Burden of tuberculosis in underserved populations in South Africa: A systematic review and meta-analysis.

Identifying case-finding strategies to reduce tuberculosis (TB) incidence in high-burden countries requires better knowledge of the disease burden in key contributing populations and settings. To inform South Africa's National Tuberculosis Strategic Plan 2023-2028, we conducted a systematic review of active TB disease and latent TB infection (LTBI) prevalence and incidence in underserved populations, defined as those living in informal settlements, townships, or impoverished communities. We identified articles published from January 2010 to December 2023, assessed study quality, and conducted a meta-analysis to estimate pooled TB and LTBI prevalence stratified by HIV status.

Qualitative system dynamics modelling to support the design and implementation of tuberculosis infection prevention and control measures in South African primary healthcare facilities.

Tuberculosis infection prevention and control (TB IPC) measures are a cornerstone of policy, but measures are diverse and variably implemented. Limited attention has been paid to the health system environment, which influences successful implementation of these measures. We used qualitative system dynamics and group-model-building methods to (1) develop a qualitative causal map of the interlinked drivers of Mycobacterium tuberculosis (Mtb) transmission in South African primary healthcare facilities, which in turn helped us to (2) identify plausible IPC interventions to reduce risk of transmission.

High sensitivity of ultrasound for the diagnosis of tuberculosis in adults in South Africa: A proof-of-concept study.

Background: There are limited data on the performance characteristics of ultrasound for the diagnosis of pulmonary tuberculosis in both HIV-positive and HIV-negative persons. The objective of this proof-of-concept study was to determine the sensitivity and specificity of ultrasound for the diagnosis of tuberculosis in adults.

Methods: Comprehensive thoracic and focused abdominal ultrasound examinations were performed by trained radiologists and pulmonologists on adults recruited from a community multimorbidity survey and a primary healthcare clinic in KwaZulu-Natal Province, South Africa.

Direct estimates of absolute ventilation and estimated Mycobacterium tuberculosis transmission risk in clinics in South Africa.

Healthcare facilities are important sites for the transmission of pathogens spread via bioaerosols, such as Mycobacterium tuberculosis. Natural ventilation can play an important role in reducing this transmission. We aimed to measure rates of natural ventilation in clinics in KwaZulu-Natal and Western Cape provinces, South Africa, then use these measurements to estimate Mycobacterium tuberculosis transmission risk.

Estimating waiting times, patient flow, and waiting room occupancy density as part of tuberculosis infection prevention and control research in South African primary health care clinics.

Transmission of respiratory pathogens, such as Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2, is more likely during close, prolonged contact and when sharing a poorly ventilated space. Reducing overcrowding of health facilities is a recognised infection prevention and control (IPC) strategy; reliable estimates of waiting times and 'patient flow' would help guide implementation. As part of the Umoya omuhle study, we aimed to estimate clinic visit duration, time spent indoors versus outdoors, and occupancy density of waiting rooms in clinics in KwaZulu-Natal (KZN) and Western Cape (WC), South Africa.

Risk Factors for Hospitalization or Death Among Adults With Advanced HIV at Enrollment for Care in South Africa: A Secondary Analysis of the TB Fast Track Trial.

Background: Individuals with advanced HIV experience high mortality, especially before and during the first months of antiretroviral therapy (ART). We aimed to identify factors, measurable in routine, primary health clinic-based services, associated with the greatest risk of poor outcome.

Methods: We included all individuals enrolled in the standard-of-care arm of a cluster-randomized trial (TB Fast Track); adults attending participating health clinics with CD4 ≤150 cells/µL and no recent ART were eligible.

Estimating the contribution of transmission in primary healthcare clinics to community-wide TB disease incidence, and the impact of infection prevention and control interventions, in KwaZulu-Natal, South Africa.

Background: There is a high risk of () transmission in healthcare facilities in high burden settings. WHO guidelines on tuberculosis (TB) infection prevention and control (IPC) recommend a range of measures to reduce transmission in healthcare settings. These were evaluated primarily based on evidence for their effects on transmission to healthcare workers in hospitals.

