Racing Zika

In May, 2015, Uriel Kitron was in Salvador, Brazil, studying dengue when a new virus showed up. At first he brushed it aside like the pesky mosquito that carried it. With his Brazilian collaborators, he published several papers—among the first—on the widespread Zika virus outbreak in northern Brazil, but like others he did not consider it a cause for alarm. The symptoms—a rash, fever, headache, muscle aches—were mild compared with dengue and disappeared within a few days.

“Even though it was spreading so rapidly, we really thought it was no big deal,” says Kitron, professor and chair of the environmental sciences department at Emory and professor of environmental health and epidemiology at Rollins.

Then came the first surprise—an increase in the cases of Guillain-Barré Syndrome (GBS), an autoimmune disorder that can result in paralysis. A few months later came another, even more disturbing surprise—a spike in the number of babies born with microcephaly, a condition characterized by small heads and underdeveloped brains. This is the first new cause of birth defects identified by the Centers for Disease Control and Prevention in 50 years and the first time ever that the cause has been spread by mosquitoes

“The fact that Zika can pass through a woman’s placenta and 
affect her unborn child is a game-changer,” says Kitron. “That goes to your deepest fear and is about as unsettling as it gets.”

That fear has leant a sense of urgency to the search for answers about the virus. Although Zika has been circulating in Africa and Asia for decades, it was considered relatively benign, especially compared with more serious mosquito-borne diseases such as malaria and dengue. Only when it made the leap into the Western Hemisphere and spread like wildfire through northern Brazil, leaving unexpected and devastating results, did scientists take notice. The virus has likely infected millions in Latin America, and more than 2,000 cases of microcephaly had been confirmed as of late September.

Zika is transmitted primarily by the Aedes aegypti mosquito—the same mosquito that carries yellow fever, dengue, and chikungunya—but cases of sexual transmission have also been reported. However, much of the biology and epidemiology of Zika remains a mystery. Can asymptomatic people still spread the disease? Are babies of asymptomatic pregnant women at risk for microcephaly? Can it be spread other than by sex or mosquitoes, as a Utah case suggests? And, the million-dollar question, how and why does it cause microcephaly?

Other countries are experiencing Zika outbreaks without the spike in microcephaly cases seen in Brazil. That spike could still come, but if it doesn’t, what is different about the Brazilian outbreak? “One of the things we are finding is that all three viruses—Zika, dengue, and chikungunya—are co-circulating in Brazil,” says Kitron. “Perhaps that is an important factor for the severe disease outcome, perhaps that’s what makes it different in Brazil. Socio-economic factors may also play a role.There is still so much we don’t know about Zika. Case control and cohorts studies that have been initiated recently will help us answer this and other questions about Zika.”

Helping with the ‘how to’

Eli Rosenberg is working with the CDC to set up one such study. The assistant professor of epidemiology has spent years developing and running HIV cohort studies in the Rollins PRISM Health Research Group. He’s helping the CDC quickly repurpose those tools and methods to study the Zika virus in Puerto Rico, the site of the largest U.S. outbreak.

“We are helping the CDC pop up a cohort study very quickly,” says Rosenberg. “We help them with the implementation—how to set up a clinic, how to move people through it, how to manage the volume of participants—and with database development—how to get the data, make sure the lab data and the survey data end up in the same place and make sense, how to generate reports.

“All of our data systems took us about five years to perfect, but they don’t have that kind of time to figure all this out with Zika,” continues Rosenberg. “The beauty of the partnership with Rollins is that we have the expertise in this type of design from our HIV studies, so we are able to translate it quickly for our CDC colleagues.”

The CDC team is testing the household members of symptomatic Zika patients to try to find out what percentage test positive for Zika. They will compare the viral load for symptomatic and asymptomatic patients to understand if both can transmit the virus equally. And they will take blood, saliva, semen, and vaginal fluid samples to see how long the virus can remain in each. “If the majority of cases don’t have symptoms then the epidemic feels like a runaway train, which points to different methods of control versus if we only have to worry about symptomatic patients,” says Rosenberg.

Uriel Kitron, professor of environmental health and epidemiology, works with a team of scientists in Salvador, Brazil, doing vector surveillance.

Training in vector control

While trying to answer the many questions about the virus, scientists are also rushing to fight the ongoing outbreak with any method at hand. And they’ve battled this mosquito before.

A aegypti carried yellow fever and was very nearly eradicated after a coordinated campaign in the Americas from the 1950s to 1970s. “Just as we were almost there, political will waned, funding waned, and the campaign ceased,” says Audrey Lenhart 02MPH PhD, who is leading the international vector-related activities for the CDC’s Zika response. “Since then, A aegypti has come back with a vengeance and recolonized most of the places where it was before. And now there is an even greater degree of available habitats for them, thanks to the huge urbanization trends in recent decades.”

That’s because A aegypti is an urban beast. It preferentially bites people and can only travel a couple hundred yards from its larval habitats in its lifetime. It can breed in a pool of water as small as a bottle cap. So the mega cities of Latin America, with people crammed together in houses that lack screens and air conditioning, are like paradise for this mosquito.

Its daytime feeding activities also mean that the insecticide-treated bed nets that successfully control mosquitoes that carry malaria don’t help with A aegypti. With lack of a magic bullet, control efforts rely on setting mosquito traps, treating breeding sites, and educating people about wearing repellant and emptying containers of water—labor-intensive and expensive endeavors.

To strengthen the capacity of local public health officers in vector surveillance, control, and management, the CDC is partnering with the Rollins Center for Humanitarian Emergencies, led by Dabney P. Evans, an assistant professor. The center will first assess the capabilities and needs of 37 individual Latin American and Caribbean countries, looking at areas such as basic computing skills, current global information systems (GIS) proficiency, and self-identified needs. Based on those results, it will then select appropriate GIS software and develop training materials. Finally, the center will offer four or five GIS training sessions—one in Columbia, one in Guatelama, two in the Caribbean, and possibly at fifth at a yet to be determined location.

“The use of spacially mapped data is fairly limited right now in many of these countries,” says Evans. “These efforts are aimed at building that capacity in order to fight Zika specifically, but this training will be very useful for future disease surveillance, as well.”

Uriel Kitron and two colleagues check for Aedes aegypti larvae in standing water.

Mapping the U.S. risk

While Zika has spread like wildfire through parts of South America and the Caribbean, a widespread outbreak in the continental U.S. is considered unlikely. As of late September, there were more than 3,600 travel-related cases of Zika infection in the continental U.S., including 85 in Georgia. Three Florida counties experienced mosquito-acquired Zika outbreaks.

But thanks to a lifestyle that includes airtight houses and better public health surveillance, A aegypti doesn’t find U.S. neighborhoods welcoming. Indeed, outbreaks of chikungunya and dengue, which are also spread by A aegypti, have been relatively small and limited to Florida, Hawaii, and Texas.

“So far we have found A aegypti only in one county in Georgia and not very many of them even there,” says Jennifer Burkholder 13N 13MPH, who is the Zika response lead for the Georgia Department of Public Health. “We are ready to respond if there is an outbreak, but we do not expect one.”

That said, even a small outbreak can have devastating consequences for a few. A group led by Saad Omer, the William H. Foege Chair in Global Health, is creating a county-by-county Zika risk map of the U.S. “We are building on work that has already been done on vectors and layering on top of that the number of women who are pregnant or giving birth to determine the potential risk for microcephaly,” says Michael Mina 14G 16MD, who is working as a postdoc with Omer. “This will help policy makers decide how best to allocate the funds they have to fight Zika and target mosquito interventions.”

Lessons to be learned

The current Zika epidemic is likely a portent of things to come, says Kitron. “We have been seeing more and more new and emerging diseases,” he says. “That’s because we’re invading natural habitats, and because anyone can be anywhere within 24 hours. So what are we doing to be better prepared for the next outbreak?”

Not enough. “Having a solid, sustainable surveillance system is at the heart of protecting against transmission and disease, but when you have elections every two to four years, investing in something that might happen in five, 10, or 20 years is a hard sell,” he continues. “But if we don’t invest many more resources in surveillance, we are running the risk of missing new diseases until much damage is done and costs skyrocket. An effective surveillance system may not prevent epidemics like Zika and West Nile virus, but it will enable us to be better prepared and react sooner.”