Vortrag C. Strahm, 8.8.12
Transcription
Vortrag C. Strahm, 8.8.12
LEPTOSPIROSE Carol Strahm Infektiologie 8.8.2012 Leptospira interrogans Historisches „Herbstfieber“ bei Reisernte im alten China und Japan 1886 A.Weil: Erstbeschreibung der Erkrankung (1907 Stimson: Spirochaeta interrogans in Nieren eines Mannes der an einem ,Gelbfieber‘ verstarb) 1915/16 Mehrere Teams (2 dt. und 1 jp.) beschreiben gleichzeitig Krankheitsbild mit Erreger 1917 Zoonose/ Berufskrankheit: Ratte wurde als Quelle entdeckt Levett, Clin Microbiol Rev, 2001 vol. 14 (2) pp. 296-326 Verbreitung/ Inzidenz Weltweite Zoonose; endemisch in (Sub)tropen 350000 - 500000 Fälle / Jahr Inzidenz (schwerere Verläufe, leichte unbekannt) 0.1 – 1 /100,000 pro Jahr in gemässigten Zonen (CH: 0.05) 10 – 100 /100,000 pro Jahr in (Sub)tropen >100 pro 100,000 während outbreaks keine genaue Zahlen (oligosymptomatisch, kein effektives Bharti, Lancet Infect Dis 2003; 3: 757–71 Überwachungssystem) Hartskeerl, CMI 2011; 17(4):494–501 Leptospirose-Erkrankungen in der Schweiz, Meldungen der Laboratorien und Ärzte 1988–1999. OFSP Epidemiologie/ Pathophysiologie meist verbreitete Zoonose weltweit Quelle: meist asymptomatische Träger bei Nagern (Mäuse, Ratten, Fledermäuse, Mungos, Beutelratten, Eichhörnchen) Auch Nutztiere/ Haustiere: Rinder, Schafe, Ziegen, Schweine, Hunde Leptospiren können lebenslang im proximalen Tubulus von infizierten Tieren persistieren und werden mit dem Urin ausgeschieden Ansteckung über Urin, kontaminiertes Wasser und Böden Levett, Clin Microbiol Rev, 2001 vol. 14 (2) pp. 296-326 Adler, Vet Microbiol, 2010 vol. 140 (3-4) pp. 287-96 mic Development by Leptospirosis he world. th water, food or r diseases. ng renal ase. atterns Investing in reliable global huma Epidemiologie burden estimates To coordinate and direct global res leptospirosis the World Health O Leptospirosis Burden Epidemio maintenance host a group of leading experts with a br ing with multiple international acto accidental host The LERG is assigned with the foll years: reviewing and appraising epid commissioned reviews and stu developing epidemiological to estimating and expressing dis measures of population healt WHO life years (DALY)) identifying technical gaps for re Leptospiren-DNA (PCR) in Nieren von Mäusen (CH) in einer Schweizer Innenstadt Arvicola terrestris (Wühlmaus) Leptospira PCR+ 13.3% (8/60) Apodemus sylvaticus (Waldmaus) Leptospira PCR+ 11.7% (7/60) Clethrionomys glareolus (Rötelmaus) Leptospira PCR+ 10.0% (5/50) Crocidura spp, Sorex spp (Spitzmäuse) Leptospira PCR+ 20.0% (4/20) Adler H et al. Epidemiol Infect 2002;128:107-109 Epidemiologie Gemässigte Zonen / Industrialisierte Welt Berufskrankheit Kanalarbeiter, Bauern, Fischer, Metzger, Tierärzte, Militär, Mineure... Protektive Massnahmen hat zu einer Verminderung der Inzidenz geführt Homeless schlechte Hygiene ,Outdooraktivitäten‘ mit Wasserkontakt Entwicklungsländer / (Sub)tropen Beruflich (zB Reisfelder) Tägliches Leben vor allem während der Regenzeit, Slums Überschwemmungen / Outbreaks Levett, Clin Microbiol Rev, 2001 vol. 14 (2) pp. 296-326 Adler, Vet Microbiol, 2010 vol. 140 (3-4) pp. 287-96 1. Berufskrankheit obiology (2004), 53, 1259–1262 Percutaneous exposure resulting in laboratoryacquired leptospirosis – a case report M A J O R A R T I C L E rt 004 DOI 10.1099/jmm.0.45735-0 A. P. Sugunan, K. Natarajaseenivasan, P. Vijayachari and S. C. Sehgal WHO Collaborative Centre for Diagnosis, Research, Reference and Training in Leptospirosis, Regional Medical Research Centre, Indian Council of Medical Research, Post Bag No. 13, Port Blair 744 101, Andaman & Nicobar Islands, India Resurgence of Field Fever in a Temperate Country: An Epidemic of Leptospirosis among Seasonal Strawberry Harvesters in Germany in 2007 A screw-capped glass tube containing a Leptospira culture accidentally broke and the laboratory 1,5 2 1 6 worker who wasvan handling the tube sustained a cut on his hand. TheSarbu, wound was flooded with the Sarika Desai, Ulrich Treeck,4 Michael Lierz, Werner Espelage, Lavinia Zota,6 Anca 7 8 3 3 Michal Czerwinski, Malgorzata Maria347 Avdicová, Jochen to Reetz, Enno Luge, Beatrizrecovered Guerra,3 culture. The3 culture wasSadkowska-Todys, that 1of strain 7MG belonging serovar Australis from a Zoonoses and Public Health Karsten Nöckler, and Andreas Jansen patient, and it had undergone 52 passages in Ellinghausen McCullough Johnson Harris medium. Robert