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Meta-Analysis
. 2024 Mar 14;3(3):CD014959.
doi: 10.1002/14651858.CD014959.pub2.

Antibiotic prophylaxis for leptospirosis

Tin Zar Win  1 , Tanaraj Perinpanathan  1   2 , Patrick Mukadi  3   4   5 , Chris Smith  1   2 , Tansy Edwards  6 , Su Myat Han  1   6 , Hsu Thinzar Maung  1 , David M Brett-Major  7 , Nathaniel Lee  1   6
Affiliations
Meta-Analysis

Antibiotic prophylaxis for leptospirosis

Tin Zar Win et al. Cochrane Database Syst Rev. .

Abstract

Background: Leptospirosis is a global zoonotic and waterborne disease caused by pathogenic Leptospira species. Antibiotics are used as a strategy for prevention of leptospirosis, in particular in travellers and high-risk groups. However, the clinical benefits are unknown, especially when considering possible treatment-associated adverse effects. This review assesses the use of antibiotic prophylaxis in leptospirosis and is an update of a previously published review in the Cochrane Library (2009, Issue 3).

Objectives: To evaluate the benefits and harms of antibiotic prophylaxis for human leptospirosis.

Search methods: We identified randomised clinical trials through electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and other resources. We searched online clinical trial registries to identify unpublished or ongoing trials. We checked reference lists of the retrieved studies for further trials. The last date of search was 17 April 2023.

Selection criteria: We included ⁠⁠randomised clinical trials of any trial design, assessing antibiotics for prevention of leptospirosis, and with no restrictions on age, sex, occupation, or comorbidity of trial participants. We looked for trials assessing antibiotics irrespective of route of administration, dosage, and schedule versus placebo or no intervention. We also included trials assessing antibiotics versus other antibiotics using these criteria, or the same antibiotic but with another dose or schedule.

Data collection and analysis: We followed Cochrane methodology. The primary outcomes were all-cause mortality, laboratory-confirmed leptospirosis regardless of the presence of an identified clinical syndrome (inclusive of asymptomatic cases), clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation, clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (exclusive of asymptomatic cases), and serious adverse events. The secondary outcomes were quality of life and the proportion of people with non-serious adverse events. We assessed the risk of bias of the included trials using the RoB 2 tool and the certainty of evidence using GRADE. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean difference (MD), with their 95% confidence intervals (CI). We used a random-effects model for our main analyses and the fixed-effect model for sensitivity analyses. Our primary outcome analyses included trial data at the longest follow-up.

Main results: We identified five randomised clinical trials comprising 2593 participants that compared antibiotics (doxycycline, azithromycin, or penicillin) with placebo, or one antibiotic compared with another. Four trials assessed doxycycline with different durations, one trial assessed azithromycin, and one trial assessed penicillin. One trial had three intervention groups: doxycycline, azithromycin, and placebo. Three trials assessed pre-exposure prophylaxis, one trial assessed postexposure prophylaxis, and one did not report this clearly. Four trials recruited residents in endemic areas, and one trial recruited soldiers who experienced limited time exposure. The participants' ages in the included trials were 10 to 80 years. Follow-up ranged from one to three months. Antibiotics versus placebo Doxycycline compared with placebo may result in little to no difference in all-cause mortality (RR 0.15, 95% CI 0.01 to 2.83; 1 trial, 782 participants; low-certainty evidence). Prophylactic antibiotics may have little to no effect on laboratory-confirmed leptospirosis, but the evidence is very uncertain (RR 0.56, 95% CI 0.25 to 1.26; 5 trials, 2593 participants; very low-certainty evidence). Antibiotics may result in little to no difference in the clinical diagnosis of leptospirosis regardless of laboratory confirmation (RR 0.76, 95% CI 0.53 to 1.08; 4 trials, 1653 participants; low-certainty evidence) and the clinical diagnosis of leptospirosis with laboratory confirmation (RR 0.57, 95% CI 0.26 to 1.26; 4 trials, 1653 participants; low-certainty evidence). Antibiotics compared with placebo may increase non-serious adverse events, but the evidence is very uncertain (RR 10.13, 95% CI 2.40 to 42.71; 3 trials, 1909 participants; very low-certainty evidence). One antibiotic versus another antibiotic One trial assessed doxycycline versus azithromycin but did not report mortality. Compared to azithromycin, doxycycline may have little to no effect on laboratory-confirmed leptospirosis regardless of the presence of an identified clinical syndrome (RR 1.49, 95% CI 0.51 to 4.32; 1 trial, 137 participants), on the clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation (RR 4.18, 95% CI 0.94 to 18.66; 1 trial, 137 participants), on the clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (RR 4.18, 95% CI 0.94 to 18.66; 1 trial, 137 participants), and on non-serious adverse events (RR 1.12, 95% CI 0.36 to 3.48; 1 trial, 137 participants), but the evidence is very uncertain. The certainty of evidence for all the outcomes was very low. None of the five included trials reported serious adverse events or assessed quality of life. One study is awaiting classification. Funding Four of the five trials included statements disclosing their funding/supporting sources, and the remaining trial did not include this. Three of the four trials that disclosed their supporting sources received the supply of trial drugs directly from the same pharmaceutical company, and the remaining trial received financial support from a governmental source.

