Five Enduring Questions About Zika

by 
from FiveThirtyEight

Zika. It’s the microscopic mascot of the troubled Rio de Janeiro Olympics. It’s an inconvenient reminder of how globalization can affect public health. And for millions of people who just want a healthy baby, it’s the threat you can’t quite see, something vicious moving just outside your peripheral vision. Roughly three years since it’s estimated to have first arrived in the Americas, the Zika virus has become many things to many people. But what Zika is not is unique — what happens with Zika doesn’t stay with Zika.

Zika evolved in sub-Saharan Africa, and it spread around the globe on mosquitoes’ wings. These are traits it shares with a whole army of diseases, such as West Nile virus, chikungunya virus and a resurgent dengue virus.1All of these have benefited in recent years from global conditions that have been a fertile mix for vector-borne diseases, in general — an army of viruses, bacteria and parasites spread by pests such as mosquitoes, ticks and fleas. More urbanization has brought more humans into contact with mosquitoes and wild host animals; more trade has carried infected humans and animals far from home; and more climate weirdness has increased the number of places friendly to the right (or, rather, right wrong) kind of mosquitoes.

Once upon a time — that is to say, in the 1950s — we thought we had these vector-borne diseases under control. Spray enough DDT, kill enough bugs, and the world is safe. Unfortunately, that system didn’t make the world safe from DDT, and as countries backed off insecticide-drenched vector control strategies, the old diseases have resurged. And others, like Zika, have emerged. More than a billion people are infected by vector-borne disease every year, and these diseases account for one-sixth of all the world’s illness and disability, according to the World Health Organization. Much of this happens in the developing world, but increasingly these diseases are affecting the United States, European nations and other countries that are used to thinking of mosquitoes as nothing more than a nuisance.

Zika may seem outstandingly scary right now. We know it can spread via sexual contact, as well as mosquitoes. More than 1,600 babies in Brazil are confirmed to have suffered from in utero contact with the virus — some were stillborn, others born alive but with microcephaly or other disabilities. Meanwhile, in the U.S., more than 400 pregnant women have tested positive for Zika virus, and 15 babies have experienced the consequences. On Friday, health officials in Florida reported that four people with Zika had probably been infected by mosquitoes in the state.

But Zika is just one pixel in a bigger image. It could disappear tomorrow, and we’d still be at risk from emerging and resurging vector-borne diseases. That’s the bad news. But it should also be a source of hope. It means that, the more we learn about Zika, the more we’re also learning about vector-borne disease in general. The questions scientists are asking — and the research they’re getting funded — has implications beyond this single outbreak of a single virus. On the eve of the Olympics, we asked a few scientists who study Zika and similar diseases which questions they’re most curious to answer. These are questions about Zika, but also ones that, if answered, could help us understand the swarm of other diseases it’s connected to.

Why did Zika suddenly explode in the Western Hemisphere?

Zika was first identified in Uganda in 1947 and remained limited to regions of sub-Saharan Africa and Southeast Asia until 2007. But then it started to travel, and as the virus stamped its passport from Asia to islands in the Pacific to South America, it seemed to become more virulent — infecting more people and spreading more quickly. Nobody knows exactly why that happened, said Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine, though scientists have pointed to mutations on a specific gene that plays a role in the virus’s ability to make copies of itself inside its hosts. The Zika that is now spreading in Brazil isgenetically different from the Zika of mid-20th century Uganda.

But Hotez doesn’t think that violent makeover is Zika-specific. At least not completely. If we decide that the change in Zika is all about the genetic mutations, he told me, then we still have to explain why chikungunya — a virus that belongs to an entirely different evolutionary family — has followed the same pattern. Chikungunya rarely kills, but it does cause painful, joint-torquing illness. From 2006 to 2013, there were maybe 28 cases a year of chikungunya in the U.S. In 2014, there were about 2,800. Same thing with dengue. In 1995, nearly 340,000 cases of dengue were reported to the Pan American Health Organization, which collects data from South, Central and North American countries. In 2015, there were more than 2 million cases. This is where the behavior of people and ecosystems — the growth in population densities, the climate change, the world travel — comes into play. Scientists have long believed that those factors have a role in the spread of vector-borne disease. What’s not known is how those factors, which are essentially anthropological, interact with the genetics of both viruses and people.

Also a mystery: the timing. Some vector-borne viruses, including dengue, broke out of Africa to travel the world centuries ago. Meanwhile, though they’re transmitted in the same way as dengue and by the same species of mosquito, local transmission of chikungunya and Zika didn’t occur in the Americas until 2013 and 2014, respectively, said Chris Barker, assistant research scientist of pathology, microbiology and immunology at the University of California, Davis. At that point, the anthropological factors had been in place for a long time, so why then? And why would those two viruses pop up in the Americas at nearly the same time? “If you find the answer to that, let me know,” Barker said.

What’s going on with Zika and the human brain?

