Alex Taranto

Using only data collected from travelers to Cuba, researchers at Yale, Scripps Research Institute and Florida Gulf Coast University detected an outbreak of the Zika virus in Cuba in 2017 that had not been previously reported.

In the study, incidence rates of Zika among travelers to Cuba were used to estimate the incidence rates among Cuban locals. After comparing Zika incidence rates in travelers and locals in Puerto Rico, Jamaica, the Dominican Republic and other countries, the researchers were able to use Zika incidence rates of travelers to Cuba to estimate the number of local Zika cases in Cuba.

“While the methods we used have been used before, the combination of methods that we used made this study the first to have reconstructed an outbreak without any data from local sources,” said Nathan Grubaugh, epidemiology professor at the Yale School of Public Health and corresponding author of the study.

The team has been following up with the Florida Department of Health since 2016, when a Zika outbreak struck Florida, to gather data on travel-related cases. These follow-ups were intended to check whether people traveling from the United States were still getting infected with the virus. While health authorities in Brazil and Puerto Rico reported Zika virus outbreaks, the researchers felt that it was odd that no such outbreak was reported in Cuba.

In 2017, the health records of people traveling from Brazil, Mexico and Puerto Rico were consistent with the fact that the epidemic was waning in these regions, Grubaugh noted. But almost 100 people who had traveled to Cuba from the United States in 2017 tested positive for the Zika virus. The researchers felt that it was odd that no data was received from Cuba about new Zika cases and decided to investigate further.

The team then sequenced the genome of the virus from these new cases and used the virus’ RNA sequence to infer relationships among the various regional variants of the virus. These relationships helped them gain insight into the outbreak that was happening in Cuba.

The researchers heavily relied on virus evolution to paint a bigger picture of an unreported outbreak in a unique situation where data from local sources was unavailable.

“If we have viruses with a certain amount of genetic diversity at a certain point in time, we can use that to figure out when the outbreak started,” Grubaugh said.

The team then built a model to compare travel cases from other locations to estimate how many Cuban locals would have been infected with the virus. The study found that nearly 5,000 cases of the Zika virus should have been reported in Cuba if the surveillance program there had been similar to that of other countries.

The scientists also looked at the transmission of the dengue virus in airline travel to figure out why the outbreak was delayed — the Florida cases happened in 2017, whereas the worldwide Zika epidemic struck in 2016. While the researchers are not completely sure, they suspect that Cuba stopped its mosquito control program in 2017 after the epidemic died down. The virus still remained in Cuba, however, and it was enough to start an outbreak the next year.

According to Grubaugh, this is an important conclusion because it highlights that even the best mosquito control efforts are not always enough to fight such epidemics — in Cuba, prevention measures simply delayed the outbreak. Stronger efforts such as vaccines for the virus could have successfully prevented the outbreak from happening, he added.

He noted that the team is now planning to use the travel data to better understand the intricacies and the effectiveness of local surveillance programs in an attempt to make recommendations that would bring other hidden outbreaks to life.

“This is going to be a very useful way to track other hidden outbreaks,” said Scott Michael, biology professor at Florida Gulf Coast University and corresponding author of the study. “It could potentially be used as a model to reconstruct other outbreaks and provide additional insight,” he said, adding that the team has already initiated similar studies of other viruses.

In 2016, 5,168 symptomatic Zika virus disease cases were reported in the United States, according to the Centers for Disease Control and Prevention.

Ishana Aggarwal | ishana.aggarwal@yale.edu