National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
Faculty of Public Health, Kasetsart University Chalermphrakiat Sakon Nakhon Province Campus, Sakon Nakhon, Thailand.
Infect Genet Evol. 2019 Nov;75:104007. doi: 10.1016/j.meegid.2019.104007. Epub 2019 Aug 28.
Infections caused by Corynebacterium diphtheriae remain endemic in many countries. Since the implementation of the DTP (Diphtheria-Tetanus-Pertussis) vaccination program in 1977, only sporadic diphtheria cases have been reported in Thailand. In 2012, a diphtheria outbreak occurred in rural Thailand and 38 cases were reported, with the majority being adults (mean 22.1 years, range 5-72 years). The current study determined the genetic diversity of C. diphtheriae isolated from 83 individuals associated with either sporadic (n = 34) from 1994, 1996, 1997, 1998, 1999, 2000, 2012, and 2018, or 2012 outbreak (n = 49) diphtheria occurrences in Thailand. Antimicrobial susceptibility testing was performed on 41/83 isolates using broth microdilution. All sporadic (n = 27) and epidemic (n = 14) C. diphtheriae isolates (41/41; 100%) were susceptible to erythromycin (≤0.5 μg/ml), clindamycin (≤0.5 μg/ml), gentamicin (≤ 4 μg/ml), ciprofloxacin (≤1 μg/ml), and vancomycin (2 μg/ml), except tetracycline with a resistance rate of 34.1% (14/41 isolates). All isolates were intermediately resistant to penicillin (MIC range, 0.25-2 μg/ml). Multilocus sequence typing (MLST) revealed 17 sequence types (STs) among 83C. diphtheriae isolates. For the 2012 outbreak isolates, the predominant ST was ST243 (n = 34/49; 69.4%), followed by ST245 (n = 5/49; 10.2%) and ST244 (n = 4/49; 8.1%), whereas the main STs among the sporadic isolates were ST248 (n = 15/34; 44.1%), followed by ST209 (n = 7/34; 20.6%) and ST258 (n = 3/34; 8.8%). The ST243 outbreak strain was a single-locus variant of sporadic ST258. Phylogenetic analysis using concatenated sequences of 7 MLST genes from 17 STs revealed that ST243, ST248, and ST258 were located in the same cluster and ST243 appeared to have evolved from ST258, an endemic strain. This study highlights the importance of epidemiological surveillance together with characterization of C. diphtheriae strains to help inform the future control and prevention of diphtheria.
白喉棒状杆菌引起的感染在许多国家仍然流行。自 1977 年实施白喉-破伤风-百日咳（DTP）疫苗接种计划以来，泰国仅报告了散发性白喉病例。2012 年，泰国农村地区发生了白喉疫情，报告了 38 例病例，其中大多数为成年人（平均年龄 22.1 岁，范围 5-72 岁）。本研究确定了从与 1994 年、1996 年、1997 年、1998 年、1999 年、2000 年、2012 年和 2018 年散发性（n=34）或 2012 年爆发（n=49）白喉发生相关的 83 个人中分离出的白喉棒状杆菌的遗传多样性。使用肉汤微量稀释法对 41/83 株分离物进行了抗生素敏感性测试。所有散发性（n=27）和流行（n=14）白喉棒状杆菌分离株（41/41；100%）对红霉素（≤0.5μg/ml）、克林霉素（≤0.5μg/ml）、庆大霉素（≤4μg/ml）、环丙沙星（≤1μg/ml）和万古霉素（2μg/ml）敏感，除四环素的耐药率为 34.1%（14/41 株）。所有分离株对青霉素均呈中介耐药（MIC 范围，0.25-2μg/ml）。多位点序列分型（MLST）显示，在 83 株白喉棒状杆菌分离株中发现了 17 种序列型（STs）。对于 2012 年的爆发分离株，主要 ST 是 ST243（n=34/49；69.4%），其次是 ST245（n=5/49；10.2%）和 ST244（n=4/49；8.1%），而散发性分离株的主要 ST 是 ST248（n=15/34；44.1%），其次是 ST209（n=7/34；20.6%）和 ST258（n=3/34；8.8%）。ST243 爆发株是散发性 ST258 的单一位点变异株。使用来自 17 个 ST 的 7 个 MLST 基因的串联序列进行系统发育分析显示，ST243、ST248 和 ST258 位于同一聚类中，ST243 似乎是从地方性 ST258 株进化而来的。本研究强调了开展流行病学监测以及对白喉棒状杆菌菌株进行特征描述的重要性，有助于为未来的白喉控制和预防提供信息。
