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

Signe Sørup, Lone G Stensballe, Tyra G Krause, Peter Aaby, Christine S Benn, Henrik Ravn, Signe Sørup, Lone G Stensballe, Tyra G Krause, Peter Aaby, Christine S Benn, Henrik Ravn

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.

Figures

Figure 1.
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.
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.
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.

References

    1. Meeting of the Strategic Advisory Group of Experts on immunization, April 2014 – conclusions and recommendations. Wkly Epidemiol Rec 2014; 89:221–36.
    1. Systematic review of the non-specific effects of BCG, DTP and measles containing vaccines. Available at: Accessed 23 October 2014.
    1. Contreras G. Effect of the administration of oral poliovirus vaccine on infantile diarrhoea mortality. Vaccine 1989; 7:211–2.
    1. Contreras G. Sabin's vaccine used for nonspecific prevention of infant diarrhea of viral etiology. Bull Pan Am Health Organ 1974; 8:123–32.
    1. Aaby P, Rodrigues A, Biai S et al. . Oral polio vaccination and low case fatality at the paediatric ward in Bissau, Guinea-Bissau. Vaccine 2004; 22:3014–7.
    1. Aaby P, Hedegaard K, Sodemann M et al. . Childhood mortality after oral polio immunisation campaign in Guinea-Bissau. Vaccine 2005; 23:1746–51.
    1. Seppala E, Viskari H, Hoppu S et al. . Viral interference induced by live attenuated virus vaccine (OPV) can prevent otitis media. Vaccine 2011; 29:8615–8.
    1. Voroshilova MK. Potential use of nonpathogenic enteroviruses for control of human disease. Prog Med Virol 1989; 36:191–202.
    1. World Health Organization. Polio Eradication & Endgame Strategic Plan 2013–2018. Available at: Accessed 27 August 2014.
    1. Plesner AM, Ronne T. [The childhood vaccination program. Background, status and future]. Ugeskr Laeger 1994; 156:7497–503.
    1. Andersen P, Rønne T, Bro-Jørgensen K. Childhood vaccination program -change by July 1, 2001. EPI-NYT 2001; 23.
    1. Benn CS, Netea MG, Selin LK, Aaby P. A small jab - a big effect: nonspecific immunomodulation by vaccines. Trends Immunol 2013; 34:431–9.
    1. Aaby P, Whittle H, Benn CS. Vaccine programmes must consider their effect on general resistance. BMJ 2012; 344:e3769.
    1. Sorup S, Benn CS, Poulsen A et al. . Live vaccine against measles, mumps, and rubella and the risk of hospital admissions for nontargeted infections. JAMA 2014; 311:826–35.
    1. Aaby P, Kollmann TR, Benn CS. Nonspecific effects of neonatal and infant vaccination: public-health, immunological and conceptual challenges. Nat Immunol 2014; 15:895–9.
    1. Pedersen CB. The Danish Civil Registration System. Scand J Public Health 2011; 39:22–5.
    1. Thygesen LC, Ersboll AK. Danish population-based registers for public health and health-related welfare research: introduction to the supplement. Scand J Public Health 2011; 39:8–10.
    1. Andersen JS, Olivarius ND, Krasnik A. The Danish National Health Service Register. Scand J Public Health 2011; 39:34–7.
    1. Lynge E, Sandegaard JL, Rebolj M. The Danish National Patient Register. Scand J Public Health 2011; 39:30–3.
    1. Kristensen K, Hjuler T, Ravn H et al. . Chronic diseases, chromosomal abnormalities, and congenital malformations as risk factors for respiratory syncytial virus hospitalization: a population-based cohort study. Clin Infect Dis 2012; 54:810–7.
    1. Knudsen LB, Olsen J. The Danish Medical Birth Registry. Dan Med Bull 1998; 45:320–3.
    1. Baadsgaard M, Quitzau J. Danish registers on personal income and transfer payments. Scand J Public Health 2011; 39:103–5.
    1. Jensen VM, Rasmussen AW. Danish Education Registers. Scand J Public Health 2011; 39:91–4.
    1. Wojcik OP, Simonsen J, Molbak K, Valentiner-Branth P. Validation of the 5-year tetanus, diphtheria, pertussis and polio booster vaccination in the Danish childhood vaccination database. Vaccine 2013; 31:955–9.
    1. Benn CS, Fisker AB, Rodrigues A et al. . Sex-differential effect on infant mortality of oral polio vaccine administered with BCG at birth in Guinea-Bissau. A natural experiment. PLoS One 2008; 3:e4056.
    1. Lund N, Andersen A, Monteiro I et al. . No effect of oral polio vaccine administered at birth on mortality and immune response to BCG. A natural experiment. Vaccine 2012; 30:6694–9.
    1. Lund N, Andersen A, Hansen AS et al. . The effect of oral polio vaccine at birth on infant mortality: a randomized trial. Clin Infect Dis 2015; 61:1504–11.
    1. Martins CL, Benn CS, Andersen A et al. . A randomized trial of a standard dose of Edmonston-Zagreb measles vaccine given at 4.5 months of age: effect on total hospital admissions. J Infect Dis 2014; 209:1731–8.
    1. Sorup S, Benn CS, Stensballe LG et al. . Measles-mumps-rubella vaccination and respiratory syncytial virus-associated hospital contact. Vaccine 2015; 33:237–45.

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