日本儿童侵袭性无乳链球菌候选疫苗靶点的流行及基因组特征

Masashi Kasai,Satoshi Nakano,Shota Koide,Shogo Otake,Meiwa Shibata,Kasumi Ishida-Kuroki,Yo Sugawara,Yukihiro Akeda,Kandai Nozu,Motoyuki Sugai
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摘要

背景:无乳链球菌(B族链球菌,GBS)是新生儿和婴儿侵袭性感染的主要原因,包括败血症和脑膜炎。尽管有产时抗生素预防,GBS仍然是一个公共卫生问题。本研究旨在评估日本儿童侵袭性GBS的疫苗覆盖率和基因组流行病学特征。方法:我们开展了一项全国性、多中心、回顾性基因组监测研究,涉及2004年至2023年日本35家医院中≤15岁儿童无菌标本中的237株GBS分离株。进行血清分型、抗菌药物敏感性测试、全基因组测序、系统发育和单核苷酸多态性(SNP)分析。结果以ⅲ型(48.1%)最为常见,其次为Ia型(27.4%)和Ib型(12.2%)。估计六价多糖疫苗的疫苗覆盖率为98.3%,GBS-NN/NN2蛋白疫苗的疫苗覆盖率为94.9%。所有分离株均对青霉素敏感。红霉素耐药率为61.2%,克林霉素耐药率为43.5%。在75株CC17分离株中,59株(78.7%)仅含有PI-2B,同时携带ermB和tetO,表明多药耐药克隆优势。基于snp的分析揭示了医院传播和持续区域传播的证据,特别是在ST17和ST23谱系中。结论:这项全国性的基因组监测研究表明,目前的母体GBS候选疫苗将为日本儿童侵袭性感染提供广泛的覆盖。确定持续和区域传播的谱系突出了调查包括环境水库在内的潜在但知之甚少的传播途径的重要性,以便为未来的预防战略提供信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Prevalence of candidate vaccine targets and genomic features of pediatric invasive Streptococcus agalactiae in Japan.
BACKGROUND Streptococcus agalactiae (Group B Streptococcus, GBS) is a leading cause of invasive neonatal and infant infections, including sepsis and meningitis. Despite intrapartum antibiotic prophylaxis, GBS remains a public health concern. This study aimed to estimate the vaccine coverage and characterize the genomic epidemiology of pediatric invasive GBS in Japan. METHODS We conducted a nationwide, multicenter, retrospective genomic surveillance study involving 237 GBS isolates from sterile specimens of children aged ≤15 years across 35 hospitals in Japan between 2004 and 2023. Serotyping, antimicrobial susceptibility testing, whole-genome sequencing, and phylogenetic and single nucleotide polymorphism (SNP)-based analyses were performed. RESULTS Serotype III was the most common (48.1%), followed by Ia (27.4%) and Ib (12.2%). The estimated vaccine coverage was 98.3% for the hexavalent polysaccharide vaccine and 94.9% for the GBS-NN/NN2 protein vaccine. All isolates were susceptible to penicillin. Erythromycin and clindamycin resistance were observed in 61.2% and 43.5%, respectively. Among the 75 CC17 isolates, 59 (78.7%) contained only PI-2B and harbored both ermB and tetO, indicating the predominance of a multidrug-resistant clone. SNP-based analysis revealed evidence of nosocomial transmission and persistent regional circulation, particularly within the ST17 and ST23 lineages. CONCLUSION This nationwide genomic surveillance study suggests that current maternal GBS vaccine candidates would provide broad coverage for pediatric invasive infections in Japan. The identification of persistent and regionally disseminated lineages highlights the importance of investigating potential, yet poorly understood, transmission routes, including environmental reservoirs, to inform future prevention strategies.
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