Feasibility and acceptability of the smart pillbox and medication label with differentiated care to support person-centered tuberculosis care among ASCENT trial participants - A multicountry study.

Introduction: Digital adherence technologies (DATs) can offer alternative approaches to support tuberculosis treatment medication adherence. Evidence on their feasibility and acceptability in high TB burden settings is limited. We conducted a cross-sectional survey among adults with drug-sensitive tuberculosis (DS-TB), participating in pragmatic cluster-randomized trials for the Adherence Support Coalition to End TB project in Ethiopia (PACTR202008776694999), the Philippines, South Africa and Tanzania (ISRCTN 17706019). Methods: From each country we selected 10 health facilities implementing the DAT intervention (smart pillbox or medication labels, with differentiated care support), ensuring inclusion of urban/rural and public/private facilities. Adults on DS-TB regimen using a DAT were randomly selected from each facility. Feasibility of the DATs was assessed using a standardized tool. Acceptability was measured using a 5-point Likert-scale, using the Capability, Opportunity, Motivation, Behavior (COM-B) model. Mean scores of Likert-scale responses within each COM-B category were estimated, adjusted for facility-level clustering. Data were summarized by country and DAT type. Results: Participants using either the pillbox (n = 210) or labels (n = 169) were surveyed. Among pillbox users, phone ownership (79%), use of pillbox reminders (87%) and taking treatment without the pillbox (22%) varied by country. Among label users, phone ownership (81%), paying extra to use the labels (8%) and taking treatment without using labels (41%) varied by country. Poor network, problems with phone charging and access, not having the pillbox and forgetting to send text were reasons for not using DATs. Overall, people with TB had a favorable impression of both DATs, with mean composite scores between 4·21 to 4·42 across COM-B categories. Some disclosure concerns were reported. Conclusion: From client-perspective, pillboxes and medication labels with differentiated care support were feasible to implement and acceptable in variety of settings. However, implementation challenges related to network, phone access, stigma, additional costs to people with TB to use DATs need to be addressed.

Digital health solutions and integrated COVID-19 and TB services to help recover TB care and prevention services in the COVID-19 pandemic: A descriptive study in four high TB burden countries.

BACKGROUND: The measures undertaken to control COVID-19 have disrupted many platforms including tuberculosis (TB) healthcare services. Consequently, declines in TB notifications have been observed in various countries. We visualized changes over time in TB and SARS-CoV-2 infection notifications and reported on country-specific strategies to retain TB care and prevention services in Kyrgyzstan, Nigeria, Tanzania, and Vietnam. METHODS: We collected and visualized quarterly, retrospective, and country-specific data (Quarter (Q) 1 2018- Q1 2021) on SARS-CoV-2 infection and TB notifications. Additionally, we conducted a country-specific landscape assessment on COVID-19 measures, including lockdowns, operational level strategy of TB care and prevention services, and strategies employed to recover and retain those services. We used negative binomial regression models to assess the association between the installation of COVID-19 measures and changes in TB notifications. RESULTS: TB notifications declined in Kyrgyzstan and Vietnam, and (slightly) increased in Nigeria and Tanzania. The changes in TB notifications were associated with the installation of various COVID-19 prevention measures for Kyrgyzstan and Vietnam (declines) and Nigeria (increases). All countries reported reduced TB screening and testing activities. Countries reported the following strategies to retain TB prevention and care services: digital solutions for treatment adherence support, capacity building, and monitor & evaluation activities; adjustment in medication supply/delivery & quantity, including home delivery, pick up points, and month supply; integrated TB/COVID-19 screening & diagnostic platform; and the use of community health care workers. CONCLUSION: Following the COVID-19 pandemic, we did not observe consistent changes in TB notifications across countries. However, all countries reported lower operating levels of TB prevention and care services. Digital health solutions, community-based interventions, and the integration of COVID-19 and TB testing services were employed to recover and retain those services.

Risk factors for poor engagement with a smart pillbox adherence intervention among persons on tuberculosis treatment in Ethiopia.

