Zika’s Long Haul: Tackling the Causes of Human Vulnerability to Mosquito-Borne Viruses

In February 2016, the World Health Organization (WHO) declared the “clusters of microcephaly and other neurological diseases in Brazil” a Public Health Emergency of International Concern (PHEIC).¹ One criterion for a PHEIC is that an event be extraordinary. In this case, the criterion was met by the link—only suspected at the time—between the epidemic and Zika infection, and the many questions that raised. The other criterion is the potential for unchecked expansion, requiring an internationally coordinated response. This was met by the wild-fire speed of the epidemic, as populations were totally susceptible, earlier efforts to eliminate the vector had failed, and the vector was ubiquitous.

WHO lifted the PHEIC declaration in November 2016, because the fundamental questions that made the event “extraordinary” had been answered and the virus was firmly established in many parts of the world. The end of the PHEIC indicated not that Zika was under control but that “WHO, and affected countries, need to manage Zika not as an emergency but in the same sustained way we manage other established, epidemic-prone pathogens, like dengue and chikungunya. We are here for the long haul.”¹

In this issue, one year after AJPH’s Special Section: Zika^2–5 and in dialogue with the article “The Zika Virus Outbreak in Brazil: Knowledge Gaps and Challenges for Risk Reduction,”⁶ we reflect on progress and challenges over the last year.

WHAT DID WE LEARN?

The fast reaction to the epidemic by national and international organizations, funders, and publishers facilitated coordination between affected countries and at-risk countries; protocol harmonization and sharing; planned joint analysis; emergency funding for research; and fast-track publication agreements. Scientists, probably speared on by scientific curiosity, conducted research. Metrics are not a perfect measure, but the remarkable acceleration in the number of scientific publications is clear: using the search terms Zika and ZIKV in the database Web of Science, I found 48 publications up to 2007 (the year of the first reported Zika outbreak, in Micronesia), another 88 up to 2015 (the year the microcephaly epidemic in Brazil was identified), and 1776 since then.

Here is some of what we have learned since the start of the epidemic: Zika virus is neurotropic—it is the cause of the epidemic of microcephaly; it can also cause Guillain–Barré syndrome and a host of other neurological diseases; it is transmitted not only by mosquito bites and from the mother to the fetus in utero but also by sexual contact, blood transfusions, and during birth; there is at least one documented case of person-to-person transmission from a patient with a high viral load. There is clear evidence that the virus can persist for long periods in blood, urine, and semen in a small proportion of cases. Viremia can be longer in pregnant women and affected neonates, and neurological damage may continue after birth. The manifestations of microcephaly associated with Zika confirmed initial reports⁵; the brain image often shows thin cerebral cortex and calcifications (sometimes consistent with fetal brain disruption syndrome); in some cases, it is associated with neurosensory loss of hearing, visual abnormalities, or limb contractions. As neonates with Zika microcephaly grow older, epilepsy, dysphagia, and severe development delays are common.

MICROCEPHALY VS CONGENITAL ZIKA SYNDROME

It is clear that Congenital Zika Syndrome (CZS) involves much more than microcephaly. In a study that followed the first cohort of women who had symptomatic Zika during pregnancy and that examined all their neonates, only about 3.5% of neonates were born with microcephaly, 46% of live births had an abnormal brain image or other abnormal clinical findings, and there was increased risk of miscarriages and stillbirths. The cohort is relatively small, but if this 3.5% to 46% ratio is confirmed in other cohorts, for each baby born with Zika-related microcephaly we can expect 12 cases of CZS, with normal head circumference but with other abnormalities; many will not be diagnosed at birth in routine care. The proportion of affected children could be higher, as neonates that are apparently normal at birth might present later with new features. We should also be prepared to identify rare, long-term effects; for example, whether CZS, like Congenital Rubella Syndrome, increases the risk of diabetes or mental disorders.

WHAT DON’T WE KNOW?

As discussed by Osario-de-Castro et al. in this issue,⁶ one of the challenges for Zika research and clinical management is the absence of validated robust diagnostic laboratory tests. This probably accounts for the lack of repeated, geographically diverse serological surveys, which might tell us more about the course of the epidemic; for example, whether the apparent periods of low incidence are related to variations in mosquito density, seasonality, or to the “exhaustion of susceptibles,” which is one the reasons epidemics end: when most people have been infected and there are too few people still susceptible to the infection to keep transmission going.

WHO has agreed on the profiles for a Zika vaccine: the priority at this stage is a Zika vaccine to be used for mass vaccination during Zika outbreaks to prevent CZS. Development of vaccines for use between outbreaks to eliminate transmission is also encouraged. There are more than 50 vaccine candidates, some with immunity in mice and nonhuman primates. Licensing may be as late as 2020.

New technologies being evaluated for mosquito control include repeated release of infertile male mosquitos, infection of mosquitos with Wolbachia to decrease their life expectancy, and insecticide-treated clothing. But as Osario-de-Castro et al.⁶ suggest, it might be time to tackle the causes of our increasingly dangerous vulnerability to mosquito-transmitted viruses: not just Zika, but others that can lead to epidemics. Although it is not possible to turn the clock back in terms of population mobility and urbanization, it is possible to improve living conditions and to build a future in which all people have homes with screens on doors and windows, a continuous water supply, sanitation and garbage collection, and an environment that is not degraded. As developments since the start of the epidemic suggest, it may be easier to do science than to improve living conditions or to develop public health provision.

REPRODUCTIVE RIGHTS

We must not forget the human face of the epidemic: the women who want to postpone pregnancy or not to continue a pregnancy after a Zika infection, the children born with disabilities, along with their care-givers. One example of how to approach this is a petition to the Brazilian Supreme Court that is still awaiting a decision. The petition, which is based on the Brazilian Constitution’s guarantee of human rights, asks that during this epidemic the government provide guaranteed easy, free, and local access to a contraception method of choice; the legal right to free, safe termination of pregnancy for women infected with Zika; adequate medical care and rehabilitation for affected children; and social protection for affected families. If we want to be consistent with WHO’s call to integrate the Zika response into core public health programs, the guidelines for the support of children with CZS disabilities and their care-givers should be inclusive; by opening newly developed Zika services to people with disabilities resulting from other causes, rehabilitation services can be strengthened for all. Those affected have a voice. In Brazil, requests to international nongovernmental organizations for drugs for medical abortion have doubled since the epidemic began,⁷ and families of children with microcephaly, organized in WhatsApp or Facebook groups, are active in shaping demands for their needs, including better support to access existing services.

A CHALLENGE

What is the role for international public health, and can we achieve all of this in the current political climate, in which austerity is so often chosen over provision of services? This is our gauntlet.