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BackgroundDigital adherence technologies have been widely promoted as a means to improve tuberculosis medication adherence. However, uptake of these technologies has been suboptimal by both patients and health workers. Not surprisingly, studies have not demonstrated significant improvement in treatment outcomes. ObjectiveThis study aimed to optimize a well-known digital adherence technology, 99DOTS, for end user needs in Uganda. We describe the findings of the ideation phase of the human-centered design methodology to adapt 99DOTS according to a set of design principles identified in the previous inspiration phase. Methods99DOTS is a low-cost digital adherence technology wherein tuberculosis medication blister packs are encased within an envelope that reveals toll-free numbers that patients can call to report dosing. We identified 2 key areas for design and testing: (1) the envelope, including the form factor, content, and depiction of the order of pill taking; and (2) the patient call-in experience. We conducted 5 brainstorming sessions with all relevant stakeholders to generate a suite of potential prototype concepts. Senior investigators identified concepts to further develop based on feasibility and consistency with the predetermined design principles. Prototypes were revised with feedback from the entire team. The envelope and call-in experience prototypes were tested and iteratively revised through focus groups with health workers (n=52) and interviews with patients (n=7). We collected and analyzed qualitative feedback to inform each subsequent iteration. ResultsThe 5 brainstorming sessions produced 127 unique ideas that we clustered into 6 themes: rewards, customization, education, logistics, wording and imagery, and treatment countdown. We developed 16 envelope prototypes, 12 icons, and 28 audio messages for prototype testing. In the final design, we altered the pill packaging envelope by adding a front flap to conceal the pills and reduce potential stigma associated with tuberculosis. The flap was adorned with either a blank calendar or map of Uganda. The inside cover contained a personalized message from a local health worker including contact information, pictorial pill-taking instructions, and a choice of stickers to tailor education to the patient and phase of treatment. Pill-taking order was indicated with colors, chevron arrows, and small mobile phone icons. Last, the call-in experience when patients report dosing was changed to a rotating series of audio messages centered on the themes of prevention, encouragement, and reassurance that tuberculosis is curable. ConclusionsWe demonstrated the use of human-centered design as a promising tool to drive the adaptation of digital adherence technologies to better address the needs and motivations of end users. The next phase of research, known as the implementation phase in the human-centered design methodology, will investigate whether the adapted 99DOTS platform results in higher levels of engagement from patients and health workers, and ultimately improves tuberculosis treatment outcomes.

Tuberculosis (TB) remains a major public health challenge and the most frequent cause of illness and death among persons living with HIV (PLHIV) (1). Globally, TB occurs in congregate settings [...]

