The Return of Yellow Fever

SEATTLE – Before the horrors of the latest Ebola outbreak in West Africa could even begin to fade from our minds, the Zika virus emerged as a major global health risk, and is now occupying researchers and doctors in South America, Central America, and the Caribbean. Yet the death toll from another virus is rising fast: yellow fever.

In southwestern Africa, Angola is facing a serious yellow fever epidemic – its first in 30 years. Since the virus emerged in Luanda, Angola’s capital and most populous city, last December, it has killed 293 people and infected a suspected 2,267. The virus has now spread to six of the country’s 18 provinces. Travelers have taken cases to China, the Democratic Republic of Congo, and Kenya. Namibia and Zambia are on high alert.

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Yellow fever virus is transmitted by Aedes aegypti – the same mosquito that spreads the Zika virus. Symptoms include fever, muscle pain, headache, nausea, vomiting, and fatigue. At least half of untreated patients with severe cases of yellow fever die within 10-14 days.

The good news is that, unlike Zika or Ebola, yellow fever can be controlled with an effective vaccine, which confers lifelong immunity within a month of administration. And, indeed, vaccination forms the core of Angola’s National Response Plan, initiated early this year with the goal of administering the yellow fever vaccine to more than 6.4 million people in Luanda Province. So far, nearly 90% of that target population has been vaccinated, thanks largely to the World Health Organization, the International Coordinating Group for Vaccine Provision, and other countries, including South Sudan and Brazil, which together made some 7.35 million doses of the vaccine available.

The mass vaccination effort has stemmed the spread of yellow fever. But to end the outbreak, vaccination has to continue not only in Luanda, where an additional 1.5 million are at risk of infection, but also encompass other affected provinces. This will be a major challenge.

One key problem is cost. In 2013, the yellow fever vaccine cost $0.82 per dose in Africa – a price that most developing countries cannot afford. A 2015 report by Médecins Sans Frontières showed that the vaccine is now almost 70 times more expensive than it was in 2001.

Making matters worse, even if countries have the money, there are serious supply constraints. Senegal’s Pasteur Institute of Dakar, one of only four facilities in the world producing yellow fever vaccines, manufactures about ten million doses per year, and the manufacturing process is extremely difficult to scale up. Moreover, the Pasteur Institute is about to close down for a five-month renovation, during which it will be unable to produce more vaccine.

Fortunately, the situation is set to improve. The Pasteur Institute is constructing a new facility about 30 kilometers from Dakar, in Diamniadio, that is expected to triple production by 2019. Another yellow fever vaccine manufacturer, Sanofi Pasteur in France, is also expanding its manufacturing capacity. (The other two manufacturers are based in Brazil and Russia.)

For now, however, supplies are tight. One way to stretch existing stores could be by administering a fractional dose (one-fifth of the usual dose), which has also been shown to protect against yellow fever.

But even that may not be enough if the virus spreads further. And, unfortunately, the high density of Aedes aegyptii mosquitoes in the affected areas means that the risk of transmission remains high.

An outbreak in a region like Asia, which lacks experience with a yellow fever epidemic and has no capacity to manufacture the vaccine, would be particularly difficult to control. According to John P. Woodall, the founder of the disease-alert service ProMED, if yellow fever spreads to parts of Asia with the right climate and mosquito species, hundreds of thousands could be infected (and possibly die) before vaccine stocks are delivered.

The virus also has the potential to spread to the Americas, which are home to Aedes mosquito vectors that transmit not only yellow fever, but also dengue, Zika, and chikungunya. Already, the Pan American Health Organization has declared an epidemiological alert for yellow fever in Latin America.

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To help limit yellow fever’s spread, international health regulations require that all travelers to the 34 countries where yellow fever is endemic present a vaccination certificate. But the implementation of those regulations depends on each country’s capacity, and is thus far from perfect. Already, a total of nine laboratory-confirmed cases of yellow fever imported from Angola have been reported by the National IHR Focal Point of China. Reports of yellow fever infection in non-immunized travelers returning from a country where vaccination against the disease is mandatory highlights the need to reinforce the implementation of vaccination requirements.

The WHO is working closely with several partners and the Angolan government to combat the current outbreak. But, as some health experts have pointed out, even more needs to be done. The WHO now must convene an emergency committee to coordinate a broader international response, mobilize funds, and spearhead the rapid scale-up of vaccine production, as well as a “standing emergency committee” capable of addressing future public-health crises quickly and effectively.