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.

HIV, sexual violence, and termination of pregnancy among adolescent and adult female sex workers in Malawi: A respondent-driven sampling study.

Female Sex Workers (FSWs) are a hard-to-reach and understudied population, especially those who begin selling sex at a young age. In one of the most economically disadvantaged regions in Malawi, a large population of women is engaged in sex work surrounding predominantly male work sites and transport routes. A cross-sectional study in February and April 2019 in Nsanje district used respondent driven sampling (RDS) to recruit women ≥13 years who had sexual intercourse (with someone other than their main partner) in exchange for money or goods in the last 30 days. A standardized questionnaire was filled in; HIV, syphilis, gonorrhea, and chlamydia tests were performed. CD4 count and viral load (VL) testing occurred for persons living with HIV (PLHIV). Among 363 study participants, one-quarter were adolescents 13-19 years (25.9%; n = 85). HIV prevalence was 52.6% [47.3-57.6] and increased with age: from 14.7% (13-19 years) to 87.9% (≥35 years). HIV status awareness was 95.2% [91.3-97.4], ART coverage was 98.8% [95.3-99.7], and VL suppression 83.2% [77.1-88.0], though adolescent FSWs were less likely to be virally suppressed than adults (62.8% vs. 84.4%). Overall syphilis prevalence was 29.7% [25.3-43.5], gonorrhea 9.5% [6.9-12.9], and chlamydia 12.5% [9.3-16.6]. 72.4% had at least one unwanted pregnancy, 17.9% had at least one abortion (40.1% of which were unsafe). Half of participants reported experiencing sexual violence (SV) (47.6% [42.5-52.7]) and more than one-tenth (14.2%) of all respondents experienced SV perpetrated by a police officer. Our findings show high levels of PLHIV-FSWs engaged in all stages of the HIV cascade of care. The prevalence of HIV, other STIs, unwanted pregnancy, unsafe abortion, and sexual violence remains extremely high. Peer-led approaches contributed to levels of ART coverage and HIV status awareness similar to those found in the general district population, despite the challenges and risks faced by FSWs.

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.

Slipping through the cracks: a qualitative study to explore pathways of HIV care and treatment amongst hospitalised patients with advanced HIV in Kenya and the Democratic Republic of the Congo.

Advanced HIV causes substantial mortality in sub-Saharan Africa despite widespread antiretroviral therapy coverage. This paper explores pathways of care amongst hospitalised patients with advanced HIV in rural Kenya and urban Democratic Republic of the Congo, with a view to understanding their care-seeking trajectories and poor health outcomes. Thirty in-depth interviews were conducted with hospitalised patients with advanced HIV who had previously initiated first-line antiretroviral therapy, covering their experiences of living with HIV and care-seeking. Interviews were audio-recorded, transcribed and translated before being coded inductively and analysed thematically. In both settings, participants' health journeys were defined by recurrent, severe symptoms and complex pathways of care before hospitalisation. Patients were often hospitalised after multiple failed attempts to obtain adequate care at health centres. Most participants managed their ill-health with limited support networks, lived in fragile economic situations and often experienced stress and other mental health concerns. Treatment-taking was sometimes undermined by strict messaging around adherence that was delivered in health facilities. These findings reveal a group of patients who had "slipped through the cracks" of health systems and social support structures, indicating both missed opportunities for timely management of advanced HIV and the need for interventions beyond hospital and clinical settings.

High Prevalence of NRTI and NNRTI Drug Resistance Among ART-Experienced, Hospitalized Inpatients.

BACKGROUND: Patients hospitalized with advanced HIV have a high mortality risk. We assessed viremia and drug resistance among differentiated care services and explored whether expediting the switching of failing treatments may be justified. SETTING: Hospitals in the Democratic Republic of (DRC) Congo (HIV hospital) and Kenya (general hospital including HIV care). METHODS: Viral load (VL) testing and drug resistance (DR) genotyping were conducted for HIV inpatients ≥15 years, on first-line antiretroviral therapy (ART) for ≥6 months, and CD4 ≤350 cells/µL. Dual-class DR was defined as low-, intermediate-, or high-level DR to at least 1 nucleoside reverse transcriptase inhibitor and 1 non-nucleoside reverse transcriptase inhibitor. ART regimens were considered ineffective if dual-class DR was detected at viral failure (VL ≥1000 copies/mL). RESULTS: Among 305 inpatients, 36.7% (Kenya) and 71.2% (DRC) had VL ≥1000 copies/mL, of which 72.9% and 73.7% had dual-class DR. Among viral failures on tenofovir disoproxil fumarate (TDF)-based regimens, 56.1% had TDF-DR and 29.8% zidovudine (AZT)-DR; on AZT regimens, 71.4% had AZT-DR and 61.9% TDF-DR, respectively. Treatment interruptions (≥48 hours during past 6 months) were reported by 41.7% (Kenya) and 56.7% (DRC). Approximately 56.2% (Kenya) and 47.4% (DRC) on TDF regimens had tenofovir diphosphate concentrations <1250 fmol/punch (suboptimal adherence). Among viral failures with CD4 <100 cells/µL, 76.0% (Kenya) and 84.6% (DRC) were on ineffective regimens. CONCLUSIONS: Many hospitalized, ART-experienced patients with advanced HIV were on an ineffective first-line regimen. Addressing ART failure promptly should be integrated into advanced disease care packages for this group. Switching to effective second-line medications should be considered after a single high VL on non-nucleoside reverse transcriptase inhibitor-based first-line if CD4 ≤350 cells/µL or, when VL is unavailable, among patients with CD4 ≤100 cells/µL.

