Taking the Bite Out of Zika

By Joe Hanson in Features, May | June 2016, Special on April 29, 2016 at 9:40 am | 1 Comment

We don’t know everything about the Zika virus—but we may know how to stop it.

My wife is the mosquito magnet in our family. We have a running joke about how lucky I am to have her around since she keeps me from getting bitten (my wife finds this considerably less funny than I do). But this year, we’re not joking. Not after we found out about Zika.

Since late 2015, thousands of babies in northeastern Brazil have been born with microcephaly, a rare birth defect characterized by an abnormally small skull and underdeveloped brain, and the Zika virus, transmitted by infected mosquitoes, is believed to be the cause. Only a few isolated cases of Zika have touched down in the United States so far, but with the Texas mosquito season upon us and the 2016 Summer Olympics in Rio de Janeiro set to begin, many in Texas and along the Gulf Coast are wondering if they’ll be next.

University of Texas researchers are among many scientists scrambling to keep another exotically named disease outside our borders. With the 2014 Ebola outbreak still fresh in their minds, some are asking why we keep finding ourselves in this position.

Zika is named for the Ugandan forest where the virus was first isolated in 1947. The earliest known human infections showed up in 1952, but only 14 cases were reported prior to 2007, as Zika flared and fizzled across Africa and Asia. A 2013 outbreak in French Polynesia infected thousands, but a significant uptick in microcephaly didn’t follow, although doctors there saw about eight times the normal cases of Guillain-Barré syndrome, which can cause paralysis. Scientists aren’t sure what makes the Brazil outbreak so different.

Sahotra Sarkar is a professor of integrative biology at the University of Texas at Austin. He finds Zika’s history puzzling. “If the disease has been around for 70 years on and off in humans,” he says, pointing to the sudden rise of microcephaly in Brazil, “why wasn’t this seen earlier?”

Sarkar has been modeling the spread of tropical diseases for years, but admits that he and other experts didn’t see this coming. “It’s a big mystery to me. I don’t think anybody has any idea why such an extreme set of cases began appearing last year.”

He is certain that Zika deserves attention here at home. At least one mosquito species capable of carrying the virus is established between Florida and Texas, and Sarkar’s models show that if other domestic mosquito species become vectors for Zika, the virus is capable of reaching all the way into Canada.

Peter Hotez joins Sarkar as one of the few people who knew about Zika before 2015. As head of the National School of Tropical Medicine at Baylor College of Medicine in Houston, obscure diseases are his job. “Honestly, up until six months ago, Zika was an additional slide you added to your lecture about arboviruses,” Hotez says. “People did not think this was a terribly important infection.”

You may recognize some other arboviruses. This group (literally arthropod-borne viruses) includes insect-transmitted infections like West Nile, Dengue, yellow fever, and chikungunya. Each differs in its biology, but all arboviruses share a common life-cycle, alternating between biting insects and the animals they feed on.

Owing to its unremarkable symptoms and unfortunate alphabetical placement, Zika was always at the bottom of the arbovirus list.

“This was a very obscure virus that was causing limited epidemics throughout the world,” says Nikos Vasilakis, an infectious disease researcher at UT Medical Branch in Galveston. “If you would have told me two years ago that Zika would have caused this epidemic, I would have laughed.”

But then came the images of sick babies, with their heads, almost too small to believe, cradled in the hands of distraught mothers, and no one was laughing.

Brazil’s birth defects began to show up in October of last year, and by November the nation was in the midst of a full-blown public health emergency, one that has since spread through Colombia and across Central America into Mexico and Haiti.

The Brazilian microcephaly cases showed a disturbing trend: The mothers had all been infected with Zika virus while pregnant.

Of course, correlation does not equal causation, so scientists were initially cautious when drawing direct connections between the virus and birth defects. But by February 2016, microscopic Zika virus particles had been collected from fetuses, amniotic fluid, and newborn babies alike. And on April 13, in the face of mounting evidence, the Centers for Disease Control left little room for doubt. “It is now clear that the virus causes microcephaly,” CDC director Tom Frieden announced, adding that microcephaly could be just “the tip of the iceberg” and that researchers are looking into whether Zika could cause other birth defects as well.

Though it could still take months or years before scientists understand exactly how Zika causes microcephaly, this is more than enough evidence for Hotez. “I would not delay any public health control measures while we’re waiting to dot the last ‘i’ and cross the last ‘t’,” he says.

Most experts share that cautious urgency, but it shows just how little we know about the virus. In February, Frieden tweeted a photo of a slim stack of papers with the comment, “Entire world literature on Zika—50 years of neglect.” Scott Weaver, another infectious disease expert at UTMB, wrote one of those papers. He published a 2009 report listing Zika as a future arboviral threat, but Weaver is quick to deny any prophetic “I told you so” moments.

