Genomic analysis suggests Zika outbreaks are underreported

2019 08 21 18 24 8995 Mosquito Aedes Aegypti Zika 400

Are outbreaks of disease caused by the Zika virus going undetected around the world? That's the suggestion of a new study published August 22 in Cell. The findings indicate that diagnostic testing for international travelers could be a good idea, even when it looks like an epidemic is on the wane.

A large disease outbreak in Cuba in 2017 was caused by Zika, but it went unreported at the time, according to an analysis of travel patterns, mosquito modeling, and sequenced virus genomes taken from infected travelers, according to Yale School of Public Health epidemiologist Nathan Grubaugh, PhD, and colleagues (Cell, Vol. 178, pp. 1-15).

Researchers studied the use of travel surveillance and viral genomic sequencing of infected travelers to find hidden epidemics. Image courtesy of N. Grubaugh, S. Saraf, K. Gangavarapu, et al.Researchers studied the use of travel surveillance and viral genomic sequencing of infected travelers to find hidden epidemics. Image courtesy of N. Grubaugh, S. Saraf, K. Gangavarapu, et al.

Cuba implemented a mosquito control program in 2016 to control the spread of the virus, and the initiative appeared to be effective, as no cases were reported locally the following year. But Grubaugh et al's study reflects a review of Zika cases in travelers reported to health authorities in Florida and in Europe.

"Our data suggest that, although mosquito control in Cuba may initially have been effective at mitigating Zika virus transmission, such measures need to be maintained to be effective," the authors explained. "Our study highlights how Zika virus may still be 'silently' spreading and provides a framework for understanding outbreak dynamics."

Challenges in tracking down Zika

The study was conducted in light of differences in testing and reporting across countries, which presents challenges for international surveillance and disease control, as well as subtleties in making the diagnosis based on clinical presentation. The Zika virus can be spread by Aedes mosquitoes, through sex, and from a pregnant woman to her child. Symptoms may be mild, in contrast with the virus' sometimes devastating consequences, such as birth defects and the paralysis-inducing Guillain-Barré syndrome.

The unreported outbreak in Cuba occurred one year after transmission of the virus peaked in other Caribbean islands. The lack of reporting was chalked up to subclinical infections and symptoms appearing similar to those of other viruses, such as dengue and chikungunya. An estimated 5,707 cases of Zika went unreported in Cuba, almost all in 2017, according to the researchers.

"Only 187 laboratory-confirmed Zika cases were reported by Cuba in 2016, and none were reported in 2017 or 2018," they wrote. "These reports are inconsistent with the outbreak dynamics that we detected using travel surveillance."

The last local case in the Caribbean was reported in August 2017, yet there was a spike in reports of Zika in travelers who had visited that region in the summer of 2017 "that were not captured by local reports," Grubaugh and colleagues also noted.

Clinical testing still necessary

The mild manifestations in terms of symptoms highlight the value of diagnostic testing, which is performed with a urine or blood sample. Just because an epidemic is presumed to be over, it doesn't mean that it actually is: Many cases can go unnoticed, so clinical testing for Zika virus, especially in travelers, is still necessary, Grubaugh commented by email to

"We showed that Zika diagnostic testing in the U.S. from international travelers is quite helpful for understanding outbreaks from source locations," he added. "Because Zika clinical testing was still occurring in Florida while the epidemic appeared to be waning, we were able to detect an unreported outbreak."

According to the U.S. Centers for Disease Control and Prevention (CDC), Zika virus disease was rarely reported in the U.S. before 2014. Cases associated with travel were reported in the U.S. in 2015 and 2016, followed by a decline. In 2019, five cases of Zika were reported in the U.S., all of which were travelers returning from affected areas, according to the agency. In U.S. territories, 24 cases of Zika were reported, one in a traveler returning from an affected area and 23 from local transmission through mosquito bites.

The Cell report, however, flagged global outbreaks outside of the U.S. in the past few years, some of which were traced to the Americas, and the authors concluded that "significant transmission of Zika virus in the Americas could still be ongoing, despite case reporting having come close to zero."

Reporting is inadequate in some countries, making it hard to control transmission of the virus, but the study results show that a surveillance framework for travelers can help bring danger zones to light, the authors concluded.

Monitoring infected travelers is well established in practice, and the researchers are trying to get their particular framework -- that is, using travelers, travel patterns, and genomics -- more widely incorporated. It will likely be used for research purposes until its utility catches on, Grubaugh said.

Page 1 of 1