BACKGROUND: Non-adherence to tuberculosis treatment increases the risk of poor treatment outcomes. Digital adherence technologies (DATs), including the smart pillbox (EvriMED), aim to improve treatment adherence and are being widely evaluated. As part of the Adherence Support Coalition to End TB (ASCENT) project we analysed data from a cluster-randomised trial of DATs and differentiated care in Ethiopia to examine individual-factors for poor engagement with the smart pillbox. METHODS: Data were obtained from a cohort of trial participants with drug-sensitive tuberculosis (DS-TB) whose treatment started between 1 December 2020 and 1 May 2022, and who were using the smart pillbox. Poor engagement with the pillbox was defined as (i) > 20% days with no digital confirmation and (ii) the count of days with no digital confirmation, and calculated over a two evaluation periods (56-days and 168-days). Logistic random effects regression was used to model > 20% days with no digital confirmation and negative binomial random effects regression to model counts of days with no digital confirmation, both accounting for clustering of individuals at the facility-level. RESULTS: Among 1262 participants, 10.8% (133/1262) over 56-days and 15.8% (200/1262) over 168-days had > 20% days with no digital confirmation. The odds of poor engagement was less among participants in the higher stratum of socio-economic position (SEP) over 56-days. Overall, 4,689/67,315 expected doses over 56-days and 18,042/199,133 expected doses over 168-days were not digitally confirmed. Compared to participants in the poorest SEP stratum, participants in the wealthiest stratum had lower rates of days not digitally confirmed over 168-days (adjusted rate ratio [RRa]:0.79; 95% confidence interval [CI]: 0.65, 0.96). In both evaluation periods (56-days and 168-days), HIV-positive status (RRa:1.29; 95%CI: 1.02, 1.63 and RRa:1.28; 95%CI: 1.07, 1.53), single/living independent (RRa:1.31; 95%CI: 1.03, 1.67 and RRa:1.38; 95%CI: 1.16, 1.64) and separated/widowed (RRa:1.40; 95%CI: 1.04, 1.90 and RRa:1.26; 95%CI: 1.00, 1.58) had higher rates of counts of days with no digital confirmation. CONCLUSION: Poorest SEP stratum, HIV-positive status, single/living independent and separated/ widowed were associated with poor engagement with smart pillbox among people with DS-TB in Ethiopia. Differentiated care for these sub-groups may reduce risk of non-adherence to TB treatment.

Pulmonary tuberculosis complicated by pneumothorax, and acute respiratory distress syndrome (ARDS) in the settings of advanced HIV disease: A case report.

Introduction: A large proportion of the global burden of HIV-associated TB occurs in sub-Saharan Africa; including 74% of new cases of TB and 79% of deaths occurs in this area. Spontaneous pneumothorax occurs more frequently in patients with AIDS than the general population with the estimated incidence to be about 2-5% of overall total cases. Tuberculosis ARDS and septic shock are rare but carries extremely poor prognosis. Case summary: A 27 year old male with advanced HIV disease with very low CD4 count presented to Wolaita Sodo University comprehensive specialized hospital, Ethiopia on July 6, 2023. The patient diagnosed with spontaneous pneumothorax secondary to drug susceptible tuberculosis after positive urine LF-LAM and sputum gene expert. He was intubated after emergency tube thoracostomy, and subsequently treated with anti-TB, corticosteroid, broad-spectrum IV antibiotics and high dose cotrimoxazole. The patient developed ARDS due to possible tuberculosis related septic shock and died of multi-organ failure. Discussion: Spontaneous pneumothorax in the setting of HIV raises concern for PCP, though in this case it could be secondary to TB. Tuberculosis related ARDS and septic shock are rare complication but carries poor prognosis especially in setting of AHD. We had limited experience and difficulties in the management of patient with persistent pneumothorax with the concomitant ARDS requiring lung protective management, and this part remain the future area of scientific research. Conclusion: In patients with advanced HIV disease, who present with signs of respiratory failure, the likelihood of spontaneous pneumothorax, TB-ARDS and septic shock should be anticipated in the differential diagnosis and optimal management plan should be designed.

Comparison of Xpert MTB/RIF Ultra Results of Stool and Sputum in Children with Presumptive Tuberculosis in Southern Ethiopia.

The introduction of stool as a readily obtainable sample and the recently developed simple one-step (SOS) stool processing method on Xpert MTB/RIF Ultra (Xpert Ultra) offer an opportunity for TB diagnosis in children. We conducted this study in secondary health facilities in Ethiopia, which are the first-level referral facilities for childhood TB diagnosis and treatment, with the aim to determine if stool-based TB diagnosis can be performed with a reasonable level of concordance with sputum tests using Xpert MTB/RIF Ultra. Eligible children 0-14 years old with presumptive pulmonary TB were asked to provide stools in addition to routinely requested sputum samples. We determined the level of agreement between the stool and sputum test results. Of the 373 children included in the study, 61% were <5 years of age and 56% were male. Thirty-six children (9.7%) were diagnosed with TB, and all started treatment. The rate of concordance between stool and sputum was high, with a kappa value of 0.83 (p < 0.001). There were more Xpert Ultra positive results on stool (n = 27 (7.2%)) than on sputum/NGA (n = 23 (6.2%)). Laboratories in secondary hospitals can perform stool-based TB diagnosis in children, with high concordance between stool and sputum test results reaffirming the applicability of the SOS stool method.

Optimization of the Simple One-Step Stool Processing Method to Diagnose Tuberculosis: Evaluation of Robustness and Stool Transport Conditions for Global Implementation.

