The Next Pandemic

The Aedes aegypti mosquito, which spreads dengue, chikungunya, and zika.

In February 2016, Margaret Chan, director-general of the World Health Organization (WHO), declared Zika virus “a public health emergency of international concern.” In a statement, Chan said the 2016 outbreak is an “extraordinary event” and a public health threat to the world.

For decades the virus, transmitted by the Aedes mosquito, affected mostly monkeys in equatorial Africa and Asia. In humans, Zika occasionally caused a mild, flu-like illness. A story in today’s New York Times also reported a case discovered in Texas earlier this week of Zika virus infection transmitted by sex, raising new concerns about how the virus is spread.

Then, something changed. In 2007, Zika started popping up in the Pacific islands, and in 2015, scientists detected the virus in the Americas, where it is now “spreading explosively,” according to the WHO. Most alarming, says Chan, is the possible connection between Zika and microcephaly—babies born with small heads and neurological deficits—and also Zika’s possible link to other neurological syndromes like Guillain-Barré.

BU Research spoke to Donald Thea, professor and director of the Center for Global Health & Development at Boston University’s School of Public Health, about Zika: what do we know and what do we still need to learn?

BU Research: This virus was discovered in 1947, and nobody’s ever freaked out about it before. When did you realize that this might be something bigger or different?

Thea: It was the reports that were coming out of northeast Brazil of microcephaly that concerned everybody. Our Brazilian colleagues noticed that there was a sharp increase in that area. And because it seemed to be concurrent with the outbreak of this virus, they put two and two together and assumed that there was a connection. However, a firm epidemiologic connection is yet to be established.

And that was in October 2015?  

Yes. Preceding that, there had been reports of increases in microcephaly in an outbreak that occurred in French Polynesia in 2013. And that was the first place that, in retrospect, we saw this disease begin to emerge. Prior to that, there had never really been any reports of microcephaly or Guillain-Barré syndrome that I’m aware of.

The microcephaly numbers in Brazil are really high.

I think we have to be a little bit careful about those numbers. The latest numbers seem to indicate that there are about 4,000 cases of microcephaly reported from Brazil. But microcephaly is a syndrome; it’s not a disease, and there are variations in how you define it. It is characterized by a small cranium, a small brain, and poor brain growth. Now, there’s normal variation in head size. So people have gone back and reassessed the first 700 cases out of the 4,000. And they have declassified as microcephaly or found other causes for about 400 of those cases. Those numbers are approximate but it’s really quite interesting. In Brazil, they’re beginning to question the numbers. A 26-fold increase in microcephaly in one year seems to be very, very high. And the term that they’ve used is “almost not credible.”

Still, it appears that there is certainly a big increase in microcephaly. Is there something else that might be causing it?

So that’s part of what we have to be careful about. Microcephaly is quite a rare condition but we do know that there are a number of other infections that cause it. Making the diagnosis of Zika can be tricky, also. It’s not particularly easy to do. You get infected, you become symptomatic, you have virus in your blood, and that virus in your blood lasts for about a week, during which time you can diagnose it with laboratory tests. But because this virus is of the same family as dengue, chikungunya, West Nile, there are cross-reactions.

What’s a cross-reaction?

When you’re infected with a virus, your body mounts an antibody response to that virus. Say you had dengue in the past, and I give you a Zika test—your Zika test may be a false positive, because your body still carries antibodies to dengue that caused the Zika test to be positive. So we have to be very careful about the tests that we use, when we use them, and how we apply them to populations. This is garden-variety disease outbreak surveillance, but it has to be done properly for us to get a really sound idea of what is the actual incidence of Zika in the population.

Is the response from WHO excessive, since we know so little? Is it a result of the widespread criticism on their slow response to Ebola?

I think our experience with Ebola was very sobering. And if, in fact, this relationship between Zika virus infection and microcephaly exists, these are potentially devastating effects on children, on the next generation. And if there is widespread transmission, affecting newborn children, it’s obviously a very, very serious problem and a deeply emotional problem. But as our opinion piece in the Boston Globe indicated, we do think that WHO may have acted prematurely in calling this an international public health emergency.

What are the other central nervous system problems that might be connected to Zika?

There appears to be evidence of central nervous system calcification on ultrasounds of some of the children. There also appears to be diminished natural brain formations. Gyri and sulci are the normal curves and indentations in the brain, and they seem to be different or less in some of these children. But again, we are absolutely at the very beginning of investigating this disease and its effects and cannot yet conclude that these changes are due to infection with Zika.

The vast majority of people who get Zika are asymptomatic, which is also a little bit worrisome. Eighty percent of people who get infected have no symptoms. Twenty percent have the typical syndrome, which is very, very mild. And prior to some of the reports of Guillain-Barré, which need to be confirmed, it’s essentially a very benign illness, not typically requiring hospitalization. So these more profound effects are obviously very worrying.

And those other central nervous system effects have not been verified?

Correct.

Given the report of a sexually transmitted case in Texas, are you more concerned about this mode of transmission?

