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.

Factors Determining Treatment Success in Children with Drug-Sensitive Tuberculosis in Ethiopia: A Three-Year Retrospective Analysis.

This study in the Amhara and Oromia regions of Ethiopia assessed the outcomes of tuberculosis (TB) treatment among children younger than 15 years. Retrospective data were collected on treatment outcomes and their determinants for children with TB for the cohorts of 2012-2014 enrolled in 40 hospitals and 137 health centers. Chi-square tests, t-tests, and logistic regression were used for the analysis. Of 2,557 children registered, 1,218 (47.6%) had clinically diagnosed pulmonary TB, 1,100 (43%) had extrapulmonary TB, and 277 (8.9%) had bacteriologically confirmed TB. Among all cases, 2,503 (97.9%) were newly diagnosed and 178 (7%) were HIV positive. Two-thirds of the children received directly observed treatment (DOT) in health centers and the remaining one-third, in hospitals. The treatment success rate (TSR) was 92.2%, and the death rate was 2.8%. The childhood TSR was high compared with those reported in focal studies in Ethiopia, but no national TSR report for children exists for comparison. Multivariate analysis showed that being older-5-9 years (adjusted odds ratio [AOR], 95% CI: 2.53, 1.30-4.94) and 10-14 years (AOR, 95% CI: 2.71, 1.40-5.26)-enrolled in DOT in a health center (AOR, 95% CI: 2.51, 1.82-3.48), and HIV negative (AOR, 95% CI: 1.77, 1.07-2.93) were predictors of treatment success, whereas underdosing during the intensive phase of treatment (AOR, 95% CI: 0.54, 0.36-0.82) was negatively correlated with treatment success. We recommend more research to determine if intensive monitoring of children with TB, dosage adjustment of anti-TB drugs based on weight changes, and training of health workers on dosage adjustment might improve treatment outcomes.

Use of indicators of standards of care to improve tuberculosis program management in Ethiopia.

BACKGROUND: Systematic monitoring of health programs and on-site mentoring of health workers are essential for the success of health care. This operations research was designed to measure the effectiveness of a new mentorship and supervisory tool for supervisors. METHODS: In 2011 the Help Ethiopia Address the Low TB Performance (HEAL TB) Project used WHO or national TB indicators as standards of care (SOC) for baseline assessment, progress monitoring, gap identification, assessment of health workers' capacity-building needs, and data quality assurance. Cut-off points were selected for poor, average, and best performers for each indicator. In this analysis we present results from 10 zones (of 28) in which 1,165 health facilities were supported from 2011 through 2015. Other zones were excluded from the analysis because they entered the project later. The data were collected by trained mentors/supervisors and entered into Microsoft Excel. We used rates and ratios to show the impact of the intervention. RESULTS: The improvement in the median composite score of 13 selected major indicators (out of 22) over four years was significant (p = 0.000). The proportion of health facilities with 100% data accuracy for all forms of TB was 55.1% at baseline and reached 96.5%. In terms of program performance, the TB cure rate improved from 71% to 91.1%, while the treatment success rate increased from 88% to 95.3%. In the laboratory area, where there was previously no external quality assurance (EQA) for sputum microscopy, 1,165 health facilities now have quarterly EQA, and 96.1% of the facilities achieved a ≥ 95% concordance rate in blinded rechecking. CONCLUSION: The SOC approach for supervision was effective for measuring progress, enhancing quality of services, identifying capacity needs, and serving as a mentorship and an operational research tool.

Vitamin D deficiency among smear positive pulmonary tuberculosis patients and their tuberculosis negative household contacts in Northwest Ethiopia: a case-control study.

