The yellow fever epidemic currently raging in parts of Africa and threatening Latin America and Asia could exhaust available vaccine supplies and trigger a new global health emergency, experts warn. The World Health Organization (WHO) should convene an emergency committee "to mobilize funds, coordinate an international response, and spearhead a surge in vaccine production."

Writing in a JAMA viewpoint published online May 9, Daniel Lucey, MD, MPH, and Lawrence O. Gostin, JD, from the O'Neill Institute for National and Global Health Law, Georgetown University, Washington, DC, also urge WHO to adopt a new structure for dealing with fast-emerging international health threats such as Ebola virus, Zika virus, and yellow fever: A permanent committee to meet regularly and advise the WHO director-general on whether to declare an emergency and/or take necessary steps to avert a crisis.

"Prior delays by the WHO in convening emergency committees for the Ebola virus, and possibly the ongoing Zika epidemic, cost lives and should not be repeated," Dr Lucey and Gostin write.

The laboratory-confirmed outbreak of yellow fever began in Angola in December 2015 and was reported to the WHO on January 21, 2016. As of last month, the country had 2023 suspected yellow fever cases and 258 deaths.

Cases arising from travelers to Angola have also been reported in China, the Democratic Republic of Congo, and Kenya. The shared border with Angola also puts Namibia and Zambia at risk.

Furthermore, the Pan American Health Organization declared an epidemiological alert on April 22 for yellow fever in Latin America, where the Aedes aegypti mosquito vector is also actively transmitting Zika and dengue viruses. Yellow fever is transmitted to humans by mosquitoes, primarily Aedes or Haemagogus species.

Vaccination with a licensed, live attenuated yellow fever vaccine confers lifelong protection in more than 90% of individuals and, along with mosquito control and surveillance, is key to control of outbreaks. However, the supply of vaccine is limited.

More than 7 million Angolans have been vaccinated, and on May 2, the Democratic Republic of Congo announced plans to vaccinate nearly 2 million more individuals.

"This campaign, along with Angola, could be a tipping point in exhausting global vaccine supplies," the authors warn. Ramping up yellow fever vaccine production will be slowed by the need for specific pathogen-free chicken eggs to produce the vaccine.

There are no specific antiviral drugs or immune therapies for yellow fever. Without vaccination, most patients recover from the acute febrile phase with attendant myalgia, headache, back pain, anorexia, nausea, and vomiting within 1 week, but about one in seven patients develops a second phase that includes high fever, jaundice, bleeding, and kidney damage. Mortality is about 50% in the patients who develop that second phase of yellow fever.

Yellow fever vaccine provision is overseen by the International Coordinating Group, for which WHO serves as the secretariat. This group maintains a vaccine stockpile for rapid response, and that stock is expected to run out if the current yellow fever epidemic spreads to other countries or regions.

The authors suggest that WHO use the Emergency Use Assessment and Listing procedures introduced to deal with Ebola to "safeguard the yellow fever vaccine supply" by cutting doses in Angola to one fifth the normal vaccine dose, but acknowledge that the duration of immunity with such doses is uncertain, "especially in children." To authorize a reduced dose, the WHO director-general would have to declare that yellow fever constitutes a public health emergency of international concern or determine such action is "in the best interest of public health," according to the authors. The WHO director-general can declare a public health emergency only by convening an emergency committee.

Peter Hotez, MD, PhD, dean, National School of Tropical Medicine; professor, Department of Pediatrics and Department of Molecular Virology and Microbiology; and head, Section of Pediatric Tropical Medicine, Baylor College of Medicine, Houston, Texas, told Medscape Medical News that the recommendation to consider using lower doses of yellow fever vaccine is supported both by reduced-dose studies in individuals with egg allergy and by a randomized controlled noninferiority trial showing protective immunity in all volunteers given intradermal yellow fever vaccine at one fifth the usual dose.

Next steps for WHO might include meetings with vaccine manufacturers "to catalyze a surge in production," funding and coordinating research on new non-egg-based vaccines, and coordinating mosquito control, according to Dr Lucey and Gostin. They also argue for a standing emergency committee, in part because the increased frequency of emerging infectious diseases and the consequences of delayed international response "make it no longer tenable to place the sole responsibility and authority with the WHO's director-general to convene currently ad hoc emergency committees."

Dr Hotez told Medscape Medical News that this recommendation echoes the post-Ebola analysis by the Harvard-LSHTM Independent Panel on the Global Response to Ebola, a project organized by the Harvard Global Health Institute and the London School of Hygiene & Tropical Medicine.

"My understanding is that a similar committee was previously recommended by the Harvard London School task force in response to WHO's handling of the Ebola outbreak," Dr Hotez said. He pointed to Recommendation 5 in the Harvard LSHTM report: "Institutionalise accountability through an independent commission for disease outbreak prevention and response."

The viewpoint authors also note that WHO is beginning the campaign for a new director-general, which might be "an opportune moment" for this type of change.

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

JAMA. Published online May 9, 2016. Full text

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