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.

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.

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.

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.

Patient and health system delay among TB patients in Ethiopia: Nationwide mixed method cross-sectional study.

BACKGROUND: Effective tuberculosis (TB) control is the end result of improved health seeking by the community and timely provision of quality TB services by the health system. Rapid expansion of health services to the peripheries has improved access to the community. However, high cost of seeking care, stigma related TB, low index of suspicion by health care workers and lack of patient centered care in health facilities contribute to delays in access to timely care that result in delay in seeking care and hence increase TB transmission, morbidity and mortality. We aimed to measure patient and health system delay among TB patients in Ethiopia. METHODS: This is mixed method cross-sectional study conducted in seven regions and two city administrations. We used multistage cluster sampling to randomly select 40 health centers and interviewed 21 TB patients per health center. We also conducted qualitative interviews to understand the reasons for delay. RESULTS: Of the total 844 TB patients enrolled, 57.8% were men. The mean (SD) age was 34 (SD + 13.8) years. 46.9% of the TB patients were the heads of household, 51.4% were married, 24.1% were farmers and 34.7% were illiterate. The median (IQR) patient, diagnostic and treatment initiation delays were 21 (10-45), 4 (2-10) and 2 (1-3) days respectively. The median (IQR) of total delay was 33 (19-67) days; 72.3% (595) of the patients started treatment after 21 days of the onset of the first symptom. Poverty, cost of seeking care, protracted diagnostic and treatment initiation, inadequate community based TB care and lack of awareness were associated with delay. Community health workers reported that lack of awareness and the expectation that symptoms would resolve by themselves were the main reasons for delay. CONCLUSION: TB patients' delay in seeking care remains a challenge due to limited community interventions, cost of seeking care, prolonged diagnostics and treatment initiation. Therefore, targeted community awareness creation, cost reduction strategies and improving diagnostic capacity are vital to reduce delay in seeking TB care in Ethiopia.

Stigma matters in ending tuberculosis: Nationwide survey of stigma in Ethiopia.

BACKGROUND: Tuberculosis (TB) affects, and claims the lives of, millions every year. Despite efforts to find and treat TB, about four million cases were missed globally in 2017. Barriers to accessing health care, inadequate health-seeking behavior of the community, poor socioeconomic conditions, and stigma are major determinants of this gap. Unfortunately, TB-related stigma remains unexplored in Ethiopia. METHODS: This mixed methods survey was conducted using multistage cluster sampling to identify 32 districts and 8 sub-cities, from which 40 health centers were randomly selected. Twenty-one TB patients and 21 family members were enrolled from each health center, and 11 household members from each community in the catchment population. RESULTS: A total of 3463 participants (844 TB patients, 836 from their families, and 1783 from the general population) were enrolled for the study. The mean age and standard deviation were 34.3 ± 12.9 years for both sexes (34.9 ± 13.2 for men and 33.8 ± 12.5 for women). Fifty percent of the study participants were women; 32.1% were illiterate; and 19.8% came from the lowest wealth quintile. The mean stigma score was 18.6 for the general population, 20.5 for families, and 21.3 for TB patients. The general population of Addis Ababa (AOR: 0.1 [95% CI: 0.06-0.17]), those educated above secondary school (AOR: 0.58 [95% CI: 0.39-0.87]), and those with a high score for knowledge about TB (AOR: 0.62 [95% CI: 0.49-0.78]) had low stigma scores. Families of TB patients who attended above secondary school (AOR: 0.37 [95% CI: 0.23-0.61]) had low stigma scores. TB patients educated above secondary school (AOR: 0.61 [95% CI: 0.38-0.97]) had lower stigma scores, while those in the first (AOR: 1.93: 95% CI 1.05-3.57) and third quintiles (AOR: 1.81: 95% CI: 1.08-3.05) had stigma scores twice as high as those in the highest quintile. Fear of job loss (32.5%), isolation (15.3%), and feeling avoided (9.3%) affected disclosure about TB. CONCLUSIONS: More than a third of Ethiopians have high scores for TB-related stigma, which were associated with educational status, poverty, and lack of awareness about TB. Stigma matters in TB prevention, care, and treatment and warrants stigma reduction interventions.

