Abstract
Since its introduction to the Western Hemisphere in 1999 in New York City, West Nile virus (WNV) has spread throughout the continental USA and moved into Canada, Mexico, Caribbean, and Central and South Americas. While WNV has caused ~7 million human infections and >59,000 cases in the USA and >6,000 cases in Canada, only few human cases have been reported in Latin America. Due to the cross-reactivity of anti-envelope antibodies, the detection of WNV infection by serology to explore its epidemiology in Latin America, where multiple flaviviruses co-circulate, remains a challenge. Previously, we reported that anti-premembrane (prM) antibodies can distinguish between four flavivirus (WNV, dengue, Zika, and yellow fever viruses) infections. In this study, we examined 73 samples from 40 Zika cases from a pediatric cohort in Nicaragua using Western blot analysis and detected anti-prM antibodies to WNV in three participants in samples collected between 2016 and 2017, suggesting previous WNV infection prior to ZIKV infection. Analysis of available archived samples revealed anti-WNV prM antibodies in the earliest samples (2007-2009), which were further confirmed by plaque reduction neutralization test, suggesting that they were infected by WNV prior to 2007-2009. Our report of WNV infection in three Nicaraguan children, corresponding to a seropositive rate of 7.5%, highlights the transmission of WNV in humans in Central America prior to 2007. Future studies with improved serological tests for WNV surveillance in Latin America are needed to enhance our understanding of the epidemiology and transmission of WNV in the Western Hemisphere. IMPORTANCE: Since its arrival to North America in 1999, West Nile virus (WNV) has caused multiple outbreaks in birds and humans, with thousands of human cases in the USA and Canada, whereas in Latin America, WNV has mainly been detected in birds and horses with few human cases. Due to cross-reactivity of anti-envelope antibodies among different flaviviruses, detection of WNV infection by serology to explore its epidemiology in Latin America remains a challenge. Previously, we reported that anti-premembrane antibodies can discriminate four flavivirus infections using Western blot analysis. Based on anti-WNV premembrane antibodies and confirmation by neutralization test, we report three Nicaraguan children with WNV infection, corresponding to a seropositive rate of 7.5%. Our findings underscore the transmission of WNV in humans in Central America and the application of improved seroepidemiological tools to address the knowledge gaps on the prevalence and distribution of WNV in Latin America and the Western Hemisphere.