Revisiting Zika

{***Pause/Music***}

{***Noah***}

Coming up on Harvard Chan: This Week in Health…

Revisiting Zika

{***Marcia Castro Soundbite***}

(Most likely it is gonna come back, because the virus is circulating; it is endemic. We just don’t know when)

More than a year after the Zika epidemic attracted global attention, we’ll take a look at its lingering impact, what we’ve learned about the virus, and the likelihood of new cases as we enter summer in the United States.

{***Pause/Music***}

{***Amie***}

Hello and welcome to Harvard Chan: This Week in Health. It’s Thursday, June 8, 2017. I’m Amie Montemurro.

{***Noah***}

And I’m Noah Leavitt.

Amie—it’s now been more than two years since an outbreak of the Zika virus sickened a million people in dozens of countries—most notably Brazil. The epidemic began in early 2015 and was declared a public health emergency by the WHO in February 2016.

{***Amie***}

Zika has been linked to microcephaly in children born to infected mothers. That’s a condition where infants are born with abnormally small heads.

And the virus is also believed to be responsible for a spike in adults with Guillain-Barré syndrome—a neurological disorder that can lead to paralysis and death.

And while Zika is primarily mosquito-borne, research has shown that it can also be sexually transmitted.

{***Noah***}

In November 2016, the WHO declared an end to that public health emergency over Zika virus. But concerns have lingered—especially in the Americas.

{***Amie***}

Just this week the U.S. territory of Puerto Rico said that the Zika epidemic there was over.

Puerto Rico saw more than 40-thousand cases of the virus—making it one of the hardest hit areas worldwide.

{***Noah***}

Brazil was hit hardest—seeing tens of thousands of Zika infections, and more than a thousand cases of infants being born with microcephaly.

Since the epidemic first began, we’ve gained new insight into the origins of the virus.

Zika was first identified in Uganda in 1947—and new Harvard Chan research showed that the virus has actually been circulating silently and unreported on the African continent for the past two decades—highlighting that the disease can persist in humans.

A separate study, from a team at the Broad Institute of MIT and Harvard found that Zika was likely circulating in the Americas for at least a year before the outbreak began in 2015.

{***Amie***}

And to get an update on Zika virus, we spoke with a Harvard Chan researcher who has the spent the last couple of years studying the effects of the virus in Brazil.

Marcia Castro is associate professor of demography in the Department of Global Health and Population.

And she told us that for the moment there is very little Zika activity—both in the Southern Hemisphere, where summer—which is peak mosquito season—has already ended—and in the Northern hemisphere where summer is just beginning.

{***Noah***}

In fact, Castro told us that Chikungunya, another mosquito-borne illness is a bigger issue at the moment.

Still, she says that vigilance is needed because infectious disease outbreaks often ebb and flow.

MARCIA CASTRO: It’s the same with dengue. So dengue– usually we have an epidemic here, and then we have two or three years that it’s endemic, things calm down, and then it comes back. And we have plenty of reasons to expect that Zika would be the same and you have new susceptibles in the area that then can be infected.

We have areas that were not heavily hit before, so then you have even more susceptibles there. Because the truth is the mosquito is still around and this year we have chikungunya and two years ago, we had an outbreak of dengue, so who knows what’s going to come next year. So most likely it is going to come back because the virus now is circulating– it’s endemic– we just don’t know when.

NOAH LEAVITT: And so I know the most notable links with Zika were microcephaly and Guillian-Barre. Has our knowledge of the effects of Zika evolved over time?

MARCIA CASTRO: It is the cause of effect of the congenital Zika syndrome. Microcephaly is just one of the possible manifestations. We are still learning all the different health outcomes that those kids have and that’s the truth.

The vision and hearing problems were pretty obvious in the beginning. The special type of epilepsy was obvious in the beginning, but there are other complications that we are learning now as the kids are aging. The relationship with Guillian-Barre is also, I think, pretty well established in several countries that had Zika before.

So the biology part– I think we’re learning more and more about how it crosses the placenta. It prefers the stem cells and the neuro cells– all of those things we are learning, but I think that the consequences are pretty well established. Probably what we don’t know is if you take a woman that got infected in week x, what is your risk?