Objective To assess the effectiveness of a community-based tuberculosis and leprosy intervention in which village health teams and health workers conduct door-to-door tuberculosis screening, targeted screenings and contact tracing. Methods We conducted a before-and-after implementation study in Uganda to assess the effectiveness of the community tuberculosis intervention by looking at reach, outputs, adoption and effectiveness of the intervention. Campaign 1 was conducted in March 2022 and campaign 2 in September 2022. We calculated percentages of targets achieved and compared case notification rates during the intervention with corresponding quarters in the previous year. We also assessed the leprosy screening. Findings Over 5 days, campaign 1 screened 1 289 213 people (2.9% of the general population), of whom 179 144 (13.9%) fulfilled the presumptive tuberculosis criteria, and 4043 (2.3%) were diagnosed with bacteriologically-confirmed tuberculosis; 3710 (91.8%) individuals were linked to care. In campaign 2, 5 134 056 people (11.6% of the general population) were screened, detecting 428 444 (8.3%) presumptive tuberculosis patients and 8121 (1.9%) bacteriologically-confirmed tuberculosis patients; 5942 individuals (87.1%) were linked to care. The case notification rate increased from 48.1 to 59.5 per 100 000 population in campaign 1, with a case notification rate ratio of 1.24 (95% confidence interval, CI: 1.22-1.26). In campaign 2, the case notification rate increased from 45.0 to 71.6 per 100 000 population, with a case notification rate ratio of 1.59 (95% CI: 1.56-1.62). Of the 176 patients identified with leprosy, 137 (77.8%) initiated treatment. Conclusion This community tuberculosis screening initiative is effective. However, continuous monitoring and adaptations are needed to overcome context-specific implementation challenges. Objectif Evaluer l'efficacite d'une intervention de lutte contre la tuberculose et la lepre au niveau communautaire, dans le cadre de laquelle des equipes et agents de sante du village effectuent un depistage en porte-a-porte, des analyses ciblees et un suivi des contacts. Methodes Nous avons mene une etude en Ouganda, avant et apres la mise en reuvre, afin de mesurer les performances de cette intervention communautaire en examinant sa portee, ses resultats, son adoption et son efficacite. La campagne 1 s'est deroulee en mars 2022 et la campagne 2 en septembre 2022. Nous avons calcule les pourcentages d'objectifs atteints et compare le taux de signalement des cas durant l'intervention avec les trimestres correspondants de l'annee precedente. Nous avons egalement evalue le depistage de la lepre. Resultats En l'espace de cinq jours, la campagne 1 a passe en revue 1 289 213 personnes (2,9% de la population generale); parmi elles, 179 144 (13,9%) remplissaient les criteres d'une tuberculose presumee, 4043 (2,3%) ont regu un diagnostic de tuberculose avec confirmation bacteriologique et 3710 (91,8%) ont fait l'objet d'un suivi medical. Lors de la campagne 2, 5 134 056 personnes (11,6% de la population generale) ont fait l'objet d'un depistage; 428 444 (8,3%) cas presumes de tuberculose ont ete detectes et 8121 (1,9%) d'entre eux ont regu une confirmation bacteriologique, tandis que 5942 individus (87,1%) ont fait l'objet d'un suivi medical. De son cote, le taux de signalement des cas a augmente, passant de 48,1 a 59,5 par 100 000 habitants durant la campagne 1, ce qui equivaut a un rapport de taux de 1,24 (intervalle de confiance (IC) de 95%: 1,22-1,26). Et durant la campagne 2, le taux de signalement des cas a progresse de 45,0 a 71,6 par 100 000 habitants, avec un rapport de taux de 1,59 (IC de 95%: 1,56-1,62). Sur les 176 patients caracterises par un diagnostic de lepre, 137 (77,8%) ont entame un traitement. Conclusion Cette initiative de depistage communautaire s'est revelee efficace. Il est cependant necessaire d'exercer une surveillance continue et de proceder a des adaptations pour surmonter les difficultes de mise en reuvre liees au contexte. Objetivo Evaluar la eficacia de una intervencion comunitaria contra la tuberculosis y la lepra en la que los equipos y los profesionales sanitarios de los pueblos realizan pruebas de deteccion de la tuberculosis puerta a puerta, pruebas de deteccion selectivas y rastreo de contactos. Metodos Se realizo un estudio de implementacion antes y despues en Uganda para evaluar la eficacia de la intervencion comunitaria contra la tuberculosis mediante el analisis del alcance, los resultados, la adopcion y la eficacia de la intervencion. La campana 1 se llevo a cabo en marzo de 2022 y la campana 2 en septiembre de 2022. Se calcularon los porcentajes de objetivos alcanzados y se compararon las tasas de notificacion de casos durante la intervencion con los trimestres correspondientes del ano anterior.Ademas, se evaluo la deteccion de la lepra. Resultados Durante cinco dias, en la campana 1, se sometio a cribado a 1 289 213 personas (el 2,9% de la poblacion general), de las cuales 179 144 (el 13,9%) cumplian los criterios de presuncion de tuberculosis y a 4043 (el 2,3%) se les diagnostico tuberculosis confirmada bacteriologicamente; 3710 (el 91,8%) personas recibieron asistencia. En la campana 2, se sometio a cribado a 5 134 056 personas (11,6% de la poblacion general), detectandose 428 444 (8,3%) pacientes con tuberculosis presunta y 8121 (1,9%) con tuberculosis confirmada bacteriologicamente; 5942 personas (87,1%) recibieron asistencia. La tasa de notificacion de casos aumento de 48,1 a 59,5 por 100 000 habitantes en la campana 1, con una razon de tasa de notificacion de casos de 1,24 (intervalo de confianza del 95%, IC: 1,22-1,26). En la campana 2, la tasa de notificacion de casos aumento de 45,0 a 71,6 por 100 000 habitantes, con una razon de tasa de notificacion de casos de 1,59 (IC del 95%: 1,56-1,62). De los 176 pacientes identificados con lepra, 137 (77,8%) iniciaron tratamiento. Conclusion Esta iniciativa comunitaria de deteccion de la tuberculosis es eficaz. Sin embargo, se necesita un seguimiento continuo y adaptaciones para superar los desafios de implementacion especificos del contexto., Introduction Tuberculosis remains one of the leading causes of death worldwide. (1) In 2022, approximately 10.6 million people fell sick with tuberculosis globally, with most cases occurring in South-East Asia [...]