High urban tuberculosis case notification rates can be misleading: evidence from an urban setting in Ethiopia.

BACKGROUND: Tuberculosis (TB) is a major public health problem. Its magnitude the required interventions are affected by changes in socioeconomic condition and urbanization. Ethiopia is among the thirty high burden countries with increasing effort to end TB. We aimed to describe the case notification rate (CNR) for urban tuberculosis (TB) and estimate the percentage of TB patients who are not from the catchment population. METHODS: This cross-sectional study used data from TB registers from 2014/15 to 2017/18. We calculated the CNR and treatment success rate for the study area. RESULTS: Of 2892 TB cases registered, 2432 (84%) were from Adama City, while 460 (16%) were from other sites. The total TB CNR (including TB cases from Adama and other sites) was between 153 and 218 per 100,000 population. However, the adjusted TB CNR (excluding cases outside Adama City) was lower, between 135 and 179 per 100,000. Of 1737 TB cases registered, 1652 (95%) were successfully treated. About 16% of TB cases notified contributing to CNR of 32 per 100,000 population is contributed by TB cases coming from outside of Adama city. The CNR of 32 per 100,000 population (ranging from 18 to 46 per 100,000) for Adama City was from the patients that came from the surrounding rural areas who sought care in the town. CONCLUSION: Although the TB CNR in Adama City was higher than the national CNR, about one-fifth of TB cases came from other sites-which led to overestimating the urban CNR and underestimating the CNR of neighboring areas. TB programs should disaggregate urban TB case notification data by place of residence to accurately identify the proportion of missed cases.

Knowledge, attitudes, beliefs, and stigma related to latent tuberculosis infection: a qualitative study among Eritreans in the Netherlands.

BACKGROUND: Tailored and culturally appropriate latent tuberculosis (TB) infection screening and treatment programs, including interventions against TB stigma, are needed to reduce TB incidence in low TB incidence countries. However, we lack insights in stigma related to latent TB infection (LTBI) among target groups, such as asylum seekers and refugees. We therefore studied knowledge, attitudes, beliefs, and stigma associated with LTBI among Eritrean asylum seekers and refugees in the Netherlands. METHODS: We used convenience sampling to interview adult Eritrean asylum seekers and refugees: 26 semi-structured group interviews following TB and LTBI related health education and LTBI screening, and 31 semi-structured individual interviews with Eritreans during or after completion of LTBI treatment (November 2016-May 2018). We used a thematic analysis to identify, analyse and report patterns in the data. RESULTS: Despite TB/LTBI education, misconceptions embedded in cultural beliefs about TB transmission and prevention persisted. Fear of getting infected with TB was the cause of reported enacted (isolation and gossip) and anticipated (concealment of treatment and self-isolation) stigma by participants on LTBI treatment. CONCLUSION: The inability to differentiate LTBI from TB disease and consequent fear of getting infected by persons with LTBI led to enacted and anticipated stigma comparable to stigma related to TB disease among Eritreans. Additional to continuous culturally sensitive education activities, TB prevention programs should implement evidence-based interventions reducing stigma at all phases in the LTBI screening and treatment cascade.

Delays to anti-tuberculosis treatment intiation among cases on directly observed treatment short course in districts of southwestern Ethiopia: a cross sectional study.

