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中国湖南地区二期和潜伏梅毒患者梅毒螺旋体DNA的分子分型及耐药基因监测

Molecular Subtyping and Surveillance of Resistance Genes In Treponema pallidum DNA From Patients With Secondary and Latent Syphilis in Hunan, China.

作者信息

Xiao Yongjian, Liu Shuangquan, Liu Zhuoran, Xie Yafeng, Jiang Chuanhao, Xu Man, Zhao Feijun, Zeng TieBing, Yu Jian, Wu Yimou

机构信息

From the *Pathogenic Biology Institute, Medical College, University of South China; †Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study; ‡Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control; §Department of Clinical Laboratory, The Second Affiliated Hospital of University of South China; ¶Department of Clinical Laboratory, The First Affiliated Hospital of University of South China; and **Department of Experimental Zoology, Medical College, University of South China, Hengyang, China.

出版信息

Sex Transm Dis. 2016 May;43(5):310-6. doi: 10.1097/OLQ.0000000000000445.

DOI:10.1097/OLQ.0000000000000445
PMID:27100768
Abstract

BACKGROUND

Over the past decade, the incidence of syphilis and widespread macrolide resistance in its etiological agent, Treponema pallidum subsp. pallidum, have become a major health concern across countries, including China. Regional trends in subtypes and antibiotic resistance can be monitored effectively by molecular surveillance programs. In this study, whole blood samples were used to assess circulating T. pallidum strains collected from various regions of Hunan, China, between 2013 and 2015.

METHODS

Traditional polymerase chain reaction, targeting polA, tpp47, bmp, and tp0319 genes, was used as preliminary screening assay. About 455 polymerase chain reaction-positive specimens were obtained from 2253 whole blood samples of patients with secondary or latent syphilis. Molecular subtyping was performed using a Centers for Disease Control and Prevention-based typing method combined with an analysis of the variable region of tp0548 gene. Resistance to macrolides was analyzed by examining point mutations in 23S rRNA, and the presence of the G1058C point mutation within 16S rRNA associated with decreased susceptibility to doxycycline was assessed.

RESULTS

Circulating T. pallidum strains were resolved into 32 subtypes, among which subtype 14d/f was predominant. A2059G mutation in 23S rRNA, and the G1058C mutation in 16S rRNA was absent, but the prevalence of A2058G mutation in 23S rRNA was 97.5%.

CONCLUSIONS

We found that it is possible to use whole blood to evaluate molecular subtypes and monitor antibiotic resistance in circulating T. pallidum strains, especially when chancres are absent. High frequency of macrolide-resistant T. pallidum indicates that macrolide antibiotics, such as azithromycin, should be avoided as a treatment option for syphilis in Hunan, China.

摘要

背景

在过去十年中,梅毒的发病率及其病原体梅毒螺旋体苍白亚种对大环内酯类药物的广泛耐药性已成为包括中国在内的世界各国主要的健康问题。通过分子监测项目能够有效地监测亚型和抗生素耐药性的区域趋势。在本研究中,我们使用全血样本评估了2013年至2015年间从中国湖南省不同地区采集的循环梅毒螺旋体菌株。

方法

采用针对polA、tpp47、bmp和tp0319基因的传统聚合酶链反应作为初步筛选检测方法。从2253例二期或潜伏梅毒患者的全血样本中获得了约455份聚合酶链反应阳性标本。使用基于疾病控制和预防中心的分型方法结合tp0548基因可变区分析进行分子亚型分型。通过检测23S rRNA中的点突变分析对大环内酯类药物的耐药性,并评估与多西环素敏感性降低相关的16S rRNA内G1058C点突变的存在情况。

结果

循环梅毒螺旋体菌株被分为32个亚型,其中14d/f亚型占主导地位。23S rRNA中不存在A2059G突变和16S rRNA中的G1058C突变,但23S rRNA中A2058G突变的发生率为97.5%。

结论

我们发现使用全血评估循环梅毒螺旋体菌株的分子亚型和监测抗生素耐药性是可行的,尤其是在没有硬下疳的情况下。梅毒螺旋体对大环内酯类药物的高耐药率表明,在中国湖南,应避免将阿奇霉素等大环内酯类抗生素作为梅毒的治疗选择。

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