Abstract Background The Karamoja subregion in north-eastern Uganda has very high Tuberculosis (TB)case notification rates and, until recently, had suboptimal treatment completion rates among patients diagnosed with TB. We evaluated community knowledge, attitudes and practices towards Tuberculosis in order to identify barriers to TB control in this region. Methods From September to October 2022, we conducted a community-based survey in four districts in the Karamoja subregion. We collected data on TB knowledge, attitudes, and practices using a structured electronic questionnaire. We generated knowledge, attitude and practice scores. We used a survey-weighted zero-truncated modified Poisson model to assess the association between knowledge/attitude scores and respondents’ characteristics and a complementary log-log model to assess the association between practice scores and respondents’ characteristics. Data analysis was carried out using STATA version 14. Results A total of 1927 respondents were interviewed. Of these, 55.5% were female, and 1320 (68.6%) had no formal education. Overall, 68.5% 95% CI (59.6–76.7%) had knowledge scores of ≥ 60%. Higher TB knowledge scores were associated with being employed (adjusted prevalence ratio, aPR = 1.22, 95% CI 1.04–1.42, p = 0.01) while being a wife in a household was associated with lower TB knowledge (aPR = 0.90, 95% CI 0.82–0.99, p = 0.03). Being 25–34 years old was associated with a positive attitude towards TB (PR = 1.06, 1.01–1.11, p = 0.01). Over 85% of respondents would go to the health facility immediately if they had TB signs and symptoms. Almost all respondents (98.6%) would start TB treatment immediately if diagnosed with the disease. Conclusion More than two thirds of patients had good knowledge and practices towards TB which can be leveraged to improve uptake of TB control interventions in the region. Additional interventions to improve TB knowledge and practice should focus on specific segments within the communities e.g., older women in the households.

BACKGROUND: Tuberculosis(TB) is among the leading causes of infectious death worldwide. Contact investigation is an evidence-based, World Health Organisation-endorsed intervention for timely TB diagnosis, treatment, and prevention but has not been widely and effectively implemented. METHODS: We are conducting a stepped-wedge, cluster-randomised, hybrid Type III implementation-effectiveness trial comparing a user-centred to a standard strategy for implementing TB contact investigation in 12 healthcare facilities in Uganda. The user-centred strategy consists of several client-focused components including (1) a TB-education booklet, (2) a contact-identification algorithm, (3) an instructional sputum-collection video, and (4) a community-health-rider service to transport clients, CHWs, and sputum samples, along with several healthcare-worker-focused components, including (1) collaborative improvement meetings, (2) regular audit-and-feedback reports, and (3) a digital group-chat application designed to develop a community of practice. Sites will cross-over from the standard to the user-centred strategy in six, eight-week transition steps following a randomly determined site-pairing scheme and timeline. The primary implementation outcome is the proportion of symptomatic close contacts completing TB evaluation within 60 days of TB treatment initiation by the index person with TB. The primary clinical effectiveness outcomes are the proportion of contacts diagnosed with and initiating active TB disease treatment and the proportion initiating TB preventative therapy within 60 days. We will assess outcomes from routine source documents using intention-to-treat analyses. We will also conduct nested mixed-methods studies of implementation fidelity and context and perform cost-effectiveness and impact modelling. The Makerere School of Public Health IRB(#554), the Uganda National Council for Science and Technology(#HS1720ES), and the Yale Institutional Review Board(#2000023199) approved the study and waived informed consent for the main trial implementation-effectiveness outcomes. We will submit results for publication in peer-reviewed journals and disseminate findings to local policymakers and representatives of affected communities. DISCUSSION: This pragmatic, quasi-experimental implementation trial will inform efforts to find and prevent undiagnosed persons with TB in high-burden settings using contact investigation. It will also help assess the suitability of human-centred design and communities of practice for tailoring implementation strategies and sustaining evidence-based interventions in low-and-middle-income countries. TRIAL REGISTRATION: The trial was registered(ClinicalTrials.gov Identifier NCT05640648) on 16 November 2022, after the trial launch on 7 March 2022.

