A Research Blog

In this week’s Research Story of 2016, we turned to Prof Wang Linfa, Director of the Emerging Infectious Diseases Programme at Duke-NUS, for his pick: the association of Zika infection during pregnancy with microcephaly births. Zika took centre stage in 2016, and will certainly continue to be a main character in research on emerging infectious diseases.

The Zika EmergencyBaby and Mozzie

On 1 February 2016, the world woke up to a new public health emergency: Zika. From then, Zika news hogged the headlines for months, with news agencies charting the spread of infection globally and tracking Zika research.   In the past year, this research has established the association of Zika infection during pregnancy with microcephaly births, while reinforcing the link of Zika infection to increased risk of Guillain-Barre syndrome, a disorder in which the body's immune system attacks part of the peripheral nervous system.

Although the Zika virus has been around for decades, with human cases confirmed since the 1960s, it was initially regarded as a rare and relatively benign infection. It was not until 2007 that a Zika outbreak in the Pacific Island of Yap, in the Federated States of Micronesia, increased visibility of the virus to the research community at large. Subsequent outbreaks in French Polynesia, Easter Island, the Cook Islands and New Caledonia in 2013–2014 are what brought Zika research to the forefront, providing evidence that the Zika virus can be sexually and vertically transmitted, while forming the first tenuous links between Zika infection and an increased risk of developing Guillain-Barre syndrome.[1]

Then, Zika hit Brazil in 2015. With the Zika outbreak accompanied by a spike in microcephalic births in the region, the World Health Organization (WHO) was spurred to declare Zika a public health emergency. But, does correlation really mean causation here?

What does the science say?

Following the declaration of a public health emergency, Zika research exploded as scientists raced to learn more about the virus, and uncover the link between Zika infection and neurodevelopment. As scientific evidence mounted, the research community came to a consensus that Zika infection during pregnancy can indeed cause microcephaly.

Studies are currently underway, with a case-control study in Brazil reporting preliminary data strongly indicating that the increase in microcephaly births observed is a result of congenital Zika infection. Prior to the Zika outbreak, Brazil was reporting microcephaly prevalence at a rate of approximately 0.5/10,000 live births; however, during the second half of 2015, the prevalence rate of microcephaly increased dramatically to approximately 20/10,000 live births. These data support the study conducted after Zika outbreak in French Polynesia, which reported microcephaly prevalence at a rate of 95/10,000 women infected with Zika in the first trimester.

Following Zika infection, the virus has been detected in amniotic fluid and neural cells, indicating the ability of the virus to be transmitted vertically, from mother to foetus, as well as, through the blood brain barrier to the nervous system where its effects can be devastating. Specifically, the Zika virus has been shown to infect neural progenitor cells of both human and mouse origin, thereby altering proliferation of these cells and resulting in cell death and cell cycle arrest, which contributes to microcephaly and other neurological complications. In addition, compelling results from animal research show that Zika infection causes microcephaly in mice, as well as neurological damage to monkey foetuses.

What is next?                                                                                                                                                                            

As research continues to build the foundation for which effective vaccines and treatments may be developed to eradicate the ability of Zika to cause human disease, it is also revealing the far reaching consequences of Zika infection on neurodevelopment, continuing after birth where Zika-infected infants exhibit signs of other neurological complications beyond microcephaly. This underscores the gap in our understanding of the true extent of Zika infection on both neurodevelopment and Guillain-Barre risk. In addition, research is continuing to ask questions on the long-term effects of Zika infection on the male sexual organ, and its implications in the sexual transmission of the virus. Finally, are all Zika strains made equal? It remains to be seen whether different strains of the Zika virus are able to cause microcephaly to similar extents.

On 18 November 2016, the WHO might have declared Zika to no longer be a global emergency, but our work is far from done!

[1] Bulletin of the World Health Organization 2016. doi: http://dx.doi.org/10.2471/BLT.16.171082


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