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Meta-Analysis
. 2009 Jul 8;2009(3):CD007342.
doi: 10.1002/14651858.CD007342.pub2.

Antibiotic prophylaxis for leptospirosis

Affiliations
Meta-Analysis

Antibiotic prophylaxis for leptospirosis

David M Brett-Major et al. Cochrane Database Syst Rev. .

Abstract

Background: Leptospira infection is a global zoonosis with significant health impact for agricultural workers and those persons whose work or recreation takes them into endemic areas.

Objectives: This systematic review assessed the current literature for evidence for or against use of antibiotic prophylaxis against Leptospira infection (leptospirosis).

Search strategy: The authors searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and SCI-Expanded as well as relevant professional society meeting abstracts until January 2009.

Selection criteria: Prospective, randomised clinical trials studying antibiotic prophylaxis against leptospirosis were selected.

Data collection and analysis: Data collection abstracted participant demographics and outcomes as well as features of trial design and quality. Trial results were analysed to independently determine outcomes, while multiple trial data was pooled when relevant.

Main results: Three trials were included, all of which evaluated doxycyline use. Trial quality suffered from a lack of intention-to-treat analysis and variability across trials in methodology and targeted outcomes. One trial assessed post-exposure prophylaxis in an indigenous population after a flood without apparent efficacy in reduction of clinical or laboratory identified Leptospira infection. Two trials assessed pre-exposure prophylaxis, one among deployed soldiers and another in an indigenous population. Despite an odds ratio of 0.05 (95% CI 0.01 to 0.36) for laboratory-identified infection among deployed soldiers on doxycyline in one of these two trials, pooled data showed no statistically significant reduction in Leptospira infection among participants (Odds ratio 0.28 (95% CI 0.01 to 7.48). Minor adverse events (predominantly nausea and vomiting) were more common among those on doxycycline with an odds ratio of 11 (95% CI 2.1 to 60).

Authors' conclusions: Regular use of weekly oral doxycycline 200 mg increases the odds for nausea and vomiting with unclear benefit in reducing Leptospira seroconversion or clinical consequences of infection.

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Conflict of interest statement

None known.

Figures

1
1
Search results by database. CHBG‐ Cochrane Hepato‐Biliary Group.
2
2
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
3
3
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
4
4
Forest plot of comparison: 1 Pre‐Exposure Prophylaxis with Doxycycline, outcome: 1.1 Laboratory Identified Infection.
5
5
Forest plot of comparison: 1 Pre‐Exposure Prophylaxis with Doxycycline, outcome: 1.2 Adverse Events, Minor.
1.1
1.1. Analysis
Comparison 1 Pre‐exposure prophylaxis with doxycycline, Outcome 1 Laboratory identified infection.
1.2
1.2. Analysis
Comparison 1 Pre‐exposure prophylaxis with doxycycline, Outcome 2 Adverse events, minor.
1.3
1.3. Analysis
Comparison 1 Pre‐exposure prophylaxis with doxycycline, Outcome 3 Clinical infection, laboratory confirmed.
1.4
1.4. Analysis
Comparison 1 Pre‐exposure prophylaxis with doxycycline, Outcome 4 Death.
1.5
1.5. Analysis
Comparison 1 Pre‐exposure prophylaxis with doxycycline, Outcome 5 Laboratory identified infection, baseline IgM titer zero.
1.6
1.6. Analysis
Comparison 1 Pre‐exposure prophylaxis with doxycycline, Outcome 6 Laboratory identified infection, baseline IgM titer non‐zero.
2.1
2.1. Analysis
Comparison 2 Post‐exposure prophylaxis with doxycycline, Outcome 1 Laboratory identified infection.
2.2
2.2. Analysis
Comparison 2 Post‐exposure prophylaxis with doxycycline, Outcome 2 Clinical infection, laboratory confirmed.
2.3
2.3. Analysis
Comparison 2 Post‐exposure prophylaxis with doxycycline, Outcome 3 Clinical infection, laboratory confirmed when IgM+ at baseline removed.

Update of

  • doi: 10.1002/14651858.CD007342

References

References to studies included in this review

Gonsalez 1998 {published data only (unpublished sought but not used)}
    1. Gonsalez CR, Casseb J, Monteiro FG, Paula‐Neto JB, Fernandez RB, Silva MV, et al. Use of doxycycline for leptospirosis after high‐risk exposure in São Paulo, Brazil. Revista do Instituto de Medicina Tropical de São Paulo 1988;40(1):59‐61. - PubMed
Sehgal 2000 {published data only (unpublished sought but not used)}
    1. Sehgal SC, Sugunan AP, Murhekar MV, Sharma S, Vijayachari P. Randomized controlled trial of doxycycline prophylaxis against leptospirosis in an endemic area. International Journal of Antimicrobial Agents 2000;13(4):249‐55. - PubMed
Takafuji 1984 {published data only (unpublished sought but not used)}
    1. Takafuji ET, Kirkpatrick JW, Miller RN, Karwacki JJ, Kelley PW, Gray MR, et al. An efficacy trial of doxycycline chemoprophylaxis against leptospirosis. New England Journal of Medicine 1984;310(8):497‐500. - PubMed