99DOTS is a low-cost digital adherence technology that allows people with tuberculosis (TB) to self-report treatment adherence. There are limited data on its implementation, feasibility, and acceptability from sub-Saharan Africa. We conducted a longitudinal analysis and cross-sectional surveys nested within a stepped-wedge randomized trial at 18 health facilities in Uganda between December 2018 and January 2020. The longitudinal analysis assessed implementation of key components of a 99DOTS-based intervention, including self-reporting of TB medication adherence via toll-free phone calls, automated text message reminders and support actions by health workers monitoring adherence data. Cross-sectional surveys administered to a subset of people with TB and health workers assessed 99DOTS feasibility and acceptability. Composite scores for capability, opportunity, and motivation to use 99DOTS were estimated as mean Likert scale responses. Among 462 people with pulmonary TB enrolled on 99DOTS, median adherence was 58.4% (inter-quartile range [IQR] 38.7-75.6) as confirmed by self-reporting dosing via phone calls and 99.4% (IQR 96.4-100) when also including doses confirmed by health workers. Phone call-confirmed adherence declined over the treatment period and was lower among people with HIV (median 50.6% vs. 63.7%, p3 consecutive doses. Surveys were completed by 83 people with TB and 22 health workers. Composite scores for capability, opportunity, and motivation were high; among people with TB, composite scores did not differ by gender or HIV status. Barriers to using 99DOTS included technical issues (phone access, charging, and network connection) and concerns regarding disclosure. 99DOTS was feasible to implement and highly acceptable to people with TB and their health workers. National TB Programs should offer 99DOTS as an option for TB treatment supervision.

BackgroundMitigating financial barriers to tuberculosis (TB) diagnosis and treatment is a core priority of the global TB agenda. We evaluated the impact of a cash transfer intervention on completion of TB testing and treatment initiation in Uganda.MethodsWe conducted a pragmatic complete stepped wedge randomised trial of a one-time unconditional cash transfer at 10 health centres between September 2019 and March 2020. People referred for sputum-based TB testing were enrolled to receive UGX 20 000 (∼USD 5.39) upon sputum submission. The primary outcome was the number initiating treatment for micro-bacteriologically confirmed TB within 2 weeks of initial evaluation. The primary analysis included cluster-level intent-to-treat and per-protocol analyses using negative binomial regression.Results4288 people were eligible. The number diagnosed with TB initiating treatment was higher in the intervention period versus the pre-intervention period (adjusted rate ratio (aRR)=1.34) with a 95% CI of 0.62-2.91 (p=0.46), indicating a wide range of plausible true intervention effects. More were referred for TB testing (aRR=2.60, 95% CI 1.86-3.62; p

