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)

Integrating family planning services into HIV care: use of a point-of-care electronic medical record system in Lilongwe, Malawi

Background: Integrating family planning (FP) services into human immunodeficiency virus (HIV) clinical care helps improve access to contraceptives for women living with HIV. However, high patient volumes may limit providers’ ability to counsel women about pregnancy risks and contraceptive options. Objectives: To assess trends in the use of contraceptive methods after implementing an  electronic medical record (EMR) system with FP questions and determine the reasons for non-use of contraceptives among women of reproductive age (15–49 years) receiving antiretroviral therapy (ART) at the Martin Preuss Center clinic in Malawi. Methods: In February 2012, two FP questions were incorporated into the ART EMR system (initial FP EMR module) to prompt providers to offer contraceptives to women. In July 2013, additional questions were added to the FP EMR module (enhanced FP EMR) to prompt providers to assess risks of unintended pregnancies, solicit reasons for non-use of contraceptives and offer contraceptives to non-pregnant women . We conducted a retrospective, longitudinal cohort study using the EMR routinely collected data. The primary outcome was the use of any modern contraceptive method. Descriptive statistics were used to describe the study population and report trends in contraceptive use during the initial and enhanced study periods. Results: Between February 2012 and December 2016, in HIV clinics, 20,253 women of reproductive age received ART, resulting in 163,325 clinic visits observations. The proportion of women using contraceptives increased significantly from 18% to 39% between February 2012 and June 2013, and from 39% to 67% between July 2013 and December 2016 (chi-square for trend p < 0.001). Common reasons reported for the non-use of contraceptives among those at risk of unintended pregnancy were: pregnancy ambivalence (n = 234, 51%) and never thought about it (n = 133, 29%). Conclusion: Incorporating the FP EMR module into HIV clinical care prompted healthcare workers to encourage the use of contraceptives