Prevalence of Mycobacterium tuberculosis in Sputum and Reported Symptoms Among Clinic Attendees Compared With a Community Survey in Rural South Africa.

Background: Tuberculosis (TB) case finding efforts typically target symptomatic people attending health facilities. We compared the prevalence of Mycobacterium tuberculosis (Mtb) sputum culture-positivity among adult clinic attendees in rural South Africa with a concurrent, community-based estimate from the surrounding demographic surveillance area (DSA).

Methods: Clinic: Randomly selected adults (≥18 years) attending 2 primary healthcare clinics were interviewed and requested to give sputum for mycobacterial culture.

Modelling the effect of infection prevention and control measures on rate of transmission to clinic attendees in primary health clinics in South Africa.

Background: Elevated rates of tuberculosis in healthcare workers demonstrate the high rate of ) transmission in health facilities in high-burden settings. In the context of a project taking a whole systems approach to tuberculosis infection prevention and control (IPC), we aimed to evaluate the potential impact of conventional and novel IPC measures on transmission to patients and other clinic attendees.

Methods: An individual-based model of patient movements through clinics, ventilation in waiting areas, and transmission was developed, and parameterised using empirical data from eight clinics in two provinces in South Africa.

Causes and Outcomes of Admission and Investigation of Tuberculosis in Adults with Advanced HIV in South African Hospitals: Data from the TB Fast Track Trial.

Tuberculosis (TB) remains the leading cause of hospitalization and in-hospital mortality in HIV-positive adults. Using data from hospital and clinic files, research databases, and autopsy, we describe causes and outcomes of admissions, and assess investigations for TB among adults with advanced HIV who were hospitalized after enrollment into the TB Fast Track trial in South Africa (2013-2015). A total of 251 adults [median CD4 count, 37.

Relational Dynamics of Treatment Behavior Among Individuals with Tuberculosis in High-Income Countries: A Scoping Review.

Although tuberculosis (TB) incidence has significantly declined in high-income, low-incidence (HILI) countries, challenges remain in managing TB in vulnerable populations who may struggle to stay on anti-TB treatment (ATT). Factors associated with non-adherence to ATT are well documented; however, adherence is often narrowly conceived as a fixed binary variable that places emphasis on individual agency and the act of taking medicines, rather than on the demands of being on treatment more broadly. Further, the mechanisms through which documented factors act upon the experience of being on treatment are poorly understood.

Dynamics of sputum conversion during effective tuberculosis treatment: A systematic review and meta-analysis.

Background: Two weeks' isolation is widely recommended for people commencing treatment for pulmonary tuberculosis (TB). The evidence that this corresponds to clearance of potentially infectious tuberculous mycobacteria in sputum is not well established. This World Health Organization-commissioned review investigated sputum sterilisation dynamics during TB treatment.

"": A qualitative study of the dynamics of treatment adherence among adults with tuberculosis in the United Kingdom.

Maintaining adherence to treatment for tuberculosis (TB) is essential if the disease is to be eliminated. As part of formative research to develop an intervention to improve adherence, we documented the lived experiences of adults receiving anti-TB treatment (ATT) in three UK cities and examined how personal, social, and structural circumstances interacted to impact on individuals' adherence to treatment. Using a topic guide that explored social circumstances and experiences of TB care, we conducted in-depth interviews with 18 adults (six women) who were being or had been treated for TB () and four adults (all women) who were caring for a friend, relative, or partner being treated for TB ().

Prevalence and Risk Factors for Infection Among Adolescents in Rural South Africa.

Background: We aimed to estimate the prevalence of and explore risk factors for infection among adolescents in a high tuberculosis (TB) and human immunodeficiency virus (HIV) prevalence setting.

Methods: A cross-sectional study of adolescents (10-19 years) randomly selected from a demographic surveillance area (DSA) in rural KwaZulu-Natal, South Africa. We determined infection status using the QuantiFERON-TB Gold-plus assay.

