The Simple One-Step (SOS) Stool Processing Method for Use with the Xpert MTB/RIF Assay for a Child-Friendly Diagnosis of Tuberculosis Closer to the Point of Care.

Young children cannot easily produce sputum for diagnosis of pulmonary tuberculosis (TB). Alternatively, Mycobacterium tuberculosis complex bacilli can be detected in stool by using the Xpert MTB/RIF (Ultra) assay (Xpert). Published stool processing methods contain somewhat complex procedures and require additional supplies. The aim of this study was to develop a simple one-step (SOS) stool processing method based on gravity sedimentation only, similar to Xpert testing of sputum samples, for the detection of M. tuberculosis in stool samples. We first assessed whether the SOS stool method could provide valid Xpert results without the need for bead-beating, dilution, and filtration steps. We concluded that this was the case, and we then validated the SOS stool method by testing spiked stool samples. By using the SOS stool method, 27 of the 29 spiked samples gave valid Xpert results, and M. tuberculosis was recovered from all 27 samples. The proof of principle of the SOS stool method was demonstrated in routine settings in Addis Ababa, Ethiopia. Nine of 123 children with presumptive TB had M. tuberculosis-positive results for nasogastric aspiration (NGA) samples, and 7 (77.8%) of those children also had M. tuberculosis-positive Xpert results for stool samples. Additionally, M. tuberculosis was detected in the stool samples but not the NGA samples from 2 children. The SOS stool processing method makes use of the standard Xpert assay kit, without the need for additional supplies or equipment. The method can potentially be rolled out to any Xpert site, bringing a bacteriologically confirmed diagnosis of TB in children closer to the point of care.

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.

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.

Comparison of the yield of tuberculosis among contacts of multidrug-resistant and drug-sensitive tuberculosis patients in Ethiopia using GeneXpert as a primary diagnostic test.

OBJECTIVES: This study compared the yield of tuberculosis (TB) among contacts of multidrug-resistant tuberculosis (MDR-TB) index cases with that in drug-sensitive TB (DS-TB) index cases in a program setting. METHODS: A comparative cross-sectional study was conducted among contacts of sputum smear-positive new DS-TB index cases and MDR-TB index cases. After contacts were screened, GeneXpert was used for the diagnosis of TB. RESULTS: The study included 111 MDR-TB and 119 DS-TB index cases. A total of 340 and 393 contacts of MDR-TB and DS-TB index cases, respectively, were traced, of whom 331 among MDR-TB contacts and 353 among DS-TB contacts were screened. There were 20 (6%) presumptive TB cases for MDR-TB contacts and 41 (11%) for DS-TB contacts. The prevalence of TB among MDR-TB contacts was 2.7% and among DS-TB contacts was 4.0%. The majority of the MDR-TB contacts diagnosed with TB had MDR-TB; the reverse was true for DS-TB. CONCLUSIONS: The yield of TB among contacts of MDR-TB and DS-TB patients using GeneXpert was high as compared to the population-level prevalence. The likelihood of diagnosing rifampicin-resistant TB among contacts of MDR-TB index cases was higher in comparison with contacts of DS-TB index cases. The use of GeneXpert in DS-TB contact investigation has the added advantage of diagnosing rifampicin-resistant TB cases when compared to the use of the nationally recommended acid-fast bacillus (AFB) microscopy for DS-TB contact investigation.

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.

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.

Beneficial effect of isoniazid preventive therapy and antiretroviral therapy on the incidence of tuberculosis in people living with HIV in Ethiopia.

BACKGROUND: IPT with or without concomitant administration of ART is a proven intervention to prevent tuberculosis among PLHIV. However, there are few data on the routine implementation of this intervention and its effectiveness in settings with limited resources. OBJECTIVES: To measure the level of uptake and effectiveness of IPT in reducing tuberculosis incidence in a cohort of PLHIV enrolled into HIV care between 2007 and 2010 in five hospitals in southern Ethiopia. METHODS: A retrospective cohort analysis of electronic patient database was done. The independent effects of no intervention, "IPT-only," "IPT-before-ART," "IPT-and-ART started simultaneously," "ART-only," and "IPT-after-ART" on TB incidence were measured. Cox-proportional hazards regression was used to assess association of treatment categories with TB incidence. RESULTS: Of 7,097 patients, 867 were excluded because they were transferred-in; a further 823 (12%) were excluded from the study because they were either identified to have TB through screening (292 patients) or were on TB treatment (531). Among the remaining 5,407 patients observed, IPT had been initiated for 39% of eligible patients. Children, male sex, advanced disease, and those in Pre-ART were less likely to be initiated on IPT. The overall TB incidence was 2.6 per 100 person-years. As compared to those with no intervention, use of "IPT-only" (aHR = 0.36, 95% CI = 0.19-0.66) and "ART-only" (aHR = 0.32, 95% CI = 0.24-0.43) were associated with significant reduction in TB incidence rate. Combining ART and IPT had a more profound effect. Starting IPT-before-ART (aHR = 0.18, 95% CI = 0.08-0.42) or simultaneously with ART (aHR = 0.20, 95% CI = 0.10-0.42) provided further reduction of TB at ∼ 80%. CONCLUSIONS: IPT was found to be effective in reducing TB incidence, independently and with concomitant ART, under programme conditions in resource-limited settings. The level of IPT provision and effectiveness in reducing TB was encouraging in the study setting. Scaling up and strengthening IPT service in addition to ART can have beneficial effect in reducing TB burden among PLHIV in settings with high TB/HIV burden.