page0021.htm)
• Tuberculosis (http://www.cdc.gov/tb/default.htm) on the CDC website
• Tuberculosis information (http://www.hpa.org.uk/infections/topics_az/tb/menu.htm) from the Health
Protection Agency in the UK
• Kaiser Family Foundation. Tuberculosis. (http://www.globalhealthfacts.org/topic.jsp?i=9)
Globalhealthfacts.org.
• United States Agency for International Development (USAID). The Tuberculosis Coalition for Technical
Assistance (TBCTA). (http://www.tbcta.org/)
• Tuberculosis and HIV: HIV InSite Knowledge Base chapter (http://hivinsite.org/InSite?page=kb-00&
doc=kb-05-01-06) and related resources (http://hivinsite.org/InSite?page=kbr-05-01-06).
• Patient information on tuberculosis
• Tuberculosis (http://www.medicinenet.com/tuberculosis/article.htm) on Medicinenet.com (HON code
compliant)
• (CDC) - TB Questions and Answers (http://www.cdc.gov/tb/?404;http://www.cdc.gov:80/tb/faqs/
default.htm)
• Nobel Prize Website Tuberculosis Educational Game (http://nobelprize.org/educational_games/medicine/
tuberculosis/tbc/index.html)
• Professional information and scientific research
• Tuberculosis Database (http://www.tbdb.org/) is an integrated platform for tuberculosis research, hosting
genomic and gene expression data for Mycobacterium tuberculosis and other related species.
• Mycobacterium tuberculosis (http://www.biohealthbase.org/GSearch/statsAutomation.
do?decorator=Mycobacterium) in the BioHealthBase (TB genomics and proteomics database)
• Tuberculosis 2007 (http://www.tuberculosistextbook.com/) - a textbook that focuses on research, diagnosis
and treatment of tuberculosis
105
Tuberculosis
• Tuberculosis: A Persistent Threat to Global Health (http://www.ibioseminars.org/index.
php?option=com_content&view=article&id=265&Itemid=261) on-line lecture by John McKinney
• Sir John Crofton (http://www.telegraph.co.uk/news/obituaries/medicine-obituaries/6702592/
Sir-John-Crofton.html) - Daily Telegraph obituary
bjn:Téréng
106
Chickenpox
107
Chickenpox
Chickenpox
Child with varicella disease
[1]
ICD-10
B 01.
ICD-9
052
DiseasesDB
29118
[2]
[3]
[5]
eMedicine
ped/2385
MeSH
C02.256.466.175
derm/74
[6]
, emerg/367
[7]
[8]
Chickenpox or chicken pox is a highly contagious illness caused by primary infection with varicella zoster virus
(VZV).[9] It usually starts with vesicular skin rash mainly on the body and head rather than at the periphery and
become itchy, raw pockmarks, which mostly heal without scarring.
Chicken pox is an airborne disease spread easily through coughing or sneezing of ill individuals or through direct
contact with secretions from the rash. A person with chickenpox is infectious from one to five days before the rash
appears.[10] The contagious period continues until all blisters have formed scabs, which may take 5 to 6 days at
which point they are no longer contagious.[11] It takes from 10 to 21 days after contact with an infected person for
someone to develop chickenpox.
Chickenpox is often heralded by a prodrome of myalgia, nausea, fever, headache, sore throat, pain in both ears,
complaints of pressure in head or swollen face, and malaise in adolescents and adults, while in children the first
symptom is usually the development of a papular rash, followed by development of malaise, fever (a body
temperature of 38 °C (100 °F), but may be as high as 42 °C (108 °F) in rare cases), and anorexia. Typically, the
disease is more severe in adults.[12] Chickenpox is rarely fatal, although it is generally more severe in adult males
than in adult females or children. Pregnant women and those with a suppressed immune system are at highest risk of
serious complications. Chicken pox is believed to be the cause of one third of stroke cases in children.[13] The most
common late complication of chicken pox is shingles, caused by reactivation of the varicella zoster virus decades
after the initial episode of chickenpox.
Chickenpox
108
Chickenpox has been observed in other primates, including chimpanzees[14] and gorillas.[15]
The disease is not related in any way to chickens; the name uses "chicken" in the sense of "weak" or "cowardly".
Diagnosis
The diagnosis of varicella is primarily clinical, with typical early
"prodromal" symptoms, and then the characteristic rash. Confirmation
of the diagnosis can be sought through either examination of the fluid
within the vesicles of the rash, or by testing blood for evidence of an
acute immunologic response.
Vesicular fluid can be examined with a Tsanck smear, or better with
examination for direct fluorescent antibody. The fluid can also be
"cultured", whereby attempts are made to grow the virus from a fluid
sample. Blood tests can be used to identify a response to acute
infection (IgM) or previous infection and subsequent immunity
(IgG).[16]
Prenatal diagnosis of fetal varicella infection can be performed using
ultrasound, though a delay of 5 weeks following primary maternal
infection is advised. A PCR (DNA) test of the mother's amniotic fluid
can also be performed, though the risk of spontaneous abortion due to
the amniocentesis procedure is higher than the risk of the baby
developing foetal varicella syndrome.[17]
A single blister, typical during the early stages of
the rash
Epidemiology
Primary varicella is an endemic disease. Cases of varicella are seen
throughout the year but more commonly in winter and early spring.
Varicella is one of the classic diseases of childhood, with the highest
prevalence in the 4–10 year old age group. Like rubella, it is
uncommon in preschool children. Varicella is highly communicable,
with an infection rate of 90% in close contacts. Most people become
infected before adulthood but 10% of young adults remain susceptible.
Historically, varicella has been a disease predominantly affecting
young school-aged children. In adults the pock marks are darker and
the scars more prominent than in children.[18]
The back of a 30-year-old male, taken on day 5 of
the rash
Pathophysiology
Exposure to VZV in a healthy child initiates the production of host immunoglobulin G (IgG), immunoglobulin M
(IgM), and immunoglobulin A (IgA) antibodies; IgG antibodies persist for life and confer immunity. Cell-mediated
immune responses are also important in limiting the scope and the duration of primary varicella infection. After
primary infection, VZV is hypothesized to spread from mucosal and epidermal lesions to local sensory nerves. VZV
then remains latent in the dorsal ganglion cells of the sensory nerves. Reactivation of VZV results in the clinically
distinct syndrome of herpes zoster (i.e., shingles), and sometimes Ramsay Hunt syndrome type II.
Chickenpox
Infection in pregnancy and neonates
For pregnant women, antibodies produced as a result of immunization or previous infection are transferred via the
placenta to the fetus.[19] Women who are immune to chickenpox cannot become infected and do not need to be
concerned about it for themselves or their infant during pregnancy.[20]
Varicella infection in pregnant women can lead to viral transmission via the placenta and infection of the fetus. If
infection occurs during the first 28 weeks of gestation, this can lead to fetal varicella syndrome (also known as
congenital varicella syndrome).[21] Effects on the fetus can range in severity from underdeveloped toes and fingers
to severe anal and bladder malformation. Possible problems include:
• Damage to brain: encephalitis,[22] microcephaly, hydrocephaly, aplasia of brain
• Damage to the eye: optic stalk, optic cup, and lens vesicles, microphthalmia, cataracts, chorioretinitis, optic
atrophy
• Other neurological disorder: damage to cervical and lumbosacral spinal cord, motor/sensory deficits, absent deep
tendon reflexes, anisocoria/Horner's syndrome
• Damage to body: hypoplasia of upper/lower extremities, anal and bladder sphincter dysfunction
• Skin disorders: (cicatricial) skin lesions, hypopigmentation
Infection late in gestation or immediately following birth is referred to as "neonatal varicella".[23] Maternal infection
is associated with premature delivery. The risk of the baby developing the disease is greatest following exposure to
infection in the period 7 days prior to delivery and up to 7 days following the birth. The baby may also be exposed to
the virus via infectious siblings or other contacts, but this is of less concern if the mother is immune. Newborns who
develop symptoms are at a high risk of pneumonia and other serious complications of the disease.[17]
Shingles
After a chickenpox infection, the virus remains dormant in the body's nerve tissues. The immune system keeps the
virus at bay, but later in life, usually as an adult, it can be reactivated and cause a different form of the virus called
shingles.[24]
Prevention
Hygiene measures
The spread of chicken pox can be prevented by isolating affected individuals. Contagion is by exposure to
respiratory droplets, or direct contact with lesions, within a period lasting from three days prior to the onset of the
rash, to four days after the onset of the rash.[25] Therefore, avoidance of close proximity or physical contact with
affected individuals during that period will prevent contagion. The chicken pox virus (VZV) is susceptible to
disinfectants, notably chlorine bleach (i.e., sodium hypochlorite). Also, like all enveloped viruses, VZV is sensitive
to desiccation, heat and detergents. Therefore these viruses are relatively easy to kill.
Vaccine
A varicella vaccine was first developed by Michiaki Takahashi in 1974 derived from the Oka strain. It has been
available in the U.S. since 1995 to inoculate against the disease. Some countries require the varicella vaccination or
an exemption before entering elementary school. Protection is not lifelong and further vaccination is necessary five
years after the initial immunization.[26] The chickenpox vaccine is not part of the routine childhood vaccination
schedule in the UK. In the UK, the vaccine is currently only offered to people who are particularly vulnerable to
chickenpox.[27]
109
Chickenpox
Treatment
Varicella treatment mainly consists of easing the symptoms as there is no actual cure of the condition. Some
treatments are however available for relieving the symptoms while the immune system clears the virus from the
body. As a protective measure, patients are usually required to stay at home while they are infectious to avoid
spreading the disease to others. Also, sufferers are frequently asked to cut their nails short or to wear gloves to
prevent scratching and to minimize the risk of secondary infections.