Koch Institute, Department for Infectious Disease Epidemiology, Free University, Veterinary Faculty, and Federal Institute for Risk O R I G Ilaboratory N A LBerlin, A R T Iand C L Eworker Assessment, State Institute of Health and Labor of North Rhine-Westphalia, Germany; European and Programme for The developed a headache 21 daysMünster, after the accident became febrile the next Intervention Epidemiology Training, European Centre for Disease Prevention and Control, Stockholm, Sweden; National Centre for Prevention and Leptospirosis in a SmallforAnimal Veterinarian: Reminder to and Regional Institute day.ofHe was hospitalized 5 days andInstitute was oftreated initially and later with Control Communicable Diseases, Bucharest, Romania; National Public Health, Warsaw,with Poland;doxycycline of Public Follow Infection Control Procedures Health, BanskáStandardized Bystrica, Slovakia ciprofloxacin. A blood sample collected on the second day of illness, after starting doxycycline R. Baer , W. Turnberg , D. Yu and R. Wohrle therapy, yielded leptospires andisthe isolate, HZ 651,ofwas identified as outbreaks serovar Australis. Background. Although leptospirosis aof Health, reemerging zoonosis global importance, related to ag-Monoclonal Communicable Disease Epidemiology, Washington State Department Shoreline, WA, USA Baer, Zoonoses Public Health. 2010 1;57(4):281–4 Thurston County Public Health and Social Services Department, Olympia, WA, USA ricultural exposures areand primarily situatedamplified in tropicalpolymorphic countries. In July 2007,fingerprinting a suspected leptospirosis antibody patterns randomly DNA patternsoutbreak of the isolate and Desai, CID 2009 15;48(6):691–7 Zoonotic and Vector-borne Disease Program, Washington State Department of Health, Olympia, WA, USA was recognized among strawberry harvesters from Eastern Europe who were working in Germany. An investigation Sugunan, J Med Microbiol. 2004 1;53:1259–62 strain MGto347 were thusand indicating that for HZinfection. 651 and MG 347 were clonal. was initiated identify the identical, outbreak source the risk factors Impacts 1 2 4 3 5 6 7 1 1 2 8 3 1 2 3 Methods. We conducted a retrospective cohort study with use of a questionnaire administered to harvesters A small animal veterinarian developed leptospirosis after exposure to pet by health rat urine.authorities in Romania, Slovakia, and Poland. Collected serum samples were tested by microscopic • Leptospirosis test is an occupational risk for both largeM andenzyme-linked small animal agglutination and immunoglobulin immunosorbent assay. A case patient was defined as a • veterinarians. Brockmann et al. BMC Infectious Diseases 2010, 10:91 http://www.biomedcentral.com/1471-2334/10/91 2. ,Outdooarktivitäten‘ RESEARCH ARTICLE Open Acce Outbreak of leptospirosis among triathlon participants in Germany, 2006 Stefan Brockmann1, Isolde Piechotowski1, Oswinde Bock-Hensley2, Christian Winter1,3, Rainer Oehme1, Stefan Zimmermann4, Katrin Hartelt1, Enno Luge5, Karsten Nöckler5, Thomas Schneider6, Klaus Stark7, Leitthema Andreas Jansen7* J. P. Sperhake · F. Schulz Institut für Rechtsmedizin, Universitätsklinikum, Hamburg-Eppendorf Abstract Background: In August 2006, a case of leptospirosis occurred in an athlete after a triathlon held around Heidelberg and in the Neckar river. In order to study a possible outbreak and to determine risk factors for infecti an epidemiological investigation was performed. Tod eines Wassersportlers durch Leptospirose Methods: Participants of the triathlon were contacted by e-mail and were asked to fill out a standardized questionnaire. In addition, they were asked to supply a serum sample for laboratory diagnosis of leptospirosis. A Rechtsmedizin 2006 16:156–160 confirmed case patient was defined as a clinical case (i.e. fever and at least Sperhake, one additional symptom suggestive Brockmann BMC Infect Dis. 2010 1;10:91 leptospirosis) with at least two of the following tests positive: ELISA IgM, latex agglutination testing, or microscop agglutination testing. Rainfall and temperature records were obtained. Nochmals Olympische Spiele... Oktober 2010 The Telegraph Forbes QJM 2012 Jul 27 3. Environmental drivers of leptospirosis Although leptospirosis is common and widespread, there remain significant gaps in our understanding of its transmission dynamics and of the trigger factors for disease outbreaks. However, epidemiological