Diagnostic accuracy of a three-gene Mycobacterium tuberculosis host response cartridge using fingerstick blood for childhood tuberculosis: a multicentre prospective study in low-income and middle-income countries

BACKGROUND: Childhood tuberculosis remains a major cause of morbidity and mortality in part due to missed diagnosis. Diagnostic methods with enhanced sensitivity using easy-to-obtain specimens are needed. We aimed to assess the diagnostic accuracy of the Cepheid Mycobacterium tuberculosis Host Response prototype cartridge (MTB-HR), a candidate test measuring a three-gene transcriptomic signature from fingerstick blood, in children with presumptive tuberculosis disease. METHODS: RaPaed-TB was a prospective diagnostic accuracy study conducted at four sites in African countries (Malawi, Mozambique, South Africa, and Tanzania) and one site in India. Children younger than 15 years with presumptive pulmonary or extrapulmonary tuberculosis were enrolled between Jan 21, 2019, and June 30, 2021. MTB-HR was performed at baseline and at 1 month in all children and was repeated at 3 months and 6 months in children on tuberculosis treatment. Accuracy was compared with tuberculosis status based on standardised microbiological, radiological, and clinical data. FINDINGS: 5313 potentially eligible children were screened, of whom 975 were eligible. 784 children had MTB-HR test results, of whom 639 had a diagnostic classification and were included in the analysis. MTB-HR differentiated children with culture-confirmed tuberculosis from those with unlikely tuberculosis with a sensitivity of 59·8% (95% CI 50·8–68·4). Using any microbiological confirmation (culture, Xpert MTB/RIF Ultra, or both), sensitivity was 41·6% (34·7–48·7), and using a composite clinical reference standard, sensitivity was 29·6% (25·4–34·2). Specificity for all three reference standards was 90·3% (95% CI 85·5–94·0). Performance was similar in different age groups and by malnutrition status. Among children living with HIV, accuracy against the strict reference standard tended to be lower (sensitivity 50·0%, 15·7–84·3) compared with those without HIV (61·0%, 51·6–69·9), although the difference did not reach statistical significance. Combining baseline MTB-HR result with one Ultra result identified 71·2% of children with microbiologically confirmed tuberculosis. INTERPRETATION: MTB-HR showed promising diagnostic accuracy for culture-confirmed tuberculosis in this large, geographically diverse, paediatric cohort and hard-to-diagnose subgroups. FUNDING: European and Developing Countries Clinical Trials Partnership, UK Medical Research Council, Swedish International Development Cooperation Agency, Bundesministerium für Bildung und Forschung; German Center for Infection Research (DZIF)

Phenotypic Changes on Mycobacterium Tuberculosis-Specific CD4 T Cells as Surrogate Markers for Tuberculosis Treatment Efficacy

Contains fulltext : 196134.pdf (publisher's version ) (Open Access

The molecular bacterial load assay replaces solid culture for measuring early bactericidal response to antituberculosis treatment

Contains fulltext : 136117.pdf (publisher's version ) (Open Access)We evaluated the use of the molecular bacterial load (MBL) assay, for measuring viable Mycobacterium tuberculosis in sputum, in comparison with solid agar and liquid culture. The MBL assay provides early information on the rate of decline in bacterial load and has technical advantages over culture in either form

Data-driven indicator classification and selection for dynamic dashboards: The case of Spanish universities

Paper submitted to EUNIS (European University Information Systems) 2018, Paris, France, 5-8 June 2018In the context of business, dashboards are visual tools that display the most important information about the organization needed to help the top management to make decisions. Since it is important to just provide the relevant and objective-oriented information, the number of indicators included in the dashboard must be kept at minimum. Therefore, the crucial aspect when designing dashboards is the selection of the suitable Key Performance Indicators. To help to carry out this task, we propose a classification and selection methodology, based on the values of the own indicators. This methodology is performed in two main steps: the classification of the indicators in three categories (emergent, hot and consolidated indicators) and the selection of the suitable set of KPIs based on the organization strategies. To illustrate the application of this methodology, we also present a practical case of indicator classification and selection for Spanish universities based on the extensive UNIVERSITIC report

The Molecular Bacterial Load Assay Replaces Solid Culture for Measuring Early Bactericidal Response to Antituberculosis Treatment

We evaluated the use of the molecular bacterial load (MBL) assay, for measuring viable Mycobacterium tuberculosis in sputum, in comparison with solid agar and liquid culture. The MBL assay provides early information on the rate of decline in bacterial load and has technical advantages over culture in either form

Additional file 1 of Study protocol: a pragmatic, cluster-randomized controlled trial to evaluate the effect of implementation of the Truenat platform/MTB assays at primary health care clinics in Mozambique and Tanzania (TB-CAPT CORE)

Additional file 1