Spatial structure and demographic decoupling of chikungunya transmission and severity in Brazil, 2015 to 2025

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Abstract Brazil bears one of the largest chikungunya burdens in the Americas (more than 1·2 million confirmed cases since 2014), and the 2024–25 wave expanded further south than any prior outbreak. IXCHIQ entered Sistema Único de Saúde (SUS) deployment in February 2026 despite an August 2025 US FDA biologics license suspension over serious adverse events in adults aged 60 years and older; regulatory authorities in the EU (EMA), Brazil (ANVISA), and Canada maintained licensing with revised prescribing guidance requiring individual benefit–risk assessment. Evidence to guide rollout targeting is lacking. We analyzed 1,235,424 confirmed chikungunya cases reported to Sistema de Informação de Agravos de Notificação SINAN (2015–2025) across 5,570 municipalities. A Bayesian hierarchical spatiotemporal model quantified spatial structure and persistence of transmission across municipalities, controlling for national arboviral co-circulation trends. Disease progression was assessed with Cox models stratified by age and sex. Municipal 2024–25 incidence rate ratios and proportions aged 65 years or older (tertiles) defined transmission-control, clinical-preparedness, and combined-priority municipalities. Transmission epicenters shifted from the Northeast (2016–17) to the Central-West (2024–25; peak municipality IRRs >2·7× the national median); clustering and seasonality persisted. Cases concentrated among adults aged 25 to 55, while post-hospitalization mortality rose steeply with age (HR 10·57, 95% CI 7·64–14·62 for ages 80 years and older versus adults aged 20 to 29). Males had faster progression to hospitalization (HR 1·26) and death (HR 1·76, onset to death) despite fewer notifications. The Central-West led transmission yet had lower case fatality among hospitalized cases (3·54%, 81 deaths out of 2,285 hospitalized) than the Southeast (4·95%, 163 deaths out of 3,291 hospitalized), reflecting demographic rather than purely clinical differences between regions. A municipality-level allocation framework classified 832 municipalities as transmission-control priority (high recent transmission, younger population; predominantly Central-West), 832 as clinical-preparedness priority (lower transmission, older population; predominantly Southeast and South), and 461 as combined-priority (high on both dimensions; predominantly Northeast and Southeast).

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