West Nile virus does attack nerve cells, and another vector-borne disease called Venezuelan equine encephalitis virus can damage a growing fetus, but Zika seems to stand alone in its ability to cause microcephaly in the children of infected women. That fact is the white-hot source of most Zika-related fears, and it’s orbited by a whole galaxy of scientific questions. “What happens when a baby in its first year of life gets infected and still has a growing and developing brain?” Hotez asked. “Why do some mothers give birth to babies with microcephaly and others don’t?”

Lark Coffey, assistant professor of pathology, microbiology and immunology at UC-Davis, had an even more basic question about Zika’s ability to cause microcephaly: “Is this new?”

We might never know the answer to that, Coffey said, because we don’t know much about the outbreaks of Zika that happened before it made the jump to the Western Hemisphere. That same sort of mystery surrounds the pasts of a lot of vector-borne diseases. Although there have been sporadic Zika outbreaks in African nations over the past 70 years, those outbreaks were poorly documented and don’t seem to have been widespread. Now that Zika has moved to densely populated urban environments in wealthier countries, it’s infecting more people and is under the scrutiny of more eyes and more technology. Before, people might not have seen microcephaly, even if it was happening, Coffey told me. “We have the luxury of finding these things that would otherwise have been missed,” she said.

Money and facts are fast friends. Before West Nile virus came to New York, scientists thought it was carried by only a small number of mosquito species and only really infected birds, and sometimes horses and humans, said Ernest Gould, retired professor of virology at Oxford University and a visiting professor of emerging viruses at Aix-Marseille University in France. But then came the influx of cash. “The result was that, within a year or two, it was realised that more than 60 different species of mosquitoes in the US could transmit West Nile virus,” Gould wrote in an email. “Moreover, alligators, rabbits, frogs and a whole variety of other animal species that had never been known to be infected by WNV were found to be susceptible to the virus.” Who knows what we’ll know about Zika in a couple of years.

Can past infections make Zika worse?

Zika is just one of many vector-borne diseases — and we don’t know yet whether and how those viruses interact with one another in the human body. The same places that have Zika outbreaks are also having outbreaks of related viruses, including West Nile. So what happens if you had West Nile one year and a case of Zika the next?

This is a question that both Hotez and Gould brought up, and Hotez even wondered whether those interactions could have something to do with the risk of microcephaly for a pregnant woman’s child. That’s because of what we know about the way different kinds of dengue virus can interact with each other weeks, months or years later. There are four dengues — distinct genetic subtypes of the virus — and contracting one doesn’t grant you immunity to the others. Instead, the immune response produced by the first infection can help other kinds of dengue invade your body more efficiently later. The result is higher quantities of virus in your bloodstream and more severe effects of the disease. It’s possible, Gould said, that there could be similar effects happening with Zika in people who have already been infected with other mosquito-borne viruses.

How does a virus choose its hosts?

In order to be a vector-borne disease, Zika must be able to exist in both the vector and the other animal it infects. “That poses a lot of difficulty if you think about it,” Coffey said. “Mosquitoes are very different from us. They have cells, but their cells are very different from what a vertebrate has. The virus has to be well-adapted in both kinds of settings, or you have a dead end.” And the difficulty means that viruses like Zika are in the minority — most viruses that infect people are limited to us or to a few closely related species, Coffey said.

So how do you explain the vector-borne lifestyle? It could happen because — different though we are — mosquitoes and humans still share some basic, bare-bones parts of our immune systems. The viruses might just adapt to what we have in common. But even then, it’s still weird. Although some vector-borne viruses such as West Nile are transmitted by lots of different species of mosquitoes and infect many kinds of animals, others, like urban yellow fever, are picky-choosy about both their mosquito species and the animals they infect. Yellow fever is spread primarily by Aedes aegypti mosquitoes, Coffey told me, and its vertebrate hosts are mostly humans and other primates. So what’s the difference between West Nile and yellow fever? And why are vector-borne diseases, in general, so different in their strategy compared with viruses as a whole? “That’s one thing that keeps me in the field,” Coffey said.

Why isn’t Florida full of dengue?

If the first question about Zika and other vector-borne diseases is why they have suddenly exploded around the world, then the last question needs to be this: Why are some countries less susceptible to these outbreaks than others? “Dengue has caused millions of cases outside the U.S. in recent years, and there are regular introductions of infected people into the U.S.,” Barker said. But, by and large, there aren’t outbreaks here. And that’s kind of strange.

The conditions are right, Barker told me. Mosquitoes that transmit the virus live here, at least in parts of the South and West. There are plenty of them. And there’s lots of travel between the parts of the U.S. that should be susceptible and nearby countries where outbreaks exist. There isn’t an obvious reason why dengue outbreaks aren’t happening. “A few studies have pointed to window screening and the tightly sealed houses associated with air conditioning as protective factors that might limit the mosquitoes’ access to people,” Barker said. “But it’s quite surprising the rarity that we have local outbreaks.” What other factors are at play? Barker hopes we can find out. If scientists can answer that question about dengue, it might help us prevent the spread of Zika. And vice versa. We might be inundated with vector-borne diseases, but at least they can teach us something about each other.

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