Stool is recommended as an alternative specimen for the diagnosis of tuberculosis (TB) in young children, as they cannot easily produce sputum. The Simple One-Step (SOS) stool processing method is a new and simple stool processing method for the detection of Mycobacterium tuberculosis (MTB) using Xpert MTB/RIF Ultra (Xpert-Ultra). We determined the robustness of the SOS stool processing method and stool specimen transport conditions in participants with confirmed TB. We processed stool using the standard protocol after simulated "transport," varying time, and temperature, and experimented with slightly modified processing steps. We included 2,963 Xpert-Ultra test results from 132 stool specimens of 47 TB participants, including 11 children aged <10 years. We compared Xpert-Ultra processing errors and MTB positivity rates between standard and modified procedures. Minor deviations from the standard SOS protocol did not significantly impact the Xpert-Ultra test outcomes. The rate of Xpert-Ultra processing errors significantly increased with noncold-chain transport, exposure of stool to sample reagent at room temperature or beyond 12 h, and adding >0.8 g of stool. We found that almost all steps in the current SOS stool processing method provide optimal Xpert-Ultra results but recommend an adjustment to use a wider range of stool amounts (0.3 to 0.8 g) than advised previously (0.8 g). With this adaptation, stool-based diagnosis of TB using the SOS stool processing method can be scaled-up. IMPORTANCE The manuscript will support the global implementation and scale-up of the SOS stool method in routine settings. It also provides important insights on the optimal stool transport conditions and robustness of the SOS method, which can be used for bacteriological diagnosis of TB in children at the lowest levels of the healthcare system, avoiding lengthy healthcare-seeking pathways and additional costs.

The association between HIV diagnosis disclosure and adherence to anti-retroviral therapy among adolescents living with HIV in Sub-Saharan Africa: A systematic review and meta-analysis.

INTRODUCTION: Nine in ten of the world's 1.74 million adolescents living with human immunodeficiency virus (ALHIV) live in Sub-Saharan Africa. Suboptimal adherence to antiretroviral therapy (ART) and poor viral suppression are important problems among adolescents. To guide intervention efforts in this regard, this review presented pooled estimates on the prevalence of adherence and how it is affected by disclosure of HIV status among ALHIV in Sub-Saharan Africa. METHODS: A comprehensive search in major databases (Excerpta Medica database (EMBASE), PubMed, Ovid/MEDLINE, HINARI, and Google Scholar) with additional hand searches for grey literature was conducted to locate observational epidemiologic studies published in English up to November 12, 2022 with the following inclusion criteria: primary studies that reported disclosure of HIV status as an exposure variable, had positive adherence to ART as an outcome, and conducted among adolescents and children. The COVIDENCE software was used for a title/abstract screening, full-text screening, the JBI quality assessment checklist, and data extraction. Random effects model was used to pool estimates. Furthermore, sensitivity analysis and subgroup analysis were also conducted by age groups and type of adherence measures used. RESULTS: This meta-analysis combines the effect estimates from 12 primary studies with 4422 participants. The prevalence of good adherence to ART was 73% (95% CI (confidence interval): 56 to 87; I2 = 98.63%, P = <0.001), and it was higher among adolescents who were aware of their HIV status, 77% (95% CI: 56 to 92; I2 = 98.34%, P = <0.001). Overall, knowledge of HIV status was associated with increased odds of adherence (odds ratio (OR) = 1.88, 95% CI: 1.21 to 2.94; I2 = 79.8%, P = <0.001). This was further supported in a subgroup analysis by age (seven studies, pooled OR = 1.89, 95% CI: 1.06 to 3.37; I2 = 81.3%, P = <0.0001) and whether primary studies controlled for confounding factors (six studies provided adjusted estimates, pooled OR = 2.61, 95% CI: 1.22 to 5.57; I2 = 88.1%, P = <0.001) confirmed this further. CONCLUSIONS: Our meta-analysis and systematic review revealed that knowledge of one's HIV status was associated with adherence to ART, particularly among adolescents. The findings underscored the importance of encouraging disclosure in order to enhance adherence among adolescents.

Effect of multicomponent interventions on tuberculosis notification in mining and pastoralist districts of Oromia region in Ethiopia: a longitudinal quasi-experimental study.

OBJECTIVE: To demonstrate the impact of interventions on tuberculosis (TB) case detection in mining and pastoralist districts in southeastern Ethiopia over a 10-year period. DESIGN: Longitudinal quasi-experimental study. SETTING: Health centres and hospitals in six mining districts implemented interventions and seven nearby districts functioned as controls. PARTICIPANTS: Data from the national District Health Information System (DHIS-2) were used for this study; therefore, people did not participate in this study. INTERVENTIONS: Directed at training, active case finding and improving treatment outcomes. PRIMARY AND SECONDARY OUTCOME MEASURES: Primarily, trends in TB case notification and percentage of bacteriologically confirmed TB-as collected by DHIS-2-between pre-intervention (2012-2015) and post-intervention (2016-2021) were analysed. Secondarily, post-intervention was split into early post-intervention (2016-2018) and late post-intervention (2019-2021) to also study the long-term effects of the intervention. RESULTS: For all forms of TB, case notification significantly increased between pre-intervention and early post-intervention (incidence rate ratio (IRR): 1.21, 95% CI: 1.13, 1.31; p<0.001) and significantly decreased between pre-intervention/early post-intervention and late post-intervention (IRR: 0.82, 95% CI: 0.76, 0.89; p<0.001 and IRR: 0.67, 95% CI: 0.62, 0.73; p<0.001). For bacteriologically confirmed cases, we found a significant decrease between pre-intervention/early post-intervention and late post-intervention (IRR: 0.88, 95% CI: 0.81, 0.97; p<0.001 and IRR: 0.81, 95% CI: 0.74, 0.89; p<0.001). The percentage of bacteriologically confirmed cases was significantly lower in the intervention districts during pre-intervention (B: -14.24 percentage points, 95% CI: -19.27, -9.21) and early post-intervention (B: -7.78, 95% CI: -15.46, -0.010; p=0.047). From early post-intervention to late post-intervention, we found a significant increase (B: 9.12, 95% CI: 0.92 to 17.33; p=0.032). CONCLUSIONS: The decrease in TB notifications in intervention districts during late post-intervention is possibly due to a decline in actual TB burden as a result of the interventions. The unabated increase in case notification in control districts may be due to continued TB transmission in the community.

