Between July 1, 2017, and April 10 this year, a total of 1,127 confirmed cases and 331 deaths have been reported in Brazil. Travelers have also taken the virus to other countries. Since January, the Centers for Disease Control and Prevention reported, there have been at least four deaths and 10 cases of the mosquito-borne virus among international travelers returning to Europe and South America from Brazil.
None of the travelers had been immunized for yellow fever prior to their trips, and many cases involved infections on Ilha Grande, an island off the coast of Rio de Janeiro that’s popular with tourists.
“There are more cases of imported yellow fever [from travelers] in the past two years than in the previous 20 years,” said Duane Gubler, a leading researcher of mosquito-borne diseases at Duke-NUS Medical School. “Sooner or later, we’ll have an introduction that takes — and then there’ll be chaos.”
There’s no cure for yellow fever, but there is a vaccine, and it’s highly effective. Within 10 days of receiving the shot, some 90 percent of people are immune to the disease.
But there’s a problem: Global supplies of the vaccine have been running short for years. These shortages have coincided with some of the largest yellow fever outbreaks in half a century. And a new study published in the Bulletin of the World Health Organization warned that this is a recipe for more outbreaks — even in the southern US, where the virus is not endemic but where mosquitoes that can carry the virus live.
The researchers found that America was among a handful countries with a high volume of travelers — 2.76 million people — coming from places with yellow fever. Yet the US also doesn’t require people to show a yellow fever card proving they’ve been vaccinated against the virus.
“At a time when global yellow fever vaccine supplies are diminished, an epidemic in a densely populated city could have substantial health and economic consequences,” the researchers warned. “The global community needs to carefully reexamine existing yellow fever travel vaccination policies and practices to prevent urban epidemics.” Here’s why.
Most cases of yellow fever are similar to the flu, but 15 percent of cases are severe and can be deadly
Yellow fever has plagued humanity for centuries. The virus is carried by infected mosquitoes that spread it when they bite humans or monkeys. Symptoms in most people are mild and flu-like: muscle pain, fever, headache, nausea, vomiting, and fatigue.
But 15 percent of patients experience a much more severe second phase of the illness, which brings high fever, yellowing of the skin and eyes, internal bleeding, and organ failure. Up to half of these patients die within two weeks. (This is why yellow fever is a hemorrhagic fever.)
The first yellow fever epidemic was reported in 1648, according to JAMA. In 1793, a yellow fever outbreak wiped out 10 percent of the population of Philadelphia (then the capital of the United States), “causing 17,000 people, including President Washington and other members of the federal government, to flee to the countryside,” according to the Gilder Lehrman Institute of American History. In 1878, an epidemic ”destroyed” Memphis, Tennessee, killing 5,000.
Yellow fever hasn’t spread in the US for 100 years, but it still plagues South America and sub-Saharan Africa. And the outbreaks in these areas have been growing worse in recent years.
Researchers don’t fully understand what’s behind the resurgence of yellow fever
Yellow fever had been controlled effectively in West Africa and South America for half a century.
Then in 2016, the virus showed up in urban areas of Angola and spread to the Democratic Republic of Congo as well as Uganda. All told, more than 900 people were infected, and it took 30 million vaccine doses to snuff out the outbreak.
“In 2016, we saw the most cases [of yellow fever] in decades,” Gubler said. “And that’s continuing this year.”
Researchers aren’t sure what’s behind this resurgence, but some believe factors like climate change, global travel, and urbanization are helping mosquito-borne diseases spread more easily than before.
Yellow fever typically circulates in forests or jungles, between monkeys and mosquitoes, in what’s known as a “sylvatic cycle.” But spillover into humans can happen when people enter these areas and get bitten by jungle mosquitoes, which carry the virus. If infected people return to cities, urban mosquitoes like the Aedes aegypti — which also carries dengue and Zika — can pick up the virus and spread it others, starting a chain of human-to-human transmission. (That’s what happened in Angola, but it hasn’t yet happened in Brazil.)