BACKGROUND: Delayed tuberculosis (TB) diagnosis and treatment increase morbidity, mortality, expenditure, and transmission in the community. This study assessed patient and provider related delays to diagnosis and treatment of TB. METHODS: A cross-sectional study was conducted among 735 new adult TB cases registered between January to December 2015 in 10 woredas equivalent to districts of southwestern Ethiopia. Data were collected through face-to-face interview of patients within the first 2 months of treatment initiation. Delay in days was tracked at three intervals: between onset of symptoms and self-presentation (Patient delay), Self-presentation to treatment initiation (Provider delay) and total delay. Days elapsed beyond median were used to define the delays. Bivariate and multiple logistic regression models were fit to identify predictors of delays and statistical significance was judged at p < 0.05. RESULT: The median (inter-quartile range) of patient, provider and total delays were 25 (IQR;15-36), 22 (IQR:9-48) and 55 (IQR:32-100) days, respectively. More than half (54.6%) of the total delay was attributed to health system. Prior self-treatment [adjusted Odds Ratio (aOR)]: 1.72, 95% confidence interval [CI]:1.07-2.75), HIV co-infection (aOR:1.8, 95% CI: 1.05-3.10) and extra-pulmonary TB (aOR: 1.54,95% CI:1.03-2.29) were independently associated with increased odds of patient delay. On the other hand initial presentation to health posts or private clinics (aOR: 1.42, 95% CI: 1.01, 2.0) and patient delay (aOR: 1.81, 95% CI: 1.33-2.50) significantly predicted longer provider delay. Finally, having extra pulmonary TB (aOR: 1.6, 95% CI: 1.07-2.38), prior consultation of traditional healer (aOR: 3.72, 95% CI: 1.01-13.77) and use of holy water (aOR: 2.73, 95% CI: 1.11, 6.70) independently predicted longer total delay. CONCLUSION: Tuberculosis patients waited too long time to initiate anti-TB treatment reflecting longer periods of morbidity and disease transmission. The delays are attributed to the patient, disease and health system related factors. Hence, improving community awareness, involving informal providers, health extension workers and TB treatment supporters can reduce the patient delay. Similarly, cough screening and improving diagnostic efficiencies of healthcare facilities should be in place to reduce the provider delays.

Improvement in tuberculosis infection control practice via technical support in two regions of Ethiopia.

BACKGROUND: Globally recommended measures for comprehensive tuberculosis (TB) infection control (IC) are inadequately practiced in most health care facilities in Ethiopia. The aim of this study was to assess the extent of implementation of TB IC measures before and after introducing a comprehensive technical support package in two regions of Ethiopia. METHODS: We used a quasi-experimental design, whereby a baseline assessment of TB IC practices in 719 health care facilities was conducted between August and October 2013. Based on the assessment findings, we supported implementation of a comprehensive package of interventions. Monitoring was done on a quarterly basis, and one-year follow-up data were collected on September 30, 2014. We used the Student's t-test and chi-squared tests, respectively, to examine differences before and after the interventions and to test for inter-regional and inter-facility associations. RESULTS: At baseline, most of the health facilities (69%) were reported to have separate TB clinics. In 55.2% of the facilities, it was also reported that window opening was practiced. Nevertheless, triaging was practiced in only 19.3% of the facilities. Availability of an IC committee and IC plan was observed in 29.11 and 4.65% of facilities, respectively. Health care workers were nearly three times as likely to develop active TB as the general population. After 12 months of implementation, availability of a separate TB room, TB IC committee, triage, and TB IC plan had increased, respectively, by 18, 32, 44, and 51% (p < 0.001). CONCLUSIONS: After 1 year of intervention, the TB IC practices of the health facilities have significantly improved. However, availability of separate TB rooms and existence of TB IC committees remain suboptimal. The burden of TB among health care workers is higher than in the general population. TB IC measures must be strengthened to reduce TB transmission among health workers.

Delays to treatment initiation is associated with tuberculosis treatment outcomes among patients on directly observed treatment short course in Southwest Ethiopia: a follow-up study.

