Single yellow fever shot does not offer long-term protection in children

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Girl with fever

Levels of protective antibodies fall by nearly 50% in the years following yellow fever vaccination in children when vaccination is first carried out in 9 to 12 months of age

Yellow fever is a serious viral infection caused by the Aedes aegypti mosquito. These mosquitoes thrive near human habitations where they breed in clean water. According to WHO, yellow fever is endemic in tropical areas of 47 countries in Africa and Central and South America. 

Infection with yellow fever virus may be asymptomatic and go unnoticed or, on the contrary, it may progress rapidly to severe illness with fever, headache, muscle pain, nausea, vomiting and fatigue. The virus affects the liver cells, often causing jaundice from which the disease gets its name. Severe bleeding occurs in 25 to 50 % of cases, with high levels of mortality observed 7 to 10 days after the onset of symptoms.

Since 2013, WHO recommends a single dose of the vaccine for life-long protection. This recommendation is based on long-term efficacy, established in adults and children over 2 years of age. But data on the long-term efficacy of primary vaccination in infants are absent, despite 9-12-month-olds being the main targets of routine vaccination in countries where yellow fever is endemic. In this respect, WHO recommended research into the long-term persistence of the immunity conferred by vaccination in this age group. 

The study verified whether children to whom the vaccine was administered at around 9 months of age were still protected several years later. The team studied two clusters, one from Mali (587 children) and the other from Ghana (436 children). The levels of specific antibodies to the yellow fever virus was measured at 4 weeks after vaccination and repeated the measurement several years later. Levels above 0.5 IU/ml is considered to protect children from infection.

the results in both cases show a substantial fall – practically by half – in the levels of protective antibodies in the years following vaccination, and which predict the absence of protection against infection for large numbers of children

In the Malian cluster, 4.5 years after vaccination, only half of the children continued to present levels of antibodies above 0.5 IU/ml. And 19.3 % presented detectable antibodies but at levels below this recommended threshold (<0.5 IU/ml). The proportion of children seropositive for these antibodies was therefore 69.7 % as opposed to 96.7 % just after vaccination.

In the Ghanaian cluster, 2.5 years after vaccination, only around 30 % of children continued to be protected against infection and 11.7 % continued to present specific antibodies but in low concentrations (<0.5 IU/ml). All in all, 39.4 % of the children were considered seropositive as opposed to 72.7 % just after vaccination.

Irrespective of the differences in vaccine efficacy between these two groups, which could be explained by ethnic and environmental factors (urban/rural population, seasonality of vaccination, diet, exposure to other infectious agents, etc.), the results in both cases show a substantial fall – practically by half – in the levels of protective antibodies in the years following vaccination, and which predict the absence of protection against infection for large numbers of children.

“Our data suggest that a booster may be necessary when the 1st vaccination is performed in 9-12-month-olds, but we will need more precise knowledge of the decrease in antibodies over time. Maintaining immunity to the virus during childhood and in adulthood is fundamental for obtaining vaccine coverage beyond the threshold of 80 % of the population in order to prevent the risk of epidemic,” concluded lead researcher, José Enrique Mejía from Unit 1043 Center for Pathophysiology of Toulouse Purpan.

The findings were published in the Lancet Infectious Diseases.