Discussion
TB, TUTT, laboratory-confirmed pulmonary TB
DISEASE, RECRUITMENT
We did not meet our stated goal of diagnosing an additional 25% more adults with laboratory-confirmed pulmonary TB by augmenting symptom-directed TB testing in clinics with systematic universal TB testing of individuals at high risk of TB disease. The primary contemporaneous between-arm comparison was a nonsignificant 14% increase in TB diagnoses in intervention clinics. However, we demonstrated that taking into account the secular decline in TB diagnoses, intervention clinics had a relative year-on-year increase in TB diagnoses per month of 17%.Novel approaches to diagnose additional patients with TB include augmenting symptom screening with chest X-rays subjected to automated diagnostic algorithms [More research is required to assess the cost-effectiveness of this strategy and, importantly, whether it would be appropriate to implement in less-resourced settings than South Africa. The TUTT approach will clearly be more costly and requires higher numbers to be tested (NNT) to identify each additional TB patient when compared to existing symptom-directed TB testing. This study highlights the urgent need for rapid, affordable, and accurate TB screening (and testing) assays that could be applied universally in high-risk populations or, alternatively, other less expensive strategies to reduce costs, such as pooling multiple specimens [Strengths of our study include its implementation in a large sample of randomly selected public sector clinics in 3 different provinces of South Africa and its use of the public sector laboratory courier and analytical systems already in place to analyze study specimens. The results, therefore, represent what would be achieved if this intervention were scaled up in South Africa.A key limitation of this study was trial interruption due to the COVID-19 pandemic. Despite stopping the study early, we do not believe that COVID-19 substantively impacted the results we report here, primarily because the number of TB diagnoses in the study period was 13,527, a rate of 20.5 per clinic month, comparable to the 13,440 TB diagnoses (60 clinics over 14 months at an average rate of 16 diagnoses per clinic month) anticipated in our power estimate. Moreover, the final day of recruitment to the study was a week prior to the introduction of lockdown when clinic procedures were starting to be amended in response to concerns about COVID-19. A cumulative total of only 1,278 patients with laboratory-confirmed SARS-CoV-2 had been diagnosed in South Africa by then [In this trial of targeted universal testing for TB, clinics randomized to the intervention diagnosed substantially more individuals by sputum testing than did routine symptom-directed TB testing and indicates that a TUTT strategy could make a contribution to identify “missing” patients with TB in South Africa. The key questions that remain are whether this approach provides a morbidity, mortality, and transmission benefit, and whether it is possible for TUTT to be implemented in a sustainable way, especially in settings with fewer resources or lower HIV prevalence than South Africa.