Beneficial Non‐Specific Effects of Measles Vaccine: Fact or Fiction?

Background: A recent Systematic Review claimed that randomised controlled trials (RCTs) showed that there are no beneficial non-specific effects (NSEs) of measles vaccine (MV); i.e. effects not explained by prevention of measles infection. The claim contradicts previous meta-analyses. Methods: We examined the reasons for these contradictory views. For ethical reasons there are few RCTs of MV in low-income countries (LIC), mainly trials of standard-titre-measles vaccine (STMV) vs high-titre-measles-vaccine (HTMV) in the 1980-90s and trials of two-dose vs one-dose of STMV in the 2000s. We reanalysed the RCTs taking the effect of subsequent vaccinations into consideration. Results: The PLOS One review claimed that there are no NSEs since the RCTs of a two-dose strategy gave a meta-estimate of 1.0. The negative effect of HTMV was considered a specific effect due to an excessive vaccine dose. 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, STMV compared with HTMV-followed-by-a-non-live vaccine had a MR of 0.72 (0.55-0.95), significantly better for females than males. Discussion: The viral dose explanation of HTMV is not valid as it did not explain why the negative effects only applied to females. The review authors did not take into consideration that most RCTs in LIC experience interactions with vaccine campaigns and subsequent routine vaccinations. When these interactions are taken into consideration, the very RCTs selected by the PLOS One review do in fact show beneficial NSEs of MV. Conclusion: NSEs are still critical factors to take into consideration in planning of vaccination policy.