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Booster doses of yellow fever vaccine may be warranted
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The immunogenicity of yellow fever vaccine given to children in Mali and Ghana at age 9 months rapidly waned, researchers reported in The Lancet Infectious Diseases.
“Our results suggest that revaccination should be considered to assure long-term immunity to yellow fever,” Christina Domingo, PhD, from the department of highly pathogenic viruses at the Robert Koch Institute in Berlin, told Infectious Diseases in Children. “However, more data are needed to draw up recommendations for yellow fever vaccination of infants in endemic countries.”
Domingo added that the findings also suggest yellow fever could occur among patients with a valid record of yellow fever vaccination during infancy.
WHO guidelines currently recommend a single dose of vaccine given between ages 9 and 12 months in endemic areas.
In a longitudinal cohort study, Domingo and colleagues measured antibodies against yellow fever in 587 children in Mali and 436 children in Ghana who were immunized between June 5, 2009, and Dec. 26, 2012. All children were vaccinated around age 9 months. Researchers defined seropositivity as an antibody concentration of 0.5 IU/mL or less.
At follow-up, which lasted between 2 to 6 years, 50.4% (95% CI, 46.4%-54.5%) of children in the Mali cohort were seropositive. Among children in Ghana, the seropositivity rate was 27.8% (95% CI, 23.5%-32%). This shows a large drop in the proportions of infants who were seropositive 28 days after vaccination — which stood at 96.7% in Mali and 72.7% in Ghana.
Seropositivity increased among children in Ghana after 6 years (43.1%; 95% CI, 38.5%-47.8%), but the researchers said this may be explained by unrecorded reimmunization or infection with wild yellow fever during an outbreak between 2011 and 2012.
“These findings are of special importance for travel medicine doctors with patients traveling to high-risk areas who have to decide on the need for booster doses,” Domingo said. “The results show that we cannot assume that an individual vaccinated against yellow fever as an infant will be protected against the disease for life and that these travelers might benefit from a vaccine booster.”
Pedro F. C. Vasconecelos , MD, and Alan D. T. Barrett, PhD, wrote in a related commentary that yellow fever booster doses were previously recommended every 10 years, but WHO advised against this schedule in 2013, excluding certain groups. They wrote that similar findings of waning immunity have been observed in Brazil among adults.
However, they noted that different vaccine manufacturers provided vaccines for the Mali and Ghana cohorts.
“Additional research is needed for this group of vaccines to determine whether the different yellow fever vaccines stimulate the immune system differently,” Vasconecelos and Barrett wrote. “Equivalent studies will also be needed in some of the other 40 countries where yellow fever is endemic, assessing all four WHO prequalified vaccines, to provide more information on whether booster doses are needed for children and, consequently, whether modifications to the current immunization regimen are necessary.” – by Katherine Bortz
References:
Domingo C, et al. Lancet Infect Dis. 2019;doi:10.1016/S1473-3099(19)30323-8.
Vasconcelos PFC, Barrett ADT. Lancet Infect Dis. 2019;doi:10.1016/S1573-3099(19)30411-6.
Disclosures: Domingo, Vasconcelos and Barrett report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Thomas M. Yuill, PhD
Yellow fever poses an ongoing risk for many people living in or visiting Africa and South America, where the virus is endemic. Cases and fatalities occur on both continents currently, eliciting extensive vaccination campaigns. WHO recommends that people living in countries where yellow fever occurs aged 9 months or older should receive the vaccine. Vaccination is, by far, the most effective measure to prevent yellow fever, which has a case fatality rate of around 30%. The WHO Expanded Programme on Immunization includes yellow fever vaccination of infants aged 9 to 12 months. It is suggested that a single dose of vaccine provides life-long protection, resulting in the elimination of recommended boosters every 10 years.
Domingo and colleagues studied persistence of yellow fever neutralizing antibodies in 587 Malian and 436 Ghanaian children vaccinated between June 5, 2009, and Dec. 26, 2012. They described the rapid decline in neutralizing antibody in these infants. Tests for neutralizing antibodies are sensitive and specific. The presence of neutralizing antibodies is indicative of immunity to yellow fever virus infection, and decline to undetectable levels is interpreted as loss of immunity to infection.
The open question is whether children with a loss of measurable neutralizing antibody are fully susceptible to yellow fever virus infection or if there is residual immunity at undetectable levels that still provides some protection. Because testing susceptibility is out of the question, the safest approach is to modify WHO recommendations and revaccinate children in that age despite current WHO advice that a single dose of the vaccine produces lifelong immunity. If a booster dose is administered, it would be interesting to see if it elicits an anamnestic antibody response in children who had antibodies previously. That would indicate there are still quiescent resident B cells capable of a rapid antibody response.
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