Mortality and associated factors among children with the double burden of human immunodeficiency virus and tuberculosis in African countries: a systematic review and meta-analysis.

Introduction: The dual burden of Human Immunodeficiency Virus (HIV) and Tuberculosis (TB) in children is leading to significant mortality. Although primary studies have reported wide ranges of mortality rates among HIV-TB co-infected children in various African countries, a comprehensive estimate of mortality and associated factors is lacking. Therefore, this study aims to assess mortality and associated factors among HIV-TB co-infected children in Africa, which will address existing inconsistencies and assist the development of preventive strategies.

Methods: A systematic search was conducted to retrieve studies from PubMed, Scopus, Embase, Google Scholar, ScienceDirect, HINARI, and other relevant sources. All studies conducted in Africa on mortality among HIV-TB co-infected children were included. The study was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. A random-effects model was used to estimate the mortality rate, and the Higgins heterogeneity statistic (I²) was applied to assess variation between studies. Sub-group analysis and meta-regression were conducted to detect the source of heterogeneity, while the quality of the studies was assessed using the Newcastle Ottawa Scale (NOS). Publication bias was checked with the funnel plots and regression tests. The summary estimates were presented with forest plots and tables.

Results: A total of 30 studies with 13,406 HIV-TB co-infected children between 2007 and 2023 in 11 African countries were included. The pooled estimate of the mortality rate was 15.89% (95%CI:13.62, 18.17) heterogeneity (I² = 92.1%, p < 0.001). The highest mortality was observed in the Central African region (41.00%, 95% CI: 27.62, 54.37), followed by Western (16.89%, 95% CI: 8.47, 25.32), Southern (14.57%, 95% CI: 10.86, 18.29), and Eastern Africa region 11.33% (95% CI:9.63, 13.04). Factors like being rural residents (Pooled Odds Ratio (POR) = 1.5, 95% CI: 1.12, 1.90), low hemoglobin (POR = 7.41, 95% CI: 2.20, 12.61), extrapulmonary tuberculosis (EPTB) (POR = 5.67, 95% CI:1.68, 9.66), severe immunosuppression (POR = 5.82, 95% CI: 1.55, 10.08), and poor antiretroviral therapy (ART) adherence (POR = 10.17, 95% CI: 3.52, 16.82) were found to increase the odds of mortality. Conversely, Cotrimoxazole Preventive Therapy (CPT) (POR = 0.38, 95% CI: 0.02, 0.73) was observed as a protective factor of mortality.

Conclusion: This study demonstrates that HIV-TB co-infected children in Africa have a high burden of mortality, underscoring the implementation of dual infection testing and prompt treatment to achieve the 2030 Sustainable Development Goal (SDG) target of mortality reduction. To reduce mortality, strengthening care and treatment are needed with a special focus on rural residents and regular screening of hemoglobin status, CD4 counts, ART adherence, and EPTB infection. Besides, CPT provision should be enforced via integrated HIV-TB health services in the continent.

Review registration: It was registered in the International Prospective Registry of Systematic Reviews (PROSPERO) with registration number CRD42024542095.