Evaluating the equity impact and cost-effectiveness of digital adherence technologies with differentiated care to support tuberculosis treatment adherence in Ethiopia: protocol and analysis plan for the health economics component of a cluster randomised trial.

BACKGROUND: Tuberculosis remains a leading infectious cause of death in resource-limited settings. Effective treatment is the cornerstone of tuberculosis control, reducing mortality, recurrence and transmission. Supporting treatment adherence through facility-based observations of medication taking can be costly to providers and patients. Digital adherence technologies (DATs) may facilitate treatment monitoring and differentiated care. The ASCENT-Ethiopia study is a three-arm cluster randomised trial assessing two DATs with differentiated care for supporting tuberculosis treatment adherence in Ethiopia. This study is part of the ASCENT consortium, assessing DATs in South Africa, the Philippines, Ukraine, Tanzania and Ethiopia. The aim of this study is to determine the costs, cost-effectiveness and equity impact of implementing DATs in Ethiopia. METHODS AND DESIGN: A total of 78 health facilities have been randomised (1:1:1) into one of two intervention arms or a standard-of-care arm. Approximately 50 participants from each health facility will be enrolled on the trial. Participants in facilities randomised to the intervention arms are offered a DAT linked to the ASCENT adherence platform for daily adherence monitoring and differentiated response for those who have missed doses. Participants at standard-of-care facilities receive routine care. Treatment outcomes and resource utilisation will be measured for each participant. The primary effectiveness outcome is a composite index of unfavourable end-of-treatment outcomes (lost to follow-up, death or treatment failure) or treatment recurrence within 6 months of end-of-treatment. For the cost-effectiveness analysis, end-of-treatment outcomes will be used to estimate disability-adjusted life years (DALYs) averted. Provider and patient cost data will be collected from a subsample of 5 health facilities per study arm, 10 participants per facility (n = 150). We will conduct a societal cost-effectiveness analysis using Bayesian hierarchical models that account for the individual-level correlation between costs and outcomes as well as intra-cluster correlation. An equity impact analysis will be conducted to summarise equity efficiency trade-offs. DISCUSSION: Trial enrolment is ongoing. This paper follows the published trial protocol and describes the protocol and analysis plan for the health economics work package of the ASCENT-Ethiopia trial. This analysis will generate economic evidence to inform the implementation of DATs in Ethiopia and globally. TRIAL REGISTRATION: Pan African Clinical Trial Registry (PACTR) PACTR202008776694999. Registered on 11 August 2020,  https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=12241 .

Effectiveness of digital adherence technologies in improving tuberculosis treatment outcomes in four countries: a pragmatic cluster randomised trial protocol.

INTRODUCTION: Successful treatment of tuberculosis depends to a large extent on good adherence to treatment regimens, which relies on directly observed treatment (DOT). This in turn requires frequent visits to health facilities. High costs to patients, stigma and burden to the health system challenged the DOT approach. Digital adherence technologies (DATs) have emerged as possibly more feasible alternatives to DOT but there is conflicting evidence on their effectiveness and feasibility. Our primary objective is to evaluate whether the implementation of DATs with daily monitoring and a differentiated response to patient adherence would reduce poor treatment outcomes compared with the standard of care (SOC). Our secondary objectives include: to evaluate the proportion of patients lost to follow-up; to compare effectiveness by DAT type; to evaluate the feasibility and acceptability of DATs; to describe factors affecting the longitudinal engagement of patients with the intervention and to use a simple model to estimate the epidemiological impact and cost-effectiveness of the intervention from a health system perspective. METHODS AND ANALYSIS: This is a pragmatic two-arm cluster-randomised trial in the Philippines, South Africa, Tanzania and Ukraine, with health facilities as the unit of randomisation. Facilities will first be randomised to either the DAT or SOC arm, and then the DAT arm will be further randomised into medication sleeve/labels or smart pill box in a 1:1:2 ratio for the smart pill box, medication sleeve/label or the SOC respectively. We will use data from the digital adherence platform and routine health facility records for analysis. In the main analysis, we will employ an intention-to-treat approach to evaluate treatment outcomes. ETHICS AND DISSEMINATION: The study has been approved by the WHO Research Ethics Review Committee (0003296), and by country-specific committees. The results will be shared at national and international meetings and will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN17706019.

