What is the recommended prophylaxis for individuals at moderate risk of leptospirosis?

Leptospirosis Prophylaxis for Moderate Risk

For individuals at moderate risk of leptospirosis, prophylaxis is generally not recommended—focus instead on exposure avoidance and protective equipment, reserving doxycycline prophylaxis only for settings with documented attack rates exceeding 10 cases per 100 person-years. 1

Risk Stratification and When to Consider Prophylaxis

Moderate risk does not typically warrant chemoprophylaxis. The WHO specifically recommends reserving doxycycline prophylaxis for high-risk settings where attack rates exceed 10 cases per 100 person-years 1, 2. Moderate risk scenarios—such as occasional agricultural work, recreational water activities in endemic areas, or routine occupational exposure without prolonged water immersion—fall below this threshold.

Settings Where Prophylaxis May Be Justified:

• Military training exercises in highly endemic areas with documented high attack rates 1
• Short-term occupational exposures with unavoidable prolonged water contact in outbreak situations 1
• Mass outbreak situations following severe flooding with documented high attack rates and widespread exposure 1

Primary Prevention Measures (Preferred for Moderate Risk)

Exposure avoidance is the cornerstone of prevention for moderate-risk individuals:

• Avoid contact with contaminated water, especially during floods 1
• Use protective equipment such as boots and gloves during agricultural or occupational activities 1
• Implement rodent control measures in endemic areas 1
• Avoid swimming or wading in water likely contaminated with animal urine 1
• Wash hands after contact with animals or soil 3

Prophylaxis Regimen (When Indicated for High-Risk Scenarios)

If prophylaxis is deemed necessary based on documented high attack rates:

• Doxycycline 200 mg orally once weekly during exposure period 4, 5
• Begin one week before exposure and continue through four weeks after last exposure 6
• Single-dose doxycycline 200 mg may provide benefit for acute flood water exposure (76.8% protective efficacy against infection, 86.3% against clinical disease) 1

Important Caveats About Prophylaxis Efficacy:

The evidence for prophylaxis is mixed and context-dependent:

• A 2018 outbreak among US Marines showed no statistical difference in attack rates whether personnel took pre- or post-exposure doxycycline (attack rate = 33.9% regardless) 7
• A 2009 Cochrane review found unclear benefit with pooled odds ratio of 0.28 (95% CI 0.01-7.48, not statistically significant) 5
• A 2021 meta-analysis showed weekly doxycycline 200 mg did not significantly reduce symptomatic leptospirosis versus placebo (OR 0.20,95% CI 0.02-1.87, p=0.16) 8
• The strongest evidence comes from one high-quality trial in soldiers showing benefit (OR 0.05,95% CI 0.01-0.36), but this was in an extremely high-risk military training environment 4, 5

Adverse Effects to Counsel Patients About

• Nausea and vomiting are common with weekly doxycycline (odds ratio 11,95% CI 2.1-60) 5
• Minor gastrointestinal side effects occur in approximately 3% of recipients 4
• Doxycycline is absolutely contraindicated in children under 8 years due to permanent tooth discoloration and enamel hypoplasia 1, 2

Alternative Prophylaxis Options

• Azithromycin 500 mg weekly decreased seropositivity similar to doxycycline in one trial, though without significant effect on clinical disease 6
• No other chemoprophylaxis regimens (penicillin, single-agent dapsone, pyrimethamine, azithromycin, or clarithromycin) have shown statistically significant benefit 8

Critical Clinical Pitfall

The most important pitfall is over-prescribing prophylaxis for moderate-risk scenarios where exposure avoidance and protective equipment are more appropriate. 1, 2 The evidence shows prophylaxis works best in very high-risk, time-limited exposures (military exercises, documented outbreaks), not for ongoing moderate occupational or recreational risk. For moderate risk, invest in education about exposure avoidance, protective equipment, and early symptom recognition rather than chemoprophylaxis with unclear benefit and definite side effects.

When Symptoms Develop Despite Prophylaxis

• Begin treatment immediately upon clinical suspicion without waiting for laboratory confirmation 2, 3
• Doxycycline 100 mg orally twice daily for 7 days for mild-to-moderate disease 3
• Hospitalize patients with systemic signs even without severe disease criteria 3
• Watch for conjunctival suffusion (distinctive finding), severe myalgias especially in calves, and biphasic illness pattern 2, 3