BackgroundDecentralised molecular testing for tuberculosis could reduce missed diagnoses and losses to follow-up in high-burden settings. The aim of this study was to evaluate the cost and cost-effectiveness of the Xpert Performance Evaluation for Linkage to Tuberculosis Care (XPEL-TB) study strategy, a multicomponent strategy including decentralised molecular testing for tuberculosis, in Uganda.MethodsWe conducted a costing and cost-effectiveness analysis nested in a pragmatic cluster-randomised trial of onsite (decentralised) versus hub-and-spoke (centralised) testing for tuberculosis with Xpert MTB/RIF Ultra (Xpert) in 20 community health centres in Uganda. We collected empirical data on the cost of the XPEL-TB strategy (decentralised Xpert testing, workflow redesign, and performance feedback) and routine tuberculosis testing (onsite smear microscopy with specimen transport for centralised Xpert testing) from the health system perspective. Time-and-motion studies were performed to estimate activity-based service costs. Cost-effectiveness was assessed as the incremental cost (2019 US$) per tuberculosis diagnosis and per 14-day treatment initiation.FindingsThe XPEL-TB study ran from Oct 22, 2018, to March 1, 2020. Effectiveness and cost-effectiveness outcomes were assessed from Dec 1, 2018, to Nov 30, 2019 and included 4867 women and 3139 men. On a per-test basis, the cost of decentralised ($20·46, range $17·85-25·72) and centralised ($18·20, range $16·58-24·25) Xpert testing was similar. However, decentralised testing resulted in more patients receiving appropriate Xpert testing, so the per-patient cost of decentralised testing was higher: $20·28 (range $17·68-25·48) versus $9·59 (range $7·62-14·34). The XPEL-TB strategy was estimated to cost $1332 (95% uncertainty range $763-5558) per incremental tuberculosis diagnosis and $687 ($501-1207) per incremental patient initiating tuberculosis treatment within 14 days. Cost-effectiveness was reduced in sites performing fewer than 150-250 tests annually.InterpretationThe XPEL-TB strategy facilitated higher rates of Xpert testing for tuberculosis at a similar per-test cost and modest incremental cost per tuberculosis diagnosis and treatment initiation. Decentralised Xpert testing, with appropriate implementation supports, should be scaled up to clinics with sufficient testing volume to support a single-module device.FundingThe National Heart, Lung, and Blood Institute.

Social protection interventions have the potential to accelerate progress towards global tuberculosis (TB) targets. We piloted a screening and linkage program at four community health centers (HC) to enroll adults seeking TB diagnostic evaluation services into existing government-supported social protection programs in Uganda. From May-December 2021, health center staff were asked to screen adults being evaluated for TB for eligibility for government-supported social protection programs, and to refer eligible people to a sub-county community development office (CDO) responsible for enrolling community members into government-supported social protection programs. Linkage was facilitated with a transportation reimbursement via mobile money and referral documentation confirming program eligibility. We assessed feasibility using programmatic data and conducted post-intervention surveys to understand experiences with the linkage program. Of 855 people undergoing TB evaluation, 655 (76%) adults met criteria for at least one government-supported social protection program. 25 (4%) of those were not interested in referral; the rest were referred to their local CDO. While 386 (61%) of the 630 participants reported to the CDO seeking social protection enrolment, only 122 (32%) of those were ultimately enrolled into a social protection scheme, representing only 19% (n = 655) of those eligible. In surveys conducted among 97 participants, 46 of the 60 (77%) people who reported that they sought enrollment at the CDO were not enrolled into a social protection program. Reasons provided for non-enrollment among these 46 participants were either unknown (n = 25, 54%) or due to operational challenges at the CDO including a lack of human resources or available groups to join in the social protection program (n = 20, 43%). 61 survey participants (63%) indicated that they would not have sought social protection enrollment without the referral program. Overall, we found that most adults seeking TB diagnostic evaluation are eligible for and interested in obtaining government-supported social protection. We found facilitated linkage from HCs to CDOs offering social protection services to be feasible, however ultimate enrollment into programs was limited. Additional research is needed to identify strategies to improve access to existing social protection programs for eligible TB-affected individuals. Trial Registration: Pan African Clinical Trials Registry (PACTR201906852160014).