Additional references

Bharti 2003
    1. Bharti AR, Nally JE, Ricaldi JN, Matthias MA, Diaz MM, Lovett MA, et al. Leptospirosis: a zoonotic disease of global importance. The Lancet Infectious Diseases 2003;3(12):757‐71. - PubMed
Dziuban 2006
    1. Dziuban EJ, Liang JL, Craun GF, Hill V, Yu PA, Painter J, et al. Surveillance for waterborne disease and outbreaks associated with recreational water ‐ United States, 2003‐2004. Morbidity Mortality Weekly Report Surveillance Summaries 2006;55(12):1‐30. - PubMed
Egger 1997
    1. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. British Medical Journal (Clinical Research Ed.) 1997;315:629‐34. - PMC - PubMed
Gaynor 2007
    1. Gaynor K, Katz AR, Park SY, Nakata M, Clark TA, Effler PV. Leptospirosis on Oahu: an outbreak associated with flooding of a university campus. The American Journal of Tropical Medicine and Hygiene 2007;76(5):882‐5. - PubMed
Gluud 2008
    1. Gluud C, Nikolova D, Klingenberg SL, Whitfield K, Alexakis N, Als‐Nielsen B, et al. Cochrane Hepato‐Biliary Group. About The Cochrane Collaboration (Cochrane Review Groups (CRGs)). 2008, Issue 4. Art. No.: LIVER.
Guidugli 2000
    1. Guidugli DF, Castro AA, Atallah AN. Antibiotics for preventing leptospirosis. Cochrane Database of Systematic Reviews 2000, Issue 4. [DOI: 10.1002/14651858.CD001305] - DOI - PubMed
Hadad 2006
    1. Hadad E, Pirogovsky A, Bartal C, Gilad J, Barnea A, Yitzhaki S, et al. An outbreak of leptospirosis among Israeli troops near the Jordan River. The American Journal of Tropical Medicine and Hygiene 2006;74(1):127‐31. - PubMed
Higgins 2008
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0 [updated February 2008]. The Cochrane Colloboration, 2008. Available from www.cochrane‐handbook.org.
Hollis 1999
    1. Hollis S, Campbell F. What is meant by intention to treat analysis? Survey of published randomised controlled trials. BMJ (Clinical Research Ed.) 1999;319:670‐4. - PMC - PubMed
ICH‐E3 1995
    1. ICH harmonized tripartite guideline. Guideline on structure and content of clinical study reports (E3). Geneva: International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. http://www.ich.org/LOB/media/MEDIA479.pdf (accessed 19 May 2008) 1995.
ICH‐GCP 1996
    1. ICH harmonised tripartite guideline. Guideline for good clinical practice E6 (R1). Geneva: International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. www.ich.org/LOB/media/MEDIA482.pdf (accessed 15 May 2008) 1996.
Kjaergard 2001
    1. Kjaergard LL, Villumsen J, Gluud C. Reported methodologic quality and discrepancies between large and small randomized trials in meta‐analyses. Annals of Internal Medicine 2001;135:982‐9. - PubMed
Moher 1998
    1. Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, et al. Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta‐analyses?. Lancet 1998;352:609‐13. - PubMed
Narita 2005
    1. Narita M, Fujitani S, Haake DA, Paterson DL. Leptospirosis after recreational exposure to water in the Yaeyama islands, Japan. The American Journal of Tropical Medicine and Hygiene 2005;73(4):652‐6. - PMC - PubMed
Niwetpathomwat 2005
    1. Niwetpathomwat A, Niwatayakul K, Doungchawee G. Surveillance of leptospirosis after flooding at Loei Province, Thailand by year 2002. The Southeast Asian Journal of Tropical Medicine and Public Health 2005;36 (Suppl 4):202‐5. - PubMed
Pappachan 2004
    1. Pappachan MJ, Sheela M, Aravindan KP. Relation of rainfall pattern and epidemic leptospirosis in the Indian state of Kerala. Journal of Epidemiology and Community Health 2004;58(12):1054. - PMC - PubMed
Pappas 2007
    1. Pappas G, Papadimitriou P, Siozopoulo V, Christou L, Akritidis N. The globalization of leptospirosis: worldwide incidence trends. International Journal of Infectious Diseases 2008;12(4):351‐7. [MEDLINE: ] - PubMed
Ramakrishnan 2003
    1. Ramakrishnan R, Patel MS, Gupte MD, Manickam P, Venkataraghavan S. An institutional outbreak of leptospirosis in Chennai, South India. The Journal of Communicable Diseases 2003;35(1):1‐8. - PubMed
RevMan 2008 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.0. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2008.
Royle 2003
    1. Royle P, Milne R. Literature searching for randomized controlled trials used in Cochrane reviews: rapid versus exhaustive searches. International Journal of Technology Assessment in Health Care 2003;19(4):591‐603. - PubMed
Russell 2003
    1. Russell KL, Montiel Gonzalez MA, Watts DM, Lagos‐Figueroa RC, Chauca G, Ore M, et al. An outbreak of leptospirosis among Peruvian military recruits. The American Journal of Tropical Medicine and Hygiene 2003;69(1):53‐7. - PubMed
Schulz 1995
    1. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273:408‐12. - PubMed
Sejvar 2003
    1. Sejvar J, Bancroft E, Winthrop K, Bettinger J, Bajani M, Bragg S, et al. Leptospirosis in "Eco‐Challenge" athletes, Malaysian Borneo, 2000. Emerging Infectious Diseases 2003;9(6):702‐7. - PMC - PubMed
Thai 2008
    1. Thai KT, Nga TT, Phuong HL, Giao PT, Hung le Q, Binh TQ, et al. Seroepidemiology and serological follow‐up of anti‐leptospiral IgG in children in Southern Vietnam. Acta Tropica 2008;106(2):128‐31. - PubMed
Wood 2008
    1. Wood L, Egger M, Gluud LL, Schulz KF, Jüni P, Altman DG, et al. Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta‐epidemiological study. BMJ (Clinical Research Ed.) 2008;336(7644):601‐5. - PMC - PubMed

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