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Background Mitigating 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. Methods We 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. Results 4288 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

Background: Tuberculosis (TB) is a leading cause of death due to infectious disease worldwide. People with TB and their households often suffer social and economic losses due to the cost of tuberculosis care. The World Health Organization 2015 End TB strategy called for socioeconomic support through social protection interventions. Social protection has the potential to enable people with TB and their households to break the cycle of TB and poverty, thereby improving both treatment and socioeconomic outcomes. This study aims to evaluate whether people with TB who are recipients of social protection interventions have better treatment and socioeconomic outcomes than those who are not recipients of social protection interventions. Methods: We will systematically review literature published in English between 2012 and 2021 from PubMed, Embase, and Web of Science, and grey literature from Google Scholar and selected, relevant databases. We will include studies that describe a social protection intervention (as defined by the World Bank) and report on TB treatment outcomes and/or socioeconomic outcomes. We will only include studies pertaining to populations in low-and-middle-income countries and/or countries with high TB burden. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Study quality will be assessed using the Cochrane Risk of Bias for randomized controlled trials and the Newcastle Ottawa Scale for non-randomised controlled studies. If sufficient quantitative data are available, we will perform a meta-analysis of aggregated outcomes. Lastly, we will use the Grading Recommendations Assessment, Development, and Evaluation to describe the overall quality of evidence. Ethics and dissemination: Ethical approval is not required for this systematic review, as all data extraction and analysis will be conducted on published documents. We will disseminate this protocol through conference presentations. The systematic review has been registered prospectively in the PROSPERO database (registration number CRD42022382181).

Abstract Background Newer molecular testing platforms are now available for deployment at lower-level community health centers. There are limited data on facility- and health worker-level factors that would promote successful adoption of such platforms for rapid tuberculosis (TB) testing and treatment initiation. Our study aimed to assess readiness to implement onsite molecular testing at community health centers in Uganda, a high TB burden country in sub-Saharan Africa. Methods To understand implementation readiness, we conducted a qualitative assessment guided by the Consolidated Framework for Implementation Research (CFIR) at 6 community health centers in central and eastern Uganda between February and April 2018. We conducted 23 in-depth, semi-structured interviews with health workers involved in TB care at each health center to assess TB-related work practices and readiness to adopt onsite molecular testing using the GeneXpert Edge platform. Interviews were transcribed verbatim and coded for thematic analysis. Results Participants (N=23) included 6 nurses/nursing assistants, 6 clinicians, 6 laboratory directors/technicians, 1 medical officer, 2 health center directors, and 2 other health workers involved in TB care. Health workers described general enthusiasm that on-site molecular testing could lead to greater efficiencies in TB diagnosis and treatment, including faster turn- around time for TB test results, lack of need for trained laboratory technicians to interpret results, and reduced need to transport sputum specimens to higher level facilities. However, health workers also expressed concerns about implementation feasibility. These included uncertainty about TB infection risk, safety risks from disposal of hazardous waste, a lack of local capacity to provide timely troubleshooting and maintenance services, and concerns about the security of GeneXpert devices and accessories. Health workers also expressed the need for backup batteries to support testing or charging when wall power is unstable. Conclusion Our study generated a nuanced understanding of modifiable contextual barriers and led to direct revisions of implementation strategies for onsite molecular testing. The findings highlight that novel diagnostics should be implemented along with health system co-interventions that address contextual barriers to their effective uptake. Pre-implementation assessment of stakeholder perspectives, collaborative work processes, and institutional contexts is essential when introducing innovative technology in complex health care settings.

Abstract 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 cartridge-based 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. Discussion The design elements and implementation approach for the XPEL-TB trial were intentionally selected to minimize disruptions to routine care procedures, with the goal of limiting their influence on key primary and secondary outcomes. Trial findings may result in increased support and funding for rapid, onsite molecular testing as the standard-of-care for all patients being evaluated for TB. Trial registration US National Institutes of Health’s ClinicalTrials.gov, NCT03044158 . Registered 06 February 2017. Pan African Clinical Trials Registry, PACTR201610001763265 . Registered 03 September 2016.