BACKGROUND: Vitamin D is a fat-soluble vitamin that increases the immunity against tuberculosis (TB), decreases the re-activation of latent TB and reduces the severity of active TB disease. Epidemiological studies on the prevalence of vitamin D deficiency, and its association with TB showed inconsistent results in different countries. This study was aimed to determine the prevalence of vitamin D deficiency and its association with TB in Northwest Ethiopia. METHODS: A case-control study was conducted among smear positive pulmonary tuberculosis patients and their household contacts without symptoms suggestive of TB. Study participants were recruited at 11 TB diagnostic health facilities in North and South Gondar zones of Amhara region between May 2013 and April 2015. The spot-morning-spot sputum samples and 5 ml blood sample were collected prior to commencing TB treatment for the diagnosis of TB and serum vitamin D assay, respectively. The diagnosis of TB was performed using smear microscopy and GeneXpert. Serum vitamin D level was analyzed using VIDAS 25 OH Vitamin D Total testing kits (Biomerieux, Marcy I'Etoile, France) on mini VIDAS automated immunoassay platform. Vitamin D status was interpreted as deficient (<20 ng/ml), insufficient (20-29 ng/ml), sufficient (30-100 ng/ml) and potential toxicity (>100 ng/ml). RESULTS: Of the total study participants, 134 (46.2%) were vitamin D deficient, and only 56 (19.3%) had sufficient vitamin D level. A total of 59 (61.5%) TB patients and 75 (38.7%) non TB controls were vitamin D deficient. Results of multivariate logistic regression analyses showed a significantly higher vitamin D deficiency among tuberculosis cases (p < 0.001), females (p = 0.002), and urban residents (p < 0.001) than their respective comparison groups. Moreover, age groups of 35-44 (p = 0.001), 45-54 (p = 0.003) and ≥55 (p = 0.001) years had significantly higher vitamin D deficiency compared with age group <15 years. CONCLUSIONS: Vitamin D deficiency is highly prevalent among TB patients and non TB controls in Ethiopia where there is year round abundant sunshine. Study participants with tuberculosis, females, older age groups, and urban residents had significantly higher prevalence of vitamin D deficiency. These findings warrant further studies to investigate the role of vitamin D supplementation in the prevention and treatment of tuberculosis in high TB burden countries like Ethiopia.

The experience of scaling up a decentralized, ambulatory model of care for management of multidrug-resistant tuberculosis in two regions of Ethiopia.

Strong strategies, including proven service delivery models, are needed to address the growing global threat of multidrug-resistant tuberculosis (MDR-TB) in low- and middle-income settings. The objective of this study was to assess the feasibility and effectiveness of the nationally approved ambulatory service delivery model for MDR-TB treatment in two regions of Ethiopia. We used routinely reported data to describe the process and outcomes of implementing an ambulatory model for MDR-TB services in a resource-limited setting. We compared percentage improvements in the number of MDR-TB diagnostic and treatment facilities, number of MDR-TB sputum samples processed per year, and MDR-TB cases ever enrolled in care between baseline and 2015. We also calculated interim and final treatment outcomes for patients who had completed at least 12 and 24 months of follow-up, respectively. Between 2012 and 2015, the number of MDR-TB treatment-initiating centers increased from 1 to 23. The number of sputum samples tested for MDR-TB increased 20-fold, from 662 to 14,361 per year. The backlog of patients on waiting lists was cleared. The cumulative number of MDR-TB patients put on treatment increased from 56 to 790, and the treatment success rate was 75%. Rapid expansion of the ambulatory model of MDR-TB care was feasible and achieved a high treatment success rate in two regions of Ethiopia. More effort is needed to sustain the gains and further decentralize services to the community level.

The Yield of Community-Based "Retrospective" Tuberculosis Contact Investigation in a High Burden Setting in Ethiopia.

OBJECTIVE: To determine the yield and determinants of retrospective TB contact investigation in selected zones in Ethiopia. MATERIALS AND METHODS: This was a community-based cross-sectional study conducted during June-October 2014.Trained lay providers performed symptom screening for close contacts of index cases with all types of TB registered for anti-TB treatment within the last three years. We used logistic regression to determine factors associated with TB diagnosis among the contacts. RESULTS: Of 272,441 close contacts of 47, 021 index cases screened, 13,886 and 2, 091 had presumptive and active TB respectively. The yield of active TB was thus 768/100, 000, contributing 25.4% of the 7,954 TB cases reported from the study zones over the study period. The yield was highest among workplace contacts (12,650/100, 000). Active TB was twice more likely among contacts whose index cases had been registered for TB treatment within the last 12 months compared with those who had been registered 24 or more months earlier (adjusted odds ratio, AOR: 1.77 95% CI 1.42-2.21). Sex or clinical type of TB in index cases was not associated with the yield. Smear negative (SS-) index cases (AOR: 1.74 955 CI 1.13-2.68), having index cases who registered for treatment within <12 months (AOR: 2.41 95% CI 1.51-3.84) and being household contact (AOR: 0.072 95% CI 0.01-0.52) were associated with the occurrence of active TB in children. CONCLUSIONS: The yield of retrospective contact investigation was about six times the case notification in the study zones, contributing a fourth of all TB cases notified over the same period. The yield was highest among workplace contacts and in those with recent past history of contact. Retrospective contact screening can serve as additional strategy to identify high risk groups not addressed through currently recommended screening approaches.

The additional yield of GeneXpert MTB/RIF test in the diagnosis of pulmonary tuberculosis among household contacts of smear positive TB cases.