Antiretroviral therapy non-adherence among children living with HIV in Dire Dawa, Eastern Ethiopia: a case-control study.

BACKGROUND: In 2018, nearly 90% of the global children living with human immunodeficiency virus (HIV) were in sub-Saharan Africa (SSA). Compared to the adult population, antiretroviral therapy (ART) coverage among children was limited. However, adherence remained a problem among children though they had limited access to ART. This study was conducted to identify the risk factors of non-adherence to ART among children aged 6 to 17 years. METHODS: This case-control study was conducted in 2020 using data obtained from clinical record reviews and self-reported data from 272 caregivers of HIV-infected children aged 6-17 years. Cases and controls represented children with poor versus children with good adherence to ART, respectively. Good adherence was defined based on a past 30-day physician adherence evaluation of taking ≥ 95% of the prescribed doses. Binary logistic regression was used to identify factors associated with non-adherence to ART. All statistical tests are defined as statistically significant at P-values < 0.05. RESULTS: Of the 272 children, for whom data were obtained, 78 were cases and 194 were controls; females accounted for 56.3%, 32% attended secondary school, and for 83.1%, the reporting caregivers were biological parents. Non-adherent children had higher odds of association with the following risk factors: a caregiver who is a current substance user (aOR = 2.87, 95% CI: 1.44, 5.71), using AZT-and ABC-based regimen compared to the TDF-regimen (AZT-based, aOR = 4.12, 95% CI: 1.43, 11.86; ABC-based, aOR = 5.58, 95% CI: 1.70, 18.30), and had an increase in viral load from baseline compared to those remained undetectable (remained at or decreased to < 1000, aOR = 4.87, 95% CI: 1.65, 14.33; remained at ≥ 1000, aOR = 9.30, 95% CI: 3.69, 23.46). In contrast, non-adherent children had 66% lower odds of being at early adolescent age compared to 6-9 years old (10-14 years, aOR = 0.34, 95% CI: 0.12, 0.99) and had 70% lower odds of being aware of their HIV status (aOR = 0.30, 95% CI: 0.13, 0.73). CONCLUSION: Technical support to caregivers to build disclosure self-efficacy, identifying the appropriate regimen for children, counseling on viral load suppression on subsequent visits, and helping caregivers avoid or reduce substance use may help improve the problem of children's non-adherence to ART.

The yield of chest X-ray based versus symptom-based screening among patients with diabetes mellitus in public health facilities in Addis Ababa, Ethiopia.

Background: Patients with diabetes mellitus (DM) are at increased risk of developing TB, but the best screening algorithm for early detection and treatment of TB remains unknown. Our objective was to determine if combining routine chest X-ray screening could have a better yield compared with symptom-based screening alone. Methods: We conducted this cross-sectional study between September 2020 and September 2021 in 26 public health facilities in Addis Ababa, Ethiopia. All DM patients attending the clinics during the study period were offered chest X-ray and symptom screening simultaneously followed by confirmatory Xpert testing. We analyzed the number and proportion of patients with TB by the diagnostic algorithm category and performed binary logistic regression analysis to identify predictors of TB diagnosis. Results: Of 7394 patients screened, 54.6 % were female, and their median age was 53 years. Type-2 diabetes accounted for 89.6 % of all participants of the patients. Of 172 symptomatic patients, chest X-ray suggested TB in 19, and 11 of these were confirmed to have TB (8 bacterilogicially confirmed and 3 clinically diagnosed). Only 2 of the 152 asymptomatic patients without X-ray findings had TB (both bacteriologically confirmed). X-ray was not done for one patient. On the other hand, 28 of 7222 symptom-negative patients had X-ray findings suggestive of TB, and 7 of these were subsequently confirmed with TB (6 clinically diagnosed). When combined with 8 patients who were on treatment for TB at the time of the screening, the overall point prevalence of TB was 380 per 100,000. The direct cost associated with the X-ray-based screening was 42-times higher. Conclusion: Chest X-ray led to detection of about a third of TB patients which otherwise would have been missed but the algorithm is more expensive. Its full cost implication needs further economic evaluation.

The Simple One-step stool processing method for detection of Pulmonary tuberculosis: A study protocol to assess the robustness, stool storage conditions and sampling strategy for global implementation and scale-up.

