Rotavirus vaccination and intussusception: a paradigm shift?

Abstract

Rotavirus (RV) is one of the leading causes of severe childhood gastroenteritis in children <5 years of age. Several countries have successfully implemented vaccination against RV disease; however, hesitancy to include RV vaccination in the national immunization program exists and relates, among other reasons, to the results of international post-licensure studies of RV vaccines that established an increased risk of intussusception (IS) in infants following immunization. IS is one of the major causes of bowel obstruction in infants between 4 and 10 months of age. Some studies have investigated the etiology of IS, including the role of natural RV infection and available evidence suggests that RV disease may be an independent risk factor for IS. In this regard, the benefit-risk profile of RV vaccination, which is recognized as positive, could potentially turn out to be even more favorable in preventing IS cases triggered by RV disease. However, further research is prompted to quantify the IS risk attributable to RV disease.

Review of Over 15 Years Postmarketing Safety Surveillance Spontaneous Data for the Human Rotavirus Vaccine (Rotarix) on Intussusception

“…Additionally, while a short-term increased IS risk may exist following vaccination, this may not hold true for the long term [ 30 , 67 ]. When taking into account the role of natural RV infection as an independent risk factor for IS, the benefit–risk profile of RV vaccination may in fact be even more advantageous than previously anticipated [ 37 ].…”

“…The overall (fixed-effect) estimate of IS risk during the 7 days after vaccination with HRV was 5.4 (95% confidence interval [CI] 3.9–7.4) after dose 1 and 1.8 (95% CI 1.3–2.5) after dose 2 [ 25 ]. Of note, as recently proposed by Vetter et al, the increased risk of IS following vaccination should be weighed against the risk of IS caused by naturally occurring RV infection [ 37 ]. A favourable benefit–risk balance for HRV has been suggested in various studies [ 35 , 38 – 40 ].…”

The Value of Rotavirus Vaccination in Europe: A Call for Action

“…Fears that implementation of rotavirus UMV would result in an overall increase in the incidence of intussusception in young children have not been realised. The evidence that currently available rotavirus vaccines do not increase the overall risk of intussusception is highly reassuring, and necessitates a shift in thinking about the risk-benefit of rotavirus vaccination [37]. If early, high rotavirus vaccine coverage can be achieved, it might be expected that more cases of 'naturally occurring' intussusception caused by rotavirus gastroenteritis would be prevented, and cases potentially caused by vaccination would be minimised, leading to an overall reduction in intussusception cases, and making the benefit-risk profile even more favourable.…”

Transient Expression in Cytoplasm and Apoplast of Rotavirus VP6 Protein Fused to Anti-DEC205 Antibody in Nicotiana benthamiana and Nicotiana sylvestris

“…On the other hand, there is evidence to suggest that rotavirus disease may be an independent risk factor for intussusception. Therefore, the WHO emphasized that the benefit-risk profile of both licensed RV vaccines remains favorable, and the benefits outweigh the risk of intussusception; however, further investigation is needed on the risk of intussusception intestinal attributable to RV disease [ 33 , 34 ]. A large group of researchers are currently focusing on generating alternatives for vaccine production; however, there are some limitations that impede their progress.…”