Human cases of yellow fever have hit their highest levels in years, said Gubler. And there are a few drivers of the trend. Cities have not kept up their mosquito control programs, allowing mosquito-spread diseases to flourish, while health officials in countries where yellow fever is common have not been routinely vaccinating their citizens, since outbreaks had become less frequent. Some countries also haven’t been looking for proof of yellow fever vaccination at borders, which can help the virus spread.
To respond to these trends, starting in 2006, the World Health Organization, with support from Gavi (an international organization focused on improving vaccine access), ramped up efforts to make sure at-risk communities got vaccinated. But the 47 countries that get support from Gavi still have yellow fever vaccine coverage rates of less than 60 percent — and that number needs to hover around 70 percent to protect the population.
The outbreaks have coincided with vaccine shortages
There’s also the vaccine supply issue. There are only four yellow fever vaccine manufacturers certified by the WHO. Because the disease had been effectively controlled for decades, and demand for the vaccine has been low, the manufacturers have not had the incentive to produce large stockpiles.
Since 2012, Gavi has been working with the four main manufacturers to modernize their production processes and ramp up stockpiles — but they were still in the midst of that push when the outbreak in Angola happened.
That outbreak depleted the WHO’s emergency stockpile of the vaccine and forced health officials to give out “fractional doses” of it — one-fifth the size of a standard dose — in the related DRC outbreak. (The fractional doses worked.) Before vaccine manufacturers could fully recover, yellow fever popped up in large numbers in Brazil.
“We are in better shape [with supplies] but it’s still fragile now,” said Seth Berkley, head of Gavi. Brazil manufactures its own yellow fever vaccine, and supplies had been short there too, particularly as health officials looked to mount the first-ever nationwide vaccination campaign.
“We now have enough vaccine for meeting the needs [of the population],” said Sylvain Aldighieri, deputy director of the emergency department at the WHO’s Pan-American Health Organization. This is, in part, because the government is giving out full vaccine doses only in the areas most at risk for yellow fever, and fractional doses in cities unaffected by yellow fever spread.
Meanwhile, stocks of the only licensed yellow fever vaccine in the US, YF-VAX, have been totally depleted in the US — the result of manufacturing problems at Sanofi Pasteur’s Pennsylvania plant. The company had been moving to a new manufacturing plant and lost a large number of doses meant to bridge their transition period. So Americans who want the vaccine may not have an easy time getting it.
The CDC has made available a searchable list of clinics that may still have some leftover YF-VAX stock, or an alternative yellow fever vaccine, Stamaril. But because of the supply shortages, only 250 clinics are currently offering yellow fever vaccines, down from the usual 400-plus. And the YF-Vax supply is only expected to return by the end of this year.
The outbreak keeps expanding
Brazil’s outbreak of yellow fever has been expanding since 2016 — and is now spreading into regions where public health experts thought vaccinations weren’t necessary.
“This wave has reached new areas on the coast of southeast Brazil where you have the biggest cities,” said Aldighieri. There’s no evidence yellow fever has popped up in Brazil’s cities, Aldighieri said, but “we are always prepared to have the emergence of human-to-human transmission through Aedes aegypti [urban mosquitoes].”
But it’s important to keep in mind the yellow fever season isn’t finished, he added. “[The season] may last until late May, early June, so we have to be very careful.”
“If Aedes aegypti mosquitoes start spreading yellow fever in Brazil, there’s a possibility that you might have an outbreak in very populous areas in Brazil, such as Rio de Janeiro and Sao Paulo,” Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, told NPR recently. ”Whether that’s going to happen, I don’t know. But if it does, we’re going to get a lot of travel-related cases in the U.S., which means physicians here have to be aware of it.”
For now, the CDC is recommending the vaccine for people who are traveling to or living in the states of Espirito Santo state, São Paulo state, and Rio de Janeiro state as well as a number of cities in Bahia state. People who fail to get the vaccine, the CDC says, should avoid going to the affected areas.
Gubler said he’d take a more conservative approach. “If I were still at CDC, I would advise travelers to any part of Brazil to get vaccinated before they go, not just where cases are reported,” he said. “These kinds of diseases have a way of sneaking into new areas without detection and are transmitted silently for a time, and identified only after a number of cases have occurred.”