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In 2020, fecal (stool) testing was recommended for diagnosing Mycobacterium tuberculosis complex (MTBC) infection in children by using the Cepheid Xpert MTB/RIF assay; since then, countries have begun implementing stool-based testing, often as part of a comprehensive strategy to enhance TB case finding among children. On the basis of an experience-sharing workshop in November 2023, we determined insights of 9 early-adopter countries. Across those countries, 71,757 children underwent stool testing over a combined period of 121 months, October 2020-September 2023. A total of 2,892 children were positive for MTBC, and rifampin resistance was confirmed for 43 stool samples. The overall yield of MTBC detection across the countries was 4.1% (range 1.1%-17.3%). Stool collection for Xpert testing was considered noninvasive and as easy as sputum testing. Stool-based testing can be integrated into peripheral healthcare levels as a routine test to increase bacteriologic confirmation among children with presumptive TB.

Tuberculosis (TB) transmission and prevalence are dynamic over time, and heterogeneous within populations. Public health programmes therefore require up-to-date, accurate epidemiological data to appropriately allocate resources, target interventions, and track progress towards End TB goals. Current methods of TB surveillance often rely on case notifications, which are biased by access to healthcare, and TB disease prevalence surveys, which are highly resource-intensive, requiring many tens of thousands of people to be tested to identify high-risk groups or capture trends. Surveys of "latent TB infection", or immunoreactivity to Mycobacterium tuberculosis (Mtb), using tests such as interferon-gamma release assays (IGRAs) could provide a way to identify TB transmission hotspots, supplementing information from disease notifications, and with greater spatial and temporal resolution than is possible to achieve in disease prevalence surveys. This cross-sectional survey will investigate the prevalence of Mtb immunoreactivity amongst young children, adolescents and adults in Blantyre, Malawi, a high HIV-prevalence city in southern Africa. Through this study we will estimate the annual risk of TB infection (ARTI) in Blantyre and explore individual- and area-level risk factors for infection, as well as investigating geospatial heterogeneity of Mtb infection (and its determinants), and comparing these to the distribution of TB disease case-notifications. We will also evaluate novel diagnostics for Mtb infection (QIAreach QFT) and sampling methodologies (convenience sampling in healthcare settings and community sampling based on satellite imagery), which may increase the feasibility of measuring Mtb infection at large scale. The overall aim is to provide high-resolution epidemiological data and provide new insights into methodologies which may be used by TB programmes globally., Competing Interests: The manufacturers of QFT-Plus and QIAreach QFT (QIAGEN) have agreed to provide tests at reduced or no cost for the purposes of research. The investigators will retain all control over research questions and design, data analysis and dissemination, and the manufacturer will play no role in study design, collection, analysis, and interpretation of data, or writing up the study findings., (Copyright: © 2024 Rickman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: TB preventive treatment (TPT) reduces morbidity and mortality among people living with HIV (PLHIV). Despite the successful scale-up of TPT in Malawi, monitoring and evaluation have been suboptimal. We utilized the Malawi Population-Based HIV Impact Assessment (MPHIA) 2020-2021 survey data to estimate TPT uptake and completion among self-reported HIV-positive persons., Methods: We estimated the proportion of HIV-positive respondents who had ever undergone TPT, and determined the percentage of those currently on TPT who had completed more than 6 months of treatment. Bivariate and multivariable logistic regression were performed to calculate the odds ratios for factors associated with ever-taking TPT. All variables were self-reported, and the analysis was weighted and accounted for in the survey design., Results: Of the HIV+ respondents, 38.8% (95% CI 36.4-41.3) had ever taken TPT. The adjusted odds of ever taking TPT were 8.0 and 5.2 times as high in the Central and Southern regions, respectively, compared to the Northern region; 1.9 times higher among those in the highest wealth quintile, and 2.1 times higher for those on antiretroviral therapy >10 years. Of those currently taking TPT, 56.2% completed >6 months of TPT., Conclusion: These results suggest low TPT uptake and >6 months' completion rates among self-reported HIV+ persons. Initiatives to create demand and strengthen adherence would improve TPT uptake., Competing Interests: Conflicts of interest: none declared.

Competing Interests: No conflict of interest.

