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Fractional Yellow Fever Vaccine Dose Remains Protective After a Decade

DEC 04, 2018 | JARED KALTWASSER
A new study shows a fractional dose of yellow fever vaccine is not just a good stop-gap measure, but can actually provide long-term protection.

Yellow fever is an incurable, highly fatal acute hemorrhagic viral disease spread by mosquitoes. It gets its name from the fact that in some patients, the disease is accompanied by jaundice. Other symptoms include fever, headaches, muscle pain, fatigue, and vomiting. According to the World Health Organization (WHO), as many as half of the people who become infected with the virus will die from it. The virus is currently endemic in Africa, Central America, and South America.

The good news is that there is a highly effective vaccine that can prevent yellow fever. The bad news is that vaccine supplies are often lacking in affected areas. Thus, when an outbreak occurs, local officials are frequently left scrambling to find sufficient vaccine supplies.

Investigators from the Leiden University Medical Center, in the Netherlands, wanted to know whether the strategy of providing fractional doses—one-fifth of the normal amount—was a good long-term strategy for dealing with vaccine shortages.

In findings published last week, the team followed up with a group of patients who had received fractional doses 10 years ago.

The results were encouraging—the patients remained protected.

First author Anna H.E. Roukens, MD, PhD, of Leiden University Medical Center, told Contagion® that at the time the patients were given the fractional dose, it was not yet clear how long the protection might last or whether a booster might be needed. However, in the intervening years, it’s become clear that the fractional dose provides long-term coverage.

Thirty-nine of 40 people who received fractional doses still had protective levels of yellow fever-neutralizing antibodies after a decade. That’s virtually identical to the 34 of 35 people who still had protection after receiving full doses.

“We were actually not surprised by the results, as we had already demonstrated that the fractional dose was noninferior to the standard dose a year after vaccination,” she said. “The immune response is unlikely to change after this period, and so to us, the response after a year equals the response after 10 years and more.”

Those findings are good news for patients in the Democratic Republic of Congo (DRC), one of the most recent countries where the fractional-dose strategy was widely used to control an outbreak.

Back in 2016, yellow fever broke out in Angola and the DRC. In the latter country, public health officials adopted a strategy that called for 10.5 million at-risk individuals to be vaccinated against the disease. The problem? The WHO had only 5.8 million doses available. In response, Congolese officials decided to ration the vaccine, giving patients just 0.1 ml of the vaccine instead of the standard 0.5 ml dose.

According to an August New England Journal of Medicine article discussing the event, the rationing strategy is effective because a typical vaccine dose far exceeds the amount of vaccine the WHO says is necessary to protect someone. On average, commercially available vaccines have between 12,874 and 43,651 international units (IU). The WHO suggests vaccines have at least 1000 IUs.

“In principle, the quantity of vaccine virus in fractional doses of standard vaccine would therefore still exceed the WHO’s minimum requirement,” Kirsten Vannice, PhD, MHS, of the US Centers for Disease Control and Prevention, and colleagues wrote.

Still, Dr. Vannice, writing this summer, said additional research is needed to confirm the efficacy of the strategy, including larger studies. And although the Dutch study demonstrates the long-lasting efficacy of fractional doses, it was also based on just 75 study enrollees, less than half of the 155 people who initially enrolled in the study and were given the vaccine.

The study, “Long-Term Protection After Fractional-Dose Yellow Fever Vaccination: Follow-up Study of a Randomized, Controlled, Noninferiority Trial,” was published December 4 in the Annals of Internal Medicine.
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