We previously discussed the central role that WHO has played in disseminating information on zika virus through social media following its declaration of a Public Health Emergency of International Concern (PHEIC) on February 1st. It’s been interesting to follow the media coverage on the issue since then. The first thing to note is that there has been a lot of misunderstanding surrounding the interpretation of the PHEIC, in some cases quite understandably. WHO’s statement is clear that the focus of the PHEIC is the unexpected clusters of microcephaly and other neurological conditions such as Guillain-Barré syndrome (GBS) in Zika-affected countries. The specific recommendations relate to the establishment of standardized criteria for diagnosis and surveillance of microcephaly and GBS, and the investigation of the aetiology of these clusters and the putative causal role of Zika virus. The explosive epidemic of Zika virus, affecting 39 countries as of February 12th, is currently associated with relatively mild disease that can currently only be contained through environmental hygiene, control of mosquito breeding habitats and personal protection against mosquito bites. Unlike the Ebola epidemic in West Africa, a known quantity that resurfaced in an unusual, primarily densely-populated urban context, this latest PHEIC resulted largely from what is not known about zika virus and its increasingly likely association with certain neurological complications. Some of the confusion is therefore understandable, because although this distinction may seem sensible to WHO, to the general public it’s much less clear what the implications are. The challenge is thus how to rapidly mobilize resources to gather the necessary evidence, while preventing the proliferation of sensationalist media stories and policy recommendations that have little scientific basis but are potentially socially harmful.
We have already seen a number of examples of the latter, including recommendations that encroach on women’s reproductive rights and that could have substantial societal implications, and stories about concerns among athletes ahead of the Olympics in Rio, with no mention of the fact that in most Zika-affected countries, dengue and chikungunya have been circulating for years and are both more probable and potentially more severe causes of febrile illness than Zika virus.
Another cause for concern is the flagrant misreporting of microcephaly and related statistics. A recent BBC story claimed that about 400 confirmed microcephaly cases are thought to be linked to zika virus infection in Brazil. This is based on the ubiquitous statistic of more than 4000 reported microcephaly cases since October 2015. Of these, 1113 have so far been investigated, of which only 17 have direct evidence of zika virus infection. A further 387 were compatible with non-specific congenital infection. It is also clear that of the reported suspected cases, a large fraction were not true microcephaly. This is not surprising – microcephaly is not itself a disease, but a clinical finding of a head circumference that is unexpectedly small according to some reference, commonly in the smallest 0.5% compared with babies of the same gestational age and sex. But determining whether head circumference is small for gestational age is challenging, because foetal growth rates can vary substantially within and between populations, and date of conception for babies is often not known exactly – being off by even one week can make a substantial difference to expected size. It is also increasingly apparent that microcephaly is grossly under-reported. A study published in the Bulletin of the WHO last week reported on a review of over 16,000 births in the Paraiba region of Brazil between 2012 and 2015. Depending on the exact microcephaly definition used, between 4% and 8% of children born over this period had microcephaly, compared to about 5 in every 100,000 live births reported by official statistics. Thus, it is still unclear how much of the recent upsurge in microcephaly is real and how much is an artefact of increased reporting as a result of the suspected association with the zika epidemic.
Some of the scientific commentary has also been unhelpful. Here is an example of an expert quotation from a Forbes article on the causal link between zika and microcephaly:
“In a perfect world, one would want to have an animal model and show that experimentally induced Zika vertical transmission leads to microencephaly,” Hymes said. “Additionally, it would be great to have clear case-control study data between infected and uninfected mothers showing the difference in microencephaly rates, controlling for as many other factors as possible. But I think those are merely ‘nice-to-haves’ and not necessary.”
In fact, establishing a causal link between zika virus and microcephaly, or other neurological complications, is merely the beginning. From a programmatic perspective, quantifying and understanding the extent of the risk is crucial to make reasonable predictions of the impact, formulate an adequate response and prioritise resources. After all, dealing with the long-term impacts of microcephaly does not end at establishing aetiology; countries will also need to figure out how to allocate health and educational resources for those affected. This also raises the issue of proportionality. There is solid evidence, for example, that common infections, including Campylobacter and influenza, can cause GBS. But despite there being recognised control measures for these infections that could prevent cases of GBS, these go relatively unnoticed. In the UK alone, there are over 1000 hospitalisations for GBS each year, at least 20% of which are estimated to be due to Campylobacter, and even more are likely to be caused by influenza. Similarly, Paraiba region in Brazil saw between 2400 and 4600 microcephaly cases in 2014, while in the US an estimated 25,000 babies are born annually with microcephaly. Yet these figures are trumped by uncertain data on an as yet inconclusively established association with an exotic re-emerging virus.
In the wake of the Ebola epidemic, there has been much soul-searching and debate around how we should best prepare for when there is an infectious disease-related crisis. Perhaps one way is to pay more attention when there isn’t one.