Endemic and Epidemic Human Alphavirus Infections in Eastern Panama: An Analysis of Population-Based Cross-Sectional Surveys

Abstract

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 MADV and UNAV infection was found near households, raising questions about its vectors and enzootic transmission cycles. Insomnia was associated with MADV and VEEV infections, depression symptoms were associated with MADV, and dizziness with VEEV and UNAV. Force-of-infection analyses suggest endemic alphavirus transmission historically, with recent increased human exposure to MADV and VEEV in Aruza and Mercadeo, respectively. The lack of additional neurological cases suggests that severe MADV and VEEV infections occur only rarely. Our results indicate that over the past five decades, alphavirus infections have occurred at low levels in eastern Panama, but that MADV and VEEV infections have recently increased-potentially during the past decade. Endemic infections and outbreaks of MADV and VEEV appear to differ spatially in some locations of eastern Panama.

Figure 1.

Map of the study sites in eastern Panama: (A) Sampling sites in the Darien Province in eastern Panama. (B) Zoom-in projection of sampling sites on a land-use layer. This figure appears in color at www.ajtmh.org.

Figure 2.

Force-of-infection (FOI) models fitted to Madariaga virus (MADV) seroprevalence data. (A) (Top panels) estimated constant (red) vs. time-varying FOI (blue) for MADV in eastern Panama over 50 years and (B) (bottom panels) fitted and observed seroprevalence. Red lines represent the estimated constant FOI and blue lines the estimated time-varying FOI. In each case, the shading represents 95% credible intervals from the model. The circles’ radii in the lower panels indicate sample size in each 5-year age-group, and the vertical lines represent 95% CIs for observed seroprevalence. This figure appears in color at www.ajtmh.org.

Figure 3.

Force-of-infection (FOI) models fitted to Venezuelan equine encephalitis virus (VEEV) seroprevalence data. (A) (Top panels) estimated constant (red) vs. time-varying FOI (blue) for VEEV in eastern Panama over 50 years and (B) (bottom panels) fitted and observed seroprevalence. Red lines represent the estimated constant FOI and blue lines the estimated time-varying FOI. In each case, the shading represents 95% credible intervals from the model. The circles’ radii in the lower panels indicate sample size in each 5-year age-group, and the vertical lines represent 95% CIs for observed seroprevalence. This figure appears in color at www.ajtmh.org.

Figure 4.

Force-of-infection (FOI) models fitted to Una virus (UNAV) seroprevalence data. (A) (Top panels) estimated constant (red) vs. time-varying FOI (blue) for UNAV in eastern Panama over 50 years and (B) (bottom panels) fitted and observed seroprevalence. Red lines represent the estimated constant FOI and blue lines the estimated time-varying FOI. In each case, the shading represents 95% credible intervals from the model. The circles’ radii in the lower panels indicate sample size in each 5-year age-group, and the vertical lines represent 95% CIs for observed seroprevalence. This figure appears in color at www.ajtmh.org.