The condition resolves by itself within a couple of weeks but meanwhile patients must pay attention to their personal
hygiene.[28] The rash caused by varicella zoster virus may however last for up to one month, although the infectious
stage does not take longer than a week or two.[29] Also, staying in a cold surrounding can help in easing the itching
as heat and sweat makes it worse.
Although there have been no formal clinical studies evaluating the effectiveness of topical application of calamine
lotion, a topical barrier preparation containing zinc oxide and one of the most commonly used interventions, it has an
excellent safety profile.[30] It is important to maintain good hygiene and daily cleaning of skin with warm water to
avoid secondary bacterial infection.[31] Scratching may also increase the risk of secondary infection.[32] Addition of a
small quantity of vinegar to the water is sometimes advocated.
To relieve the symptoms of chicken pox, people commonly use anti-itching creams and lotions. These lotions are not
to be used on the face or close to the eyes. An oatmeal bath also might help ease discomfort.[33]
Natural chicken pox remedies include pea water, baking soda, vitamin E oil, honey, herbal tea or carrot and
coriander. It is believed that the irritation of the skin can be relieved to some extent with water in which fresh peas
have been cooked.[34] A lotion made of baking soda with water can be sponged onto the skin of the patients to ease
the itching. Also, rubbing vitamin E oil or honey on the skin is thought to have a healing effect on the marks that
could remain after the infection has been cured. Some people claim that the mild sedative effect of green tea is
effective in relieving the symptoms. It is not however known to what extent these home remedies can actually help
the patients cope better with their symptoms.
A varicella vaccine is available for people who have been exposed to the virus, but have not experienced symptoms.
The vaccine is more effective if administered within three days and up to five days after exposure. It has been shown
that the chicken pox vaccine may prevent or reduce the symptoms in 90% of cases, if given within three days after
exposure. People who have been exposed to the virus but who are contraindicated to receive the vaccine, there is a
medication available, called varicella zoster immunoglobulin or VZIG which may prevent or reduce the symptoms
after exposure. VZIG is primarily administered to individuals who are at risk of developing complications due to its
high costs and temporary protection. This type of treatment is only recommended in newborns whose mothers have
had chicken pox few days prior or after delivery, children with leukemia or lymphoma, people with a poor immune
system or pregnant women. VZIG is recommended to be administered no later than 96 hours after exposure to the
virus.
Children
If oral acyclovir is started within 24 hours of rash onset it decreases symptoms by one day but has no effect on
complication rates. Use of acyclovir therefore is not currently recommended for immunocompetent individuals (i.e.,
otherwise healthy persons without known immunodeficiency or those on immunosuppressive medication).[35]
Treatment of chicken pox in children is aimed at symptoms whilst the immune system deals with the virus.[36] With
children younger than 12 years cutting nails and keeping them clean is an important part of treatment as they are
more likely to deep scratch their blisters. Children younger than 12 years old and older than one month are not meant
to receive antiviral medication if they are not suffering from another medical condition which would put them at risk
of developing complications.
110
Chickenpox
Increased amounts of water are recommended to avoid dehydration, especially if the child develops fever. Fever,
headaches or pain can be relieved with painkillers such as paracetamol. Children who are older than one year may be
administered antihistamine tablets or liquid medicines which are helpful in cases when the child is not able to sleep
because of the itching. There is some uncertainty about the use and safety with ibuprofen
Acyclovir or immunoglobulin is generally prescribed in children who are at risk of complications from chicken pox.
They receive the same treatment as the one mentioned above plus antiviral medication additionally. The category of
children that are considered at risk to develop complications includes infants less than one month old, those with a
suppressed immune system, those who are taking steroids or immune suppressing medication or children with severe
heart, lung and skin conditions. Moreover, adults and teenagers are considered at risk of complications and they are
normally administered antiviral medication.
Aspirin is highly contraindicated in children younger than 16 years as it has been related with a potentially fatal
condition known as Reye's syndrome.
Adults
Infection in otherwise healthy adults tends to be more severe and active; treatment with antiviral drugs (e.g.
acyclovir) is generally advised, as long as it is started within 24–48 hours from rash onset.[37]
Remedies to ease the symptoms of chicken pox in adults are basically the same as those used on children. Moreover,
adults are often prescribed antiviral medication as it is effective in reducing the severity of the condition and the
likelihood of developing complications. Antiviral medicines are not however aimed to kill the virus, but to stop it
from multiplying.
Adults are also advised to increase water intake to reduce dehydration and to relieve headaches. Painkillers such as
paracetamol and ibuprofen are also recommended as they are effective in relieving itching and other symptoms such
as fever or pains. Antihistamines may be used in cases when the symptoms cause the inability to sleep, as they are
efficient for easing the itching and they are acting as a sedative.
As with children, antiviral medication is considered more useful for those adults who are more prone to develop
complications. These include pregnant women or people who have a poor immune system.[38]
Sorivudine, a nucleoside analogue has been found in few case reports effective in the treatment of primary varicella
in healthy adults. Larger scale clinical trials are needed to demonstrate the efficacy of this medication.[39]
Prognosis
The duration of the visible blistering caused by varicella zoster virus varies in children usually from 4 to 7 days, and
the appearance of new blisters begins to subside after the 5th day. Chickenpox infection is milder in young children,
and symptomatic treatment, with sodium bicarbonate baths or antihistamine medication may ease itching.[40]
Paracetamol (acetaminophen) is widely used to reduce fever. Aspirin, or products containing aspirin, should not be
given to children with chickenpox as it can cause Reye's Syndrome.[41]
In adults, the disease is more severe,[42] though the incidence is much less common. Infection in adults is associated
with greater morbidity and mortality due to pneumonia,[43] hepatitis, and encephalitis. In particular, up to 10% of
pregnant women with chickenpox develop pneumonia, the severity of which increases with onset later in gestation.
In England and Wales, 75% of deaths due to chickenpox are in adults.[17] Inflammation of the brain, or encephalitis,
can occur in immunocompromised individuals, although the risk is higher with herpes zoster.[44] Necrotizing fasciitis
is also a rare complication.[45]
Secondary bacterial infection of skin lesions, manifesting as impetigo, cellulitis, and erysipelas, is the most common
complication in healthy children. Disseminated primary varicella infection usually seen in the immunocompromised
may have high morbidity. Ninety percent of cases of varicella pneumonia occur in the adult population. Rarer
complications of disseminated chickenpox also include myocarditis, hepatitis, and glomerulonephritis.[46]
111
Chickenpox
112
Hemorrhagic complications are more common in the immunocompromised or immunosuppressed populations,
although healthy children and adults have been affected. Five major clinical syndromes have been described: febrile
purpura, malignant chickenpox with purpura, postinfectious purpura, purpura fulminans, and anaphylactoid purpura.
These syndromes have variable courses, with febrile purpura being the most benign of the syndromes and having an
uncomplicated outcome. In contrast, malignant chickenpox with purpura is a grave clinical condition that has a
mortality rate of greater than 70%. The etiology of these hemorrhagic chickenpox syndromes is not known.[46]
History
Chickenpox was first identified by Persian scientist Muhammad ibn
Zakariya ar-Razi (865–925), known to the West as "Rhazes", who
clearly distinguished it from smallpox and measles.[47] Giovanni
Filippo (1510–1580) of Palermo later provided a more detailed
description of varicella (chickenpox).
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varicella/ dis-faqs-gen-treatment. htm). CDC Guidelines. CDC. . Retrieved 2007-08-23.
[42] Jill M Baren MD, Philip L Henneman MD, Roger J Lewis MD, PhD (August 1996). "Primary Varicella in Adults: Pneumonia, Pregnancy,
and Hospital Admissions" (http:/ / www. sciencedirect. com/ science?_ob=ArticleURL& _udi=B6WB0-4HG68T8-7& _user=10& _rdoc=1&
_fmt=& _orig=search& _sort=d& _docanchor=& view=c& _searchStrId=1152674350& _rerunOrigin=scholar. google&
_acct=C000050221& _version=1& _urlVersion=0& _userid=10& md5=079d9dd0e57fad57f6095f23278630aa). Annals of Emergency
Medicine 28 (2): 165–169. doi:10.1016/S0196-0644(96)70057-4. PMID 8759580. .
[43] http:/ / www. erj. ersjournals. com/ cgi/ content/ abstract/ 21/ 5/ 886
[44] "Definition of Chickenpox" (http:/ / www. medterms. com/ script/ main/ art. asp?articlekey=2702). MedicineNet.com. . Retrieved
2006-08-18.
[45] "Is Necrotizing Fasciitis a complication of Chickenpox of Cutaneous Vasculitis?" (http:/ / www. atmedstu. com/ exam plus/ Is Necrotizing
Fasciitis a complication of Chickenpox or of Cutaneous Vasculitis. php). atmedstu.com. . Retrieved 2008-01-18.
[46] Chicken Pox Complications (http:/ / dermatology. about. com/ cs/ chickenpox/ a/ chickencomp. htm)
[47] Otri AM, Singh AD, Dua HS (October 2008). "Abu Bakr Razi" (http:/ / bjo. bmj. com/ cgi/ pmidlookup?view=long& pmid=18815419). The
British Journal of Ophthalmology 92 (10): 1324. PMID 18815419. . Retrieved 2009-06-20.
External links
• Chickenpox (http://www.dmoz.org/Health/Child_Health/Conditions_and_Diseases/Infectious_Diseases/
Chickenpox//) at the Open Directory Project
113
Scabies
114
Scabies
Scabies
A photomicrograph of an itch mite (Sarcoptes scabiei).
[1]
ICD-10
B 86.
ICD-9
133.0
DiseasesDB
11841
[2]
[3]
eMedicine
derm/382
MeSH
D012532
[5]
emerg/517
[6]
ped/2047
[7]
[8]
Scabies is a contagious skin infection that occurs among humans and animals. It is caused by a tiny and usually not
directly visible parasite—the mite Sarcoptes scabiei—which burrows under the host's skin, causing intense allergic
itching. The word scabies is derived from the Latin word scabere, which means scratch. Colloquially it is the disease
known as the seven year itch. The infection in animals (caused by different but related mite species) is called
sarcoptic mange.
