Risk of Nontargeted Infectious Disease Hospitalizations Among US Children Following Inactivated and Live Vaccines, 2005–2014

Abstract

Background Recent studies have shown that some vaccines have beneficial effects that could not be explained solely by the prevention of their respective targeted disease(s). Methods We used the MarketScan® United States (US) Commercial Claims Databases from 2005–2014 to assess the risk of hospital admission for non-targeted infectious diseases (NTI) in children from 16 through 24 months according to the last vaccine type (live and/or inactivated). We included children continuously enrolled within a month of birth through 15 months who received at least three doses of Diphtheria-Tetanus-acellular Pertussis vaccine by end of 15 months of age. We used Cox regression to estimate hazard ratios (HRs), stratifying by birthdate to control for age, year and seasonality, and adjusting for sex, chronic diseases, prior hospitalizations, number of outpatient visits, region of residence, urban/rural area of domicile, prematurity, low birth weight, and mother’s age. Results 311,663 children were included. In adjusted analyses, risk of hospitalization for non-targeted infections from ages 16 through 24 months was reduced for those who received live vaccine alone compared with inactivated alone or concurrent live and inactivated vaccines (HR 0.50, 95% CI 0.43, 0.57 and HR 0.78, 95% CI 0.67, 0.91, respectively), and for those who received live and inactivated vaccines concurrently compared with inactivated only (HR 0.64, 95% CI 0.58, 0.70). Conclusions We found lower risk of non-targeted infectious disease hospitalizations from 16 through 24 months among US children whose last vaccine received was live compared with inactivated vaccine, as well as concurrent receipt compared with inactivated vaccine.

Non-specific effects of MMR vaccines on infectious disease related hospitalizations during the second year of life in high-income countries: a systematic review and meta-analysis

“…The search term was confined to MMR vaccines. One study, 6 however, included varicella vaccination, another live vaccine, in the analysis, assuming similar effects for MMR and the varicella vaccine. Because it was impossible to disentangle the effects and because the number of children receiving varicella alone was small (of the live vaccines, 88% received MMR containing vaccines by the age of 16 months), 6 we included this study in the analysis.…”

“…12 The study from the USA investigating both concurrent administration and live vaccine alone as the most recent vaccine included 311,663 children. 6 The study addressing RSV hospitalization had MMR alone for intervention, it included 168,511 children. 13 The Danish studies 4,12,13 investigating MMR compared to children with DTaP containing vaccine as last vaccine required at least two doses of DTaP containing vaccines as a prerequisite to be included in the study.…”

“…In the Dutch study, 7 the requirement was four doses DTaP, while it was three doses in the US study. 6 In the three studies with no overlapping populations 4,6,7 MMR containing vaccines as most recent vaccination was assessed as the intervention.…”

“…Pneumococcal conjugate vaccination was given on the same day in the Dutch study. 7 The US study 6 defined live vaccines as MMR, Varicella or MMRV. In this study, inactivated vaccines included diphtheria-tetanus-acellular pertussis, inactivated polio virus, Haemophilus influenzae type b, pneumococcal conjugate vaccine, hepatitis B vaccine, and hepatitis A vaccine (and combined vaccines with these antigens).…”

“…For two studies 4,7 the overall risk of bias was classified as critical because of a significant association to the control outcome in the same direction (reduced risk for injuries with MMR as last vaccine). For the other three studies 6,12,13 risk of bias was classified as serious because structural inequality between intervention and control group could not be ruled out. Design factors seem plausible which influence the time point of the intervention and therefore the group status of a child as well as the observed outcome.…”