Abstract Background The World Health Organization (WHO) recommends household contact investigation for tuberculosis (TB) in high-burden countries. However, household contacts who complete evaluation for TB during contact investigation may have difficulty accessing their test results. Use of automated short-messaging services (SMS) to deliver test results could improve TB status awareness and linkage to care. We sought to explore how household contacts experience test results delivered via SMS, and how these experiences influence follow-up intentions. Methods We conducted semi-structured interviews with household contacts who participated in a randomized controlled trial evaluating home sputum collection and delivery of TB results via SMS (Pan-African Clinical Trials Registry #201509000877140). We asked about feelings, beliefs, decisions, and behaviors in response to the SMS results. We analyzed the content and emerging themes in relation to the Theory of Planned Behavior. Results We interviewed and achieved thematic saturation with ten household contacts. Nine received TB-negative results and one a TB-positive result. Household contacts reported relief upon receiving SMS confirming their TB status, but also said they lacked confidence in the results delivered by SMS. Some worried that negative results were incorrect until they spoke to a lay health worker (LHW). Household contacts said their long-term intentions to request help or seek care were influenced by perceived consequences of not observing the LHW’s instructions related to the SMS and follow-up procedures; beliefs about the curability of TB; anticipated support from LHWs; and perceived barriers to responding to an SMS request for further evaluation. Conclusion Household contacts experienced relief when they received results. However, they were less confident about results delivered via SMS than results delivered by LHWs. Delivery of results by SMS should complement continued interaction with LHWs, not replace them.

Abstract Background Many high burden countries are scaling-up GeneXpert® MTB/RIF (Xpert) testing for tuberculosis (TB) using a hub-and-spoke model. However, the effect of scale up on reducing TB has been limited. We sought to characterize variation in implementation of referral-based Xpert TB testing across Uganda, and to identify health system factors that may enhance or prevent high-quality implementation of Xpert testing services. Methods We conducted a cross-sectional study triangulating quantitative and qualitative data sources at 23 community health centers linked to one of 15 Xpert testing sites between November 2016 and May 2017 to assess health systems infrastructure for hub-and-spoke Xpert testing. Data sources included a standardized site assessment survey, routine TB notification data, and field notes from site visits. Results Challenges with Xpert implementation occurred at every step of the diagnostic evaluation process, leading to low overall uptake of testing. Of 2192 patients eligible for TB testing, only 574 (26%) who initiated testing were referred for Xpert testing. Of those, 54 (9.4%) were Xpert confirmed positive just under half initiated treatment within 14 days (n = 25, 46%). Gaps in required infrastructure at 23 community health centers to support the hub-and-spoke system included lack of refrigeration (n = 14, 61%) for sputum testing and lack of telephone/mobile communication (n = 21, 91%). Motorcycle riders responsible for transporting sputum to Xpert sites operated variable with trips once, twice, or three times a week at 10 (43%), nine (39%) and four (17%) health centers, respectively. Staff recorded Xpert results in the TB laboratory register at only one health center and called patients with positive results at only two health centers. Of the 15 Xpert testing sites, five (33%) had at least one non-functioning module. The median number of tests per day was 3.57 (IQR 2.06–4.54), and 10 (67%) sites had error/invalid rates > 5%. Conclusions Although Xpert devices are now widely distributed throughout Uganda, health system factors across the continuum from test referral to results reporting and treatment initiation preclude effective implementation of Xpert testing for patients presenting to peripheral health centers. Support for scale up of innovative technologies should include support for communication, coordination and health systems integration.

