N-acetylcysteine modulates markers of oxidation, inflammation and infection in tuberculosis.

Background: Half the global tuberculosis health burden is due to post-tuberculosis lung disease. Host-directed therapies have been proposed to reduce this burden. N-acetylcysteine (NAC) provides the conditionally essential amino acid cysteine required for synthesis of glutathione, an antioxidant thiol.

A cluster randomized trial assessing the effect of a digital health algorithm on quality of care in Tanzania (DYNAMIC study).

Digital clinical decision support tools have contributed to improved quality of care at primary care level health facilities. However, data from real-world randomized trials are lacking. We conducted a cluster randomized, open-label trial in Tanzania evaluating the use of a digital clinical decision support algorithm (CDSA), enhanced by point-of-care tests, training and mentorship, compared with usual care, among sick children 2 to 59 months old presenting to primary care facilities for an acute illness in Tanzania (ClinicalTrials.

Optimizing delivery strategies for 3HP TB preventive treatment in Tanzania: A qualitative study on acceptability of family approach in HIV care and treatment centers.

Tanzania rolled-out a 12-dose, weekly regimen of isoniazid plus rifapentine (3HP) TB preventive treatment in January 2024. The 3HP completion rate is generally ≥80%, varying by delivery strategy and programmatic setting. Before the roll-out, a mixed methods study was conducted to assess whether a family approach involving family member support, SMS reminders, and three health education sessions was acceptable and optimized 3HP uptake and completion.

Triage test for all-oral drug-resistant tuberculosis (DR-TB) regimen: a phase IV study to assess effectiveness, feasibility, acceptability and cost-effectiveness of the Xpert MTB/XDR assay for rapid triage and treatment of DR-TB.

Introduction: The TriAD study will assess the Xpert MTB/XDR (Xpert XDR; Cepheid) assay to detect tuberculosis (TB) drug resistance in sputum testing positive for TB to rapidly triage and treat patients with a short all-oral treatment regimen.

Methods And Analysis: In this study, approximately 4800 Xpert MTB/RIF or Ultra MTB-positive patients (irrespective of rifampicin (RIF) resistance (RR) status) from several clinical sites across South Africa, Nigeria and Ethiopia will be enrolled over 18-24 months and followed-up for approximately 6 months post-TB treatment completion. Participants will be enrolled into one of two cohorts based on Xpert MTB/RIF and Xpert XDR results: () positive participants with RR in Cohort 1 (n=880) and positive RIF susceptible TB patients with isoniazid mono-resistance irrespective of presence of resistance to fluoroquinolones, second-line injectable drugs or ethionamide in Cohort 2 (n=400).

Impact of point-of-care birth test-and-treat on clinical outcomes among infants with HIV: A cluster randomized trial in Mozambique and Tanzania.

Background: We assessed the impact of point-of-care (PoC) test-and-treat at birth on clinical outcomes and viral suppression among HIV-positive infants in Mozambique and Tanzania.

Methods: This cluster-randomized trial allocated health facilities to intervention, providing PoC-testing and antiretroviral treatment (ART) at birth and week 4-8, or control, starting these at week 4-8. The primary outcome was proportions of clinical events (mortality, morbidity, retention, virological failure, toxicity) among HIV-positive infants at month-18.

New admissions and asymptomatic TB cases seem to fuel TB epidemic in prisons, a cross sectional survey in Tanzania.

There is an increased risk for tuberculosis (TB) infection and disease progression in prison settings. TB prevalence in prisons in low- and middle-income countries have been measured to be up to 50 -times higher than in the general population. The aim of the study was to perform active TB screening and estimate the burden of TB in central prisons in Tanzania mainland.

Spirometric reference equations and lung function testing in adults from Southwestern Tanzania.

Background: The increasing relevance of lung function testing in diagnosing and treating pulmonary diseases globally requires adequate spirometric reference equations. However, locally derived reference standards from African countries are widely missing.

Methods: This cross-sectional study was conducted in Southwestern Tanzania.

Adjunctive N-Acetylcysteine and Lung Function in Pulmonary Tuberculosis.

Background: Tuberculosis remains a global health concern, and half of cured patients have permanent lung injury. N-acetylcysteine (NAC) has shown beneficial antimicrobial, antioxidant, and immunomodulatory effects in preclinical tuberculosis models. We examined its effects on tuberculosis treatment outcomes.

Expanding Xpert MTB/RIF Ultra® and LF-LAM testing for diagnosis of tuberculosis among HIV-positive adults admitted to hospitals in Tanzania and Mozambique: a randomized controlled trial (the EXULTANT trial).

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.

Perceived access to social support during and after TB treatment in Mbeya and Songwe regions, Tanzania: perspectives from TB patients and survivors set against health care providers.

Introduction: Pulmonary tuberculosis (PTB) remains a life-threatening disease in Tanzania, with negative physical, financial, economic and psychosocial consequences to individuals and the society. It mainly lowers the quality of life of patients, survivors and their families, especially those in the poorest and socially deprived categories.

Objectives: To report and discuss a qualitative study that assessed the nature of social support desired and received by PTB patients and survivors.

A pilot cross-sectional study of non-communicable diseases in TB household contacts.

Background: Data on the prevalence of non-communicable diseases (NCDs) in TB household contacts (HHCs) are limited, yet important to inform integrated screening and care for NCD within contact investigations. It is also unclear if screening these contacts reveals more people with NCDs than individuals in the same neighbourhood.

Method: We conducted a pilot cross-sectional study in South Africa and Tanzania, enrolling adult HHCs of TB and individuals in neighbourhood households (controls).

Improved Diagnosis and Treatment Monitoring of Tuberculosis Using Stool and the Tuberculosis Bacterial Load Assay (TB-MBLA).

