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 substantially 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 presenting with AUF at a referral hospital and health centre in Hoima, western 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, or at least a fourfold titre rise or seroconversion in paired sera. Seroconversion was defined as a change from negative or 1:50 to 1:100 (conservative) or 1:200 (lenient). Seroprevalence was defined as a MAT titre of 1:100 or above in any sample. Risk factors were identified by multivariable logistic regression. Results: Among 330 AUF patients, acute leptospirosis prevalence was 27.0% (95% CI 22.3 to 32.1; conservative) and 32.7% (95% CI 27.7 to 38.1; lenient), comparable to malaria at 30.3% (95% CI 25.3 to 35.3), with co-infection in 8.8% (95% CI 5.7 to 11.8). qPCR detected Leptospira DNA in 9.1%, with 63.3% of qPCR-positive cases serologically confirmed and 24.4% of serological cases, qPCR-positive. Seroprevalence was 35.8% (95% CI 30.6 to 41.2); L. interrogans serovar Bataviae was predominant (18.2% of serological cases), 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 the only independent risk factors in multivariable analysis. Discussion: Leptospirosis occurs as frequently as malaria among AUF patients in Hoima and warrants inclusion in Uganda's national febrile illness guidelines. The association of leptospirosis with skinning of animals suggests a potential role of animal exposure in leptospirosis transmission. Poor qPCR-MAT concordance confirms that accurate case ascertainment requires combined molecular and serological diagnostics.