Co-creation of a gender responsive TB intervention in Nigeria: a researcher-led collaborative study.

Background: In Nigeria, men constitute over half of the people notified with tuberculosis (TB), experience longer delays before reaching care, and are estimated to account for two thirds of people who miss out on care. The higher TB risk and burden in men has implications for the whole population and reaching them earlier with TB services will reduce onward transmission in households, communities, and workplaces. The absence of a comprehensive guidance and the lack of substantial empirical evidence on TB care approaches that are responsive to the needs of men in Nigeria exacerbates this problem.

Finding the missed millions: innovations to bring tuberculosis diagnosis closer to key populations.

Current strategies to promptly, effectively, and equitably screen people with tuberculosis (TB) and link them to diagnosis and care are insufficient; new approaches are required to find the millions of people around the world with TB who are missed each year. Interventions also need to be designed considering how people interact with health care facilities and where appropriate should be suitable for use in the community. Here, the historical, new, and reemerging technologies that are being utilised for TB diagnosis globally are discussed, whilst highlighting that how we use and evaluate tests is just as important as the tests themselves.

Long-term efficacy and safety of two short standardised regimens for the treatment of rifampicin-resistant tuberculosis (STREAM stage 2): extended follow-up of an open-label, multicentre, randomised, non-inferiority trial.

Background: STREAM stage 2 showed that two bedaquiline-containing regimens (a 9-month all-oral regimen and a 6-month regimen with 8 weeks of aminoglycoside) had superior efficacy to a 9-month injectable-containing regimen for rifampicin-resistant tuberculosis up to 76 weeks after randomisation. Our objective in this follow-up analysis was to assess the durability of efficacy and safety, including mortality, at 132 weeks.

Methods: We report the long-term outcomes from STREAM stage 2, a randomised, phase 3 non-inferiority (10% margin) trial in participants (aged ≥15 years) with rifampicin-resistant tuberculosis without fluoroquinolone or aminoglycoside resistance at 13 clinical sites in seven countries (Ethiopia, Georgia, India, Moldova, Mongolia, South Africa, and Uganda).

Drug-resistant tuberculosis treatments, the case for a phase III platform trial.

Most phase III trials in drug-resistant tuberculosis have either been underpowered to quantify differences in microbiological endpoints or have taken up to a decade to complete. Composite primary endpoints, dominated by differences in treatment discontinuation and regimen changes, may mask important differences in treatment failure and relapse. Although new regimens for drug-resistant tuberculosis appear very effective, resistance to new drugs is emerging rapidly.

Cost of digital technologies and family-observed DOT for a shorter MDR-TB regimen: a modelling study in Ethiopia, India and Uganda.

Background: In 2017, the WHO recommended the use of digital technologies, such as medication monitors and video observed treatment (VOT), for directly observed treatment (DOT) of drug-susceptible TB. The WHO's 2020 guidelines extended these recommendations to multidrug-resistant tuberculosis (MDR-TB), based on low evidence. The impact of COVID on health systems and patients underscored the need to use digital technologies in the management of MDR-TB.

Protocol for the Addressing the Social Determinants and Consequences of Tuberculosis in Nepal (ASCOT) pilot trial.

The World Health Organization's End TB (tuberculosis) Strategy advocates social and economic support for TB-affected households but evidence from low-income settings is scarce. We will evaluate the feasibility and acceptability of a locally-appropriate socioeconomic support intervention for TB-affected households in Nepal. We will conduct a pilot randomised-controlled trial with mixed-methods process evaluation in four TB-endemic, impoverished districts of Nepal: Pyuthan, Chitwan, Mahottari, and Morang.

Economic evaluation of shortened, bedaquiline-containing treatment regimens for rifampicin-resistant tuberculosis (STREAM stage 2): a within-trial analysis of a randomised controlled trial.

Background: The STREAM stage 2 trial assessed two bedaquiline-containing regimens for rifampicin-resistant tuberculosis: a 9-month all-oral regimen and a 6-month regimen containing an injectable drug for the first 2 months. We did a within-trial economic evaluation of these regimens.

