2008-2015 年台灣侵襲性乙型鏈球菌感染與 血清型分子流行學分析

Molecular Epidemiology, Genotype Distribution and Clinical Characterization of Invasive Group B Streptococcus Disease in Taiwan, 2008-2015

研究目的：乙型鏈球菌（Group B Streptococcus 或 Streptococcus agalactiae；簡稱GBS）是新生兒與免疫力低下的老年人造成侵襲性感染的重要病原之一。為 了瞭解台灣本土的流行病資料，本研究分析來自彰化秀傳醫院與彰濱秀傳醫院以及台北榮民總醫院從血液檢體所分離乙型鏈球菌菌株，透過莢膜多醣體 血清型（Capsular Polysaccharide Genotype）、毒性基因（virulence genes）、多位點序列分型法（Multilocus Sequence Typing; MLST）、抗生素敏感試驗 分析、綜合探討乙型鏈球菌型別分部與疾病的危險因子之間的關聯性。

檢體來源與方法：本研究檢體來源包括彰化秀傳醫院與彰濱秀傳醫院 2008 到 2015 年所凍存血液感染的 111 個 GBS 菌株以及 2014-2015 年間台北榮民總醫院所凍存 60 個 GBS 菌株，總共 171 株。除了針對臨床 8 種抗生素抗藥性分析 外，我們也運用分子技術分析多套式聚合酶連鎖反應（Multiplex polymerase chain reaction）進行莢膜多醣體血清型分型、毒性基因分析、多點位基因序 列分型探討 GBS 血液感染菌株分子型別分佈及相關性。

實驗結果：研究 GBS 菌株從 2008 到 2015 年共 171 株，菌株莢膜多醣體分佈前三名 依序是 Type III（18.1%），Type II（17%），Type Ib。我們更進一步挑選 142株進行 MLST 分析，主要依序為 ST1/Genotype VI（26.7%），其次為 ST12/ Genotype Ib（13.3%），及 ST17（7.7%），及其他分型。七個毒性基因的探討方面主要 rib 基因主要分布於 Type III（80.6%）而 bac 基因分布於 Type Ib （96.2%），而其餘的五個基因則無型別的差異性，均呈現 100% 陽性反應。除此之外，本實驗也針對 ST17 之型別加做 hvgA 基因探討高致病型別之毒力分 析，結果顯示 ST17 菌株均帶有此毒性基因。

結論：在 2008-2015 年間，台灣乙型鏈球菌主要莢膜型別依序是 Type III、Type II 及 Type Ib。而 MLST 型別則是以 ST1/Genotype VI 最常見，其次為 ST12/Genotype Ib 及 ST17。所有菌株仍對 penicillin 具有高度敏感性，不過 ST12 /Genotype Ib GBS 則對 Erythromycin 和 Clindamycin 具高度抗藥性。追蹤GBS 感染可進一步了解菌種生態演化趨勢。

 

Objectives: Group B Streptococcus (GBS) is an important pathogen for invasive diseases in not only neonates and pregnant women but also elderly patients with underlying diseases. This study was aimed to delineate the molecular genotype distribution and virulence factors of invasive GBS isolates from north and central Taiwan, from 2008-2015.

Methods: A total of 171 clinical GBS bloodstream isolates from Show Chwan Memorial Hospital, Chang Bing Show Chwan Memorial Hospital, and Taipei Veterans General Hospital from 2008-2015 were determined for molecular serotyping, multi-locus sequence typing (MLST), distribution of 7 virulence genes and susceptibilities to 8 non-beta-lactam antimicrobial agents.

Results: In the present study, the three leading GBS genotypes in order were Type III (18.1%), Type II (17%) and Type Ib. For MLST, ST1/genotype VI (26.7%) was predominated, followed by ST12/Genotype Ib (13.3%) and ST17/genotype III (7.7%). In terms of virulence genes, rib and bac genes were carried by genotype III (80.6%) and genotype Ib (96.2%), respectively, but were rarely detected amongst other genotypes. ST17 was exclusively found in genotype III with 100% harboring of the hvgA gene. All GBS isolates remained 100% susceptible to penicillin and ampicillin but high resistances to erythromycin and clindamycin were seen, particularly in genotype Ib.

Conclusions: Genotype III and ST 1 GBS strains were the most prevailing types in this study. Virulence gene distributions characterized certain genotypes, particularly in the ST17 strain. Molecular epidemiological analysis of GBS presents a picture of evolution over time and offers fundamental information for GBS vaccine development.