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机会性感染的诊断:HIV合并感染 - 结核病

Diagnosis of opportunistic infections: HIV co-infections - tuberculosis.

作者信息

Scott Lesley, da Silva Pedro, Boehme Catharina C, Stevens Wendy, Gilpin Christopher M

机构信息

aDepartment of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa bNational Priority Programs, National Health Laboratory Service, Johannesburg, Gauteng, South Africa cFoundation for Innovative New Diagnostics, Geneva dGlobal TB Program, WHO, Geneva, Switzerland.

出版信息

Curr Opin HIV AIDS. 2017 Mar;12(2):129-138. doi: 10.1097/COH.0000000000000345.

Abstract

PURPOSE OF REVIEW

Tuberculosis (TB) incidence has declined ∼1.5% annually since 2000, but continued to affect 10.4 million individuals in 2015, with 1/3 remaining undiagnosed or underreported. The diagnosis of TB among those co-infected with HIV is challenging as TB remains the leading cause of death in such individuals. Accurate and rapid diagnosis of active TB will avert mortality in both adults and children, reduce transmission, and assist in timeous decisions for antiretroviral therapy initiation. This review describes advances in diagnosing TB, especially among HIV co-infected individuals, highlights national program's uptake, and impact on patient care.

RECENT FINDINGS

The TB diagnostic landscape has been transformed over the last 5 years. Molecular diagnostics such as Xpert MTB/RIF, which simultaneously detects Mycobacterium tuberculosis (MTB) resistance to rifampicin, has revolutionized TB control programs. WHO endorsed the use of Xpert MTB/RIF in 2010 for use in HIV/TB co-infected patients, and later in 2013 for use as the initial diagnostic test for all adults and children with signs and symptoms of pulmonary TB. Line probe assays (LPAs) are recommended for the detection of rifampicin and isoniazid resistance in sputum smear-positive specimens and mycobacterial cultures. A second-line line probe assay has been recommended for the diagnosis of extensively drug-resistant (XDR)-TB Assays such as the urine lateral flow (LF)-lipoarabinomannan (LAM), can be used at the point of care (POC) and have a niche role to supplement the diagnosis of TB in seriously ill HIV-infected, hospitalized patients with low CD4 cell counts of less than 100 cells/μl. Polyvalent platforms such as the m2000 (Abbott Molecular) and GeneXpert (Cepheid) offer potential for integration of HIV and TB testing services. While the Research and Development (R&D) pipeline appears to be rich at first glance, there are actually few leads for true POC tests that would allow for earlier TB diagnosis or rapid, comprehensive drug susceptibility testing, especially when considering the very high attrition rates observed between biomarker discovery and product market entry.

SUMMARY

In this review, we describe diagnostic strategies specifically for HIV and TB co-infected individuals. Molecular diagnostics in particular within the past 5 years have revolutionized and 'disrupted' this field. They lend themselves to integration of services with platforms capable of polyvalent testing. Impact on patient care is, however, still debatable. What has been highlighted is the need for health system strengthening and for true POC testing that can be used in active case finding.

摘要

综述目的

自2000年以来,结核病发病率每年下降约1.5%,但2015年仍有1040万人受到影响,其中三分之一未被诊断或报告不足。在合并感染艾滋病毒的人群中诊断结核病具有挑战性,因为结核病仍是这些人群的主要死因。准确、快速地诊断活动性结核病将避免成人和儿童死亡,减少传播,并有助于及时决定开始抗逆转录病毒治疗。本综述描述了结核病诊断方面的进展,特别是在合并感染艾滋病毒的人群中,强调了国家项目的采用情况及其对患者护理的影响。

最新发现

在过去5年里,结核病诊断领域发生了变革。分子诊断技术,如同时检测结核分枝杆菌(MTB)对利福平耐药性的Xpert MTB/RIF,彻底改变了结核病控制项目。世界卫生组织于2010年认可在合并感染艾滋病毒/结核病的患者中使用Xpert MTB/RIF,后来在2013年认可将其用作所有有肺结核症状和体征的成人及儿童的初始诊断检测。推荐使用线性探针分析(LPA)检测痰涂片阳性标本和分枝杆菌培养物中的利福平和异烟肼耐药性。推荐使用二线线性探针分析诊断广泛耐药(XDR)结核病。尿液侧向流动(LF)-脂阿拉伯甘露聚糖(LAM)等检测方法可在床旁使用,在补充诊断病情严重、合并感染艾滋病毒、住院且CD4细胞计数低于100个/μl的患者的结核病方面具有特定作用。m2000(雅培分子公司)和GeneXpert(赛沛公司)等多价平台为整合艾滋病毒和结核病检测服务提供了潜力。虽然研发渠道乍一看似乎丰富,但实际上真正能实现床旁检测的线索很少,而床旁检测能实现更早的结核病诊断或快速、全面的药敏试验,尤其是考虑到在生物标志物发现和产品进入市场之间观察到的极高淘汰率。

总结

在本综述中,我们描述了专门针对合并感染艾滋病毒和结核病患者的诊断策略。特别是在过去5年里,分子诊断技术彻底改变并“颠覆”了这一领域。它们便于与能够进行多价检测的平台整合服务。然而,对患者护理的影响仍存在争议。所强调的是加强卫生系统以及需要可用于主动病例发现的真正床旁检测。

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