Mbeya Medical Research Centre, National Institute for Medical Research (NIMR), Mbeya, Tanzania.
Centro de Investigação Em Saúde de Manhiça (CISM), Manhica, Mozambique.
BMC Infect Dis. 2024 Aug 15;24(1):831. doi: 10.1186/s12879-024-09651-z.
Tuberculosis (TB) is an important cause of morbidity and mortality among people living with HIV (PLHIV). Current WHO-recommended strategies for diagnosing TB among hospitalized PLHIV rely on symptom screening and disease severity to assess eligibility for urine lipoarabinomannan lateral flow (LF-LAM) and molecular testing. Despite these recommendations, autopsy studies show a large burden of undiagnosed TB among admitted PLHIV. The EXULTANT trial aims to assess the impact of an expanded screening strategy using three specimens (sputum, stool, and urine) for TB diagnosis among PLHIV admitted to hospitals in two high HIV and TB burden African countries.
This is a multicenter, pragmatic, individually randomized controlled trial conducted across eleven hospitals in Tanzania and Mozambique. Participants in the intervention arm will be tested with Xpert MTB/RIF Ultra® from expectorated sputum, stool, and urine samples, with additional urine LF-LAM testing in the first 24 h after hospital admission, irrespective of the presence of the symptoms. The control arm will implement the WHO standard of care recommendations. Hospitalized adults (≥ 18 years) with a confirmed HIV-diagnosis, irrespective of antiretroviral (ART) therapy status or presence of TB symptoms will be assessed for eligibility at admission. Patients with a pre-existing TB diagnosis, those receiving anti-tuberculosis therapy or tuberculosis preventive treatment in the 6 months prior to enrolment, and those transferred from other hospitals will not be eligible. Also, participants admitted for traumatic reasons such as acute abdomen, maternal conditions, scheduled surgery, having a positive SARS-CoV2 test will be ineligible. The primary endpoint is the proportion of participants with microbiologically confirmed TB starting treatment within 3 days of enrolment.
The EXULTANT trial investigates rapid implementation after admission of a new diagnostic algorithm using Xpert MTB/RIF Ultra® in several non-invasive specimens, in addition to LF-LAM, in hospitalized PLHIV regardless of TB symptoms. This enhanced strategy is anticipated to detect frequently missed TB cases in this population and is being evaluated as an implementable and scalable intervention.
Trial reference number: NCT04568967 (ClinicalTrials.gov) registered on 2020-09-29.
结核病（TB）是导致艾滋病毒（HIV）感染者（PLHIV）发病和死亡的一个重要原因。目前，世界卫生组织（WHO）推荐的针对住院 PLHIV 的结核病诊断策略依赖于症状筛查和疾病严重程度来评估尿液脂阿拉伯甘露聚糖侧向流（LF-LAM）和分子检测的适用性。尽管有这些建议，但尸检研究表明，在住院的 PLHIV 中，结核病的未确诊病例负担很大。EXULTANT 试验旨在评估在两个高艾滋病毒和结核病负担的非洲国家的 11 家医院中，使用三种标本（痰、粪便和尿液）进行结核病诊断的扩展筛查策略对 PLHIV 的影响。
这是一项在坦桑尼亚和莫桑比克的 11 家医院进行的多中心、实用、个体随机对照试验。干预组的参与者将使用 Xpert MTB/RIF Ultra®从咳出的痰、粪便和尿液样本中进行检测，并在入院后 24 小时内进行额外的尿液 LF-LAM 检测，无论是否存在症状。对照组将实施世界卫生组织的标准护理建议。入院的成年人（≥18 岁），无论 HIV 诊断是否确诊、抗逆转录病毒（ART）治疗状况或是否存在结核病症状，均将在入院时评估其是否符合条件。患有预先存在的结核病诊断、在入组前 6 个月内接受抗结核治疗或结核病预防性治疗、或从其他医院转来的患者将不符合条件。此外，因急性腹痛、产妇情况、择期手术、SARS-CoV2 检测呈阳性等创伤原因入院的患者也将不符合条件。主要终点是在入组后 3 天内开始治疗的有微生物学确诊结核病的参与者比例。
EXULTANT 试验调查了在住院 PLHIV 中，无论是否有结核病症状，在几种非侵入性标本中（除 LF-LAM 外，还包括 Xpert MTB/RIF Ultra®）快速实施新诊断算法的情况。预计这种增强策略将能够检测到该人群中经常遗漏的结核病病例，并正在评估其作为一种可实施和可扩展的干预措施的适用性。
试验参考编号：NCT04568967（ClinicalTrials.gov）于 2020 年 9 月 29 日注册。