Initial global-level estimates reported in June 2020 by the World Health Organization suggested that levels of disruption to TB service delivery could be as high as 25%-50% and result in an additional 6·3 million cases of tuberculosis (TB) and an additional 1·4 million TB-related deaths attributable to COVID-19 between 2020 and 2025. Quarterly epidemiological estimates and programmatic TB data capturing disruption levels to each TB service were collected by National TB Programmes in Indonesia, Kyrgyzstan, Malawi, Mozambique, and Peru. Data from 2019, for a pre-COVID-19 baseline, and throughout 2020, together with the NTP's COVID-19 response plans, were used within Optima TB models to project TB incidence and deaths over five years because of COVID-19-related disruptions, and the extent to which those impacts may be mitigated through proposed catch-up strategies in each country. Countries reported disruptions of up to 64% to demand-driven TB diagnosis. However, TB service availability disruptions were shorter and less severe, with TB treatment experiencing levels of disruption of up to 21%. We predicted that under the worse-case scenario cumulative new latent TB infections, new active TB infections, and TB-related deaths could increase by up to 23%, 11%, and 20%, respectively, by 2024. However, three of the five countries were on track to mitigate these increases to 3% or less by maintaining TB services in 2021 and 2022 and by implementing proposed catch-up strategies. Indonesia was already experiencing the worse-case scenario, which could lead to 270,000 additional active TB infections and 36,000 additional TB-related deaths by the end of 2024. The COVID-19 pandemic is projected to negatively affect progress towards 2035 End TB targets, especially in countries already off-track. Findings highlight both successful TB service delivery adaptions in 2020 and the need to proactively maintain TB service availability despite potential future waves of more transmissible COVID-19 variants., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Martin-Hughes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: People with recurrent or drug-resistant TB require long courses of intramuscular injections. We evaluate a novel system in which patient-nominated lay carers were trained to deliver intramuscular injections to patients in their own homes., Methods: A pragmatic, individually randomised non-inferiority trial was conducted at two hospitals in Malawi. Adults starting TB retreatment were recruited. Patients randomised to the intervention received home-based care from patient-nominated lay people trained to deliver intramuscular streptomycin. Patients receiving standard care were admitted to hospital for 2 months of streptomycin. The primary outcome was successful treatment (alive and on treatment) at the end of the intervention., Results: Of 456 patients screened, 204 participants were randomised. The trial was terminated early due to futility. At the end of the intervention, 97/101 (96.0%) in the hospital arm were still alive and on treatment compared with 96/103 (93.2%) in the home-based arm (risk difference -0.03 (95% CI -0.09 to 0.03); p value 0.538). There were no differences in the proportion completing 8 months of anti-TB treatment; or the proportion experiencing 2-month sputum culture conversion. The mean cost of hospital-based management was US$1546.3 per person, compared to US$729.2 for home-based management. Home-based care reduced risk of catastrophic household costs by 84%., Conclusions: Although this trial failed to meet target recruitment, the available data demonstrate that training patient-nominated lay people has potential to provide a feasible solution to the operational challenges associated with delivering long-term-injectable drugs to people with recurrent or drug-resistant TB in resource-limited settings, and substantially reduce costs. Further data under operational conditions are required., Trial Registration Number: ISRCTN05815615., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: Current guidelines recommend the use of the lateral flow urine lipoarabinomannan assay (LAM) in HIV-positive, ambulatory patients with signs and symptoms of tuberculosis (TB) only if they are seriously ill or have CD4 count ≤ 100 cells/μl. We assessed the diagnostic yield of including LAM in TB diagnostic algorithms in HIV-positive, ambulatory patients with CD4 < 200 cells/μl, as well as the risk of mortality in LAM-positive patients who were not diagnosed using other diagnostic tools and not treated for TB., Methods and Findings: We conducted a prospective observational study including HIV-positive adult patients with signs and symptoms of TB and CD4 < 200 cells/μl attending 6 health facilities in Malawi and Mozambique. Patients were included consecutively from 18 September 2015 to 27 October 2016 in Malawi and from 3 December 2014 to 22 August 2016 in Mozambique. All patients had a clinical exam and LAM, chest X-ray, sputum microscopy, and Xpert MTB/RIF assay (Xpert) requested. Culture in sputum was done for a subset of patients. The diagnostic yield was defined as the proportion of patients with a positive assay result among those with laboratory-confirmed TB. For the 456 patients included in the study, the median age was 36 years (IQR 31-43) and the median CD4 count was 50 cells/μl (IQR 21-108). Forty-five percent (205/456) of the patients had laboratory-confirmed TB. The diagnostic yields of LAM, microscopy, and Xpert were 82.4% (169/205), 33.7% (69/205), and 40.0% (84/205), respectively. In total, 50.2% (103/205) of the patients with laboratory-confirmed TB were diagnosed only through LAM. Overall, the use of LAM in diagnostic algorithms increased the yield of algorithms with microscopy and with Xpert by 38.0% (78/205) and 34.6% (71/205), respectively, and, specifically among patients with CD4 100-199 cells/μl, by 27.5% (14/51) and 29.4% (15/51), respectively. LAM-positive patients not diagnosed through other tools and not treated for TB had a significantly higher risk of mortality than LAM-positive patients who received treatment (adjusted risk ratio 2.57, 95% CI 1.27-5.19, p = 0.009). Although the TB diagnostic conditions in the study sites were similar to those in other resource-limited settings, the added value of LAM may depend on the availability of microscopy or Xpert results., Conclusions: LAM has diagnostic value for identifying TB in HIV-positive patients with signs and symptoms of TB and advanced immunodeficiency, including those with a CD4 count of 100-199 cells/μl. In this study, the use of LAM enabled the diagnosis of TB in half of the patients with confirmed TB disease; without LAM, these patients would have been missed. The rapid identification and treatment of TB enabled by LAM may decrease overall mortality risk for these patients., Competing Interests: The authors have declared that no competing interests exist.