Clinical and serological findings of Madariaga and Venezuelan equine encephalitis viral infections: A follow-up study five years after an outbreak in Panama

Background Human cases of Madariaga virus (MADV) infection were first detected during an outbreak in 2010 in eastern Panama, where Venezuelan equine encephalitis virus (VEEV) also circulates. Little is known about the long-term consequences of either alphavirus infection. Methods A follow-up study of the 2010 outbreak was undertaken in 2015. An additional survey was carried out two weeks after a separate 2017 alphavirus outbreak in a neighboring population in eastern Panama. Serological studies and statistical analysis were undertaken in both populations. Results Amongst the originally alphavirus-seronegative subjects (n=35 of 65), seroconversion was observed at a rate of 14.3% (95% CI: 4.8%-30.3%) for MADV and 8.6% (95% CI: 1.8%-23.1%) for VEEV over 5 years. Amongst the originally MADV seropositive subjects (n=14 of 65), VEEV seroconversion occurred in 35.7% (95% CI: 12.8%-64.9%). In the VEEV seropositive subjects (n=16 of 65), MADV seroconversion occurred in 6.3% (95% CI: 0.2%-30.2%). MADV seroreversion was observed in 14.3% (95% CI: 1.8%-42.8%) of those originally seropositive in 2010. VEEV seroconversion in the baseline MADV-seropositive subjects was significantly higher than in alphavirus-negative subjects. In the population sampled in 2017, MADV and VEEV seroprevalence was 13.2% and 16.8%, respectively. Memory loss, insomnia, irritability and seizures were reported significantly more frequently in alphavirus-seropositive subjects than in seronegative. Conclusions High rates of 5-year seroconversions to MADV and VEEV suggest continuous circulation of both viruses in Panama. Enhanced susceptibility may be conferred by MADV towards VEEV. We provide evidence of persistent neurologic symptoms up to 5 years following MADV and VEEV exposure. summary We estimate seroconversion rates over a 5-year period to Madariaga (MADV) and Venezuelan equine encephalitis (VEEV) alphaviruses in Panama. Individuals with MADV antibodies seroconverted to VEEV at a rate greater than individuals who were alphavirus-negative at baseline. This was not observed in individuals with VEEV antibodies, suggesting asymmetric cross-immunity. Neurological sequelae were reported more frequently by MADV and/or VEEV seropositive-versus seronegative subjects.