Dataset Information

Measles-mumps-rubella vaccine at 6?months of age, immunology, and childhood morbidity in a high-income setting: study protocol for a randomized controlled trial.

ABSTRACT: Background: Measles is a highly contagious and serious infection. Before the introduction of vaccination, measles caused yearly epidemics putting vulnerable children at risk of brain damage and death. Despite safe and cost-effective vaccines, measles remains a leading cause of death in children globally. Due to insufficient vaccine coverage and low levels of in utero transferred antibodies from vaccinated mothers, outbreaks of measles in Denmark and other high-income countries are observed at increasing frequency. The current vaccine was introduced in Denmark in 1987 as a one-shot measles-mumps-rubella vaccine at 15?months, a timing chosen to avoid inhibition of the infant's immune response by maternal antibodies. One generation later, the MMR vaccinated mothers have lower antibody levels compared to the naturally infected, and their infants are already susceptible at 6 months of age or earlier, thus increasing the risk of epidemics.

Methods: The Danish MMR trial is a double-blind randomized clinical trial recruiting between March 2019 and December 2021 with last patient last visit in February 2022. Altogether N?=?6500 infants aged 6 months will be randomly assigned to intramuscular vaccination with routine MMR (M-M-R VaxPro) or placebo (solvent only). According to the Danish Childhood vaccination program, all infants will receive a routine MMR vaccination at 15?months of age. At randomization, 1 month later, and 1 month after routine MMR vaccination at 15?months of age, a blood sample is drawn from app. 10% (N?=?600) of the population. Additionally, hair, saliva, and urine are sampled at randomization. The co-primary study outcomes are immunogenicity 1 month after MMR vaccination at 6 months of age assessed as plaque-reduction neutralization test, and incidence of infectious disease hospitalizations from randomization to 12?months of age. Six weeks post randomization, all participants are interviewed regarding adverse events.

Trial registration: The trial is registered in the EU Clinical Trials Registry. EudraCT registration number: 2016-001901-18 . Registered on 14 February 2017.

SUBMITTER: Vittrup DM

PROVIDER: S-EPMC7727227 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Measles-mumps-rubella vaccine at 6 months of age, immunology, and childhood morbidity in a high-income setting: study protocol for a randomized controlled trial.

Vittrup Dorthe Maria DM Laursen Anne Cathrine Lund ACL Malon Michelle M Soerensen Jesper Kiehn JK Hjort Jakob J Buus Soren S Svensson Jannet J Stensballe Lone Graff LG

Trials 20201210 1

<h4>Background</h4>Measles is a highly contagious and serious infection. Before the introduction of vaccination, measles caused yearly epidemics putting vulnerable children at risk of brain damage and death. Despite safe and cost-effective vaccines, measles remains a leading cause of death in children globally. Due to insufficient vaccine coverage and low levels of in utero transferred antibodies from vaccinated mothers, outbreaks of measles in Denmark and other high-income countries are observe ...[more]

PMID: 33303011

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Project description:ObjectiveTo test for potential non-specific effects of an additional, early measles, mumps, and rubella (MMR) vaccine at age 5-7 months on risk of infection related hospitalisation before age 12 months.DesignRandomised, double blinded, placebo controlled trial.SettingDenmark, a high income setting with low exposure to MMR.Participants6540 Danish infants aged 5 to 7 months.InterventionsInfants were randomly allocated 1:1 to intramuscular injection with standard titre MMR vaccine (M-M-R VaxPro) or placebo (solvent only).Main outcome measuresHospitalisations for infection, defined as all hospital contacts of infants referred from primary care for hospital evaluation and with an infection diagnosed, analysed as recurrent events, from randomisation to 12 months of age. In secondary analyses implications of censoring for date of subsequent diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type B, and immunisation with pneumococci conjugate vaccine (DTaP-IPV-Hib+PCV), potential effect modification by sex, prematurity (<37 weeks' gestation), season, and age at randomisation were tested, and the secondary outcomes of hospitalisations ≥12 hours and antibiotic use were evaluated.Results6536 infants were included in the intention-to-treat analysis. 3264 infants randomised to MMR vaccine experienced 786 hospitalisations for infection before age 12 months compared with 762 for the 3272 infants randomised to placebo. In the intention-to-treat analysis the rate of hospitalisations for infection did not differ between the MMR vaccine and placebo groups (hazard ratio 1.03, 95% confidence interval 0.91 to 1.18). For infants randomised to MMR vaccine compared with those randomised to placebo, the hazard ratio of hospitalisations for infection with a duration of at least 12 hours was 1.25 (0.88 to 1.77), and for prescriptions of antibiotics was 1.04 (0.88 to 1.23). No significant effect modifications were found by sex, prematurity, age at randomisation, or season. The estimate did not change when censoring at the date infants received DTaP-IPV-Hib+PCV after randomisation (1.02, 0.90 to 1.16).ConclusionFindings of this trial conducted in Denmark, a high income setting, do not support the hypothesis that live attenuated MMR vaccine administered early to infants aged 5-7 months decreases the rate of hospitalisations for non-targeted infection before age 12 months.Trial registrationEU Clinical Trials Registry EudraCT 2016-001901-18 and ClinicalTrials.gov NCT03780179.

