Department of Internal Medicine, RK Khan Hospital, Department of Internal Medicine, University of Kwa-Zulu Natal, Chatsworth, Kwa-Zulu Natal, South Africa.
Centre for Lung Infection and Immunity, Division of Pulmonology and University of Cape Town Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Int J Infect Dis. 2019 Feb;79:37-43. doi: 10.1016/j.ijid.2018.09.024. Epub 2018 Oct 4.
The World Health Organization (WHO) recommends the use of adjunctive urine lipopolysaccharide lipoarabinomannan (LAM) testing in hospitalized HIV-infected persons with suspected tuberculosis (TB) and a CD4 count <100cells/ml. However, the recommendation is conditional, and uptake by individual treatment programmes depends on perceived additional benefit. The aim of this study was to determine whether adjunctive LAM testing has additional clinical benefits including a reduction in healthcare-related use of resources.
A post hoc analysis was performed of a published multicentre, multi-country, randomized controlled trial that showed an approximate 20% mortality benefit in HIV-infected hospitalized patients who underwent adjunctive LAM testing as part of their diagnostic workup. In that parent study, adult HIV-infected hospitalized patients with suspected TB (n=2528) were randomly allocated to either routine diagnostics (smear microscopy, Xpert MTB/RIF, and culture; n=1271), or routine diagnostics plus adjunctive urine LAM testing (n=1257). Data were further analyzed to determine whether there were other potential benefits of LAM usage based on CD4 count and illness severity. Aspects evaluated included: (1) the reduction in number of diagnostic sputum samples tested, (2) the utilization of additional imaging, (3) disease resolution based on follow-up signs and symptoms of illness severity, and (4) the reduction in hospital readmission.
Adjuvant LAM did not reduce the number of diagnostic sputum samples requested, the need for additional imaging, or the hospital readmission rate. However, adjunctive LAM was associated with a more rapid rate of disease resolution (dyspnoea) in the severely ill subgroup. Higher LAM grade (grades 4 and 5), compared to lower grade positivity (≤3), was associated with lower use of ultrasound, lower Karnofsky performance score, lower CD4 cell count, and shorter time to culture positivity.
Although, adjunct LAM was associated with a mortality benefit in the parent study, no benefit could be demonstrated in the secondary analysis with respect to the number of diagnostic sputum samples requested, the use of additional imaging, or hospital readmission rates. However, given the limitations of the present study, further appropriately designed studies are required to determine the effect of adjunct urine LAM on the utilization of healthcare resources.
世界卫生组织(WHO)建议在疑似结核病(TB)且 CD4 计数<100 个细胞/ml 的住院 HIV 感染者中使用辅助尿液脂多糖阿拉伯甘露聚糖(LAM)检测。然而,该建议是有条件的,个别治疗方案的采用取决于对额外获益的认知。本研究旨在确定辅助 LAM 检测是否具有额外的临床获益,包括减少与医疗保健相关的资源使用。
对已发表的一项多中心、多国家、随机对照试验进行了事后分析,该试验显示在接受辅助 LAM 检测的 HIV 住院患者中,死亡率约降低 20%,这些患者是作为其诊断性检查的一部分接受了辅助 LAM 检测。在该原始研究中,随机分配 2528 名患有疑似 TB 的成年 HIV 住院患者接受常规诊断(涂片显微镜检查、Xpert MTB/RIF 和培养;n=1271)或常规诊断加辅助尿液 LAM 检测(n=1257)。进一步分析数据,以确定根据 CD4 计数和疾病严重程度,LAM 使用是否具有其他潜在获益。评估的方面包括:(1)减少测试的诊断性痰样本数量,(2)使用额外的影像学检查,(3)根据随访症状和疾病严重程度判断疾病是否缓解,以及(4)减少住院再入院率。
辅助 LAM 并未减少诊断性痰样本的数量、对额外影像学检查的需求或住院再入院率。然而,辅助 LAM 与严重疾病亚组疾病更快缓解(呼吸困难)相关。与较低的阳性分级(≤3)相比,较高的 LAM 分级(4 级和 5 级)与较低的超声使用、较低的 Karnofsky 表现评分、较低的 CD4 细胞计数和培养阳性时间更短相关。
尽管辅助 LAM 在原始研究中与死亡率降低相关,但在二次分析中,辅助 LAM 与要求的诊断性痰样本数量、额外影像学检查的使用或住院再入院率方面的获益均无法得到证实。然而,鉴于本研究的局限性,需要进一步设计适当的研究来确定辅助尿液 LAM 对医疗资源利用的影响。