As the World Is Hit with Vaccine Shortages, Will This Mosquito-Borne Virus Find Its Way to Asia?

Yellow fever—a virus transmitted through the bite of an infected mosquito—has recently made headlines in relation to the recent outbreak that sprung up in Brazil this year, an outbreak that occurred at the same time as a global vaccine shortage.

In a “Late Breakers II” symposium at ID Week 2017, Daniel Lucey, MD, MPH, from the department of Medicine/Infectious Diseases at Georgetown University Medical Center, provided insight on past yellow fever outbreaks, vaccine shortages, and what needs to be done in order to prevent future outbreaks in susceptible countries, such as those in Asia.

Dr. Lucey opened his presentation by providing a brief overview of the 2 different types of epidemiologic cycles for the virus: the urban and the sylvatic. He shared that the urban cycle “is the one we know best.” It occurs in cities where Aedes aegypti mosquitoes, or yellow fever mosquitoes, exist and spread the disease from person-to-person. In contrast, the sylvatic cycle occurs mostly in forests or jungles, involving non-Aedes aegypti mosquitoes—such as the hemophagus—and monkeys. Sometimes humans get infected as well, as can be seen in the ongoing epidemic in Brazil.

Another notable yellow fever epidemic that occurred in 2016 started in Luanda, the capital of Angola, and continued to spread throughout the country, moving north until it crossed the border into the Democratic Republic of Congo (DRC), ravaging cities and rural regions alike. It didn’t stop there; the disease continued to spread north to the DRC’s capital, Kinshasa. “Personally, I was very concerned that it was going to cross the river and go into Brazzaville, and then perhaps extend through the Republic of Congo, and eventually get to Nigeria,” Dr. Lucey admitted. Fortunately, an international response that included mass vaccination throughout Angola and consisted of dozens of millions of doses of vaccine, managed to stop the disease before it spread further.

Nevertheless, Dr. Lucey mentioned that the disease managed to reach China because 10 infected travelers brought it home with them. “For me, this is a very large red flag about what could easily happen in the near future—meaning in the coming months or years—in terms of the yellow fever virus coming to Asia where there haven’t been yellow fever epidemics,” despite the fact that Aedes aegypti mosquitoes are present in the continent and are known to transmit other infectious diseases such as dengue. You can listen to Dr. Lucey talk about this threat further in the interview clip below.

With an eye on the spread of the disease through Angola, Dr, Lucey shared that investigators recommended the use of one-fifth or even one-tenth of the regular dose of the regular vaccine just in case of shortage (The study was published in the Lancet.) Following that, he also spoke about an article that he co-authored, published in the Journal of American Medicine, that further anticipated a vaccine shortage, especially if the disease spread to Asia. “What we were very worried about actually, unfortunately, came to pass,” Dr. Lucey said. “A yellow fever vaccine shortage in the face of a yellow fever epidemic in Angola.”

When this happened in Kinshasa in July and August of 2016, health officials from all different international organizations came together for a “valiant” vaccination effort, in which they administered one-fifth, or 20% of a regular dose of vaccine to upwards of 7 million individuals; this was the first time that a fractional dose had ever been given in a mass vaccination campaign and, consequentially, had succeeded in stopping an epidemic. The question remains though—how long does immunity against the disease last with a fractioned dose?

The answer to this question could have “very important implications” Dr. Lucey explained. "If there had been one other city, if the virus had crossed over to Brazzaville (which is within eyesight of Kinshasa), then there probably wouldn't have been enough vaccine to give full dosing, so it would have to have been reduced dosing." He stated that 3 small studies published in the past thought the answer to be 12 months. “[The authors] stated that probably immunity after a one-fifth dose lasts for longer than 1 year, but it’s never been studied,” he said.

Following the successful vaccination campaign— “the first of its kind, ever, in history”—a World Health Organization (WHO) committee met again to create the Global Strategy to Eliminate Yellow Fever Epidemics (EYE), a ten-year plan, ranging from 2016 to 2026. The plan is to “create all together a stockpile of yellow fever vaccine: it’s estimated that about 1.38 billion doses would be necessary to eliminate yellow fever from sub-Saharan Africa and Latin America,” Dr. Lucey explained. Although WHO recognized the potential of Asia falling victim to an epidemic, there is no vaccine stockpiling plan in place for the continent. “In the moderate to a longer-term time frame, that could become a focus for emphasis,” Dr. Lucey said. “In my view, it should be emphasis now, in the short-term.”

He also highlighted the “unanticipated and fairly large” outbreak that sprung up in Brazil, an outbreak that spread “right up to the edge of several large cities, include Rio de Janeiro and San Paulo.” At the same time, Brazil was experiencing a yellow fever vaccine shortage. “Brazil produces more yellow fever vaccine, to my knowledge than any other country in the world,” Dr. Lucey shared. Despite this, they still had to import 3.5 million doses from the global stockpile to fight the outbreak, which consists of 798 lab-confirmed cases and over 2000 suspected cases thus far. “There’s no urban transmission, and there hasn’t been in many decades in Brazil but we came very, very close,” he stressed. “And if it had reached the cities, then I think the issue would have been brought up again: if there’s not enough vaccine, then use reduced doses of yellow fever vaccine for people within the cities.”

Brazil is not the only country that is experiencing vaccine shortage, the United States is as well. In past coverage, Contagion^® reported on the shortage that occurred unrelated to the international global shortage. While moving from one vaccination facility into another, doses of the US Food and Drug Administration (FDA)-licensed yellow fever vaccine (YF-VAX) were lost. Because of the shortage, an alternate yellow fever vaccine (Stamaril), not yet licensed, is available under the FDA’s investigational new drug (IND) protocol. Although it is currently available in the United States, there is a limited supply, and thus, fewer locations have it as compared with the many locations that once held the YF-VAX.

One big change regarding yellow fever vaccination occurred in July 2016, when WHO no longer required individuals to get re-vaccinated every 10 years. “The WHO said that a single dose—for the great majority of people—gives lifelong immunity,” Dr. Lucey explained. “That’s a major change, and it’s certainly good news, especially now that there are shortages of the yellow fever vaccine.”

Taking such shortages into consideration, and looking to the future Dr. Lucey and his colleagues called for the following:

• Stockpiling of yellow fever vaccine for Asia
• Initiating studies to test new technologies, such as cell culture- or DNA-derived vaccines
• Asking the Coalition on Epidemic Preparedness Innovation to prioritize yellow fever vaccine production

“I would argue that a clear and present danger, a predictable catastrophe, is yellow fever coming to Asia. So, we should take all the countermeasures now, including stockpiling the vaccine,” Dr. Lucey concluded.