Age of administration of rotavirus vaccines

In April 2009, WHO’s Strategic Advisory Group of Experts (SAGE) reviewed recent data on the effectiveness and safety of 2 rotavirus vaccines the pentavalent RV5 (RotaTeq,® Merck & Co., Whitehouse Station, NJ, USA) and the monovalent RV1 (Rotarix,® GlaxoSmithKline Biologicals, Rixensart, Belgium). Based on its review of the evidence, SAGE recommended that vaccination against rotavirus be included for infants in all national immunization programmes. Introduction of the vaccine is strongly recommended in countries where deaths from diarrhoeal diseases account for ≥10% of mortality among children aged <5 years.⁴

In pivotal trials with RotaTeq, children were vaccinated with dose 1 between 6 weeks and 12 weeks of age; with Rotarix, children were vaccinated between 6 weeks and 14 weeks of age (in Latin America) or between 6 weeks and 15 weeks of age (in Europe). RotaTeq is delivered in a 3-dose schedule; Rotarix requires only 2 doses. The maximum age recommended for the last dose of RotaTeq is 32 weeks; it is 24 weeks and 6 days for Rotarix. In the United States, where RotaTeq has been generally administered at ages corresponding to those studied in the pivotal trials, post-licensure safety data do not suggest an increased risk of intussusception.

Based on these data, and in order to harmonize schedules between the vaccines, SAGE recommended that the first dose of either Rotarix or RotaTeq be administered at between 6 weeks to 15 weeks of age, and the maximum age recommended for administering the last dose of either vaccine should be 32 weeks. SAGE noted that this expansion of the age range for use of these vaccines might potentially increase coverage of the first dose in developing countries, from about 57% to 70%, and full-course coverage from about 36% to 54%.

The Committee supported SAGE’s recommendation to expand the age eligibility for rotavirus vaccination. Administration of rotavirus vaccines at the recommended ages early in infancy would provide high protection from rotavirus diarrhoea among vaccinated children. However, in many developing countries, not all children receive immunizations according to recommended dosing schedules, and the challenges of delivering timely immunization may be most acute in countries with high rates of early childhood mortality. The data on Rotarix and RotaTeq support the safety and effectiveness of both new rotavirus vaccines. The level of risk of intussusception identified with the previous vaccine (RotaShield,®) can be ruled out with confidence, and there may be no increased risk since neither Rotarix nor RotaTeq has given a signal of increased risk. It has been hypothesized that giving rotavirus vaccines outside of the recommended ages may be associated with an increased risk of intussusception. No adequate data directly support this hypothesis, and the Committee concluded that even if there were a theoretical increase in risk, the benefits of vaccination would exceed any possible risk of intussusception. Therefore, the Committee recommended expanding the age eligibility for vaccination beyond the maximum age recommended by SAGE in order to maximize coverage of the vaccines, especially in countries with high rates of early childhood mortality caused by diarrhoeal illness.

Although data support the safety and effectiveness of both Rotarix and RotaTeq, ongoing evaluation is needed to provide additional data for the expanded age groups. National immunization programmes that elect to extend age eligibility for the first dose of rotavirus vaccine to infants aged >15 weeks or the last dose beyond 32 weeks of age should be encouraged to initiate monitoring for effectiveness and safety. Rates of intussusception in unvaccinated children are higher among older infants, and even without an increased risk associated with vaccination, cases of intussusception in temporal association with vaccination are more likely to occur in infants vaccinated when aged >15 weeks than in younger infants. A systematic approach to monitoring intussusception will be essential in order to interpret the significance of these cases and reported rates. Effective risk-communication strategies will also be essential.

⁴See, No. 84, 2009, pp. 232–236.

Full report of GACVS meeting of 17-18 June 2009, published in the WHO Weekly Epidemiological Record on 7 August 2009