Leptospirosis occurs as frequently as malaria among adolescent and adult acute febrile patients in Hoima, Uganda: A prospective health facility-based study

BACKGROUND: Leptospirosis is underdiagnosed across sub-Saharan Africa, with its contribution to acute undifferentiated fever (AUF) poorly characterized. We determined the prevalence, risk factors, and clinical profile of leptospirosis among adolescents and adults with AUF at a referral hospital and health centre in Hoima, Uganda. METHODS: In a prospective health facility-based study with convalescent follow-up, blood and urine from AUF patients were tested by LipL32 real-time PCR (qPCR) and microscopic agglutination (MAT). Leptospirosis was confirmed by qPCR positivity, a single test MAT titre of ≥1:800, a fourfold titre rise or seroconversion (change from negative or 1:50 to ≥1:100 (lenient) or ≥1:200 (conservative)) in paired sera. Risk factors were identified by multivariable logistic regression. RESULTS: Among 330 AUF patients, acute leptospirosis prevalence was 27.0% under the conservative definition (95% CI 22.3 to 32.1) and 32.7% under the lenient definition (95% CI 27.7 to 38.1). This was comparable to malaria at 30.3% (95% CI 25.3 to 35.3), and 8.8% of patients had both infections (95% CI 5.7 to 11.8). qPCR detected Leptospira DNA in 9.1% of patients. Agreement between qPCR and serology was low: 63.3% of qPCR-positive cases were confirmed by MAT, and only 24.4% of serologically confirmed cases were qPCR-positive. Seroprevalence (MAT titre 1:100 or above) was 35.8% (95% CI 30.6 to 41.2). L. interrogans serovar Bataviae was the predominant serovar, reported here for the first time in Uganda. Skinning animals (aOR 5.19, 95% CI 1.40 to 21.16) and mosquito exposure (aOR 2.31, 95% CI 1.17 to 4.70) were independent risk factors. DISCUSSION: Leptospirosis occurs as frequently as malaria among AUF patients in Hoima warranting inclusion in Uganda's national febrile illness guidelines. The association of leptospirosis with skinning suggests a role of animal exposure in leptospirosis transmission. Poor qPCR-MAT concordance confirms that accurate case ascertainment requires combined molecular and serological diagnostics. While findings are regional, their implications are broader, highlighting the need to include zoonotic diseases in diagnosis and surveillance. Targeted treatment can reduce morbidity, mortality, and economic burden, while limiting antimicrobial resistance by decreasing broad-spectrum antibiotic use.