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Low body mass index (BMI) is a globally important risk factor for TB progression. Little is known about this association in people living with HIV (PLHIV) and the functional form of the BMI-TB incidence curve.Secondary analysis of a randomised controlled trial of TB preventive therapy among PLHIV in South Africa, Mozambique, and Ethiopia. Participants received 3 months of weekly high-dose rifapentine-isoniazid given once or twice over a period of 2 years. Multivariable fractional polynomials (MFPs) were used to investigate functional forms of BMI. Time to incident TB was modelled using Cox's proportional hazard regression.A total of 76 TB events were documented, giving an overall TB incidence rate of 1.2 per 100 person-years (95%CI 1.0-1.6). Baseline BMI <18.5 kg/m² was associated with a 2.6-fold increased hazard of TB compared with BMI 18.5-24.9 kg/m² (aHR 2.6, 95% CI 1.4-4.8, P < 0.001). BMI ≥30 kg/m² was associated with a lower hazard of TB (aHR 0.5, 95% CI 0.2-1.0). Continuous and categorical BMI showed weak evidence of quadratic dose-response relationships ( P = 0.08 and P = 0.09, respectively). MFP analysis was consistent with a decline in TB incidence for increasing BMI to around 25 kg/m², followed by a less steep decline in TB incidence for increasing BMI >25 kg/m².In PLHIV, BMI showed an inverse log-linear association with TB incidence. The MFP approach showed that the relationship is more complex than a simple log-linear association..

Introduction: Tuberculosis (TB) is an important cause of morbidity and mortality among people living with HIV (PLHIV). Current WHO-recommended strategies for diagnosing TB among hospitalized PLHIV rely on symptom screening and disease severity to assess eligibility for urine lipoarabinomannan lateral flow (LF-LAM) and molecular testing. Despite these recommendations, autopsy studies show a large burden of undiagnosed TB among admitted PLHIV. The EXULTANT trial aims to assess the impact of an expanded screening strategy using three specimens (sputum, stool, and urine) for TB diagnosis among PLHIV admitted to hospitals in two high HIV and TB burden African countries., Methods: This is a multicenter, pragmatic, individually randomized controlled trial conducted across eleven hospitals in Tanzania and Mozambique. Participants in the intervention arm will be tested with Xpert MTB/RIF Ultra® from expectorated sputum, stool, and urine samples, with additional urine LF-LAM testing in the first 24 h after hospital admission, irrespective of the presence of the symptoms. The control arm will implement the WHO standard of care recommendations. Hospitalized adults (≥ 18 years) with a confirmed HIV-diagnosis, irrespective of antiretroviral (ART) therapy status or presence of TB symptoms will be assessed for eligibility at admission. Patients with a pre-existing TB diagnosis, those receiving anti-tuberculosis therapy or tuberculosis preventive treatment in the 6 months prior to enrolment, and those transferred from other hospitals will not be eligible. Also, participants admitted for traumatic reasons such as acute abdomen, maternal conditions, scheduled surgery, having a positive SARS-CoV2 test will be ineligible. The primary endpoint is the proportion of participants with microbiologically confirmed TB starting treatment within 3 days of enrolment., Discussion: The EXULTANT trial investigates rapid implementation after admission of a new diagnostic algorithm using Xpert MTB/RIF Ultra® in several non-invasive specimens, in addition to LF-LAM, in hospitalized PLHIV regardless of TB symptoms. This enhanced strategy is anticipated to detect frequently missed TB cases in this population and is being evaluated as an implementable and scalable intervention., Trial Registration: Trial reference number: NCT04568967 (ClinicalTrials.gov) registered on 2020-09-29., (© 2024. The Author(s).)

Background: In 2020, the WHO-approved Molbio Truenat platform and MTB assays to detect Mycobacterium tuberculosis complex (MTB) and resistance to rifampicin directly on sputum specimens. This primary health care center-based trial in Mozambique and Tanzania investigates the effect of Truenat platform/MTB assays (intervention arm) combined with rapid communication of results compared to standard of care on TB diagnosis and treatment initiation for microbiologically confirmed TB at 7 days from enrolment., Methods: The Tuberculosis Close the Gap, Increase Access, and Provide Adequate Therapy (TB-CAPT) CORE trial employs a pragmatic cluster randomized controlled design to evaluate the impact of a streamlined strategy for delivery of Truenat platform/MTB assays testing at primary health centers. Twenty-nine centers equipped with TB microscopy units were selected to participate in the trial. Among them, fifteen health centers were randomized to the intervention arm (which involves onsite molecular testing using Truenat platform/MTB assays, process process optimization to enable same-day TB diagnosis and treatment initiation, and feedback on Molbio platform performance) or the control arm (which follows routine care, including on-site sputum smear microscopy and the referral of sputum samples to off-site Xpert testing sites). The primary outcome of the study is the absolute number and proportion of participants with TB microbiological confirmation starting TB treatment within 7 days of their first visit. Secondary outcomes include time to bacteriological confirmation, health outcomes up to 60 days from first visit, as well as user preferences, direct cost, and productivity analyses., Ethics and Dissemination: TB-CAPT CORE trial has been approved by regulatory and ethical committees in Mozambique and Tanzania, as well as by each partner organization. Consent is informed and voluntary, and confidentiality of participants is maintained throughout. Study findings will be presented at scientific conferences and published in peer-reviewed international journals., Trial Registration: US National Institutes of Health's ClinicalTrials.gov, NCT04568954. Registered 23 September 2020., (© 2024. The Author(s).)

