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在肯尼亚西部,HIV 阴性和阳性结核病患者中耐药结核分枝杆菌的耐药分布模式。

Distribution patterns of drug resistance Mycobacterium tuberculosis among HIV negative and positive tuberculosis patients in Western Kenya.

机构信息

School of Public Health, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya.

School of Biomedical Sciences, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya.

出版信息

BMC Infect Dis. 2021 Nov 22;21(1):1175. doi: 10.1186/s12879-021-06887-x.

Abstract

INTRODUCTION

Globally anti-tuberculosis drug resistance is one of the major challenges affecting control and prevention of tuberculosis. Kenya is ranked among 30 high burden TB countries globally. However, there is scanty information on second line antituberculosis drug resistance among tuberculosis patients. Therefore, this study aimed at determining Mycobacterium tuberculosis drug resistant strain distribution pattern in 10 counties of Western Kenya among HIV positive and negative patients.

METHOD

A cross-sectional study was conducted in Western Kenya, which comprises 10 counties. A multistage sampling method was used where a single sub-county was randomly selected followed by sampling one high volume health facility from each sub-county. Consenting study subjects with at least two smear positive sputum at the time of enrolment were randomly selected. The collected sputum was decontaminated with N-acetyl-L-cysteine-sodium hydroxide (NALC-NaOH) and then stained with Ziehl Neelsen Stain before visualizing the presence of bacilli under microscope at ×100 magnification with oil immersion. Further, the identified bacilli were cultured and susceptibility test carried out using known first and second line antimycobacterial tuberculosis. HIV testing was carried out using Determine HIV-1/2 rapid test (Abbot Diagnostics, Maidenhead, United Kingdom). Those who had smear converted were dropped from the study. Finally, drug susceptibility pattern across the 10 counties of Western Kenya was evaluated.

RESULTS

Our study showed that Mycobacterium tuberculosis drug resistance among HIV negative and positive cases in Western Kenya was prevalent in all the 10 counties surveyed. Based on the drug susceptibility tests, 53.2% and 42.7% of the study samples were resistant to at least one antituberculosis drug among HIV negative and HIV positive patients respectively. The data analysis revealed that among the HIV-positive and HIV-negative patients, resistance to INH was predominant (28.5%, and 23.6%, respectively), followed by RIF (16.4% and 14.6% respectively). Second-line drug resistant strains identified among HIV negative patients included Ethionamide (0.3%), Gatifloxacin (0.3%), Amikacin (0.3%) and Capreomycin (0.3%). There was no second line drug monoresistance among HIV positive TB patients. Multi/poly drug resistance were noted among HIV-negative patients in, INH + AMK (0.7%), INH + PZA (1%), INH + GFX (0.7%, INH + ETO (0.7%, STY + ETO (1%), ETH + ETO (1.0%), INH + KAN (0.7%) and INH + CAP (0.7%) strains/cases at 95% confidence interval. Among HIV positive patients INH + GFX (1.1%), INH + ETO (0.4%) and INH + KAN (0.4%) strains of M. tuberculosis were identified with a confidence interval of 95%. Geographical distribution patterns analysis of M. tuberculosis drug polyresistant strains across the 10 counties were recorded. Among HIV TB patients, resistant strains were identified in Nyamira (INH + GFX, INH + KAN), Bungoma ((ETO + STY), Busia (ETH + ETO and STY + ETO) Homabay (RIF + AMK. ETO + ETH and ETO + STY), Kisumu (ETH + ETO and PZA + ETO) and in Kakamega, Kisii and Vihiga (INH + KAN and RIF + AMK). There was no M. tuberculosis polyresistant strain identified in Migori and Siaya counties. Among HIV positive TB patients, M. tuberculosis resistant strains were identified in three counties, Nyamira (INH + KAN) Homabay (INH + GFX and INH + AMK) and Kakamega (INH + GFX). There was no polyresistant M. tuberculosis strain identified in Migori, Bungoma, Kisii, Vihiga, Busia, Siaya and Kisumu Counties.

DISCUSSION

The distribution patterns of M. tuberculosis drug resistance among HIV negative and positive TB patients could be as a result of reported high prevalence of HIV in Western Kenya counties especially the area under study. Tuberculosis is one of the opportunistic diseases that have been shown to be the major cause of AIDS among HIV infected patients. Resent reports by National AIDS Control Council shows that Kisumu, Siaya, Homabay, Migori, Busia have the overall leading in HIV prevalence in Kenya. The low prevalence of drug resistant strains among HIV tuberculosis patients could be as a result of drug adherence attitude adopted by HIV patients, availability of continuous counselling and close follow up and notification by healthcare workers and community health volunteers.

CONCLUSION

Drug resistant M. tuberculosis strains prevalence is still high among HIV negative and positive patients in Western Kenya with the most affected being HIV negative TB patients. It is therefore probable that the existing control measures are not adequate to control transmission of drug resistant strains. Further, miss diagnosis or delayed diagnosis of TB patients could be contributing to the emergence of M. tuberculosis drug polyresistant strains.

RECOMMENDATION

Based on the result of this study, regular TB drug resistance surveillance should be conducted to ensure targeted interventions aimed at controlling increased transmission of the tuberculosis drug resistant strains among HIV/AIDS and HIV negative patients. There is also need for improved drug resistant infection control measures, timely and rapid diagnosis and enhanced and active screening strategies of tuberculosis among suspected TB patients need to be put in place. Further, studies using a larger patient cohort and from counties across the country would shed much needed insights on the true national prevalence of different variants of M. tuberculosis drug resistance.

