Background There is a dearth of high-quality evidence from digital health interventions in routine program settings in low- and middle-income countries. We previously conducted a randomized controlled trial (RCT) in Zimbabwe, demonstrating that 2-way texting (2wT) was safe and effective for follow-up after adult voluntary medical male circumcision (VMMC). Objective To demonstrate the replicability of 2wT, we conducted a larger RCT in both urban and rural VMMC settings in South Africa to determine whether 2wT improves adverse event (AE) ascertainment and, therefore, the quality of follow-up after VMMC while reducing health care workers’ workload. Methods A prospective, unblinded, noninferiority RCT was conducted among adult participants who underwent VMMC with cell phones randomized in a 1:1 ratio between 2wT and control (routine care) in North West and Gauteng provinces. The 2wT participants responded to a daily SMS text message with in-person follow-up only if desired or an AE was suspected. The control group was requested to make in-person visits on postoperative days 2 and 7 as per national VMMC guidelines. All participants were asked to return on postoperative day 14 for study-specific review. Safety (cumulative AEs ≤day 14 visit) and workload (number of in-person follow-up visits) were compared. Differences in cumulative AEs were calculated between groups. Noninferiority was prespecified with a margin of −0.25%. The Manning score method was used to calculate 95% CIs. Results The study was conducted between June 7, 2021, and February 21, 2022. In total, 1084 men were enrolled (2wT: n=547, 50.5%, control: n=537, 49.5%), with near-equal proportions of rural and urban participants. Cumulative AEs were identified in 2.3% (95% CI 1.3-4.1) of 2wT participants and 1.0% (95% CI 0.4-2.3) of control participants, demonstrating noninferiority (1-sided 95% CI −0.09 to ∞). Among the 2wT participants, 11 AEs (9 moderate and 2 severe) were identified, compared with 5 AEs (all moderate) among the control participants—a nonsignificant difference in AE rates (P=.13). The 2wT participants attended 0.22 visits, and the control participants attended 1.34 visits—a significant reduction in follow-up visit workload (P<.001). The 2wT approach reduced unnecessary postoperative visits by 84.8%. Daily response rates ranged from 86% on day 3 to 74% on day 13. Among the 2wT participants, 94% (514/547) responded to ≥1 daily SMS text messages over 13 days. Conclusions Across rural and urban contexts in South Africa, 2wT was noninferior to routine in-person visits for AE ascertainment, demonstrating 2wT safety. The 2wT approach also significantly reduced the follow-up visit workload, improving efficiency. These results strongly suggest that 2wT provides quality VMMC follow-up and should be adopted at scale. Adaptation of the 2wT telehealth approach to other acute follow-up care contexts could extend these gains beyond VMMC. Trial Registration ClinicalTrials.gov NCT04327271; https://www.clinicaltrials.gov/ct2/show/NCT04327271

BACKGROUND There is a dearth of high-quality evidence from digital health innovations from routine program settings in low- and middle-income countries (LMIC). We previously conducted a successful randomized control trial (RCT) in Zimbabwe demonstrating that two-way texting (2wT) follow-up was a safe and effective alternative to routine in-person follow-up for post-operative male circumcision (MC) care. To demonstrate robustness of the 2wT approach and cement the evidence for support, we conducted a larger RCT in both urban and rural MC contexts in South Africa (SA). OBJECTIVE To determine if 2wT improves ascertainment of adverse events (AEs) and, therefore, the quality of post-MC follow-up while reducing healthcare worker (HCW) workload. METHODS A prospective, un-blinded, non-inferiority RCT of 1084 adult MC participants with cell phones were randomized 1:1 and distributed between rural and urban district facilities providing MC in North West and Gauteng provinces. Non-inferiority was prespecified with a margin of -0.25%. 2wT participants responded to a daily text with in-person follow-up only if desired or an AE suspected. The control group (routine) were requested to attend in-person visits on post-operative days 2 and 7 as per national MC guidelines. All men were asked to return on post-operative day 14 for study-specific review. The safety outcome (cumulative AEs ≤ the day 14 visit) and the workload outcome (number of in-person visits) were compared. Differences in cumulative AEs were calculated and 95% confidence intervals (CIs) were calculated using Manning score method. RESULTS Study recruitment started June 7, 2021 and follow-up concluded February 21, 2022. In total, 1084 men were enrolled with 547 randomized to 2wT and 537 to routine care with near equal proportions of rural and urban participants across groups. Cumulative AEs were identified in 2.3% (95% CI: 1.3, 4.1) of 2wT participants as compared to 1.01% (95% CI: 0.4, 2.3) of routine patients, meeting a criterion for non-inferiority (one-sided 95% CI: -0.09, ∞). Among 2wT men, 11 AEs (9 moderate and 2 severe) were identified as compared to 5 AEs (all moderate) among routine men, a non-significant difference (p=0.13). 2wT men attended 0.22 visits as compared to 1.34 visits among routine men, a significant workload reduction (p<0.001). 2wT reduced unnecessary post-operative visits by 84.8%. Daily response rates ranged from 86% on day 3 to 74% on day 13; 514/547 (94%) 2wT arm men responded to a daily message at least once over 13 days. CONCLUSIONS 2wT was found non-inferior to routine in-person visits for AE ascertainment, demonstrating safety for MC follow-up. 2wT also significantly reduced workload, improving care efficiency. These findings were similar in both rural and urban contexts. These results strongly suggest that 2wT provides quality MC follow-up and should be adopted for MC service provision at scale. Adaptation of this 2wT telehealth approach for other acute follow-up care contexts could extend these gains beyond MC CLINICALTRIAL This trial, “Expanding and Scaling Two-way Texting to Reduce Unnecessary Follow-Up and Improve Adverse Event Identification Among Voluntary Medical Male Circumcision (VMMC) Participants in the Republic of South Africa,” is registered at ClinicalTrials.gov (ID: NCT04327271).

