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, I2=64%), HIV and anxiety (15.2%, 95%CI 11.3%-19.7%, 4 studies, 1,413 participants, I2=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 ### Competing Interest Statement EMT declared that he attended the Tuberculosis Modelling and Analytics Consortium meetings (one in-person meeting in the previous 3 years. Istanbul 30/09/2019 - 03/10/2019), for which his travel and expenses were covered (total expenses claimed <150 GBP, reimbursed to him directly). All other authors declare no competing interests. ### Clinical Protocols ### Funding Statement This work was supported by Medical Research Council UK, grant number MC\_PC\_MR/T037806/1. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All the collected data is in the public domain.