“If you had asked 100 people who worked on these viruses, ‘What do you think the threats may be?’, not very many people would have mentioned it,” Weaver explains. “It wasn’t until microcephaly started showing up in Brazil that this was considered a serious public health issue.”

More than 100 cases have since been carried into the United States by travelers returning from affected areas, but Zika has so far failed to spread within our borders. Of course, the U.S. mosquito season is just getting started.

Zika’s insect of choice is a mosquito named Aedes aegypti. “Aedes aegypti was the mosquito in my yard last fall,” says Alex Wild, curator of entomology at UT-Austin. This fact has many people wondering if what’s happening in Brazil might also play out here.

When I ask Wild how to pick out Aedes aegypti in my backyard, he describes a small, brown mosquito with a white-flecked body and a distinctive lyre shape across its back. It turns out I’m not much good at identifying mosquitoes since I tend to only collect flattened specimens, but it’s likely that Aedes aegypti lives where I do.

Thankfully, only a fraction of the more than 3,000 known mosquito species bite humans. When a mosquito inserts its dagger-like mouthparts to take a bloodmeal, it injects a tiny amount of saliva, containing chemicals that prevent the insect’s sanguine snack from clotting. The virus, transmitted along with that saliva, then tricks the host’s cells into making thousands of copies of itself.  After a second mosquito bites this infected host, the virus enters a new set of salivary glands, ready to repeat the cycle.

I ask Vasilakis to lay out what it would take to get a Zika outbreak in Texas. “It would not be a simple event,” he explains.

Imagine an infected traveler steps off a plane at George Bush Intercontinental Airport. They then make their way to some area of Houston that’s home to a high concentration of Aedes aegypti, and donate some blood to a hungry mosquito. This is just the first step. It takes about two weeks before the virus makes its way to the mosquito’s salivary glands, where it can be passed to another person. These viruses don’t spread directly among the mosquito population, but rather have to be constantly shuttled from mosquito to human to mosquito to human and so on. That means even in an area where Aedes aegypti is common, it takes a lot of bites to ignite an epidemic.

“It doesn’t matter if you have the mosquito population here in the U.S.,” Vasilakis says. “It doesn’t matter if we have it in the human population. What does matter is our habits.”

When it comes to habits, draining standing water and wearing mosquito repellant are two that Wild recommends to fight off any mosquito, infected or otherwise. “The game with these diseases is you really need to get the biting rate down,” he says. “You don’t actually need to get rid of all the mosquitoes, you just need there to be few enough of them that you knock transmission down.” Gutters are a particularly overlooked breeding ground, Wild says. “All it takes is one jerk in your neighborhood not cleaning the gutter and there you have them.”

Ridding Earth of mosquitoes would indeed be impossible, but scientists are working on ways to eradicate just those species that most threaten humans. The most famous of these efforts, bioengineered mosquitoes whose larvae carry suicide genes, is currently being tested in Brazil. UT-Austin biologist David Herrin is developing another method that he thinks will be cheaper to deploy and will control more mosquito species at once. Herrin has inserted mosquito-killing genes into an algae that mosquito larvae eat. When this algae is dispersed in water where mosquitoes breed, the larvae die before maturing. While some mosquitoes are important food sources for insects and bats, Aedes aegypti isn’t native to the Americas, and isn’t likely to be missed. But even this technology is years away from being ready.

For now, Wild believes our comfortable lifestyles may be our best defense. “Texans love to sit in their air-conditioned buildings, go in their air-conditioned cars to their air-conditioned places of work, traveling around in these little capsules, maybe being exposed to mosquitoes on Saturday and Sunday for a bit,” he says. “But that’s a really different situation epidemiologically than coastal Brazil where people are living outside and basically exposed all the time.”

But Hotez isn’t buying the “have air conditioning, won’t travel” idea. He believes we’re overlooking a huge Zika risk factor right in our own backyard.

Aedes prefer to breed in small pools of standing water rather than vast swamps—think discarded plastic bottles or the nooks and crannies inside a junked-out car. Aedes albopictus mosquitoes, a cousin of Aedes aegypti, were actually imported to the United States via puddles inside a shipment of used tires. Now imagine, surrounding that trash-strewn scene are dilapidated houses, with broken windows and no screens. This is the ideal breeding ground for Aedes mosquitoes and the tropical diseases they carry, and you don’t have to look to sprawling Brazilian favelas to find it. Just look to a northeast corner of downtown Houston.

The Fifth Ward is one of the poorest places in Texas, home to many of the more than one million American households surviving on less than $2 a day. Hotez estimates that in such poverty-ridden places, more than 12 million Americans are currently infected with a neglected tropical disease.

