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首页 » 体外诊断 » Lancet:临床试验证实简单的尿液结核测试可降低HIV病人死亡率

Lancet:临床试验证实简单的尿液结核测试可降低HIV病人死亡率

来源:生物谷 2016-03-14 09:48

2016年3月14日/生物谷BIOON/--根据一项新的研究,对HIV感染者进行一项低成本的操作简便的尿液测试用于诊断是否患有结核病(tuberculosis , TB)有助降低HIV阳性患者在医院的TB死亡率。相关研究结果于2016年3月9日在线发表在The Lancet期刊上,论文标题为“Effect on mortality of point-of-care, urine-based lipoarabinomannan testing to guide tuberculosis treatment initiation in HIV-positive hospital inpatients: a pragmatic, parallel-group, multicountry, open-label, randomised controlled trial”。

在非洲,将近40%感染上HIV的成年人是由于TB而死亡。在这项研究中,来自南非开普敦大学等多家研究机构的研究人员在撒哈拉以南非洲地区的10家医院开展这项研究。他们认为如果能够更广泛地执行,那么这种低成本的检测方法每年可能拯救上千条性命。

论文通信作者Keertan Dheda教授解释道,“这是TB诊断性测试的首次临床试验,它证实死亡人数显著下降。这种死亡率下降可能是因为尿液测试与常规测试联合使用,从而导致更多的病人较早地开始接受TB治疗。”

在低收入和中等收入国家,HIV感染者经常因TB而死亡。常见的TB诊断方法包括X射线胸透和微生物学痰液(病人咳出的粘液)检测。然而,对病情严重的同时感染上TB和HIV的病人而言,他们很难产生痰液,而且替代性方法(如痰液诱导,或者其他的侵入式取样方法)经常也很难实施。

为了解决这一难题,研究人员开发出一种脂阿拉伯甘露糖(lipoarabinomannan, LAM)检测方法,该方法以尿液为检测对象,可以即时检测(POCT)尿液中的LAM分子,其中LAM分子与TB相关联。它可在25分钟内给出检测结果,而且每次检测只需大约2.66美元。

在这项研究中,研究人员随机地分配来自撒哈拉以南非洲地区四个国家10家医院(南非4家、坦桑尼亚2家,津巴布韦2家)的2528名HIV感染者同时接受常规测试(涂片检查,Xpert MTP/RIF和体外培养)和LAM尿液测试(即LAM组,共计1257人),或者只是接受常规测试(非LAM组,1271人)。

研究人员发现,LAM测试对死亡率的影响在不同的国家存在差异,但在CD4+ T细胞水平最低的HIV感染者体内观察到最高灵敏度,这是因为仅仅利用常规测试最难诊断这些人是否患有TB。他们发现LAM尿液测试的灵敏度为46%,特异性为90%。

终上所述,研究人员在一项临床试验中提供关键性的证据证实尿液LAM测试能够高效地、快速地和低成本地在病人生前诊断HIV相关性TB。鉴于世界卫生组织也推荐进行尿液LAM测试,这种测试方法应当被纳入撒哈拉以南非洲地区各国的国家结核防治规划中以便降低HIV感染者这因TB而死亡。(生物谷 Bioon.com)

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Effect on mortality of point-of-care, urine-based lipoarabinomannan testing to guide tuberculosis treatment initiation in HIV-positive hospital inpatients: a pragmatic, parallel-group, multicountry, open-label, randomised controlled trial

doi:10.1016/S0140-6736(15)01092-2

Jonny G Peter, PhD*, Lynn S Zijenah, PhD*, Duncan Chanda, MD*, Petra Clowes, MD*, Maia Lesosky, PhD, Phindile Gina, MD, Nirja Mehta, MSc, Greg Calligaro, MD, Carl J Lombard, PhD, Gerard Kadzirange, MD, Tsitsi Bandason, PhD, Abidan Chansa, MD, Namakando Liusha, MD, Chacha Mangu, MD, Bariki Mtafya, MD, Henry Msila, MD, Andrea Rachow, PhD, Michael Hoelscher, PhD, Peter Mwaba, MD, Grant Theron, PhD†, Dr Keertan Dheda, PhD
HIV-associated tuberculosis is difficult to diagnose and results in high mortality. Frequent extra-pulmonary presentation, inability to obtain sputum, and paucibacillary samples limits the usefulness of nucleic-acid amplification tests and smear microscopy. We therefore assessed a urine-based, lateral flow, point-of-care, lipoarabinomannan assay (LAM) and the effect of a LAM-guided anti-tuberculosis treatment initiation strategy on mortality.

Methods
We did a pragmatic, randomised, parallel-group, multicentre trial in ten hospitals in Africa—four in South Africa, two in Tanzania, two in Zambia, and two in Zimbabwe. Eligible patients were HIV-positive adults aged at least 18 years with at least one of the following symptoms of tuberculosis (fever, cough, night sweats, or self-reported weightloss) and illness severity necessitating admission to hospital. Exclusion criteria included receipt of any anti-tuberculosis medicine in the 60 days before enrolment. We randomly assigned patients (1:1) to either LAM plus routine diagnostic tests for tuberculosis (smear microscopy, Xpert-MTB/RIF, and culture; LAM group) or routine diagnostic tests alone (no LAM group) using computer-generated allocation lists in blocks of ten. All patients were asked to provide a urine sample of at least 30 mL at enrolment, and trained research nurses did the LAM test in patients allocated to this group using the Alere Determine tuberculosis LAM Ag lateral flow strip test (Alere, USA) at the bedside on enrolment. On the basis of a positive test result, the nurses made a recommendation for initiating anti-tuberculosis treatment. The attending physician made an independent decision about whether to start treatment or not. Neither patients nor health-care workers were masked to group allocation and test results. The primary endpoint was 8-week all-cause mortality assessed in the modified intention-to-treat population (those who received their allocated intervention). This trial is registered with ClinicalTrials.gov, number NCT01770730.

Findings
Between Jan 1, 2013, and Oct 2, 2014, we screened 8728 patients and randomly assigned 2659 to treatment (1336 to LAM, 1323 to no LAM). 108 patients did not receive their allocated treatment, mainly because they did not meet the inclusion criteria, and 23 were excluded from analysis, leaving 2528 in the final modified intention-to-treat analysis (1257 in the LAM group, 1271 in the no LAM group). Overall all-cause 8-week mortality occurred in 578 (23%) patients, 261 (21%) in LAM and 317 (25%) in no LAM, an absolute reduction of 4% (95% CI 1–7). The risk ratio adjusted for country was 0·83 (95% CI 0·73–0·96), p=0·012, with a relative risk reduction of 17% (95% CI 4–28). With the time-to-event analysis, there were 159 deaths per 100 person-years in LAM and 196 per 100 person-years in no LAM (hazard ratio adjusted for country 0·82 [95% CI 0·70–0·96], p=0·015). No adverse events were associated with LAM testing.

Interpretation
Bedside LAM-guided initiation of anti-tuberculosis treatment in HIV-positive hospital inpatients with suspected tuberculosis was associated with reduced 8-week mortality. The implementation of LAM testing is likely to offer the greatest benefit in hospitals where diagnostic resources are most scarce and where patients present with severe illness, advanced immunosuppression, and an inability to self-expectorate sputum.

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