BACKGROUND: Despite reported long delays to initiate anti-TB treatment and poor outcomes in different parts of Ethiopia and elsewhere, evidences on association between the delay and treatment outcomes are scanty. METHODS: A follow up study among 735 new TB cases registered at health facilities in districts of southwest Ethiopia was conducted from January 2015 to June 2016. Patients reported days elapsed between onset of illness and treatment commencement of 30 days cutoff was considered to ascertain exposure. Thus, those elapsed beyond 30 days to initiate anti-TB treatment since onset of illness were exposed and otherwise non-exposed. The cases were followed until earliest outcome was observed. Treatment outcomes was ascertained as per the World Health Organization standard definitions and dichotomized into 'successful' when cured or treatment completed and 'unsuccessful' when lost to follow-up or died or treatment failure. Bivariate and multiple log-binomial models were fitted to identify predictors of unsuccessful outcomes. RESULTS: The overall treatment success among the treatment cohort was 89.7% (88.4% vs. 94.2%, p = 0.01 respectively among those initiated treatment beyond and within of 30 days of onset of illness. Higher risk of unsuccessful outcome was predicted by treatment initiation beyond 30 days of onset [Adjusted Relative Risk (ARR) = 1.92, 95%CI:1.30, 2.81], HIV co-infection (ARR = 2.18, 95%CI:1.47, 3.25) and received treatment at hospital (ARR = 3.73, 95%CI:2.23, 6.25). On the other hand, lower risk of unsuccessful outcome was predicted by weight gain (ARR = 0.40, 95%CI:0.19, 0.83) and sputum smear negative conversion (ARR = 0.17,95% CI:0.09, 0.33) at the end of second month treatment. CONCLUSION: Higher risk of unsuccessful outcome is associated with prolonged days elapsed between onset of illness and treatment commencement. Hence, promotion of early care seeking, improving diagnostic and case holding efficiencies of health facilities and TB/HIV collaborative interventions can reduce risk of unsuccessful outcome.

Caregiver-reported antiretroviral therapy non-adherence during the first week and after a month of treatment initiation among children diagnosed with HIV in Ethiopia.

To achieve optimal virologic suppression for children undergoing antiretroviral therapy (ART), adherence must be excellent. This is defined as taking more than 95% of their prescribed doses. To our knowledge, no study in Ethiopia has evaluated the level of treatment adherence at the beginning of the child's treatment. Our aim was therefore to evaluate caregiver-reported ART non-adherence among children and any predictors for this during the early course of treatment. We conducted a prospective cohort study of 306 children with HIV in eight health facilities in Ethiopia who were registered at ART clinics between 20 December 2014 and 20 April 2015. The adherence rate reported by caregivers during the first week and after a month of treatment initiation was 92.8% and 93.8%, respectively. Our findings highlight important predictors of non-adherence. Children whose caregivers were not undergoing HIV treatment and care themselves were less likely to be non-adherent during the first week of treatment (aOR = 0.17, 95% CI: 0.04, 0.71) and the children whose caregivers did not use a medication reminder after one month of treatment initiation (aOR = 5.21, 95% CI: 2.23, 12.16) were more likely to miss the prescribed dose. Moreover, after one month of the treatment initiation, those receiving protease inhibitor (LPV/r) or ABC-based treatment regimens were more likely to be non-adherent (aOR = 12.32, 95% CI: 3.25, 46.67). To promote treatment adherence during ART initiation in children, particular emphasis needs to be placed on a baseline treatment regimen and ways to issue reminders about the child's medication to both the health care system and caregivers. Further, large scale studies using a combination of adherence measuring methods upon treatment initiation are needed to better define the magnitude and predictors of ART non-adherence in resource-limited settings.

Tuberculosis treatment outcomes of six and eight month treatment regimens in districts of Southwestern Ethiopia: a comparative cross-sectional study.

BACKGROUND: A switch of continuation phase tuberculosis (TB) treatment regimen from Ethambutol (E) and Isoniazid (H) combination for 6 months (6EH) to Rifampicin (R) and Isoniazid (H) combination for 4 months (4RH) was recommended. However, the effect of the regimen switch in Ethiopian setting is not known. METHODS: A comparative cross-sectional study among 790 randomly selected new cases of TB (395 each treated with 4RH and 6EH during the continuation phase) was conducted in nine health centers and one hospital in three zones in southwestern Ethiopia. Data were abstracted from the standard unit TB register composed of standard case and treatment outcome definitions. Data were analyzed using STATA version 13 where binary logistic regression was fitted to identify independent predictors of unsuccessful treatment outcomes at 5 % significance level. RESULTS: Over all, 695 (88 %) of the patients had a successful treatment outcome with statistically significant difference (85.3 % vs 90.6 %, p = 0.02) among the 6HE and 4RH regimens, respectively. After adjusting for confounders, 4RH continuation phase treatment regimen adjusted odds ratio (AOR) [(95 % confidence interval (CI)) 0.55 (0.34,0.89)], age [AOR (95 % CI 1.02 (1.001,1.022)], rural residence [AOR (95 % CI) 2.1 (1.18,3.75)] Human Immunodeficiency virus (HIV) positives [AOR (95 % CI) 2.39 (1.12,5.07)] and increased weight at the end of the second month [AOR (95 % CI 0.28 (0.11,0.72)] independently predicted treatment outcome. CONCLUSION: The switch of continuation phase TB treatment regimen from 6EH to 4RH has brought better treatment outcomes which imply applicability of the recommendation in high prevalent and resource constrained settings. Therefore, it should be maintained and augmented through further studies on its impact among the older, rural residents and HIV positives.

