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fast-spreading outbreak of yellow fever has taken hold in central Africa, alarming infectious disease experts and threatening to spread far wider if not brought under control quickly.

Even as the spread of another virus, Zika, commands the attention of global health officials, yellow fever could prove far more worrisome. The disease, which like Zika is transmitted by mosquitoes, kills an estimated 60,000 people a year.

“I think we’re sitting on a time bomb,” Duane Gubler, one of the world’s leading experts on mosquito-spread viruses, told STAT.

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“You think SARS was bad? This would make it pale by comparison.”

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The outbreak started in Angola’s capital, Luanda, in December, and has spread to six of the country’s 18 provinces. Case numbers are not thought to be precise, but the most recent reports from the World Health Organization suggest 450 people have been infected and 225 have died.

To put that in context, it often takes only a single diagnosis of yellow fever for a city to launch an emergency response, said Dr. Sylvie Briand, director of the WHO’s department of pandemic and epidemic diseases.

Already, people infected in Angola have made their way to Kenya, Mauritania, the Democratic Republic of Congo, and China — underscoring the fact that the virus is unlikely to stay put if the outbreak is not brought under control.

There is no cure for yellow fever, but there is a vaccine that protects people against it. It is, however, in very short supply.

The WHO has sent its entire vaccine stockpile — 6 million doses — to Angola, which would like to vaccinate its population of nearly 20 million people.

“Luanda is 7.2 million inhabitants. So already it’s more than what we have in the emergency stockpile,” said Briand. “It’s all gone.”

Briand told STAT that the WHO has asked Angola to hold off on its plan to vaccinate the entire country for a month or two, until more vaccine is available.

As of last week, 5.7 million people had been vaccinated.

“You think SARS was bad? This would make it pale by comparison.”

Duane Gubler, Duke-NUS Medical School

Yellow fever is related to both Zika and dengue. Zika infection during pregnancy can trigger birth defects in the fetus. And dengue infection can be life-threatening in a small proportion of cases.

But yellow fever is in a class of its own, experts say. An initial phase — characterized by fever and the aches and pains common to dengue, chikungunya, and other similar viruses — is followed by a so-called toxic phase in about 15 percent of cases. About half of people who develop the severe form die, the WHO said.

The severe form of the disease can cause internal bleeding and organ failure. It can also cause jaundice, which is what gives yellow fever its name.

“It’s a very bad disease,” Briand said. “Even if not all the patients die, the ones with the severe form are really likely to die, especially in countries like Angola,” where access to advanced medical care is limited.

For decades, yellow fever has mainly been seen in jungle settings in sub-Saharan Africa and South America. The WHO estimates between 84,000 and 170,000 cases occur each year.

But Gubler, who teaches at the Duke-NUS Medical School in Singapore, warned that a number of factors are combining to create conditions that could let the virus reestablish itself in urban areas, starting with densely populated mega-cities where large numbers of the poor live in conditions that are ideal for breeding of Aedes aegypti mosquitoes. (These are the mosquitoes that also spread Zika, dengue, and chikungunya viruses.)

If yellow fever takes hold in urban populations of Aedes aegypti mosquitoes, the world will have a big problem on its hands.

“If you had a major outbreak in capital cities, it would be very difficult to control in due time. And it’s very hard to prevent people from traveling. So it would be very, very difficult,” Briand said.

The yellow fever vaccine is highly effective. But it is not made in large quantities because demand for it hasn’t existed in the recent past. In fact, in the early 2000s manufacturers — only four in the world make yellow fever vaccine — were talking about scaling back production.

Briand, who was then leading the WHO’s yellow fever program, convinced GAVI — the international vaccine alliance — to finance mass vaccination efforts in countries at high risk of having outbreaks. It was both a means of lowering the risk and stablizing the market for the vaccine.

“Many countries didn’t want to buy the vaccine because they couldn’t see the risk,” she said.

Gubler said he’s been pressing the largest manufacturer of yellow fever vaccine, Sanofi Pasteur, for years to stockpile more yellow fever vaccine.

The company, which sent 4 million doses of vaccine to Angola through UNICEF, has recently received the green light to produce in a newly constructed facility in France that will double its output. It has released 415 million doses of its yellow fever vaccine, Stamaril, over the past 30 years, a spokesperson said.

Gubler, though, foresees a need for much, much more.

So does Jack Woodall, one of the founders of ProMED — the Program for Monitoring Emerging Diseases — an Internet-based reporting system run under the auspices of the International Society for Infectious Diseases.

In a recent ProMED post, Woodall — who used to work at the WHO and is a former director of the Centers for Disease Control’s dengue operation — didn’t mince words about the dangers he sees in the current situation.

“If yellow fever were to spread in Asia, where 2 billion are at risk in 18 dengue-affected countries, hundreds of thousands could die before yellow fever vaccine stocks could be boosted and delivered,” he wrote.

“Apocalyptic forecasts of the numbers of fatalities from Ebola turned out to be wildly wrong, and we can hope that will again be the case here, but given the way Zika has exploded in the Western hemisphere, we can’t count on it,” Woodall added.

This story was originally published March 31, 2016

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