Background Adherence to and completion of tuberculosis (TB) treatment remain problematic in many high-burden countries. 99DOTS is a low-cost digital adherence technology that could increase TB treatment completion. Methods and findings We conducted a pragmatic stepped-wedge cluster-randomized trial including all adults treated for drug-susceptible pulmonary TB at 18 health facilities across Uganda over 8 months (1 December 2018–31 July 2019). Facilities were randomized to switch from routine (control period) to 99DOTS-based (intervention period) TB treatment supervision in consecutive months. Patients were allocated to the control or intervention period based on which facility they attended and their treatment start date. Health facility staff and patients were not blinded to the intervention. The primary outcome was TB treatment completion. Due to the pragmatic nature of the trial, the primary analysis was done according to intention-to-treat (ITT) and per protocol (PP) principles. This trial is registered with the Pan African Clinical Trials Registry (PACTR201808609844917). Of 1,913 eligible patients at the 18 health facilities (1,022 and 891 during the control and intervention periods, respectively), 38.0% were women, mean (SD) age was 39.4 (14.4) years, 46.8% were HIV-infected, and most (91.4%) had newly diagnosed TB. In total, 463 (52.0%) patients were enrolled on 99DOTS during the intervention period. In the ITT analysis, the odds of treatment success were similar in the intervention and control periods (adjusted odds ratio [aOR] 1.04, 95% CI 0.68–1.58, p = 0.87). The odds of treatment success did not increase in the intervention period for either men (aOR 1.24, 95% CI 0.73–2.10) or women (aOR 0.67, 95% CI 0.35–1.29), or for either patients with HIV infection (aOR 1.51, 95% CI 0.81–2.85) or without HIV infection (aOR 0.78, 95% CI 0.46–1.32). In the PP analysis, the 99DOTS-based intervention increased the odds of treatment success (aOR 2.89, 95% CI 1.57–5.33, p = 0.001). The odds of completing the intensive phase of treatment and the odds of not being lost to follow-up were similarly improved in PP but not ITT analyses. Study limitations include the likelihood of selection bias in the PP analysis, inability to verify medication dosing in either arm, and incomplete implementation of some components of the intervention. Conclusions 99DOTS-based treatment supervision did not improve treatment outcomes in the overall study population. However, similar treatment outcomes were achieved during the control and intervention periods, and those patients enrolled on 99DOTS achieved high treatment completion. 99DOTS-based treatment supervision could be a viable alternative to directly observed therapy for a substantial proportion of patients with TB. Trial registration Pan-African Clinical Trials Registry (PACTR201808609844917).

IntroductionLow-cost digital adherence technologies (DATs) such as 99DOTS have emerged as an alternative to directly observed therapy (DOT), the current standard for tuberculosis (TB) treatment supervision. However, there are limited data to support DAT scale-up. The ‘DOT to DAT’ trial aims to evaluate the effectiveness and implementation of a 99DOTS-based TB treatment supervision strategy.Methods and analysisThis is a pragmatic, stepped-wedge cluster randomised trial, with hybrid type 2 effectiveness-implementation design. The trial will include all adults (estimated N=1890) treated for drug-susceptible pulmonary TB over an 8-month period at 18 TB treatment units in Uganda. Three sites per month will switch from routine care (DOT) to the intervention (99DOTS-based treatment supervision) beginning in month 2, with the order determined randomly. 99DOTS enables patients to be monitored while self-administering TB medicines. Patients receive daily automated short message service (SMS) dosing reminders and confirm dosing by calling toll-free numbers. The primary effectiveness outcome is the proportion of patients completing TB treatment. With 18 clusters randomised into six steps and an average cluster size of 15 patients per month, the study will have 89% power to detect a 10% or greater increase in treatment completion between the routine care and intervention periods. Secondary outcomes include more proximal effectiveness measures as well as quantitative and qualitative assessments of the reach, adoption and implementation of the intervention.Ethics and disseminationEthics approval was granted by institutional review boards at Makerere University School of Public Health and the University of California San Francisco. Findings will be disseminated through peer-reviewed publications, presentations at scientific conferences and presentations to key stakeholders.Trial registration numberPACTR201808609844917.

BackgroundPre-treatment loss to follow-up is common for patients diagnosed with tuberculosis (TB) in high-burden countries. Delivering test results by Short-Messaging-Service (SMS) is increasingly being considered as a solution, but there is limited information about its feasibility as a public health tool in low resourced settings.ObjectiveWe sought to assess the feasibility of utilizing SMS technology to deliver TB test results during routine TB diagnostic evaluation in Uganda.MethodsWe conducted a single arm interventional pilot study at four community health centers in Uganda that referred sputum samples to a district hospital for GeneXpert-MTB/RIF (Xpert) testing (Cepheid, USA). Using existing GxAlert-software (SystemOne,USA), we set up an automated SMS platform to send Xpert results to patients and referring health centers. We assessed each step of the SMS delivery cascade for consecutive patients who presented to these four community health centers between December 2015 and March 2016 and underwent Xpert testing.ResultsOf 233 patients enrolled, 161 (69%) had phone numbers recorded on individual Xpert referral forms. Phone numbers were entered into Xpert device software in the correct format for 152 (94%) patients. GxAlert-software generated an automated SMS reporting Xpert results for 151 (99%) patients and delivered it successfully to mobile phone service providers for 145/151 (96%). Of the 123 patients reached by phone to determine receipt of test results, 114 (93%) confirmed SMS receipt. SMS-based delivery of Xpert results was verified for 114/233 (49%) patients overall. In contrast, phone calls to health centers confirmed that health centers received messages for 222/233 (95%) patients.ConclusionReporting Xpert results via automated SMS is technically feasible and results in approximately half of patients receiving their test results immediately. Additional research should be done to address process inefficiencies in order to maximize impact of this technology and link its successful utilization to improved patient outcomes.

Background: Delays in diagnosis and treatment of tuberculosis (TB) remain common in high-burden countries. To improve case detection, substantial investments have been made to scale-up Xpert MTB/RIF (Xpert), a cartridgebased nucleic acid amplification test that can detect TB within 2 hours, as a replacement for sputum smear microscopy. However, the optimal strategy for implementation of Xpert testing remains unclear. Methods: The Xpert Performance Evaluation for Linkage to Tuberculosis Care (XPEL-TB) trial uses an ultra-pragmatic, hybrid type II effectiveness-implementation design to assess the effectiveness and implementation of a streamlined strategy for delivery of Xpert testing in real-world settings. Twenty health centers with TB microscopy units were selected to participate in the trial, with ten health centers randomized to the intervention strategy (onsite molecular testing using GeneXpert Edge, process redesign to facilitate same-day TB diagnosis and treatment, and performance feedback) or routine care (onsite sputum smear microscopy plus referral of sputum samples to Xpert testing sites). The primary outcome is the number of patients with microbiologically confirmed TB who were initiated on treatment within 14 days of presentation to the health center, which reflects successful completion of the TB diagnostic evaluation process. Secondary outcomes include health outcomes (6-month vital status), as well as measures of the reach, adoption, and implementation of the intervention strategy.

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