Experiences and perceptions of urine sampling for tuberculosis testing among HIV patients: a multisite qualitative descriptive study.

OBJECTIVES: Evidence on the acceptability of urine-based assays for tuberculosis (TB) diagnosis among patients remains limited. We sought to describe patients' experiences and perceptions of urine sampling for TB testing at point of care. SETTING: Study sites in Kenya, Uganda, Mozambique and South Africa. PARTICIPANTS: Adult ambulatory HIV patients enrolled in a TB diagnostic study were selected purposively. INTERVENTION: For this qualitative descriptive study, audiorecorded individual interviews conducted with consenting participants were translated, transcribed and analysed using content analysis. Ethical agreement was obtained from relevant ethical review committees. RESULTS: Fifty-eight participants were interviewed. Three domains were identified. Overall, participants described urine sampling as easy, rapid and painless, with the main challenge being lacking the urge. Urine was preferred to sputum sampling in terms of simplicity, comfort, stigma reduction, convenience and practicality. While perceptions regarding its trustworthiness for TB diagnosis differed, urine sampling was viewed as an additional mean to detect TB and beneficial for early diagnosis. Participants were willing to wait for several hours for same-day results to allay the emotional, physical and financial burden of having to return to collect results, and would rather not pay for the test. Facilitators of urine sampling included cleanliness and perceived privacy of sampling environments, comprehensive sampling instructions and test information, as well as supplies such as toilet paper and envelopes ensuring confort and privacy when producing and returning samples. Participants motivation for accepting urine-based TB testing stemmed from their perceived susceptibility to TB, the value they attributed to their health, especially when experiencing symptoms, and their positive interactions with the medical team. CONCLUSIONS: This study suggests that urine sampling is well accepted as a TB diagnostic method and provides insights on how to promote patients' uptake of urine-based testing and improve their sampling experiences. These results encourage the future broad use of urine-based assays at point of care.

Novel FujiLAM assay to detect tuberculosis in HIV-positive ambulatory patients in four African countries: a diagnostic accuracy study.

BACKGROUND: Development of rapid biomarker-based tests that can diagnose tuberculosis using non-sputum samples is a priority for tuberculosis control. We aimed to compare the diagnostic accuracy of the novel Fujifilm SILVAMP TB LAM (FujiLAM) assay with the WHO-recommended Alere Determine TB-LAM Ag test (AlereLAM) using urine samples from HIV-positive patients. METHODS: We did a diagnostic accuracy study at five outpatient public health facilities in Uganda, Kenya, Mozambique, and South Africa. Eligible patients were ambulatory HIV-positive individuals (aged ≥15 years) with symptoms of tuberculosis irrespective of their CD4 T-cell count (group 1), and asymptomatic patients with advanced HIV disease (CD4 count <200 cells per µL, or HIV clinical stage 3 or 4; group 2). All participants underwent clinical examination, chest x-ray, and blood sampling, and were requested to provide a fresh urine sample, and two sputum samples. FujiLAM and AlereLAM urine assays, Xpert MTB/RIF Ultra assay on sputum or urine, sputum culture for Mycobacterium tuberculosis, and CD4 count were systematically carried out for all patients. Sensitivity and specificity of FujiLAM and AlereLAM were evaluated against microbiological and composite reference standards. FINDINGS: Between Aug 24, 2020 and Sept 21, 2021, 1575 patients (823 [52·3%] women) were included in the study: 1031 patients in group 1 and 544 patients in group 2. Tuberculosis was microbiologically confirmed in 96 (9·4%) of 1022 patients in group 1 and 18 (3·3%) of 542 patients in group 2. Using the microbiological reference standard, FujiLAM sensitivity was 60% (95% CI 51-69) and AlereLAM sensitivity was 40% (31-49; p<0·001). Among patients with CD4 counts of less than 200 cells per µL, FujiLAM sensitivity was 69% (57-79) and AlereLAM sensitivity was 52% (40-64; p=0·0218). Among patients with CD4 counts of 200 cells per µL or higher, FujiLAM sensitivity was 47% (34-61) and AlereLAM sensitivity was 24% (14-38; p=0·0116). Using the microbiological reference standard, FujiLAM specificity was 87% (95% CI 85-89) and AlereLAM specificity was 86% (95 CI 84-88; p=0·941). FujiLAM sensitivity varied by lot number from 48% (34-62) to 76% (57-89) and specificity from 77% (72-81) to 98% (93-99). INTERPRETATION: Next-generation, higher sensitivity urine-lipoarabinomannan assays are potentially promising tests that allow rapid tuberculosis diagnosis at the point of care for HIV-positive patients. However, the variability in accuracy between FujiLAM lot numbers needs to be addressed before clinical use. FUNDING: ANRS and Médecins Sans Frontières.

