Leprosy Drug Resistance Surveillance in Colombia: The Experience of a Sentinel Country.
Leprosy Drug Resistance Surveillance in Colombia: The Experience of a Sentinel Country.
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DOI：
10.1371/journal.pntd.0005041
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发表时间：
2016-10
影响因子：
3.8
通讯作者：
Cardona-Castro N
中科院分区：
文献类型：
--
作者：
Beltrán-Alzate C;López Díaz F;Romero-Montoya M;Sakamuri R;Li W;Kimura M;Brennan P;Cardona-Castro N
对麻风分枝杆菌耐药性进行了积极的研究，2004年至2013年，来自哥伦比亚流行地区的243例多杆菌患者被纳入监测计划。该项目是世界卫生组织在麻风病耐药性监测方面的一项举措，哥伦比亚是一个哨点国家。M.对来自皮肤涂片和/或皮肤活检样本的麻风DNA进行扩增和测序，以鉴定rpoB、folP 1、gyrA和gyrB中的耐药决定区（DRDR）突变，这些基因分别负责利福平、氨苯砜和氧氟沙星耐药。3株分离株显示DRDR rpoB基因突变（Asp 441 Tyr、Ser 456 Leu、Ser 458 Met），2株DRDR folP 1基因突变（Thr 53 Ala、Pro55 Leu），1株分离株显示DRDR rpoB（Ser 456 Met）和DRDR folP 1（Pro55 Leu）突变，提示多重耐药。1株folP 1基因存在Thr 53 Ala和Thr 88 Pro双突变。此外，我们检测到DRDR以外的突变，需要在体内评价它们与耐药性的相关性：rpoB Arg 505 Trp，folP 1 Asp 91 His，Arg 94 Trp和Thr 88 Pro，以及gyrA Ala 107 Leu。70%的M。麻风突变与耐药性有关，并从复发患者中分离出来;复发的可能性与确认的耐药性突变的存在显著相关（OR范围20.1-88.7，p < 0.05）。其中5例复发患者接受氨苯砜单药治疗作为主要治疗。总之，目前的研究呼吁注意M。哥伦比亚的麻风病耐药性，特别是已证实的耐药性突变与麻风病患者复发之间的显著关联。在氨苯砜单药治疗广泛使用的地区，发现利福平的DRDR突变频率较高。由于麻风复发病例的增加，麻风分枝杆菌耐药性是监测的原因。世界卫生组织的麻风抗药性监测倡议将哥伦比亚作为一个监测国家，该国被认为处于消除后阶段。10年来（2004-20013），对M.麻风抗药性在自愿患者中进行（每个患者签署同意书），所述患者从哥伦比亚14个省的诊断为麻风病的患者的便利样本中招募：Amazonas、安蒂奥基亚、马拉恩蒂科、玻利瓦尔、卡克塔、塞萨尔、昆迪纳马卡、乔科、乌伊拉、马格达莱纳、北桑坦德省、桑坦德、托利马和瓦莱。243例多菌血症患者在不同阶段的多药治疗（MDT）的目的是寻找原发性和继发性M。麻风抗药性：治疗前33例新患者，136例正在接受MDT，MDT后3个月或更长时间病灶未临床改善，36例MDT后细菌指数（BI）持续阳性，4例不依从MDT，34例复发病例。M.对来自患者样本的麻风病DNA进行了检测，以确定rpoB、folP 1、gyrA和gyrB中耐药决定区（DRDR）的突变，这些基因分别负责利福平、氨苯砜和氧氟沙星耐药。我们获得了DRDR突变的分离株，3株rpoB基因突变，2株folP 1基因突变，1株rpoB和folP 1均突变，提示多重耐药。一个分离株在folP 1上有双突变。此外，我们检测到DRDR以外的突变，需要在体内测试验证。70%的M。麻风确认的耐药突变分离自复发患者（OR范围20.1-88.7，p < 0.05）。其中5例复发患者接受氨苯砜单药治疗作为主要治疗。目前的研究呼吁注意M。哥伦比亚的麻风病耐药性，特别是已证实的耐药突变与麻风病患者复发之间的显著关联。
An active search for Mycobacterium leprae drug resistance was carried out, 243 multibacillary patients from endemic regions of Colombia were included from 2004 to 2013 in a surveillance program. This program was a World Health Organization initiative for drug resistance surveillance in leprosy, where Colombia is a sentinel country. M. leprae DNA from slit skin smear and/or skin biopsy samples was amplified and sequenced to identify mutations in the drug resistance determining region (DRDR) in rpoB, folP1, gyrA, and gyrB, the genes responsible for rifampicin, dapsone and ofloxacin drug-resistance, respectively. Three isolates exhibited mutations in the DRDR rpoB gene (Asp441Tyr, Ser456Leu, Ser458Met), two in the DRDR folP1 gene (Thr53Ala, Pro55Leu), and one isolate exhibited mutations in both DRDR rpoB (Ser456Met) and DRDR folP1 (Pro55Leu), suggesting multidrug resistance. One isolate had a double mutation in folP1 (Thr53Ala and Thr88Pro). Also, we detected mutations outside of DRDR that required in vivo evaluation of their association or not with drug resistance: rpoB Arg505Trp, folP1 Asp91His, Arg94Trp, and Thr88Pro, and gyrA Ala107Leu. Seventy percent of M. leprae mutations were related to drug resistance and were isolated from relapsed patients; the likelihood of relapse was