Authors' conclusions: We do not know if antibiotics versus placebo or another antibiotic has little or have no effect on all-cause mortality or leptospirosis infection because the certainty of evidence is low or very low. We do not know if antibiotics versus placebo may increase the overall risk of non-serious adverse events because of very low-certainty evidence. We lack definitive rigorous data from randomised trials to support the use of antibiotics for the prophylaxis of leptospirosis infection. We lack trials reporting data on clinically relevant outcomes.

PubMed Disclaimer

Conflict of interest statement

TZW: none.

TP: none.

PM: none.

CS: none.

TE: none.

SMH: none.

HTM: none.

DMB: none.

NL: none.

Figures

1
1
PRISMA flow diagram.
1.1
1.1. Analysis
Comparison 1: Antibiotics versus placebo or no intervention, Outcome 1: All‐cause mortality
1.2
1.2. Analysis
Comparison 1: Antibiotics versus placebo or no intervention, Outcome 2: Proportion of people with laboratory‐confirmed leptospirosis regardless of the presence of an identified clinical syndrome (inclusive of asymptomatic cases)
1.3
1.3. Analysis
Comparison 1: Antibiotics versus placebo or no intervention, Outcome 3: Sensitivity analysis: laboratory‐confirmed leptospirosis (best‐case scenario)
1.4
1.4. Analysis
Comparison 1: Antibiotics versus placebo or no intervention, Outcome 4: Sensitivity analysis: laboratory‐confirmed leptospirosis (worst‐case scenario)
1.5
1.5. Analysis
Comparison 1: Antibiotics versus placebo or no intervention, Outcome 5: Sensitivity analysis: laboratory‐confirmed leptospirosis (only pre‐exposure prophylaxis)
1.6
1.6. Analysis
Comparison 1: Antibiotics versus placebo or no intervention, Outcome 6: Sensitivity analysis: laboratory‐confirmed leptospirosis (only postexposure prophylaxis)
1.7
1.7. Analysis
Comparison 1: Antibiotics versus placebo or no intervention, Outcome 7: Sensitivity analysis: laboratory‐confirmed leptospirosis (including only endemic community)
1.8
1.8. Analysis
Comparison 1: Antibiotics versus placebo or no intervention, Outcome 8: Proportion of people with clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation
1.9
1.9. Analysis
Comparison 1: Antibiotics versus placebo or no intervention, Outcome 9: Sensitivity analysis: clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation (best‐case scenario)
1.10
1.10. Analysis
Comparison 1: Antibiotics versus placebo or no intervention, Outcome 10: Sensitivity analysis: clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation (worst‐case scenario)
1.11
1.11. Analysis
Comparison 1: Antibiotics versus placebo or no intervention, Outcome 11: Proportion of people with clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (exclusive of asymptomatic cases)
1.12
1.12. Analysis
Comparison 1: Antibiotics versus placebo or no intervention, Outcome 12: Sensitivity analysis: clinical diagnosis confirmed by laboratory diagnosis (best‐case scenario)
1.13
1.13. Analysis
Comparison 1: Antibiotics versus placebo or no intervention, Outcome 13: Sensitivity analysis: clinical diagnosis confirmed by laboratory diagnosis (worst‐case scenario)
1.14
1.14. Analysis
Comparison 1: Antibiotics versus placebo or no intervention, Outcome 14: Proportion of people with non‐serious adverse events
1.15
1.15. Analysis
Comparison 1: Antibiotics versus placebo or no intervention, Outcome 15: Sensitivity analysis: non‐serious adverse events (best‐case scenario)
1.16
1.16. Analysis
Comparison 1: Antibiotics versus placebo or no intervention, Outcome 16: Sensitivity analysis: non‐serious adverse events (worst‐case scenario)
2.1
2.1. Analysis
Comparison 2: Antibiotic prophylaxis versus another antibiotic, or another dose, or schedule of the same antibiotic, Outcome 1: Proportion of people with laboratory‐confirmed leptospirosis regardless of the presence of an identified clinical syndrome (inclusive of asymptomatic cases)
2.2
2.2. Analysis
Comparison 2: Antibiotic prophylaxis versus another antibiotic, or another dose, or schedule of the same antibiotic, Outcome 2: Proportion of people with clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation
2.3
2.3. Analysis
Comparison 2: Antibiotic prophylaxis versus another antibiotic, or another dose, or schedule of the same antibiotic, Outcome 3: Proportion of people with clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (exclusive of asymptomatic cases)
2.4
2.4. Analysis
Comparison 2: Antibiotic prophylaxis versus another antibiotic, or another dose, or schedule of the same antibiotic, Outcome 4: Proportion of people with non‐serious adverse events
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Update of

