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April 3, 2016

Zika virus: tracking an evolving public health crisis

The World Health Organization has declared the Zika virus outbreak in South and Central America a global public health emergency, citing the potential for the virus to spread rapidly and a lack of vaccines and reliable diagnostic tests. Virologist Dr Edward Wright of the University of Westminster discusses the epidemic, the prospects for a vaccine and the challenges involved in tracking the virus's geographic spread.

By Chris Lo

Zika virus

On 1 February 2016, the World Health Organization (WHO) declared the current Zika virus outbreak, which began in Brazil in early 2015 and has since spread to other countries in Latin America as well as the Caribbean and Mexico, as a public health emergency of international concern. This designation means the epidemic, which infected between 400,000 and 1.3 million Brazilians in 2015 alone according to estimates by the country’s Ministry of Health, is an extraordinary event that also poses a public health threat to other parts of the world.

In many ways, however, the Zika virus outbreak does not follow the same pattern as other serious epidemics such as the recent Ebola outbreak in West Africa that is only now drawing to a close. Rather than posing a direct threat to those who contract it, the Zika virus – which is transmitted by mosquito bite – either presents no detectable symptoms or is limited to relatively mild, flu-like effects.

The emerging threat of the virus is its "implication", as WHO director general Margaret Chan put it, as the possible cause of a number of other serious health conditions.

While scientists suspect there could be a link between Zika virus infection and a serious peripheral nervous system disorder called Guillain-Barré syndrome, the main concern for public health officials is an association between pregnant women who have contracted the virus and microcephaly and other birth defects in their newborn babies. These links have not yet been scientifically proven, but evidence that they exist is building up, with a corresponding rise in birth defects noted in some regions that have been affected by the virus.

The Zika virus, a flavivirus in the same genus as the dengue virus and yellow fever virus, has been known to be endemic to areas of equatorial Africa and Asia since the late 1940s, and over the decades has gradually migrated across the Pacific ocean – causing outbreaks in the Yap Islands and French Polynesia along the way – before exploding into a major epidemic in Brazil. With its lack of obvious symptoms making the tracking of the virus difficult and vaccine development having to start from scratch due to the previous assumption that it presented a low risk, there are still many unanswered questions regarding Zika virus and the best ways to tackle it.

Virologist and senior lecturer in Medical Microbiology at Westminster University Dr Edward Wright lends his insight into the issues being thrown up by the Zika virus outbreak.

Chris Lo: The Zika virus has been known to occur in equatorial Africa and Asia since the 1950s – why has it become such an emergency now?

Dr Edward Wright: That is one of those questions that people are trying to answer as quickly as possible. The short answer is we still don’t know. It could be that you’ve got a population that is unexposed to this virus so they don’t have any immunity to it, and the mosquito that is the vector that transmits the virus from person to person is abundant. It’s found in large quantities in South America. And so it lends itself to the virus being spread very rapidly.

But why this hasn’t occurred in other areas where the mosquito is equally prevalent? That’s something we don’t know at the moment. It’s being looked into, so hopefully in the next few months there will be more information and we’ll have a bit more of an idea of why exactly there has been this explosion, this epidemic.

CL: It has become vital to establish a definite link between pregnant women contracting the virus and birth defects later on, but what makes doing this so complicated?

EW: There is a growing body of evidence – case reports and cohort studies – that is starting to build up and provide more evidence that this link is there. But at the moment, there is still conflicting evidence – in some countries, there isn’t a rise in these birth defects. There is virological evidence where the mothers have antibodies to the virus, and babies have been born with microcephaly.

One study was able to detect the genome of Zika virus in a baby’s neuronal cells, and that baby had microcephaly. But again, that’s one case against however many hundreds of thousands or millions of people who are becoming infected. I think it’s a case of waiting to see how the evidence stacks up. At the start of this year there wasn’t evidence but now we’re getting case reports and cohort reports where they’ve followed a number of women, and they’ve shown a certain percentage of those who are Zika virus-positive – about a third, as one study in the New England Journal of Medicine showed – have experienced births with foetal abnormalities.

CL: If this link exists, why do you think it hasn’t been spotted in the regions where it has been endemic for decades or more?

EW: Again, it’s a very good question and one that people are trying to answer. The first large outbreak that had been recorded was in the Yap Islands [in 2007], and that was a few hundred cases. Looking back, there were no reports of any increase in microcephaly or birth defects. They were able to show that three quarters of the population had antibodies to the virus, but only a very small percentage actually show any clinical symptoms. The next [outbreak] was in 2013-14 in French Polynesia; you had 30,000 or so people becoming infected. Retrospectively they have suggested there was a link in that outbreak between microcephaly and Guillain-Barré syndrome, but it’s very difficult to do these studies retrospectively. While you can look for antibodies, that doesn’t tell you when the person was infected.

But why hasn’t this happened before, and if the links between the virus and birth defects or Guillain-Barré syndrome are real, then why haven’t we seen huge numbers of cases in other areas where we’ve seen this virus circulating? All these unanswered questions are what drove the WHO to declare [Zika virus] as a public health emergency of international concern.