Aims: We present a field evaluation of the diagnostic accuracy of Xpert MTB/RIF ("Xpert") and Xpert MTB/RIF Ultra ("Ultra") using two cohorts in a high tuberculosis/HIV burden setting in Southern Mozambique., Methods: Single respiratory specimens from symptomatic adults accessing healthcare services (passive case finding (PCF) cohort) and from household and community close contacts (active case finding (ACF) cohort) were tested by smear microscopy, culture, Xpert and Ultra. Liquid and solid culture served as a composite reference standard. We explored the impact of trace results on specificity via their recategorisation to negative (in all and just among those previously treated individuals)., Results: 1419 and 252 participants were enrolled in the PCF and ACF cohorts, respectively. For the PCF cohort, Ultra showed higher sensitivity than Xpert overall (0.95 (95% CI 0.90-0.98) versus 0.88 (96% CI 0.82-0.93); p<0.001) and among smear-negative patients (0.84 (96% CI 0.71-0.93) versus 0.63 (96% CI 0.48-0.76)). Ultra's specificity was lower than Xpert's (0.96 (96% CI 0.95-0.97) versus 0.98 (96% CI 0.97-0.99); p=0.008). For ACF, sensitivities were the same (0.67 (95% CI 0.22-0.96) for both tests), although Ultra detected a higher number of microbiologically confirmed samples than Xpert (4.7% (12 out of 252) versus 2.7% (seven out of 252)). Conditional recategorisation of trace results among previously treated participants maintained differences in specificity in the PCF cohort., Conclusion: These results add evidence on the improved sensitivity of Ultra and support its use in different case finding scenarios., Competing Interests: Conflict of interest: B. Saavedra has nothing to disclose. Conflict of interest: E. Mambuque has nothing to disclose. Conflict of interest: D. Nguenha has nothing to disclose. Conflict of interest: N. Gomes has nothing to disclose. Conflict of interest: S. Munguambe has nothing to disclose. Conflict of interest: J.I. Garcia has nothing to disclose. Conflict of interest: S. Izco has nothing to disclose. Conflict of interest: S. Acacio has nothing to disclose. Conflict of interest: A. Murias-Closas has nothing to disclose. Conflict of interest: M. Cossa has nothing to disclose. Conflict of interest: I. Losada has nothing to disclose. Conflict of interest: H. Pernas-Pardavila has nothing to disclose. Conflict of interest: L. Oliveras has nothing to disclose. Conflict of interest: G. Theron has nothing to disclose. Conflict of interest: A.L. García-Basteiro has nothing to disclose., (Copyright ©The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org.)

Strengthening tuberculosis diagnosis is an international priority and the advocacy for multi-disease testing devices raises the possibility of improving laboratory efficiency. However, the advantages of centralized platforms might not translate into real improvements under operational conditions. This study aimed to evaluate the field use of the Abbott RealTime MTB (RT-MTB) and Xpert MTB/RIF assays, in a large cohort of HIV-positive and TB presumptive cases in Southern Mozambique. Over a 6-month period, 255 HIV-positive TB presumptive cases were consecutively recruited in the high TB/HIV burden district of Manhiça. The diagnostic performance of both assays was evaluated against two different reference standards: a microbiological gold standard (MGS) and a composite reference standard (CRS). Results from the primary analysis (MGS) showed improved sensitivity (Se) and reduced specificity (Sp) for the Abbott RT-MTB assay compared to the Xpert MTB/RIF (RT-MTB Se: 0.92 (95% CI: 0.75;0.99) vs Xpert Se: 0.73 (95% CI: 0.52;0.88) p value = 0.06; RT-MTB Sp: 0.80 (0.72;0.86) vs Xpert Sp: 0.96 (0.92;0.99) p value < 0.001). The lower specificity may be due to cross-reactivity with non-tuberculous mycobacteria (NTMs), the detection of non-viable MTBC, or the identification of true TB cases missed by the gold standard., (© 2021. The Author(s).)

Tuberculosis (TB) misdiagnosis remains a public health concern, especially among people living with HIV (PLHIV), given the high mortality associated with missed TB diagnoses. The main objective of this study was to describe the all-cause mortality, TB incidence rates and their associated risk factors in a cohort of PLHIV with presumptive TB in whom TB was initially ruled out. We retrospectively followed a cohort of PLHIV with presumptive TB over a 2 year-period in a rural district in Southern Mozambique. During the study period 382 PLHIV were followed-up. Mortality rate was 6.8/100 person-years (PYs) (95% CI 5.2-9.2) and TB incidence rate was 5.4/100 PYs (95% CI 3.9-7.5). Thirty-six percent of deaths and 43% of TB incident cases occurred in the first 12 months of the follow up. Mortality and TB incidence rates in the 2-year period after TB was initially ruled out was very high. The TB diagnostic work-up and linkage to HIV care should be strengthened to decrease TB burden and all-cause mortality among PLHIV with presumptive TB.