Prevalence, clusters, and burden of complex tuberculosis multimorbidity in low- and middle-income countries: a systematic review and meta-analysis

Objectives The co-occurrence of tuberculosis (TB) and multiple chronic communicable and non-communicable diseases is a growing concern in low- and middle-income countries (LMICs). Understanding this ‘complex TB multimorbidity’ (cTBMM) can contribute to improved patient care. We aimed to synthesise the prevalence of clusters of cTBMM and their impact on patient outcomes. Design Systematic review and meta-analysis. Setting LMICs. Papers We searched major databases from inception to 01/10/2020 to identify observational studies reporting primary (prevalence or risk) or secondary (related to disease burden) outcome data for people in LMICs with cTBMM. Titles, abstracts and full text screening, data extraction, and quality assessment were done in duplicate by independent reviewers, and random-effects meta-analyses were performed. Primary and secondary outcome measures Prevalence or risk of cTBMM (primary); any measure of burden of disease (secondary). Results From 21,884 search results, 82 studies representing 773,828 TB patients were included, reporting data on 78 different clusters of cTBMM. In TB patients, the most prevalent co-occurring conditions where depression and anxiety (15.3%, 95% confidence interval [CI] 10.7%-20.5%, 3 studies, 1,473 participants, I 2 =64%), HIV and anxiety (15.2%, 95%CI 11.3%-19.7%, 4 studies, 1,413 participants, I 2 =77%), and HIV and post-traumatic stress disorder (14.8%, 95%CI 13.9%-15.8%, 2 studies, 5,400 participants). Sparse evidence indicated lower treatment success and higher risks of death in people with cTBMM. Conclusions Although limited by high heterogeneity, this first systematic review and meta-analysis on cTBMM highlights that multiple conditions co-occurring in TB patients are common and that mental disorders often cluster together or with HIV. Further research assessing the burden of cTBMM and identifying effective health systems responses is required. Registration Prospero CRD42020214021. Strengths and limitations of this study To our knowledge, this is the first systematic review summarising the prevalence of the different clusters of complex TB multimorbidity (cTBMM) in LMICs. While our focus was on cTBMM in LMICs overall, subgroup analyses by type of TB, country, and socio-economic group allow for a more nuanced assessment on cTBMM. We used a broad definition for the term ‘chronic condition’ to be as inclusive as possible, but which could lead to heterogeneity in the definition of some clusters of cTBMM.