studies have identified various environmental risk factors for infection or outbreaks that differ between ecological settings. A number of these factors are likely to be influenced by climate change and urbanisation and will be discussed below. environmental forces, including sociodemographic factors, climate and land use. 3.1. Rainfall and flooding Heavy rainfall and flooding increase the risk of leptospirosis by bringing bacteria and their animal hosts into closer contact with humans. Numerous outbreaks of leptospirosis have been reported following extreme weather events around the world, in geographically diverse areas including India,10,11 Laos,12 Indonesia,13 Italy,14 Brazil,15 3. Endemiegebiete Table 1 Examples of leptospirosis outbreaks associated with heavy rainfall and flooding Country/region Year Flooding event Mumbai, India10 2005 Kerala, India11 Orissa, India22 2002 1999 Laos12 Indonesia13 Italy14 Guyana16 Nicaragua17 2006 2002 2002 2008 1995 Puerto Rico18 1996 New Caledonia20 2008 944 mm of rain in 24 h resulted in an eight-fold rise in the number of cases compared with the previous 4 years Peaks in leptospirosis incidence seen 7–10 days after peaks of heavy rainfall Rodents and Leptospirosis in Hyper-Endemic Areas 19.2% of study subjects in flooded villages after a cyclone were found to have serological evidence of symptomatic leptospiral infection Flooding in home property associated with seropositivity for leptospirosis (odds ratio 2.12) Outbreak followed massive flooding in Jakarta in January 2002 Devastating flooding in suburban area resulted in 6.8% seroconversion rate for leptospirosis Epidemic followed severe flooding, with 30% of Guyana’s inhabitants displaced from their homes Epidemic of leptospirosis followed severe rainfall and flooding in 2005. Over 5000 mm of rain compared with annual average of 1300 mm Leptospirosis Leptospirosis diagnosed in 6% of non-dengue febrile illnesses pre-hurricane versus 24% of non-dengue febrile illnesses post-hurricane High rainfall and flooding associated with La Niña in early 2008. Epidemic of leptospirosis in 135 people. Incidence of 500/100 000 population in Bourail region Review Perez PLoS Negl Trop Dis. 2011;5(10):e1361 Lau, Trans R Soc Trop Med Hyg. 2010;104(10):631–8 Figure 1. Hot spots of leptospirosis and identification of the study site and meteorological data collection point. (Map produced using PopGis, as described in the Methods section and demographic data from the Institut de la Statistique et des Études Économiques, http://www.isee. nc/.). Leptospirosis and Weil’s disease in the UK Klinik prominent features at outset are, headache, fever and myalgia.38–41 A study of leptospirosis in eight developing countries commonly visited by British tourists, found result in cardiovascular collapse and pulmonary haemorrhagic pneumonitis where the mortality rate can reach 50%.3,44,45 In the UK, the mortality for Weil’s disease was in 9 Downloaded from http://qjmed.oxfordjournals.org/ at Universitaet Z Forbes QJM 2012 Jul 27 Figure 6. Clinical features of leptospirosis and Weil’s disease. The number of cases in the UK with asymptomatic infection is unknown, as is the number who suffer only brief, uncomplicated febrile illness. Other symptoms are shown in order of incidence (not to scale) depicting the small proportion of infections that result in severe (Weil’s) disease and death in the UK. (1) Mild disease ‘Phase 1’: this may be self-limiting or may progress to severe disease after a period of resolution of symptoms and (2) severe disease ‘Phase 2’. 353 patients. Persons without formal employment (e.g., unemployed, retired, student, homemaker) accounted for 102 (31%) of 328 cases. Farmers or ranchers (including sugarcane workers) accounted for 92 cases (28%). Blue-collar workers (e.g., construction workers, day laborers, carpenters) accounted for 51 cases (16%). Twelve cases (4%) were in active-duty military personnel. Information allowing for an exposure “classification” was possible for 335 (95%) of 353 cases. Occupationally related exposures were reported for 137 (41%) of 335 cases (e.g., farming, ranching, aquaculture, abattoir, veterinarian); 143 (43%) of 335 cases were exposed through recreational activities, including freshwater swimming, hiking, camping, and hunting. Among confirmed cases, 81 (23%) of 353 were diagnosed by culture isolates from the following clinical specimens: