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Infect Genet Evol. 2019 Aug 28;75:104007. doi: 10.1016/j.meegid.2019.104007. [Epub ahead of print]

Molecular epidemiology and antimicrobial susceptibility of outbreak-associated Corynebacterium diphtheriae in Thailand, 2012.

Author information

1
National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
2
Faculty of Public Health, Kasetsart University Chalermphrakiat Sakon Nakhon Province Campus, Sakon Nakhon, Thailand. Electronic address: anusak.ke@ku.th.

Abstract

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.

KEYWORDS:

Antimicrobial susceptibility; Corynebacterium diphtheriae; MLST; Outbreak; Thailand

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