The disease in humans may be transmitted from objects or bedding (like matresses,etc.), but is most often
transmitted by direct skin-to-skin contact, with prolonged contact being more efficient. Initial infections of scabies
require four to six weeks to become symptomatic. However, persons who have recently been cured of the disease,
upon re-infection, may manifest symptoms within as little as 24 hours. Because the symptoms are allergic, their
delay in onset is often mirrored by a significant delay in relief after the parasites have been eradicated.
Scabies mites prefer thin hairless skin, and for this reason concentrate on intertriginous parts of the body below the
neck, (between fingers and in skin folds), avoiding callused areas. Infants may be infected over any part of the body,
as may also immunosuppressed persons. Otherwise healthy persons with good hygeine may be infected with only an
average of 11 mites. Crusted scabies, formerly known as "Norwegian scabies," is a more severe form of the
infection often associated with immunosuppressed hosts. In crusted scabies, the mites, numbering thousands in such
cases, cause scaly rashes and thick crusts of skin.
Scabies
115
In both humans and animals, the disease can be effectively treated with a number of medications. Permethrin cream
is the most effective, but expensive compared to other treatments. Crotamiton is less effective, but also nontoxic and
soothing, allowing it to be used more often. Ivermectin is also used orally and topically, subject to restrictions
involving treatment toxicity differences between hosts. Treatment with lindane preparations have fallen out of favor
due to high toxicity and parasite resistance. In order to prevent re-infection, the host's contacts are also often treated.
Signs and symptoms
The characteristic symptoms of a scabies infection include intense itching and rashes.[9] The symptoms are caused by
an allergic reaction of the host's body to mite proteins, though exactly which proteins remains a topic of study. The
mite proteins are also present from the gut, in mite feces, which are deposited under the skin. The allergic reaction is
both of the delayed (cell mediated) and immediate (antibody mediated) type, and involves IgE (antibodies probably
mediate the very rapid symptoms on re-infection).[10] The allergy-type symptoms (itching) continue for some days,
and even several weeks, after all mites are killed. New "lesions" may even appear for a few days after mites are
eradicated. Nodular lesions from scabies may continue to be symptomatic for weeks after the mites have been
killed.[10]
The itching associated with scabies is histaminic, each lesion often similar-feeling to the moderate or severe reaction
from a mosquito bite. The symptoms are usually experienced as being worse at night, possibly because there are
fewer distractions.[9] [11] Classically the itch is also made worse by warmth, such as bathing in warm water. Itching
is a less common symptom among elderly sufferers of scabies.[9]
In most hosts, the trails of the burrowing mites show as linear or s-shaped tracks in the skin, often accompanied by
what appear as rows of small pimple-like mosquito, or insect bites. These signs are often found in crevices of the
body, such as on the webs of fingers and toes, around the genital area, and under the breasts of women.[12] Relatively
thin-skinned areas of the body, such as the inner wrists and buttocks, are also preferentially infected. The mites avoid
areas of skin with calluses, or thick hair. Thus, the face and scalp are rarely affected in adults. Infants infected with
the parasites, however, may have acropustulosis, which refers to blisters and pustules on their palms and soles of
their feet. Infants also may have infection of the scalp (which may mimic cradle cap).
The onset of the symptoms typically appear 2–6 weeks after infestation for individuals never before exposed to
scabies. For those who have been previously exposed, the symptoms can appear within several days after infestation.
However, it is not unknown for symptoms to appear after several months or years.[13]
Scabies of the foot
Scabies of the arm
Scabies of the
hand
Scabies of the finger
Scabies
116
Crusted scabies
Elderly and people who have an impaired immune system, such as
HIV and cancer sufferers or transplant patients on immunosuppressive
drugs, are susceptible to crusted scabies (formerly called "Norwegian
scabies").[14] [9] [13] With a weaker immune system, the host becomes a
more fertile breeding ground for the mites, who spread over his or her
body, except the face. Sufferers of crusted scabies exhibit scaly rashes,
slight itching, and thick crusts of skin that contain thousands of
mites.[15] Such areas make eradication of mites particularly difficult, as
the crusts protect the mites from topical miticides, necessitating
prolonged treatment of these areas.
Crusted scabies in a person with AIDS
Cause
In the 18th century, Italian biologist Diacinto Cestoni (1637-1718)
described the mite now called Sarcoptes scabiei, variety hominis,
as the cause of scabies. Sarcoptes is a genus of skin parasites and
part of the larger family of mites collectively known as "scab
mites". These organisms have 8 legs as adults, and are placed in
the same phylogenetic class (Arachnida) as spiders and ticks.
Sarcoptes scabiei are microscopic, but sometimes are visible as
pinpoints of white. Pregnant females tunnel into the stratum
corneum of a host's skin and deposit eggs in the burrows. The eggs
hatch into larvae in 3–10 days. These young mites move about on
Video of the sarcoptes scabiei mite.
the skin and molt into a "nymphal" stage, before maturing as
adults, which live 3–4 weeks in the host's skin. Males roam on top of the skin, occasionally burrowing into the skin.
Generally, there are usually few mites on a healthy hygeinic person who is infested with non-crusted scabies;
approximately 11 females in burrows can be found on such a person.[16]
The movement of mites within and on the skin produces an intense itch, which has the characteristics of a delayed
cell-mediated inflammatory response to allergens. IgE antibodies are present in the serum and the site of infection,
which react to multiple protein allergens the body of the mite. Some of these cross-react to allergens from house-dust
mites. Immediate antibody-mediated allergic reactions (wheals) have been elicited in infected persons, but not in
healthy persons; immediate hypersensitivity of this type is thought to explain the observed far more rapid allergic
skin response to reinfection seen in persons who have been previously infected (especially who has been infected
within the previous year or two).[17] Because the host develops the symptoms as a reaction to the mites' presence
over time, there is usually a 4–6 week incubation period after the onset of infestation. As noted, those who were
previously infected with scabies and cured, may exhibit the symptoms of a new infection in a much shorter
period—as little as 1–4 days.[18]
Scabies is contagious, and can be spread by scratching an infected area, thereby picking up the mites under the
fingernails, or through physical contact with a scabies-infected person for a prolonged period of time.[19] Scabies is
usually transmitted by direct skin-to-skin physical contact. It can also be spread through contact with other objects,
such as clothing, bedding, furniture, or surfaces that a person infected with scabies might have come in contact with,
but these are uncommon ways to transmit scabies.[20] Scabies mites can survive without a human host for 24 to
36 hours.[21] As with lice, scabies can be transmitted through sexual intercourse even if a latex condom is used,
because it is transmitted from skin-to-skin at sites other than sex organs.[22]
Scabies
117
Diagnosis
Scabies may be accurately diagnosed clinically in places where it is
common when diffuse itching presents along with either lesions in two
typical spots or a household member is also itchy. The classical proof
of scabies is the detection of burrows made by the mites in the skin.[23]
Typically, the suspected area is rubbed with ink from a fountain pen or
a topical tetracycline solution, which glows under a special light. The
skin is then wiped with an alcohol pad. If the person is infected with
scabies, the characteristic zigzag or "S" pattern of the burrow will
appear across the skin; however, this may be difficult as the burrows
are scarce and may be obscured by scratch marks.[23] A definitive
diagnosis is made by finding either the scabies mites or their eggs and
fecal pellets.[23] Searches for these signs involve either scraping a
suspected area, mounting the sample in potassium hydroxide, and
examining it under a microscope, or using dermoscopy to examine the
skin directly.[9]
Magnified view of the burrowing trail of a
scabies mite: the scaly patch on the left (caused
by the host's scratching) marks the mite's entry
point into the skin. The mite has burrowed to the
top right, where it can be seen as a dark spot at
the end.
