Oral Polio Vaccination and Hospital Admissions With Non-Polio Infections in Denmark: Nationwide Retrospective Cohort Study

Abstract

Background. Live vaccines may have nonspecific beneficial effects on morbidity and mortality. This study examines whether children who had the live-attenuated oral polio vaccine (OPV) as the most recent vaccine had a different rate of admissions for infectious diseases than children with inactivated diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b vaccine (DTaP-IPV-Hib) or live measles-mumps-rubella vaccine (MMR) as their most recent vaccine. Methods. A nationwide, register-based, retrospective cohort study of 137 403 Danish children born 1997-1999, who had received 3 doses of DTaP-IPV-Hib, were observed from 24 months (first OPV dose) to 36 months of age. Results. Oral polio vaccine was associated with a lower rate of admissions with any type of non-polio infection compared with DTaP-IPV-Hib as most recent vaccine (adjusted incidence rate ratio [IRR], 0.85; 95% confidence interval [CI], .77-.95). The association was separately significant for admissions with lower respiratory infections (adjusted IRR, 0.73; 95% CI, .61-.87). The admission rates did not differ for OPV versus MMR. Conclusions. Like MMR, OPV was associated with fewer admissions for lower respiratory infections than having DTaP-IPV-Hib as the most recent vaccination. Because OPV is now being phased-out globally, further studies of the potential beneficial nonspecific effects of OPV are warranted.

Keywords: heterologous immunity; immunization; nonspecific effects; nontargeted effects; oral polio vaccination.

Figure 1.

Flowchart of inclusion in the study. ^aFourth dose of inactivated vaccine against diphtheria, tetanus, pertussis (acellular), polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) (N = 3077; 70.3%), second dose of vaccination against measles, mumps, and rubella (MMR) (N = 605; 13.8%), not recommended combination of vaccines (N = 358; 8.2%), DTaP-IPV or Hib alone (N = 286; 6.5%), booster dose against different combinations of diphtheria, tetanus, pertussis (acellular), and polio (N = 32; 0.7%), or oral polio vaccine (OPV)2 (N = 20; 0.5%). ^bSome children had missing information on more than 1 variable. The number of children with missing information on each variable and in parentheses the percentage among the total number of children with missing information was as follows: 9732 (65.3%) with missing information on maternal smoking during pregnancy, 4315 (29.0%) with missing information on educational level for the female adult in the household, 1775 (11.9%) with missing information on birth weight, 955 (6.4%) with missing information on gestational age, 795 (5.3%) with missing information on household income, 276 (1.9%) with missing information on adult composition of the household, 107 (0.7%) with uncertain vaccine allocation for twins or triplets, 102 (0.7%) with missing information on parental place of birth, 80 (0.5%) with missing information on caesarean section, 12 (0.1%) with missing information on population density, and 6 (0.0%) with missing information on maternal age at birth of the child. (Note: Infectious disease admissions are counted from 24 months of age and until date of censoring for the children included in the study or until 36 months of age for the children excluded from the study, because these children did not have a censoring date.)

Figure 2.

Distribution of the children on the sequence of vaccine groups at 24, 30, and 36 months of age (in parentheses the number of children). (Note: At 24 months of age 137 403 children were included in the study, but at 30 months of age 1303 children had been censored leaving 136 100 children in the study. At 36 months of age another 11 825 children had been censored leaving 124 275 children in the study.) Abbreviations: DTaP-IPV-Hib, inactivated vaccine against diphtheria, tetanus, pertussis (acellular), polio, and Haemophilus influenzae; MMR, vaccination against measles, mumps, and rubella; OPV, oral polio vaccine.

Figure 3.

Incidence rate and incidence rate ratio (IRR) according to the most recent vaccine and sequence. ^aThe incidence rate per 100 person years and in brackets the number of admissions and number of person years. ^bThe IRRs for the vaccine type the arrow points at relative to the previous vaccine type in the sequence and in brackets 95% confidence interval. Estimated from Cox proportional hazards model with age as underlying time, stratified by date of birth and adjusted for maternal smoking during pregnancy, sex, birth weight, gestational age, caesarean section, chronic diseases, number of infectious disease admissions before 24 months of age, admitted to hospital for any cause within the last 30 days, maternal age at birth of the child, highest educational level for the female adult in the household, parental place of birth, adults in the household, income quintiles for the household, other children in the household, and population density. ^cP value from a Wald test of the equality of rates for live vaccine against measles, mumps, and rubella (MMR) as most recent vaccine in the adjusted model. ^dP value from a Wald test of the equality of rates for live oral polio vaccine (OPV)1 as most recent vaccine in the adjusted model. Abbreviations: Adj, adjusted; DTaP-IPV-Hib, inactivated vaccine against diphtheria, tetanus, pertussis (acellular), polio, and Haemophilus influenzae type b.