Project description:Objectives To investigate whether measles, mumps, and rubella (MMR) vaccine has positive non-specific effects in a high income setting and to compare rates of hospital admissions for infections between children aged ≤2 years who received live MMR vaccine and those who received an inactivated vaccine against diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) as their most recent vaccination.Design Nationwide population based cohort study.Setting In the Netherlands, DTaP-IPV-Hib+pneumococcal vaccination (PCV) is recommended at ages 2, 3, 4, and 11 months and MMR + meningococcal C (MenC) vaccination at age 14 months. Data from the national vaccine register were linked to hospital admission data.Participants 1 096 594 children born in 2005-11 who received the first four DTaP-IPV-Hib+PCV vaccines.Main outcome measures Hazard ratio for admission to hospital for infection in children with MMR+MenC compared with the fourth DTaP-IPV-Hib+PCV as their most recent vaccination. Cox regression was performed with most recent vaccination as time dependent variable, adjusted for potential confounders. Analyses were repeated with admission for injuries or poisoning as a negative control outcome. In addition, rate of admission for infection was compared between the fourth and third DTaP-IPV-Hib+PCVas most recent vaccination.Results Having had MMR+MenC as the most recent vaccination was associated with a hazard ratio of 0.62 (95% confidence interval 0.57 to 0.67) for admission to hospital for infection and 0.84 (0.73 to 0.96) for injuries or poisoning, compared with the fourth DTaP-IPV-Hib+PCV as most recent vaccination. The fourth DTaP-IPV-Hib+PCV as most recent vaccination was associated with a hazard ratio of 0.69 (0.63 to 0.76) for admission to hospital for infection, compared with the third DTaP-IPV-Hib+PCV as most recent vaccination.Conclusions Healthy vaccinee bias could at least partly explain the observed lower rate of admission to hospital with infection after MMR vaccination. The lower rate is associated with receipt of any additional vaccine, not specifically MMR vaccine. This emphasises the caution required in the interpretation of findings from observational studies on non-specific effects of vaccination.

Project description:BackgroundThe reported coverage of the measles-rubella (MR) or measles-mumps-rubella (MMR) vaccine is greater than 99.0% in Zhejiang province. However, the incidence of measles, mumps, and rubella remains high. In this study, we assessed MMR seropositivity and disease distribution by age on the basis of the current vaccination program, wherein the first dose of MR is administered at 8 months and the second dose of MMR is administered at 18-24 months.MethodsCross-sectional serological surveys of MMR antibodies were conducted by collecting epidemiological data in Zhejiang province, China in 2011. In total, 1015 participants were randomly selected from two surveillance sites. Serum MMR-specific immunoglobulin G levels were tested by enzyme-linked immunosorbent assay. The geometric mean titers and seroprevalence with 95% confidence intervals (CIs) were calculated by age and gender. Proportions of different dose of vaccine by age by vaccine were also identified. Statistically significant differences between categories were assessed by the Chi-square test.ResultsOver 95% seroprevalence rates of measles were seen in all age groups except <7 months infants. Children aged 5-9 years were shown lower seropositivity rates of mumps while elder adolescences and young adults were presented lower rubella seroprevalence. Especially, rubella seropositivity was significantly lower in female adults than in male. Nine measles cases were unvaccinated or unknown vaccination history. Among them, 66.67% (6/9) patients were aged 20-29 years while 33.33% (3/9) were infants aged 8-12 months. In addition, 57.75% (648/1122) patients with mumps were children aged 5-9 years, and 50.54% (94/186) rubella cases were aged 15-39 years.ConclusionsA timely two-dose MMR vaccination schedule is recommended, with the first dose at 8 months and the second dose at 18-24 months. An MR vaccination speed-up campaign may be necessary for elder adolescents and young adults, particularly young females.

Dataset Information

Measles-mumps-rubella vaccine at 6?months of age, immunology, and childhood morbidity in a high-income setting: study protocol for a randomized controlled trial.

Publications

Measles-mumps-rubella vaccine at 6 months of age, immunology, and childhood morbidity in a high-income setting: study protocol for a randomized controlled trial.

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