BackgroundEffective strategies are needed to facilitate the prompt diagnosis and treatment of tuberculosis in countries with a high burden of the disease.MethodsWe conducted a cluster-randomized trial in which Ugandan community health centers were assigned to a multicomponent diagnostic strategy (on-site molecular testing for tuberculosis, guided restructuring of clinic workflows, and monthly feedback of quality metrics) or routine care (on-site sputum-smear microscopy and referral-based molecular testing). The primary outcome was the number of adults treated for confirmed tuberculosis within 14 days after presenting to the health center for evaluation during the 16-month intervention period. Secondary outcomes included completion of tuberculosis testing, same-day diagnosis, and same-day treatment. Outcomes were also assessed on the basis of proportions.ResultsA total of 20 health centers underwent randomization, with 10 assigned to each group. Of 10,644 eligible adults (median age, 40 years) whose data were evaluated, 60.1% were women and 43.8% had human immunodeficiency virus infection. The intervention strategy led to a greater number of patients being treated for confirmed tuberculosis within 14 days after presentation (342 patients across 10 intervention health centers vs. 220 across 10 control health centers; adjusted rate ratio, 1.56; 95% confidence interval [CI], 1.21 to 2.01). More patients at intervention centers than at control centers completed tuberculosis testing (adjusted rate ratio, 1.85; 95% CI, 1.21 to 2.82), received a same-day diagnosis (adjusted rate ratio, 1.89; 95% CI, 1.39 to 2.56), and received same-day treatment for confirmed tuberculosis (adjusted rate ratio, 2.38; 95% CI, 1.57 to 3.61). Among 706 patients with confirmed tuberculosis, a higher proportion in the intervention group than in the control group were treated on the same day (adjusted rate ratio, 2.29; 95% CI, 1.23 to 4.25) or within 14 days after presentation (adjusted rate ratio, 1.22; 95% CI, 1.06 to 1.40).ConclusionsA multicomponent diagnostic strategy that included on-site molecular testing plus implementation supports to address barriers to delivery of high-quality tuberculosis evaluation services led to greater numbers of patients being tested, receiving a diagnosis, and being treated for confirmed tuberculosis. (Funded by the National Heart, Lung, and Blood Institute; XPEL-TB ClinicalTrials.gov number, NCT03044158.).

Tuberculosis (TB) is the leading cause of illness and death globally among persons living with HIV (PLHIV) (1,2). In 2021, among [approximately equal to] 38.4 million PLHIV worldwide, 703,000 TB [...]

Tuberculosis (TB) and non-communicable diseases (NCD) share predisposing risk factors. TB-associated NCD might cluster within households affected with TB requiring shared prevention and care strategies. We conducted an individual participant data meta-analysis of national TB prevalence surveys to determine whether NCD cluster in members of households with TB. We identified eligible surveys that reported at least one NCD or NCD risk factor through the archive maintained by the World Health Organization and searching in Medline and Embase from 1 January 2000 to 10 August 2021, which was updated on 23 March 2023. We compared the prevalence of NCD and their risk factors between people who do not have TB living in households with at least one person with TB (members of households with TB), and members of households without TB. We included 16 surveys (n = 740,815) from Asia and Africa. In a multivariable model adjusted for age and gender, the odds of smoking was higher among members of households with TB (adjusted odds ratio (aOR) 1.23; 95% CI: 1.11-1.38), compared with members of households without TB. The analysis did not find a significant difference in the prevalence of alcohol drinking, diabetes, hypertension, or BMI between members of households with and without TB. Studies evaluating household-wide interventions for smoking to reduce its dual impact on TB and NCD may be warranted. Systematically screening for NCD using objective diagnostic methods is needed to understand the actual burden of NCD and inform comprehensive interventions.

Public randomization ceremonies have been proposed as a strategy to strengthen stakeholder engagement and address concerns and misconceptions associated with trial randomization. However, there are few published examples that describe how to conduct a public randomization ceremony with meaningful stakeholder engagement or how such ceremonies impact stakeholder perceptions about randomization and the randomization process. Cluster randomization for the GeneXpert Performance Evaluation for Linkage to Tuberculosis Care (XPEL-TB) trial was conducted at a public randomization ceremony attended by 70 stakeholders in Kampala, Uganda. Presentations given by the Acting Assistant Commissioner from the Uganda National Tuberculosis and Leprosy Programme and trial investigators emphasized how the trial aimed to further national TB goals, as well as how stakeholders contributed to the intervention design. The purpose and process of randomization were described using simple text and visuals. Randomization was an interactive activity that required participation of stakeholders from each trial site. A survey administered to stakeholders at the end of the ceremony suggested high comprehension of randomization (98%), trust in the randomization process (96%), and satisfaction with randomization outcomes (96%). Public randomization ceremonies should be considered more routinely to engage stakeholders in and address potential concerns about the fairness and impartiality of the randomization process for community-based trials.

