Explore the vast range of titles available.

Background Tuberculosis (TB)-associated mortality in South Africa remains high. This review aimed to systematically assess risk factors associated with death during TB treatment in South African patients. Methods We conducted a systematic review of TB research articles published between 2010 and 2018. We searched BioMed Central (BMC), PubMed®, EBSCOhost, Cochrane, and SCOPUS for publications between January 2010 and December 2018. Searches were conducted between August 2019 and October 2019. We included randomised control trials (RCTs), case control, cross sectional, retrospective, and prospective cohort studies where TB mortality was a primary endpoint and effect measure estimates were provided for risk factors for TB mortality during TB treatment. Due to heterogeneity in effect measures and risk factors evaluated, a formal meta-analysis of risk factors for TB mortality was not appropriate. A random effects meta-analysis was used to estimate case fatality ratios (CFRs) for all studies and for specific subgroups so that these could be compared. Quality assessments were performed using the Newcastle-Ottawa scale or the Cochrane Risk of Bias Tool. Results We identified 1995 titles for screening, 24 publications met our inclusion criteria (one cross-sectional study, 2 RCTs, and 21 cohort studies). Twenty-two studies reported on adults ( n  = 12561) and two were restricted to children < 15 years of age ( n  = 696). The CFR estimated for all studies was 26.4% (CI 18.1–34.7, n  = 13257 ); 37.5% (CI 24.8-50.3, n  = 5149) for drug-resistant (DR) TB; 12.5% (CI 1.1–23.9, n  = 1935) for drug-susceptible (DS) TB; 15.6% (CI 8.1–23.2, n  = 6173) for studies in which drug susceptibility was mixed or not specified; 21.3% (CI 15.3-27.3, n  = 7375) for people living with HIV/AIDS (PLHIV); 19.2% (CI 7.7–30.7, n  = 1691) in HIV-negative TB patients; and 6.8% (CI 4.9–8.7, n  = 696) in paediatric studies. The main risk factors associated with TB mortality were HIV infection, prior TB treatment, DR-TB, and lower body weight at TB diagnosis. Conclusions In South Africa, overall mortality during TB treatment remains high, people with DR-TB have an elevated risk of mortality during TB treatment and interventions to mitigate high mortality are needed. In addition, better prospective data on TB mortality are needed, especially amongst vulnerable sub-populations including young children, adolescents, pregnant women, and people with co-morbidities other than HIV. Limitations included a lack of prospective studies and RCTs and a high degree of heterogeneity in risk factors and comparator variables. Systematic review registration The systematic review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42018108622. This study was funded by the Bill and Melinda Gates Foundation (Investment ID OPP1173131) via the South African TB Think Tank.

Individuals exposed to a person with infectious multidrug-resistant or rifampicin-resistant (MDR-RR) tuberculosis are at risk of developing tuberculosis disease. Historically, insufficient empirical evidence for preventive treatment in this group has permitted inadequate guidance for clinical decision making. However, several high-quality studies have been published detailing preventive treatment options for these contacts at high risk. In this Review, we discuss the management of individuals exposed to patients with infectious MDR-RR tuberculosis. We pay particular attention to the entire spectrum of clinical care for this population, including baseline assessment, possible preventive treatments, follow-up, and shared decision making. We discuss the available evidence, the rationales for different management strategies, and the interactions with (and implications of) secondary comorbidities such as HIV or malnutrition.