Yellow Fever Immunity Wanes Rapidly After Vaccination During Infancy

By Will Boggs MD

October 15, 2019

NEW YORK (Reuters Health) - Many children vaccinated against yellow fever in infancy lose immunity within a few years after vaccination, according to a longitudinal study.

"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," said Dr. Cristina Domingo of the WHO Collaborating Center for Emerging Infections and Biological Threats, in Berlin.

"For physicians working in yellow fever endemic areas, this means that cases of yellow fever could occur in patients with a valid record of yellow fever vaccination administered during infancy," she told Reuters Health by email.

Although the World Health Organization (WHO) advocates a single dose of yellow fever vaccine for lifelong protective immunity, the resurgence of yellow fever in 34 African countries and 13 countries in the Americas has been attributed largely to lapses of vaccination coverage and waning of population immunity. Some studies have shown seroreversion rates as high as 40% 5-10 years after vaccination.

Dr. Domingo and colleagues evaluated the long-term persistence of neutralizing antibodies to yellow fever virus following routine vaccination in healthy infants aged around 9 months. The study included 436 children from rural communities in Ghana and 587 children from urban communities in Mali.

Among Ghanaian children, 72.7% were seropositive four weeks after vaccination, but only 27.8% (121/436) remained seropositive to yellow fever virus 2.3 years after vaccination. Another 11.7% (51/436) were classified as borderline.

Similarly, seropositivity rates among Malian children decreased from 96.7% four weeks after vaccination to 50.4% (296/587) 4.5 years after vaccination. Another 19.3% of children were classified as borderline, the researchers report in The Lancet Infectious Diseases, online September 19.

In the Ghanaian group, seropositivity rates increased (to 43.1%) six years after vaccination, but this might be confounded by unrecorded revaccination or natural infection with wild yellow fever virus during a 2011-12 outbreak in northern Ghana.

"The results suggest that revaccination should be considered to assure long-term immunity to yellow fever," Dr. Domingo said. "However, more data are needed to draw up recommendations for yellow fever vaccination of the very young in endemic countries."

"While the observed outcome of this study certainly depends on multiple conceivable predictors (which may explain the differences we observed between the Ghana and Mali children), we must not lose sight of one of the most consequential factors: time, which undeniably has a large negative effect on yellow fever immunity in both children populations," she said. "It is important now to measure the decay of immunity dependent on the passage of time in children vaccinated at 9-12 months of age."

"Similar indications have come from studies in adults, especially in Brazil, with strong evidence that a booster dose is needed at 10 years to obtain long-term protection against yellow fever," write Dr. Pedro F. C. Vasconcelos of Para State University, in Belem, Brazil, and Dr. Alan D. Barrett of the University of Texas Medical Branch, in Galveston, in a linked editorial.

"Although Domingo and colleagues suggest that the WHO recommendations on vaccination be revisited, the differences between the Malian and Ghanaian cohorts indicate that other factors, which remain to be identified, are involved in the duration of immunity and seropositivity," they note. "Vaccines from different producers were used for the two cohorts, which presumably contain different quantities of vaccine virus and might stimulate the immune system differently."

"Additional research is needed for this group of vaccinees to determine whether different yellow fever vaccines stimulate the immune system differently," the editorial concludes. "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."

Wellcome Trust provided funding for the study but was otherwise uninvolved in its conduct. The researchers report no link to vaccine manufacturers.


Lancet Infect Dis 2019.