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 (conservative) or ≥1:200 (lenient)) in paired sera. Risk factors were identified by multivariable logistic regression.

Results

Among 330 AUF patients, acute leptospirosis prevalence was 27.0% (95% CI 22.3–32.1; conservative) and 32.7% (95% CI 27.7–38.1; lenient), comparable to malaria at 30.3% (95% CI 25.3–35.3), with co-infection in 8.8% (95% CI 5.7–11.8). 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 (MAT titre ≥1:100) was 35.8% (95% CI 30.6–41.2); L. interrogans serovar Bataviae was predominant, reported for the first time in Uganda. Skinning animals (aOR 5.19, 95% CI 1.40–21.16) and mosquito exposure (aOR 2.31, 95% CI 1.17–4.70) 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.

Author Summary

Fever is one of the most common reasons people seek care in East Africa, and malaria is almost always the first diagnosis considered. But many patients with fever do not have malaria, and we wanted to understand what else might be causing their illness.

We studied 330 patients with fever at two health facilities in Hoima, western Uganda, testing blood and urine for leptospirosis, a bacterial infection spread through contact with urine from infected animals such as cattle, pigs, and rodents. We found nearly one in three patients had leptospirosis, almost identical to malaria prevalence in the same patients.

People who reported skinning animals were five times more likely to have leptospirosis, pointing to animal contact during slaughter as a key transmission route. We also identified a strain of the bacteria not previously documented in Uganda, with livestock as the most likely source.

Leptospirosis is treatable with doxycycline, a widely available antibiotic, but it is not included in Uganda’s national treatment guidelines for fever. Our findings show it should be. Greater awareness and access to testing in Uganda and similar settings could prevent serious illness and death from a disease currently almost entirely missed.