IMPLEMENTATION AND EVALUATION OF ACTIVE AND PASSIVE CASE FINDINGS OF MULTI-FOCUS INTEGRATED SCREENING PACKAGE TO END TUBERCULOSIS IN ETHIOPIA

Abstract

Background: In Ethiopia, one-third of tuberculosis (TB) cases are missed each year, and delay in the diagnosis of TB is hampering the whole cascade of care. Recent surveys have showed very high prevalence of confirmed TB, even among those with a low duration of cough with more than 50% having a bacteriologically confirmed pulmonary TB (PTB). Furthermore, there is an increase in the incidence of smear-negative PTB patients who may potentially serve as a source of infection. Aim: This study was aimed to evaluate active and passive case finding interventions aiming at halting the burden of TB in Ethiopia, by assessing the burden of TB and challenges related to screening and diagnosis; prevalence and predictors; impact of early chest X-ray (CXR) on delay among TB cases; and diagnostic performance of CXR among health care-seeking people screened for cough of any duration. Methods: A two-phase implementation study was conducted in four administrative regions in Ethiopia. During Phase I, a facility-based cross-sectional study was conducted in seven healthcare facilities selected from four administrative regions selected by stratified random sampling procedures to assess TB burden and identify challenges related to TB screening and diagnosis. In this Phase, data of 1,059,065 patients were included from the outpatient department, HIV clinic, diabetic, and reproductive and child health units. Data were collected from October to December 2018 using a retrospective review of three years' facility data (2015 to 2017) supplemented by a semi-structured interview with purposively selected health care workers and heads of the health facilities. During Phase II, a facility-based cross-sectional study was conducted among all consented patients who attended healthcare at outpatient departments, reproductive and child health units in the study facilities. The patients were screened for cough of any duration and grouped into two groups: group I included patients with cough ≥ 2 weeks, and group II included patients with cough of < 2 weeks. Both groups underwent CXR followed by sputum Xpert MTB/RIF assay or smear microscopy tests depending on the type of test available in the facility where participants recruited. CXR results were read and interpreted by radiologists. Pregnant women, HIV patients on antiretroviral therapy, and patients with diabetes were exempted from CXR; xvii thus, evaluated for TB as group III. TB prevalence was calculated across the three groups. For Phase I, descriptive analysis was done using Excel. For Phase II, analysis was performed using Stata 14.0. The TB case predictors were analyzed using modified Poisson regression to compute adjusted prevalence ratio (aPR) with a 95% confidence interval (CI). Delays were calculated using median and inter-quartile range (IQR) and summarized into the following; patient delay (first onset of cough to first facility visit, ≥ 15 days), diagnosis delay (first facility visit to date of PTB diagnosis, > 7 days), and total delay (first onset of cough to date of PTB diagnosis, > 21 days). Kruskal-Wallis and Mann-Witney tests were used to compare the delays among independent variables. Evaluation was done to check if early CXR in patients with cough irrespective of duration may reduce TB diagnostic and treatment delays. The diagnostic performance of CXR as a TB triage test before Xpert MTB/RIF assay among people with respiratory complaints. Area under the curve (AUC), sensitivity, specificity, and predictive values of CXR against Xpert MTB/RIF as the reference standard and further comparison with clinical symptoms. Results: The Phase I initial assessment data showed that a total of 1,059,065 patients visited the healthcare facilities in three years. Of these, 978,480 (92.4%) were outpatients among which 20,284 (2%) were presumptive TB cases (with 14 days or more cough) and of which, 12.2% (2483/20,284) had TB. About a quarter, 604 (24.3%), were smear-positive pulmonary TB (PTB), 789 (31.8%) were smear-negative PTB, and 719 (29%) were extra-pulmonary TB. The study showed that, TB screening was integrated into HIV clinic, outpatient department, diabetic clinic but not with the reproductive and child health clinics. High patient load, weak TB laboratory specimen referral system, and shortage of TB diagnostic tools including Xpert MTB/RIF assay and chest X-ray, were the major challenges in the screening and diagnosis of TB. During Phase II, the study screened 195,713 people who sought healthcare for cough of any duration, of which, 2647 (1.4%) reported cough symptom of any duration, of whom 1853 (70%) underwent further diagnostic tests as they fulfilled the criteria for presumptive TB. Overall, 309/1853 (16.7%) were diagnosed with PTB. Of the 309 positive cases, 81.2% (251/309) were in group I (cough ≥ 2 weeks), 44/309 (14.2%) in group II (cough of < 2 weeks), and 4.5% (14/309) in group III (CXR exempted). The majority of predictors of PTB were age group of xviii 25-34 (aPR = 2.0 [95% CI 1.3-2.8]), history of weight loss (aPR = 1.2 [95% CI 1.1-1.3]), and TB suggestive CXRs (aPR = 41.1 [95% CI 23.2-72.8]). Among 309 diagnosed PTB cases, the median (IQR) of patient delay, diagnosis delay, and the total delay was 30 (16-44), 1 (0-3), and 31 (19-48) days, respectively. Patients’ delay contributed a great role in the total delay, 201/209 (96.2%). Median diagnosis delay was higher among those who visited health center, diagnosed at a facility that had no Xpert MTB/RIF assay, radiologist, or CXR (p<0.05). Factors associated with patients’ delay were history of previous TB treatment (aPR [adjusted Prevalence Ratio] = 0.79, 95% CI: 0.63-0.99) and history of weight loss (aPR = 1.12; 95% CI: 1.0-1.25). Early CXR screening for cough of < 2 weeks duration significantly reduced the patients’ delay and thus the total delay. Of the 2647 cases reported of having a cough, 757 had both CXR results and Xpert, hence included in this analysis. Overall, 152/757 (20%) were Xpert confirmed PTB. The sensitivity and specificity of CXR findings were 77.6% (95% CI: 70-84%) and 97.5% (95% CI: 96-99%), respectively, when compared with the Xpert standard. The AUC of the CXR was 87.6% (95% CI: 84-91%). Inclusion of night sweats as initial symptom screening before CXR improved the sensitivity at 91.7% (95% CI 84-96, with the AUC of 93% (95% CI: 90-97%). Conclusion: The burden of TB was high in the study setting, and frequent interruption of laboratory reagents and supplies hampered TB screening and diagnostic services during passive and active screening. A large number of PTB cases were diagnosed among people who sought health care when screened for cough of any duration. CXR is an important tool for triaging and screening for PTB before Xpert MTB/RIF assay among people with respiratory complaints in Ethiopia. Early screening using CXR minimized delays in the diagnosis of PTB among people with cough of any duration. Patients’ delay was prevalent and contributed significant role in the delay of TB cases. Screening by cough of any duration and/or CXR among people seeking healthcare along with ensuring the availability of Xpert MTB/RIF assay and skilled human resources at primary healthcare facilities are important to reduce patient and diagnostic delays of PTB in order to end TB in Ethiopia.