Community Engagement in Vaccination Promotion: Systematic Review and Meta-Analysis.

BACKGROUND: Community engagement plays a vital role in global immunization strategies, offering the potential to overcome vaccination hesitancy and enhance vaccination confidence. Although there is significant backing for community engagement in health promotion, the evidence supporting its effectiveness in vaccination promotion is fragmented and of uncertain quality. OBJECTIVE: This review aims to systematically examine the effectiveness of different contents and extent of community engagement for promoting vaccination rates. METHODS: This study was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive and exhaustive literature search was performed in 4 English databases (PubMed, Embase, Web of Science, and Cochrane Library) and 2 Chinese databases (CNKI and Wan Fang) to identify all possible articles. Original research articles applying an experimental study design that investigated the effectiveness of community engagement in vaccination promotion were eligible for inclusion. Two reviewers independently performed the literature search, study selection, quality assessment, and data extraction. Discrepancies were resolved through discussion, with the arbitration of a third reviewer where necessary. RESULTS: A total of 20 articles out of 11,404 records from 2006 to 2021 were retrieved. The studies used various designs: 12 applied single-group pre-post study designs, 5 were cluster randomized controlled trials (RCTs), and 3 were non-RCTs. These studies targeted multiple vaccines, with 8 focusing on children's immunization, 8 on human papillomavirus vaccine, 3 on hepatitis B virus vaccine, and 1 on COVID-19 vaccine. The meta-analysis revealed significant increases in vaccination rates both in pre-post comparison (rate difference [RD] 0.34, 95% CI 0.21-0.47, I2=99.9%, P<.001) and between-group comparison (RD 0.18, 95% CI 0.07-0.29, I2=98.4%, P<.001). The meta-analysis revealed that participant recruitment had the largest effect size (RD 0.51, 95% CI 0.36-0.67, I2=99.9%, P<.001), followed by intervention development (RD 0.36, 95% CI 0.23-0.50, I2=100.0%, P<.001), intervention implementation (RD 0.35, 95% CI 0.22-0.47, I2=99.8%, P<.001), and data collection (RD 0.34, 95% CI 0.19-0.50, I2=99.8%, P<.001). The meta-analysis indicated that high community engagement extent yielded the largest effect size (RD 0.49, 95% CI 0.17-0.82, I2=100.0%, P<.001), followed by moderate community engagement extent (RD 0.45, 95% CI 0.33-0.58, I2=99.6%, P<.001) and low community engagement extent (RD 0.15, 95% CI 0.05-0.25, I2=99.2%, P<.001). The meta-analysis revealed that "health service support" demonstrated the largest effect sizes (RD 0.45, 95% CI 0.25-0.65, I2=99.9%, P<.001), followed by "health education and discussion" (RD 0.39, 95% CI 0.20-0.58, I2=99.7%, P<.001), "follow-up and reminder" (RD 0.33, 95% CI 0.23-0.42, I2=99.3%, P<.001), and "social marketing campaigns and community mobilization" (RD 0.24, 95% CI 0.06-0.41, I2=99.9%, P<.001). CONCLUSIONS: The results of this meta-analysis supported the effectiveness of community engagement in vaccination promotion with variations in terms of engagement contents and extent. Community engagement required a "fit-for-purpose" approach rather than a "one-size-fits-all" approach to maximize the effectiveness of vaccine promotion. TRIAL REGISTRATION: PROSPERO CRD42022339081; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=339081.

Comparative Whole-Genomic Analysis of an Ancient L2 Lineage Mycobacterium tuberculosis Reveals a Novel Phylogenetic Clade and Common Genetic Determinants of Hypervirulent Strains.

Background: Development of improved therapeutics against tuberculosis (TB) is hindered by an inadequate understanding of the relationship between disease severity and genetic diversity of its causative agent, Mycobacterium tuberculosis. We previously isolated a hypervirulent M. tuberculosis strain H112 from an HIV-negative patient with an aggressive disease progression from pulmonary TB to tuberculous meningitis-the most severe manifestation of tuberculosis. Human macrophage challenge experiment demonstrated that the strain H112 exhibited significantly better intracellular survivability and induced lower level of TNF-α than the reference virulent strain H37Rv and other 123 clinical isolates. Aim: The present study aimed to identify the potential genetic determinants of mycobacterial virulence that were common to strain H112 and hypervirulent M. tuberculosis strains of the same phylogenetic clade isolated in other global regions. Methods: A low-virulent M. tuberculosis strain H54 which belonged to the same phylogenetic lineage (L2) as strain H112 was selected from a collection of 115 clinical isolates. Both H112 and H54 were whole-genome-sequenced using PacBio sequencing technology. A comparative genomics approach was adopted to identify mutations present in strain H112 but absent in strain H54. Subsequently, an extensive phylogenetic analysis was conducted by including all publically available M. tuberculosis genomes. Single-nucleotide-polymorphisms (SNPs) and structural variations (SVs) common to hypervirulent strains in the global collection of genomes were considered as potential genetic determinants of hypervirulence. Results:Sequencing data revealed that both H112 and H54 were identified as members of the same sub-lineage L2.2.1. After excluding the lineage-related mutations shared between H112 and H54, we analyzed the phylogenetic relatedness of H112 with global collection of M. tuberculosis genomes (n = 4,338), and identified a novel phylogenetic clade in which four hypervirulent strains isolated from geographically diverse regions were clustered together. All hypervirulent strains in the clade shared 12 SNPs and 5 SVs with H112, including those affecting key virulence-associated loci, notably, a deleterious SNP (rv0178 p. D150E) within mce1 operon and an intergenic deletion (854259_ 854261delCC) in close-proximity to phoP. Conclusion: The present study identified common genetic factors in a novel phylogenetic clade of hypervirulent M. tuberculosis. The causative role of these mutations in mycobacterial virulence should be validated in future study.