A systematic review of risk factors for mortality among tuberculosis patients in South Africa

Abstract

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.

Changes in tuberculosis burden and its associated risk factors in Guizhou Province of China during 2006–2020: an observational study

“…Additionally, it is important to highlight that PTB mortality and DALYs had an upward trend in the past 15 years in Guizhou, primarily due to the continuous increase in deaths from other causes over the same period. Death from other causes in PTB patients might be caused by adverse drug effects [ 49 ] and common comorbidities, such as TB-DM (diabetes mellitus) [ 50 ], TB-HIV positivity [ 51 ] and other age-associated comorbidities [ 49 ]. Therefore, our findings suggest that reducing the TB disease burden in Guizhou will require a multipronged approach, including health system strengthening, integration of TB and common comorbidity services, and person-centered approaches to support treatment.…”

“…Similar results have been reported in other studies. Low income [ 29 ] and illiterate schooling [ 32 ], previous TB treatment [ 30 , 31 , 51 ]and the use of DOT during the entire treatment [ 55 ] were independently associated with death in TB patients. A possible explanation for the correlation between DOT and death was that DOT was utilized by providers according to decreased social support or increased severity of illness [ 55 ].…”

Treatment of Multidrug-resistant or Rifampicin-resistant Tuberculosis With an All-oral 9-month Regimen Containing Linezolid or Ethionamide in South Africa: A Retrospective Cohort Study

“…Two-year mortality was substantial within both cohorts, 22% and 20% in the ethionamide and linezolid cohort, respectively. This may be reflective of a population with high rates of comorbidity, including HIV and high rates of previous TB treatment, both factors associated with poorer outcomes and challenges with regimen adherence [ 24 ]. It is important to note it is not possible to distinguish mortality due to treatment from other causes within this data set.…”

Long-term outcomes of the global tuberculosis and COVID-19 co-infection cohort

“…[ 20 ] reported that the mortality among TB patients was higher in older subjects, and in those with a high comorbidity index. In addition, HIV infection remains a major risk factor for TB mortality in our COVID-19 co-infected cohort [ 21 , 22 ]. As expected, the likelihood that a person with TB would die was significantly higher if they needed invasive ventilation [ 24 ].…”