The spread of Zika in Brazil in 2015 ahead of the Rio 2016 Olympic Games and its reported association with microcephaly received much attention. In the event there were no cases at the Games and Zika reports faded as fast as they had arrived. The WHO’s statement that Zika was a global health emergency ended 9 months after it was called and Brazil’s state of emergency was also declared over 6 months later. The virus itself however has continued to spread (see timeline) and it made a brief return to notoriety this month with the first reports of cases in India[1]. As the closely related Dengue virus circulates in India it is very likely that Zika numbers will go up there but whether this should be a public concern remains hard to judge.

Infection of adults by Zika gives a mild aches and pains type of infection which resolves naturally. The issue is surrounding the virus is if women who contract the virus during pregnancy, particularly the first three months of pregnancy, have an increased risk of delivering a baby with fetal abnormalities, the most serious of which is microcephaly. This issue, does it or doesn’t it cause microcephaly, remains unclear.

Some arboviruses, that is viruses transmitted by insect bite, have long been associated with birth defects, particularly in the case of animal infections [2] but viruses that are the most related to Zika are not among them, despite circulating widely. Zika itself has been on the move since the 1950s and no association was reported before the Brazilian epidemic. The virus has been reported to have changed to a pandemic strain during this spread so it is conceivable that the “new” virus has more aggressive properties than the old, and there is some experimental evidence from laboratory studies to support this, but that too doesn’t really explain the differences in the rates of microcephaly reported in different locations.

Zika infection and cases of microcephaly (or Congenital Zika Syndrome – CZS) are tracked by the WHO and updated regularly (see [3]) but the numbers are hard to understand. Adjacent countries with similar numbers of claimed Zika infections, all by the pandemic strain, have hugely different numbers of microcephaly cases. The Dominican Republic for example claims 345 confirmed Zika infections and 93 cases of CZS, a rate of around 1 in 4 whereas Puerto Rico claims 40,274 cases and only 35 cases of CZS, a rate of less than 1 in 1000. Guatemala states 921 confirmed infections and 59 cases of CZS whereas Costa Rica, almost next door, states twice the number of infections but only 5 cases of CZS. Of course these numbers are subject to reporting errors but the reported rates of microcephaly are so different that they leave open the question of whether the virus is involved at all.
This lack of a confirmed relationship between infections and microcephaly was published as a correspondence in the New England Journal of Medicine recently with both Brazilian Ministry of Health and WHO authors [4].  This paper has not been cited as widely as it should, perhaps because, as a correspondence, no abstract appears on PubMed and similar sites, but the study is careful, clear and telling.  The authors plotted the cases of Zika infection for five regions of Brazil over the course of two complete seasons, 2015 and 2016 and co-plotted the number of cases of microcephaly and another condition attributed to Zika, Guillain–Barré Syndrome or GBS. GBS is a complication that can occur following a number of infections not just Zika and its inclusion here acts as sort of control – if there is Zika infection in the population you would expect a certain number of GBS cases to follow, and that is what is observed, for both of the years studied. But what about microcephaly?

The data is quite clear (see figure): microcephaly cases rose about 23 weeks after the Zika outbreak in 2015 (so consistent with births to mothers infected in the first trimester) but there was no such rise in numbers during 2016. There are various hypotheses to explain this discrepancy, perhaps not all the infections were Zika for example, but an obvious conclusion is that the association of Zika with microcephaly has been overstated. Their conclusion states it diplomatically “Further investigations are needed…..to clarify the causal links between arbovirus infections, GBS, and microcephaly in Brazil” – quite.

[1] http://www.firstpost.com/india/zika-virus-reaches-india-who-confirms-3-cases-in-ahmedabad-3488985.html

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581091/

[3] http://www.paho.org/hq/index.php?option=com_content&view=article&id=12390&Itemid=42090&lang=en

[4] http://www.nejm.org/doi/full/10.1056/NEJMc1608612