Yes, a little. One or two cases is a curiosity, more cases are a trend and imply that this might not be a completely rare event. We know that infectious virus exists in the blood for about a week after symptoms begin and this is likely the period when sexual transmission can occur. Thus, it is prudent to abstain from intercourse during, and for a reasonable time after, symptoms subside. Again, we don’t know how long infectious virus remains in the semen and hopefully as more cases are identified, we can learn more about this. But until we have proven no association between  Zika and birth defects, it is imperative that anyone who is pregnant abstain from unprotected intercourse with someone who might be at-risk of Zika and certainly one who is symptomatic. Lastly, we need to remain focused on the mosquito, which will always be the major route of infection, by far.

Will sexual transmission of the disease make it more difficult to prevent outbreaks of Zika?

It will depend on the efficiency of sexual transmission and the length of time that Zika persists in the semen or female genital tract. That said, I doubt that sexual transmission will ever become a major route of transmission. But then again, as we’ve seen with Ebola, Zika also could also be sheltered in the testes and remain in the semen for some time.

So right now the mosquitoes are the big worry, right?

Yes, Aedes aegypti and Aedes albopictus.

Aedes aegypti is the worst mosquito ever. It spreads everything. Right?

Well, for sheer devastation, Anopheles, which carries malaria, is worse. But Aedes is a particularly difficult mosquito because unlike Anopheles, which breeds in clean water, Aedes seems to have an affinity for dirty water. So it tends to breed in small pools of dirty water like you would find in tires in the backyard during the rainy season, or plates, or pots, or any kind. And so urban transmission is more prevalent with diseases of Aedes than is rural transmission.

What measures are being taken to prevent transmission right now? Are people just spraying for the mosquitoes? Are they spraying DEET all over themselves? You can’t be a pregnant woman and spray DEET all over yourself, can you?

Well, you may have to. Brazil has mobilized 220,000 army recruits who are fanning out over the urban and peri-urban area of Rio, where the Olympics are going to be, spraying with insecticides to try to bring the mosquitoes under control. But basically, we have no vaccine; we have no treatment. The only thing we can do to protect ourselves is to wear protective clothing or apply insect repellant, or remove ourselves from areas where the mosquito tends to be active—go behind screen doors, in air-conditioned rooms.

This sounds like a real problem for pregnant women in Brazil.

Potentially it is. And the recommendation by the authorities there to simply not get pregnant is very problematic, because there are all sorts of issues related to the availability of family planning services. Birth control pills and other products can be difficult to obtain, even if you have a highly motivated population.

How is the virus spreading to other countries? Are the mosquitoes, like, piggybacking on people and getting on airplanes?

No, the more important factor is the transfer of the reservoir of the virus. So people who have the virus in their bloodstream travel to an area that does not have Zika, get bit by a mosquito, and then it goes on to bite other people. That is how it starts out.

Not to be too provincial, but do we have these mosquitoes in Boston?

We really don’t have Aedes aegypti in Boston. We certainly don’t have it during the winter, during the fall, during the early spring. However, we do have Aedes albopictus, which is also known as the Asian tiger mosquito. It’s much hardier than Aedes aegypti and has been able to sustain colder temperatures.

It seems like every day, the world map has bigger splotches of Zika on it.

But we have to be really careful, because that could be an artifact in the same way that the microcephaly could be an artifact. It may well be that there had been lots of Zika in these areas, we just never looked for it. It’s not a common test. It’s not a highly available test. It’s a disease presentation that mimics others, looks like dengue, looks like chikungunya. So it may well be that there’s lots of Zika out there that we just never knew about.

So you’re saying a lot of research needs to happen really quickly. How?

Funds need to be mobilized, and national and international bodies like Pan American Health Organization and the World Health Organization really need to step up and convene expert panels so we can get the best and most current information available on the table for everybody to see, and the best minds together to plan out in a structured and rational way to study this disease.

Do you see that starting to happen?

Yes. I mean, the health system and the public health research community in South and Central America is quite sophisticated, and there’s obviously a lot of concern. They’re beginning to do some of these epidemiologic studies. There’s a Phase 1 candidate vaccine that hopefully will be tested sometime during this calendar year. So there’s a lot of effort and energy being mobilized. But we will need more.

We talked a little bit about Ebola and you said it was sobering. But are there things that happened there, lessons learned, that might be applied now?

I think one of the lessons that we learned in West Africa was that it’s important to react quickly. And I think one of the other lessons that we learned is that it’s really important to have global surveillance, and it’s really important to build local capacity to do the kind of surveillance you need to get the earliest warning of these disease outbreaks.

Some experts are saying they’re “concerned” about Zika. But Chan said it’s “alarming.” What are you? Are you concerned or alarmed?

I’m concerned, but prepared to be alarmed. I’m prepared to be alarmed when there’s new data.

What would be the step down from “concerned”? “Relaxed”? Do you think it’s going to drop to “relaxed”?

I don’t think so. When it comes to the kinds of effects that may be linked to this, I don’t think anybody’s ever going to feel relaxed, unless we show conclusively that these devastating effects are not due to Zika. But we should never relax regarding the global nature of infectious diseases. There’s always a new one just around the corner.