The diagnosis and monitoring of tuberculosis treatment is difficult as many patients are unable to produce sputum. This means that many patients are treated on the basis of clinical findings and consequently some will be exposed to anti-tuberculosis drugs unnecessarily. Moreover, for those appropriately on treatment and unable to produce a sputum sample, it will be impossible to monitor the response to treatment.

Quantifying Viable M. tuberculosis Safely Obviating the Need for High Containment Facilities.

Mycobacterium tuberculosis is an infectious pathogen that requires biosafety level-3 laboratory for handling. The risk of transmission is high to laboratory staff, and to manage the organism safely, it is necessary to construct high containment laboratory facilities at great expense. This limits the application of tuberculosis diagnostics to areas where there is insufficient capital to invest in laboratory infrastructure.

Bedaquiline-pretomanid-moxifloxacin-pyrazinamide for drug-sensitive and drug-resistant pulmonary tuberculosis treatment: a phase 2c, open-label, multicentre, partially randomised controlled trial.

Background: The current tuberculosis (TB) drug development pipeline is being re-populated with candidates, including nitroimidazoles such as pretomanid, that exhibit a potential to shorten TB therapy by exerting a bactericidal effect on non-replicating bacilli. Based on results from preclinical and early clinical studies, a four-drug combination of bedaquiline, pretomanid, moxifloxacin, and pyrazinamide (BPaMZ) regimen was identified with treatment-shortening potential for both drug-susceptible (DS) and drug-resistant (DR) TB. This trial aimed to determine the safety and efficacy of BPaMZ.

Xpert HIV-1 qual point-of-care testing for HIV early infant diagnosis in Tanzania: experiences and perceptions of health care workers in a 2016 study.

Background: HIV early infant diagnosis (HEID) at the centralized laboratory faces many challenges that impact the cascade of timely HEID. Point of Care (PoC) HEID has shown to reduce test turnaround times, allow for task shifting and has the potential to reduce infant mortality. We aimed at assessing the feasibility of nurse based PoC-HEID in five facilities of Mbeya region.

Safety and Immunogenicity of Accelerated Heterologous 2-Dose Ebola Vaccine Regimens in Adults With and Without HIV in Africa.

Background: Shorter prophylactic vaccine schedules may offer more rapid protection against Ebola in resource-limited settings.

Methods: This randomized, observer-blind, placebo-controlled, phase 2 trial conducted in 5 sub-Saharan African countries included people without human immunodeficiency virus (HIV) (PWOH, n = 249) and people with HIV (PWH, n = 250). Adult participants received 1 of 2 accelerated Ebola vaccine regimens (MVA-BN-Filo, Ad26.

Performance of a stool-based quantitative PCR assay for the diagnosis of tuberculosis in adolescents and adults: a multinational, prospective diagnostic accuracy study.

Background: Despite increasing availability of rapid molecular tests for the diagnosis of tuberculosis in high-burden settings, many people with tuberculosis are undiagnosed. Reliance on sputum as the primary specimen for tuberculosis diagnostics contributes to this diagnostic gap. We evaluated the diagnostic accuracy and additive yield of a novel stool quantitative PCR (qPCR) assay for the diagnosis of tuberculosis in three countries in Africa with high tuberculosis burdens.

Humoral Immune Responses following COVID-19 Vaccinations among Adults in Tanzania.

COVID-19 vaccination remains to be the most important intervention in the fight against the pandemic. The immunity among the vaccinated population and its durability can significantly vary due to various factors. This study investigated the humoral immune responses among individuals who received any of the COVID-19 vaccines approved for use in Tanzania.

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).

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.

Point-of-care glycated hemoglobin a1c testing for the identification of hyperglycemia severity among individuals with dual tuberculosis and diabetes mellitus in Tanzania.

Background: Poor glycemic control during tuberculosis (TB) treatment is challenging, as the optimum treatment strategy remains unclear. We assessed hyperglycemia severity using glycated hemoglobin (HbA1c) test and predictors of severe hyperglycemia at the time of TB diagnosis in three resources-diverse regions in Tanzania.

Methods: This was a substudy from a large cohort study implemented in three regions of Tanzania.

A digital health algorithm to guide antibiotic prescription in pediatric outpatient care: a cluster randomized controlled trial.

Excessive antibiotic use and antimicrobial resistance are major global public health threats. We developed ePOCT+, a digital clinical decision support algorithm in combination with C-reactive protein test, hemoglobin test, pulse oximeter and mentorship, to guide health-care providers in managing acutely sick children under 15 years old. To evaluate the impact of ePOCT+ compared to usual care, we conducted a cluster randomized controlled trial in Tanzanian primary care facilities.

Burden and associated phenotypic characteristics of tuberculosis infection in adult Africans with diabetes: a systematic review.

Diabetes mellitus (DM) increases the risk of developing tuberculosis infection (TBI). However, the evidence on the burden and phenotypic characteristics of TBI in African patients with DM is limited. This study aimed to determine the prevalence and characterisation of TBI in native African patients living with DM.

Dynamics and durability of HIV-1 neutralization are determined by viral replication.

Human immunodeficiency virus type 1 (HIV-1)-neutralizing antibodies (nAbs) that prevent infection are the main goal of HIV vaccine discovery. But as no nAb-eliciting vaccines are yet available, only data from HIV-1 neutralizers-persons with HIV-1 who naturally develop broad and potent nAbs-can inform about the dynamics and durability of nAb responses in humans, knowledge which is crucial for the design of future HIV-1 vaccine regimens. To address this, we assessed HIV-1-neutralizing immunoglobulin G (IgG) from 2,354 persons with HIV-1 on or off antiretroviral therapy (ART).