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尼日利亚 HIV 感染者中耐药结核病的遗传决定因素。

Genetic determinants of drug-resistant tuberculosis among HIV-infected patients in Nigeria.

机构信息

Harvard School of Public Health, Immunology and Infectious Diseases, Boston, Massachusetts, USA.

出版信息

J Clin Microbiol. 2012 Sep;50(9):2905-9. doi: 10.1128/JCM.00982-12. Epub 2012 Jun 27.

DOI:10.1128/JCM.00982-12
PMID:22740709
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3421781/
Abstract

Tuberculosis (TB) is the most common opportunistic infection in human immunodeficiency virus (HIV)-infected patients and the emergence of drug-resistant tuberculosis (DR-TB) is a growing problem in resource-limited settings. Adequate infrastructure for testing drug sensitivity and sufficient evidence of first-line resistance are currently unavailable in Nigeria. We collected sputum samples from HIV-infected patients enrolled in the Harvard PEPFAR/APIN Plus program over 12 months at two PEPFAR antiretroviral therapy (ART) clinics in the southwest and north central regions in Nigeria. Smear-positive sputum samples were submitted for GenoType MTBDRplus testing (n = 415); mutations were confirmed through sequencing. Our results show high rates of DR-TB in Nigerian HIV-infected individuals (7.0% for rifampin [RIF] and 9.3% for RIF or isoniazid [INH]). Total RIF resistance indicative of MDR-TB in treatment-naive patients was 5.52%, far exceeding the World Health Organization predictions (0 to 4.3%). RIF resistance was found in 6/213 (2.8%) cases, INH resistance was found in 3/215 (1.4%) cases, and MDR-TB was found in 8/223 (3.6%) cases. We found significantly different amounts of DR-TB by location (18.18% in the south of the country versus 3.91% in the north central region [P < 0.01]). Furthermore, RIF resistance was genetically distinct, suggesting possible location-specific strains are responsible for the transmission of drug resistance (P < 0.04). Finally, GenoType MTBDRplus correctly identified the drug-resistant samples compared to sequencing in 96.8% of cases. We found that total DR-TB in HIV-infection is high and that transmission of drug-resistant TB in HIV-infected patients in Nigeria is higher than predicted.

摘要

结核病(TB)是人类免疫缺陷病毒(HIV)感染患者中最常见的机会性感染,而耐药结核病(DR-TB)的出现是资源有限环境中的一个日益严重的问题。尼日利亚目前缺乏检测药物敏感性的充分基础设施,也没有足够的一线耐药证据。我们在尼日利亚西南部和中北部地区的两个哈佛 PEPFAR/APIN Plus 项目的抗逆转录病毒治疗(ART)诊所,在 12 个月的时间内收集了入组该项目的 HIV 感染患者的痰液样本。对 415 份涂片阳性痰液样本进行了 GenoType MTBDRplus 检测;通过测序确认了突变。我们的研究结果表明,尼日利亚 HIV 感染个体中 DR-TB 发生率较高(利福平[RIF]耐药率为 7.0%,RIF 或异烟肼[INH]耐药率为 9.3%)。未经治疗的患者中总 RIF 耐药表明 MDR-TB 的发生率为 5.52%,远远超过世界卫生组织的预测(0 至 4.3%)。在 213 例患者中发现 6 例(2.8%)RIF 耐药,在 215 例患者中发现 3 例(1.4%)INH 耐药,在 223 例患者中发现 8 例(3.6%)MDR-TB。我们发现地理位置不同,DR-TB 的发生率也不同(该国南部为 18.18%,中北部地区为 3.91%[P < 0.01])。此外,RIF 耐药的基因存在明显差异,表明可能存在特定于地理位置的菌株导致耐药性的传播(P < 0.04)。最后,与测序相比,GenoType MTBDRplus 在 96.8%的情况下正确识别耐药样本。我们发现,HIV 感染患者中的总 DR-TB 发生率较高,尼日利亚 HIV 感染患者中耐药结核病的传播率高于预期。

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