Leptospirosis Rivals Malaria as a Cause of Acute Fever in Hoima, Uganda

Leptospirosis was nearly as common as malaria among adolescents and adults seeking care for acute undifferentiated fever at two health facilities in Hoima, Uganda, according to a prospective health facility-based study published in PLOS Neglected Tropical Diseases. Among 330 patients with acute undifferentiated fever, acute leptospirosis had a prevalence of 27.0% under a conservative case definition (95% CI 22.3 to 32.1) and 32.7% under a lenient definition (95% CI 27.7 to 38.1), compared with malaria at 30.3% (95% CI 25.3 to 35.3). Some 8.8% of patients carried both infections at once (95% CI 5.7 to 11.8).

The study enrolled febrile adolescents and adults at a referral hospital and a health centre in Hoima and followed them convalescently. Blood and urine samples were tested with LipL32 real-time PCR (qPCR), which detects Leptospira DNA, and with the microscopic agglutination test (MAT), the reference serological method. Researchers classified leptospirosis as confirmed under several criteria: qPCR positivity, a single MAT titre of at least 1:800, or a fourfold titre rise or seroconversion in paired sera, with seroconversion defined either leniently as a change from negative or 1:50 to at least 1:100 or conservatively as a rise to at least 1:200.

The two diagnostic approaches told strikingly different stories. qPCR alone found Leptospira DNA in 9.1% of patients, yet seroprevalence, defined as a MAT titre of 1:100 or above, reached 35.8% (95% CI 30.6 to 41.2). Agreement between the methods was low: 63.3% of qPCR-positive cases were confirmed by MAT, while only 24.4% of serologically confirmed cases were qPCR-positive. The authors conclude that accurate case ascertainment in this setting requires combining molecular and serological diagnostics rather than relying on either test alone.

Leptospira interrogans serovar Bataviae was the predominant serovar, reported here for the first time in Uganda.

Risk factor analysis using multivariable logistic regression pointed to specific exposures. Skinning animals was associated with roughly a fivefold increase in odds of leptospirosis (adjusted odds ratio 5.19, 95% CI 1.40 to 21.16), and mosquito exposure was associated with roughly a doubling of odds (adjusted odds ratio 2.31, 95% CI 1.17 to 4.70).

Across sub-Saharan Africa the disease is considered underdiagnosed, and its contribution to acute undifferentiated fever has been poorly characterized, which is the gap this study set out to address.

The authors argue that leptospirosis occurring as frequently as malaria among fever patients in Hoima warrants its inclusion in Uganda’s national febrile illness guidelines. They note that targeted treatment could reduce morbidity, mortality and economic burden, and could also limit antimicrobial resistance by decreasing the use of broad-spectrum antibiotics that are often prescribed empirically when the true cause of fever is unknown.

The findings come with geographic and methodological caveats. The study was conducted at two facilities in a single Ugandan district, so the prevalence estimates apply to that regional setting and cannot be assumed to represent the whole country. The low concordance between qPCR and MAT also means that prevalence figures depend on which case definition is applied, as the conservative and lenient definitions produced estimates differing by nearly six percentage points. Even so, the authors suggest the implications extend more broadly, highlighting the need to include zoonotic diseases in febrile illness diagnosis and surveillance across similar settings.

Subject of Research: Prevalence, risk factors and clinical profile of leptospirosis among adolescents and adults with acute undifferentiated fever in Hoima, Uganda

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

Article References: Kirabo, A. V., Alinaitwe, L., Kobba, K., Ndawula, E. C., Ogwang, J., Kirungi, M., Ndagire, A., Kankya, C., Kakooza, F., Lamorde, M., Mayito, J., & Dreyfus, A. (2026). Leptospirosis occurs as frequently as malaria among adolescent and adult acute febrile patients in Hoima, Uganda: A prospective health facility-based study. PLOS Neglected Tropical Diseases, 20(10), e0014772. https://doi.org/10.1371/journal.pntd.0014772

Image Credits: AI Generated

DOI: 10.1371/journal.pntd.0014772

Keywords: leptospirosis, Uganda, acute undifferentiated fever, malaria, MAT, qPCR, zoonotic disease, Leptospira interrogans, serovar Bataviae, risk factors, diagnostics, febrile illness