Differential diagnoisis
Symptoms of early scabies infestation mirror other skin diseases, including dermatitis, syphilis, allergic reactions and
other ectoparasites such as lice and fleas.[24]
Prevention
Mass treatment programs that use topical permethrin or oral ivermectin have been effective in reducing the
prevalence of scabies in a number of populations.[23] There is no vaccine available for scabies. The simultaneous
treatment of all close contacts is recommended, even if they show no symptoms of infection (asymptomatic), to
reduce rates of recurrence.[23] Asymptomatic infection is relatively common.[23] Formites pose little risk of
transmission except in the case of crusted scabies thus cleaning of the environment is of little importance.[23] In
hospitals, rooms used by a patient who was diagnosed with crusted scabies are often thoroughly cleaned because an
outbreak is hard to control.[25]
Management
A number of medications have proved effective in treating scabies, however treatment must often involve the entire
household or community to prevent re-infection.[23] Options to symptomatically combat the resulting itchiness
include antihistamines.[26] Topical low-strength corticosteroids decrease symptoms (and are sometimes
recommended for a short time, while treating diagnosed cases), but there have been four cases of crusted scabies
associated with prolonged steroid treatment of undiagnosed cases of scabies, suggesting that in the long term, topical
steroids worsen host defenses against the parasite.[27] Nodular scabies (a more severe immunological reaction) have
been reported successfully treated with prolonged application of crotamiton, combined with injection of low-strength
corticosteroids into the lesions.[28]
Scabies
118
Permethrin
Permethrin is the most effective treatment for scabies,[29] and the treatment of choice.[23] [30] It is applied to skin
below the neck usually before bedtime and left on for about 8 to 14 hours, then showered off in the morning.[23] One
application is normally sufficient for mild infections. For moderate to severe cases, another dose is applied
7–14 days later.[23] [30] [31] Permethrin causes slight irritation of the skin, but the sensation is tolerable.[9] The
medication, however, is the most costly of topical treatments.[9]
Ivermectin
Ivermectin is an oral medication shown by many clinical studies to be effective in eradicating scabies, often in a
single dose.[23] [32] It is the treatment of choice for crusted scabies, and is often used in combination with a topical
agent.[9] [23] It has not been tested on infants and is not recommended for children under six years of age.[9]
More recently, topical 1% ivermectin preparations have been found to be effective for scabies in adults, and have
been attractive due to their low cost, ease of preparation, and low toxicity by this route.[33] Topical ivermectin has
also been useful for sarcoptic mange (the veterinary analog of human scabies).[34]
Others
Other treatments include lindane, benzyl benzoate, crotamiton, malathion, and sulfur preparations.[9] [23] Lindane is
effective; however, concerns over potential neurotoxicity has limited its availability in many countries.[9] It is
approved in the United States for use as a second-line treatment.[35] Sulfur ointments or benzyl benzoate are often
used in the developing world due to their low cost;[9] 10% sulfur solutions have been shown to be effective,[36] and
sulfur ointments are typically used for at least a week.[9] Benzyl benzoate must be applied and left on the body for at
least 24 hours to be effective.[37] Crotamiton in limited studies has been found to be less effective than permethrin.[9]
Crotamiton creme is frequently prescribed for use five times a day instead of the recommended two times a day by
the manufacturer, but has the advantage that the creme itself is a topical anti-irritant, and because of lower toxicity
than lindane, may be used at will until the disease is clearly under control, by symptom. It is unknown if crotamiton
is toxic if applied to the face.[38] Crotamiton or a sulfur preparation is often recommended instead of permethrin for
children, due to concerns over dermal absorption of permethrin.[23]
Day 4
Day 8 (treatment begins)
Day 12 (under treatment)
Healed
Epidemiology
Scabies is one of the three most common skin disorders in children along with tinea and pyoderma.[23] The mites are
distributed around the world and equally infects all ages, races, and socioeconomic classes in different climates.[15]
Scabies is more often seen in crowded areas with unhygienic living conditions.[39] Globally, it is estimated that
300 million cases of scabies occur each year, although various parties claim the figure is either over- or
underestimated.[13] [40] There are one million cases of scabies in the United States annually.[18] About 1–10% of the
global population is estimated to be infected with scabies, but in certain populations, the infection rate may be as
high as 50–80%.[41]
Scabies
History
Scabies is an ancient disease. Archeological evidence from Egypt and the Middle East suggests that scabies was
present as early as 494 BC.[18] [42] The first recorded reference to scabies is believed to be from the Bible (Leviticus,
the third book of Moses) ca. 1200 BC. Later in fourth century BC, the ancient Greek philosopher Aristotle reported
on "lice" that "escape from little pimples if they are pricked";[43] scholars believe this was actually a reference to
scabies.
Nevertheless it was Roman physician Celsus who is credited with naming the disease "scabies" and describing its
characteristic features.[43] The parasitic etiology of scabies was later documented by the Italian physician Giovanni
Cosimo Bonomo (1663–99 AD) in his famous 1687 letter, "Observations concerning the fleshworms of the human
body."[43] With this (disputed) discovery, scabies became one of the first diseases with a known cause.[18] [42] In
1844 Ferdinand von Hebra discovered the cause of scabies.[44]
In other animals
Scabies may occur in a number of domestic and wild animals; the
mites that cause these infestations are of different scabies subspecies.[9]
These subspecies can infest animals or humans that are not their usual
hosts, but such infections do not last long.[9] Scabies-infected animals
suffer severe itching and secondary skin infections. They often lose
weight and become frail.
The most frequently diagnosed form of scabies in domestic animals is
sarcoptic mange, which is found on dogs. The scab mite Psoroptes is
the mite responsible for mange. Scabies-infected domestic fowls suffer
A street dog in Bali, Indonesia, suffers from
what is known as "scabies leg". Domestic animals that have gone feral
sarcoptic mange.
and have no veterinary care are frequently afflicted with scabies and a
host of other ailments.[45] Non-domestic animals have also been observed to suffer from scabies. Gorillas, for
instance, are known to be susceptible to infection via contact with items used by humans.[46]
See also
• List of parasites (human)
References
[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
http:/ / www. emedicine. com/ derm/ topic382. htm
http:/ / www. emedicine. com/ emerg/ topic517. htm#
Hay RJ (2009). "Scabies and pyodermas—diagnosis and treatment". Dermatol Ther 22 (6): 466–74. doi:10.1111/j.1529-8019.2009.01270.x.
PMID 19889132.
[10] See PMID 17428886 below online reference. (http:/ / cmr. asm. org/ cgi/ content/ full/ 20/ 2/ 268?view=long)
[11] Taber, Clarence Wilbur; Venes, Donald (2009). Taber's cyclopedic medical dictionary. F a Davis Co. pp. 2073–4. ISBN 0-8036-1559-0.
[12] "Scabies" (http:/ / www. dermnetnz. org/ arthropods/ pdf/ scabies-dermnetnz. pdf). DermNet NZ. New Zealand Dermatological Society
Incorporated. .
119
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[13] Bouvresse, S.; Chosidow, O. (Apr 2010). "Scabies in healthcare settings.". Curr Opin Infect Dis 23 (2): 111–8.
doi:10.1097/QCO.0b013e328336821b. PMID 20075729.
[14] Hicks MI, Elston DM (2009). "Scabies". Dermatol Ther 22 (4): 279–92. doi:10.1111/j.1529-8019.2009.01243.x. PMID 19580575.
[15] "DPDx—Scabies" (http:/ / www. dpd. cdc. gov/ dpdx/ HTML/ Scabies. htm). Laboratory Identification of Parasites of Public Health
Concern. CDC. .
[16] See PMID 17428886 below online reference (http:/ / cmr. asm. org/ cgi/ content/ full/ 20/ 2/ 268?view=long)
[17] Clinical Microbiology Reviews, April 2007, p. 268-279, Vol. 20, No. 2 0893-8512/07/$08.00+0 doi:10.1128/CMR.00042-06 Problems in
Diagnosing Scabies, a Global Disease in Human and Animal Populations online reference (http:/ / cmr. asm. org/ cgi/ content/ full/ 20/ 2/
268?view=long) PMID 17428886
[18] Markell, Edward K.; John, David C.; Petri, William H. (2006). Markell and Voge's medical parasitology (9th ed.). St. Louis, Mo: Elsevier
Saunders. ISBN 0-7216-4793-6.
[19] Carol Turkington and Jeffrey S. Dover, M.D. (2006). The Encyclopedia of Skin and Skin Disorders. New York: Facts on File inc.
ISBN 978-0-8160-6403-8.
[20] Causes "Scabies Causes" (http:/ / www. emedicinehealth. com/ scabies/ page2_em. htm#Scabies). WebMD. October 2010. Causes.
[21] Chosidow O (April 2006). "Clinical practices. Scabies". N. Engl. J. Med. 354 (16): 1718–27. doi:10.1056/NEJMcp052784.
PMID 16625010.
[22] "Scabies—Fast Facts" (http:/ / www. ashastd. org/ learn/ learn_scabies_facts. cfm). American Social Health Association. . Retrieved
2010-10-09.
[23] Andrews RM, McCarthy J, Carapetis JR, Currie BJ (December 2009). "Skin disorders, including pyoderma, scabies, and tinea infections".
Pediatr. Clin. North Am. 56 (6): 1421–40. doi:10.1016/j.pcl.2009.09.002. PMID 19962029.
[24] Arlian LG (1989). "Biology, host relations, and epidemiology of Sarcoptes scabiei" (http:/ / arjournals. annualreviews. org/ doi/ abs/ 10.
1146/ annurev. en. 34. 010189. 001035?url_ver=Z39. 88-2003& rfr_id=ori:rid:crossref. org& rfr_dat=cr_pub=ncbi. nlm. nih. gov). Annu. Rev.
Entomol. 34: 139–61. doi:10.1146/annurev.en.34.010189.001035. PMID 2494934. .
[25] "CDC—Prevention and Control—Scabies" (http:/ / www. cdc. gov/ scabies/ prevent. html). Center for Disease Control and Prevention. .
[26] doi: 10.3949/ccjm.75.7.474 Cleveland Clinic Journal of Medicine July 2008 vol. 75 7 474–478 online link (http:/ / ccjm. org/ content/ 75/ 7/
474. full)
[27] see for case reports of Norwegian scabies from topical steroids. (http:/ / archderm. ama-assn. org/ cgi/ reprint/ 134/ 2/ 143. pdf)
[28] Mittal RR, Jain C, Jindal R. Treatment of nodular scabies (le). Indian J Dermatol Venereol Leprol [serial online] 1998 [cited 2010 Nov
13];64:157-8. Available from: http:/ / www. ijdvl. com/ text. asp?1998/ 64/ 3/ 157/ 4680
[29] Strong M, Johnstone PW (2007). "Interventions for treating scabies". Cochrane Database Syst Rev (3): CD000320.
doi:10.1002/14651858.CD000320.pub2. PMID 17636630.
[30] "Scabies" (http:/ / www. idph. state. il. us/ public/ hb/ hbscab. htm). Illinois Department of Public Health. January 2008. . Retrieved
2010-10-07.
[31] The Pill Book. Bantam Books. 2010. pp. 867–869. ISBN 978-0-553-59340-2.
[32] "WHO -Water-related Disease" (http:/ / www. who. int/ water_sanitation_health/ diseases/ scabies/ en/ ). World Health Organization. .
[33] Victoria J, Trujillo R (2001). "Topical ivermectin: a new successful treatment for scabies". Pediatr Dermatol 18 (1): 63–5. PMID 11207977.
[34] "Parasitology Research, Volume 78, Number 2" (http:/ / www. springerlink. com/ content/ v84881343215g085/ ). SpringerLink. . Retrieved
2010-11-14.
[35] "FDA Public Health Advisory: Safety of Topical Lindane Products for the Treatment of Scabies and Lice" (http:/ / www. fda. gov/ Drugs/
DrugSafety/ PostmarketDrugSafetyInformationforPatientsandProviders/ ucm110845. htm). Fda.gov. 2009-04-30. . Retrieved 2010-11-14.