Methods: STREAM stage 2 was an international, phase 3, non-inferiority randomised trial in which participants with rifampicin-resistant tuberculosis were randomly assigned (1:2:2:2) to the 2011 WHO regimen (terminated early), a 9-month injectable-containing regimen (control regimen), a 9-month all-oral regimen with bedaquiline (oral regimen), or a 6-month regimen with bedaquiline and an injectable for the first 2 months (6-month regimen).

Evaluation of two short standardised regimens for the treatment of rifampicin-resistant tuberculosis (STREAM stage 2): an open-label, multicentre, randomised, non-inferiority trial.

Background: The STREAM stage 1 trial showed that a 9-month regimen for the treatment of rifampicin-resistant tuberculosis was non-inferior to the 20-month 2011 WHO-recommended regimen. In STREAM stage 2, we aimed to compare two bedaquiline-containing regimens with the 9-month STREAM stage 1 regimen.

Methods: We did a randomised, phase 3, non-inferiority trial in 13 hospital clinics in seven countries, in individuals aged 15 years or older with rifampicin-resistant tuberculosis without fluoroquinolone or aminoglycoside resistance.

TB morbidity estimates overlook the contribution of post-TB disability: evidence from urban Malawi.

Introduction: Despite growing evidence of the long-term impact of tuberculosis (TB) on quality of life, Global Burden of Disease (GBD) estimates of TB-related disability-adjusted life years (DALYs) do not include post-TB morbidity, and evaluations of TB interventions typically assume treated patients return to pre-TB health. Using primary data, we estimate years of life lost due to disability (YLDs), years of life lost due to premature mortality (YLL) and DALYs associated with post-TB cardiorespiratory morbidity in a low-income country.

Methods: Adults aged ≥15 years who had successfully completed treatment for drug-sensitive pulmonary TB in Blantyre, Malawi (February 2016-April 2017) were followed-up for 3 years with 6-monthly and 12-monthly study visits.

Palliative care and catastrophic costs in Malawi after a diagnosis of advanced cancer: a prospective cohort study.

Background: Inclusive universal health coverage requires access to quality health care without financial barriers. Receipt of palliative care after advanced cancer diagnosis might reduce household poverty, but evidence from low-income and middle-income settings is sparse.

Methods: In this prospective study, the primary objective was to investigate total household costs of cancer-related health care after a diagnosis of advanced cancer, with and without the receipt of palliative care.

Socio-protective effects of active case finding on catastrophic costs from tuberculosis in Ho Chi Minh City, Viet Nam: a longitudinal patient cost survey.

Background: Many tuberculosis (TB) patients incur catastrophic costs. Active case finding (ACF) may have socio-protective properties that could contribute to the WHO End TB Strategy target of zero TB-affected families suffering catastrophic costs, but available evidence remains limited. This study measured catastrophic cost incurrence and socioeconomic impact of an episode of TB and compared those socioeconomic burdens in patients detected by ACF versus passive case finding (PCF).

Barriers and facilitators to accessing tuberculosis care in Nepal: a qualitative study to inform the design of a socioeconomic support intervention.

Objective: Psychosocial and economic (socioeconomic) barriers, including poverty, stigma and catastrophic costs, impede access to tuberculosis (TB) services in low-income countries. We aimed to characterise the socioeconomic barriers and facilitators of accessing TB services in Nepal to inform the design of a locally appropriate socioeconomic support intervention for TB-affected households.

Design: From August 2018 to July 2019, we conducted an exploratory qualitative study consisting of semistructured focus group discussions (FGDs) with purposively selected multisectoral stakeholders.

Computer-aided X-ray screening for tuberculosis and HIV testing among adults with cough in Malawi (the PROSPECT study): A randomised trial and cost-effectiveness analysis.

Background: Suboptimal tuberculosis (TB) diagnostics and HIV contribute to the high global burden of TB. We investigated costs and yield from systematic HIV-TB screening, including computer-aided digital chest X-ray (DCXR-CAD).

Methods And Findings: In this open, three-arm randomised trial, adults (≥18 years) with cough attending acute primary services in Malawi were randomised (1:1:1) to standard of care (SOC); oral HIV testing (HIV screening) and linkage to care; or HIV testing and linkage to care plus DCXR-CAD with sputum Xpert for high CAD4TBv5 scores (HIV-TB screening).