OBJECTIVE: The objective of this study was to compare the diagnostic yield of GeneXpert MTB/RIF with Ziehl-Neelson (ZN) sputum smear microscopy among index TB cases and their household contacts. METHODS: A cross sectional study was conducted among sputum smear positive index TB cases and their household contacts in Northern Ethiopia. RESULTS: Of 353 contacts screened, 41 (11%) were found to have presumptive TB. GeneXpert test done among 39 presumptive TB cases diagnosed 14 (35.9%) cases of TB (one being rifampicin resistant), whereas the number of TB cases diagnosed by microscopy was only 5 (12.8%): a 64.3% increased positivity rate by GeneXpert versus ZN microscopy. The number needed to screen and number needed to test to diagnose a single case of TB was significantly lower with the use of GeneXpert than ZN microscopy. Of 119 index TB cases, GeneXpert test revealed that 106 (89.1%) and 5 (4.2%) were positive for rifampicin sensitive and rifampicin resistant TB, respectively. CONCLUSION: GeneXpert test led to increased TB case detection among household contacts in addition to its advantage in the diagnosis of Rifampicin resistance among contacts and index TB cases. There should be a consideration in using GeneXpert MTB/RIF as a point of care TB testing tool among high risk groups.

Uptake of Isoniazid Preventive Therapy among Under-Five Children: TB Contact Investigation as an Entry Point.

A child's risk of developing tuberculosis (TB) can be reduced by nearly 60% with administration of 6 months course of isoniazid preventive therapy (IPT). However, uptake of IPT by national TB programs is low, and IPT delivery is a challenge in many resource-limited high TB-burden settings. Routinely collected program data was analyzed to determine the coverage and outcome of implementation of IPT for eligible under-five year old children in 28 health facilities in two regions of Ethiopia. A total of 504 index smear-positive pulmonary TB (SS+) cases were reported between October 2013 and June 2014 in the 28 health facilities. There were 282 under-five children registered as household contacts of these SS+ TB index cases, accounting for 17.9% of all household contacts. Of these, 237 (84%) were screened for TB symptoms, and presumptive TB was identified in 16 (6.8%) children. TB was confirmed in 5 children, producing an overall yield of 2.11% (95% confidence interval, 0.76-4.08%). Of 221 children eligible for IPT, 64.3% (142) received IPT, 80.3% (114) of whom successfully completed six months of therapy. No child developed active TB while on IPT. Contact screening is a good entry point for delivery of IPT to at risk children and should be routine practice as recommended by the WHO despite the implementation challenges.

Decentralization of Acid Fast Bacilli (AFB) External Quality Assurance Using Blind Rechecking for Sputum Smear Microscopy in Ethiopia.

INTRODUCTION: Ethiopia achieved a rapid expansion of TB microscopic centers for acid fast bacilli (AFB). However, external quality assurance (EQA) services were, until recently, limited to few regional and sub-regional laboratories. In this paper, we describe the decentralization experience and the result of EQA using random blinded rechecking. MATERIALS AND METHODS: The routine EQA quarterly report was compiled and analyzed. A positive result by the microscopic center while the EQA center reported negative result is categorized as false positive (FP). A negative result by the microscopic center while the EQA center reported positive is considered false negative (FN). The reading of EQA centers was considered a gold standard to compute the sensitivity, specificity, positive predictive (PPV) and negative predictive values (NPV) of the readings of microscopic centers. RESULTS: We decentralized sputum smear AFB EQA from 4 Regional Laboratories (RRLs) to 82 EQA centers and enrolled 956 health facilities in EQA schemes. Enrollment of HFs in EQA was gradual because it required training and mentoring laboratory professionals, institutionalizing internal QA measures, equipping all HFs to perform diagnosis, and establishing more EQA centers. From 2012 to 2014 (Phase I), the FP rate declined from 0.6% to 0.2% and FN fell from as high as 7.6% to 1.6% in supported health facilities (HFs). In HFs that joined in Phase II, FN rates ranged from 5.6 to 7.3%. The proportion of HFs without errors has increased from 77.9% to 90.5% in Phase I HFs and from 82.9% to 86.9% in Phase II HFs. Overall sensitivity and specificity were 95.0% and 99.7%, respectively. PPV and NPV were 93.3% and 99.7%, respectively. CONCLUSION: Decentralizing blinded rechecking of sputum smear microscopy is feasible in low-income settings. While a comprehensive laboratory improvement strategy enhanced the quality of microscopy, laboratory professionals' capacity in slide reading and smear quality requires continued support.