[36] Jin-Gang A, Sheng-Xiang X, Sheng-Bin X, et al. (March 2010). "Quality of life of patients with scabies". J Eur Acad Dermatol Venereol 24:
1187. doi:10.1111/j.1468-3083.2010.03618.x. PMID 20236379.
[37] "BENZYL BENZOATE (Topical route)". Detailed Drug Information for the Consumer. Thomson Healthcare, Inc.. 2010.
[38] Turkington, Carol; Jeffrey S. Dover (2006). "crotamiton cream". The Encyclopedia of Skin and Skin Disorders (3rd edition ed.). New York,
New York: Facts on File.
[39] Green MS (1989). "Epidemiology of scabies" (http:/ / epirev. oxfordjournals. org/ cgi/ reprint/ 11/ 1/ 126). Epidemiol Rev 11: 126–50.
PMID 2509232. .
[40] Seite, F.; Delelis-Fanien, AS.; Valero, S.; Pradère, C.; Poupet, JY.; Ingrand, P.; Paccalin, M. (Nov 2009). "Compliance with guidelines for
proton pump inhibitor prescriptions in a department of geriatrics.". J Am Geriatr Soc 57 (11): 2169–70.
doi:10.1111/j.1532-5415.2009.02540.x. PMID 20121973.
[41] Andrews, RM.; McCarthy, J.; Carapetis, JR.; Currie, BJ. (Dec 2009). "Skin disorders, including pyoderma, scabies, and tinea infections.".
Pediatr Clin North Am 56 (6): 1421–40. doi:10.1016/j.pcl.2009.09.002. PMID 19962029.
[42] "SCABIES HOMEPAGE" (http:/ / www. stanford. edu/ group/ parasites/ ParaSites2005/ Scabies/ SCABIES. html). Stanford University. .
[43] Roncalli RA (July 1987). "The history of scabies in veterinary and human medicine from biblical to modern times" (http:/ / linkinghub.
elsevier. com/ retrieve/ pii/ 0304-4017(87)90104-X). Vet. Parasitol. 25 (2): 193–8. doi:10.1016/0304-4017(87)90104-X. PMID 3307123. .
120
Scabies
[44] , http:/ / www. whonamedit. com/ doctor. cfm/ 708. html
[45] "Bali Animal Welfare Association" (http:/ / www. bawabali. com/ ). . Retrieved 2009-07-28.
[46] [ Uganda: Out of the Wild (http:/ / www. pbs. org/ wgbh/ pages/ frontline/ story/ 2009/ 11/ doomsday-thinking. html|FRONTLINE/
World)]. Transcript (http:/ / www. pbs. org/ wgbh/ pages/ frontline/ tehranbureau/ deathintehran/ etc/ script. html).
External links
• American Academy of Dermatology pamphlet on Scabies (http://www.aad.org/public/publications/
pamphlets/common_scabies.html)
• Scabies FAQ from the National Pediculosis Association (http://www.headlice.org/faq/scabies.htm)
121
122
A culture positive case of streptococcal pharyngitis with typical tonsillar exudate in a 16 year old.
[1]
ICD-10
J 02.0
ICD-9
034.0
DiseasesDB
12507
MedlinePlus
000639
eMedicine
med/1811
[2]
[3]
[4]
[5]
Streptococcal pharyngitis, streptococcal tonsillitis, or streptococcal sore throat (known colloquially as strep
throat) is a type of pharyngitis caused by a group A streptococcal infection[6] . It affects the pharynx including the
tonsils and possibly the larynx. Common symptoms include fever, sore throat, and enlarged lymph nodes. It is the
cause of 37% of sore throats among children.[7]
Strep throat is a contagious infection, spread through close contact with an infected individual. A definitive diagnosis
is made based on the results of a throat culture. However, this is not always needed as treatment may be decided
based on symptoms. In highly likely or confirmed cases, antibiotics are useful to both prevent complications and
speed recovery.[8]
Signs and symptoms
The typical symptoms of streptococcal pharyngitis are a sore throat, fever of greater than 38 °C (100 °F), tonsillar
exudates (pus on the tonsils), and large cervical lymph nodes.[8]
Other symptoms include:
•
•
•
•
•
Headache[9]
Nausea and vomiting[9]
Abdominal pain[9]
Myalgia (muscle pain)[10]
Scarlatiniform rash or palatal petechiae[8]
The incubation period and thus the start of symptoms for strep throat is between one to three days post contact.[8]
A throat infection which on culture tested positive for group A streptococcus. Note the large
tonsils with white exudate. Note the petechiae, or small red spots, on the soft palate. This is an uncommon but highly specific finding in
streptococcal pharyngitis.[8]
123
124
A culture positive case of streptococcal pharyngitis with typical tonsillar
exudate in an 8 year old. Cause
Strep throat is caused by group A beta-hemolytic streptococcus (GAS).[11] Other bacteria such as non–group A
beta-hemolytic streptococci and fusobacterium may also cause pharyngitis.[8] [10] It is spread by direct, close contact
with an infected person and thus crowding as may be found in the military and schools increases the rate of
transmission.[10] [12] It has been found that dried bacteria in dust are not infectious, although moist bacteria on
toothbrushes or similar items can persist for up to fifteen days.[10] Rarely, contaminated food can result in
outbreaks.[10] Of children with no signs or symptoms 12% carry GAS in their pharynx.[7]
Diagnosis
Modified Centor score
Points
Probability of Strep
Management
1 or less
<10%
No antibiotic or culture needed
2
11–17%
Antibiotic based on culture or RADT
3
28–35%
4 or 5
52%
Empiric antibiotics
The modified Centor score is used to determine the management of people with pharyngitis. Based on 5 clinical
criteria, it indicates the probability of a streptococcal infection.[8]
One point is given for each of the criteria:[8]
•
•
•
•
•
Absence of a cough
Swollen and tender cervical lymph nodes
Temperature >38 °C (100 °F)
Tonsillar exudate or swelling
Age less than 15 (a point is subtracted if age >44)
125
Laboratory testing
A throat culture is the gold standard[13] for the diagnosis of streptococcal pharyngitis with a sensitivity of 90–95%.[8]
A rapid strep test (also called rapid antigen detection testing or RADT) may also be used. While the rapid strep test
is quicker, it has a lower sensitivity (70%) and statistically equal specificity (98%) as throat culture.[8]
A positive throat culture or RADT in association with symptoms establishes a positive diagnosis in those in which
the diagnosis is in doubt.[14] Asymptomatic individuals should not be routinely tested with a throat culture or RADT
because a certain percentage of the population persistently "carries" the streptococcal bacteria in their throat without
any harmful results.[14]
Differential diagnosis
As the symptoms of streptococcal pharyngitis overlap with other conditions it can be difficult to make the diagnosis
clinically.[8] Coughing, nasal discharge, diarrhea, and red, irritated eyes in addition to fever and sore throat are more
indicative of a viral sore throat than of strep throat.[8] The presence of marked lymph node enlargement along with
sore throat, fever and tonsillar enlargement may also occur in infectious mononucleosis.[15]
Prevention
Tonsillectomy may be a reasonable preventative measure in those with frequent throat infections.[16]
more a year was seen as sufficient in 2003.[18] Watchful waiting is also appropriate.[16]
[17]
Three or
Treatment
Untreated streptococcal pharyngitis usually resolves within a few days.[8] Treatment with antibiotics shortens the
duration of the acute illness by about 16 hours.[8] The primary reason for treatment with antibiotics is to reduce the
risk of complications such as rheumatic fever and retropharyngeal abscesses[8] and they are effective if given within
9 days of the onset of symptoms.[11]
Analgesics
Analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol (acetaminophen) help
significantly in the management of pain associated with strep throat.[19] Steroids are also useful in this respect[11] [20]
as is viscous lidocaine.[21] Aspirin may be used in adults but is not recommended in children due to the risk of Reye's
syndrome.[11]
Antibiotics
The antibiotic of choice in the United States for streptococcal pharyngitis is penicillin V due to safety, cost, and
effectiveness.[8] Amoxicillin is preferred in Europe.[22] In India, where the risk of rheumatic fever is higher,
intramuscular benzathine penicillin G is the first choice for treatment.[11] Appropriate antibiotics decrease the
average 3–5 day duration of symptoms by about one day, and also reduce contagiousness.[14] They are primarily
prescribed out of a motivation to reduce rare complications such as acute rheumatic fever and peritonsillar
abscess.[23] The arguments in favour of antibiotic treatment should be balanced by the consideration of possible side
effects,[10] and it is reasonable to suggest that no antimicrobial treatment be given to healthy adults who have
adverse reactions to medication.[23] Antibiotics are prescribed for strep throat at a higher rate than would be expected
from its prevalence.[24] Erythromycin and other macrolides are recommended for people with severe penicillin
allergies.[8] First, general cephalosporins may be used in those with less severe allergies.[8] Streptococcal infections
may also lead to acute glomerulonephritis, however the incidence of this side effect is not reduced by the use of
antibiotics.[11]
Prognosis
The symptoms of strep throat usually improve irrespective of treatment within three to five days.[14] Treatment with
antibiotics reduces the risk of complications and transmission; children may return to school 24 hours after
antibiotics are administered.[8]
Complications arising from streptococcal throat infections include:
•
•
•
•
•
Acute rheumatic fever[9]
Scarlet fever[25]
Streptococcal toxic shock syndrome[25] [26]
Glomerulonephritis[27]
PANDAS syndrome[27]
Epidemiology
Pharyngitis, the broader category into which Streptococcal pharyngitis falls, is diagnosed in 11 million people
annually in the United States.[8] Although most cases are viral, group A beta-hemolytic streptococcus is the cause in
15–30% of the pharyngitis cases in children and 5–20% in adults.[8] Cases usually occur in late winter and early
spring.[8]
References
[1]
[2]
[3]
[4]
[5]
[6]
http:/ / apps. who. int/ classifications/ apps/ icd/ icd10online/ ?gj00. htm+ j020
streptococcal pharyngitis (http:/ / www. mercksource. com/ pp/ us/ cns/ cns_hl_dorlands_split. jsp?pg=/ ppdocs/ us/ common/ dorlands/
dorland/ nine/ 100014400. htm) at Dorland's Medical Dictionary
[7] Shaikh N, Leonard E, Martin JM (September 2010). "Prevalence of streptococcal pharyngitis and streptococcal carriage in children: a
meta-analysis". Pediatrics 126 (3): e557–64. doi:10.1542/peds.2009-2648. PMID 20696723.