blood samples, for 66 cases; urine samples, for 6 cases; CSF specimens, for 2 cases; blood and urine samples, for 1 case; blood and CSF samples, for 1 case; and an unspecified source, for 5 cases. The 81 culture-confirmed cases included 48 with diagnostic MAT results and 33 diagnosed using culture alone. The diagnoses were made using serologic testing without culture confirmation for 270 cases, and 2 cases demonstrated antibodies to Leptospira species in postmortem tissue specimens by means of a direct fluorescent antibody test. Among confirmed cases, the most frequently reported symptoms were fever, myalgia, and headache. Pertinent laboratory results included evidence of renal abnormalities, hepatic abnormalities, or both in 49%–73% of patients (table 1). Moresevere disease manifestations associated Katz, Clin Infect Dis, 2001 vol. 33were (11) pp. 1834-41 with infection by the Icterohemorrhagiae serogroup (table 2). Among 353 confirmed cases during this 25-year interval, 5 patients died (case- Klinik Hawaii 1974-1998, 350 Fälle 90% selbstlimitierende milde febrile Krankheit! Table 1. Clinical findings for 353 confirmed cases of leptospirosis, Hawaii, 1974–1998. No. of patients with data available No. (%) of patients affected Fever 346 343 (99) Myalgia 333 304 (91) Headache 329 292 (89) Chills 321 280 (87) Anorexia 303 248 (82) Nausea 306 235 (77) Vomiting 300 220 (73) Arthralgia 285 168 (59) Diarrhea 290 154 (53) Abdominal pain 283 144 (51) Backache 275 139 (51) Jaundice 286 111 (39) Conjunctival suffusion 265 74 (28) Nuchal rigidity 268 73 (27) Oliguria or anuria 270 71 (26) Hepatomegaly 234 38 (16) Pneumonia 175 29 (17) Rash 253 21 (8) Splenomegaly 218 9 (4) Elevated blood urea nitrogen (120 mg/dL) 241 118 (49) Elevated creatinine (11.5 mg/dL) 142 77 (54) Hematuria 239 171 (72) Proteinuria 229 124 (54) Sign, symptom, and result (definition) Selected sign or symptom Laboratory results Renal CSF samples, for 1 case; and an unspecified source, for 5 cases. The 81 culture-confirmed cases included 48 with diagnostic MAT results and 33 diagnosed using culture alone. The diagnoses were made using serologic testing without culture confirmation for 270 cases, and 2 cases demonstrated antibodies to Leptospira species in postmortem tissue specimens by means of a direct fluorescent antibody test. Among confirmed cases, the most frequently reported symptoms were fever, myalgia, and headache. Pertinent laboratory results included evidence of renal abnormalities, hepatic abnormalities, or both in 49%–73% of patients (table 1). Moresevere disease manifestations were associated with infection by the Icterohemorrhagiae serogroup (table 2). Among 353 confirmed cases during this 25-year interval, 5 patients died (casefatality rate, 1.4%). Increasing age was associated with an increase in leptospirosis related mortality (x2 for linear trend, 5.5; P p .02). Initial clinical impressions were recorded for 312 (88%) of 353 patients. The most common initial diagnoses were leptospirosis (193 cases [62%]), influenza (20 cases [6%]), viral syndrome (19 cases [6%]), hepatitis (19 cases [6%]), fever of unknown etiology (12 cases [4%]), gastroenteritis (10 cases [3%]), and meningitis (9 cases [3%]). An incubation period was estimated for 150 patients for whom exposure and onset dates were recorded. The incubation period ranged in duration from 1 to 21 days (median, 8 days). Information on the duration of illness was obtained from 245 patients and ranged from 2 to 84 days (median, 14 days). A total of 239 (68%) of 349 patients were hospitalized. Information regarding antibiotic therapy was obtained from Clin Infect Dis, 2001 33 (11) pp. 1834-41 327 Katz, of 353 patients. Twovol. hundred ninety-four (90%) of the 327 patients received antibiotics. Untreated patients had a minimum 7-day duration of illness, whereas ∼25% of those treated Labor - sehr hohes Bilirubin bei nur leicht erhöhter ALAT, erhöhtes Kreatinin (DD virale Hepatitis) - Thrombopenie - Hypokaliämie Backache 275 139 (51) Jaundice 286 111 (39) Conjunctival suffusion 265 74 (28) Nuchal rigidity 268 73 (27) Oliguria or anuria 270 71 (26) Hepatomegaly 234 38 (16) Pneumonia 175 29 (17) Rash 253 21 (8) Splenomegaly 218 9 (4) Elevated blood urea nitrogen (120 mg/dL) 241 118 (49) Elevated creatinine (11.5 mg/dL) 142 77 (54) Hematuria 239 171 (72) Proteinuria 229 124 (54) Elevated alanine aminotransferase level (serum