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Original Investigation |

Live Vaccine Against Measles, Mumps, and Rubella and the Risk of Hospital Admissions for Nontargeted Infections

Signe Sørup, PhD1; Christine S. Benn, DMSc1,2,3; Anja Poulsen, PhD4; Tyra G. Krause, PhD5; Peter Aaby, DMSc1,3; Henrik Ravn, PhD1,3
[+] Author Affiliations
1Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark
2Institute of Clinical Research, University of Southern Denmark, and Odense University Hospital, Odense, Denmark
3Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau
4Child and Adolescent Clinic, Rigshospitalet, Copenhagen, Denmark
5Department of Infectious Disease Epidemiology, Statens Serum Institut, Copenhagen, Denmark
JAMA. 2014;311(8):826-835. doi:10.1001/jama.2014.470.
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Importance  In low-income countries, live measles vaccine reduces mortality from causes other than measles infection. Such nonspecific effects of vaccines might also be important for the health of children in high-income settings.

Objective  To examine whether the live vaccine against measles, mumps, and rubella (MMR) is associated with lower rates of hospital admissions for infections among children in Denmark.

Design, Setting, and Participants  Population-based cohort study of Danish children born 1997-2006 and followed up from ages 11 months to 2 years (last follow-up, August 31, 2008). Nationwide Danish registers provided data on vaccinations and hospital admissions. The recommended vaccination schedule was inactivated vaccine against diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) administered at ages 3, 5, and 12 months and MMR at age 15 months.

Main Outcomes and Measures  Incidence rate ratios (IRRs) of hospital admissions for any infection, comparing receipt of MMR vs DTaP-IPV-Hib as the most recent vaccine. Risks, risk difference, and number needed to vaccinate were calculated for receiving MMR on time.

Results  The study included 495 987 children contributing with 56 889 hospital admissions for any type of infection during 509 427 person-years (rate, 11.2 per 100 person-years). For the 456 043 children who followed the recommended schedule and received MMR after the third dose of DTaP-IPV-Hib, MMR (rate, 8.9 per 100 person-years) vs the third dose of DTaP-IPV-Hib (rate, 12.4 per 100 person-years) as the most recent vaccine was associated with an adjusted IRR of 0.86 (95% CI, 0.84-0.88) for any admission for infection. There were 19 219 children immunized out of sequence. The adjusted IRR was 0.87 (95% CI, 0.80-0.95) for those receiving MMR (rate, 9.9 per 100 person-years) after the second dose of DTaP-IPV-Hib (rate, 15.1 per 100 person-years). However, in the 1981 children who subsequently received the third dose of DTaP-IPV-Hib (rate, 12.8 per 100 person-years) after MMR, the IRR for hospital admissions for infection was significantly greater (adjusted IRR, 1.62 [95% CI, 1.28-2.05]). The risk of admission for an infection between ages 16 months and 24 months was 4.6% (95% CI, 4.5%-4.7%) for receiving MMR on time and 5.1% (95% CI, 5.0%-5.2%) for not receiving MMR on time. The risk difference was 0.5 percentage point (95% CI, 0.4-0.6), and the number needed to vaccinate with MMR before age 16 months to prevent 1 admission for any infection was 201 (95% CI, 159-272).

Conclusions and Relevance  In a cohort of Danish children, receipt of live MMR vs inactivated DTaP-IPV-Hib as the most recent vaccine was associated with a lower rate of hospital admissions for any infections. These findings require replication in other high-income populations.

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Figure.
Study Flow of the Recommended-Schedule and Reversed-Schedule Cohorts

Infectious disease admissions are counted from the latest of the following events: 11 months of age, received diphtheria, tetanus, pertussis (acellular), polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine (recommended-schedule cohort) or measles, mumps, and rubella (MMR) vaccine (reversed-schedule cohort) and until date of censoring for the children included in the study or until age 2 years for the children excluded from the study.aOf these children, 5403 (21.6%) received DTaP-IPV-Hib3 and MMR together.bDTaP or Hib alone (n = 14 277 [61.6%]), not recommended combination of vaccines (n = 5055 [21.8%]), booster dose against different combinations of diphtheria, tetanus, pertussis (acellular), and polio (n = 1649 [7.1%]), whole-cell pertussis vaccine (n = 862 [3.7%]), vaccine against hepatitis B (n = 783 [3.4%]), oral polio vaccine (n = 392 [1.7%]), fourth dose of DTaP-IPV-Hib (n = 144 [0.6%]), pneumococcal conjugate vaccine (n = 28 [0.1%]), and second dose of MMR (n = 1 [0.0%]).

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