[8] Choby BA (March 2009). "Diagnosis and treatment of streptococcal pharyngitis". Am Fam Physician 79 (5): 383–90. PMID 19275067.
[9] Brook I, Dohar JE (December 2006). "Management of group A beta-hemolytic streptococcal pharyngotonsillitis in children". J Fam Pract 55
(12): S1–11; quiz S12. PMID 17137534.
[10] Hayes CS, Williamson H (April 2001). "Management of Group A beta-hemolytic streptococcal pharyngitis" (http:/ / www. aafp. org/ afp/
20010415/ 1557. html). Am Fam Physician 63 (8): 1557–64. PMID 11327431. .
[11] Baltimore RS (February 2010). "Re-evaluation of antibiotic treatment of streptococcal pharyngitis". Curr. Opin. Pediatr. 22 (1): 77–82.
doi:10.1097/MOP.0b013e32833502e7. PMID 19996970.
[12] Lindbaek M, Høiby EA, Lermark G, Steinsholt IM, Hjortdahl P (2004). "Predictors for spread of clinical group A streptococcal tonsillitis
within the household". Scand J Prim Health Care 22 (4): 239–43. doi:10.1080/02813430410006729. PMID 15765640.
[13] Smith, Ellen Reid; Kahan, Scott; Miller, Redonda G. (2008). In A Page Signs & Symptoms. In a Page Series. Hagerstown, Maryland:
Lippincott Williams & Wilkins. pp. 312. ISBN 0-7817-7043-2.
[14] Bisno AL, Gerber MA, Gwaltney JM, Kaplan EL, Schwartz RH (July 2002). "Practice guidelines for the diagnosis and management of
group A streptococcal pharyngitis. [[Infectious Diseases Society of America (http:/ / www. journals. uchicago. edu/ doi/ abs/ 10. 1086/
340949)]"]. Clin. Infect. Dis. 35 (2): 113–25. doi:10.1086/340949. PMID 12087516. .
[15] Ebell MH (2004). "Epstein-Barr virus infectious mononucleosis" (http:/ / www. aafp. org/ afp/ 20041001/ 1279. html). Am Fam Physician
70 (7): 1279–87. PMID 15508538. .
[16] Paradise JL, Bluestone CD, Bachman RZ, et al. (March 1984). "Efficacy of tonsillectomy for recurrent throat infection in severely affected
children. Results of parallel randomized and nonrandomized clinical trials". N. Engl. J. Med. 310 (11): 674–83.
doi:10.1056/NEJM198403153101102. PMID 6700642.
[17] Alho OP, Koivunen P, Penna T, Teppo H, Koskela M, Luotonen J (May 2007). "Tonsillectomy versus watchful waiting in recurrent
streptococcal pharyngitis in adults: randomised controlled trial" (http:/ / www. pubmedcentral. nih. gov/ articlerender. fcgi?tool=pmcentrez&
artid=1865439). BMJ 334 (7600): 939. doi:10.1136/bmj.39140.632604.55. PMID 17347187. PMC 1865439.
[18] Johnson BC, Alvi A (March 2003). "Cost-effective workup for tonsillitis. Testing, treatment, and potential complications". Postgrad Med
113 (3): 115–8, 121. PMID 12647478.
126
[19] Thomas M, Del Mar C, Glasziou P (October 2000). "How effective are treatments other than antibiotics for acute sore throat?" (http:/ /
www. pubmedcentral. nih. gov/ articlerender. fcgi?tool=pmcentrez& artid=1313826). Br J Gen Pract 50 (459): 817–20. PMID 11127175.
PMC 1313826.
[20] "Effectiveness of Corticosteroid Treatment in Acute Pharyngitis: A Systematic Review of the Literature." (http:/ / www3. interscience.
wiley. com/ journal/ 123372200/ abstract). Andrew Wing. 2010; Academic Emergency Medicine. .
[21] "Generic Name: Lidocaine Viscous (Xylocaine Viscous) side effects, medical uses, and drug interactions" (http:/ / www. medicinenet. com/
lidocaine_viscous/ article. htm). MedicineNet.com. . Retrieved 2010-05-07.
[22] Bonsignori F, Chiappini E, De Martino M (2010). "The infections of the upper respiratory tract in children". Int J Immunopathol Pharmacol
23 (1 Suppl): 16–9. PMID 20152073.
[23] Snow V, Mottur-Pilson C, Cooper RJ, Hoffman JR (March 2001). "Principles of appropriate antibiotic use for acute pharyngitis in adults"
(http:/ / www. annals. org/ cgi/ reprint/ 134/ 6/ 506. pdf). Ann Intern Med 134 (6): 506–8. PMID 11255529. .
[24] Linder JA, Bates DW, Lee GM, Finkelstein JA (November 2005). "Antibiotic treatment of children with sore throat" (http:/ / jama.
ama-assn. org/ cgi/ content/ full/ 294/ 18/ 2315). J Am Med Assoc 294 (18): 2315–22. doi:10.1001/jama.294.18.2315 (inactive 2009-11-10).
PMID 16278359. .
[25] "UpToDate Inc." (http:/ / www. utdol. com/ online/ content/ topic. do?topicKey=upp_resp/ 4610). .
[26] Stevens DL, Tanner MH, Winship J, et al. (July 1989). "Severe group A streptococcal infections associated with a toxic shock-like
syndrome and scarlet fever toxin A". N. Engl. J. Med. 321 (1): 1–7. doi:10.1056/NEJM198907063210101. PMID 2659990.
[27] Hahn RG, Knox LM, Forman TA (May 2005). "Evaluation of poststreptococcal illness". Am Fam Physician 71 (10): 1949–54.
PMID 15926411.
127
128
16-month-old with erythema infectiosum
ICD-10
B 08.3
ICD-9
057.0
[1]
[2]
DiseasesDB 4442 [3]
eMedicine
emerg/378
MeSH
D016731
[4]
derm/136
[5]
ped/192
[6]
[7]
Erythema infectiosum or fifth disease is one of several possible manifestations of infection by erythrovirus
previously called parvovirus B19.[8] The disease is also referred to as slapped cheek syndrome, slapcheek, slap
face or slapped face.[9] [10] In Japan the disease is called 'apple sickness' or 'ringo-byou' (りんご病）in reference to
the symptom of facial redness.
History
The name "fifth disease" derives from its historical classification as the fifth of the classical childhood skin rashes or
exanthems. The other common skin rashes are:
1.
2.
3.
4.
5.
6.
Measles
Scarlet fever
Rubella
Duke's disease
Roseola
It was first described by Robert Willan in 1799 as "Rubeola, sine catarrho". It was better defined by Anton Tschamer
in 1889 as a rubella variant ("Ortliche Rotheln"), identified as a distinct condition in 1896 by T. Escherich, and given
the name "erythema infectiosum" in 1899.[11]
Symptoms
Bright red cheeks are a defining symptom of the infection in children (hence the name "slapped cheek disease").
Occasionally the rash will extend over the bridge of the nose or around the mouth. In addition to red cheeks, children
often develop a red, lacy rash on the rest of the body, with the upper arms and legs being the most common
locations. The rash typically lasts a couple of days and may itch; some cases have been known to last for several
weeks. Patients are usually no longer infectious once the rash has appeared.[9] [10]
Teenagers and adults may present with a self-limited arthritis. It manifests in painful swelling of the joints that feels
similar to arthritis. Older children and adults with Fifth Disease may have difficulty in walking and in bending joints
such as wrists, knees, ankles, fingers, and shoulders.[9] [10]
The disease is usually mild,[12] but in certain risk groups it can have serious consequences:
• In pregnant women, infection in the first trimester has been linked to hydrops fetalis, causing spontaneous
abortion.
• In people with sickle-cell disease or other forms of chronic hemolytic anemia such as hereditary spherocytosis,
infection can precipitate an aplastic crisis.[9] [10]
Transmission
Fifth disease is transmitted primarily by respiratory secretions (saliva, mucus etc.) but can also be spread by contact
with infected blood. The incubation period (the time between the initial infection and the onset of symptoms) is
usually between 4 and 21 days. Individuals with fifth disease are most infectious before the onset of symptoms.
Typically, school children, day-care workers, teachers and mothers are most likely to be exposed to the virus. When
symptoms are evident, there is little risk of transmission; therefore, symptomatic individuals need not be isolated.[9]
[10]
Epidemiology
Any age may be affected although it is most common in children aged five to fifteen years.[13] By the time adulthood
is reached about half the population will have become immune following infection at some time in their past.[9] [10]
Outbreaks can arise especially in nursery schools, preschools, and elementary schools.
See also
References
[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
http:/ / www. emedicine. com/ derm/ topic136. htm#
Weir E (March 2005). "Parvovirus B19 infection: fifth disease and more" (http:/ / www. cmaj. ca/ cgi/ pmidlookup?view=long&
pmid=15767606). CMAJ 172 (6): 743. doi:10.1503/cmaj.045293. PMID 15767606. PMC 552884. .
[9] Sabella C, Goldfarb J (October 1999). "Parvovirus B19 infections" (http:/ / www. aafp. org/ afp/ 991001ap/ 1455. html). Am Fam Physician
60 (5): 1455–60. PMID 10524489. . Retrieved 2009-11-06.