BACKGROUND: The Xpert MTB/RIF Ultra (Xpert-Ultra) assay provides timely results with good sensitivity and acceptable specificity with stool specimens in children for bacteriological confirmation of tuberculosis (TB). This study aims to optimize the Simple One-Step (SOS) stool processing method for testing stool specimens using the Xpert-Ultra in children and adults in selected health facilities in Addis Ababa, Ethiopia. The study is designed to assess the robustness of the SOS stool method, to help fine-tune the practical aspects of performing the test and to provide insights in stool storage conditions and sampling strategies before the method can be implemented and scaled in routine settings in Ethiopia as well as globally. METHODS AND DESIGN: The project "painless optimized diagnosis of TB in Ethiopian children" (PODTEC) will be a cross sectional study where three key experiments will be carried out focusing on 1) sampling strategy to investigate if the Xpert-Ultra M. tuberculosis (MTB) -positivity rate depends on stool consistency, and if sensitivity can be increased by taking more than one stool specimen from the same participant, or doing multiple tests from the same stool specimen, 2) storage conditions to determine how long and at what temperature stool can be stored without losing sensitivity, and 3) optimization of sensitivity and robustness of the SOS stool processing method by varying stool processing steps, stool volume, and storage time and conditions of the stool-sample reagent mixture. Stool specimens will be collected from participants (children and adults) who are either sputum or naso-gastric aspiration (NGA) and/or stool Xpert-Ultra MTB positive depending on the experiment. Stool specimens from these participants, recruited from 22 sites for an ongoing related study, will be utilized for the PODTEC experiments. The sample size is estimated to be 50 participants. We will use EpiData for data entry and Stata for data analysis purposes. The main analyses will include computing the loss or gain in the Xpert-Ultra MTB positivity rate and rates of non-determinate Xpert-Ultra test results per experiment compared to the Xpert-Ultra MTB result of stool processed according to the published standard operating procedures for SOS stool processing. The differences in the MTB positivity rate by regarding testing more than one sample per child, and using different storage, and processing conditions, will be also compared to the baseline (on-site) Xpert-Ultra result.

Effectiveness of women-led community interventions in improving tuberculosis preventive treatment in children: results from a comparative, before-after study in Ethiopia.

OBJECTIVES: Our objective was to evaluate the impact of a service delivery model led by membership-based associations called Iddirs formed by women on tuberculosis preventive treatment (TPT) initiation and completion rates among children. DESIGN: Comparative, before-and-after study design. SETTING: Three intervention and two control districts in Ethiopia. PARTICIPANTS: Children who had a history of close contact with adults with infectious forms of tuberculosis (TB). Child contacts in whom active TB and contraindications to TPT regimens were excluded were considered eligible for TPT. INTERVENTIONS: Between July 2020 and June 2021, trained women Iddir members visited households of index TB patients, screened child household contacts for TB, provided education and information on the benefits of TPT, linked them to the nearby health centre and followed them at home for TPT adherence and side effects. Two control zones received the standard of care, which comprised of facility-based provision of TPT to children. We analysed quarterly TPT data for treatment initiation and completion and compared intervention and control zones before and after the interventions and tested for statistical significance using Poisson regression. PRIMARY AND SECONDARY OUTCOME MEASURES: There were two primary outcome measures: proportion of eligible children initiated TPT and proportion completed treatment out of those eligible. RESULTS: TPT initiation rate among eligible under-15-year-old children (U15C) increased from 28.7% to 63.5% in the intervention zones, while it increased from 34.6% to 43.2% in the control zones, and the difference was statistically significant (p<0.001). TPT initiation rate for U5C increased from 13% (17 out of 131) to 93% (937 out of 1010). Of the U5C initiated, 99% completed treatment; two discontinued due to side effects; three parents refused to continue; and one child was lost to follow-up. CONCLUSION: Women-led Iddirs contributed to significant increase in TPT initiation and completion rates. The model of TPT delivery should be scaled-up.

Predictors of loss to follow-up among adult tuberculosis patients in Southern Ethiopia: a retrospective follow-up study.

BACKGROUND: Loss to follow-up (LTFU) from tuberculosis (TB) treatment and care is a major public health problem as patients can be infectious and also may develop a multi-drug resistant TB (MDR-TB). The study aimed to assess whether LTFU differs by the distance TB patients travelled to receive care from the nearest health facility. METHODS: A total of 402 patient cards of TB patients who received care were reviewed from March 1-30, 2020. The Kaplan-Meir curve with the Log-rank test was used to compare differences in LTFU by the distance travelled to reach to the nearest health facility for TB care. The Cox proportional hazard regression model was used to identify predictors. All statistical tests are declared significant at a p-value< 0.05. RESULTS: A total of 37 patients were LTFU with the incidence rate of 11.26 per 1000 person-months of observations (PMOs) (95% CI: 8.15-15.53). The incidence rate ratio was 12.19 (95% CI: 5.01-35.73) among the groups compared (those who travelled 10 km or more versus those who travelled less than 10 km). Age ≥ 45 years (aHR = 7.71, 95% CI: 1.72, 34.50), educational status (primary schooling, aHR = 3.54, 95% CI: 1.49, 8.40; secondary schooling, aHR = 2.75, 95% CI: 1.08, 7.03), lack of family support (aHR = 2.80, 95% CI: 1.27, 6.19), nutritional support (aHR = 3.40, 95% CI:1.68, 6.89), ≥ 10 km distance to travel to a health facility (aHR = 6.06, 95% CI: 2.33, 15.81) had significantly predicted LTFU from TB treatment and care. CONCLUSIONS: LTFU from adult TB care and treatment was 12 times higher among those who travelled ≥10 km to reach a health facility compared to those who travelled less. To retain adult TB patients in care and ensure appropriate treatment, health professionals and other stakeholders should give due attention to the factors that drive LTFU. We suggest identifying concerns of older patients at admission and those who travel long distance and establish social support platforms that could help people to complete TB treatment.

