July 4, 2018

Pettersson et al. – Emerging Microbes & Infections, May 2018

Zika virus (ZIKV) has attracted much attention globally, primarily because of its association with microcephaly in newborn babies, Guillain-Barre syndrome, acute disseminated encephalomyelitis in adults and transmission via the oral and sexual route. Much attention has been focused on the clinical symptoms, emergence, epidemiology and evolution of ZIKV in the Pacific region and the Americas. However, during 2016 and 2017, many new sequences were submitted from regions in Asia where there had been few previous reports of the presence of ZIKV.

We took the view that a critical and to some extent neglected objective in studies focused on ZIKV, should be to understand how and where the virus circulated during its early stages of evolution and emergence in Asia and what are the possible reasons for its apparent “silent” circulation? Accordingly, we reconstructed a unique dataset focused on sequences from Asian countries, i.e. after its migration out of Africa but prior to its emergence in the Pacific islands and the Americas. Using this dataset, we predicted the evolutionary history and dispersal patterns of ZIKV and analysed their possible epidemiological implications.

In this study, we predicted that, following its emergence out of Africa, ZIKV had most likely been established in South East Asia (SE Asia) since the early 1950s, i.e. significantly earlier than had previously been believed, whilst circulating silently among the human population and adapting to its primary mosquito vector, viz., Aedes aegypti. Furthermore, our study also showed that different countries in SE Asia have experienced different epidemiological scenarios during its spread and emergence. For example, Thailand appears to have experienced multiple introductions as well as being the source of ZIKV in many neighbouring countries. Conversely, the Philippines appear to have hosted a single strain of ZIKV that has circulated for many years.

We also argued that the extended period of silent circulation and long-term presence in SE Asia could be explained by (i) relatively lower vector transmission efficiency of the Asian lineages largely due to a lack of key adaptive mutations when compared with the epidemic Oceanic and tropical American lineages, and (ii) relatively high background levels of cross-reactive immunity in Asians, as the result of a range of antigenically related flaviviruses circulating in this region. This contrasts with the immunologically naïve populations in Oceania and the urban areas of tropical America. Based on the existing evidence and our recent analyses, we believe these are valid interpretations of the present situation of ZIKV in SE Asia.

It is recognised that in some regions of SE Asia, where ZIKV is known to circulate and cause outbreaks, e.g. Pakistan, India, Bangladesh and Myanmar, few field isolates of the virus are currently available. Clearly these regions should be the focus for future field sample collections of viruses and mosquito vectors to enable the development of a more comprehensive understanding of the early dissemination and evolution of ZIKV.

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