And one of the challenges to be able to measure this is we don’t know what the attack rate of Zika is. We don’t know how many people got infected because you have the asymptomatic. And what we need is a very nice serology test that you can go out in the field, test people, and to know if they had Zika, dengue, chikungunya, or any combination of those and we don’t have that yet.

So even if somebody wants to say, I want to do a survey now and see what percentage of the population in the Northeast of Brazil got infected– we don’t have a very good test to do that. And that hampers our ability to really run a model and say for sure that’s your risk if you are in week 27 and you got Zika. We don’t have that yet.

NOAH LEAVITT: And so I know a lot of resources and time had been rapidly pushed into trying to develop a Zika vaccine. Is that still a goal that should be pursued or is it worth investing more money in building up these surveillance systems now while it’s dormant in a sense?

MARCIA CASTRO: Well I guess those things should be happening concurrently. It would be terrific to have a vaccine, but that said there’s all those ethical issues around the vaccines. We cannot test vaccines in pregnant women. Then the question is, would you vaccinate pregnant women? If we have those concerns with antibody-dependant enhancement that the evidence is basically showing if you had dengue before and then you get Zika, you could have a worse infection.

So what are the real implications of vaccinating, particularly the pregnant women. So it would be terrific to have the vaccine, but getting the vaccine– we still would have a lot of steps to move forward to be able to say, now we can go ahead and vaccinate all women, including those who are pregnant, and then the problem is done. That said, we can’t neglect surveillance at all because usually what happens is by the time we react, the problem is so widespread that it’s going to take much more time to solve the problem than if you were really with a good surveillance system to pick up things in the beginning.

NOAH LEAVITT: With Zika coming on the heels of Ebola, there is a lot of talk about how this exposed a lot of fundamental issues with global health systems, especially epidemic disease response. Do you see that any of those concerns have been addressed or are there still major gaps that need to be filled?

MARCIA CASTRO: I think that each time we have an outbreak, it’s going to be a different story. That’s the truth because there is a flavor of politics in the middle you can never predict how those things are going to go. So Brazil– despite all the challenges and all the novelty, all the problems– they put out a response, they came up with money, with resources.

And in the meantime, the US took nine months vote for the money to be used. Now Brazil is completely messy politically. If we have an outbreak, what’s going to happen now? I have no idea.

I don’t even want to think about this because I don’t think it would be good. So I don’t think we have two responses that are the same because of that– because the people are taking the decisions are different actors, different responses. And it could be great, it could be a disaster.

{***Noah***}

Despite those concerns, Castro says there have been some encouraging responses to Zika virus.

For example, in one state, every infant born with microcephaly has been receiving care and long-term therapy.

{***Amie***}

But Zika has also highlighted lingering concerns related to women’s health in Brazil—where abortion is illegal and contraception is difficult to access.

Castro’s research has shown that despite warnings from the government that women should delay pregnancy, Brazil’s birth rate remained relatively stable after the Zika outbreak.

{***Noah***}

And so while we know much more about the immediate health effects of Zika on women and infants, Castro is specifically focusing on the long-term health of those affected by Zika.

MARCIA CASTRO: One thing that has been puzzling me a lot is the care that the mothers also need to receive. One thing is the level of depression among those mothers may be extremely high and then there would be a demand for mental health services that they are not receiving at all. The other issue is those mothers may have other kids and those kids may be receiving less attention or less care, which means that you can impact the development of the older children. And then the mother can end up with both kids, or however many kids she has, with developmental problems because of the inability of giving them the attention they need.

There’s the other thing– that is, the dissolution of unions of households– the lack of income because of all the trips you have to take to provide the care for the children if they had to give up their jobs. We also don’t know what percentage of women had to give up their jobs. So there is a lot of a social impact of the epidemics that we know close to nothing about. And that’s one of the things that, hopefully, this summer we are going to be able to bring light to some of those questions, and then provide this data to the government so they can actually implement some actions that would address those gaps.

NOAH LEAVITT: And so I know some of your research looked at the birth rates post-Zika and found that there really wasn’t the drop in birth rates that was expected. But you did find that there were some changes with regards to the timing of abortions. So what have you found with regards to that when it comes to Zika and birth rates, abortions, contraception?

