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The Angola military administers yellow fever vaccine at the Quilometro 30 market in Luanda in February.

The Angola military administers yellow fever vaccine at the Quilometro 30 market in Luanda in February.


Angolan yellow fever outbreak highlights dangerous vaccine shortage

The three people dressed in baby blue plastic suits and goggles form a human conveyor belt for chicken embryos. The first takes a tray of eggs that were injected with a yellow fever vaccine virus, then left to incubate for 4 days, and cuts the top off each egg. The second tweezes the embryos out of the eggs and deposits them in a large bottle. The last person adds some liquid, then blends the embryos into a rich, red broth that contains millions of weakened virus particles.

The end result of this procedure, repeated dozens of times every week at the Pasteur Institute of Dakar, is a highly effective vaccine that offers lifelong protection against yellow fever. But the 80-year-old process is decidedly low-tech and hard to scale up—and that's become a problem, because a big yellow fever outbreak that started in December 2015 in Luanda, Angola's capital, has emptied the world's strategic reserves of the vaccine.

The Pasteur Institute, which makes about 10 million doses a year, is one of only four facilities around the world producing yellow fever shots, joining two government-run plants in Russia and Brazil and French vaccine company Sanofi Pasteur. Their combined output has long fallen short of the world's needs, and the Angola outbreak has worsened the shortfall. Another major outbreak—for instance in Asia, where yellow fever has never gained a foothold—could be impossible to control, says Jack Woodall, a retired virologist in London, formerly of the Centers of Disease Control and Prevention and the World Health Organization. “I hate being alarmist," says Woodall, who's also a moderator at the Program for Monitoring Emerging Diseases, an online alert system for disease outbreaks. "But this is something I’m really panicking about.”

The vaccine is the only bulwark against yellow fever, a formidable killer without a cure that's transmitted primarily through the bite of Aedes aegypti, also known as the yellow fever mosquito. Most infected people have no symptoms at all; some experience fever, joint pains, and headaches. But roughly 15% progress to a more severe stage in which their eyes and skin turn yellow; they may also bleed from the eyes, nose, and mouth. Up to half of these serious cases are fatal. Although yellow fever is endemic in much of Latin America, Africa bears by far the highest burden. Exact numbers are hard to come by, but a study published in 2014 in PLOS Medicine estimated that the disease kills 78,000 Africans every year—although many experts felt that number was too high.

Most infections occur in or close to the jungle, where mosquitoes spread the virus primarily between monkeys and occasionally infect a human bystander as well. Urban outbreaks, like the one in Angola, can be far more severe, because mosquitoes can transmit the virus from person to person. “That’s when the disease can really take off,” says William Perea, of the World Health Organization's (WHO’s) Control of Epidemic Diseases department in Geneva, Switzerland. Angola has seen 490 confirmed cases and 198 deaths so far, but experts say the real toll may be 10 times as high. “We haven’t seen an outbreak like this in many years,” Perea says.

A huge vaccination campaign launched in February has already reached almost 6 million of Luanda's roughly 7.5 million inhabitants. But the disease has since spread to six of the country's 18 provinces, and the global emergency stockpile of 6 million vaccines is empty. "This is definitely a stressful situation,” says Melissa Malhame of Gavi, the Vaccine Alliance, a Geneva-based public-private partnership that aims to increase immunization in poor countries.

A ramped-up battle against yellow fever had already strained the global supply of vaccine. Many countries have made the shot part of their routine vaccination schedules for children, while massive catch-up campaigns were launched to protect entire populations that never received the vaccine before. A United Nations Children's Emergency Fund report last year estimated that the organization needed 42% more vaccine in the next 3 years than is available to it. A 2013 report put global production in 2009 at 75 million doses, up from 30 million in 2000 but well short of the 105 million doses needed that year. The exact annual production today is unknown, but it's probably about 80 million doses, says Tom Monath, a virologist who has studied yellow fever for decades and currently works at NewLink Genetics, a biotech company in Ames, Iowa. To make matters worse, the factory in Dakar is about to shut down for a 5-month renovation.

Things may get better in the long run. Demand for the vaccine should decline in a few years, after countries wrap up their catch-up campaigns. The Pasteur Institute is building a new facility in Diamniadio, about 30 kilometers from Dakar, that could triple production by 2019; Sanofi Pasteur has built a new facility in France.

In the meantime WHO has urged Angola to only vaccinate in areas where yellow fever is spreading. But infected travelers have already brought the disease from Angola to three other countries in Africa, including the Democratic Republic of the Congo; if the disease started circulating in its sprawling capital, Kinshasa, that could be catastrophic, Monath says.

"I think all the specialists in my field agree that there is a real and present danger of having a major outbreak of yellow fever that is uncontrollable,” adds medical entomologist Paul Reiter of the Pasteur Institute in Paris. "It’s a ticking time bomb.” One stopgap measure might be to lower the vaccine dose, Monath says; some studies have shown that just one-fifth or one-tenth of the current dose could protect people.

Spread to Asia is the nightmare scenario for yellow fever experts. Angola is home to many Chinese workers, and in at least six cases they have already brought the virus to China. Five of these cases occurred in Beijing, where Aedes aegypti does not occur, so the disease could not spread. But the mosquito is abundant in southern China and elsewhere in Asia—and so are vulnerable people. Oddly, however, yellow fever has never taken off on that continent.

There is a real and present danger of having a major outbreak of yellow fever that is uncontrollable.

Paul Reiter, a medical entomologist at the Pasteur Institute in Paris

Perhaps Asia has just been unbelievably lucky. "It didn’t happen before, but does that mean it is not going to happen now?" Perea asks. "Nobody knows.”