A team of University of Miami Miller School of Medicine researchers worked with a team of scientists at The Scripps Research Institute in California and investigators at other leading institutions to solve a mystery about the first U.S. outbreak of Zika virus in 2016.

Sequencing the Zika virus RNA of infected people and Aedes aegypti mosquitoes revealed some surprises. It turns out that the virus was introduced to Miami at least four times last year, and possibly as many as 40 times. No “patient zero” was responsible, therefore, for the 256 locally spread infections reported to health officials.

The Zika virus in South Florida also came primarily from endemic areas of the Caribbean, not Brazil or other countries in South America, as some people expected, according to the study published online May 24 in the journal Nature.

New RNA technology and genetic epidemiology make rapid and rigorous investigations like this possible, a crucial advance because speed counts for developing diagnostics and deploying safety measures to protect the public from future outbreaks.

“Unfortunately, Florida will likely remain susceptible to yearly Zika virus outbreaks,” said David I. Watkins, PhD, study author, professor and vice chair of research in the Department of Pathology at the Miller School of Medicine. “I am desperately hoping that this is not the case. However, developing better diagnostics and novel preventative therapies will be central to controlling this epidemic. Therefore, these have been major areas of research in my laboratory.”

As a leading medical and health research facility at the University of Miami, the Watkins laboratory is perfectly situated – and not just geographically – to uncover how and when Zika virus transmission occurred, and may occur again. “We are on the front lines of the battle against Zika. This has helped us acquire samples that are well characterized and critical for the development of new rapid diagnostics,” said Michael J. Ricciardi, another scientist working with Watkins and Magnani. “Having the resources we need here at the University of Miami has allowed us to move the scientific process along very swiftly.”

Although South Florida was the epicenter of the 2016 outbreak, the University of Miami investigators quickly realized the implications could spread much further. So they collaborated with Nathan D. Grubaugh, PhD, and Kristian G. Andersen, PhD, at The Scripps Research Institute in La Jolla, California, to fast track the research on Zika transmission. In fact, the Andersen laboratory, in collaboration with the Watkins laboratory, published the RNA sequence for one of the first locally acquired cases online last year so that other scientists could conduct research simultaneously.

Looking at tiny RNA sequences allowed researchers to also see the big picture. The study revealed that Zika virus first arrived earlier than expected, most likely during the spring of 2016, several months before the first detection. “The finding that multiple strains of Zika virus were introduced in South Florida, and that the travelers were coming from different countries in the Caribbean, helps explain the spread of the virus in an area that is very dynamic,” said Paola N. Lichtenberger, MD, an infectious disease specialist at the University of Miami Health System. The University of Miami research team analyzed surveillance and genetic data to demonstrate that Zika virus moved among different transmission zones in Miami. Matching RNA from locally acquired cases and endemic cases in the Caribbean confirmed those islands as the predominant source of Zika virus coming ashore in the United States.

In addition, the investigators further verified these transmission routes with travel data for South Florida that aligned with high incidence and traffic volume from the Caribbean to Miami.