CL: What are the challenges involved in tracking and containing the spread of Zika virus? The lack of fast diagnostic testing has been cited as a complicating factor…

EW: Yes. There are many things that make it difficult to track the virus. In 80% of people, you don’t see any symptoms and in the other 20%, it’s common cold-like symptoms. So tracking the virus through the symptoms is very difficult. The window of detecting someone who has an active infection is very short – it’s about five days, the current reports suggest, that the virus can survive in the blood. So getting someone when they are actively infected is very difficult, because those symptoms are so generic. You’re not going to immediately think to test them for Zika virus, although I’m sure they are now in Latin America and South America.

We don’t have reliable tests that can detect the genome and genetic material of the virus, which is the most accurate way to track the virus as it spreads. These are obviously in development; I think the National Institutes for Health [NIH] in America recently said they’ve got a test that can now differentiate between a number of viruses that are circulating in South America. Zika virus is what’s called a flavivirus, a group of virus that are very similar genetically, including dengue virus and West Nile virus.

So to have a test that can differentiate between the genomes to find out which of those viruses is present is crucial, because the antibody tests, the ones that are available at the moment, aren’t able to do that.

CL: American researchers working towards a vaccine have said it could be another 10 ten years before such a vaccine is approved by regulators and ready to hit the market – would you agree with that assessment?

EW: Unfortunately we’re not in the place where we were, say for example, with Ebola, where thanks to money that had been given for bio-threat preparedness, we had vaccines for Ebola that had gone through laboratory tests. With Zika virus, it wasn’t deemed a biological threat, and so we are pretty much starting from scratch. It was five, six, seven years of work on those Ebola vaccines that happened up until the outbreak.

On average, you could give a figure of ten or 12 twelve years for a [Zika virus] vaccine to go from those initial stages of development through to clinical trials. You could have these vaccines in laboratory tests within a year or two, but getting them through clinical trials and regulations so they can be used on a wider scale is the thing that takes a long time.

CL: Would you say the development of effective vaccines for other flaviviruses like yellow fever virus and, more recently, the dengue virus, could inform the development of a Zika virus vaccine, or even accelerate it?

EW: Because they’re flaviviruses, they have a similar genetic structure and the composition and the structure of the actual virus particles is very similar. With the dengue vaccine, that can be quickly manipulated so you can take out the dengue virus gene and put in a Zika virus gene. I know the NIH in America is doing that, and the Jenner Institute in Oxford is doing similar things with some of the vaccines that they have. So you can work with that information we have from previous closely-related viruses. It’s still relatively unknown how that will react – will it work the same as they dengue virus? You don’t know until you’ve tried but because it’s closely -related, you’d like to think that there’s a better chance that it would.

CL: Outside of developing a vaccine, what potential is there for limiting the spread of the virus through reducing the population of the mosquitoes that carry it?

EW: Yes, I think that’s what people are focussing on at the moment. If you can stop the mosquito from biting people or if you can remove the mosquito from an area, there’s no way that the virus can be transmitted from person to person.

There are trials that have been done with genetically -modified mosquitoes. Oxitec in Oxford has a mosquito that produces sterile offspring – they will die while they are still larvae so they’re self-limiting. So they are released into the population and they have a dramatic effect on the amount of mosquitoes. They’ve done five or six studies, and in each of those areas, the number of mosquitoes present was reduced by 90%. There are also studies where you can infect a mosquito with specific bacteria called wolbachia, and that causes the mosquitoes to die. So there are methods, and controlling the mosquito population and mosquito avoidance is by far the best method that we have at the moment, until vaccines come along.

CL: What role do you think commercial biotech and pharmaceutical companies can play in combating the virus? Is there enough incentive for private companies to start investing in the development of vaccines, antiviral treatments and diagnostic technologies?

EW: Yes, partly because there has been more funding made available by governments, by research councils, by charities to tackle this. This means there’s not so much of a risk for these companies; they can do research and development activities for the diagnostics and for the vaccines. The same goes for academic and public health laboratories.

Prior to Ebola there was very little funding available for these neglected tropical diseases or emerging viruses, but after what happened with Ebola and now that we have Zika, there are various strategies and schemes that have been opened up, and people are now looking into what will be the next thing. The WHO in December last year sent out a call for technologies or platforms that can be developed generically, so not for a specific target, but platforms that could be easily adapted to an outbreak situation. At Westminster [University] we’ve been shortlisted and we’re going to the WHO to discuss this with them further, along with other organisations. Because it’s difficult to predict what’s going to be the next [outbreak], can you develop platforms that can easily, rapidly be channelled and adapted to tackle whatever is going to be the next large cause of outbreak?

So there is the incentive now, there is the awareness of the large impact that these infections can have, and so hopefully with any developments over the next five or ten years, for any outbreaks in the future we will have a diagnostic device that you can develop or adjust within a matter of weeks so you can use it in that outbreak, and a vaccine system where you can quickly change things and have an effective vaccine.

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