Systematic Review of Pooling Sputum as an Efficient Method for Xpert MTB/RIF Tuberculosis Testing during the COVID-19 Pandemic.

GeneXpert-based testing with Xpert MTB/RIF or Ultra assays is essential for tuberculosis diagnosis. However, testing may be affected by cartridge and staff shortages. More efficient testing strategies could help, especially during the coronavirus disease pandemic.

Tuberculosis diagnosis cascade in Blantyre, Malawi: a prospective cohort study.

Background: Tuberculosis (TB) control relies on early diagnosis and treatment. International guidelines recommend systematic TB screening at health facilities, but implementation is challenging. We investigated completion of recommended TB screening steps in Blantyre, Malawi.

Economic evaluation protocol of a short, all-oral bedaquiline-containing regimen for the treatment of rifampicin-resistant tuberculosis from the STREAM trial.

Introduction: A December 2019 WHO rapid communication recommended the use of 9-month all-oral regimens for treating multidrug-resistant tuberculosis (MDR-TB). Besides the clinical benefits, they are thought to be less costly than the injectable-containing regimens, for both the patient and the health system. STREAM is the first randomised controlled trial with an economical evaluation to compare all-oral and injectable-containing 9-11-month MDR-TB treatment regimens.

Evaluating the yield of systematic screening for tuberculosis among three priority groups in Ho Chi Minh City, Viet Nam.

Background: In order to end tuberculosis (TB), it is necessary to expand coverage of TB care services, including systematic screening initiatives. However, more evidence is needed for groups among whom systematic screening is only conditionally recommended by the World Health Organization. This study evaluated concurrent screening in multiple target groups using community health workers (CHW).

Research protocol for a mixed-methods study to characterise and address the socioeconomic impact of accessing TB diagnosis and care in Nepal.

WHO's 2015 End TB Strategy advocates social and economic (socioeconomic) support for TB-affected households to improve TB control. However, evidence concerning socioeconomic support for TB-affected households remains limited, especially in low-income countries. This mixed-methods study in Nepal will: evaluate the socioeconomic impact of accessing TB diagnosis and care (Project 1); and create a shortlist of feasible, locally-appropriate interventions to mitigate this impact (Project 2).

Provider-initiated HIV testing and TB screening in the era of universal coverage: Are the right people being reached? A cohort study in Blantyre, Malawi.

Introduction: Patients with tuberculosis (TB) symptoms have high prevalence of HIV, and should be prioritised for HIV testing.

Methods: In a prospective cohort study in Bangwe primary care clinic, Blantyre, Malawi, all adults (18 years or older) presenting with an acute illness were screened for TB symptoms (cough, fever, night sweats, weight loss). Demographic characteristics were linked to exit interview by fingerprint bioidentification.

Developing Feasible, Locally Appropriate Socioeconomic Support for TB-Affected Households in Nepal.

Tuberculosis (TB), the leading single infectious diseases killer globally, is driven by poverty. Conversely, having TB worsens impoverishment. During TB illness, lost income and out-of-pocket costs can become "catastrophic", leading patients to abandon treatment, develop drug-resistance, and die.

Economic evaluation of short treatment for multidrug-resistant tuberculosis, Ethiopia and South Africa: the STREAM trial.

Objective: To investigate cost changes for health systems and participants, resulting from switching to short treatment regimens for multidrug-resistant (MDR) tuberculosis.

Methods: We compared the costs to health systems and participants of long (20 to 22 months) and short (9 to 11 months) MDR tuberculosis regimens in Ethiopia and South Africa. Cost data were collected from participants in the STREAM phase-III randomized controlled trial and we estimated health-system costs using bottom-up and top-down approaches.

Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient data.

Background: The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI.

Methods: We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older.

Study protocol for a single-centre observational study of household wellbeing and poverty status following a diagnosis of advanced cancer in Blantyre, Malawi - study.

: Many households in low-and-middle income countries face the additional burden of crippling out-of-pocket expenditure when faced with a diagnosis of life-limiting illness. Available evidence suggests that receipt of palliative care supports cost-savings for cancer-affected households. This study will explore the relationship between receipt of palliative care, total household out-of-pocket expenditure on health and wellbeing following a first-time diagnosis of advanced cancer at Queen Elizabeth Central Hospital in Blantyre, Malawi.