Abstract
BACKGROUND: West Nile virus (WNV) is a mosquito-borne flavivirus that can cause neurological and fatal disease in animals and humans. Since its introduction into the USA in 1999, WNV has become the leading arbovirus in North America. In contrast, no major WNV outbreak has been reported in South America. Our study investigated active WNV circulation in Brazil. METHODS: We examined WNV epidemiological, molecular, genomic, and serological data from Brazil from January 2014 to December 2024. We also conducted WNV testing in 561 patients with febrile illness, neuroinvasive disease, or death between January 2019 and January 2024 in Ceará State, Brazil. Next, we conducted time series, mapping, ecological niche modeling, age-sex distribution, phylogenetic analyses, and statistical hypothesis tests. FINDINGS: Between January 2014 and December 2024, 110 West Nile cases were reported from 13 of 27 Brazilian states. In addition, our retrospective study in Ceará State revealed 12.1% (68 of 561 patients) were WNV cases, peaking in 2023, when 42.6% (29 of 68) of cases occurred. Among WNV cases, 7 (10.3%) had detected WNV RNA in serum, cerebrospinal fluid, or both, whereas 62 (89.7%) were IgM-positive, with 29 presenting with neurological complications, 35 with febrile illness, and four fatalities. WNV cases were reported in all months, with the highest numbers between May and August. Most cases were female (female-to-male ratio, 1.1:1), and the median age of patients was 40 years (interquartile range, 20-57). Our phylogenetic analysis showed that WNV lineage 1a circulated in Ceará State and caused a fatal horse case. Our ecological niche models identified several areas, mainly situated in the Northeast region, linked to a potentially higher risk of human exposure to local WNV circulation. INTERPRETATION: These findings comprehensively described consistent WNV circulation in Brazil and may contribute to informing public health policy, focusing on the strategies to determine the WNV burden in South America. FUNDING: Burroughs Wellcome Fund, Wellcome Trust, National Institutes of Health, São Paulo Research Foundation, Brazilian Ministry of Science, and Brazilian National Council for Scientific and Technological Development.