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      Immunogenicity and persistence of trivalent measles, mumps, and rubella vaccines: a systematic review and meta-analysis

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      , MD a , * , , PhD a , b , , PhD c , , Prof, PhD c , , Prof, PhD d , , Prof, PhD a , d
      The Lancet. Infectious Diseases
      Elsevier Ltd.

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          Abstract

          Background

          Despite the universal use of the two-dose trivalent measles-mumps-rubella (MMR) vaccine in the past two decades, outbreaks of these diseases still occur in countries with high vaccine uptake, giving rise to concerns about primary and secondary failure of MMR vaccine components. We aimed to provide seroconversion and waning rate estimates for the measles, mumps, and rubella components of MMR vaccines.

          Methods

          In this systematic review and meta-analysis we searched PubMed (including MEDLINE), Web of Science, and Embase for randomised controlled trials, cohort studies, or longitudinal studies reporting the immunogenicity and persistence of MMR vaccines, published in English from database inception to Dec 31, 2019. Studies were included if they investigated vaccine-induced immunity in healthy individuals who received a trivalent MMR vaccine, including different dosages and timepoints of vaccine administration. Studies featuring coadministration of MMR with other vaccines, maternal immunity to the MMR vaccine, or non-trivalent formulations of the vaccine were excluded. Pooled seroconversion and waning rates were estimated by random-effects meta-analyses. This study is registered with PROSPERO, CRD42019116705.

          Findings

          We identified 3615 unique studies, 62 (1·7%) of which were eligible for analysis. Estimated overall seroconversion rates were 96·0% (95% CI 94·5–97·4; I 2=91·1%) for measles, 93·3% (91·1–95·2; I 2=94·9%) for mumps when excluding the Rubini strain, 91·1% (87·4–94·1; I 2=96·6%) for mumps when including the Rubini strain, and 98·3% (97·3–99·2; I 2=93·0%) for rubella. Estimated overall annual waning rates were 0·009 (95% CI 0·005–0·016; I 2=85·2%) for measles, 0·024 (0·016–0·039; I 2=94·7%) for mumps, and 0·012 (0·010–0·014; I 2=93·3%) for rubella.

          Interpretation

          Our meta-analysis provides estimates of primary and secondary vaccine failure, which are essential to improve the accuracy of mathematical and statistical modelling to understand and predict the occurrence of future measles, mumps, and rubella outbreaks in countries with high vaccine uptake.

          Funding

          European Research Council.

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          Most cited references52

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          Measuring inconsistency in meta-analyses.

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            Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

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              Bias in meta-analysis detected by a simple, graphical test.

              Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews. Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution.
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                Author and article information

                Journal
                Lancet Infect Dis
                Lancet Infect Dis
                The Lancet. Infectious Diseases
                Elsevier Ltd.
                1473-3099
                1474-4457
                1 September 2020
                February 2021
                1 September 2020
                : 21
                : 2
                : 286-295
                Affiliations
                [a ]Data Science Institute, I-BioStat, UHasselt, Diepenbeek, Belgium
                [b ]Global Health Institute, Department of Epidemiology and Social Medicine, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
                [c ]Centre for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
                [d ]Centre for Health Economic Research and Modelling Infectious Diseases, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
                Author notes
                [* ]Correspondence to: Julie Schenk, Data Science Institute, I-BioStat, UHasselt, Diepenbeek 3590, Belgium
                Article
                S1473-3099(20)30442-4
                10.1016/S1473-3099(20)30442-4
                9665966
                32888410
                c6412e7f-b60a-4268-b716-888f715bae1a
                © 2020 Elsevier Ltd. All rights reserved.

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                Infectious disease & Microbiology

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