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 However, we encountered obstacles such as lack of staffing, material ruptures, outdated government protocols, and decreased case presentation due to COVID-19.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.

Treatment success using novel and adapted treatment regimens in registered DR-TB children in Dushanbe, Tajikistan, 2013-2019.

INTRODUCTION: Approximately 3% of all pediatric TB cases develop MDR-TB, with only 3-4% of such children receiving MDR-TB treatment. In Tajikistan, children as a proportion of all DR-TB in the country increased from 4.3 to 7.5% during 2013-2018. Despite limited evidence on the use of new anti-TB drugs in children, WHO has updated its guidelines for DR-TB treatment for children, and Tajikistan did so in 2013 and 2017. Novel and adapted regimens included individual regimens for RR/MDR, XDR (with and without Bedaquiline and Delamanid) and short treatment regimens with and without injectables. It is important to document the outcomes of the treatment regimens. Therefore, the aim of this study was to describe characteristics of children receiving different treatment regimens for DR-TB, the culture conversion and treatment outcomes. METHODOLOGY: Cohort study of children enrolled in DR-TB treatment by the National Tuberculosis Program in Dushanbe, Tajikistan, January 2013 to July 2019. RESULTS: The study included 60 DR-TB children. The male to female ratio was 1:2 and mean age 13.6 years. Median time to culture conversion was 66 days [IQR:31-103; Range:2-232]. In children with treatment outcomes (N = 58), 93% had favorable outcomes. There were four children (7%) with unfavorable treatment outcomes, all of whom were female 15-17 years, on standard (RR/MDR) treatment during 2013-2015. Favorable outcomes by DR-TB type were 91%, 90%, and 100% in RR/MDR, PreXDR, and XDR-TB patients, respectively. CONCLUSIONS: All children enrolled after the introduction of modified guidelines for novel and adapted regimens for DR-TB showed positive TB treatment outcomes.

Tuberculosis in key populations in Tajikistan - a snapshot in 2017.

INTRODUCTION: WHO End TB Strategy aims at achieving targets of 90% mortality reduction and 80% reduction in tuberculosis (TB) incidence by 2030, recommending better addressing TB and multidrug-resistant TB (MDR-TB) issues in key populations. AIM: The study aimed at having a snapshot of the epidemiological characteristics of the key populations among the new TB patients, registered in Tajikistan during 2017. METHODOLOGY: A cross-sectional study was conducted, using official TB registration data for all new TB case notification in Tajikistan in 2017. RESULTS: The key population included 1,029 (19.8%) patients among all 5,182 new TB cases registered in 2017. The following selected sub-populations were identified: migrant workers - 728 (70.7%), diabetics - 162 (15.7%), HIV-positive - 138 (13.4%), heavy drinkers - 74 (7.2%), drug users - 50 (4.8%), ex-prisoners - 50 (4.8%), and homeless - 9 (0.9%). Among the key population, 307 (29.8%) patients were smear-positive, 145 (14.1%) were drug-sensitive and 116 (11.3%) had MonoDR/MDR-TB. Time to treatment initiation for smear-positive cases was ≤ 5 days for 303 (98.7%) patients. Being a key population was inversely related to gender (female) (OR = 0.25, 95% CI (0.21, 0.29)) and population type (rural) (OR = 0.64, 95% CI (0.55, 0.74)). CONCLUSION: Among the key population the identified overlaps of selected sub-populations would enable more efficiently reaching the certain groups. TB case detection at PHC levels needs to be targeted for improved rates for key population detection. In the key population sub-group of migrant workers' special migration destinations are recommended to be explored and find out possible associations with drug resistance.

A case report of a child with probable drug resistant tuberculous pericarditis with a review of challenges involved in diagnosis, treatment and follow up of children with DR-TB pericarditis.

BACKGROUND: There are unique challenges in the diagnosis and management of multi drug resistant tuberculosis (MDR-TB) in children. It is difficult to obtain confirmatory microbiological diagnosis in TB pericarditis. It is essential to differentiate between drug sensitive and drug resistant forms of TB as it has a major bearing on the regimen used, and inappropriate TB treatment combined with steroid use for pericarditis can lead to deterioration. With lack of samples, the treatment decision relies on the drug resistance pattern of the close contact if available. Therapeutic challenges of MDR-TB management in a child involve use of toxic drugs that need to be judiciously handled. We report a 2 years 4 months old male child who was diagnosed with TB pericarditis and treated based on the resistance pattern of his mother who was on treatment for pulmonary MDR-TB. CASE PRESENTATION: This 2 years 4 months old male child was diagnosed with TB involving his pericardium. Getting him started on an appropriate regimen was delayed due to the difficulty in establishing microbiological confirmation and drug susceptibility. He was commenced on a regimen based on his mother's drug resistance pattern and required surgery due to cardiac failure during the course of his treatment. He successfully completed 2 years of therapy. CONCLUSIONS: This child's case demonstrates that despite unique challenges in diagnosis and management of drug resistant extra pulmonary tuberculosis in children, treatment of even complex forms can be successful. The need for high suspicion of MDR-TB, especially when there is close contact with pulmonary TB, careful design of an effective regimen that is tolerated by the child, indications for invasive surgical management of pericarditis, appropriate follow-up and management of adverse effects are emphasised.

Factors contributing to drug-resistant tuberculosis treatment outcome in five countries in the Eastern Europe and Central Asia region.

Drug-resistant tuberculosis (DR-TB) is a global challenge and a major contributor of death from anti-microbial resistance. With the main aim to determine factors contributing to treatment outcomes observed among DR-TB patients in the countries in Eastern Europe and Central Asia (EECA), a multi-method study was conducted in: Azerbaijan, Belarus, Romania, Tajikistan and Ukraine. Both quantitative and qualitative methodologies were used for data collection and analysis. The quantitative approaches included a desk review of documents related to the DR-TB responses and an analysis of clinical records of DR-TB patients in selected health facilities of the five countries. Qualitative methods included in-depth interviews with national TB programme (NTP) managers, other healthcare providers and non-governmental organizations (NGOs) workers, as well as interviews and Focus Group Discussions (FGDs) with DR-TB patients. The desk review of 38 reports identified as the main challenges to address DR-TB financial and/or management issues and adverse events of the medicines. The most common recommendations related to treatment outcome focussed on general programme management, treatment regimen composition, clinical management and social support for the patients. In all the five countries the NTPs still have a vertical structure. Some integration into the primary health care system (PHC) already exists but further involvement of PHC facilities is feasible and recommended. Interviews with stakeholders indicated that alcoholism and homelessness and a lack of appropriate response to these issues remain as major challenges for a sub-set of patients. Civil society groups, NGOs and communities are substantially engaged in providing different services to DR-TB patients, especially in Ukraine, Romania and Tajikistan. Data from clinical records of 212 patients revealed that independent risk factors for unfavourable treatment outcome (death, loss to follow-up, failure) were culture-positivity at two months of treatment, history of treatment with second-line drugs and homelessness. More powerful, less toxic and shorter oral treatment regimens as well as comprehensive patient support are needed to improve treatment outcome of patients with DR-TB.