Background Rifampicin-resistant tuberculosis (RR-TB) remains an important global health problem. Ideally, the complete drug-resistance profile guides individualized treatment for all RR-TB patients, but this is only practised in high-income countries. Implementation of whole genome sequencing (WGS) technologies into routine care in low and middle-income countries has not become a reality due to the expected implementation challenges, including translating WGS results into individualized treatment regimen composition. Methods This trial is a pragmatic, single-blinded, randomized controlled medical device trial of a WGS-guided automated treatment recommendation strategy for individualized treatment of RR-TB. Subjects are 18 years or older and diagnosed with pulmonary RR-TB in four of the five health districts of the Free State province in South Africa. Participants are randomized in a 1:1 ratio to either the intervention (a WGS-guided automated treatment recommendation strategy for individualized treatment of RR-TB) or control (RR-TB treatment according to the national South African guidelines). The primary effectiveness outcome is the bacteriological response to treatment measured as the rate of change in time to liquid culture positivity during the first 6 months of treatment. Secondary effectiveness outcomes include cure rate, relapse rate (recurrence of RR-TB disease) and TB free survival rate in the first 12 months following RR-TB treatment completion. Additional secondary outcomes of interest include safety, the feasibility of province-wide implementation of the strategy into routine care, and health economic assessment from a patient and health systems perspective. Discussion This trial will provide important real-life evidence regarding the feasibility, safety, cost, and effectiveness of a WGS-guided automated treatment recommendation strategy for individualized treatment of RR-TB. Given the pragmatic nature, the trial will assist policymakers in the decision-making regarding the integration of next-generation sequencing technologies into routine RR-TB care in high TB burden settings. Trial registration ClinicalTrials.gov NCT05017324. Registered on August 23, 2021.

Introduction Voluntary medical male circumcision (VMMC) clients are required to attend multiple post-operative follow-up visits in South Africa (SA). However, up to 98% of VMMC clients heal without adverse events (AEs). With demonstrated VMMC safety across global programs, stretched clinic staff in SA may conduct more than 400,000 unnecessary reviews for males without complications per year. As part of a randomized controlled trial (RCT) to test two-way texting (2wT) follow-up as compared to routine, in-person visits for adult VMMC clients, the objective of this study was to compare costs of 2wT-based telehealth to routine post-VMMC care in both rural and urban SA settings. Methods We used an activity-based costing (ABC) approach to estimate the costs in post-VMMC care, including counselling, follow-ups, and tracing activities. All costs were estimated in $US dollars for both 2wT and routine care to test the hypotheses that 2wT follow-up would result in per-client cost savings. Data were collected from routine National Department of Health VMMC forms, the RCT database, and time-and-motion surveys. Sensitivity analysis presents different scale-up scenarios. Results We included 1,084 clients: 537 in routine care and 547 in 2wT. Average client follow-up cost is $6.48 for routine care and $4.25 for 2wT. 2wT saved costs in both rural and urban locations. Average savings of $2.23 was greater in rural ($1.61) than urban areas ($0.62). 2wT would save $0.88, $2.23, and $4.93, respectively, if: men attended one visit; men attended visits in similar proportions to that observed in the RCT; and men attended both visits. Conclusion 2wT reduces post-VMMC care costs by supporting most men to heal at home while using telehealth to triage clients with potential AEs to timely, in-person care. 2wT savings are higher in rural areas. Scale-up of 2wT-based follow-up could significantly reduce overall VMMC costs while maintaining service quality.