Expanding the potential of rotavirus vaccines (RV) to reduce mortality by optimizing the immunization schedules

Policy Questions

What are the optimal immunization schedules for rotavirus vaccines (RV) for children living in different WHO mortality strata?

Overall Conclusions

Both rotavirus vaccines are efficacious but, data show that they are more efficacious in low mortality under five mortality settings (VE ~ 90%) than in high mortality under five settings (VE ~ 60%). Observational studies have reported similar findings.

A review estimated that the median age at infection for rotavirus for all the studies was 43.5 weeks (inter-quartile range 38 to 52 weeks). This review reported that of all the cases of rotavirus diarrhoea in children less than 3 years old that are severe enough for hospital admission, about 3% will occur before the child is 9 weeks old. About 6% will occur before 13 weeks, about 10% before 17 weeks, and 32% before they are 32 weeks old. Ideally vaccination schedules should be designed to provide benefits to those at highest risk. This might imply extending the evidence base to age distributions for different socio-economic groups.

Currently, there is limited data on whether children receiving rotavirus vaccines are at increased risk of intussusception. There is even less evidence regarding risk of IS after each vaccine dose. Most RCTs lack precision to examine the impact of RV1 and RV5 on intussusception with different schedules.

Despite there are thirteen observational studies reporting on specific surveillance for intussusception, most of these studies did not provide risk estimation or compared the results with unvaccinated children. Results from a case-control study reported an increased risk after RV1 doses one and two in Mexico and after the second dose of RV1 in Brazil up to 14 days after vaccination, and a surveillance study from Australia an increased risk after the first RV5 dose in children aged one to three months up to seven days and up to 21 days after vaccination. Studies were performed mainly in countries on strata A and B.

Trade-offs exists when considering various rotavirus vaccine schedule options. On the benefits side, unrestricted schedule would prevent additional 48,400 rotavirus deaths due to ~23-25% increase in vaccine coverage. On the risks side, the unrestricted schedule is estimated to cause ~333 excess intussusception deaths compared to current age restricted schedule.

Access to Country level data

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