High rates of undiagnosed diabetes mellitus among patients with active tuberculosis in Addis Ababa, Ethiopia.

Background: Tuberculosis (TB) and diabetes mellitus (DM) have negative synergistic impact on each other. Global guidelines recommend collaborative efforts to address this synergy, but implementation has been slow. Part of the reason is lack of adequate evidence on the operational feasibility of existing tools and mechanisms of collaboration. The objective of this study was to assess the yield of DM screening among TB patients using risk scoring tools combined with blood tests as a feasible strategy for early detection to improve TB/DM treatment outcomes. Methods: Between September 2020 and December 2021, we conducted a cross-sectional study among patients receiving TB treatment in public health facilities in Addis Ababa, Ethiopia. Trained health workers collected data on symptoms and risk scoring checklists before testing for random and fasting blood glucose levels. We used logistic regression analyses techniques to determine factors associated with increased DM detection. A receiver-operating characteristic curve was constructed to determine the performance of the risk scoring checklist. Results: Of 2381 TB patients screened, 197 (8.3%) had DM of which 48.7% were newly diagnosed. Having a family history of DM predicted DM with Odds Ratio (OR) of 5.36 (95% Confidence Interval, [3.67, 7.83]) followed by age ≥ 45 years (OR = 4.64, [3.18, 6.76]). Having one or more "symptoms" of DM was a significant predictor (OR 2.88, 95% CI, 2.06-4.01). Combining risk scores with symptoms predicted DM diagnosis with sensitivity of 94.7%, but specificity was low at 29.4%. In patients with known treatment outcome status, death rate was high. Conclusions: Almost a half of TB patients with DM did not know their status. A simple tool that combined risk factors with symptoms accurately predicted a subsequent diagnosis of DM. Such tools can help avoid high rates of death among TB patients suffering from DM through early detection.

Prospects for tuberculosis elimination in Ethiopia: feasibility, challenges, and opportunities.

To end the global tuberculosis (TB) epidemic and eliminate TB, countries around the world committed to significantly expanding the scope of their efforts, including rapid uptake of new tools, interventions, and strategies, and envisioned a world free of TB. Between 2010 and 2020, Ethiopia experienced a 5% average annual decline in TB incidence. However, at that current rate, ending the TB epidemic (<10 TB cases/100,000 population) may not be possible soon. As a high TB and TB/HIV burden country, Ethiopia's TB epidemic is characterized by a high rate of transmission in the general population and hard-to-reach areas and progression of latent TB infection (LTBI) rather than cross-border migration. Studies suggest that a combination of interventions, such as intensive household screening with TB preventive therapy, has the potential to significantly decrease the incidence of TB. The feasibility of reducing the population-level TB incidence by a combination of interventions in Ethiopia is unknown. Based on the World Health Organization's TB elimination framework and the END TB strategic documents and previously published reviews in TB elimination we conducted a narrative review to summarize and estimated the effect of a combined intervention package (community-based TB screening for active case finding and TB and LTBI prevention and treatment among high-risk groups like household and close contacts). The projected annual decline of TB incidence was above 16%. With this level of impact and nationwide scale-up of the interventions, Ethiopia aligns well with ending the TB epidemic before 2035 and shifting toward TB elimination in the foreseeable future. In the Ethiopia setting, we recommend future studies generating evidence on the impact of the combination intervention package to reduce TB incidence in Ethiopia, which is aiming to shift from control to TB elimination.

Poor adult tuberculosis treatment outcome and associated factors in Gibe Woreda, Southern Ethiopia: An institution-based cross-sectional study.