Prevention and treatment of cardiovascular disease in Ethiopia: a cost-effectiveness analysis.

BACKGROUND: The coverage of prevention and treatment strategies for ischemic heart disease and stroke is very low in Ethiopia. In view of Ethiopia's meager healthcare budget, it is important to identify the most cost-effective interventions for further scale-up. This paper's objective is to assess cost-effectiveness of prevention and treatment of ischemic heart disease (IHD) and stroke in an Ethiopian setting. METHODS: Fifteen single interventions and sixteen intervention packages were assessed from a healthcare provider perspective. The World Health Organization's Choosing Interventions that are Cost-Effective model for cardiovascular disease was updated with available country-specific inputs, including demography, mortality and price of traded and non-traded goods. Costs and health benefits were discounted at 3 % per year. Incremental cost-effectiveness ratios are reported in US$ per disability adjusted life year (DALY) averted. Sensitivity analysis was undertaken to assess robustness of our results. RESULTS: Combination drug treatment for individuals having >35 % absolute risk of a CVD event in the next 10 years is the most cost-effective intervention. This intervention costs US$67 per DALY averted and about US$7 million annually. Treatment of acute myocardial infarction (AMI) (costing US$1000-US$7530 per DALY averted) and secondary prevention of IHD and stroke (costing US$1060-US$10,340 per DALY averted) become more efficient when delivered in integrated packages. At an annual willingness-to-pay (WTP) level of about US$3 million, a package consisting of aspirin, streptokinase, ACE-inhibitor and beta-blocker for AMI has the highest probability of being most cost-effective, whereas as WTP increases to > US$7 million, combination drug treatment to individuals having >35 % absolute risk stands out as the most cost-effective strategy. Cost-effectiveness ratios were relatively more sensitive to halving the effectiveness estimates as compared with doubling the price of drugs and laboratory tests. CONCLUSIONS: In Ethiopia, the escalating burden of CVD and its risk factors warrants timely action. We have demonstrated that selected CVD intervention packages could be scaled up at a modest budget increase. The level of willingness-to-pay has important implications for interventions' probability of being cost-effective. The study provides valuable evidence for setting priorities in an essential healthcare package for CVD in Ethiopia.

Pre-ART retention in care and prevalence of tuberculosis among HIV-infected children at a district hospital in southern Ethiopia.

BACKGROUND: The Ethiopian epidemic is currently on the wane. However, the situation for infected children is in some ways lagging behind due to low treatment coverage and deficient prevention of mother-to-child transmission. Too few studies have examined HIV infected children presenting to care in low-income countries in general. Considering the presence of local variations in the nature of the epidemic a study in Ethiopia could be of special value for the continuing fight against HIV. The aim of this study is to describe the main characteristics of children with HIV presenting to care at a district hospital in a resource-limited area in southern Ethiopia. The aim was also to analyse factors affecting pre-ART loss to follow-up, time to ART-initiation and disease stage upon presentation. METHODS: This was a prospective cohort study. The data analysed were collected in 2009 for the period January 2003 through December 2008 at Arba Minch Hospital and additional data on the ART-need in the region were obtained from official reports. RESULTS: The pre-ART loss to follow-up rate was 29.7%. Older children (10-14 years) presented in a later stage of their disease than younger children (76.9% vs. 45.0% in 0-4 year olds, chi-square test, χ2 = 8.8, P = 0.01). Older girls presented later than boys (100.0% vs. 57.1%, Fisher's exact test, P = 0.02). Children aged 0-4 years were more likely to be lost to follow-up (40.0 vs. 21.8%, chi-square test, χ2 = 5.4, P = 0.02) and had a longer time to initiate ART (Cox regression analysis, HR: 0.50, 95% CI: 0.25-0.97, P = 0.04, controlling for sex, place of residence, enrollment phase and WHO clinical stage upon presentation). Neither sex was overrepresented in the sample. Tuberculosis prevalence upon presentation and previous history of tubercolosis were 14.5% and 8% respectively. CONCLUSIONS: The loss to follow-up is alarmingly high and children present too late. Further research is needed to explore specific causes and possible solutions.

