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Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review.

ABSTRACT: OBJECTIVES: To evaluate the effects on non-specific and all cause mortality, in children under 5, of Bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP), and standard titre measles containing vaccines (MCV); to examine internal validity of the studies; and to examine any modifying effects of sex, age, vaccine sequence, and co-administration of vitamin A. DESIGN: Systematic review, including assessment of risk of bias, and meta-analyses of similar studies. STUDY ELIGIBILITY CRITERIA: Clinical trials, cohort studies, and case-control studies of the effects on mortality of BCG, whole cell DTP, and standard titre MCV in children under 5. DATA SOURCES: Searches of Medline, Embase, Global Index Medicus, and the WHO International Clinical Trials Registry Platform, supplemented by contact with experts in the field. To avoid overlap in children studied across the included articles, findings from non-overlapping birth cohorts were identified. RESULTS: Results from 34 birth cohorts were identified. Most evidence was from observational studies, with some from short term clinical trials. Most studies reported on all cause (rather than non-specific) mortality. Receipt of BCG vaccine was associated with a reduction in all cause mortality: the average relative risks were 0.70 (95% confidence interval 0.49 to 1.01) from five clinical trials and 0.47 (0.32 to 0.69) from nine observational studies at high risk of bias. Receipt of DTP (almost always with oral polio vaccine) was associated with a possible increase in all cause mortality on average (relative risk 1.38, 0.92 to 2.08) from 10 studies at high risk of bias; this effect seemed stronger in girls than in boys. Receipt of standard titre MCV was associated with a reduction in all cause mortality (relative risks 0.74 (0.51 to 1.07) from four clinical trials and 0.51 (0.42 to 0.63) from 18 observational studies at high risk of bias); this effect seemed stronger in girls than in boys. Seven observational studies, assessed as being at high risk of bias, have compared sequences of vaccines; results of a subset of these suggest that administering DTP with or after MCV may be associated with higher mortality than administering it before MCV. CONCLUSIONS: Evidence suggests that receipt of BCG and MCV reduce overall mortality by more than would be expected through their effects on the diseases they prevent, and receipt of DTP may be associated with an increase in all cause mortality. Although efforts should be made to ensure that all children are immunised on schedule with BCG, DTP, and MCV, randomised trials are needed to compare the effects of different sequences.

SUBMITTER: Higgins JP

PROVIDER: S-EPMC5063034 | biostudies-other | 2016 Oct

REPOSITORIES: biostudies-other

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Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review.

Higgins Julian P T JP Soares-Weiser Karla K López-López José A JA Kakourou Artemisia A Chaplin Katherine K Christensen Hannah H Martin Natasha K NK Sterne Jonathan A C JA Reingold Arthur L AL

BMJ (Clinical research ed.) 20161013

<h4>Objectives</h4> To evaluate the effects on non-specific and all cause mortality, in children under 5, of Bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP), and standard titre measles containing vaccines (MCV); to examine internal validity of the studies; and to examine any modifying effects of sex, age, vaccine sequence, and co-administration of vitamin A.<h4>Design</h4> Systematic review, including assessment of risk of bias, and meta-analyses of similar studies.<h4>Study e ...[more]

PMID: 27737834

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Project description:BackgroundTwo of the most prevalent causes of severe bacterial meningitis in children, Haemophilus influenzae type B (Hib) and Streptococcus pneumoniae, are preventable by existing vaccines increasingly available in developing countries. Our objective was to estimate the dose-specific effect of Hib and pneumococcal conjugate vaccines (PCV) on childhood meningitis mortality in low-income countries for use in the Lives Saved Tool (LiST).MethodsWe systematically searched and reviewed published vaccine efficacy trials and observational studies reporting the effect of Hib or PCV vaccines on organism-specific meningitis, bacterial meningitis and all-cause meningitis incidence and mortality among children less than five years old in low- and middle-income countries. Data collection and quality assessments were performed using standardized guidelines. For outcomes available across multiple studies (≥ 2) and approximating meningitis mortality, we pooled estimates reporting dose-specific effects using random effects meta-analytic methods, then combined these with meningitis etiology data to determine the preventable fraction of childhood meningitis mortality for inclusion in LiST.ResultsWe identified 18 studies of Hib conjugate vaccines reporting relevant meningitis morbidity and mortality outcomes (2 randomized controlled trials [RCTs], 16 observational studies) but few provided dose-specific effects. A meta-analysis of four case-control studies examined the dose-specific effect of Hib conjugate vaccines on Hib meningitis morbidity (1 dose: RR=0.64, 95% CI 0.38-1.06; 2 doses: RR=0.09, 95% CI 0.03-0.27; 3 doses: RR=0.06, 95% CI 0.02-0.22), consistent with results from single RCTs. Pooled estimates of two RCTs provided evidence for the effect of three doses of PCV on vaccine-serotype meningitis morbidity (RR=0.16, 95% CI 0.02-1.20). We considered these outcomes of severe disease as proxy estimates for meningitis mortality and combined the estimates of protective effects with meningitis etiology data to provide an estimate of the preventable fraction of childhood meningitis mortality with three doses of Hib (38-43%) and pneumococcal conjugate vaccines (28-35%) for use in LiST.ConclusionsFew RCTs or vaccine effectiveness studies evaluated the dose-specific impact of Hib and PCV vaccines on childhood meningitis mortality, necessitating use of proxy measures to estimate population impact in LiST. Our analysis indicates that approximately three-quarters of meningitis deaths are preventable with existing Hib and PCV vaccines.

Project description:ImportanceChildhood adversity (CA) is a powerful determinant of long-term physical and mental health that is associated with elevated risk for chronic disease and psychopathology. However, the degree to which CA contributes to mortality as a preventable driver of ill-health and death is unknown.ObjectiveTo estimate the contribution of CA to health behaviors, including smoking and sedentary behavior, as well as the annual mortality attributable to CA in the US through influences on leading causes of death (eg, cardiovascular disease).Evidence reviewFor this systematic review, the PsycINFO and MEDLINE databases were searched on November 15, 2019. The databases were searched for publications from inception (1806 for PsycINFO, 1946 for MEDLINE) to November 15, 2019. Meta-analyses of the associations between CA and morbidity outcomes were included. The population attributable fraction (PAF) was calculated from these associations along with the estimated US prevalence of CA. The PAF was then applied to the number of annual deaths associated with each cause of death to estimate the number of deaths that are attributable to CA. Additionally, the PAF was applied to the incidence of health behaviors to derive the number of cases attributable to CA. Exposure to 1 or more experiences of adversity before the age of 18 years was analyzed, including abuse, neglect, family violence, and economic adversity.FindingsA total of 19 meta-analyses with 20 654 832 participants were reviewed. Childhood adversity accounted for approximately 439 072 deaths annually in the US, or 15% of the total US mortality in 2019 (2 854 838 deaths), through associations with leading causes of death (including heart disease, cancer, and suicide). In addition, CA was associated with millions of cases of unhealthy behaviors and disease markers, including more than 22 million cases of sexually transmitted infections, 21 million cases of illicit drug use, 19 million cases of elevated inflammation, and more than 10 million cases each of smoking and physical inactivity. The greatest proportion of outcomes attributable to CA were for suicide attempts and sexually transmitted infections, for which adversity accounted for up to 38% and 33%, respectively.Conclusions and relevanceThe results of this systematic review suggest that CA is a leading contributor to morbidity and mortality in the US and may be considered a preventable determinant of mortality. The prevention of CA and the intervention on pathways that link these experiences to elevated disease risk should be considered a critical public health priority.

Dataset Information

Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review.

Publications

Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review.

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