  • doi: 10.1002/14651858.CD014959

References

References to studies included in this review

Alikhani 2018 {published data only}
    1. Alikhani A, Salehifar E, Zameni F, Rafiei A, Yazdani-charati J, Delavaryan L, et al. Comparison of azithromycin vs doxycycline prophylaxis in leptospirosis, a randomized double blind placebo-controlled trial. Journal of Infection in Developing Countries 2018;12(11):991-5. [DOI: 10.3855/jidc.10126] - DOI - PubMed
    1. IRCT2015052322383N1. Clinical trial azithromycin versus doxycycline chemoprophylaxis in leptospirosis in farmers. trialsearch.who.int/Trial2.aspx?TrialID=IRCT2015052322383N1 (first received 29 June 2016).
Gonsalez 1998 {published data only}
    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 Sao Paulo, Brazil. Revista do Instituto de Medicina Tropical de São Paulo 1998;40(1):59-61. - PubMed
Illangasekera 2008 {published data only}
    1. Illangasekera VL, Kularatne SA, Kumarasiri PV, Pussepitiya DM, Premaratne MD. Is oral penicillin an effective chemoprophylaxis against leptospirosis? A placebo controlled field study in the Kandy District, Sri Lanka. Southeast Asian Journal of Tropical Medicine and Public Health 2008;39:882-4. - PubMed
Sehgal 2000 {published data only}
    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;13:249-55. - PubMed
Takafuji 1984 {published data only}
    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;310:497-500. - PubMed

References to studies excluded from this review

Chusri 2014 {published data only}
    1. Chusri S, McNeil EB, Hortiwakul T, Charernmak B, Sritrairatchai S, Santimaleeworagun W, et al. Single dosage of doxycycline for prophylaxis against leptospiral infection and leptospirosis during urban flooding in southern Thailand: a non-randomized controlled trial. Journal of Infection and Chemotherapy 2014;20(11):709-15. [DOI: http://dx.doi.org/10.1016/ j.jiac.2014.07.016] - PubMed
    1. TCTR20131106001. Risk factors and chemoprophylaxis for leptospirosis infection during urban flooding in southern Thailand: a case-control study. trialsearch.who.int/Trial2.aspx?TrialID=TCTR20131106001 (date of registration 6 November 2013).