Intervention fidelity and factors affecting the process of implementing a mobile phone text messaging intervention among adolescents living with HIV: a convergent mixed-methods study in southern Ethiopia.

OBJECTIVE: To assess the intervention fidelity and explore contextual factors affecting the process of implementing a mobile phone text messaging intervention in improving adherence to and retention in care among adolescents living with HIV, their families and their healthcare providers in southern Ethiopia. DESIGN: A convergent mixed-methods design guided by the process evaluation theoretical framework and the Reach, Effectiveness, Adoption, Implementation and Maintenance framework was used alongside a randomised controlled trial to examine the fidelity and explore the experiences of participants in the intervention. SETTING: Six hospitals and five health centres provide HIV treatment and care to adolescents in five zones in southern Ethiopia. PARTICIPANTS: Adolescents (aged 10-19), their families and their healthcare providers. INTERVENTION: Mobile phone text messages daily for 6 months or standard care (control). RESULTS: 153 participants were enrolled in the process evaluation. Among the 153 enrolled in the intervention arm, 78 (49.02%) were male and 75 (43.8%) were female, respectively. The mean and SD age of the participants is 15 (0.21). The overall experiences of implementing the text messages reminder intervention were described as helpful in terms of treatment support for adherence but had room for improvement. During the study, 30 700 text messages were sent, and fidelity was high, with 99.4% successfully delivered text messages during the intervention. Barriers such as failed text messages delivery, limitations in phone ownership and technical limitations affected fidelity. Technical challenges can hinder maintenance, but a belief in the future of digital communication permeates the experiences of the text message reminders. CONCLUSIONS: Overall fidelity was high, and participants' overall experiences of mobile phone text messages were expressed as helpful. Contextual factors, such as local telecommunications networks and local electric power, as well as technical and individual factors must be considered when planning future interventions. TRIAL REGISTRATION NUMBER: PACTR202107638293593.

Mapping the existing body of knowledge on new and repurposed TB vaccine implementation: A scoping review.

There is global consensus on the urgent need for a safe and effective TB vaccine for adults and adolescents to improve global TB control, and encouragingly, several promising candidates have advanced to late-stage trials. Significant gaps remain in understanding the critical factors that will facilitate the successful implementation of new and repurposed TB vaccines in low- and middle-income countries (LMICs), once available. By synthesizing the existing body of knowledge, this review offers comprehensive insights into the current state of research on implementation of these adult and adolescent vaccines. This review explores four key dimensions: (1) epidemiological impact, (2) costing, cost-effectiveness, and/or economic impact, (3) acceptability, and the (4) feasibility of implementation; this includes implementation strategies of target populations, and health system capabilities. Results indicate that current research primarily consists of epidemiological and costing/cost-effectiveness/economic studies in India, China, and South Africa, mainly modelling with M72/AS01, BCG revaccination, and hypothetical vaccines. Varying endpoints, vaccine efficacies, and vaccination coverages were used. Globally, new, and repurposed TB vaccines are estimated to save millions of lives. Economically, these vaccines also demonstrate promise with expected cost-effectiveness in most countries. Projected outcomes were dependent on vaccine characteristics, target population, implementation strategy, timing of roll out, TB burden/country context, and vaccination coverage. Potential barriers for vaccine acceptability included TB-related stigma, need for a second dose, and cost, while low pricing, community and civil society engagement and heightened public TB awareness were potential enablers in China, India, and South Africa. Potential implementation strategies considered spanned from mass campaigns to integration within existing vaccine programs and the primary target group studied was the general population, and adults and adolescents. In conclusion, future research must have broader geographical representations to better understand what is needed to inform tailored vaccine programs to accommodate diverse country contexts and population groups to achieve optimal implementation and impact. Furthermore, this review underscores the scarcity of research on acceptability of new and repurposed TB vaccines and their delivery among potential beneficiaries, the most promising implementation strategies, and the health system capabilities necessary for implementation. The absence of this knowledge in these areas emphasizes the crucial need for future research to ensure effective TB vaccine implementation in high burden settings worldwide.