“Most of the world’s neglected diseases are actually among the poor living in wealthy countries,” Hotez says. “We’ve got to recognize that the wealthiest countries are highly susceptible. It’s mostly the poor in wealthy countries that will get hit the hardest.”

Such diseases are notoriously underreported in the U.S., either because those infected lack access to medical care, or they are otherwise hesitant to contact medical authorities.

Sarkar has seen this all play out before. He explained that an insect-borne infection called Chagas disease had only been seen in Texas a handful of times before 2010, but when researchers looked more closely, they uncovered hundreds of unreported cases, many among undocumented immigrants.

“They’re worried there is such ill feeling toward them that they will be reported to the federal authorities,” Sarkar says. “The current rhetoric in politics is not exactly helping this stuff.”

As long as public health officials continue to ignore these pockets of vulnerability, Hotez fears for the Gulf Coast. On March 2, he delivered a sober warning before the U.S. House of Representatives: “It’s not going to be easy to track outbreaks of Zika. If the observation holds that most people with Zika show mild or no symptoms, without actively looking for the disease in mosquitoes we might not learn of a Zika outbreak on the Gulf Coast until babies with microcephaly appear next fall or winter in our obstetrical wards and labor and delivery suites.”

Mustapha Debboun is working to make sure that doesn’t happen. The head of the Harris County mosquito control office and former Army colonel deploys his troops weekly to collect mosquitoes and test them for disease. This is business as usual in a city that’s played host to West Nile and other viruses, but this year they are working closely with UTMB geneticists to screen for Zika.

Debboun’s teams are also working in neighborhoods like the Fifth Ward to clean up trash and debris, but it’s unclear whether just fighting mosquitoes will be enough to halt Zika or another arbovirus. “This is the million-dollar question,” Vasilakis says. “I really don’t think we can prevent that. Epidemics happen all the time, especially in South American countries where there are a lot of socioeconomic factors that breed these epidemics.”

In addition to mosquito control, Vasilakis and others believe breaking these cycles of disease will ultimately require an effective vaccine. But if we wait until after an epidemic begins to develop one, it will already be too late.

Hotez points to 2014’s Ebola epidemic as a stark reminder of what happens when we play catch-up with a tropical virus. “The technology to make the Ebola vaccine was published in 2003, and it sat there for a decade because there’s no commercial interest,” Hotez explains. “The model is broken.” By the time serious vaccine trials began in 2015, Ebola had killed more than 11,000 people.

Researchers like Vasilakis admit that neither governments nor private companies alone can commit the billions of dollars required to develop vaccines and other tools, but he thinks the academic, private, and public sectors should develop more coordinated efforts, a “divide and conquer” mentality.

Such public-private partnerships are already at work in the fight against Zika. With help from the Gates Foundation, Tim Riedel and his team of UT-Austin undergrads are developing a DIY device they think will make tracking Zika virus in Aedes aegypti populations much easier than it is today.

“Not everyone has a full molecular lab. What we’re trying to offer is you don’t need that lab,” Riedel says. Their device can be carried in a backpack and runs off a 12-volt battery, and with it, “people can get data back to decision-makers’ hands quickly and stay ahead of this or whatever next year’s emerging disease is.”

No one knows if their DIY approach will prove effective against Zika, or the next virus, but it’s a refreshing effort.

Zika is just one of many invisible diseases whose burdens fall on the world’s helpless, trapping them in continuing cycles of poverty and pain, and it won’t be the last to press at our border.

“This is a country filled with travelers and immigrants,” Sarkar says. “Every disease that occurs elsewhere in the world may end up here.” To him and the other scientists working to bring these threats into the light, it’s apparent that we can no longer treat these problems like they’re a world away.

Photos from top:

A team of specialists fumigates the city of Mérida in Mexico’s Yucatán peninsula in hopes of detecting and eliminating breeding grounds of the Aedes aegypti mosquito, carrier of the Zika Virus; Hugo Borges/Notimex/NC via ZUMA Press

Integrative biology and philosophy professor Sahotra Sarkar says the Zika outbreak is less dangerous than the Ebola outbreak in 2014; Joshua Guerra, Daily Texan Staff

Manuelly Araujo da Cruz was born with microcephaly in Rio de Janeiro. Her mother, Leticia Araujo, caught the virus during her third month of pregnancy; Antonio Lacerda/EFE via ZUMA Press

Residents of the Antimano sector of Caracas, Venezuela, wait outside as their homes are fumigated against the Aedes aegypti mosquito on Feb. 19, 2016. By the end of January, the country had 4,500 suspected cases of Zika; Cristian Hernandez/Xinhua via ZUMA Wire

Tags: research, zika, zika virus