Experts Alarmed by Yellow Fever Cases in Asia

Janis C. Kelly

October 03, 2017

Eleven cases of yellow fever (YF) brought to China in 2016 were quickly contained but set off fear that the disease might gain a foothold in Asia, where 1.8 billion unvaccinated people could be at risk.

The introduction, by workers returning to China from Angola, highlight the dire straits epidemiologists face in trying to contain a disease with limited vaccine supplies. Shortages of YF vaccine developed because of outbreaks and the need for mass vaccinations in Angola and Brazil. By July 24, 2017, stocks of the only YF vaccine approved in the United States had been depleted, and supplies are not expected to become available for routine civilian use again until mid-2018.

Daniel R. Lucey, MD, MPH, and Halsie Donaldson, MS, both from the Division of Infectious Diseases, Georgetown University Medical, Washington, DC, write that the new risk for YF in Asia means that "the global vaccine stockpile must contain more than the projected 1.38 billion doses needed to eliminate existing YF epidemics by 2026." They published their findings online September 25 in Annals of Internal Medicine. The authors also explain that the 80-year-old, egg-based method currently used to manufacture YF vaccine cannot be scaled up quickly enough to stop urban epidemics.

"Thus, new YF vaccines based on cell culture and DNA technologies should be developed now, rather than in the mid to long term cited in the [World Health Organization's] Global Strategy to Eliminate Yellow fever Epidemics," the authors write.

Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine, professor of Pediatrics and Molecular & Virology and Microbiology, and head of Pediatric Tropical Medicine at Baylor College of Medicine, Houston, Texas, agreed that new methods for producing YF vaccine are urgently needed, even without the potential for YF outbreaks in Asia.

"With regard to Asia, it remains somewhat of a mystery as to why YF has not spread there, as has Japanese encephalitis. Some have speculated that circulating dengue and [Japanese encephalitis] strains may provide some cross-protective herd immunity, but we really don't know the answer," Dr Hotez told Medscape Medical News. "But there are 3 million Chinese working in Africa now, through their belts-and-road initiative, and there is a theoretical threat to Asia. Moreover, we can be sufficiently concerned about YF in the western hemisphere and Africa alone to raise the issue of YF vaccine shortage."

Dr Hotez said that Dr Lucy and Donaldson are right to be concerned about the potential for YF outbreaks in both Africa and the Americas, as well as the possibility of YF vaccine shortages. "In the western hemisphere, we have seen during the last few years the rise of dengue, Zika, chikungunya, and other arboviruses transmitted by Aedes aegypti, so the threat of YF is very real. This is due to shifts in poverty and climate change. The risk to other areas, including the United States, has been further heightened by increased population density in urban areas, making transmission more likely, and by the widespread presence of mosquitoes able to transmit the virus," he said.

However, Dr Hotez also echoed the comment by Seth Berkley, MD, chief executive from Global Alliance for Vaccines and Immunization, that emergency vaccine stockpiles should be the last line of defense against YF, after better mosquito control, routine YF immunization, and preemptive vaccination campaigns. According to Dr Berkley, emergency YF vaccine stockpiles are essential, but "if we have to call upon them, we have in some way already failed. They should be our last line of defense."

Dr Berkley notes that the current global emergency stockpile of YF vaccine is about 6 million doses, a supply that could be quickly exhausted if Rio (population 12 million) and one other major city had YF outbreaks.

Meanwhile, shortages in the United States are already limiting the availability of YF travel vaccinations, which are required for travelers to enter some countries.

Dr Hotez told Medscape Medical News that part of the problem is the demand for YF vaccine has not been high until recently. "There is not always a high market incentive for vaccine manufacturers to make vaccines for pandemic threats, which is why the new organization [Coalition for Epidemic Preparedness Innovations] has been established," he said.

In the United States, YF vaccination is not routinely recommended except for patients traveling to an endemic area. Containing a potential outbreak is likely to be complicated by the fact that few US physicians have ever seen a case of YF, which causes a self-limited fever in 85% of patients but black vomit; bleeding from nose, mouth, and eyes; jaundice; and renal damage in the other 15%, half of whom die from the infection.

The authors and Dr Hotez have disclosed no relevant financial relationships.

Ann Intern Med. Published online September 26, 2017. Abstract

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