BackgroundAdherence 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 findingsWe 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.Conclusions99DOTS-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 registrationPan-African Clinical Trials Registry (PACTR201808609844917).

IntroductionCatastrophic costs incurred by tuberculosis (TB) patients have received considerable attention, however little is known about costs and pathways to care after a negative TB evaluation.Materials and methodsWe conducted a cross-sectional study of 70 patients with a negative TB evaluation at four community health centres in rural and peri-urban Uganda. Patients were traced 9 months post-evaluation using contact information from TB registers. We collected information on healthcare visits and implemented locally-validated costing questionnaires to assess the financial impact of their symptoms post-evaluation.ResultsOf 70 participants, 57 (81%) were traced and 53 completed the survey. 31/53 (58%) surveyed participants returned to healthcare facilities post-evaluation, making a median of 2 visits each (interquartile range [IQR] 1-3). 11.3% (95%CI 4.3-23.0%) of surveyed patients and 16.1% (95%CI 5.5-33.7%) of those returning to healthcare facilities incurred catastrophic costs (i.e., spent >20% annual household income). Indirect costs related to lost work represented 80% (IQR 32-100%) of total participant costs.ConclusionsPatients with TB symptoms who experience financial catastrophe after negative TB evaluation may represent a larger absolute number of patients than those suffering from costs due to TB. They may not be captured by existing definitions of non-TB catastrophic health expenditure.

BackgroundVariation in healthcare delivery is increasingly recognized as an important metric of healthcare quality. Directly observed therapy (DOT) has been the standard of care for tuberculosis (TB) treatment supervision for decades based on World Health Organization (WHO) guidelines. However, variation in implementation of DOT and associated TB treatment supervision practices remains poorly defined.MethodsWe collected individual patient data from TB treatment registers at 18 TB treatment units in Uganda including District Health Centers, District Hospitals, and Regional Referral Hospitals. We also administered a survey and did observations of TB treatment supervision practices by health workers at each site. We describe variation in TB treatment outcomes and TB treatment supervision practices.ResultsOf 2767 patients treated for TB across the 18 clinical sites between January 1 and December 31, 2017, 1740 (62.9%) were men, most were of working age (median 35 years, interquartile range [IQR] 27 - 46), 2546 (92.0%) had a new TB diagnosis, and nearly half (45.9%, n = 1283) were HIV positive. The pooled treatment success proportion was 69.4% (95% confidence interval [CI] 67.8 - 71.1) but there was substantial variation across sites (range 42.6 - 87.6%, I-squared 92.7%, p

Summary: Background: Non-communicable diseases (NCDs) and NCD risk factors, such as smoking, increase the risk for tuberculosis (TB). Data are scarce on the risk of prevalent TB associated with these factors in the context of population-wide systematic screening and on the association between NCDs and NCD risk factors with different manifestations of TB, where ∼50% being asymptomatic but bacteriologically positive (subclinical). We did an individual participant data (IPD) meta-analysis of national and sub-national TB prevalence surveys to synthesise the evidence on the risk of symptomatic and subclinical TB in people with NCDs or risk factors, which could help countries to plan screening activities. Methods: In this systematic review and IPD meta-analysis, we identified eligible prevalence surveys in low-income and middle-income countries that reported at least one NCD (e.g., diabetes) or NCD risk factor (e.g., smoking, alcohol use) through the archive maintained by the World Health Organization and by searching in Medline and Embase from January 1, 2000 to August 10, 2021. The search was updated on March 23, 2023. We performed a one-stage meta-analysis using multivariable multinomial models. We estimated the proportion of and the odds ratio for subclinical and symptomatic TB compared to people without TB for current smoking, alcohol use, and self-reported diabetes, adjusted for age and gender. Subclinical TB was defined as microbiologically confirmed TB without symptoms of current cough, fever, night sweats, or weight loss and symptomatic TB with at least one of these symptoms. We assessed heterogeneity using forest plots and I2 statistic. Missing variables were imputed through multi-level multiple imputation. This study is registered with PROSPERO (CRD42021272679). Findings: We obtained IPD from 16 national surveys out of 21 national and five sub-national surveys identified (five in Asia and 11 in Africa, N = 740,815). Across surveys, 15.1%–56.7% of TB were subclinical (median: 38.1%). In the multivariable model, current smoking was associated with both subclinical (OR 1.67, 95% CI 1.27–2.40) and symptomatic TB (OR 1.49, 95% CI 1.34–1.66). Self-reported diabetes was associated with symptomatic TB (OR 1.67, 95% CI 1.17–2.40) but not with subclinical TB (OR 0.92, 95% CI 0.55–1.55). For alcohol drinking ≥ twice per week vs no alcohol drinking, the estimates were imprecise (OR 1.59, 95% CI 0.70–3.62) for subclinical TB and OR 1.43, 95% CI 0.59–3.46 for symptomatic TB). For the association between current smoking and symptomatic TB, I2 was high (76.5% (95% CI 62.0–85.4), while the direction of the point estimates was consistent except for three surveys with wide CIs. Interpretation: Our findings suggest that current smokers are more likely to have both symptomatic and subclinical TB. These individuals can, therefore, be prioritised for intensified screening, such as the use of chest X-ray in the context of community-based screening. People with self-reported diabetes are also more likely to have symptomatic TB, but the association is unclear for subclinical TB. Funding: None.

