Soccer spectators can breathe a sigh of relief: Travelers to the 2014 World Cup in Brazil were not responsible for introducing the Zika virus to the Americas after all.
New genomic analysis of a small number of Brazilian Zika patients puts a better clock on the travel history of the mosquito-borne virus and suggests that it landed in the Americas at least a year earlier than previously thought—as early as spring 2013.
That timeline throws cold water on the two prevailing theories of how the virus traveled from Asia to the Americas. In addition to debunking the World Cup theory, the revised timing suggests that travelers coming to cheer on the Va’a World Sprints canoe event in Brazil—held in August 2014—also were not the first carriers of the virus to the Americas.
The revelation, extrapolated from new analysis of seven Brazilian genome sequences, also raises doubts about the major remaining theory—that the virus traveled to Brazil in the bloodstream of travelers to the 2013 Confederations Cup soccer tournament from French Polynesia.
The FIFA Confederations Cup soccer event, in June 2013, ended several months before Zika cases were first reported in French Polynesia that fall, which would suggest that either the virus went undetected in French Polynesia for a period of time or a traveler brought the virus to the Americas under different circumstances altogether.
“We will never be able to directly test the theory about the Confederations Cup because the virus wasn’t [detected] at the time,” says Oliver Pybus, a senior author on the new Science paper and an evolutionary biologist at the University of Oxford.
To underscore the myriad potential infection possibilities, the team of Brazilian and Oxford scientists who led the study instead culled data on the thousands of commercial airline flights that traversed between Brazil and countries with reported Zika transmission (such as Cambodia, Indonesia and Malaysia) between January 2012 and December 2014.
Sketching out the evolution of a virus is a complex science. Viruses accumulate genetic changes at a rapid rate so the authors compared the available genome samples and catalogued any alterations. That process helped them to map out a likely family tree of Zika.
“If we can estimate how fast the changes are accumulating in the genome it allows us to extrapolate backwards in time and work out when the virus shared a common ancestor,” Pybus says. The team fitted different molecular clock models to the virus and found the one that assumes the virus mutated at a constant rate was the best fit, he says. More genome sequences in the future, however, may complicate that model.
Their current high-tech molecular family tree suggests Zika likely circulated—undetected—for at least a year in patients in the Americas who did not get particularly ill or were mistakenly diagnosed with chikungunya or dengue. Moreover, the study concludes that it is likely there was a single introduction of the virus to the Americas sometime between May and December 2013.
Already, the region has seen Zika cases quickly multiply. Since 2015 more than 4,000 cases have been confirmed there, with more than 180,000 cases suspected. There are currently 33 countries or territories in the Americas that have active transmission of the virus.
The new Science analysis on Zika’s history draws from the genomes of four adult Zika patients who did not travel outside Brazil; one blood donor who tested positive for Zika; one deceased newborn with microcephaly and other birth defects; and another Zika patient who appears to have died from complications of the virus (the person also had lupus and rheumatoid disease).
Ultimately, the model compares those new genomes against available historical samples of the virus. The 50-plus researchers on the team concluded that the new Zika virus samples from Brazil were similar enough to Asian ones that they must share a common ancestor with the Zika strain that circulated in French Polynesia in October 2013 and caused a large outbreak there.
Yet it is still unclear if the virus traveled directly from French Polynesia to Brazil or occurred somewhere in Southeast Asia and then was transported independently to both locations. Earlier reporting of the virus in the Americas suggested that the virus was circulating on Easter Island—which is part of Chile but geographically close to French Polynesia—as early as 2014, but no analysis had yet put Zika in the Americas in 2013.
“The data looks solid,” says Nikos Vasilakis, a pathologist studying Zika at The University of Texas Medical Branch at Galveston who was not involved in the analysis. “It looks plausible that there was a single introduction of Zika but with more comprehensive sampling from that time period, that may change,” he cautioned. Because the analysis only included a small number of genome sequences it is possible that the evolution of the virus may be more complicated. The virus may have been introduced to the area multiple times, for example, but failed to sicken many humans or survive. That history, unfortunately, may not be knowable.