Assessing the global threat from Zika virus

Global spread of Zika virus Zika virus was identified in Uganda in 1947; since then, it has enveloped the tropics, causing disease of varying severity. Lessler et al. review the historical literature to remind us that Zika's neurotropism was observed in mice even before clinical case reports in Nigeria in 1953. What determines the clinical manifestations; how local conditions, vectors, genetics, and wild hosts affect transmission and geographical spread; what the best control strategy is; and how to develop effective drugs, vaccines, and diagnostics are all critical questions that are begging for data. Science, this issue p. 663 Assessing the global threat from Zika virus. BACKGROUND First discovered in 1947, Zika virus (ZIKV) received little attention until a surge in microcephaly cases was reported after a 2015 outbreak in Brazil. The size of the outbreak and the severity of associated birth defects prompted the World Health Organization (WHO) to declare a Public Health Emergency of International Concern on 1 February 2016. In response, there has been an explosion in research and planning as the global health community has turned its attention to understanding and controlling ZIKV. Still, much of the information needed to evaluate the global health threat from ZIKV is lacking. The global threat posed by any emerging pathogen depends on its epidemiology, its clinical features, and our ability to implement effective control measures. Whether introductions of ZIKV result in epidemics depends on local ecology, population immunity, regional demographics, and, to no small degree, random chance. The same factors determine whether the virus will establish itself as an endemic disease. The burden of ZIKV spread on human health is mediated by its natural history and pathogenesis, particularly during pregnancy, and our ability to control the virus’s spread. In this Review, we examine the empirical evidence for a global threat from ZIKV through the lens of these processes, examining historic and current evidence, as well as parallel processes in closely related viruses. ADVANCES Because ZIKV was not recognized as an important disease in humans until recently, it was little studied before the recent crisis. Nevertheless, the limited data from the decades following its discovery provide important clues into ZIKV’s epidemiology and suggest that some populations were at risk for the virus for years in the mid-20th century, although this risk may predominantly have been the result of spillover infections from a sylvatic reservoir. Recent outbreaks on Yap Island (2007) and in French Polynesia (2014) provide the only previous observations of large epidemics and are the basis for the little that we do know about ZIKV’s acute symptoms (e.g., rash, fever, conjunctivitis, and arthralgia), the risk of birth defects, such as microcephaly (estimated to be 1 per 100 in French Polynesia), and the incidence of severe neurological outcomes (e.g., Guillain-Barré is estimated to occur in approximately 2 out of every 10,000 cases). The observation of an association between ZIKV and a surge in microcephaly cases in Brazil and the subsequent declaration of a Public Health Emergency of International Concern by the WHO have rapidly accelerated research into the virus. Small, but very important, studies have begun to identify the substantial risk the virus can pose throughout a pregnancy, and careful surveillance has established that ZIKV can be transmitted sexually. Numerous modeling studies have helped to estimate the potential range of ZIKV and measured its reproductive number R0 (estimates range from 1.4 to 6.6), a key measure of transmissibility in a number of settings. Still, it remains unclear whether the recent epidemic in the Americas is the result of fundamental changes in the virus or merely a chance event. OUTLOOK ZIKV research is progressing rapidly, and over the coming months and years our understanding of the virus will undoubtedly deepen considerably. Key questions about the virus’s range, its ability to persist, and its clinical severity will be answered as the current epidemic in the Americas runs its course. Moving forward, it is important that information on ZIKV be placed within the context of its effect on human health and that we remain cognizant of the structure of postinvasion epidemic dynamics as we respond to this emerging threat. The effect of ZIKV is a function of the local transmission regime and viral pathogenesis. (A) Many countries cannot maintain ongoing vector-mediated ZIKV transmission and are only at risk from importation by travelers and limited onward transmission (e.g., through sex). (B) If conditions are appropriate, importations can lead to postinvasion epidemics with high incidence across age ranges, after which the virus may go locally extinct or remain endemic. (C) There is evidence of ongoing ZIKV incidence in humans over years (e.g., a 1952 serosurvey in Nigeria), but it is unknown whether this is the result of ongoing circulation in humans or frequent spillover infections from a sylvatic cycle. (D) In other areas, ZIKV appears to have been maintained in animals with few human infections. (E) The majority of infections are asymptomatic, and severe outcomes, such as Guillain-Barré syndrome, are rare. (F) However, there is considerable risk of microcephaly and other fetal sequelae when infection occurs during pregnancy. First discovered in 1947, Zika virus (ZIKV) infection remained a little-known tropical disease until 2015, when its apparent association with a considerable increase in the incidence of microcephaly in Brazil raised alarms worldwide. There is limited information on the key factors that determine the extent of the global threat from ZIKV infection and resulting complications. Here, we review what is known about the epidemiology, natural history, and public health effects of ZIKV infection, the empirical basis for this knowledge, and the critical knowledge gaps that need to be filled.