A family tree can reveal a lot, especially if it belongs to a microscopic troublemaker with a knack for genetic shape-shifting.
DNA sleuthing can outline the route an emerging pathogen might take once it makes landfall in the Americas and encounters a wholly unprotected population. It’s a modern take on old-fashioned public health surveillance strategies that focused on the exhaustive collection and analysis of samples from the field. Now they’ve been bolstered by rapid genome sequencing — and the result can be a picture of an epidemic rendered in exquisite detail, and in near-real time.
For those trying to anticipate the shape of the next pandemic of human disease, the resulting road map could be invaluable.
Three independent research groups demonstrated the promise of such an approach by creating a family tree of the Zika virus, the latest scourge to hit the Americas. Their work was published Wednesday in the journal Nature.
The family tree reveals that the virus may have made landfall in Brazil sometime in late 2013 or early 2014, probably arriving from a group of Pacific islands then in the grips of an outbreak.
Upon finding ideal conditions in northeastern Brazil — including dense human populations and hordes of the Aedes aegypti mosquitoes that spread the virus — Zika circulated widely throughout the country for more than a year before its presence was first detected in mid-2015, one of the studies found. By then, physicians had begun to take note of a sharp rise in births of babies with unusually small heads — the first of 2,366 babies with Zika-related microcephaly eventually born in Brazil by the end of 2016.
But the Zika virus didn’t stay put. By late 2014, it had broken out of Brazil and was circulating in the Caribbean, following a well-worn path of human migrants. As 2015 dawned, the same strain was also tearing through the populations of Honduras and Colombia.
Brazil’s final direct export of Zika was to Puerto Rico, where it began to circulate widely in 2015.
From there, a second study led by researchers from the Scripps Research Institute in La Jolla suggests that the island nations of the Caribbean became the springboard for Zika’s onward travel.
The Caribbean strain jumped northwest, across the Tropic of Cancer, via Zika-infected mosquitoes and people who were traveling aboard cruise ships and planes mainly bound for Miami.
Like tinder that didn’t catch immediately, Florida withstood at least four — and perhaps as many as 40 — small but unsustained ignitions of the Zika virus in 2015. A few local infections would take place, but the density of mosquitoes or humans was too low for an outbreak to pick up steam.
But these repeated sparks eventually ignited a fire. By the early days of 2016, Zika was spreading in Florida. Public health officials would eventually confirm 256 cases of local infection in 2016, all but 15 of them in Miami-Dade County.
It had taken a year, give or take, for the sustained spread of Zika to be detected in Brazil, Honduras and the Caribbean. But U.S. public health authorities were quick to determine that the virus was spreading in Puerto Rico and Florida: in both places, only a few months separated the start of Zika’s circulation and the detection of that event.
The three research groups painstakingly collected mosquitoes and human viral samples from across 11 countries and territories. The teams subjected those samples to genetic analysis — sometimes right on the spot using field versions of genome sequencers described in a study in Nature Protocols.
Altogether, the researchers analyzed the full or partial genomes of 183 Zika samples. One of them was the earliest known Zika sample collected in the Americas.
Like all viruses, as Zika spread from person to person and from country to country, its genetic blueprint changed in small but discernible ways. The RNA in each sample steadily picked up mutations over time as it gained exposure to new people and the viruses they hosted. (In fact, in a study published last week in Nature, researchers identified a much earlier mutation in the South Pacific version of the Zika virus that appears to have contributed to its rapid spread through the Americas.)
The result of the 183 genetic analyses is a sprawling family tree of Zika viruses — all related, but each just a tiny bit different from its predecessors or its progeny.
By carefully recording the dates and locations of the Zika samples collected between 2013 and 2016, the three research teams in effect show when and where Zika virus began circulating in a given country or territory. They looked at mutations in the genetic fine print of the samples and lined them up end to end, allowing them to refine the dates, pedigrees and origins of each.
The family tree allowed them to trace Zika’s path as it traveled through the Americas. It provides evidence for the potent effect that international travel, migration and mosquito-control efforts can exert over the spread of a virus.
It also serves as a test bed for tracking the progress of future disease-causing viruses as they encounter dense populations with no resistance to them.
In a comment published alongside the three papers, University of Arizona evolutionary biologist Michael Worobey wrote that the new studies collectively “set a new standard for what can be achieved by studying disease outbreaks in tantalizingly close to real time, using rapidly-obtained genome sequences.”
But its future, he added, is hardly assured.
“Such work is possible mostly through the sustained efforts of a fairly small number of scientists supported by modest grants from a few enlightened funders,” Worobey writes. “Systematic pathogen surveillance is within our grasp, but is still undervalued and underfunded relative to the magnitude of the threat.”