Financial burden of tuberculosis diagnosis and treatment for patients in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Despite the diagnosis and treatment of tuberculosis (TB) given free of charge in many high-burden countries, the costs that patients face in the cascade of care remain a major concern. Here, we aimed to investigate the financial burden of TB diagnosis and treatment for people with TB in Ethiopia. METHOD: For this systematic review and meta-analysis, we searched PubMed/MEDLINE, Embase, and Cochrane Center for Clinical Trials from December 1 2022 to 31 June 2023 for articles reporting the cost of diagnosis and treatment for patients regardless of their age with all forms of TB in Ethiopia. Major study outcomes were catastrophic costs, direct (out-of-pocket) pre-diagnosis, medical cost, and post-diagnosis costs, indirect (income loss) costs, coping costs, and total costs. We have used a threshold of 20% to define catastrophic costs. We used random-effects meta-analyses to calculate summary estimates of costs. R-studio software was used for analysis. The study is registered with PROSPERO: CRD42023387687. RESULT: Twelve studies, with a total of 4792 patients with TB, were included in our analysis. At the 20% threshold of total expenses, 51% of patients (2301 participants from 5 studies, 95% CI: 36-65%, I2 = 97%) faced catastrophic costs due to bacteriologically confirmed drug-sensitive pulmonary TB. Private facility diagnosis, drug-resistance TB, TB-HIV co-infection, hospitalization, and occupation were found to be associated with catastrophic costs. Reduction in the total cost spent by the patients was associated with digital adherence interventions, community-based direct observed therapy, short-course MDR-TB treatment regimens, and active case-finding. Pre-diagnosis costs had a positive correlation with diagnosis delays and the number of facilities visited until diagnosis. Post-diagnosis costs had a positive correlation with rural residence and inpatient treatments. CONCLUSION: Irrespective of a national policy of free TB service, more than half of TB patients are suffering catastrophic costs due to drug-sensitive pulmonary TB in Ethiopia and most of the patients spend a lot of money during the pre-diagnosis period and intensive phase, but declined drastically over time. Active case-finding, digital adherence interventions, community-based treatment, and comprehensive health insurance coverage have the potential to minimize the financial burden of TB diagnosis and treatment.

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.

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.

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.

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.