The first sign of trouble was the monkeys dropping dead in the forest. Then people started getting sick and dying, too.
Brazil is in the midst of its worst yellow fever outbreak since the 1940s, when the country started mass vaccination and mosquito eradication campaigns to thwart the virus.
The first cases in this current outbreak were detected in December among men living in rural parts of the Brazilian state of Minas Gerais, an agricultural region just north of Sao Paulo and Rio de Janeiro. As of the first week of February, the Brazilian Ministry of Health has reported more than 1,000 suspected human cases of yellow fever and hundreds more probable cases in monkeys since December.
Usually there are only a handful or at most a few dozen cases of yellow fever a year in Brazil, and they're found deeper in the Amazon, not hundreds of miles to the south in Minas Gerais.
Most of these cases are sylvatic or "jungle" cases in which a person who's working in or visiting a forest is bitten by an infected mosquito, says Anna Durbin, a professor of international health at the Bloomberg School of Public Health at Johns Hopkins. Human outbreaks tend to follow larger outbreaks among primates in the jungle.
"One of the proverbs is that 'when the howler monkey falls silent, everyone starts to worry,' because they know yellow fever is in the area," Durbin says. In this outbreak more than a thousand monkeys have been found dead. Health officials are analyzing the corpses to confirm whether the animals actually died from yellow fever.
Durbin says this is a significant outbreak.
"What we are starting to see now is a larger number of cases," she says. "And the concern is it could spread to a city and you'd have urban yellow fever, which they haven't really had in South America in something like 50 years."
In an urban outbreak, Aedes aegypti mosquitoes spread it from person to person. A different strain of mosquitoes circulates the virus in jungle outbreaks.
Mosquito control programs nearly wiped out the Aedes aegypti in the Americas in the latter half of the 20th century, but that mosquito has since staged a comeback.
That's the same mosquito that fueled the yellow fever outbreak in Angola last year and allowed Zika to infect millions throughout the Americas in 2015 and 2016. (WHO announced this week that the Angolan outbreak is now officially over.)
Public health officials say there's the potential for yellow fever to spread like wildfire if it takes hold in a place that has Aedes aegypti mosquitoes and where vaccination rates are low. Unfortunately that's the case throughout much of the tropics of this hemisphere.
"The nightmare scenario for me is San Juan, Puerto Rico," says Mariano Garcio-Blanco, an emerging infectious disease specialist and the chair of biochemistry and molecular biology at the University of Texas Medical Branch in Galveston. Given how deadly yellow fever can be, an outbreak in a crowded city like San Juan, Puerto Rico, or Sao Paulo, Brazil, could be a public health disaster.
"San Juan hasn't seen yellow fever in probably a century. Aedes aegypti is rampant," says Garcio-Blanco. "It [yellow fever] could spread. Yes, it could spread rapidly." San Juan also happens to be where he grew up.
The disease itself doesn't hit everyone hard. Most victims have only mild symptoms, like fever and chills, aches and nausea. Some have no symptoms at all. About 15 percent of patients develop a more severe form that can lead to high fever, bleeding, shock, organ failure and death. In the current outbreak the Brazilian Ministry of Health is pegging the fatality rate among confirmed cases at 36 percent. Among people who develop severe symptoms, there is no specific cure and as many as half the patients die.
Yet a highly effective vaccine is available to prevent the disease. The vaccine is relatively expensive and can cause adverse side effects. Also there's been a global shortage of the vaccine recently as tens of millions of doses were shipped last year to Angola and the DRC (including from Brazil) to battle the outbreak in Africa. But even before that, yellow fever vaccination rates in the Americas have been fairly low.
"The great majority of the population in all of South America and Central America and the Caribbean are unvaccinated [against yellow fever]," Garcio-Blanco says.
Officials in Brazil have launched mass vaccination campaigns in areas around where the cases have been detected. In addition, the governor in Minas Gerais has declared a public health emergency. The Brazilian government already has shipped 10 million doses of vaccine to five states in the south to try to stem the outbreak and has ordered additional stockpiles to be used in other hot spots as needed.
The World Health Organization is monitoring the Brazil outbreak and offers a rather pessimistic assessment of the region's preparedness. WHO's website states: "Latin America is now at greater risk of urban epidemics [of yellow fever] than at any time in the past 50 years."