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Cambridge University Science Magazine
In mid-2015, media attention shifted from the subsiding Ebola outbreak in West Africa to a new viral epidemic: Zika. Emerging from relative obscurity, Zika virus swept across the Americas within a single year, infecting over 1.5 million people and leaving an unforeseen trail of children born with neurological defects. Coinciding with the Rio 2016 Olympics, the Zika virus epidemic alarmed the scientific community and general public alike. One year after the epidemic, the number of cases has fallen considerably, but important questions remain. How did such an inconspicuous disease rise to prominence so quickly – and more importantly, what advances have been made towards finding a cure?

Zika virus is a small, positive stranded RNA virus of the Flavivirus family, and is primarily spread by the bite of female mosquitoes of the Aedes genus. In almost all cases, Zika virus is either asymptomatic or causes a mild rash-associated fever, with joint pains and headaches. Unfortunately, as revealed by the 2015-2016 outbreak, the virus has been shown to cross the placenta in infected mothers to cause Congenital Zika Syndrome (CZS). This causes a condition known as microcephaly, in which infants show problems in brain development and reduced head size. Zika has also been linked to the development of Guillain Barre syndrome in infected adults; this is an auto-immune disease in which the immune system mistakenly attacks parts of the nervous system, leading to muscle weakness and paralysis. Equally worryingly, Zika can also be sexually transmitted in semen, and has been found to persist in both the male and female genital tracts for up to two months.

The virus was first isolated in a 1947 in a rhesus macaque in the Zika Forest of Uganda by researchers monitoring Yellow Fever.  Despite discovery of human infection in 1954, the newly discovered Zika virus was largely ignored for over fifty years. Further work established that people across Africa and Asia had antibodies against Zika virus, suggesting they had previously been infected, but the lack of overt disease meant even this seemed little cause for concern. As a result, Zika was largely overshadowed by more well-known relatives such as Yellow Fever, Dengue and Chikungunya viruses.

The first sign of something more sinister came in 2007, when an outbreak on the Yap islands in the South-Western Pacific caused around 100 infections. Before this, only 14 cases of Zika had ever been reported. A further outbreak in 2013 in French Polynesia unexpectedly led to over 30,000 cases, and was associated with a number of cases of Guillain-Barre syndrome. However, the full potential of Zika virus was only realised after early 2015, when sporadic cases in northern Brazil developed into a Zika outbreak of unprecedented scale. The Ministry of Health in Brazil declared a public health emergency in October, which was deemed to be of international concern by the World Health Organisation (WHO) in February 2016 after continued spread across the Americas. The outbreak coincided with the 2016 Rio Olympics, which fuelled greater public alarm at the threat of a worldwide pandemic – by this time, however, the number of cases had peaked, and the WHO announced the end of the crisis in November 2016. By this time, the virus had spread to over 92 countries, infecting potentially over 1.5 million people, and had led to a suspected 3,700 cases of microencephaly.

"A major question remaining in the aftermath of the outbreak was simply – why now?"

A major question remaining in the aftermath of the outbreak was simply – why now? The timing of the outbreak, occurring just as the Ebola epidemic drew to its long-awaited conclusion, agitated worries in the general population that public health crises such as these were becoming more frequent and more sinister. These concerns were perhaps encouraged by overly-sensationalist reporting, but as is often the case contain an essence of truth. Multiple possibilities have been suggested for the emergence of Zika: perhaps increased urbanisation and rising population density helped the spread of disease. Likewise, climate change may have helped Aedes mosquitoes survive in more areas – in Brazil, for example, Zika-susceptible mosquitoes are found in 80% of the country, despite covering just a quarter of this area ten years ago. Meanwhile, higher levels of international travel in an increasingly globalised world have allowed infected individuals to carry the disease between increasingly distant populations. The relative importance of these factors is unknown – however, it is clear that these issues are symptoms of far larger global changes that are unlikely to simply disappear. As a result, the 2015-2016 outbreak is unlikely to be the last Zika epidemic we see over the coming years.

This may seem scary – it is – but there is still some cause for optimism. Successful vaccines for similar flaviviruses such as Yellow Fever and Japanese encephalitis virus already exist, and in 2016 multiple organisations around the world embarked on an accelerated vaccine development program. Although we are still a long way from rolling out an effective vaccine, the most recent results have been very exciting and show great promise for the future. One approach uses a candidate DNA vaccine, in which DNA copies of two Zika genes are injected; the protein products of these genes assemble into virus-like particles, which are non-infectious but can still be detected by the immune system. In August 2016, the US National Institute for Allergies and Infectious Disease (NIAID) announced that this vaccine was entering Phase 1 clinical trials. Other strategies include an inactivated Zika virus, or designing vaccines based on less dangerous viruses like VSV that are made to express Zika proteins. Even more excitingly, a paper published in February 2017 showed that an mRNA based vaccine, based on the mRNA for two Zika proteins, leads to the development rapid and durable immunity in Rhesus macaques. Crucially, this vaccine requires only one dose, making it far more suited to use in areas of Africa and South America with severe gaps in healthcare infrastructure. Whilst these vaccines have been shown to be very effective in reducing the number of virus particles in the bloodstream, it remains to be seen whether they suppress viral replication in tissue sufficiently to prevent transmission across the placenta.

The rise of Zika from obscure tropical disease to global public health emergency led to widespread alarm. In the end, some of these fears were misplaced - the epidemic did not spread to Europe, and whilst its spread was startling and the number of children born with microencephaly was significant, the outbreak was smaller than many had estimated. In mid-2016, a wave of stories denouncing Zika hysteria hit headlines; a year on, it is important to reflect critically on the outbreak. If we are entering a period where epidemics such as Ebola and Zika are the norm, then our responses to these early public health crises may be decisive in how we face future challenges posed by infectious disease. Knowing that concerted efforts at accelerated programmes of drug and vaccine development can lead to successes would be very important in epidemics to come. The story of Zika is far from over, but we have already learnt valuable lessons – at the very least, it is encouraging that partially effective vaccines can be developed in such a short time. This is particularly remarkable given how little research had been done in the past on Zika. Whether these advances can translate to effective control strategies, and what this means for how we approach future challenges in infectious disease, mean the implications of the Zika epidemic will be felt in one way or another for many years to come.

Image credit: NASA Goddard Photo and Video