An investigation of Zika virus-associated microcephaly in Northeastern Brazil
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Zika virus (ZIKV) had remained a relatively obscure flavivirus until an unexpected series of epidemics that began in Micronesia brought the virus into the forefront of global public health consciousness. Unlike its closely related flaviviruses, such as dengue, West Nile, and Japanese encephalitis viruses, that cause severe diseases, ZIKV causes asymptomatic or mild febrile infections that are dengue-like in infected individuals. However, ZIKV has exhibited teratogenic effects and infection of pregnant women can lead to microcephaly, a neurodevelopmental disorder in newborns. The teratogenic effects of ZIKV was most clearly highlighted during the epidemic in Brazil, due to the alarming 20-fold increase in microcephaly incidence experienced by the northeastern states where the first outbreak of the Western Hemisphere began, and quickly brought this virus into the spotlight. Although public health officials predicted that other Latin American countries would also experience an increase in microcephaly numbers of comparable scale, such an increase was not observed. This thesis seeks to understand the mechanisms underlying what appears to be a relatively out-of-proportion increase in microcephaly numbers in Brazil compared to other ZIKV-affected countries. The role that differences in vector survival and control, women’s behavior, interactions between ZIKV and dengue virus, and timing of the outbreak may have played in causing the different magnitudes of microcephaly in Brazil, Colombia, and the U.S., in particular, is discussed. Understanding the factors that may have caused the abnormally large outbreak of ZIKV and microcephaly in Brazil versus other regions may assist countries that have not yet been affected by ZIKV develop effective programs to prevent future outbreaks and lessen the impact of a potential outbreak on microcephaly numbers. Experiments to elucidate the mechanism by which ZIKV infects the fetus to cause central nervous system damage will provide an understanding to develop safe and effective vaccines that may assist in efforts to prevent future rise in ZIKV-associated microcephaly cases.