摘要

引言

全球范围内的抗结核药物耐药性是影响结核病控制和预防的主要挑战之一。肯尼亚在全球 30 个结核病高负担国家中排名较高。然而,关于 HIV 阳性和阴性结核病患者二线抗结核药物耐药性的信息很少。因此,本研究旨在确定肯尼亚西部 10 个县的 HIV 阳性和阴性结核病患者中结核分枝杆菌耐药株的分布模式。

方法

本研究在肯尼亚西部进行了一项横断面研究,该研究由 10 个县组成。采用多阶段抽样方法,随机选择一个次级县,然后从每个次级县中选择一个高容量的卫生机构。在入组时至少有两个涂片阳性痰的同意研究对象被随机选择。收集的痰液用 N-乙酰-L-半胱氨酸-氢氧化钠(NALC-NaOH)进行去污染,然后用齐尔-尼尔森染色进行染色,然后在 ×100 倍放大倍数下用油浸镜观察存在的杆菌。进一步,对鉴定出的杆菌进行培养,并使用已知的一线和二线抗结核药物进行药敏试验。使用 Determine HIV-1/2 快速检测(Abbot Diagnostics,英国 Maidenhead)进行 HIV 检测。那些痰转化的人被从研究中排除。最后,评估了肯尼亚西部 10 个县的药物敏感性模式。

结果

我们的研究表明,肯尼亚西部 HIV 阴性和阳性病例中的结核分枝杆菌耐药性在所有调查的 10 个县均普遍存在。根据药敏试验结果,HIV 阴性和 HIV 阳性患者的研究样本中分别有 53.2%和 42.7%至少对一种抗结核药物耐药。数据分析显示,在 HIV 阳性和 HIV 阴性患者中,对 INH 的耐药性最为普遍(分别为 28.5%和 23.6%),其次是 RIF(分别为 16.4%和 14.6%)。在 HIV 阴性患者中,二线耐药菌株包括乙硫异烟胺(0.3%)、加替沙星(0.3%)、阿米卡星(0.3%)和卷曲霉素(0.3%)。HIV 阳性结核病患者中没有二线药物单耐药株。在 HIV 阴性患者中,观察到多药/耐多药,包括 INH+AMK(0.7%)、INH+PZA(1%)、INH+GFX(0.7%)、INH+ETO(0.7%)、STY+ETO(1%)、ETH+ETO(1.0%)、INH+KAN(0.7%)和 INH+CAP(0.7%)菌株/病例,置信区间为 95%。在 HIV 阳性患者中,发现 INH+GFX(1.1%)、INH+ETO(0.4%)和 INH+KAN(0.4%)的结核分枝杆菌耐药株,置信区间为 95%。记录了肯尼亚西部 10 个县结核分枝杆菌多耐药株的地理分布模式。在 HIV 结核病患者中,在 Nyamira 县(INH+GFX、INH+KAN)、Bungoma 县(ETO+STY)、Busia 县(ETH+ETO 和 STY+ETO)、Homabay 县(RIF+AMK、ETO+ETH 和 ETO+STY)、Kisumu 县(ETH+ETO 和 PZA+ETO)和 Kakamega 县发现了耐药菌株。在 Migori 和 Siaya 县未发现结核分枝杆菌多耐药株。在 HIV 阳性结核病患者中,在 Nyamira 县(INH+KAN)、Homabay 县(INH+GFX 和 INH+AMK)和 Kakamega 县(INH+GFX)发现了耐药菌株。在 Migori、Bungoma、Kisii、Vihiga、Busia、Siaya 和 Kisumu 县未发现多耐药结核分枝杆菌菌株。

讨论

HIV 阴性和阳性结核病患者中结核分枝杆菌耐药性的分布模式可能是由于肯尼亚西部各县报告的 HIV 流行率较高,尤其是研究区域。结核病是报告的艾滋病毒感染者中机会性疾病之一,是导致艾滋病的主要原因。国家艾滋病控制委员会的最新报告显示,Kisumu、Siaya、Homabay、Migori、Busia 在肯尼亚的 HIV 流行率中处于领先地位。HIV 结核病患者中耐药菌株的低流行率可能是由于 HIV 患者采用了药物依从性态度、医护人员和社区卫生志愿者持续提供咨询和密切随访以及通知。

结论

肯尼亚西部 HIV 阴性和阳性患者中仍然存在较高的耐药结核分枝杆菌菌株流行率,受影响最严重的是 HIV 阴性结核病患者。因此,现有的控制措施可能不足以控制耐药菌株的传播。此外,TB 患者的误诊或延迟诊断可能导致结核分枝杆菌多耐药株的出现。

建议

根据本研究的结果,应定期进行结核病耐药监测,以确保针对 HIV/AIDS 和 HIV 阴性患者实施有针对性的干预措施,以控制耐药菌株的传播。还需要改进耐药感染控制措施,及时快速诊断,并加强和积极筛查疑似结核病患者中的结核病。此外,使用更大的患者队列和来自全国各地的研究将为了解该国不同类型结核分枝杆菌耐药性的真实流行率提供更多的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0639/8607708/f4746a75b556/12879_2021_6887_Fig1_HTML.jpg

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