[10] Servey JT, Reamy BV, Hodge J (February 2007). "Clinical presentations of parvovirus B19 infection" (http:/ / www. aafp. org/ afp/
20070201/ 373. html). Am Fam Physician 75 (3): 373–6. PMID 17304869. . Retrieved 2009-11-06.
[11] Altman, Lawrence K (November 30, 1982). "THE DOCTOR'S WORLD" (http:/ / www. nytimes. com/ 1982/ 11/ 30/ science/
the-doctor-s-world. html?pagewanted=all). The New York Times. . Retrieved November 7, 2009.
129
[12] Mankuta D, Bar-Oz B, Koren G (March 1999). "Erythema infectiosum (Fifth disease) and pregnancy" (http:/ / www. pubmedcentral. nih.
gov/ articlerender. fcgi?tool=pmcentrez& artid=2328398). Can Fam Physician 45: 603–5. PMID 10099795. PMC 2328398.
[13] Kwon, Kenneth T (March 19, 2009). "Pediatrics, Fifth Disease or Erythema Infectiosum" (http:/ / www. emedicine. com/ emerg/ topic378.
htm). eMedicine. . Retrieved November 7, 2009.
External links
•
•
•
•
CDC (http://www.cdc.gov/ncidod/diseases/parvovirus/B19.htm)
Parvovirus Information (http://www.b19virus.com/)
Slapped Cheek Information (http://www.slappedcheek.com/)
www.fifthdisease.org (http://www.fifthdisease.org/)
130
Conjunctivitis
131
Conjunctivitis
Conjunctivitis
An eye with viral conjunctivitis.
[1]
ICD-10
H 10.
ICD-9
372.0
DiseasesDB
3067
MedlinePlus
001010
eMedicine
emerg/110
MeSH
D003231
[2]
[3]
[4]
[5]
[6]
Conjunctivitis (also called pink eye[7] or madras eye[8] ) refers to inflammation of the conjunctiva (the outermost
layer of the eye and the inner surface of the eyelids).[7] It is most commonly due to an infection (usually viral, but
sometimes bacterial[9] ) or an allergic reaction.
Classification
Classification can be either by cause or by extent of the inflamed area.
By cause
•
•
•
•
•
Allergic conjunctivitis
Bacterial conjunctivitis
Viral conjunctivitis
Chemical conjunctivitis
Neonatal conjunctivitis is often defined separately due to different organisms
Conjunctivitis
132
By extent of involvement
Blepharoconjunctivitis is the dual combination of conjunctivitis with blepharitis (inflammation of the eyelids).
Keratoconjunctivitis is the combination of conjunctivitis and keratitis (corneal inflammation).
Episcleritis is an inflammatory condition that produces a similar appearance to conjunctivitis, but without discharge
or tearing.
Signs and symptoms
Red eye (hyperaemia), irritation (chemosis) and watering (epiphora) of
the eyes are symptoms common to all forms of conjunctivitis. However
the pupils should be normally reactive. and the visual acuity normal.
Viral
Eyes with conjunctivitis
Viral conjunctivitis is often associated with an infection of the upper
respiratory tract, a common cold, and/or a sore throat. Its symptoms
include watery discharge and variable itch. The infection usually
begins with one eye, but may spread easily to the other.
Viral conjunctivitis, commonly known as "pink eye" shows a fine
diffuse pinkness of the conjunctiva which is easily mistaken for the
'ciliary injection' of iritis, but there are usually corroborative signs on
microscopy, particularly numerous lymphoid follicles on the tarsal
conjunctiva, and sometimes a punctate keratitis.
An eye, red due to acute conjunctivitis.
Bacterial
Bacterial conjunctivitis due to the common pyogenic (pus-producing)
bacteria causes marked grittiness/irritation and a stringy, opaque,
greyish or yellowish mucopurulent discharge that may cause the lids to
stick together, especially after sleep. Another symptom that could be
caused by bacterial conjunctivitis is severe crusting of the infected eye
and the surrounding skin. However discharge is not essential to the
diagnosis, contrary to popular belief. Bacteria such as Chlamydia
An eye with bacterial conjunctivitis.
trachomatis or Moraxella can cause a non-exudative but persistent
conjunctivitis without much redness. The gritty and/or scratchy feeling is sometimes localized enough for patients to
insist they must have a foreign body in the eye. The more acute pyogenic infections can be painful. Like viral
conjunctivitis, it usually affects only one eye but may spread easily to the other eye. However, it is dormant in the
eye for three days before the patient shows signs of symptoms.
Chemical
Irritant or toxic conjunctivitis is irritable or painful when the infected eye is pointed far down or far up. Discharge
and itch are usually absent. This is the only group in which severe pain and discomfort may occur.
Irritant or toxic conjunctivitis show primarily marked redness. If due to splash injury, it is often present only in the
lower conjunctival sac. With some chemicals, above all, with caustic alkalis such as sodium hydroxide—there may
be necrosis of the conjunctiva with a deceptively white eye due to vascular closure, followed by sloughing of the
dead epithelium. This is likely to be associated with slit-lamp evidence of anterior uveitis.
Conjunctivitis
Other
Inclusion conjunctivitis of the newborn (ICN) is a conjunctivitis that may be caused by the bacteria Chlamydia
trachomatis, and may lead to acute, purulent conjunctivitis.[10] However, it is usually self-healing.[10]
Conjunctivitis is identified by irritation and redness of the conjunctiva. Except in obvious pyogenic or toxic/chemical
conjunctivitis, a slit lamp (biomicroscope) is needed to have any confidence in the diagnosis. Examination of the
tarsal conjunctiva is usually more diagnostic than the bulbar conjunctiva.
Causes
Conjunctivitis is most commonly caused by viral infection, but bacterial infections, allergies, other irritants and
dryness are also common etiologies for its occurrence. Both bacterial and viral infections are contagious. Commonly,
conjunctival infections are passed from person-to-person, but can also spread through contaminated objects or water.
The most common cause of viral conjunctivitis is adenoviruses . Herpetic keratoconjunctivitis (caused by herpes
simplex viruses) can be serious and requires treatment with acyclovir. Acute hemorrhagic conjunctivitis is a highly
contagious disease caused by one of two enteroviruses, Enterovirus 70 and Coxsackievirus A24. These were first
identified in an outbreak in Ghana in 1969 and have spread worldwide since then, causing several epidemics.[11]
Differential diagnosis
Conjunctivitis is a relatively non-specific symptom.[7] Even after bio microscopy, laboratory tests are often necessary
if proof of etiology is needed.
A purulent discharge (a whitish-yellow, yellow or yellow-brown substance more commonly known as pus) strongly
suggests a cause from fecal matter, unless there is known exposure to toxins. It can also be caused by bacteria from
feces, pet hair, or by smoke or other fumes. Infection with Neisseria gonorrhoeae should be suspected if the
discharge is particularly thick and copious.
Itching (rubbing eyes) is the hallmark symptom of allergic conjunctivitis. Other symptoms include past history of
eczema, or asthma.
A diffuse, less "injected" conjunctivitis (looking pink rather than red) suggests a viral cause, especially if numerous
follicles are present on the lower tarsal conjunctiva on bio microscopy.
Scarring of the tarsal conjunctiva suggests trachoma, especially if seen in endemic areas, if the scarring is linear (von
Arlt's line), or if there is also corneal vascularisation.
Clinical tests for lagophthalmos, dry eye (Schirmer test) and unstable tear film may help distinguish the various
types of conjunctivitis.
Other symptoms including pain, blurring of vision and photophobia should not be prominent in conjunctivitis.
Fluctuating blurring is common, due to tearing and mucoid discharge. Mild photophobia is common. However, if
any of these symptoms are prominent, it is important to exclude other diseases such as glaucoma, uveitis, keratitis
and even meningitis or caroticocavernous fistula.
Many people who have conjunctivitis have trouble opening their eyes in the morning because of the dried mucus on
their eyelids. There is often excess mucus over the eye after sleeping for an extended period.
133
Conjunctivitis
Diagnosis
These are done infrequently because most cases of conjunctivitis are treated empirically and (eventually)
successfully, but often only after running the gamut of the common possibilities.
Swabs for bacterial culture are necessary if the history and signs suggest bacterial conjunctivitis, but there is no
response to topical antibiotics. Research studies indicate that many bacteria implicated in low-grade conjunctivitis
are not detected by the usual culture methods of medical microbiology labs, so false negative results are common.
Viral culture may be appropriate in epidemic case clusters. Conjunctival scrapes for cytology can be useful in
detecting chlamydial and fungal infections, allergy and dysplasia, but are rarely done because of the cost and the
general lack of laboratory staff experienced in handling ocular specimens. Conjunctival incisional biopsy is
occasionally done when granulomatous diseases (e.g., sarcoidosis) or dysplasia are suspected.
Management
Conjunctivitis resolves in 65% of cases without treatment, within 2 – 5 days. The prescribing of antibiotics to most
cases is not necessary.[12]
Allergic
For the allergic type, cool water poured over the face with the head inclined downward constricts capillaries, and
artificial tears sometimes relieve discomfort in mild cases. In more severe cases, non-steroidal anti-inflammatory
medications and antihistamines may be prescribed. Persistent allergic conjunctivitis may also require topical steroid
drops.
Bacterial
Bacterial conjunctivitis usually resolves without treatment. Antibiotics, eye drops, or ointment are thus only needed
if no improvement is observed after 3 days.[13] In patients receiving no antibiotics recovery was in 4.8 days,
immediate antibiotics 3.3 days, delayed antibiotics 3.9 days. No serious effects were noted either with or without
treatment.[14] [15]
Viral
Although there is no specific treatment for viral conjunctivitis, symptomatic relief may be achieved with cold
compresses[16] and artificial tears. People are often advised to avoid touching their eyes or sharing towels and
washcloths.
