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.

Effectiveness of case-area targeted interventions including vaccination on the control of epidemic cholera: protocol for a prospective observational study.

INTRODUCTION: Cholera outbreaks in fragile settings are prone to rapid expansion. Case-area targeted interventions (CATIs) have been proposed as a rapid and efficient response strategy to halt or substantially reduce the size of small outbreaks. CATI aims to deliver synergistic interventions (eg, water, sanitation, and hygiene interventions, vaccination, and antibiotic chemoprophylaxis) to households in a 100-250 m 'ring' around primary outbreak cases. METHODS AND ANALYSIS: We report on a protocol for a prospective observational study of the effectiveness of CATI. Médecins Sans Frontières (MSF) plans to implement CATI in the Democratic Republic of the Congo (DRC), Cameroon, Niger and Zimbabwe. This study will run in parallel to each implementation. The primary outcome is the cumulative incidence of cholera in each CATI ring. CATI will be triggered immediately on notification of a case in a new area. As with most real-world interventions, there will be delays to response as the strategy is rolled out. We will compare the cumulative incidence among rings as a function of response delay, as a proxy for performance. Cross-sectional household surveys will measure population-based coverage. Cohort studies will measure effects on reducing incidence among household contacts and changes in antimicrobial resistance. ETHICS AND DISSEMINATION: The ethics review boards of MSF and the London School of Hygiene and Tropical Medicine have approved a generic protocol. The DRC and Niger-specific versions have been approved by the respective national ethics review boards. Approvals are in process for Cameroon and Zimbabwe. The study findings will be disseminated to the networks of national cholera control actors and the Global Task Force for Cholera Control using meetings and policy briefs, to the scientific community using journal articles, and to communities via community meetings.

High prevalence of multidrug-resistant tuberculosis, Swaziland, 2009-2010.

In Africa, although emergence of multidrug-resistant (MDR) tuberculosis (TB) represents a serious threat in countries severely affected by the HIV epidemic, most countries lack drug-resistant TB data. This finding was particularly true in the Kingdom of Swaziland, which has the world's highest HIV and TB prevalences. Therefore, we conducted a national survey in 2009-2010 to measure prevalence of drug-resistant TB. Of 988 patients screened, 420 new case-patients and 420 previously treated case-patients met the study criteria. Among culture-positive patients, 15.3% new case-patients and 49.5% previously treated case-patients harbored drug-resistant strains. MDR TB prevalence was 7.7% and 33.8% among new case-patients and previously treated case-patients, respectively. HIV infection and past TB treatment were independently associated with MDR TB. The findings assert the need for wide-scale intervention in resource-limited contexts such as Swaziland, where diagnostic and treatment facilities and health personnel are lacking.