Risk of fatal adverse events associated with 17DD yellow fever vaccine

Abstract

Yellow fever (YF), an acute infectious disease, is endemic in the north and central-west of Brazil. This disease can be prevented by the use of a vaccine. In Brazil, four fatal adverse events have been associated with the YF vaccine used in the country (17DD vaccine). We briefly describe the last two fatalities, and estimate the risk of 17DD-associated fatal adverse events under different epidemiological scenarios. Controversies regarding the appropriate denominator that enters the estimation of risk serve as a motivation for each proposed scenario. The statistical procedures used show optimum behaviour when assessing the risk of rare events. Risk estimates vary from 0.043 (95 % CI 0.017-0.110) to 2.131 (95 % CI 0.109-12.071) fatalities per million doses administered. The robust estimates of the risk of fatal adverse events we present constitute an important element in future risk-benefit analysis and point to the need for good quality vaccine coverage and adverse-events surveillance data to assess the risk of vaccination. Although vaccination of YF endemic regions is necessary to maintain low disease prevalence, preventive administration of YF vaccine to the entire population should be cautiously analysed.

Incubation Periods of Yellow Fever Virus

“…However, increasing concerns regarding the safety of the vaccine may curtail its use and diminish its effectiveness in outbreak prevention. [17][18][19][20] Understanding the temporal dynamics of yellow fever infections is critical to assessing transmission risk. Transmission of the virus from human to human requires a competent mosquito to feed on an infected human, survive an extrinsic incubation period in which the virus replicates and disseminates to the salivary glands, and finally, feed on another, susceptible, human.…”

Nucleic Acid-Based Infectious and Pseudo-Infectious Flavivirus Vaccines

“…Safety concerns have also been raised over the currently licensed vaccine preparations. Although they are highly effective at preventing lethal infections when correctly administered, several adverse reactions have been observed in patients following immunisation with commercial flavivirus vaccines [8,[20][21][22][23][24]. Thus, flavivirus research continues to be driven by the need for cheap, stable, safe, and efficacious vaccines.…”

“…However, this method does little to address the rare instances of vaccine-associated diseases observed with the currently licensed live-attenuated vaccines [20,21]. An elegant solution to this problem is to limit the infectivity of a vaccine strain by disabling its ability to package replicating RNA into virus particles, an approach that was previously used for developing vaccines against herpesviruses [71].…”

“…Severe and often fatal yellow fever vaccine-associated neurotropic disease and yellow fever vaccineassociated viscerotropic disease have been estimated to affect 1.3-16 individuals per million vaccinated and 2.13-2.5 individuals per million vaccinated, respectively [8,20,21]. The inactivated, mouse brain-derived JEV vaccine has also been associated with allergic reactions and neurological adverse events (estimated to affect 0.1-1% and 1-2 patients per million vaccinated, respectively) [8,[22][23][24].…”

Controvérsias sobre a ampliação das áreas com vacinação de rotina contra a febre amarela no Brasil

“…Even with serious and rare adverse events, the risk-benefit margin of vaccination has been considered highly favorable in endemic areas and in other situations of yellow fever risk 30,31 .…”