significantly associated with the presence of confirmed resistance mutations (OR range 20.1–88.7, p < 0.05). Five of these relapsed patients received dapsone monotherapy as a primary treatment. In summary, the current study calls attention to M. leprae resistance in Colombia, especially the significant association between confirmed resistance mutations and relapse in leprosy patients. A high frequency of DRDR mutations for rifampicin was seen in a region where dapsone monotherapy was used extensively. Mycobacterium leprae drug resistance is cause of surveillance due to the increase of leprosy relapsed cases. World Health Organization initiative for drug resistance surveillance in leprosy included Colombia, a country considered in post-elimination stage, as a sentinel country. During 10 years (2004–20013) an active search for M. leprae drug resistance was carried out in volunteer patients (each of whom signed a consent form) recruited from a convenience sample of patients diagnosed with leprosy in fourteen departments of Colombia: Amazonas, Antioquia, Atlántico, Bolívar, Caquetá, Cesar, Cundinamarca, Chocó, Huila, Magdalena, Norte de Santander, Santander, Tolima, and Valle. 243 multibacillary patients in various stages of multi drug therapy (MDT) were enrolled with the aim to search for primary and secondary M. leprae drug resistance: 33 new patients before treatment, 136 currently undergoing MDT with not clinical improvement of lesions after three months or more of MDT, 36 post-MDT with positive bacillary index (BI) persistence, 4 non-adherent to MDT, and 34 relapsed cases. M. leprae DNA from patient´s samples was tested to identify mutations in the drug resistance determining region (DRDR) in rpoB, folP1, gyrA, and gyrB, the genes responsible for rifampicin, dapsone and ofloxacin drug-resistance, respectively. We obtained isolates that exhibited mutations in the DRDR, three in rpoB gene, two in folP1 gene, and one isolate exhibited mutations in both rpoB and folP1, suggesting multidrug resistance. One isolate had a double mutation in folP1. Also, we detected mutations outside of DRDR that required in vivo test validation. 70% of M. leprae confirmed resistance mutations were isolated from relapsed patients (OR range 20.1–88.7, p < 0.05). Five of these relapsed patients received dapsone monotherapy as a primary treatment. The current study calls attention to M. leprae resistance in Colombia, especially the significant association between confirmed resistance mutations and relapsed in leprosy patients.
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影响因子：
9.4
作者：
Dauendorffer, JN;Guillemin, I;Cambau, E
通讯作者：
Cambau, E
影响因子：
3.8
作者：
Cambau E;Chauffour-Nevejans A;Tejmar-Kolar L;Matsuoka M;Jarlier V
通讯作者：
Jarlier V
影响因子：
4.9
作者：
Matrat, Stephanie;Cambau, Emmanuelle;Aubry, Alexandra
通讯作者：
Aubry, Alexandra
DOI：
10.1016/0035-9203(93)90064-w
发表时间：
1993-09-01
影响因子：
2.2
作者：
COLSTON, MJ
通讯作者：
COLSTON, MJ
DOI：
10.1590/s1020-49892008000200001
发表时间：
2008-02-01
期刊：
Revista Panamericana de Salud Pública
影响因子：
--
作者：
Hernández, Elkin;Cardona-Castro, Nora;Gómez, Yenny
通讯作者：
Gómez, Yenny