In the spring of 2015, Zika virus swept across the Americas and the Caribbean, infecting an estimated 800,000 people over the next year and a half. By the end of 2016, reports of the virus had dwindled down to almost nothing—and it seemed that the epidemic had finally begun to wane.
Blood, however, tells a different story. In truth, an outbreak was just beginning—one that may have affected tens of thousands of people in Cuba in 2017, according to new research published this week in the journal Cell.
By analyzing viral RNA from the blood of infected travelers, an international team of scientists estimates that 5,707 cases of Zika went unreported in Cuba. Most of the infections occurred in 2017—many months after what the World Health Organization (WHO) declared to be a global public health emergency had ended. Because roughly 90 percent of outbreak infections go unconfirmed, the true number of infections could be about 10 times larger, reports Carl Zimmer for The New York Times.
Zika is believed to have first appeared in the Americas in 2014, when people began to fall ill in Brazil. It wasn’t until the following spring, however, that the mosquito-borne virus was identified by health officials. By then, Zika had spread into neighboring countries, leaving hundreds—and eventually thousands—of newborn infants of infected mothers with severe brain damage.
Containment efforts began on a global scale, and the number of reported cases declined. In November of 2016, WHO announced that the emergency was over. But researchers like Kristian Andersen, an infectious disease researcher at Scripps Research Translational Institute who had been monitoring the outbreak, were hesitant to hang up their hats.
To keep tabs on lingering infections, Andersen and his colleagues thumbed through travel records from the Florida Department of Health and the European Centre for Disease Prevention and Control. They uncovered something startling: In 2017 and 2018, 155 travelers had returned to the United States or Europe with Zika in their blood. All but two had visited Cuba.
Based on the number of travelers who had gone to Cuba and returned with an infection, the researchers came up with a statistical model that predicted that the country’s “hidden” outbreak had likely been comparable in size to counts on other Caribbean islands.
None of this matched up with public records, which reflected little, if any, viral presence remaining in Cuba. To pinpoint the outbreak’s origin, the researchers sequenced Zika RNA from nine infected travelers and compared them to data from viruses collected from other parts of the Americas and the Caribbean. Their analysis revealed that the virus had likely arrived in Cuba multiple times from several different locations in the summer of 2016. Then, after a year of relative quietude, the Cuban outbreak peaked—a year after most other countries had endured the worst of the epidemic.
It’s not clear what was behind this delay, but it’s possible that Cuba’s aggressive campaign of pesticide spraying, targeting the Aedes mosquitoes that carry the virus, may have played a role. After global emergency status was lifted at the end of 2016, the eradication efforts ebbed—and Zika took the opening.
Even after epidemics emerge, they can be difficult to track, especially for viruses like Zika, which is difficult to diagnose, Ester Sabino, the director of the Institute of Tropical Medicine at the University of São Paulo in Brazil, who was not involved in the study, told Zimmer. Infected people often don’t feel symptoms, and those that do may mistake the mild fevers they get for other, more common illnesses. Zika also exits the body fairly rapidly, and tests can confuse it for the closely related dengue virus.
In other parts of the world, including Angola, Thailand, and India, Zika transmission is still a concern. It’s also unclear where else in the world the virus may continue to lurk unreported, due in part to a lack of diagnostic resources in many countries. But the researchers’ methods, including the monitoring of viral RNA, could help researchers home in on difficult-to-detect outbreaks, Jennifer Gardy, a genomic epidemiologist in the global health program at the Bill & Melinda Gates Foundation who was not involved in the study, told Jon Cohen at Science.
The team’s technique, which intertwines travel data with genetic information, could also be applied to other infectious diseases, Andersen told Cohen. “This [work] sets up a framework for investigating infectious diseases more closely,” he said. “It’s a really important new tool to monitor infectious diseases around the world.”