Community and Universal Testing for TB among close contacts of microbiologically confirmed pulmonary TB patients in two high TB burden countries: a protocol for a pragmatic cluster-randomised control trial.

Background: Tuberculosis (TB) symptom screening and testing using either smear microscopy or GeneXpert MTB/RIF Ultra (Xpert Ultra) have been the mainstay for diagnosing TB disease in case finding. Reliance on symptom-based TB screening results in missed TB cases, and universal TB testing approach might be more suitable to find missing TB cases in high-risk populations. Universal TB testing involves testing for TB disease regardless of TB symptoms in those at risk of TB. However, limited evidence exists to support its adoption including cost-effectiveness. In this study, we will evaluate the effectiveness of universal TB testing for detection of TB and uptake of TB preventive therapy (TPT) among eligible household and community contacts in high TB settings as per country guidelines.

Methods: This is a pragmatic cluster-randomised trial conducted in Lesotho and Tanzania. Drug-sensitive TB (DS-TB) index patients aged ≥ 18 years, who have at least one contact, will be enrolled if they are microbiologically confirmed with TB within ≤ 6 weeks of diagnosis at the time of recruitment by study team at health facilities in selected districts or regions. Each TB index patient and their contact(s) will be randomised into either universal TB testing or standard TB screening arms. Household and community contacts listed by each TB index case will be enumerated and invited to participate in the study after providing informed consent or assent during household visits. The study has four sub-studies including health economics and modelling, paediatrics, microbiology, and socio-behavioural. A preparatory cross-sectional study will be conducted before delivery of the pragmatic cluster-randomised trial. It will determine the prevalence of TB infection (TBI), TPT eligibility in household contacts (HHCs), and compare the performance of QuantiFERON-TB-Gold-Plus (QFT-Plus) and QIAreach for diagnosing TBI among HHCs of TB index patients. Cluster-randomised trial and community contact tracing will be conducted in phase II.

Significance: This trial will provide evidence for a more intensive approach which is hypothesised to increase cost-effectiveness of TB case finding. In addition, it will provide evidence for high TB burden countries with inherently different cost structures compared to intermediate and low burden settings where previous cost-effectiveness analyses have been undertaken.

Clinical Trial Registration Number: BMC Trial Registry ISRCTN10003903. Registered on December 22, 2020. Protocol version number and date. Version 1.2, dated 15 January 2023. Date recruitment began. 1 March 2022. Estimated date of recruitment completion. 31 July 2025.