References to studies awaiting assessment

Shivaraj 2012 {published data only}
    1. Shivaraj B, Ts R, Anithraj BY, Bayari R. A study on prophylactic doxycycline to reduce the incidence of leptospirosis among paddy field farmers in a coastal district of India. International Journal of Infectious Diseases 2012;16(Suppl 1):E462.

Additional references

Aklil 2018
    1. Aklil MA, Aznida MZ, Azman A, Haneef MA, Him NA, Sharizman SA, et al. Effectiveness of antibiotics prophylaxis for leptospirosis among adults: a systematic review. Malaysian Journal of Applied Sciences 2018;3(2):46-56.
Bhardwaj 2010
    1. Bhardwaj P, Kosambiya JK, Vikas KD, Karan J. Chemoprophylaxis with doxycycline in suspected epidemic of leptospirosis during floods: does this really work? African Health Sciences 2010;10(2):199-200. - PMC - PubMed
Bharti 2003
    1. Bharti AR, Nally JE, Ricaldi JN, Matthias MA, Diaz MM, Lovett MA, et al. Leptospirosis: a zoonotic disease of global importance. Lancet Infectious Diseases 2003;3:757-71. - PubMed
Boutron 2022
    1. Boutron I, Page MJ, Higgins JP, Altman DG, Lundh A, Hróbjartsson A. Chapter 7: Considering bias and conflicts of interest among the included studies. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane, 2022. Available from training.cochrane.org/handbook/archive/v6.3.
Brett‐Major 2012
    1. Brett-Major DM, Coldren R. Antibiotics for leptospirosis. Cochrane Database of Systematic Reviews 2012, Issue 2. Art. No: CD008264. [DOI: 10.1002/14651858.CD008264.pub2] - DOI - PMC - PubMed
Brok 2008
    1. Brok J, Thorlund K, Gluud C, Wetterslev J. Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses. Journal of Clinical Epidemiology 2008;61:763-9. - PubMed
Brok 2009
    1. Brok J, Thorlund K, Wetterslev J, Gluud C. Apparently conclusive meta-analyses may be inconclusive – Trial Sequential Analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta-analyses. International Journal of Epidemiology 2009;38(1):287-98. - PubMed
Budihal 2014
    1. Budihal SV, Perwez K. Leptospirosis diagnosis: competancy of various laboratory tests. Journal of Clinical and Diagnostic Research : JCDR 2014;8(1):199-202. - PMC - PubMed
Castellini 2018
    1. Castellini G, Bruschettini M, Gianola S, Gluud C, Moja L. Assessing imprecision in Cochrane systematic reviews: a comparison of GRADE and Trial Sequential Analysis. Systematic Reviews 2018;7(110):1-10. - PMC - PubMed
CDC 2018
    1. Center for Disease Control and Prevention. Leptospirosis: fact sheet for clinicians. www.cdc.gov/leptospirosis/pdf/fs-leptospirosis-clinicians-eng-508.pdf (accessed 16 November 2021).
Chierakul 2014
    1. Chierakul W. Leptospirosis. In: Farrar J, Hotez PJ, Junghanss T, Kang G, Lalloo D, White NJ, editors(s). Manson's Tropical Diseases. 23 edition. London (UK): Saunders Ltd., 2014:433-40. [DOI: 10.1016/C2010-0-66223-7] - DOI
Costa 2015
    1. Costa F, Hagan JE, Calcagno J, Kane M, Torgerson P, Ko AI, et al. Global morbidity and mortality of leptospirosis: a systematic review. PLOS Neglected Tropical Disease 2015;9(9):e0003898. [DOI: 10.1371/journal.pntd.0003898] - DOI - PMC - PubMed
Covidence [Computer program]
    1. Covidence systematic review software. Melbourne, Australia: Veritas Health Innovation, accessed on 14 August 2023. Available at covidence.org.
Deeks 2022
    1. Deeks JJ, Higgins JP, Altman DG. Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane, 2022. Available from training.cochrane.org/handbook/archive/v6.3.
Eldridge 2021