Stockouts of HIV commodities in public health facilities in Kinshasa: Barriers to end HIV.

Stockouts of HIV commodities increase the risk of treatment interruption, antiretroviral resistance, treatment failure, morbidity and mortality. The study objective was to assess the magnitude and duration of stockouts of HIV medicines and diagnostic tests in public facilities in Kinshasa, Democratic Republic of the Congo. This was a cross-sectional survey involving visits to facilities and warehouses in April and May 2015. All zonal warehouses, all public facilities with more than 200 patients on antiretroviral treatment (ART) (high-burden facilities) and a purposive sample of facilities with 200 or fewer patients (low-burden facilities) in Kinshasa were selected. We focused on three adult ART formulations, cotrimoxazole tablets, and HIV diagnostic tests. Availability of items was determined by physical check, while stockout duration until the day of the survey visit was verified with stock cards. In case of ART stockouts, we asked the pharmacist in charge what the facility coping strategy was for patients needing those medicines. The study included 28 high-burden facilities and 64 low-burden facilities, together serving around 22000 ART patients. During the study period, a national shortage of the newly introduced first-line regimen Tenofovir-Lamivudine-Efavirenz resulted in stockouts of this regimen in 56% of high-burden and 43% of low-burden facilities, lasting a median of 36 (interquartile range 29-90) and 44 days (interquartile range 24-90) until the day of the survey visit, respectively. Each of the other investigated commodities were found out of stock in at least two low-burden and two high-burden facilities. In 30/41 (73%) of stockout cases, the commodity was absent at the facility but present at the upstream warehouse. In 30/57 (54%) of ART stockout cases, patients did not receive any medicines. In some cases, patients were switched to different ART formulations or regimens. Stockouts of HIV commodities were common in the visited facilities. Introduction of new ART regimens needs additional planning.

Suicide Among Farmers in France: Occupational Factors and Recent Trends.

Numerous studies have found agricultural workers, including farmers, at elevated risk of suicide, and socioeconomic conditions have been suggested as one of the important determinants of this mortality cause. The real agricultural income per worker in Europe increased steadily from 2005 to 2007 and then fell by 1.8% in 2008 and by 11.6% in 2009. This drop was particularly pronounced in France. Repeated cross-sectional studies were conducted to investigate suicide mortality rates among French farmers in 2007-2009. The study population included all French farmers enrolled yearly in the compulsory Agricultural Social Security and Health Insurance (CCMSA). Most of the mean of 500,164 subjects per year were men (68%). National cause-specific mortality rates were used to calculate standardized mortality ratios (SMRs) and associated 95% confidence intervals (95% CIs) for both genders and for each of the 3 years. During the 3-year study period, 2,769 men and 997 women died. Suicide accounted for 417 of the men's (15%) and 68 of the women's (6.8%) deaths. Hanging was the most frequent method of suicide for both. Compared with the general population, the increased rate of suicide deaths among male farmers was 28% in 2008 and 22% in 2009. This increased rate was particularly high among those aged 45-54 years (31%) and 55-64 years (47%) in 2008 (and in the 55-64-year-old group in 2009 (64%). Two specific types of farming activity were associated with increased suicide mortality rates in both 2008 and 2009: dairy cattle farming (SMR = 1.56 [95% CI: 1.09-2.15] and SMR=1.47 [95% CI: 1.01-2.04]) and beef cattle farming (SMR = 2.27 [95% CI: 1.59-3.10] and SMR = 1.57 [95% CI: 1.01-2.27]). These results may be useful for a better understanding of the situation from an epidemiological standpoint and for improving suicide prevention policies in this particular population.

Revisiting Plant Plasma Membrane Lipids in Tobacco: A Focus on Sphingolipids.

The lipid composition of plasma membrane (PM) and the corresponding detergent-insoluble membrane (DIM) fraction were analyzed with a specific focus on highly polar sphingolipids, so-called glycosyl inositol phosphorylceramides (GIPCs). Using tobacco (Nicotiana tabacum) 'Bright Yellow 2' cell suspension and leaves, evidence is provided that GIPCs represent up to 40 mol % of the PM lipids. Comparative analysis of DIMs with the PM showed an enrichment of 2-hydroxylated very-long-chain fatty acid-containing GIPCs and polyglycosylated GIPCs in the DIMs. Purified antibodies raised against these GIPCs were further used for immunogold-electron microscopy strategy, revealing the distribution of polyglycosylated GIPCs in domains of 35 ± 7 nm in the plane of the PM. Biophysical studies also showed strong interactions between GIPCs and sterols and suggested a role for very-long-chain fatty acids in the interdigitation between the two PM-composing monolayers. The ins and outs of lipid asymmetry, raft formation, and interdigitation in plant membrane biology are finally discussed.