Nucleic acid amplification tests such as Xpert MTB/RIF (Xpert) have the potential to revolutionize tuberculosis (TB) diagnostics and improve case finding in resource-poor settings. However, since its introduction over a decade ago in Uganda, there remain significant gaps along the cascade of care for patients undergoing TB diagnostic evaluation at peripheral health centers. We utilized a systematic, implementation science-based approach to identify key reasons at multiple levels for attrition along the TB diagnostic evaluation cascade of care. Provider- and health system-level barriers fit into four key thematic areas: human resources, material resources, service implementation, and service coordination. Patient-level barriers included the considerable costs and time required to complete health center visits. We developed a theory-informed strategy using the PRECEDE framework to target key barriers by streamlining TB diagnostic evaluation and facilitating continuous quality improvement. The resulting SIMPLE TB strategy involve four key components: 1) Single-sample LED fluorescence microscopy; 2) Daily sputum transport to Xpert testing sites; 3) Text message communication of Xpert results to health centers and patients; and 4) Performance feedback to health centers using a quality improvement framework. This combination of interventions was feasible to implement and significantly improved the provision of high-quality care for patients undergoing TB diagnostic evaluation. We conclude that achieving high coverage of Xpert testing services is not enough. Xpert scale-up should be accompanied by health system co-interventions to facilitate effective implementation and ensure that high quality care is delivered to patients.

Introduction:Nonadherence to treatment remains an obstacle to tuberculosis (TB) control worldwide. The aim of this study was to evaluate the feasibility of using video directly observed therapy (VDOT) for supporting TB treatment adherence in Uganda. Methods:From May to December 2018, we conducted a pilot cohort study at a TB clinic in Kampala City. We enrolled patients aged 18-65 years with ≥3 months remaining of their TB treatment. Participants were trained to use a smartphone app to record videos of medication intake and submit them to a secured system. Trained health workers logged into the system to watch the submitted videos. The primary outcome was adherence measured as the fraction of expected doses observed (FEDO). In a secondary analysis, we examined differences in FEDO by sex, age, phone ownership, duration of follow-up, reasons for missed videos and patients' satisfaction at study exit. Results:Of 52 patients enrolled, 50 were analysed. 28 (56%) were male, the mean age was 31 years (range 19-50 years) and 35 (70%) owned smartphones. Of the 5150 videos expected, 4231 (82.2%) were received. The median FEDO was 85% (interquartile range 66%-94%) and this significantly differed by follow-up duration. Phone malfunction, uncharged battery and VDOT app malfunctions were the commonest reasons for missed videos. 92% of patients reported being very satisfied with using VDOT. Conclusion:VDOT was feasible and acceptable for monitoring and supporting TB treatment. It resulted in high levels of adherence, suggesting that digital technology holds promise in improving patient monitoring in Uganda.