glutamic-pyruvic transaminase; 140 U/L) 172 126 (73) Elevated total bilirubin level (11.0 mg/dL) 178 128 (70) Elevated WBC count (110,000 cells/mm3) 238 92 (39) Decreased WBC count (!4300 cells/mm3) 230 17 (7) Thrombocytopenia (!140,000 cells/mm3) 239 139 (58) Decreased hematocrit (!34%) 236 76 (32) Laboratory results Renal Hepatic Hematologic with antibiotics recovered within 7 days. However, the observed difference in illness duration for people treated with or without antibiotics was not statistically significant (Wilcoxon-MannWhitney test, P p .4). For 210 (71%) of 294 patients who received antibiotics, we had information on date of symptom onset and date of initiation of antibiotic therapy. Of 210 patients who received antibiotics, 205 (98%) had initiated therapy within 9 days of onset Klinik Aseptische Meningitis Uveitis 105 Ikterische Leptospirose 5-10% Temperature (° F) 104 103 102 101 100 99 98 97 0 10 20 30 Day of illness 40 M. Weil Akutes Nierenversagen 16-40% Hämorrhagien Myocarditis 10%? Pulmonale Hämorrhagie fast immer, oft subklinisch 50 specially an body cratches mbranes irosis is reational ies such ded rice ies with of cases so been that the /100,000 00 cases/ [14, 15]. osure to pulation n in the predomiferences y do not me popce, men nfection problem nvolving Biphasischer Verlauf Lung (2011) 189:1–9 Table 1 Clinical features of leptospirosis Unspecific febrile Anicteric. Headache, chills, abdominal pain, and disease conjunctival suffusion. Myalgias are remarkable. Normal CSF. May be self-limited or progress to the forms described below. Easily confounded with dengue fever, yellow fever, malaria, and other acute febrile diseases. Meningitis 1 ‘‘leptospiremic’’ phase lasts 4–9 days May follow the anterior form or appear unaccompanied. CSF pleocytosis. Benign, selflimited, and ‘‘aseptic’’ meningitis usually mistaken as viral. Weil syndrome Deep jaundice despite mild hepatic involvement. Severe renal dysfunction and usually minor hemorrhagic manifestations. Dialysis is the standard supportive therapy. High mortality rate ([10%). Severe pulmonary Hemorrhagic pneumonitis. May occur in the form absence of jaundice or as an element of Weil syndrome. Adult respiratory distress syndrome and sudden massive pulmonary hemorrhages result in high mortality ([50%) even when optimal treatment is provided. Must be distinguished from atypical pneumonias and hantavirus pulmonary syndrome. 2 ‘‘immune’’ phase 3 CSF cerebral spinal fluid high ([10% and [50%, respectively), even when optimal treatment is provided [10]. 4 Ausheilung Marchiori, Lung. 2011Feb.;189(1):1–9. Mortalität und Spätfolgen Leichte Formen haben eine gute Prognose Mortalität in hospitalisierten Fällen: 4-52% M. Weil (Trias: Ikterus, ANV, Blutungen) >10% SPHS (severe pulmonary hemorrhagic syndrome) >50% Spätfolgen (10-Jahresdaten aus aus Holland) 27% hatten Langzeitbeschwerden (Müdigkeit, Myalgien, Arthralgien, Kopfschmerzen, Tinnitus, ...) 11% schwere Beschwerden (>1 Jahr, Arztbesuche) 1.3% konnten nicht mehr arbeiten Hartskeerl, CMI 2011; 17(4):494–501 Diagnose Serologie ELISA (Se >90% / Sp 88-95%), MAT (Goldstandard) (90% / >90%) MAT microscopic agglutination test Kultur (5-50% / 100%) schwierig, Spezialkulturmedien erforderlich, 6-8 Wochen (optimal bis 4 Monate) Bebrütung nötig PCR (100% / 93%) Hartskeerl, CMI 2011; 17(4):494–501 Prävention / Therapie Berufskleidung: Handschuhe, Brillen und gutes Schuhwerk Tiere: Impfung für Vieh, Hunde und Schweine Mensch: Impfung nur in China, Kuba, Frankreich und Russland Therapie: Penicillin, Doxycyclin 5-7 Tage, cave Jarisch-Herxheimer-Reaktion Hartskeerl, CMI 2011; 17(4):494–501 Antibiotics for leptospirosis (Review) Brett-Major DM, Coldren R random-effects OR is 1.16 (95% CI 0.23 to 5.95). The heterogeneity among these four trials for the mortality outcome was moderate (I 2 = 50%). Only one trial (253 patients) reported days of hospitalisation. It compared parenteral penicillin to placebo without significant effect of therapy (8.9 versus 8.8 days; mean difference (MD) 0.10 days, 95% CI -0.83 to 1.03). The difference in days of clinical illness was reported in two of these trials (71 patients). While parenteral penicillin therapy conferred 4.7 to 5.6 days of clinical illness in contrast to 7.7 to 11.6 days in the placebo arm, the size of the estimate of effect increased but statistical significance was lost under the random-effect model (fixed-effect: