Correcting drug-resistance prevalence in tuberculosis using a predictive model of diagnostic access

Background Drug resistance (DR) poses a major challenge to tuberculosis (TB) elimination. Incomplete access to diagnostic tests can lead to under detection and biased DR-TB prevalence indicators. This study aimed to estimate the prevalence of DR-TB, identified through any available diagnostic method, while correcting for disparities in access to rapid molecular testing (Xpert®MTB/RIF), used as a proxy for overall diagnostic capacity.

We conducted a cross-sectional study of new TB cases in individuals aged over 18 (n=406,331), using 2015-2020 data from the Brazilian Information System on Notifiable Diseases (SINAN). We assumed that access to Xpert®MTB/RIF was an indicator of better diagnostic conditions for detecting drug resistance in general, because patients who underwent this test had a higher prevalence of all forms of resistance (not just to rifampicin). We developed a multilevel mixed-effects logistic regression model, incorporating individual- and municipality-level variables, to predict access to Xpert®MTB/RIF testing in a random sample of 81,027 observations. The model was validated using out-of-sample observations across geographic areas. We then used inverse probability weighting based on predicted access to calculate corrected estimates of DR-TB prevalence.

The model showed good performance (AUC=80·93%, 95%CI: 80·71%-81·33%). The prevalence of DR-TB reported by the surveillance system was 1·54% (95%CI: 1·50%-1·57%). Among patients tested with Xpert®MTB/RIF, DR-TB prevalence was 3·86% (95%CI: 3·75%-3·96%), and the corrected weighted prevalence was 5·95% (95%CI: 5·54%-6·38%).

The prevalence of DR-TB may be substantially underestimated due to uneven access to testing. Our approach highlights the importance of correcting for diagnostic access to improve surveillance indicators. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study did not receive any funding 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: The data supporting the findings of this study are not publicly available but can be accessed upon reasonable request to the Brazilian Ministry of Health (https://www.gov.br). This study used publicly available data and did not include personal information of TB patients. According to Resolution no. 510 of the Brazilian National Health Council, this type of research does not require evaluation by an institutional review board. 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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes Tel: E-mail: jhancy.aguilar{at}usp.br. E-mail: frediazq{at}usp.br Data Availability The data supporting the findings of this study are not publicly available but can be accessed upon reasonable request to the Brazilian Ministry of Health (https://www.gov.br) List of abbreviations - DR - Drug resistance - TB - tuberculosis - SINAN - Brazilian Information System on Notifiable Diseases - DR-TB - drug-resistant tuberculosis - 95% CI - 95% Confidence Interval - MDR-TB - multidrug-resistant - RR-TB - rifampicin-resistant TB - WHO - World Health Organization - WRD - WHO-recommended rapid diagnostic test - AUC-ROC - area under the receiver operating characteristic curve.