A comprehensive review of yellow fever cases has found strong evidence that a single dose of the yellow fever vaccine provides lifelong immunity, reinforcing the World Health Organization's (WHO) 2015 recommendation against booster shots. The study, published in The Lancet Microbe, analyzed data spanning from 1936 to 2023, examining instances of yellow fever breakthrough infections after primary vaccination.
The research team conducted a systematic review and meta-analysis, scrutinizing studies reporting symptomatic yellow fever in vaccinated individuals. Their search encompassed major databases, including Global Index Medicus, EMBASE, and Medline. The analysis included randomized controlled trials, cohort studies, case reports, and outbreak reports that met specific quality criteria.
The study considered cases as effectively vaccinated if the vaccine was administered at least 30 days before the onset of symptoms. Confirmed cases were diagnosed via virological testing, while probable cases were identified through seroconversion. The primary outcome measured was the proportion of vaccinated individuals who developed yellow fever symptoms at least 30 days post-vaccination.
The review identified 37 eligible studies, encompassing 40,850 suspected cases and 6,951 laboratory-diagnosed cases. Among the laboratory-diagnosed cases, only 537 individuals were effectively vaccinated. Notably, only one individual had received a second vaccine dose.
Key Findings on Breakthrough Infections
The analysis revealed only nine confirmed yellow fever breakthrough infections between 1942 and 2020. Three of these occurred within three months to three years after primary vaccination, and no confirmed breakthrough infections were observed in individuals vaccinated 10 or more years prior. A meta-analysis of five studies indicated that the pooled proportion of verified yellow fever breakthrough infections was just 3% among confirmed and probable cases.
Implications for Vaccination Policy
The findings support the WHO's current stance that a single yellow fever vaccination can provide lifelong protection against symptomatic disease. The study's authors suggest that the rarity of breakthrough infections, particularly after a decade post-vaccination, underscores the durability of the immune response elicited by the vaccine.
Considerations and Future Research
The researchers acknowledge that their strict inclusion criteria, requiring both vaccination proof and virological confirmation, may have led to an underestimation of breakthrough infections. They also noted that a higher proportion of breakthrough infections occurred among individuals vaccinated in childhood compared to adults.
"Future research should focus on the immunogenicity of vaccination in those vaccinated at younger ages and the incidence of breakthrough infections in these age groups," the authors stated. Understanding the long-term protection in those vaccinated as children is crucial for refining vaccination strategies.
Yellow fever remains a significant public health concern in South America and sub-Saharan Africa, with an estimated 30,000 deaths annually. This study provides reassurance that the current vaccination strategy is effective in providing long-term protection against this potentially fatal disease.
