Leptospirosis Prophylaxis
Doxycycline 200 mg orally once weekly is the recommended prophylaxis for leptospirosis in high-risk exposure settings, though its efficacy remains controversial and should be reserved for specific military or occupational scenarios with documented high attack rates.
Evidence for Doxycycline Prophylaxis
Pre-Exposure Prophylaxis
- Doxycycline 200 mg weekly demonstrated 95% efficacy in preventing leptospirosis among U.S. soldiers training in Panama, with only 1 case (0.2% attack rate) in the treatment group versus 20 cases (4.2% attack rate) in placebo group 1
- However, a 2014 outbreak among U.S. Marines in Okinawa showed no statistical difference in attack rates whether personnel took pre-exposure doxycycline or not, with 33.9% overall attack rate despite prophylaxis protocols 2
- Pooled analysis from multiple trials showed no statistically significant reduction in Leptospira infection (Odds ratio 0.28,95% CI 0.01 to 7.48) 3
Post-Exposure Prophylaxis
- A single 200 mg dose of doxycycline after high-risk exposure in São Paulo showed a protective trend (RR = 2.3 for confirmed cases) but was not statistically significant due to small sample size 4
- Post-exposure prophylaxis after flooding in indigenous populations showed no apparent efficacy in reducing clinical or laboratory-identified infection 3
Adverse Effects and Tolerability
- Minor gastrointestinal side effects (predominantly nausea and vomiting) are significantly more common with doxycycline prophylaxis, with odds ratio of 11 (95% CI 2.1 to 60) 3
- Adverse effects occurred in 3% of doxycycline recipients versus 0.2% of placebo recipients 5
- Number needed-to-harm is 39 (95% CI 25 to 100) 5
Clinical Recommendations by Setting
High-Risk Military/Occupational Settings
- Consider weekly doxycycline 200 mg for soldiers or workers with prolonged freshwater exposure in endemic areas during training exercises lasting 2-3 weeks 1
- Begin prophylaxis before exposure and continue weekly throughout the exposure period 1
- Number needed-to-treat is 24 (95% CI 17 to 43) in optimal conditions 5
General Population and Flood Exposure
- Prophylaxis is NOT routinely recommended for general population exposure, including post-flood scenarios 3
- Focus instead on avoiding contact with contaminated water, especially during floods 6
- Protective measures include avoiding swimming or wading in potentially contaminated freshwater sources 6
Key Risk Factors to Assess
When considering prophylaxis, evaluate these specific exposures that increase infection risk:
- Swallowing stagnant water (attack rate ratio 2.3,95% CI 1.4-3.7) 2
- Open cuts or broken skin during water exposure (ARR 1.5,95% CI 1.01-2.11) 2
- Insect bites in endemic areas (ARR 2.0,95% CI 1.2-3.4) 2
- Agricultural work in flooded rice fields or areas with flood irrigation 6
- Occupational exposure to animals (rats, cattle, pigs, dogs) or their urine 6
Important Caveats
- The evidence base is limited and conflicting, with only three randomized trials available, all with methodological limitations including lack of intention-to-treat analysis 3
- The landmark 1984 Panama study showing 95% efficacy has not been consistently replicated in subsequent real-world settings 2, 1
- Pre-existing immunity may be present in endemic populations, with 22% of volunteers in one study already having IgM antibodies at baseline 4
- Prophylaxis efficacy appears highly dependent on exposure intensity and environmental conditions specific to each outbreak 2
Alternative to Prophylaxis
Primary prevention through exposure avoidance is more reliable than chemoprophylaxis:
- Avoid contact with potentially contaminated water, soil, or animal urine 6
- Use protective equipment (boots, gloves) during high-risk agricultural or occupational activities 6
- Implement rodent control measures in endemic areas 7
When Prophylaxis May Be Justified
Reserve doxycycline prophylaxis for: