Mosquito spraying efforts, shown here at a cemetery in Peru, likely had little to do with the steep drop in Zika cases.

MARTIN MEJIA/ASSOCIATED PRESS

Zika has all but disappeared in the Americas. Why?

One. That is the total number of locally transmitted Zika cases confirmed in the continental United States this year, as of mid-August. That single case, recorded on 26 July in Hidalgo County in Texas, which borders Mexico, contrasts with hundreds of cases of local transmission last year.

Better control of Zika's vector, the Aedes aegypti mosquito that thrives in the hotter, southern part of the country, doesn't explain the dearth of cases. Nor are other factors such as climate change at work, experts say. Instead, Zika cases have plummeted in Latin America and the Caribbean, where the virus raged over the past 2 years, and much of the population is now immune to it. That, in turn, means fewer infected people entering the United States, reducing the chances of mosquitoes spreading the virus to susceptible people. The respite, experts say, could last for years.

Zika, a member of the flavivirus family, has circulated in Africa and Asia for decades but had never been seen in the Americas before it surfaced in Brazil in 2015. It had been considered relatively harmless, but in February 2016 the World Health Organization (WHO) in Geneva, Switzerland, declared a Public Health Emergency of International Concern after compelling evidence from Brazil began to link the virus to devastating brain damage in thousands of babies whose mothers were infected while they were pregnant. Still, infectious disease experts expected that, like most mosquito-borne flaviviruses—which include dengue, West Nile, and yellow fever—it would initially tear through the population but then fade into the background as people developed immunity.

But few predicted that cases would disappear so abruptly. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, says he's not "entirely surprised" about the precipitous drop, "but I am impressed by how steep it has been." Vast swaths of populations have probably become immune to the virus; this "herd immunity" has reduced the number of susceptible people until the virus could no longer easily move between humans and mosquitoes.

Cases plunged. Brazil, the hardest hit country, had 205,578 probable Zika cases in 2016, according to its Ministry of Health. As of 26 July of this year, only 13,253 had been reported, and all occurred by mid-April (fall in the Southern Hemisphere). Similar drops have been recorded throughout the Americas. Last year in the United States, the Centers for Disease Control and Prevention (CDC) recorded 224 probable or confirmed cases of local transmission—all in Florida and Texas—and 4830 travel-related cases. This year, CDC has logged only 200 travel-related cases and just the one local transmission in Texas.

The rise and fall of Zika

Rapid spread of mosquito-borne viruses often leads to widespread immunity and drops in disease.

CREDITS: (GRAPHIC) J. YOU/SCIENCE; (DATA) PAN AMERICAN HEALTH ORGANIZATION/WORLD HEALTH ORGANIZATION

"I think it's highly unlikely we will see any resumption of significant transmission for at least a decade," says Neil Ferguson, a mathematical biologist at Imperial College London. He co-wrote a study in the 22 July 2016 issue of Science that argued the Zika epidemic would be "largely over" by 2018. But biostatistician Ira Longini, a disease modeler at the University of Florida in Gainesville, disagrees. His own models suggest Zika will still thrive in susceptible populations that have yet to be hit by the first wave of transmission, leading to "flare-ups here and there," he says.

Transmission persists at low but steady levels in some parts of Latin America, including Mexico, Peru, and Colombia, agrees Alessandro Vespignani, a modeler at Northeastern University in Boston who collaborates with Longini. And recorded cases are just the tip of the iceberg because 80% of infected people have no symptoms, he says. "If the number of cases is very small, you'll have no signal."

Attempts to track Zika's spread are further confounded by the dengue virus, a close cousin, and chikungunya—both of which are also transmitted by A. aegypti and are endemic in much of Latin America and the Caribbean. Antibodies against dengue and Zika are so similar that standard diagnostic tests can't distinguish one from the other. (This also makes it difficult to accurately measure the extent of herd immunity.) In a study this spring in The New England Journal of Medicine, epidemiologist Christopher Dye of WHO and his co-authors suggest that many cases of chikungunya may have been misclassified as Zika in Brazil in 2016, because both viruses cause fever, rash, and, occasionally, a neurologic condition in adults called Guillain-Barré syndrome. "There's a real confusion between Zika, chikungunya, and dengue," Dye says.

The transmission patterns of those three viruses in the Americas suggest it's too early to write off Zika, says Lyle Petersen, who heads CDC's vector-borne disease division in Fort Collins, Colorado. "These are very episodic diseases that are very difficult to predict," often dying down and exploding again, he says. Lyle also notes that Zika cases increased in northern Mexico this year, which he says "is a little concerning" because it could lead to outbreaks in Texas communities on the border over the next few months. "Just because cases go down, it doesn't mean we should stop worrying about it," he says. "We need to maintain our vigilance."

Nor does the sharp decline in Zika cases lessen the need for a vaccine, Petersen and others say. But it does complicate clinical trials, which can't test a vaccine's worth if the disease isn't spreading. A vaccine developed by NIAID has moved furthest and is now entering a placebo-controlled study of 2400 people in Zika-affected sites in the United States, Peru, Brazil, Costa Rica, Panama, and Mexico. But with so little viral spread, the trial "probably has little hope of success," says Longini, who helps design vaccine trials.

Fauci says the trial can expand to 5000 people if necessary, and NIAID can quickly "reassign slots" to places having outbreaks. Peru has recently had several "blips" of cases, he notes. "There's a reasonable chance that there will be low to moderate spread that leads to an efficacy signal," Fauci says. In the worst case, he says the NIAID team could still gather data on immune responses and safety that they could combine with animal studies. That might be enough to get a Zika vaccine licensed, as the disease will certainly flare somewhere in the world again.