Leptospirosis Prevalence and Risk Factors Among Patients Presenting With Fever to 4 Healthcare Sites in Sub-Saharan Africa and South East Asia: An International Multisite Observational and Nested Case-Control Study

BACKGROUND: We investigated the prevalence, diversity, and risk factors for acute leptospirosis in the Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE) study.
METHODS: Febrile patients aged >/=2 months in Laos, Malawi, Mozambique, and Zimbabwe underwent a standardized clinical and exposure assessment. Acute and convalescent serum were tested by Leptospira microscopic agglutination test (MAT) and acute plasma by lfb1 polymerase chain reaction. A >/=4-fold rise in antibody titer, or a single reciprocal titer >/=800, or Leptospira PCR positive defined confirmed leptospirosis. The identity of possible infecting strains was investigated by MAT and sequencing of PCR products.
RESULTS: Of 7851 febrile participants enrolled, 134 (1.7%) had confirmed leptospirosis: 88 (4.6%) in Laos, 17 (1.0%) Malawi, 7 (0.3%) Mozambique, and 22 (1.2%) Zimbabwe, and 23 (0.8%) had supportive evidence of leptospirosis. Participants with leptospirosis had greater odds of headache (adjusted odds ratio [aOR] 2.20, P < .001), rash (aOR 1.45, P < .001), conjunctivitis (aOR 3.33, P < .001), and jaundice (aOR 1.75, P < .001); and had greater odds of being older (aOR 1.02 per year, P < .001), working in rice fields (aOR 6.24, P < .001), drinking river water (aOR 5.11, P = .001). Predominant reactive Leptospira serogroups were Ballum and Icterohemorrhagiae at African sites, and Australis in Laos. Identified species were Leptospira borgpetersenii, L. interrogans, and L. kirschneri.
CONCLUSIONS: Leptospirosis was a cause of febrile illness at all sites. Some clinical features helped to identify patients with leptospirosis. Interventions related to rice field work and river exposure may prevent disease. Diverse Leptospira serogroup reactivity was observed and may suggest potential hosts.