Parametric Bayesian Modelling of Tuberculosis Mortality determinants and Facility level heterogeneity effect using Gamma and Gaussian shared frailty techniques

Background In a normal regression analysis for determinants of TB outcomes, assumptions that the sample is homogenous is made. This model does not account for the overall effect of unobserved or unmeasured covariates. This study aims to quantify the amount of heterogeneity that exists at community level, and to ascertain the determinants of TB mortality across all the catchment areas in Lesotho. Methods This was a retrospective record review of patients on TB treatment registered between January 2015 to December 2020 at 12 health care facilities in the district of Butha Buthe, Lesotho. Data collected from patient medical and statistical analysis was performed using R and INLA statistical software. Descriptive statistics were presented using frequency tables. Differences between binary outcomes were analysed using Person’s X 2 test. Mixed effect model with five Bayesian regression models of varying distributions were used to assess heterogeneity at facility level. Kaplan-Meier curves were used to demonstrate time-to-death events Results The total number of patients included in the analysis were 1729 of which 70% were males. And half of them were employed (54.2%). Being over 60 years (HR: 0.02, Cl: 0.01-0.04) and having a community health worker as a treatment contact person (HR: 0.36, Cl: 0.19-0.71) decreased the risk of dying. Miners had 1.73 times increased risk of dying from TB (HR: 1.73, Cl: 1.07-2.78). The frailty variance was observed to be very minimal (<0.001), but significant indicating heterogeneity between catchment areas. Although similar hazard ratios and confidence intervals of covariates are seen between Gamma and Gaussian frailty log-logistic models, the credibility intervals for the Gamma model are consistently narrower. Conclusion The results from both Gamma and Gaussian demonstrate that heterogeneity affected significance of the determinants for TB mortality. The results showed community level to significantly affect the risk of dying indicating differences between catchment areas. Highlights 1. Reports of being employed as a miner associated with higher TB mortality is worrying. This finding may help authorities in Lesotho and the Southern African region to design health strategies that can target miners and those living within the mining catchment areas 2. The use of community health workers and close relatives reduced the risk of dying among TB patients. This is a key factor that can be considered in designing effective TB interventions in Lesotho. Ensuring that each patient is assigned a community health worker may reduce mortality. 3. The risk of death was significantly higher in treatment phase 2 among patients with pulmonary TB compared to patients in treatment phase 1 and among those with extra pulmonary TB Strength of the study ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the South African Medical Research Council. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of Ministry of Health, Lesotho gave ethical approval for this work. 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 data produced in the present work are contained in the manuscript