Decline of Yellow Fever Long-Term Immunity in Children Vaccinated During Infancy

Background: The vaccine against yellow fever is routinely administered to infants aged 9-12 months under the Expanded Programme on Immunization, but the long-term outcome of vaccination in this age group is unknown. This information is critical in the context of current guidelines recommending a single dose of the vaccine for life.   Methodology: We used a microneutralization assay to measure protective antibodies against yellow fever in 587 Malian and 436 Ghanaian children vaccinated around age 9 months and followed for 4·5 years (Mali), or 2·3 and 6 years (Ghana). We standardized antibody concentrations with reference to the yellow fever WHO International Standard. Findings: In the Malian group, 50·4% of children (95% CI 46·4-54·5) were seropositive (antibody concentration =0·5 IU/ml) 4·5 years after vaccination. Among the Ghanaian children, only 27·8% (95% CI 23·5-32·0) were seropositive after 2·3 years. This represented a sharp drop from the rates reported for both populations 28 days postvaccination. Seropositivity increased to 43·1% (95% CI 38·5-47·8) in the Ghanaian group 6 years after vaccination, but this result is confounded by possible secondary exposure to yellow fever virus.   Interpretation: Rapid waning of immunity during the early years after vaccination of 9-month-old infants argues for a revision of the single-dose recommendation for this target population in endemic countries. In addition, the short duration of immunity in many vaccinees suggests that booster vaccination is necessary to meet the 80% population immunity threshold for prevention of yellow fever outbreaks.   Funding Statement: Wellcome Trust Foundation.   Declaration of Interests: SOS received grants from PATH during the conduct of the present study. SOS is the Minister of Health and Public Hygiene of the Republic of Mali but was not at the time of the collection of the samples used in this study. NB and CK received grants from the Bill and Melinda Gates Foundation during the conduct of this study. CD, JF, POA, and JEM declare no conflicts of interest. Ethics Approval Statement: The study protocol was approved by the ethics committees for studies involving human subjects at the Navrongo Health Research Centre, Navrongo, Ghana, and the National Institute for Research in Public Health (INRSP), Bamako, Mali. All the procedures complied with the Declaration of Helsinki. Informed consent was provided in writing by the participants’ parents or legal guardians in accordance with international ethical guidelines for epidemiological studies and with applicable local ethical guidance and requirements.