This research was supported by a grant fromSENACYT FID 16-201 to J. P. C. and A. V., Secretar ́ıa Nacional deCiencia y Tecnolog ́ıa from Panama; by the grant for neglected dis-eases studies in Panama 1.11.1.3.703.01.55.120 from the Ministry ofEconomy and Finance of Panama to J. P. C. and A. V.; and byERANet17/HLH-0271. Scott Weaver also supported this studythrough the World Reference Center for Emerging Viruses and Arbo-viruses, NIH grant R24AI120942. Dr. Lescano is sponsored by thetraining grant D43 TW007393 awarded by the Fogarty InternationalCenter of the US National Institutes of Health. J. L. M. is a doctoralcandidate studying an Epidemiological Research Doctorate at Uni-versidad Peruana Cayetano Heredia under FONDECYT/CIENCIAC-TIVA scholarship EF033-235-2015 and also supported by traininggrant D43 TW007393. A. V. is a member of the Sistema Nacional deInvestigaci ́on de Panam �...

Madariaga virus (MADV) has recently been associated with severe human disease in Panama, where the closely related Venezuelan equine encephalitis virus (VEEV) also circulates. In June 2017, a fatal MADV infection was confirmed in a community of Darien Province. We conducted a cross-sectional outbreak investigation with human and mosquito collections in July 2017, where sera were tested for alphavirus antibodies and viral RNA. In addition, by applying a catalytic, force-of-infection (FOI) statistical model to two serosurveys from Darien Province in 2012 and 2017, we investigated whether endemic or epidemic alphavirus transmission occurred historically. In 2017, MADV and VEEV IgM seroprevalences were 1.6% and 4.4%, respectively; IgG antibody prevalences were MADV: 13.2%, VEEV: 16.8%, Una virus (UNAV): 16.0%, and Mayaro virus: 1.1%. Active viral circulation was not detected. Evidence of MAD...