Unusually active outbreaks of yellow fever in rural areas of Brazil are stoking fears among experts that the deadly mosquito virus could go the way of Zika and spark a massive and devastating epidemic in the Americas.

In a commentary published Wednesday in the New England Journal of Medicine, infectious disease experts at the National Institutes of Health note that, so far, the outbreaks are mostly in rural areas and involve forest mosquitoes transmitting the virus to nonhuman primates as well as incidental humans. Since February, there have been 234 confirmed human infections, with 80 deaths and hundreds more cases currently under investigation. But those outbreaks are encroaching on densely packed urban areas.

“This proximity raises concern that, for the first time in decades, urban transmission of yellow fever will occur in Brazil,” experts Catharine Paules, of the NIH’s National Institute of Allergy and Infectious Diseases, and Anthony S. Fauci, director of the NIAID, write.

If that spillover happens, and yellow fever virus begins spreading among people through Aedes aegypti—the kind of mosquito spreading Zika, dengue, and chikungunya—the disease could explode the same way Zika did. Paules and Fauci speculate that the virus could quickly blaze across South and Central America and into US Territories. “As we have seen with dengue, chikungunya, and Zika, A. aegypti–mediated arbovirus epidemics can move rapidly through populations with little preexisting immunity and spread more broadly owing to human travel.”

Like those virus relatives (in a group called arboviruses), yellow fever is unlikely to spread widely in the continental US given lower mosquito populations and better disease controls. But some southern areas, such as Florida and along the Texas-Mexico border, could see outbreaks like we’ve seen with Zika. Plus, it would likely be carried in by travelers.

But there is one big difference between yellow fever and those other relatives: yellow fever is more deadly. In fact, yellow fever is the most severe arbovirus ever to circulate in the Americas. Infections start out a lot like the flu and can disappear on their own. But for 15 to 20 percent of infected people, things get better for a day or so and then get a lot worse, transitioning to a severe stage. In this, the “intoxication” stage, people experience high fevers, hemorrhaging, kidney failure, heart problems, central nervous system dysfunction, plus the telltale jaundice of yellow fever. Up to 60 percent of people who reach the intoxication stage die of the disease. And there’s no treatment for the infection, just ways to ease symptoms.

There is an effective vaccine. It protects 99 percent of people for life. But vaccines aren’t regularly administered in many places in the Americas, including the US and some urban areas of Brazil. Health authorities there are now stepping up vaccination. But in many other places, doctors may not be able to quickly spot and respond to yellow fever since it initially looks so much like the flu. This could help the virus to take root and spread in new places.

There’s also the problem of vaccine shortages. During a yellow fever outbreak that started in Angola in December of 2015 and spread to the Democratic Republic of Congo, the world’s emergency stockpile of yellow fever vaccine ran empty, stymying control efforts.

If yellow fever makes its way to the US, it will be its first major comeback since the early 1900s, shortly after scientists figured out it was spread by A. aegypti. Prior to that, yellow fever has regularly stalked the country since it made its debut in the latter half of the seventeenth century. For instance, in 1793, a yellow fever outbreak killed off 10 percent of Philadelphia’s population.

To avoid any such devastation, we must be vigilant, Paules and Fauci conclude. "As with all potentially reemerging infectious diseases," they write, "public health awareness and preparedness are essential to prevent a resurgence of this historical threat."