Surveillance for TB drug resistance using routine rapid diagnostic testing data: Methodological development and application in Brazil

Effectively responding to drug-resistant tuberculosis (TB) requires accurate and timely information on resistance levels and trends. In contexts where use of drug susceptibility testing has not been universal (i.e. not all patients are offered testing), surveillance for rifampicin-resistance-one of the core drugs in the TB treatment regimen-has relied on resource-intensive and infrequent nationally-representative prevalence surveys. The expanded availability of rapid diagnostic tests (RDTs) over the past decade has increased testing coverage in many settings. However, RDT data collected in the course of routine (but not universal) use may provide biased estimates of resistance if the subset of patients receiving RDTs is not representative of the overall cohort. Here, we developed a method that attempts to correct for non-random use of RDT testing in the context of routine TB diagnosis to recover unbiased estimates of resistance among new and previously treated TB cases. Specifically, we employed statistical corrections to model rifampicin resistance among TB notifications with observed Xpert MTB/RIF (a WHO-recommended RDT) results using a hierarchical generalized additive regression model, and then used model output to impute results for untested individuals. We applied this model to 2017-2023 case-level data on over 800,000 patients from Brazil. Modeled estimates of the prevalence of rifampicin resistance were substantially higher than naïve estimates, with estimated prevalence ranging between 28-44% higher for new cases and 2-17% higher for previously treated cases. Our estimates of RR-TB incidence were estimated with narrower uncertainty intervals relative to WHO estimates for the same time period, and were robust to alternative model specifications. Our approach provides a generalizable method to leverage routine RDT data to derive timely estimates of RR-TB prevalence among notified TB cases in settings where testing for TB drug resistance is not universal.