    1. Eldridge S, Campbell MK, Campbell MJ, Drahota AK, Giraudeau B, Reeves BC, et al. Revised Cochrane risk of bias tool for randomized trials (RoB 2). Additional considerations for cluster-randomized trials (RoB 2 CRT). drive.google.com/file/d/1yDQtDkrp68_8kJiIUdbongK99sx7RFI-/view (accessed 12 June 2023).
Enzler 2011
    1. Enzler MJ, Berbari E, Osmon DR. Antimicrobial prophylaxis in adults. Mayo Clinic Proceedings 2011;86(7):686-701. - PMC - PubMed
Fergusson 2002
    1. Fergusson D, Aaron SD, Guyatt G, Hebert P. Post-randomisation exclusions: the intention to treat principle and excluding patients from analysis. BMJ (Clinical Research Ed.) 2002;325:625-4. [DOI: 10.1136/bmj.325.7365.652] - DOI - PMC - PubMed
Galloway 2020
    1. Galloway RL, Schafer IJ, Stoddard RS. Travel-related infectious diseases – leptospirosis. wwwnc.cdc.gov/travel/yellowbook/2024/infections-diseases/leptospirosis (accessed 14 August 2023).
Gartlehner 2019
    1. Gartlehner G, Nussbaumer-Streit B, Wagner G, Patel S, Swinson-Evans T, Dobrescu A, et al. Increased risks for random errors are common in outcomes graded as high certainty of evidence. Journal of Clinical Epidemiology 2019;106:50-9. [DOI: 10.1016/j.jclinepi.2018.10.009] - DOI - PubMed
Goarant 2016
    1. Goarant C. Leptospirosis: risk factors and management challenges in developing countries. Research and Reports in Tropical Medicine 2016;7:49-62. - PMC - PubMed
GRADEpro GDT [Computer program]
    1. GRADEpro GDT. Hamilton (ON): McMaster University (developed by Evidence Prime), (accessed 14 August 2023). Available from gradepro.org.
Griffith 2006
    1. Griffith ME, Hospenthal DR, Murray CK. Antimicrobial therapy of leptospirosis. Current Opinion in Infectious Diseases 2006;19(6):533-7. - PubMed
Guidugli 2000
    1. Guidugli F, Castro AA, Atallah AN. Antibiotics for preventing leptospirosis [withdrawn 2000]. Cochrane Database of Systematic Reviews 2000, Issue 4. Art. No: CD001305. [DOI: 10.1002/14651858.CD001305] - DOI - PubMed
Haake 2015
    1. Haake DA, Levett PN. Leptospirosis in humans. Current Topics in Microbiology and Immunology 2015;387:65-97. - PMC - PubMed
Higgins 2020
    1. Higgins JP, Li T, Sterne J. Revised Cochrane risk of bias tool for randomized trials (RoB 2). Additional considerations for crossover trials. drive.google.com/file/d/18Ek-uW8HYQsUja8Lakp1yOhoFk0EMfPO/view (accessed 14 August 2023).
Higgins 2022a
    1. Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane, 2022. Available from training.cochrane.org/handbook/archive/v6.3.
Higgins 2022b
    1. Higgins JP, Savović J, Page MJ, Elbers RG, Sterne JA. Chapter 8: Assessing risk of bias in a randomized trial. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane, 2022. Available from training.cochrane.org/handbook/archive/v6.3.
Higgins 2022c
    1. Higgins JP, Eldridge S, Li T. Chapter 23: Including variants on randomized trials. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane, 2022. Available from training.cochrane.org/handbook/archive/v6.3.
Higgins 2022d
    1. Higgins JP, Li T, Deeks JJ. Chapter 6: Choosing effect measures and computing estimates of effect. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane, 2022. Available from training.cochrane.org/handbook/archive/v6.3.
ICH‐GCP 2016
    1. International Council for Harmonisation of technical requirements for pharmaceuticals for human use (ICH). ICH Harmonised Guideline. Integrated addendum to ICH E6(R1): guideline for good clinical practice E6(R2). Available from database.ich.org/sites/default/files/E6_R2_Addendum.pdf (accessed 14 August 2023).
Israel 2011
