肯尼亚西部HIV流行区异烟肼和利福平结核耐药情况

Fred Ogumbo, R. Odero, B. Odhiambo, Patrick Emojong, A. Okumu, J. Nonoh, S. Wandiga, B. Guya
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引用次数: 0

摘要

背景:结核病耐药通常与不适当的抗结核治疗方案有关,导致抗结核药物产生耐药性的突变。结核病和艾滋病毒(人类免疫缺陷病毒)之间的协同关系加剧了这种情况。全球结核病死亡的25%以上发生在非洲,肯尼亚是30个高负担国家之一,这些国家加起来占世界结核病病例的80%以上。根据世界卫生组织的数据,2018年,肯尼亚耐多药结核病的患病率在新发病例中为1.3%,在再治疗病例中为4.4%。基苏木县的艾滋病毒流行率为18.6%,位居第二,而2020年全国流行率为4.5%。在肯尼亚西部,耐药结核病和艾滋病毒合并感染的区域负担程度尚未得到确切界定。方法:这是一项前瞻性横断面研究,旨在探讨肯尼亚基苏木县新发和以前治疗过的肺结核病例中结核病耐药性与艾滋病毒状态之间的关系。招募结核病临床疑似患者加入研究,根据其临床资料将其分为HIV阳性或阴性。对肺结核临床疑似患者的痰标本进行了荧光显微镜、表型培养和线探针检测。结果:在256份样本中,有效率为216例,其中HIV阳性119例(55.1%),阴性97例(44.9%)。研究发现,在11例表型异烟肼耐药病例中,8例(6.7%)来自HIV阳性病例,3例(3.2%)来自HIV阴性病例。HIV阳性者8例(6.7%),HIV阴性者2例(2.1%)。所有2例(1.7%)MDR病例均来自HIV阳性参与者。研究发现,HIV感染状况与肺结核病例显著相关(p< 0.05)。与新发病例相比,HIV阳性病例更可能与再治疗病例相关(OR=1.4,95CI:1.00-1.90)。研究发现,HIV阳性人群中常见的突变探针是katG mut1.4(2.6%),而HIV阴性人群中常见的突变探针是hA mut1.1(0.7%)、katG mut1.1(0.7%)和roB MUT2A 1(0.7%)。HIV阳性病例中,探针katG WT 3(2.1%)、roB WT7、katG WT1(0.7%)存在野生型基因缺失;HIV阴性病例中,探针hA WT1 1(0.7%)、hA WT1/inhAWT2 1(0.7%)、katG WT1(0.7%)存在野生型基因缺失。结论:迫切需要针对艾滋病流行地区采取措施,阻断结核病耐药传播。发展和改善干预措施的效力将需要更好地了解耐多药结核病在肯尼亚西部基苏木县等艾滋病毒流行环境中的传播情况。
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Isoniazid and Rifampicin Tuberculosis Drug Resistance in HIV Endemic Region of Western Kenya
Background: Tuberculosis drug resistance is often associated with inadequate anti-tuberculosis treatment regimen resulting to mutations that confers resistance to anti-tuberculosis agents. This is aggravated by synergetic relationship between Tuberculosis and HIV (Human Immunodeficiency Virus). Over 25% of Global Tuberculosis deaths occur in Africa and Kenya is one of the 30 high burden countries that together account for more than 80% of the world’s TB cases. According to World Health Organization, in 2018, Multi drug resistant Tuberculosis prevalence in Kenya was 1.3% in new cases and 4.4% in retreatment cases. Kisumu County recorded the second highest HIV prevalence at 18.6% against the national prevalence of 4.5% in 2020. The extent of regional burden of DR-TB and HIV co-infection has not been exactly well-defined in Western Kenya. Methods: This was a prospective cross sectional study that aimed to explore the association between Tuberculosis drug resistance and HIV status among new and previously treated pulmonary tuberculosis cases in Kisumu County, Kenya. Tuberculosis clinical suspects were recruited into the study and classified as HIV positive or negative based on their clinical data. Sputum samples from tuberculosis clinical suspects were subjected to fluorescent microscopy, phenotypic culture and line probe assay. Results: Out of a sample of 256, response rate was 216 of which HIV positive cases were 119(55.1%) and negative were 97 (44.9%). The study found that out of 11 that were phenotypic Isoniazid resistance 8(6.7%) were from HIV positive cases while 3 (3.2%) were from HIV negative cases. Phenotypic rifampicin resistance among the HIV positive were 8 (6.7%) while HIV negative were 2 (2.1%). All the 2(1.7%) MDR cases were from HIV positive participants. The study found out that HIV status and Tuberculosis cases were significantly associated at p<.05. HIV positive cases were more likely associated with retreatment cases (OR=1.4,95CI:1.00-1.90) compared to new cases. The study found out that the common mutant probe among the HIV positive was katG MUT1 4(2.6%), while mutant probes among the HIV negative were in hA MUT1 1(0.7%), katG MUT1 1(0.7%) and roB MUT2A 1(0.7%). Wild type gene deletion among the HIV positive cases were observed in probes katG WT 3(2.1%), roB WT7, katG WT 1(0.7%) while wild type gene deletion among the HIV negative cases were inhA WT1 1(0.7%), in hA WT1/inhAWT2 1(0.7%), katG WT 1(0.7%). Conclusion: Interventions specific to HIV-endemic areas are urgently needed to block tuberculosis drug resistance transmission. Development and improvement of the efficacy of interventions will require a greater understanding of the transmission of multidrug-resistant tuberculosis in HIV-endemic settings like Kisumu County, Western Kenya.
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