Chemical
Conjunctivitis due to chemicals is treated via irrigation with Ringer's lactate or saline solution. Chemical injuries
(particularly alkali burns) are medical emergencies as they can lead to severe scarring, and intraocular damage.
References
[1]
[2]
[3]
[4]
[5]
[6]
http:/ / apps. who. int/ classifications/ apps/ icd/ icd10online/ ?gh10. htm+ h10
[7] Richards A, Guzman-Cottrill JA (May 2010). "Conjunctivitis". Pediatr Rev 31 (5): 196–208. doi:10.1542/pir.31-5-196. PMID 20435711.
[8] "Beware, `Madras eye' is here!" (http:/ / www. hinduonnet. com/ 2001/ 10/ 12/ stories/ 0412402c. htm). The Hindu. 2001-10-12. . Retrieved
2008-10-30.
134
Conjunctivitis
[9] Langley JM. Adenoviruses. Pediatr Rev. 2005;26:238-242.
[10] Fisher, Bruce; Harvey, Richard P.; Champe, Pamela C. (2007). Lippincott's Illustrated Reviews: Microbiology (Lippincott's Illustrated
Reviews Series). Hagerstown, MD: Lippincott Williams & Wilkins. ISBN 0-7817-8215-5.
[11] Lévêque N, Huguet P, Norder H, Chomel JJ (April 2010). "[Enteroviruses responsible for acute hemorrhagic conjunctivitis]" (in French).
Med Mal Infect 40 (4): 212–8. doi:10.1016/j.medmal.2009.09.006. PMID 19836177.
[12] Rose P (August 2007). "Management strategies for acute infective conjunctivitis in primary care: a systematic review". Expert Opin
Pharmacother 8 (12): 1903–21. doi:10.1517/14656566.8.12.1903. PMID 17696792.
[13] "Evidence-based treatment of acute infective conjunctivitis: Breaking the cycle of antibiotic prescribing -- Visscher et al. 55 (11): 1071 -Canadian Family Physician" (http:/ / www. cfp. ca/ cgi/ content/ abstract/ 55/ 11/ 1071?etoc). .
[14] Sheikh A, Hurwitz B (2006). "Antibiotics versus placebo for acute bacterial conjunctivitis". Cochrane Database Syst Rev (2): CD001211.
doi:10.1002/14651858.CD001211.pub2. PMID 16625540.
[15] Hazel A Everitt, Paul S Little, Peter W F Smith (July 16 2006). "A randomised controlled trial of management strategies for acute infective
conjunctivitis in general practice" (http:/ / bmj. bmjjournals. com/ cgi/ content/ short/ bmj. 38891. 551088. 7Cv1?etoc). BMJ 333 (7563): 321.
doi:10.1136/bmj.38891.551088.7C. PMID 16847013. PMC 1539078. .
[16] "Conjunctivitis, Viral: Treatment & Medication" (http:/ / emedicine. medscape. com/ article/ 1191370-treatment). Retrieved 2009-12-17.
External links
• Facts About the Cornea and Corneal Disease (http://www.nei.nih.gov/health/cornealdisease/index.asp) The
National Eye Institute (NEI).
• Conjunctivitis (http://www.mayoclinic.com/health/pink-eye/DS00258) Mayo Clinic website.
• Comparison of symptoms of Conjunctivitis versus Orbital Cellulitis (http://www.eyeinfectionphotos.com/)
Medical notes and photographs of a real patient experience.
• Differentiating Viral and Bacterial conjunctivitis (http://www.medscape.com/viewarticle/522242) Medscape
Article.
• Bacterial conjunctivitis: A review for internists (http://www.ccjm.org/content/75/7/507.full.pdf) AHMAD
B. TARABISHY and BENNIE H. JENG. Cleveland Clinic Journal of Medicine July 2008 vol. 75 7 507-512.
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Hepatitis A Source: http://en.wikipedia.org/w/index.php?oldid=400248936 Contributors: 7, A. B., AaronSw, Aka042, Akerans, Alansohn, Alex.tan, Aliewishus, AndreniW, Arcadian,
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Jr., G716, Gadfium, Gail, Gak, Gholam, Giftlite, Glane23, GrahamColm, GregorB, Gurch, Hankwang, Harangutan, Hdt83, Heathhunnicutt, HepCMO, Hepatitis Australia, Himynameisjaime,
Hluup, Hu12, Ioeth, Irangeologist, J.delanoy, JForget, JaGa, Jainparisorboulder, Jake Wartenberg, Jalohones, Jfdwolff, Jivee Blau, Jkpjkp, Jmh649, Jonathan Drain, Josh Grosse, Kbh3rd,
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477 anonymous edits
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137
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QueenCake, Quihn, Qxz, R.chung3886, RDBrown, RHaworth, Radon210, Rags11749, Ransack, Rbgroomes, Realm of Shadows, Reasearch290188, Renato Caniatti, Retahmapsog, Rhys, Rich
Farmbrough, Richard Keatinge, Rjwilmsi, Roudoudou, Rouenpucelle, RoyBoy, Russellfsm, Ryanenglish, SFHndymn, SHAHINOVE, SMcCandlish, Salvadorjo, Samir, Sanders muc, Saopaulo1,
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Should Not Be, The Transhumanist, Thingg, Tide rolls, Timberframe, Tmstjohn, Tpbradbury, Treesinbelize, Tristanb, Trsed, Trusilver, Truthstands, Ur Wurst Enema, User27091, Uthbrian,
VELVET, Variable, Veinor, Versus22, Vint, Vsmith, Vze4p6c2, WGozz, WLU, Wallyworld14, Warrhedd, Watplay, Wavelength, Wayne Slam, Wcd480, Wfaldas, Wfirst, Wha.CG.RJ, Wikipelli,
Wikiric, Wilke, Will Blake, Willking1979, Winston365, Wouterstomp, Wrinkles, Wtmitchell, Yamamoto Ichiro, Yefi, Ynahmias, ZooFari, Zzuuzz, Zzyzx11, Саша Стефановић, 868 anonymous
edits
Hepatitis D Source: http://en.wikipedia.org/w/index.php?oldid=400389613 Contributors: Adnan saqib, AlphaEta, Appraiser, Arcadian, ArmadilloFromHell, Azhyd, Capricorn42, Cholga,
Chrumps, ChyranandChloe, Cromwellcty, D.c.camero, Droll, Eleassar777, Eletitia, EncycloPetey, Evenios, G716, Grendelkhan, Hadal, Hepatitis Australia, Hu12, Jfdwolff, Joelmills,
JonEastham, Josh Grosse, LittleT889, MarcoTolo, Mattbr, Maxxicum, Momet, Mushin, Nick, Noah Salzman, OwenBlacker, Philippe Le Mercier, Qrc2006, Renato Caniatti,
ReturnOfLobsterJesus, Rich Farmbrough, Richard Arthur Norton (1958- ), Robodoc.at, Rsabbatini, SMcCandlish, Samir, Samwisefoxburr, Sgamer1770, Shizhao, Slacka123, Smith609, Someone
else, Template namespace initialisation script, TimVickers, Tom.k, Truth is relative, understanding is limited, Viralzone, WhatamIdoing, Whosasking, William Avery, WriterHound, Zoe, आशीष
भटनागर, 58 anonymous edits
Hepatitis E Source: http://en.wikipedia.org/w/index.php?oldid=399544569 Contributors: Anomo, Arcadian, Azhyd, Beta34, Bonus Onus, Bpickett, Brossow, Chrumps, Claus Diff, D.c.camero,
Darth Panda, DerHexer, Doseiai2, DrMicro, Eesnyder24060, Eleassar777, Frankie1969, Gabbe, Gaff, Gak, Goblin, Grendelkhan, HalJor, Hepatitis Australia, Hu12, Huangcjz, J.delanoy,
Jfdwolff, Joana, Josh Grosse, JurrienB, Kell, Leolaursen, MarcoTolo, Markk01, Matt Gies, Metodicar, Nannerpuss09, Orlandoturner, OwenBlacker, Patricbrc, Phlegm Rooster, Qrc2006,
Raul654, Rich Farmbrough, SHAHINOVE, SMcCandlish, Samir, Saritamackita, Scray, Seasurfer, Shizhao, Slacka123, Snowmanradio, Theda, Trevor Andersen, WhatamIdoing, WriterHound,
YUL89YYZ, आशीष भटनागर, 75 anonymous edits
Hepatitis F virus Source: http://en.wikipedia.org/w/index.php?oldid=372186936 Contributors: D.c.camero, DocWatson42, Eleassar, Jfdwolff, MarcoTolo, Mushin, Pgvolff, Rich Farmbrough,
Richard Arthur Norton (1958- ), SMcCandlish, Scray, Sodaplayer, WriterHound, 3 anonymous edits
Tuberculosis Source: http://en.wikipedia.org/w/index.php?oldid=400131968 Contributors: -- April, .:Ajvol:., 1297, 1988ja, 200.191.188.xxx, 203.51.8.xxx, 4a42, 5 albert square, 7, 9014user,
A. B., A3RO, A8UDI, AVand, Aao2107, Aarchiba, Aaron Schulz, Abanima, AbsolutDan, Acroterion, Adam Bishop, Adamrossi, AdjustShift, Adoniscik, Adrian, AdultSwim, AgentPeppermint,
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Altenmann, Alucard (Dr.), Aminullah, Amityadav8, Ancient Apparition, Andbir, Andre Engels, Andrew Dalby, Andrewlp1991, Andrij Kursetsky, Andris, Andycjp, Andyjsmith, Angel caboodle,
Angela, Angr, Antandrus, Anthonyhcole, Antiuser, Apayne, Apers0n, Apollo the Archer, Arcadian, Arch dude, ArchStanton69, Arcyqwerty, Ardonik, Arteyu, Arundhati bakshi, Ashenai,
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