Feasibility and acceptability of using the novel urine-based FujiLAM test to detect tuberculosis: A multi-country mixed-methods study.

Background: The novel urine-based FujiLAM test identifies tuberculosis in HIV-positive patients but may be challenging to use at point-of-care (POC). Objectives: We assessed the feasibility and acceptability of using the FujiLAM test at point of care in outpatient settings. Methods: We conducted a mixed methods study in four outpatient settings in Kenya, Mozambique, South Africa, and Uganda between November 2020 and September 2021. The test was performed at POC in existing clinic laboratories and consultation spaces. We performed direct observations in the four health facilities, individual questionnaires, proficiency testing evaluations, and individual interviews among healthcare workers performing the FujiLAM test (healthcare workers), and group discussions with programme managers. Results: Overall, 18/19 (95%) healthcare workers and 14/14 (100%) managers agreed to participate in the study. Most assessed healthcare workers, including lay health workers (10/11; 91%), met the minimum required theoretical knowledge and practical skill in performing the FujiLAM test. Most healthcare workers (17/18; 94%) found the FujiLAM test overall "Easy/Very easy" to perform. Some challenges were mentioned: many timed steps (5/18; 28%); ensuring correct incubation period (5/18; 28%); test result readability (4/18; 22%); and difficulties with cartridge buttons (3/18; 17%). Half of the healthcare workers regularly performing the test (4/7; 57%) found it "Easy" to integrate into routine activities. Most healthcare workers and managers believed that any healthcare worker could perform the test after adequate training. Conclusions: Implementing the FujiLAM test in outpatient POC settings is feasible and acceptable to healthcare workers and managers. This test can be performed in various clinic locations by any healthcare worker. The timed, multi-step test procedure is challenging and may affect the workload in resource-constrained health facilities.

Framework for the implementation of advanced HIV disease diagnostics in sub-Saharan Africa: programmatic perspectives.

Patients with advanced HIV disease have a high risk of mortality, mainly from tuberculosis and cryptococcal meningitis. The advanced HIV disease management package recommended by WHO, which includes diagnostics, therapeutics, and patient psychosocial support, is barely implemented in many different countries. Here, we present a framework for the implementation of advanced HIV disease diagnostics. Laboratory and point-of-care-based reflex testing, coupled with provider-initiated requested testing, for cryptococcal antigen and urinary Mycobacterium tuberculosis lipoarabinomannan antigen, should be done for all patients with CD4+ cell counts of 200 cells per µL or less. Implementation of the advanced HIV disease package should be encouraged within primary health-care facilities and task shifting of testing to lay cadres could facilitate access to rapid results. Implementation of differentiated antiretroviral therapy delivery models can allow clinicians enough time to focus on the management of patients with advanced HIV disease. Efficient up-referral and post-discharge systems, including the development of patient-centric advanced HIV disease literacy, are also crucial. Implementation of the advanced HIV disease package is feasible at all health-care levels, and it should be part of the core of the global response towards ending AIDS as a public health threat.