Tuberculosis (TB) remains a major medical and public health problem throughout the world, especially in developing countries including Ethiopia. Its control program is currently being challenged by the spread of drug-resistant TB, which is the result of poor treatment outcomes. Hence, this study assessed poor adult TB treatment outcomes and associated factors in Gibe Woreda, Southern Ethiopia. An institution-based cross-sectional study was conducted from March 1, 2020 to March 30, 2020, using a standard checklist to review clinical charts of TB patients who enrolled on first-line TB treatment under DOTS between June 2016 and June 2019. Poor treatment outcomes constituted death during treatment, treatment failure, and loss to follow-up (LTFU). Descriptive statistics were used to describe the characteristics of study participants. A binary logistic regression model was fitted to identify factors influencing treatment outcome and adjusted odds ratios with a 95% confidence interval were reported. The statistical significance of all tests in this study was declared at P-value <5%. A total of 400 adult TB patients were participated. The mean age of study participants was 39.2±16.7 years, 55.5% were males and 79.8% were pulmonary tuberculosis cases. Regarding the treatment outcomes, 58% completed treatment, 27.5% cured, 9.3% were LTFU, 3.2% died, and 2.0% failed. The overall poor treatment outcome was 14.5% (95% CI: 11.1-17.9). Age (aOR = 1.02; 95%CI: 1.01-1.04), male gender (aOR = 1.82; 95% CI: 0.99-3.73), travel ≥ 10 kilometres to receive TB treatment (aOR = 6.55; 95% CI: 3.02-14.19), and lack of family support during the course of treatment (aOR = 3.03; 95% CI: 1.37-6.70), and bedridden baseline functional status (aOR = 4.40; 95% CI: 0.96-20.06) were factors associated with poor treatment outcome. Successful TB treatment outcome in this study area was below the national TB treatment success rate. To improve positive treatment outcomes, remote areas should be prioritized for TB interventions, and stakeholders in TB treatment and care should give special emphasis to adults over the age of 45 years, males, those who travel more than 10 kilometres to receive TB care, having bedridden baseline functional status and those who had no family support.

Antiretroviral Therapy and Retention in Care Experiences and Needs of Adolescents Living with HIV in Southern Ethiopia.

BACKGROUND: Adolescents with HIV are faced with challenges when taking care of their medication, which affects their treatment adherence. Therefore, this study aimed to explore the experiences and needs of adolescents living with HIV regarding their antiretroviral therapy adherence and retention in care in southern Ethiopia. METHODS: An inductive qualitative study design was applied to explore adolescents' experiences and needs regarding antiretroviral treatment adherence and retention in care in southern Ethiopia. Eighteen adolescents were selected from five HIV care and treatment facilities by purposive sampling. The interviews followed an interview guide, translated into the participants' national language. The interviews were transcribed verbatim and the first author developed a coding frame for the analysis by using NVivo software including meaning units and codes, which were discussed by all authors. Then, sub-themes and themes were identified and analyzed by qualitative content analysis. RESULTS: The results were described in two themes: barriers and facilitators for treatment adherence and retention in care. Barriers were described in seven subthemes and facilitators in three subthemes. Forgetting to take medication, hiding information, or non-disclosure of HIV status, being afraid to collect treatment drugs, being in an orphanage, and school activities were described as barriers while support from health care workers, families, personal motivation to cope with medication-related problems were described as facilitators for antiretroviral therapy adherence and retention in care. CONCLUSION: Adherence is a major challenge among adolescents living with HIV in Ethiopia, with barriers that are unique to this age group and their living conditions. Therefore, interventions should be targeted to address privacy barriers, stigma, and lack of support.

Evaluation of implementation and effectiveness of digital adherence technology with differentiated care to support tuberculosis treatment adherence and improve treatment outcomes in Ethiopia: a study protocol for a cluster randomised trial.

BACKGROUND: Digital adherence technologies (DATs) are recommended to support patient-centred, differentiated care to improve tuberculosis (TB) treatment outcomes, but evidence that such technologies improve adherence is limited. We aim to implement and evaluate the effectiveness of smart pillboxes and medication labels linked to an adherence data platform, to create a differentiated care response to patient adherence and improve TB care among adult pulmonary TB participants. Our study is part of the Adherence Support Coalition to End TB (ASCENT) project in Ethiopia. METHODS/DESIGN: We will conduct a pragmatic three-arm cluster-randomised trial with 78 health facilities in two regions in Ethiopia. Facilities are randomised (1:1:1) to either of the two intervention arms or standard of care. Adults aged ≥ 18 years with drug-sensitive (DS) pulmonary TB are enrolled over 12 months and followed-up for 12 months after treatment initiation. Participants in facilities randomised to either of the two intervention arms are offered a DAT linked to the web-based ASCENT adherence platform for daily adherence monitoring and differentiated response to patient adherence for those who have missed doses. Participants at standard of care facilities receive routine care. For those that had bacteriologically confirmed TB at treatment initiation and can produce sputum without induction, sputum culture will be performed approximately 6 months after the end of treatment to measure disease recurrence. The primary endpoint is a composite unfavourable outcome measured over 12 months from TB treatment initiation defined as either poor end of treatment outcome (lost to follow-up, death, or treatment failure) or treatment recurrence measured 6 months after the scheduled end of treatment. This study will also evaluate the effectiveness, feasibility, and cost-effectiveness of DAT systems for DS-TB patients. DISCUSSION: This trial will evaluate the impact and contextual factors of medication label and smart pillbox with a differentiated response to patient care, among adult pulmonary DS-TB participants in Ethiopia. If successful, this evaluation will generate valuable evidence via a shared evaluation framework for optimal use and scale-up. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR202008776694999, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=12241 , registered on August 11, 2020.