Detection of Mycobacterium tuberculosis Complex Using the Xpert MTB/RIF Ultra Assay on the Stool of Pediatric Patients in Dushanbe, Tajikistan.

We report the findings of a prospective laboratory diagnostic accuracy study to evaluate the sensitivity, specificity, and predictive values of the Xpert MTB/RIF Ultra assay for Mycobacterium tuberculosis detection in fresh stool specimens from children under 15 years of age with confirmed tuberculosis (TB) disease from Dushanbe, Tajikistan. Six hundred eighty-eight (688) participants were enrolled from April 2019 to October 2021. We identified 16 participants (2.3%) with confirmed TB disease, defined as ≥1 TB sign/symptom plus microbiologic confirmation. With the Xpert MTB/RIF Ultra assay for stool, we found a sensitivity of 68.8% (95% CI, 46.0 to 91.5) and a specificity of 98.7% (95% CI, 97.8 to 99.5) in confirmed TB disease. Our results are comparable to other published studies; however, our cohort was larger and our confirmed TB disease rate lower than most. We also demonstrated that this assay was feasible to implement in a centralized hospital laboratory in a low-middle-income Central Asian country. However, we encountered obstacles such as lack of staffing, material ruptures, outdated government protocols, and decreased case presentation due to COVID-19. We found eight patients whose only positive test was an Xpert Ultra stool assay. None needed treatment during the study; however, three were treated later, suggesting such cases require close observation. Our report is the first from Central Asia and one of a few from a low-middle-income country. We believe our study demonstrates the generalizability of the Xpert MTB/RIF Ultra assay on fresh stool specimens from children and provides further evidence supporting WHO's approval of this diagnostic strategy. IMPORTANCE The importance of this report is that it provides further support for WHO's recent recommendation that fresh stool is an acceptable sample for GeneXpert TB testing in children, especially small children who often cannot produce an adequate sputum sample. Diagnosing TB in this age group is difficult, and many cases are missed, leading to unacceptable rates of TB illness and death. In our large cohort of children from Dushanbe, Tajikistan, the GeneXpert stool test was positive in 69% of proven cases of TB, and there were very few false-positive tests. We also showed that this diagnostic strategy was feasible to implement in a low-middle-income country with an inefficient health care delivery system. We hope that many more programs will adopt this form of diagnosing TB in children.

Scale-up and impact of digital and molecular diagnostic technologies on TB diagnosis and timely linkage to care in Tajikistan.

INTRODUCTION: Tajikistan is scaling up molecular diagnostic and digital technologies to strengthen its fight against drug-resistant TB (DR-TB). The study aimed to document national scale-up GeneXpert/GxAlert and Open MRS from 2012-2019 and compare time taken from TB diagnosis to treatment and quality of data recording before and after the introduction of GxAlert. METHODOLOGY: This was a longitudinal study that included a comparison of historical cohorts. Continuous variables were compared using Wilcoxon Rank-Sum test and categorical variables using the chi square test. RESULTS: GeneXpert was introduced in 2011 and scaled up to 46 instruments in 43 (51%) diagnostic laboratories by May 2019. GxAlert was introduced in August 2018 and connected with all GeneXpert instruments by February 2019. Open MRS was introduced in 2014 and implemented in all 108 treatment centers by mid-2018. Time from diagnosis to treatment pre-GxAlert (range 0-749, median 3, days) was significantly longer than with GxAlert (range 0-273, median 3, days) (p <0.001). The proportion of patients whose time from diagnosis to treatment was > 2 weeks was 16% (282/1740) pre-GxAlert and 11% (206/1902) with GxAlert (p < 0.001). Between 31%-34% of patients with DR-TB results in Open MRS did not have results available in GeneXpert/GxAlert systems. Where results were present in both systems, there were discrepancies in 8.2% of patients pre-GxAlert and 4.3% with GxAlert (p = 0.25). CONCLUSIONS: The scale-up of GeneXpert and digital technologies in Tajikistan was associated with a reduction in the proportion of patients with delays more than 2 weeks between diagnosis and treatment, but data quality recording improved only slightly.

Risk factors associated with loss to follow-up from tuberculosis treatment in Tajikistan: a case-control study.

BACKGROUND: There are very few studies on reasons for loss to follow-up from TB treatment in Central Asia. This study assessed risk factors for LTFU and compared their occurrence with successfully treated (ST) patients in Tajikistan. METHODS: This study took place in all TB facilities in the 19 districts with at least 5 TB patients registered as loss to follow-up (LTFU) from treatment. With a matched case control design we included all LTFU patients registered in the selected districts in 2011 and 2012 as cases, with ST patients from the same districts being controls. Data were copied from patient records and registers. Conditional logistic regressions were run to analyse associations between collected variables and LTFU as dependent variable. RESULTS: Three hundred cases were compared to 592 controls. Half of the cases had migrated or moved. In multivariate analysis, risk factors associated with increased LTFU were migration to another country (OR 10.6, 95% CI 6.12-18.4), moving within country (OR 11.0, 95% CI 3.50-34.9), having side effects of treatment (OR 3.67, 95% CI 1.68-8.00) and being previously treated for TB (OR 2.03, 95% CI 1.05-3.93). Medical staff also mentioned patient refusal, stigma and family problems as risk factors. CONCLUSIONS: LTFU of TB patients in Tajikistan is largely a result of migration, and to a lesser extent associated with side-effects and previous treatment. There is a need to strengthen referral between health facilities within Tajikistan and with neighbouring countries and support patients with side effects and/or previous TB to prevent loss to follow-up from treatment.