Zika virus: a little less speculation, a little more action

Abstract

The Zika virus has recently gone from an obscure infectious agent—first identified in Uganda in 1947—to a global public health emergency as WHO calls for a coordinated international response because of its potential link with neurological disorders. Soon after the Pan American Health Organization (PAHO)/WHO confirmed the first Zika virus infection in the Americas in May, 2015, Brazil and neighbouring countries began reporting a seemingly disproportionate increase in the numbers of cases of Guillain-Barré syndrome and babies born with microcephaly. As alarm continues to grow with the rising number of suspected cases of these disorders, reliable information is in short supply and questions about the neurological effects of Zika virus remain to be addressed. The main question is, if there is a link, why are we only seeing these neurological manifestations now, when the virus has been present in human beings in Africa and Asia for over 60 years? The answer may lie in the size of previous outbreaks and a lack of recognition of new cases of neurological disorders by health authorities at the time. Until the 2007 outbreak on Yap, an island in the Federated States of Micronesia, Zika virus was associated with small and sporadic outbreaks that were often mistaken for other diseases or infections with a similar range of flu-like symptoms. As the virus spread through the South Pacific islands from 2007 to 2014, thousands of symptomatic cases of Zika virus infection were reported to local public health departments. However, even with this increased number of reported cases, retrospectively verifying a suspected increase in neurological disorders with low prevalence in a small population is challenging. Although there are case reports of Guillain-Barré syndrome associated with these earlier outbreaks, detailed scientific reporting is sparse, making it impossible to establish a causative link. The ongoing public health emergency in Brazil presents the largest affected population to date and a unique opportunity to rigorously study the potential link between Zika virus and Guillain-Barré syndrome, and microcephaly. There are reports of detection of Zika virus in fetal tissue, and in amniotic fluid and placenta in infected pregnant women; however, the missing evidence supporting a causal association between Zika virus and these neurological disorders will need to come from the combination of large-scale epidemiological studies and reliable laboratory data. First, epidemiological studies in geographical areas with a high Zika virus burden and those with the highest number of reported cases of Guillain-Barré syndrome or microcephaly should be examined for overlap. To address the association with Guillain-Barré syndrome, case-control studies need to be done to look at serum antibodies against viral epitopes and cross-reaction with epitopes on human peripheral nerve; for microcephaly, pregnant mothers from affected areas need to be examined for evidence of past Zika virus infection, and viral load in amniotic fluid and placenta should be measured. Fetal brain tissue from microcephalic infants who died should also be examined for evidence of Zika virus infection. Following PAHO/WHO's initial reports of increased neurological disorders in Brazil, the US Centers for Disease Control and Prevention (CDC) forged collaborations with the Brazilian Government to provide local assistance in developing protocols and undertaking rigorous investigations to establish causality. An initial investigation into a reported increase in cases of Guillain-Barré syndrome in Salvador, in Bahia state, has recently been completed, and the Brazilian Government and CDC are working on analysing the data with the goal of disseminating the epidemiological and clinical findings as quickly as possible. Laboratory data will take longer to analyse, but will be reported as soon as results are available. The microcephaly epidemiology investigation in Brazil is set to begin in late February and end in March, with preliminary results disseminated as soon as possible. With 30 countries reporting active infection at the time this editorial went to press, more studies on the potential neurological effects of Zika virus are expected. Quick collection and dissemination of new data are paramount, but it is essential that research protocols are rigorous so as to obtain reliable and meaningful data. Although the public health departments of countries where investigations into Zika virus are done are likely to report their national findings separately, coordination of case definitions and protocol designs may allow for combination of data and a more robust analysis of these fairly rare neurological outcomes. It is hoped that direct comparison of the Zika virus studies will be possible and experts will soon be able to establish whether Zika virus infection is associated with Guillain-Barré syndrome or microcephaly.