World Cup fans are probably not to blame for bringing Zika virus to Brazil in June and July 2014. And, contrary to other speculation, neither are the teams that attended a championship canoe race in September 2014. According to a new genome analysis, the virus, first detected in northeastern Brazil in March 2015, had likely been spreading there long before either event, having arrived sometime between May and December 2013. The researchers say it most likely slipped in on one of thousands of airline flights from French Polynesia or Southeast Asia.
That is an important insight, says Matthew Ferrari, an epidemiologist and modeler at Pennsylvania State University, University Park, who wasn’t involved in the study. “Starting with [one-time events] as hypotheses can be distracting,” he says. “The genome data suggest an entirely different timeline.”
More than 50 researchers from Brazil, the United Kingdom, Canada, and the United States collaborated on the study, published online today in Science. The scientists sequenced the full genome of virus samples taken from seven Brazilian patients who were infected with Zika between March and November 2015. The virus has now raced through the Americas, with local transmission reported in at least 33 countries. It usually causes only mild symptoms, but it has recently been linked to a striking increase in babies born with microcephaly, corresponding brain damage, and other neurological effects in adults.
Four of the virus samples came from patients with uncomplicated cases. One sample was from a baby born with microcephaly, who died shortly after birth. Another was taken from a 35-year-old man who died from complications of encephalitis after being infected with Zika. And the last came from a blood donor who developed a rash—a typical symptom of Zika—2 days after donating blood. The scientists looked for, but did not find, genetic signatures that would point to a mutation that might be fueling the virus’s rapid spread or the serious complications.
To try to retrace the virus’s route, the scientists compared the genomes of the Brazilian samples to those from patients in nine other countries, six from the current outbreak in the Americas and one each from French Polynesia, the Cook Islands, and Thailand. The sequences from the Americas were the most closely related; the sequence from a patient in Thailand in 2013 was the most distant. That’s consistent with the leading theory that the virus entered Brazil only once, from someone infected in the 2013 Zika epidemic in French Polynesia, and spread to the rest of the Americas from there, says Oliver Pybus, an evolutionary biologist at the University of Oxford in the United Kingdom, and a co-author on the paper.
It could have arrived, the authors say, during the Confederations Cup soccer tournament in late June 2013. That event brought the Tahitian national team to a stadium in Recife, near the epicenter of the Brazilian epidemic. (Tahiti lost to Uruguay, 8–0.) But that was several months before cases of Zika were reported in Tahiti, and Pybus thinks it’s more fruitful to look at broader travel patterns rather than discrete events.
“If we can map flows of people and animals,” researchers might be able to find patterns that could help forecast outbreaks, Pybus says. “No amount of looking at individual events is ever going to do that for us.” He and his co-authors calculated that during 2013, air travel from Zika-endemic areas to Brazil increased by almost 50%, from roughly 3500 passengers arriving per month to nearly 5000.
Although researchers tend to focus on the well-studied outbreak in French Polynesia, other Zika-endemic countries have much larger populations and send more travelers to Brazil, Pybus notes. More than 1000 airline passengers arrived from the Philippines per month in 2013; Indonesia and Thailand sent similar numbers. It’s plausible, he says, that travelers brought the virus directly from Southeast Asia to Brazil, and not from French Polynesia. Scott Weaver from the University of Texas Medical Branch in Galveston agrees. “The Philippines is a very likely source, it just hasn’t been sampled,” he says.
Scientists need more virus genomes from those countries to sort out the route Zika took to Brazil, Pybus says. “We have a bit of a black hole when it comes to understanding Zika transmission in Southeast Asia.” The Tahitian team playing in Recife “is a great story,” Pybus says, “but who knows if it’s true.”