By Annette M. Boyle
FALLS CHURCH, VA—In mid-2016, Sanofi Pasteur announced that manufacturing issues could produce a YF-VAX shortage that might last for several months. Continued problems are expected to result in complete depletion of supplies this summer, and a new stock will not be available until mid-2018.
Though YF-VAX is the only yellow fever vaccine approved by the U.S. Food and Drug Administration and Sanofi is its only manufacturer, DoD has no concerns.
“DoD maintains a supply of yellow fever vaccine adequate to meet current and projected operational needs,” said Kevin Dwyer, spokesman for the Defense Health Agency. “We do not anticipate a complete depletion of supply prior to resumption of manufacturing.”
Yellow fever is endemic to 47 countries in sub-Saharan Africa and tropical areas of Central and South America. In the past two years, Angola, the Democratic Republic of the Congo and Brazil have experienced major outbreaks of the disease, which is caused by a flavivirus transmitted by the Aedes aegypti mosquito. Chad, Colombia, Ghana, Peru and Uganda also have reported recent outbreaks.
Nearly 85% of individuals infected with yellow fever exhibit no symptoms. Symptoms, including fever, headache, jaundice, muscle pain, nausea, vomiting and fatigue, occur among the other 15%, starting three to six days after infection. Among those who develop symptoms, fatality rates range from 20%-50%.
According to the DHA, 18 African countries require proof of yellow fever immunization. So do several countries within the DoD’s SOUTHCOM area of responsibility of Central and South America. Service members who cannot show immunization within the last decade may be denied entry, which could affect their mission or lead to quarantine or other detainment.
In a typical year, the DoD receives about 170,000 doses of the vaccine, according to the U.S. Centers for Disease Control and Prevention. In 2016, however, DoD facilities had to request additional doses through a tightly-controlled requisition process.
With the continued delay in production, the DoD has pursued a two-pronged strategy to ensure that servicemembers continue to have protection from yellow fever: careful husbanding of the available supplies of YF-VAX and an emergency investigational new drug (eIND) protocol for Stamaril, another yellow fever vaccine made by Sanofi and used in 70 countries worldwide.
To extend availability of YF-VAX, “DoD has worked with Sanofi Pasteur to maintain that inventory and to ensure that the health of service members deploying to areas where the vaccine is needed won’t be jeopardized,” Dwyer told U.S. Medicine.
Steps implemented last year remain in effect, including:
- No immunization at accession sites.
- No routine yellow fever vaccination, unless a servicemember is traveling to country with endemic yellow fever.
- No authorization of routine 10-year booster doses.
Immunization for beneficiaries is restricted to those within 30 days of travel to yellow fever endemic areas. To preserve available doses for operational needs, the DHA advises individuals traveling to areas with endemic yellow fever for nonoperational reasons to follow Advisory Committee on Immunization Practices (ACIP) guidelines. ACIP “recommends that a single lifetime dose of yellow fever vaccine is sufficient for most travelers,” Dwyer noted.
In addition to reducing nonessential immunizations, DHA urged all organizations with YF-VAX stock to carefully monitor expiration days and to vigilantly monitor storage and handling processes to ensure no vaccine supplies go to waste. In a similar vein, DHA strongly advocated careful use of the five-dose vials of the vaccine, noting that military treatment facilities “should ensure five people are ready to receive the vaccination at one time as the vaccine must be used within 60 minutes of reconstitution.” The vaccine comes in both single-dose and five-dose vials.
“Provided the current utilization is maintained, DoD does not anticipate need to implement eIND during this shortage,” Dwyer said.
To stay on the safe side, however, the DoD developed an eIND protocol for Stamaril late last year, similar to the civilian expanded access IND submitted by Sanofi Pasteur and accepted by the FDA in October to ensure the U.S. continues to have access to a yellow fever vaccine. The eIND allows importation of Stamaril for military use at a restricted number of sites. Stamaril and YF-VAX utilize the same vaccine substrain and have similar safety and efficacy.
“Our focus has been to provide a continuous supply of yellow fever vaccine in the U.S. for travelers, government employees, military and other response groups,” said David Greenberg, MD, associate vice president and regional medical head of Sanofi Pasteur, North America in an update to ACIP on the U.S. supply. “To that end, we have held stakeholder discussions for over a year with the CDC, FDA, Department of Defense and others to manage the remaining supply of YF-VAX and to import the alternative vaccine.”
Production issues had caused intermittent yellow fever vaccine shortages in previous years, Greenberg noted. The current shortage of YF-VAX arose from a decision in 2015 to transfer domestic production of the vaccine to a newer facility that would open in 2018. A manufacturing issue led to the loss of a significant number of doses. The production of a limited number of doses in late 2016 delayed the predicted total depletion date until this summer but was insufficient to meet expected demand until the new facility opens next year.