Post-licensure data confirm benefits of rotavirus vaccine

A complete three-dose series of pentavalent rotavirus vaccine was 85% to 89% effective against rotavirus gastroenteritis severe enough to cause ED visits or hospital admission in children aged 15 days through 23 months, results of a recently published study indicate.

From February through June 2008, researchers from several U.S. sites conducted a case-controlled evaluation to analyze the effectiveness of a complete three-dose or partial one- to two-dose immunization with RV5 . Four hundred children who presented to the ED or were admitted for inpatient care with either diarrhea, vomiting or both symptoms met study inclusion criteria; 90 children had confirmed rotavirus from fecal specimens.

The researchers compared immunization data for these children with three control groups: patients with non-rotavirus acute gastroenteritis (n=115), patients with acute respiratory infection who did not meet acute gastroenteritis inclusion criteria (n=228) and up to 10 age- and ZIP code- matched children sampled from the Houston-Harris County Immunization Registry, in Texas, for each case patient aged older than 8 months.

Although vaccine effectiveness rates were lower than those demonstrated in prelicensure trials (94% to 96%), the researchers noted that this may be due to higher levels of disease severity among prelicensure-study participants.

Study data also revealed positive results for partial immunization, with one dose conferring 69% protection and two doses conferring 81% protection. As the severity of disease increased, the level of protection also increased, the researchers noted (severity score ¡Ý11 on a 20-point severity scale; 79% with one dose, 89% with two doses).

¡°Importantly, our findings indicate that partial immunization with RV5 confers good protection against severe rotavirus disease,¡± the researchers noted. ¡°Approximately 10% to 15% of severe rotavirus disease in U.S. children aged less than 5 years occurs before the age of 6 months, when a child can be fully immunized, and the benefits of partial immunization are key for the prevention of severe rotavirus acute gastroenteritis in young infants and children who do not complete their vaccination series.¡±

This study represented the first postlicensure examination of RV5¡¯s performance in U.S. clinical practice. Although they acknowledged that further research is needed to confirm their findings, they concluded that RV5 was extremely effective in protecting against rotavirus acute gastroenteritis.

Determining the effectiveness of the monovalent rotavirus vaccine (Rotarix, GlaxoSmithKline) independent of, and in conjunction with RV5 is another priority, as well as documenting the duration of protection from either vaccine and the evolution of nonvaccine rotavirus strains. ¨C by Melissa Foster

Boom JA. Pediatrics. 2010;125:e199-e207.

This is an important study because it confirms that the efficacy predicted in the pre-licensure clinical trials is actually being seen in the post-licensure setting. One of the methods employed, using test negatives as controls, corrects for one of the potential confounders in any observational study of vaccine effectiveness ¡ª health-seeking behavior. The concern is that children who seek health care may be more likely to access the health care system for other things, such as vaccination, compared with other children in the community.This could lead to a falsely low vaccine effectiveness.

By using test-negatives as controls, the investigators decrease the potential for this bias. The authors report a complete RV5 series conferred 100% protection against severe disease, compatible with results seen in the pre-licensure trials. The study also suggests one or two doses provide substantial protection, although the confidence limits are wide, meaning that the actual magnitude of protection could not be measured precisely. The study results support the major benefits that accrue to children from vaccination against rotavirus.

¨C Walter M. Orenstein, MD
Infectious Diseases in Children Editorial Board