The risk of non-specific hospitalised infections following MMR vaccination given with and without inactivated vaccines in the second year of life. Comparative self-controlled case-series study in England.

Observational cohort studies in high-income settings have suggested that vaccination order may affect children's subsequent risk of a heterologous infection, with live vaccines reducing and inactivated vaccines (given on their own or with a live vaccine), increasing the risk. We used the self-controlled case-series method, which automatically controls for the individual level confounding to which such cohort studies are prone, to test this hypothesis. We compared the relative incidence (RI) of infections post-vaccination in two calendar periods in England; in Period 1 (September 2002-August 2006) live measles, mumps, rubella (MMR) vaccine was given on its own and in Period 2 (September 2006-April 2010) inactivated vaccines (7-valent pneumococcal conjugate vaccine (PCV7) and sometimes the combined Haemophilus influenzae type b/meningococcal group C vaccine (Hib-MenC)) were given concomitantly with MMR. Admissions for an infection of the upper or lower respiratory tract, gastrointestinal system or other site in children aged 11-23 months were selected from the Hospital Episode Statistics database in England and linked to child health immunisation histories. The analysis included a total of 24,144 infections in 21,067 children in Period 1 and 36,880 in 31,616 children in Period 2. The RI of admission for any infection in Period 1 was 1.00 (95% confidence interval 0.95-1.06) compared with 0.95 (95% confidence interval 0.90-1.00) in Period 2. Comparing the two periods showed no evidence of a difference in the relative incidence estimates with a ratio of RI of 0.94 (95% confidence interval 0.87-1.02), RIs within 90 days of vaccination were 0.94 (0.91-0.97) in Period 1 and 0.94 (0.91-0.97) in Period 2, consistent with a temporary healthy vaccinee effect. In conclusion, we found no evidence to support the hypothesis that there is a reduction in heterologous infections after MMR on its own or an increase after MMR given concomitantly with an inactivated vaccine.