    1. Israel H, Richter RR. A guide to understanding meta-analysis. Journal of Orthopaedic and Sports Physical Therapy 2011;41(7):496-504. [DOI: 10.2519/jospt.2011.3333] - DOI - PubMed
Jakobsen 2014
    1. Jakobsen JC, Wetterslev J, Winkel P, Lange T, Gluud C. Thresholds for statistical and clinical significance in systematic reviews with meta-analytic methods. BMC Medical Research Methodology 2014;14:120. [DOI: 10.1186/1471-2288-14-120] - DOI - PMC - PubMed
Karpagam 2020
    1. Karpagam KB, Ganesh B. Leptospirosis: a neglected tropical zoonotic 13 infection of public health importance – an updated review. European Journal of Clinical & Microbiology and Infectious Diseases 2020;39(5):835-46. - PubMed
Kobayashi 2001
    1. Kobayashi Y. Clinical observation and treatment of leptospirosis. Journal of Infection and Chemotherapy 2001;7(2):59-68. [DOI: 10.1007/s101560100011] [PMID: ] - DOI - PubMed
Koizumi 2020
    1. Koizumi N. Laboratory diagnosis of leptospirosis. Methods in Molecular Biology (Clifton, N.J.) 2020;2134:277-87. - PubMed
Lasserson 2022
    1. Lasserson T, Churchill R, Chandler J, Tovey D, Higgins JP. Standards for the conduct and reporting of new Cochrane intervention reviews, reporting of protocols and the planning, conduct and reporting of updates. community.cochrane.org/mecir-manual (accessed 12 June 2023).
Lefebvre 2022
    1. Lefebvre C, Glanville J, Briscoe S, Littlewood A, Marshall C, Metzendorf M-I, et al. Technical Supplement to Chapter 4: Searching for and selecting studies. In: Higgins JP, Thomas J, Chandler J, Cumpston MS, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane, 2022. Available from training.cochrane.org/handbook/archive/v6.3.
Levett 2001
    1. Levett PN. Leptospirosis. Clinical Microbiology Reviews 2001;14(2):296-326. - PMC - PubMed
Lewis 2001
    1. Lewis S, Clarke M. Forest plots: trying to see the wood and the trees. BMJ (Clinical Research Ed.) 2001;322(7300):1479-80. [DOI: 10.1136/bmj.322.7300.1479] - DOI - PMC - PubMed
Lundh 2017
    1. Lundh A, Lexchin J, Mintzes B, Schroll JB, Bero L. Industry sponsorship and research outcome. Cochrane Database of Systematic Reviews 2017, Issue 2. Art. No: MR000033. [DOI: 10.1002/14651858.MR000033.pub3] - DOI - PMC - PubMed
Mavridis 2014
    1. Mavridis D, Chaimani A, Efthimiou O, Leucht S, Salanti G. Addressing missing outcome data in meta-analysis. Evidence-Based Mental Health 2014;17(3):85-9. [DOI: 10.1136/eb-2014-101900] - DOI - PubMed
McKenzie 2022a
    1. McKenzie JE, Brennan SE, Ryan RE, Thomson HJ, Johnston RV, Thomas J. Chapter 3: Defining the criteria for including studies and how they will be grouped for the synthesis. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane, 2022. Available from training.cochrane.org/handbook/archive/v6.3.
McKenzie 2022b
    1. McKenzie JE, Brennan SE. Chapter 12: Synthesizing and presenting findings using other methods. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane, 2022. Available from training.cochrane.org/handbook/archive/v6.3.
Moffa 2019
    1. Moffa M, Brook I. Tetracyclines, glycylcyclines, and chloramphenicol. In: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 9th edition. Philadelphia (PA): W.B. Saunders, 2019:318-37.
Munoz‐Zanzi 2020
    1. Munoz-Zanzi C, Groene E, Morawski BM, Bonner K, Costa F, Bertherat E, et al. A systematic literature review of leptospirosis outbreaks worldwide, 1970–2012. Revista Panamericana de Salud Pública 2020;44:e78. [DOI: ] - PMC - PubMed
Nemeth 2006
    1. Nemeth G. Health related quality of life outcome instruments. European Spine Journal 2006;15:S44-51. [DOI: 10.1007/s00586-005-1046-8] - DOI - PMC - PubMed