MD -2.13 days, 95% CI -2.46 to -1.80; random-effects: MD -4.04, 95% CI -8.66 to 0.58). I2 for this outcome was high (81%). When duration of fever alone was assessed between antibiotics and placebo in a single trial (79 patients), no significant difference existed (6.9 versus 6.6 days; MD 0.30, 95% CI -1.26 to 1.86). Two trials with 332 patients in relatively severe and possibly late leptospirosis, resulted in trends towards increased dialysis when penicillin was used rather than placebo, but the estimate of effect was small and did not reach statistical significance (42/163 (25.8%) versus 31/169 (18.4%); OR 1.54, 95% CI 0.91 to 2.60). When one antibiotic was assessed against another antibiotic, there were no statistically significant results. For mortality in particular, these comparisons included cephalosporin versus penicillin (2 trials, 6/176 (3.4%) versus 9/175 (5.2%); fixed-effect: OR 0.65, 95% CI 0.23 to 1.87, I2 = 16%), doxycycline versus penicillin (1 trial, 2/81 (2.5%) versus 4/89 (4.5); OR 0.54, 95% CI 0.10 to 3.02), cephalosporin versus doxycycline (1 trial, 1/88 (1.1%) versus 2/81 (2.5%); OR 0.45, 95% CI 0.04 to 5.10). There were no adverse events of therapy which reached statistical significance. Antibiotische Therapie Cochrane 2012 Authors’ conclusions This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2012, Issue 2 http://www.thecochranelibrary.com Insufficient evidence is available to advocate for or against the use of antibiotics in the therapy for leptospirosis. Among survivors who were hospitalised for leptospirosis, use of antibiotics for leptospirosis may have decreased the duration of clinical illness by two to four days, though this result was not statistically significant. When electing to treat with an antibiotic, selection of penicillin, doxycycline, or cephalosporin does not seem to impact mortality nor duration of fever. The benefit of antibiotic therapy in the treatment of leptospirosis remains unclear, particularly for severe disease. Further clinical research is needed to include broader panels of therapy tested against placebo. Antibiotics for leptospirosis (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. PLAIN LANGUAGE SUMMARY Antibiotics for the treatment of leptospirosis Leptospirosis is a common disease both in the developed and developing world. It is caused by a bacteria spread by the urine of animals. Zukunft der Leptospiren... globale Erwärmung vermehrt Regen / Überschwemmungen Migration / Krisengebiete Wachstum der Weltbevölkerung und zunehmende Urbanisierung / Slums tropische Länder als beliebte Reisedestinationen Hochrisikoaktivitäten: Rafting, Höhlenbesuche, Urwaldbesuche Hartskeerl, CMI 2011; 17(4):494–501 reported to the NRC between July 1999 and February 2000, of whom 22 were excluded from further analysis because they were either not hospitalized (14 patients), had died (5), resided outside of France (2), or could not be traced (1). Of the remaining 102 case patients, correctly matched control subjects were recruited for 90 (88%). Of the 189 control subjects who were recruited, 20 were excluded because of incorrect matching of age (11 control subjects), history of hospitalization (5), or having been hospitalized 11 month before or after the case patient (4). The matched case-control analysis was performed tospirosis by univariable analysis were included in the multivariable conditional logistic regression analysis (table 1). Only 4 such variables were independently associated with a case of leptospirosis (table 1): skin lesions (aOR, 7.01; 95% CI, 2.70– 17.56), canoeing (aOR, 15.53; 95% CI, 1.64–147.00), contact with wild rodents (aOR, 4.75; 95% CI, 1.39–16.21), and a home in the countryside (aOR, 2.87; 95% CI, 1.09–7.57). No interaction between having a skin lesion and either canoeing or contact with wild rodents was reported. The etiologic fraction in the population demonstrated that nearly two-thirds (65.5%) Zurück zum Patient Table 1. Univariable analysis and conditional logistic regression of risk factors associated with leptospirosis in France, 1999–2000. Multivariate analysis Univariate analysis Risk factor Skin lesions High-risk occupation Professional risks Location of residence Countryside Near a canal Near a river Leisure activity Camping Walking in the countryside Paddling Swimming Fishing Canoeing Travel outside France Animal contact Rodents Any At home At work Farm animals