5 unanswered questions about Zika

The World Health Organisation (WHO) has declared the Zika virus outbreak in South and Central American a Public Health Emergency of International Concern (PHEIC). It is the first time since the Ebola outbreak that began in 2014 that the WHO has declared this status, and only the fourth time in its history.

A coordinated international response will now see resources concentrated on disease surveillance, mosquito control and research in an attempt to control the spread of infection in the Americas and beyond. But how did a virus that many people had never heard of until a few weeks ago so quickly become a global health concern and what efforts are needed to tackle it?

What is Zika?

The Zika virus was first discovered in a rhesus monkey from the Zika forest, Uganda in 1947. There were very few significant outbreaks of the disease reported before 2007 and since then there have been relatively small outbreaks reported in the Western Pacific, the Americas and Africa, all causing very mild illness and limited epidemics.

Zika belongs to the same family tree of viruses as Yellow Fever, Dengue and West Nile fever – known collectively as Flaviviridae. It is transmitted by Aedes mosquitoes which are present in large numbers in tropical regions including South and Central America, Africa, South East Asia and the Western Pacific.

There has been at least one documented case of sexual transmission of Zika, but these events are expected to be very rare and almost all transmission in the present outbreak is thought to be through being bitten by an infected Aedes mosquito. Given the geographical spread of the Aedes mosquito it’s possible, but not certain, that the virus will spread to all of these regions if efforts to contain it are not successful.

It is thought that the vast majority of people who contract Zika have no symptoms at all or experience only a very mild illness with a fever, rash and aching joints. However, evidence from the current outbreak in South America is beginning to suggest that infection with Zika may cause serious complications during pregnancy.

Microcephaly and other complications

In early 2016, reports began to emerge from Brazil of an unusually high number of babies born with abnormally small heads – a condition called microcephaly. There have been around 4,000 cases reported since October 2015, compared with the few hundred a year that Brazil normally experiences. Health authorities investigating this unexplained increase noticed that the spike in cases overlapped with the areas experiencing the Zika outbreak, suggesting a possible link between the virus and microcephaly. However, although the evidence is growing, this has not yet been proven definitively.

An outbreak in 2013 in French Polynesia also coincided with an unusual increase in Guillain-Barré syndrome – a rare condition where the body’s immune system attacks parts of the nervous system causing muscle weakness and problems with coordination. El Salvador has also reported a similar rise in cases of the syndrome since its first confirmed case of Zika in 2015. Efforts are ongoing to look back at the French Polynesian outbreak to investigate a possible link between Zika and Guillain-Barré.

Unanswered questions

Because there were no recorded large-scale outbreaks of Zika prior to 2007, there are currently many unanswered questions about the virus, how it causes disease in people and the possible complications including for pregnant women. Research is needed to address these questions and also to establish:

The link between Zika infection and microcephaly and, if proven how this process occurs, how many pregnancies are affected and when during pregnancy is the most dangerous time to contract the virus.

The actual number of Zika cases and the geographical spread. This is likely to be difficult as there is no reliable diagnostic test for previous Zika infection and many of the asymptomatic cases go unreported.

Whether something has changed, either in the virus or in the mosquito, or in their interaction, which has led to the sudden rise in the number of cases.

If people who have been infected with Zika go on to have long-term immunity to the virus. This will be important for determining whether a vaccine approach is likely to be successful in controlling the spread of the virus.

How best to control the Aedes mosquito.

Prospects for a vaccine

With Ebola, we were in a relatively advantageous position as several promising vaccine and treatment candidates had already been developed and tested in animals. This allowed scientists involved in the Ebola response to quickly set up human clinical trials of promising drugs and vaccines in the worst affected countries.

Our knowledge of the Zika virus is at a much earlier stage and the fact that the condition appears to be most dangerous for pregnant women makes the prospect of developing preventative vaccines far more challenging.

For ethical reasons, pregnant women are often excluded from taking part in clinical trials of new medical products until their safety has been assessed over many years and in many different populations. Therefore, although vaccine prototypes for dengue and West Nile fever could be adapted towards Zika, and that work has started, assessing these vaccines will be difficult.

Finding a treatment for Zika would perhaps be even more problematic, given that there has been limited success in developing drugs that work well against acute viral infections and the same issues of testing medicines on pregnant women would also arise.

Mosquito control

One of the most effective methods for containing Zika in the medium term is likely to be through controlling populations of Aedes mosquitoes that spread the infection. This may be through traditional preventative measures such as wearing long sleeves, removing standing water where the insects like to lay eggs and ‘fogging’ residential areas with insecticide.

There are also some interesting new methods that involve modifying mosquitoes in a laboratory to inhibit their ability to carry and spread disease. Methods include genetically altering male mosquitoes so that they produce sterile young and infecting the insects with naturally occurring bacteria that stop the virus growing. Field trials of these approaches are already underway in several countries, including Brazil.

For further reading on the Zika virus, the Centre for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota has put together a comprehensive list of resources and literature.