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.

Diagnostic accuracy, feasibility and acceptability of stool-based testing for childhood tuberculosis.

Background: Childhood tuberculosis (TB) diagnosis remains challenging, partly because children cannot provide sputum. This study evaluated the diagnostic accuracy of the Simple One-Step (SOS) stool method with Xpert MTB/RIF Ultra (Xpert-Ultra) for childhood TB compared to culture and Xpert-Ultra on a respiratory sample (RS) and clinical diagnosis. It also assessed the feasibility and acceptability of stool testing according to laboratory staff, and caregivers' sample preference. Methods: We enrolled children (≤10 years) with presumptive pulmonary tuberculosis in Ethiopia. RS was tested using Xpert-Ultra and culture; stool samples were tested using the SOS stool method with Xpert-Ultra. Laboratory staff and caregivers' opinions were assessed using standardised questionnaires. Results: Of the 898 children enrolled, 792, 832 and 794 were included for assessing the diagnostic accuracy of SOS stool with Xpert-Ultra against culture, RS Xpert-Ultra and clinical diagnosis, respectively, yielding sensitivity estimates for SOS stool with Xpert-Ultra of 69.1% (95% confidence interval (CI) 56.0-79.7%), 76.8% (95% CI 64.2-85.9%) and 59.0% (95% CI 47.9-69.2%), respectively. The specificity was ≥98.8% for all comparisons. The rate of non-determinate test results was 2.8% after one repeat test. According to laboratory staff, stool collection was feasible and acceptable and the SOS stool method was easy to perform. Most caregivers (75%) preferred stool for TB diagnosis over RS. Conclusion: This study shows that SOS stool Xpert-Ultra testing offers a good alternative to RS testing for TB in children who cannot spontaneously produce a sputum sample and would otherwise need to undergo invasive procedures to obtain RS for diagnosis.

Lessons from a decade of adult vaccine rollout in low- and middle-income countries: a scoping review.

INTRODUCTION: The historical focus of vaccines on child health coupled with the advent of novel vaccines targeting adult populations necessitates exploring strategies for adult vaccine implementation. AREAS COVERED: This scoping review extracts insights from the past decade's experiences introducing adult vaccines in low- and middle-income countries. Among 25 papers reviewed, 19 focused on oral cholera vaccine, 2 on Meningococcal A vaccines, 2 on tetanus toxoid vaccine, 1 on typhoid vaccine, and 1 on Ebola vaccine. Aligned with WHO's Global Framework for New TB Vaccines for Adults and Adolescents, our findings center on vaccine availability, accessibility, and acceptance. EXPERT OPINION: Availability findings underscore the importance of understanding disease burden for prioritization, multi-sectoral collaboration during planning, and strategic resource allocation and coordination. Accessibility results highlight the benefits of leveraging existing health infrastructure and adequately training healthcare workers, and contextually tailoring vaccine delivery approaches to reach challenging sub-groups like working male adults. Central to fostering acceptance, resonant sensitization, and communication campaigns engaging the communities and utilizing trusted local leaders countered rumors and increased awareness and uptake. As we approach the introduction of a new adult TB vaccine, insights from this review equips decision-makers with key evidence-based recommendations to support successful and equitable vaccinations targeting adults.