To accelerate tuberculosis (TB) control and elimination, reliable data is needed to improve the quality of TB care. We assessed agreement between a surveillance dataset routinely collected for Uganda's national TB program and a high-fidelity dataset collected from the same source documents for a research study from 32 health facilities in 2017 and 2019 for six measurements: 1) Smear-positive and 2) GeneXpert-positive diagnoses, 3) bacteriologically confirmed and 4) clinically diagnosed treatment initiations, and the number of people initiating TB treatment who were also 5) living with HIV or 6) taking antiretroviral therapy. We measured agreement as the average difference between the two methods, expressed as the average ratio of the surveillance counts to the research data counts, its 95% limits of agreement (LOA), and the concordance correlation coefficient. We used linear mixed models to investigate whether agreement changed over time or was associated with facility characteristics. We found good overall agreement with some variation in the expected facility-level agreement for the number of smear positive diagnoses (average ratio [95% LOA]: 1.04 [0.38-2.82]; CCC: 0.78), bacteriologically confirmed treatment initiations (1.07 [0.67-1.70]; 0.82), and people living with HIV (1.11 [0.51-2.41]; 0.82). Agreement was poor for Xpert positives, with surveillance data undercounting relative to research data (0.45 [0.099-2.07]; 0.36). Although surveillance data overcounted relative to research data for clinically diagnosed treatment initiations (1.52 [0.71-3.26]) and number of people taking antiretroviral therapy (1.71 [0.71-4.12]), their agreement as assessed by CCC was not poor (0.82 and 0.62, respectively). Average agreement was similar across study years for all six measurements, but facility-level agreement varied from year to year and was not explained by facility characteristics. In conclusion, the agreement of TB surveillance data with high-fidelity research data was highly variable across measurements and facilities. To advance the use of routine TB data as a quality improvement tool, future research should elucidate and address reasons for variability in its quality.

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.

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.

Background: Pre-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. Objective: We sought to assess the feasibility of utilizing SMS technology to deliver TB test results during routine TB diagnostic evaluation in Uganda. Methods: We 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. Results: Of 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. Conclusion: Reporting 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. Keywords: Mobile technology, Information and communication technology, SMS

Rationale: Many high-burden countries are scaling-up Xpert MTB/RIF using a hub-and-spoke model. We evaluated the quality of care for patients undergoing TB evaluation at microscopy centers (spokes) linked to Xpert testing sites (hubs) in Uganda. Objectives: To characterize the extent to which patients were receiving care in accordance with international and national guidelines. Methods: We conducted a prospective cohort study of all adults with presumptive pulmonary TB at 24 health centers linked to Xpert testing sites. Health center staff photographed TB registers, and uploaded photos to a secure server bi-weekly. We assessed the proportion of patients (1) initiating testing; (2) completing testing; and (3) treated for confirmed TB within 14 days. Measurements and Main Results: Between January to December 2017, 6744 patients underwent evaluation for pulmonary TB. Only 1316 patients had sputum referred for Xpert testing, including 1075/3229 (33.3%) people living with HIV and 241/3515 (6.9%) without HIV. Of 119 patients confirmed to have TB by Xpert testing, 44 (36%) did not initiate treatment. There were significant losses along the entire diagnostic cascade of care, with only 5330/6744 (79.0%) patients having samples referred for sputum-based testing, 2978/5330 (55.9%) patients completing recommended testing if referred, and 313/418 (74.9%) patients initiating treatment within 14 days if confirmed to have TB. Conclusions: Although coverage of Xpert testing services across Uganda is high, the quality of care delivered to patients undergoing TB evaluation remains poor. Further research is needed to identify health system interventions to facilitate uptake of Xpert testing and high-quality care. Keywords: Tuberculosis, Diagnosis, Quality of care

Abstract Background Studies of malaria in well-defined cohorts offer important data about the epidemiology of this complex disease, but few have been done in urban African populations. To generate a sampling frame for a longitudinal study of malaria incidence and treatment in Kampala, Uganda, a census, mapping and survey project was conducted. Methods All households in a geographically defined area were enumerated and mapped. Probability sampling was used to recruit a representative sample of children and collect baseline descriptive data for future longitudinal studies. Results 16,172 residents living in 4931 households in a densely-populated community (18,824 persons/km2) were enumerated. A total of 582 households were approached with at least one child less than 10 years of age in order to recruit 601 children living in 322 households. At enrollment, 19% were parasitaemic, 24% were anaemic, 43% used bednets, and 6% used insecticide-treated nets. Low G6PD activity (OR = 0.33, P = 0.009) and bednet use (OR = 0.64, P = 0.045) were associated with a decreased risk of parasitaemia. Increasing age (OR = 0.62 for each year, P < 0.001) and bednet use (OR = 0.58, P = 0.02) were associated with a decreased risk of anaemia Conclusion Detailed surveys of target populations in urban Africa can provide valuable descriptive data and provide a sampling frame for recruitment of representative cohorts for longitudinal studies. Plans to use a multi-disciplinary approach to improve the understanding of the distribution and determinants of malaria incidence and response to therapy in this population are discussed.