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Three Part Question

After [immersion in water] should [prophylactic antibiotics] be given to prevent [infection from Leptospirosis]?

Clinical Scenario

A drainage engineer comes to the Emergency Department following a fall and total immersion in standing water. He is concerned about Weil's disease. You do not know whether prophylactic antibiotics are of any use in disease prevention.

Search Strategy

MEDLINE(R) Ovid interface 1950-September week 4 2011
Google Scholar
EMBASE
[(exp Immersion)OR(immersion.mp)OR(exp water)OR(water.mp)OR(exp Fresh Water)OR(exp Water Supply)OR(river.mp)OR(stream.mp)OR(exp Near Drowning)OR(exp Drowning)] AND [(rat adj urine)OR(leptospirosis.mp)OR(exp Leptospirosis)OR(exp Leptospira interrogans)OR(exp Weil)OR(weils adj syndrome)OR(exp Leptospira interrogans serovar canicola)OR(canicola fever.mp)OR(seven day fever.mp)] AND [(antibiotics.mp)OR(exp Anti-bacterials)OR(exp Anti-bacterial Agents)OR(anti-microbials.mp)OR(exp Antibiotic prophylaxis)OR(prophylactic antibiotics.mp)]
LIMIT to Humans

Search Outcome

30 articles.
4 were of relevance to the scenario

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Takafuji E et al Feb 23 1984 US	military personnel undergoing jungle training . 469 given prophylactic Doxycycline vs 471 given placebo	Double-blinded placebo-controlled trial	Number who developed symptoms compatible with Leptosira infection up to 6/52 post exposure and had positive lab result	Doxycycline group 1 (0.2%) vs placebo 20 (4.2%). p<0.001	Relevant mainly to high risk area. Population very different from UK general population. Specific symptoms asked rather than allowed to freely express.
Gonzalez C et al 1998 Brazil	82 residents of an area with a high risk of flooding and leptospira infection randomised into 40 taking prophylactic doxycycline vs 42 placebo following flooding	Double-blind randomised control trial	Doxycycline vs placebo for leptospira infection confirmed clinically and from lab results, asymptomatic infection, suspected clinical infection and the positive protective effect of doxycycline.	Doxycycline vs placebo: confirmed 2 v 5, asymptomatic 11 vs 6, suspected 6 vs 5. Protective RR2.3 CI 0.4-11.5	Low numbers. Underpowered. Very high risk area cf risk in UK.
Seghal S et al 2000 India	386 people over 10 years took prophylactic doxycycline vs 396 with placebo in high risk area for endemic leptospira infection	Double blind randomised control trial	Evidence of leptospiral infection and symptomatic leptospiral infection in the 2 groups	Evidence of infection, doxycycline group vs placebo: 112 vs 101 p=0.27; clinical infection, doxycycline vs placebo 12 vs 27 p=0.017	No evidence of intention to treat Population investigated often had background evidence of leptospiral infection
Sejvar J et al June 2003 US	80 athletes who had completed multiple outdoor activities in Malaysia and had symptoms of possible leptospirosis compared with 109 controls	Retrospective survey	Protective effect of doxycycline; independent risk factors for leptospiral infection	protective effect RR0.4, 95%CI 0.1-1.1, p=0.1; independent risk factor, swimming in Segama River RR 2.0 CI 1.3-3.1	Low numbers especially those who had taken antibiotics 38% of those taking part in the activities not contacted Retrospective Inclusion criteria bias from how participants sourced

Comment(s)

All these trials were carried out in parts of the world with endemic leptospiral infection and so the effect of good evidence of decreased infection following prophylactic doxycycline would not necessarily import well to the UK. There is only consistant evidence that symptomatic infection is reduced as there was evidence of prior exposure in many of the trial subjects. It would therefore be prudent for UK nationals to take antibiotics if exposed to water immersion in an endemic area. In the UK the threat of infection must be lower

Clinical Bottom Line

If there is immersion in an endemic area for leptospirosis, or if there is higher risk of water contamination e.g standing water, known rat infestation, drainage channels etc then doxycycline would have to be recommended. Other scenarios are not as clear

References

1. Takafuji E, Kirkpatrick J, Miller R, Karwacki J, Kelley P, Gray M et al An efficacy trial of doxycycline chemoprophylaxis against leptospirosis New England Journal of Medicine Feb 23 1984;310(8):497-500
2. Gonzalez C, Casseb J, Monteiro G, Paula-Neto J, Fernandez R, Silva M et al Use of doxycycline for leptospirosis after high-risk exposure in Sao Paulo Revista do Instituto de Medicina Tropical de Sao Paulo Feb 1998;40:59-61
3. Sehgal S, Sugunan A, Murhekar M, Sharma P, Vijayachari P Randomised control trial of doxycycline prophylaxis against leptospirosis in an endemic area International Journal of Antimicrobial Agents 2000;13:249-255
4. Sejvar J,Bancroft E, Winthrop K, et al Leptospirosis in Eco-Challenge athletes, Malaysian Borneo,2000. Emerging Infectious Diseases June 2003;9(6);702-707