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Abstract
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 2 weeks after a separate 2017 alphavirus outbreak in a neighboring population in eastern Panama. Serological studies and statistical analyses were undertaken in both populations.
Results
Among the originally alphavirus-seronegative participants (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. Among the originally MADV-seropositive participants (n = 14 of 65), VEEV seroconversion occurred in 35.7% (95% CI, 12.8%–64.9%). In the VEEV-seropositive participants (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 who were originally seropositive in 2010. VEEV seroconversion in the baseline MADV-seropositive participants was significantly higher than in alphavirus-negative participants. 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 participants than in seronegative participants.
Conclusions
High rates of seroconversion to MADV and VEEV over 5 years suggest frequent circulation of both viruses in Panama. Enhanced susceptibility to VEEV infection may be conferred by MADV infection. We provide evidence of persistent neurologic symptoms up to 5 years following MADV and VEEV exposure.
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Details

1 Department of Zoology, University of Oxford, Oxford, UK; Department of Research in Virology and Biotechnology, Gorgas Memorial Institute of Health Studies, Panama City, Panama
2 Department of Research in Virology and Biotechnology, Gorgas Memorial Institute of Health Studies, Panama City, Panama
3 National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
4 Department of Epidemiology, Ministry of Health, Panama, Panama
5 Clinical Research Unit, Gorgas Memorial Institute of Health Studies, Panama City, Panama
6 Department of Research in Emerging and Zoonotic Diseases, Gorgas Memorial Institute of Health Studies, Panama City, Panama
7 Institute for Human Infection and Immunity, Department of Microbiology and Immunology, Department of Pathology, and World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, Texas, USA
8 MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK; Department of Statistics, University of Oxford, Oxford, UK
9 Division of Infectious Disease and Global Medicine, Department of Medicine, University of Florida, Gainesville, Florida, USA