Tracing Zika Back to Patient Zero

Researchers must work their way backward to understand the mutations that made the disease a pandemic.

It’s not enough to know where Zika originally came from.

Today, researchers also want to know how and why the virus mutated as it leapt from Africa to Asia to the Americas.

Scientists have established that Zika causes grave abnormalities in fetuses, and can cause serious nerve disorders in children and adults, too. But it seems the virus wasn’t always this way. Learning how and when the Zika mutated could be one of the keys to unlocking why it’s so dangerous now, at a time when it appears poised to work its way through the Americas and possibly extend to the Mediterranean.

Zika was first discovered in Uganda in 1947, but it was five more years before the first human cases of the virus were detected in the region. “It is challenging to state definitively who the first patient is who ever contracted the virus or brought it to a new country,” said Ann Powers, the acting chief of the Arboviral Diseases Branch at the Centers for Disease Control and Prevention. “We may sometimes report the first ‘detected’ case as such, but that doesn’t necessarily mean it is really the first time. What is more important than finding the one specific person is to understand overall movement patterns and assess if there are changes that have occurred—either in the virus, the vectors, or the host behaviors—that may be impacting the epidemiology.”

Up until the 1980s, human infections occurred across Africa and Asia, but those who contracted Zika typically only suffered mild illness. It wasn’t until 2007 that a large outbreak was recorded, this time in Micronesia. Up to three-quarters of the population of the Island of Yap were infected. “Like many arboviral agents, given the appropriate environmental and human conditions, new pathogens can be easily moved around the globe,” Powers said.

And that’s what Zika did. The virus began to ripple across the Pacific—and as it traveled, it seemed to change. In an outbreak in French Polynesia, in 2013, researchers linked the neurological disorder Guillain-Barré syndrome to Zika infections, according to a World Health Organization bulletin about the virus’s history. In May 2015, the first reports of locally transmitted infection in Brazil emerged. Because no Zika-endemic nations competed in the World Cup, held in Brazil in 2014, some scientists now believe Zika may have traveled from French Polynesia to Rio de Janeiro during the Va’a World Sprint Championship canoe race in August 2014.

In October last year, doctors noticed a spike in Brazil of cases of microcephaly, a birth defect that impedes brain development, and wondered if it could be linked to the uptick of Zika. By April, they had their answer: “Zika virus is a cause of microcephaly and other severe fetal brain defects,” the Centers for Disease Control and Prevention wrote last month. Since last spring, the virus has been linked to some 5,000 cases of microcephaly in Brazil alone.

“Here in Brazil, it is very clear, after the 2015 transmission season, that the epidemic is not over,” said Christopher Dye, the strategy director in the Office of the Director-General at the World Health Organization. “We are near-certain that Zika will reach all areas that are inhabited by the (supposed) principal vector, Aedes aegypti. Probably all countries in the Americas, except Canada. ... Maybe to the Mediterranean. It might move further north, through the range of Aedes albopictus, in the United States. Could there be other mosquito vectors?”

A crucial part of looking to Zika’s uncertain future means understanding its past. And as researchers trace the origin of the virus, they’re left with more questions than answers. For example, scientists still don’t know whether Zika is widely endemic in Africa and Asia, where it was found for decades before it traveled to Micronesia and French Polynesia en route to South America. They also don’t know the extent to which it may have caused birth defects and other severe health problems in the 20th century.

“Did [Zika] cause neurological disorders, but at a low and undiscovered incidence rate? Or did the virus somehow change, genetically or epidemiologically, as it crossed the Pacific?” Dye asked. “Could a new virus—if it is new—reinvade Africa and Asia and cause new and severe epidemics in places where infection was previously benign? All these questions are critical for public health, but we do not yet have answers.”

One way to find answers has been to analyze different strains of Zika over time. Some scientists have taken to propagating the virus in their own labs as a way of reverse engineering what makes the current strain so dangerous. (This is how, as The New York Times recently reported, a neurologist and a virologist worked together to find evidence to support the idea that Zika is most dangerous to a fetus during a pregnant woman’s first trimester.) Another group of scientists who analyzed the genetic evolution of the virus identified more than a dozen mutations between the virus in Brazil compared with earlier strains isolated in Asia. They wrote about their findings in the journal Cell Host & Microbe, in April. Those mutations could explain why Zika appears to be more virulent now, and the possibility that the virus is more adept at mosquito-to-human transmission compared with earlier strains. “Clearly, more studies are urgently needed,” to understand these mutations and their implications for public health, the researchers wrote.

Genetically speaking, the Zika virus that’s making people sick in Brazil resembles the Polynesian strain but differs from the African strain, which “allowed us to postulate that the virus underwent a mutation that gave it pandemic properties” somewhere in the Pacific, said Peter Hotez, the dean of the National School of Tropical Medicine at Baylor College. “It also allowed us to go back to do studies showing that microcephaly and Guillain Barré Syndrome probably first began with the Asian strain.”

Looking back at Zika’s trajectory, it seems there are at least two separate lines of mutation: one, from 2007, when the virus hit Micronesia; and the second, from sometime before the French Polynesia outbreak of 2013.

“The Brazil strain bears some similarities to the French Polynesia strain, in that both result in microcephaly and [Guillain-Barré Syndrome], but it's possible that the virus underwent still more mutations going from French Polynesia to Brazil,” Hotez said. “The scientific community is still sorting it out.”

What scientists eventually find will, they hope, help public health officials prepare for what’s to come—whether that means more Zika, or another mosquito-borne virus, or, likely, all of the above. In an essay about how human activity has shaped the transmission of Zika and other tropical diseases, Hotez says the latest outbreak should make people seriously consider humanity’s potentially disastrous influence on the biosphere in the age of globalization. “The Anthropocene could become a dominant theme for spreading [neglected tropical diseases] or creating catastrophic human epidemics in the years to come,” he wrote.

Many of his peers are thinking this way already. “Zika is the latest flavivirus to have escaped from its historical distribution, and to have turned from benign to malignant,” said Dye, of the World Health Organization. “We previously saw the spread of dengue, Japanese encephalitis, and West Nile viruses. ... Will yellow fever be next? Is the current yellow fever outbreak in Angola an omen of things to come?”