Page 2021a
    1. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ (Clinical Research Ed.) 2021;372:n71. - PMC - PubMed
Page 2021b
    1. Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ (Clinical Research Ed.) 2021;372:n160. - PMC - PubMed
Page 2022
    1. Page MJ, Higgins JP, Sterne JA. Chapter 13: Assessing risk of bias due to missing results in a synthesis. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane, 2022. Available from training.cochrane.org/handbook/archive/v6.3.
Pequeno 2020
    1. Pequeno NP, Cabral NL, Marchioni DM, Lima SC, Lyra CO. Quality of life assessment instruments for adults: a systematic review of population based studies. Health and Quality of Life Outcomes 2020;18(1):208. [DOI: 10.1186/s12955-020-01347-7] - DOI - PMC - PubMed
Perez 2021
    1. Perez MG, Sancho JJ, Luque JC, Rodriguez FM, Alfaro EM, Pozo JS. Current evidence on the antimicrobial treatment and chemoprophylaxis of human leptospirosis: a meta-analysis. Pathogens 2021;10:1125. [DOI: 10.3390/pathogens10091125] - DOI - PMC - PubMed
Peryer 2022
    1. Peryer G, Golder S, Junqueira D, Vohra S, Loke YK. Chapter 19: Adverse effects. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane, 2022. Available from training.cochrane.org/handbook/archive/v6.3.
RevMan 2023 [Computer program]
    1. Review Manager (RevMan). Version 5.8.0. The Cochrane Collaboration, 2023. Available at revman.cochrane.org.
Rodrigo 2014
    1. Rodrigo C, Silva NL, Goonaratne R, Samarasekara K, Wijesinghe I, Parththipan B, et al. High dose corticosteroids in severe leptospirosis: a systematic review. Transactions of the Royal Society of Tropical Medicine and Hygiene 2014;108(12):743-50. - PubMed
Schneider 2017
    1. Schneider MC, Velasco-Hernandez J, Min K, Leonel DG, Baca-Carrasco D, Gompper ME, et al. The use of chemoprophylaxis after floods to reduce the occurrence and impact of leptospirosis outbreaks. International Journal of Environmental Research and Public Health 2017;14(6):594-615. [DOI: 10.3390/ijerph14060594] - DOI - PMC - PubMed
Schünemann 2013
    1. Schünemann H, Brożek J, Guyatt G, Oxman A, editors. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available from gdt.gradepro.org/app/handbook/handbook.html.
Schünemann 2022
    1. Schünemann HJ, Vist GE, Higgins JP, Santesso N, Deeks JJ, Glasziou P, et al. Chapter 15: Interpreting results and drawing conclusions. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane, 2022. Available from training.cochrane.org/handbook/archive/v6.3.
Soler 2021
    1. Soler MC, Mogliani S, Benítez ST, Cabillón LN, Rollié RD, Martins GM. Glucocorticoids in leptospira alveolar hemorrhage [Glucocorticoides en hemorragia alveolar por leptospira]. Medicina 2021;81:107-10. - PubMed
Sterne 2019
    1. Sterne JA, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ (Clinical Research Ed.) 2019;366:l4898. [DOI: 10.1136/bmj.l4898] - DOI - PubMed
Storebø 2018
    1. Storebø OJ, Pedersen N, Ramstad E, Kielsholm ML, Nielsen SS, Krogh HB, et al. Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents - assessment of adverse events in non-randomised studies. Cochrane Database of Systematic Reviews 2018, Issue 5. Art. No: CD012069. [DOI: 10.1002/14651858.CD012069.pub2] - DOI - PMC - PubMed
Suneth 2011
    1. Suneth BA, Sharon JP, Vasanthi T, Danaseela BN, Lee S, Janjira T, et al. Leptospirosis outbreak in Sri Lanka in 2008: lessons for assessing the global burden of disease. American Journal of Tropical Medicine and Hygiene 2011;85(3):471-8. - PMC - PubMed
