Commentary: Beneficial non-specific effects of measles vaccine: Fact or fiction?

A PLOS One review has claimed that randomized controlled trials (RCTs) show no beneficial nonspecific effects (NSEs) of measles vaccine (MV). Since this claim contradicts previous meta-analyses, we examined the contradictory views. RCTs of MV in low-income countries have mainly tested standard-titer-measles vaccine (STMV) vs high-titer-measles-vaccine (HTMV) (1980-90s) and two-dose vs one-dose of STMV (2000-10s). The PLOS One review claimed no NSEs in the RCTs of two-dose MV. The negative effect of HTMV was considered a specific effect due to an excessive vaccine dose. However, this does not explain why the negative effects only applied to females. Taking subsequent vaccinations into consideration in our reanalysis, one dose of STMV/HTMV versus control vaccine in the age interval 4-9 months, before controls received routine MV, was associated with a mortality ratio of 0.61 (0.37-0.99). After 9 months, randomization to STMV compared with HTMV-followed-by-a-non-live-vaccine had an MR of 0.72 (0.55-0.95), significantly better for females. Most RCTs in low-income countries experience interactions with vaccine campaigns and subsequent routine vaccinations. When these interactions are considered, the RCTs selected by the PLOS One review do show beneficial NSEs. NSEs are still critical factors to take into consideration in planning of vaccination policy.