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Accounting for indirect protection in the benefit-risk ratio estimation of rotavirus vaccination in children under the age of 5 years, France, 2018.

ABSTRACT: BackgroundRotavirus is a major cause of severe gastroenteritis in children worldwide. The disease burden has been substantially reduced in countries where rotavirus vaccines are used. Given the risk of vaccine-induced intussusception, the benefit-risk balance of rotavirus vaccination has been assessed in several countries, however mostly without considering indirect protection effects.AimWe performed a benefit-risk analysis of rotavirus vaccination accounting for indirect protection in France among the 2018 population of children under the age of 5 years.MethodsTo incorporate indirect protection effects in the benefit formula, we adopted a pseudo-vaccine approach involving mathematical approximation and used a simulation design to provide uncertainty intervals. We derived background incidence distributions from quasi-exhaustive health claim data. We examined different coverage levels and assumptions regarding the waning effects and intussusception case fatality rate.ResultsWith the current vaccination coverage of < 10%, the indirect effectiveness was estimated at 6.4% (+/-?0.4). For each hospitalisation for intussusception, 288.2 (95% uncertainty interval: (173.8-480.0)) hospitalisations for rotavirus gastroenteritis were prevented. Should 90% of infants be vaccinated, indirect effectiveness would reach 57.9% (+/-?3.7) and the benefit-risk ratio would be 297.6 (95% uncertainty interval: 179.4-497.3). Indirect protection accounted for almost half of the prevented rotavirus gastroenteritis cases across all coverage levels. The balance remained in favour of the vaccine even in a scenario with a high assumption for intussusception case fatality.ConclusionsThese findings contribute to a better assessment of the rotavirus vaccine benefit-risk balance.

SUBMITTER: Escolano S

PROVIDER: S-EPMC7441603 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Accounting for indirect protection in the benefit-risk ratio estimation of rotavirus vaccination in children under the age of 5 years, France, 2018.

Escolano Sylvie S Mueller Judith E JE Tubert-Bitter Pascale P

Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 20200801 33

Background Rotavirus is a major cause of severe gastroenteritis in children worldwide. The disease burden has been substantially reduced in countries where rotavirus vaccines are used. Given the risk of vaccine-induced intussusception, the benefit–risk balance of rotavirus vaccination has been assessed in several countries, however mostly without considering indirect protection effects. Aim We performed a benefit–risk analysis of rotavirus vaccination accounting for indirect protection in Franc ...[more]

PMID: 32820718

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Project description:Early observations from countries that have introduced rotavirus vaccination suggest that there may be indirect protection for unvaccinated individuals, but it is unclear whether these benefits will extend to the long term. Transmission dynamic models have attempted to quantify the indirect protection that might be expected from rotavirus vaccination in developed countries, but results have varied. To better understand the magnitude and sources of variability in model projections, we undertook a comparative analysis of transmission dynamic models for rotavirus. We fit five models to reported rotavirus gastroenteritis (RVGE) data from England and Wales, and evaluated outcomes for short- and long-term vaccination effects. All of our models reproduced the important features of rotavirus epidemics in England and Wales. Models predicted that during the initial year after vaccine introduction, incidence of severe RVGE would be reduced 1.8-2.9 times more than expected from the direct effects of the vaccine alone (28-50% at 90% coverage), but over a 5-year period following vaccine introduction severe RVGE would be reduced only by 1.1-1.7 times more than expected from the direct effects (54-90% at 90% coverage). Projections for the long-term reduction of severe RVGE ranged from a 55% reduction at full coverage to elimination with at least 80% coverage. Our models predicted short-term reductions in the incidence of RVGE that exceeded estimates of the direct effects, consistent with observations from the United States and other countries. Some of the models predicted that the short-term indirect benefits may be offset by a partial shifting of the burden of RVGE to older unvaccinated individuals. Nonetheless, even when such a shift occurs, the overall reduction in severe RVGE is considerable. Discrepancies among model predictions reflect uncertainties about age variation in the risk and reporting of RVGE, and the duration of natural and vaccine-induced immunity, highlighting important questions for future research.

Project description:Transforming growth factor β (TGF-β) has been shown to play a role in immunity against different pathogens in vitro and against parasites in vivo However, its role in viral infections in vivo is incompletely understood. Using a neonatal mouse model of heterologous rhesus rotavirus (RV) vaccination, we show that the vaccine induced rotavirus-specific CD4 T cells, the majority of which lacked expression of KLRG1 or CD127, and a few regulatory rotavirus-specific CD4 T cells that expressed surface latency-associated peptide (LAP)-TGF-β. In these mice, inhibiting TGF-β, with both a neutralizing antibody and an inhibitor of TGF-β receptor signaling (activin receptor-like kinase 5 inhibitor [ALK5i]), did not change the development or intensity of the mild diarrhea induced by the vaccine, the rotavirus-specific T cell response, or protection against a subsequent challenge with a murine EC-rotavirus. However, mice treated with anti-LAP antibodies had improved protection after a homologous EC-rotavirus challenge, compared with control rhesus rotavirus-immunized mice. Thus, oral vaccination with a heterologous rotavirus stimulates regulatory RV-specific CD4 LAP-positive (LAP+) T cells, and depletion of LAP+ cells increases vaccine-induced protection.IMPORTANCE Despite the introduction of several live attenuated animal and human rotaviruses as efficient oral vaccines, rotaviruses continue to be the leading etiological agent for diarrhea mortality among children under 5 years of age worldwide. Improvement of these vaccines has been partially delayed because immunity to rotaviruses is incompletely understood. In the intestine (where rotavirus replicates), regulatory T cells that express latency-associated peptide (LAP) play a prominent role, which has been explored for many diseases but not specifically for infectious agents. In this paper, we show that neonatal mice given a live oral rotavirus vaccine develop rotavirus-specific LAP+ T cells and that depletion of these cells improves the efficiency of the vaccine. These findings may prove useful for the design of strategies to improve rotavirus vaccines.

Dataset Information

Accounting for indirect protection in the benefit-risk ratio estimation of rotavirus vaccination in children under the age of 5 years, France, 2018.

Publications

Accounting for indirect protection in the benefit-risk ratio estimation of rotavirus vaccination in children under the age of 5 years, France, 2018.

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