NOTE. No. of samples Mantel-Haenszel OR (95% CI) 220 257 257 257 259 259 P Adjusted OR (95% CI) P 7.7 (3.8–22.6) 3.1 (1.4–7.7) 3.0 (1.5–14.7) !.001 7.0 (2.7–17.6) … … !.001 4.8 (2.4–8.8) 1.8 (1.0–3.1) 3.0 (1.6–5.6) !.001 .002 !.001 … .031 !.001 2.9 (1.1–7.6) … … .033 … … 259 259 259 259 259 259 259 5.3 2.3 3.1 2.8 5.1 21.5 3.0 (1.2–29.8) (1.2–4.5) (1.6–7.9) (1.0–7.8) (2.4–12.6) (3.1–907.5) (1.0–10.0) .010 .004 !.001 .021 !.001 !.001 .026 … … … … … 15.5 (1.6–147.0) … … … … … … .017 … 259 249 239 259 3.0 3.1 3.5 2.4 (1.6–7.6) (1.7–6.0) (1.3–11.4) (1.1–5.7) !.001 4.8 (1.4–16.2) … … … .013 … … … !.001 !.001 .011 There were 201 records included in the multiple logistic regression analysis. 752 • CID 2004:39 (1 September) • BRIEF REPORT Case control study aus Frankreich 90 Cases und 169 Kontrollgruppe Nardone, CID, 2004 vol. 39 (5) pp. 751-3 reported to the NRC between July 1999 and February 2000, of whom 22 were excluded from further analysis because they were either not hospitalized (14 patients), had died (5), resided outside of France (2), or could not be traced (1). Of the remaining 102 case patients, correctly matched control subjects were recruited for 90 (88%). Of the 189 control subjects who were recruited, 20 were excluded because of incorrect matching of age (11 control subjects), history of hospitalization (5), or having been hospitalized 11 month before or after the case patient (4). The matched case-control analysis was performed tospirosis by univariable analysis were included in the multivariable conditional logistic regression analysis (table 1). Only 4 such variables were independently associated with a case of leptospirosis (table 1): skin lesions (aOR, 7.01; 95% CI, 2.70– 17.56), canoeing (aOR, 15.53; 95% CI, 1.64–147.00), contact with wild rodents (aOR, 4.75; 95% CI, 1.39–16.21), and a home in the countryside (aOR, 2.87; 95% CI, 1.09–7.57). No interaction between having a skin lesion and either canoeing or contact with wild rodents was reported. The etiologic fraction in the population demonstrated that nearly two-thirds (65.5%) Zurück zum Patient Table 1. Univariable analysis and conditional logistic regression of risk factors associated with leptospirosis in France, 1999–2000. Multivariate analysis Univariate analysis Risk factor Skin lesions High-risk occupation Professional risks Location of residence Countryside Near a canal Near a river Leisure activity Camping Walking in the countryside Paddling Swimming Fishing Canoeing Travel outside France Animal contact Rodents Any At home At work Farm animals NOTE. No. of samples Mantel-Haenszel OR (95% CI) 220 257 257 257 259 259 P Adjusted OR (95% CI) P 7.7 (3.8–22.6) 3.1 (1.4–7.7) 3.0 (1.5–14.7) !.001 7.0 (2.7–17.6) … … !.001 4.8 (2.4–8.8) 1.8 (1.0–3.1) 3.0 (1.6–5.6) !.001 .002 !.001 … .031 !.001 2.9 (1.1–7.6) … … .033 … … 259 259 259 259 259 259 259 5.3 2.3 3.1 2.8 5.1 21.5 3.0 (1.2–29.8) (1.2–4.5) (1.6–7.9) (1.0–7.8) (2.4–12.6) (3.1–907.5) (1.0–10.0) .010 .004 !.001 .021 !.001 !.001 .026 … … … … … 15.5 (1.6–147.0) … … … … … … .017 … 259 249 239 259 3.0 3.1 3.5 2.4 (1.6–7.6) (1.7–6.0) (1.3–11.4) (1.1–5.7) !.001 4.8 (1.4–16.2) … … … .013 … … … !.001 !.001 .011 There were 201 records included in the multiple logistic regression analysis. 752 • CID 2004:39 (1 September) • BRIEF REPORT Case control study aus Frankreich 90 Cases und 169 Kontrollgruppe Nardone, CID, 2004 vol. 39 (5) pp. 751-3 reported to the NRC between July 1999 and February 2000, of whom 22 were excluded from further analysis because they were either not hospitalized (14 patients), had died (5), resided outside of France (2), or could not be traced (1). Of the remaining 102 case patients, correctly matched control subjects were recruited for 90 (88%). Of the 189 control subjects who were recruited, 20 were excluded because of incorrect matching of age (11 control subjects), history of hospitalization (5), or having been hospitalized 11 month before or after the case patient (4). The matched case-control analysis was performed tospirosis by univariable analysis were included in the multivariable conditional logistic regression analysis (table 1). Only 4 such variables were independently associated with a case of leptospirosis (table 1): skin lesions (aOR, 7.01; 95% CI, 2.70– 17.56), canoeing (aOR, 15.53; 95% CI, 1.64–147.00), contact with wild rodents (aOR, 4.75; 95% CI, 1.39–16.21), and a home in the countryside (aOR, 2.87; 