Thai 2008
    1. Thai KT, Nga TT, Phuong HL, Giao PT, Hung LQ, Binh TQ. Seroepidemiology and serological follow-up of anti-leptospiral IgG in children in Southern Vietnam. Acta Tropica 2008;106(2):128-31. [DOI: 10.1016/j.actatropica.2008.02.005] - DOI - PubMed
Thorlund 2010
    1. Thorlund K, Anema A, Mills E. Interpreting meta-analysis according to the adequacy of sample size. An example using isoniazid chemoprophylaxis for tuberculosis in purified protein derivative negative HIV-infected individuals. Clinical Epidemiology 2010;2:57-66. - PMC - PubMed
Thorlund 2017
    1. Thorlund K, Engstrøm J, Wetterslev J, Brok J, Imberger G, Gluud C. User Manual for Trial Sequential Analysis (TSA); 2nd edition. Copenhagen Trial Unit, 2017. Available from ctu.dk/tsa/learn-more (accessed 12 June 2023).
Torgerson 2015
    1. Torgerson PR, Hagan JE, Costa F, Calcagno J, Kane M, Silveira MS, et al. Global burden of leptospirosis: estimated in terms of disability adjusted life years. PLOS Neglected Tropical Diseases 2015;9(10):e0004122. [DOI: 10.1371/journal.pntd.0004122] - DOI - PMC - PubMed
TSA 2021 [Computer program]
    1. TSA – Trial Sequential Analysis. Version 0.9.5.10 Beta. Copenhagen: Copenhagen Trial Unit, 2021. Available from ctu.dk/tsa/downloads/.
Vijayachari 2008
    1. Vijayachari P, Sugunan AP, Shriram AN. Leptospirosis: an emerging global public health problem. Journal of Biosciences 2008;33(4):557-69. - PubMed
Vinetz 2020
    1. Vinetz JM, Watt G. Leptospirosis. In: Ryan ET, Hill DR, Solomon T, Aronson NE, Endy TP, editors(s). Hunter's Tropical Medicine and Emerging Infectious Diseases. 10th edition. Edinburgh (UK): Elsevier, 2020:636-40.
Wetterslev 2008
    1. Wetterslev J, Thorlund K, Brok J, Gluud C. Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis. Journal of Clinical Epidemiology 2008;61(1):64-75. - PubMed
Wetterslev 2009
    1. Wetterslev J, Thorlund K, Brok J, Gluud C. Estimating required information size by quantifying diversity in a random-effects meta-analysis. BMC Medical Research Methodology 2009;9:86. - PMC - PubMed
Wetterslev 2017
    1. Wetterslev J, Jakobsen JC, Gluud C. Trial Sequential Analysis in systematic reviews with meta-analysis. BMC Medical Research Methodology 2017;17(1):39. - PMC - PubMed
WHO 2003
    1. World Health Organization. Human leptospirosis: guidance for diagnosis, surveillance and control. Revista do Instituto de Medicina Tropical de São Paulo 2003;45(5):292-310. [DOI: 10.1590/S0036-46652003000500015] - DOI
WHO 2020
    1. World Health Organization. Fact sheets – health emergency and disaster risk management (EDRM). www.who.int/publications/m/item/health-emergency-and-disaster-risk-manag... (accessed 14 August 2023).

References to other published versions of this review

Brett‐Major 2008
    1. Brett-Major DM, Martinez LJ, Lipnick RJ. Antibiotic prophylaxis for leptospirosis. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No: CD007342. [DOI: 10.1002/14651858.CD007342] - DOI - PMC - PubMed
Brett‐Major 2009
    1. Brett-Major DM, Lipnick RJ. Antibiotic prophylaxis for leptospirosis. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No: CD007342. [DOI: 10.1002/14651858.CD007342.pub2] - DOI - PMC - PubMed
Tabei 2022
    1. Tabei K, Win TZ, Kitashoji E, Brett-Major DM, Edwards T, Smith C, et al. Antibiotic prophylaxis for leptospirosis. Cochrane Database of Systematic Reviews 2022, Issue 2. Art. No: CD014959. [DOI: 10.1002/14651858.CD014959] - DOI - PMC - PubMed

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