MARCIA CASTRO: Yes, so one of the challenges in doing this work is that because abortion is not legal in Brazil– with rare exceptions– we don’t have data on that. What we have is women that show up in the hospital with a complication due to an abortion, be it voluntary or induced. And we can use that data as a proxy of problems that are happening because of an abortion.

And there are ways that you can use that data to estimate unsafe abortion, so I’m using that data as a proxy to see do we observe more women showing up at a hospital because of a complication of an abortion? And the other thing is I have a longtime series of monthly births by states in Brazil, so we look at that as well. And I look at the fetal deaths– so do we see an increasing number of fetal deaths because of Zika. So fetal deaths basically don’t change at all– that’s one thing we saw, regardless of the state.

The number of births– what I observed is there is indeed a lower than forecasted number of births. And up to a certain month, it’s still within the confidence interval and once we start reaching September, October 2016, what we are forecasting is significantly lower. And now I’m quantifying how much lower this really is and in which states this is more significant.

And then for some states, what we observe is when you relate the time series of births and the time series of abortions– there is a lag between those years because the conception happened at a certain point and if you go full term, you deliver. And within usually the first trimester there is an abortion, so if you try to see what’s the lag that bring those series together. For some states, it seems that after the Zika outbreak, the lag is earlier, meaning that women would have abortions earlier than the usual, and in some states it’s later.

In fact, this could really go either way– so either you have an infection or you are just afraid that you might have had an infection and you can have an abortion. Or you are, let’s say, beyond the first trimester and then you had a rash or you had an ultrasound that shows a problem and then you decide to have an abortion. So that’s one thing that we’re seeing– for some states there’s no difference, but for some, and in particular, the ones that we’re seeing some difference are states that were hit by Zika.

So now we’re putting all this together, but I think we have at least some initial evidence that there is something going on. What is driving this? If it’s postponing pregnancies, abortion, whatever the reason we cannot nail down. But certainly there is some sort of behavior response, in terms of conception, that is producing a lower number of births than we would expect.

NOAH LEAVITT: Do you think, in some sense, the risk perception was lower in Brazil when it should have been higher and it was higher in the US when the risk perception could have been lower?

MARCIA CASTRO: I think the risk perception was high at the time that everything was in the news. But the catch is Zika, like dengue or any of those vector-borne diseases, they have a seasonality. So when it’s in the news, especially with Zika– so when all those kids are being born, remember those kids were infected months earlier.

So by the time that kids are not being born, it’s probably when you’re in the high season for infection and now you think you don’t have a problem. So there is a lag time and it’s cruel in that sense because by the time you are very afraid, its transmission is going down, but then all those babies are being born. And that’s one of the problems with Zika– that the perception is connected to what’s in the news.

But that does not necessarily match with the season of the disease, which is pretty much the reason why they were so afraid about the Olympics, right? But again, the season during the Olympics was the low season, and sure enough, we had zero cases. But that’s the disconnect and when you were building your perception, you don’t take that into account because a lot of people don’t even know you have a seasonality.

NOAH LEAVITT: And so you mentioned the seasonality– obviously, here in the US, we are heading into that summertime when it is the high time for mosquito-borne illnesses of all varieties. So should there be a higher level of concern in the US? Do you see states, especially Florida, territories like Puerto Rico– do you see them already taking action now to prepare for an increase in cases?

MARCIA CASTRO: Yes. So your best bet in intensifying vector control is exactly before the peak. I don’t think Puerto Rico is going to be an issue because the infection was so widespread that I don’t think you have enough susceptibles to have another major outbreak.

But you take places like in Florida, in Texas, and you could have a small outbreak. So if you intensify now in doing everything– you use larvicides, you try to destroy some of those places that are heavy breeding habitats, you modify the environment. So if you do it now before it really picks up, that’s your best bet.

{***Noah***}

The takeaway message from Castro: In order to prevent Zika virus, the time to take action is now, when the virus is largely dormant.

And that takes the form of mosquito control—which can start in the home.

{***Amie***}

Castro says we should all take action to remove breeding grounds for mosquito larvae—such as eliminating standing water in our yards, or monitoring appliances, such as refrigerators or air conditioners where water can pool.

{***Noah***}

And if you want to learn more about Zika virus prevention, we’ll have some more information and links to resources on our website, hsph.me/thisweekinhealth.