95% CI, 1.09–7.57). No interaction between having a skin lesion and either canoeing or contact with wild rodents was reported. The etiologic fraction in the population demonstrated that nearly two-thirds (65.5%) Zurück zum Patient Table 1. Univariable analysis and conditional logistic regression of risk factors associated with leptospirosis in France, 1999–2000. Multivariate analysis Univariate analysis Risk factor Skin lesions High-risk occupation Professional risks Location of residence Countryside Near a canal Near a river Leisure activity Camping Walking in the countryside Paddling Swimming Fishing Canoeing Travel outside France Animal contact Rodents Any At home At work Farm animals NOTE. No. of samples Mantel-Haenszel OR (95% CI) 220 257 257 257 259 259 P Adjusted OR (95% CI) P 7.7 (3.8–22.6) 3.1 (1.4–7.7) 3.0 (1.5–14.7) !.001 7.0 (2.7–17.6) … … !.001 4.8 (2.4–8.8) 1.8 (1.0–3.1) 3.0 (1.6–5.6) !.001 .002 !.001 … .031 !.001 2.9 (1.1–7.6) … … .033 … … 259 259 259 259 259 259 259 5.3 2.3 3.1 2.8 5.1 21.5 3.0 (1.2–29.8) (1.2–4.5) (1.6–7.9) (1.0–7.8) (2.4–12.6) (3.1–907.5) (1.0–10.0) .010 .004 !.001 .021 !.001 !.001 .026 … … … … … 15.5 (1.6–147.0) … … … … … … .017 … 259 249 239 259 3.0 3.1 3.5 2.4 (1.6–7.6) (1.7–6.0) (1.3–11.4) (1.1–5.7) !.001 4.8 (1.4–16.2) … … … .013 … … … !.001 !.001 .011 There were 201 records included in the multiple logistic regression analysis. 752 • CID 2004:39 (1 September) • BRIEF REPORT Case control study aus Frankreich 90 Cases und 169 Kontrollgruppe Nardone, CID, 2004 vol. 39 (5) pp. 751-3 reported to the NRC between July 1999 and February 2000, of whom 22 were excluded from further analysis because they were either not hospitalized (14 patients), had died (5), resided outside of France (2), or could not be traced (1). Of the remaining 102 case patients, correctly matched control subjects were recruited for 90 (88%). Of the 189 control subjects who were recruited, 20 were excluded because of incorrect matching of age (11 control subjects), history of hospitalization (5), or having been hospitalized 11 month before or after the case patient (4). The matched case-control analysis was performed tospirosis by univariable analysis were included in the multivariable conditional logistic regression analysis (table 1). Only 4 such variables were independently associated with a case of leptospirosis (table 1): skin lesions (aOR, 7.01; 95% CI, 2.70– 17.56), canoeing (aOR, 15.53; 95% CI, 1.64–147.00), contact with wild rodents (aOR, 4.75; 95% CI, 1.39–16.21), and a home in the countryside (aOR, 2.87; 95% CI, 1.09–7.57). No interaction between having a skin lesion and either canoeing or contact with wild rodents was reported. The etiologic fraction in the population demonstrated that nearly two-thirds (65.5%) Zurück zum Patient Table 1. Univariable analysis and conditional logistic regression of risk factors associated with leptospirosis in France, 1999–2000. Multivariate analysis Univariate analysis Risk factor Skin lesions High-risk occupation Professional risks Location of residence Countryside Near a canal Near a river Leisure activity Camping Walking in the countryside Paddling Swimming Fishing Canoeing Travel outside France Animal contact Rodents Any At home At work Farm animals NOTE. No. of samples Mantel-Haenszel OR (95% CI) 220 257 257 257 259 259 P Adjusted OR (95% CI) P 7.7 (3.8–22.6) 3.1 (1.4–7.7) 3.0 (1.5–14.7) !.001 7.0 (2.7–17.6) … … !.001 4.8 (2.4–8.8) 1.8 (1.0–3.1) 3.0 (1.6–5.6) !.001 .002 !.001 … .031 !.001 2.9 (1.1–7.6) … … .033 … … 259 259 259 259 259 259 259 5.3 2.3 3.1 2.8 5.1 21.5 3.0 (1.2–29.8) (1.2–4.5) (1.6–7.9) (1.0–7.8) (2.4–12.6) (3.1–907.5) (1.0–10.0) .010 .004 !.001 .021 !.001 !.001 .026 … … … … … 15.5 (1.6–147.0) … … … … … … .017 … 259 249 239 259 3.0 3.1 3.5 2.4 (1.6–7.6) (1.7–6.0) (1.3–11.4) (1.1–5.7) !.001 4.8 (1.4–16.2) … … … .013 … … … !.001 !.001 .011 There were 201 records included in the multiple logistic regression analysis. 752 • CID 2004:39 (1 September) • BRIEF REPORT Case control study aus Frankreich 90 Cases und 169 Kontrollgruppe Nardone, CID, 2004 vol. 39 (5) pp. 751-3 Weltweite Zoonose, vor allem (Sub)tropen ,neglected tropical diseases‘ In der Schweiz Rarität keine typische DD bei Hepatitis u/o ANV nur bei entsprechenden Risikoexpositionen (Beruf, Tierkontakte, Wassersport, Reiserückkehrer) suchen Schwierige Diagnose; meist harmlos, potentiell tödlich LEPTOSPIROSE Take Home Messages