Predicting tuberculosis relapse in patients treated with the standard 6-month regimen: an individual patient data meta-analysis

Abstract

BackgroundRelapse continues to place significant burden on patients and tuberculosis (TB) programmes worldwide. We aimed to determine clinical and microbiological factors associated with relapse in patients treated with the WHO standard 6-month regimen and then evaluate the accuracy of each factor at predicting an outcome of relapse.MethodsA systematic review was performed to identify randomised controlled trials reporting treatment outcomes on patients receiving the standard regimen. Authors were contacted and invited to share patient-level data (IPD). A one-step IPD meta-analysis, using random intercept logistic regression models and receiver operating characteristic curves, was performed to evaluate the predictive performance of variables of interest.ResultsIndividual patient data were obtained from 3 of the 12 identified studies. Of the 1189 patients with confirmed pulmonary TB who completed therapy, 67 (5.6%) relapsed. In multipredictor analysis, the presence of baseline cavitary disease with positive smear at 2 months was associated with an increased odds of relapse (OR 2.3(95% CI 1.3 to 4.2)) and a relapse risk of 10%. When area under the curve for each multipredictor model was compared, discrimination between low-risk and higher-risk patients was modest and similar to that of the reference model which accounted for age, sex and HIV status.ConclusionDespite its poor predictive value, our results indicate that the combined presence of cavitary disease and 2-month positive smear status may be the best currently available marker for identifying individuals at an increased risk of relapse, particularly in resource-limited setting. Further investigation is required to assess whether this combined factor can be used to indicate different treatment requirements in clinical practice.

Cryptic Resistance Mutations Associated With Misdiagnoses of Multidrug-Resistant Tuberculosis

“…Findings of sputum and culture analyses became negative within 2 months after treatment initiation, and the patient was considered cured 4 months later, based on World Health Organization guidelines. However, relapse occurred in 2013 despite no risk factor for relapse during the initial episode [5]. Two years later, the patient was not responding to therapy despite compliance with treatment, close monitoring, and infection with a drug-susceptible strain, based on results of the hospital’s routine rapid phenotypic DST and genotypic testing.…”

Towards individualised treatment of tuberculosis

“…Cavitary chest X-ray findings is well known to correlate with bacillary load (115) and the combined presence of cavitary disease and two-month positive smear/culture status was the best predictive marker of TB relapse in a recent systematic review (116).…”

Genetic models of latent tuberculosis in mice reveal differential control by adaptive immunity

“…TB chemotherapy often fails to sterilize Mtb infections, resulting in individuals at risk of relapse TB, even in the absence of bacterial drug resistance (Malherbe et al, 2016). In fact, 5% of TB patients that have been treated with standard TB chemotherapy develop recurrent TB (Romanowski et al, 2019; Colangeli et al, 2018; Merle et al, 2014) and recurrent TB may account for up to 10-30 % of all TB cases (Chaisson and Churchyard, 2010). In patients with recurrent TB the Mtb strain that caused the primary infection regrows to lead to a second episode of active TB (relapse), or infection with a new strain causes the second episode (reinfection)(McIvor et al, 2017).…”