All nonadherence is equal but is some more equal than others? Tuberculosis in the digital era.

Adherence to treatment for tuberculosis (TB) has been a concern for many decades, resulting in the World Health Organization's recommendation of the direct observation of treatment in the 1990s. Recent advances in digital adherence technologies (DATs) have renewed discussion on how to best address nonadherence, as well as offering important information on dose-by-dose adherence patterns and their variability between countries and settings. Previous studies have largely focussed on percentage thresholds to delineate sufficient adherence, but this is misleading and limited, given the complex and dynamic nature of adherence over the treatment course.

Evidence for the Use of Triage, Respiratory Isolation, and Effective Treatment to Reduce the Transmission of Mycobacterium Tuberculosis in Healthcare Settings: A Systematic Review.

Evidence is limited for infection prevention and control (IPC) measures reducing Mycobacterium tuberculosis (MTB) transmission in health facilities. This systematic review, 1 of 7 commissioned by the World Health Organization to inform the 2019 update of global tuberculosis (TB) IPC guidelines, asked: do triage and/or isolation and/or effective treatment of TB disease reduce MTB transmission in healthcare settings? Of 25 included articles, 19 reported latent TB infection (LTBI) incidence in healthcare workers (HCWs; absolute risk reductions 1%-21%); 5 reported TB disease incidence in HCWs (no/slight [high TB burden] or moderate [low burden] reduction) and 2 in human immunodeficiency virus-positive in-patients (6%-29% reduction). In total, 23/25 studies implemented multiple IPC measures; effects of individual measures could not be disaggregated.

Tuberculosis infection prevention and control: why we need a whole systems approach.

Infection prevention and control (IPC) measures to reduce transmission of drug-resistant and drug-sensitive tuberculosis (TB) in health facilities are well described but poorly implemented. The implementation of TB IPC has been assessed primarily through quantitative and structured approaches that treat administrative, environmental, and personal protective measures as discrete entities. We present an on-going project entitled Umoya omuhle ("good air"), conducted in two provinces of South Africa, that adopts an interdisciplinary, 'whole systems' approach to problem analysis and intervention development for reducing nosocomial transmission of Mycobacterium tuberculosis (Mtb) through improved IPC.

Sensitivity of the lateral flow urine lipoarabinomannan assay in ambulant adults with advanced HIV disease: data from the TB Fast Track study.

Background: WHO guidelines recommend the lateral flow urine lipoarabinomannan assay (LF-LAM) for TB diagnosis in hospitalised HIV-positive individuals. The role of LF-LAM among ambulant patients remains less well defined. We investigated the sensitivity of LF-LAM among ambulant HIV-positive adults in primary health clinics in South Africa.

Algorithm-guided empirical tuberculosis treatment for people with advanced HIV (TB Fast Track): an open-label, cluster-randomised trial.

Background: Tuberculosis, which is often undiagnosed, is the major cause of death among HIV-positive people. We aimed to test whether the use of a clinical algorithm enabling the initiation of empirical tuberculosis treatment by nurses in primary health-care clinics would reduce mortality compared with standard of care for adults with advanced HIV disease.

Methods: In this open-label cluster-randomised controlled trial, we recruited individuals from 24 primary health-care clinics in South Africa.

Cryptococcal-related Mortality Despite Fluconazole Preemptive Treatment in a Cryptococcal Antigen Screen-and-Treat Program.

Background: Cryptococcal antigen (CrAg) screening and treatment with preemptive fluconazole reduces the incidence of clinically evident cryptococcal meningitis in individuals living with advanced human immunodeficiency virus (HIV) disease. However, mortality remains higher in CrAg-positive than in CrAg-negative patients with similar CD4+ T-lymphocyte counts.

Methods: We conducted a cohort study to investigate causes of morbidity and mortality during 6 months of follow-up among asymptomatic CrAg-positive and CrAg-negative (ratio of 1:2) patients living with HIV with CD4 counts <100 cells/µL attending 2 hospitals in Johannesburg, South Africa.