Incidence and predictors of mortality among persons receiving second-line tuberculosis treatment in sub-Saharan Africa: A meta-analysis of 43 cohort studies

• Published in: PloS one Vol. 16; no. 12; p. e0261149
• Main Authors: Edessa, Dumessa, Adem, Fuad, Hagos, Bisrat, Sisay, Mekonnen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10-12-2021; Public Library of Science (PLoS)
• Subjects: Africa South of the Sahara - epidemiology; Antitubercular agents; Biology and Life Sciences; Care and treatment; Clinical outcomes; Cohort analysis; Cohort Studies; Diagnosis; Documents; Dosage and administration; Drug resistance; Drug resistance in microorganisms; Health risk assessment; Health risks; HIV; Human immunodeficiency virus; Humans; Incidence; Medical ethics; Medicine and Health Sciences; Meta-analysis; Methods; Mortality; Mycobacterium tuberculosis; Mycobacterium tuberculosis - isolation & purification; Patients; Pharmacy; Physical Sciences; Predictive Value of Tests; Public health; Rehabilitation; Research and Analysis Methods; Risk factors; Search engines; Sexually transmitted diseases; STD; Substance use; Survival Rate; Systematic review; Technology assessment; Treatment Outcome; Tuberculosis; Tuberculosis - drug therapy; Tuberculosis - epidemiology; Tuberculosis - mortality; Africa South of the Sahara; Ethiopia; Sub-Saharan Africa; Africa
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0261149

Drug resistance remains from among the most feared public health threats that commonly challenges tuberculosis treatment success. Since 2010, there have been rapid evolution and advances to second-line anti-tuberculosis treatments (SLD). However, evidence on impacts of these advances on incidence of mortality are scarce and conflicting. Estimating the number of people died from any cause during the follow-up period of SLD as the incidence proportion of all-cause mortality is the most informative way of appraising the drug-resistant tuberculosis treatment outcome. We thus aimed to estimate the pooled incidence of mortality and its predictors among persons receiving the SLD in sub-Saharan Africa.
We systematically identified relevant studies published between January, 2010 and March, 2020, by searching PubMed/MEDLINE, EMBASE, SCOPUS, Cochrane library, Google scholar, and Health Technology Assessment. Eligible English-language publications reported on death and/or its predictors among persons receiving SLD, but those publications that reported death among persons treated for extensively drug-resistant tuberculosis were excluded. Study features, patients' clinical characteristics, and incidence and/or predictors of mortality were extracted and pooled for effect sizes employing a random-effects model. The pooled incidence of mortality was estimated as percentage rate while risks of the individual predictors were appraised based on their independent associations with the mortality outcome.
A total of 43 studies were reviewed that revealed 31,525 patients and 4,976 deaths. The pooled incidence of mortality was 17% (95% CI: 15%-18%; I2 = 91.40; P = 0.00). The studies used varied models in identifying predictors of mortality. They found diagnoses of clinical conditions (RR: 2.36; 95% CI: 1.82-3.05); excessive substance use (RR: 2.56; 95% CI: 1.78-3.67); HIV and other comorbidities (RR: 1.96; 95% CI: 1.65-2.32); resistance to SLD (RR: 1.75; 95% CI: 1.37-2.23); and male sex (RR: 1.82; 95% CI: 1.35-2.44) as consistent predictors of the mortality. Few individual studies also reported an increased incidence of mortality among persons initiated with the SLD after a month delay (RR: 1.59; 95% CI: 0.98-2.60) and those persons with history of tuberculosis (RR: 1.21; 95% CI: 1.12-1.32).
We found about one in six persons who received SLD in sub-Saharan Africa had died in the last decade. This incidence of mortality among the drug-resistant tuberculosis patients in the sub-Saharan Africa mirrors the global average. Nevertheless, it was considerably high among the patients who had comorbidities; who were diagnosed with other clinical conditions; who had resistance to SLD; who were males and substance users. Therefore, modified measures involving shorter SLD regimens fortified with newer or repurposed drugs, differentiated care approaches, and support of substance use rehabilitation programs can help improve the treatment outcome of persons with the drug-resistant tuberculosis.
CRD42020160473; PROSPERO.