ABSTRACT
BACKGROUND: A novel skin test-called Diaskintest (DT)-containing specific M. tuberculosis antigens is in clinical use in the Russian Federation (RF). This test may improve diagnosis of tuberculosis (TB) infection. The use and performance of the DT was described and compared to the tuberculin skin test (TST). METHODS: Data on children <18 years referred to a TB reference centre (Jan/2018- Dec/2019) with ≥1 DT and TST result available were analysed. An immune correlate of TB infection was defined as a positive TST (≥10 mm induration) or a positive DT (any induration). RESULTS: Of 2710 included cases, the median age was 9.0 (IQR 5.7-13.1) years and 97.5% were BCG immunised. Overall, 1976 (79.9%) were TB uninfected, 724 (26.7%) had an immune correlate of TB infection and 10 (0.4%) TB disease. Reasons for referral were: positive or increasing skin test results in routine screening (992, 36.6%), screening before admission to a health care institution (501, 18.5%) and TB contact (457, 16.9%). DT was positive in 11.7% (308/2625) and TST in 63.1% (467/740) (Kappa 0.08, 95% CI:0.013-0.14). A positive DT was associated with older age (OR 1.16 (95% CI: 1.13-1.19) per year). Among TB contacts DT positivity was associated with contagiousness: highest proportion of positivity of 12.0% was observed when the index case was smear positive. CONCLUSION: In a setting with universal BCG vaccination and regular screening with TST, DT was used to rule out TB infection as TST was commonly positive. We found an association of DT positivity and contagiousness of the index case in children contacts. These observations may suggest improved specificity and sensitivity of DT compared to TST.
Subject(s)
Tuberculin Test , Tuberculosis , Humans , Child , Tuberculin Test/methods , Male , Female , Child, Preschool , Adolescent , Tuberculosis/diagnosis , Mycobacterium tuberculosis/immunology , Skin Tests/methods , BCG Vaccine/immunology , Infant , Antigens, Bacterial/immunology , Antigens, Bacterial/analysisABSTRACT
INTRODUCTION: Sputum-based tuberculosis diagnosis does not address the needs of certain categories of patients. Active development of a noninvasive urine-based diagnosis could provide an alternative approach. We reviewed publications covering more than 30 urine biomarkers proposed as significant for TB diagnosis. Analytical approaches were heterogeneous in design and methods; few studies on diagnostic outcome prediction described a formal specificity and sensitivity analysis. AREAS COVERED: This review describes studies of non-sputum diagnostic approaches of pulmonary TB based on urine using specific TB biomarkers. The search was performed until December 2021, using terms [Tuberculosis] + [urine] + [biomarkers] in PubMed and Cochrane databases. Publications concerning LAM urine diagnostics were excluded as they have been described elsewhere. EXPERT OPINION: Microbiological culture of sputum is considered to be the 'gold standard' diagnostic for pulmonary TB but the methodology is slow due to the slow growth of the TB bacteria. Urine provides a large volume of sample. Investigators have evaluated urine for either TB pathogen biomarkers or host biomarkers with some success as the review demonstrates. Detection sensitivity remains a significant problem. In future, combination of host and pathogen biomarkers could increase the sensitivity and specificity of TB diagnosis.
Subject(s)
HIV Infections , Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Tuberculosis , Biomarkers , Humans , Lipopolysaccharides , Sensitivity and Specificity , Tuberculosis/diagnosis , Tuberculosis, Pulmonary/diagnosisABSTRACT
BACKGROUND: Nontuberculous mycobacteria (NTM) are acid-fast bacilli (AFB) that can cause disease in human. Patients with NTM pulmonary disease can be falsely diagnosed with pulmonary tuberculosis (TB) due detection of AFB in sputum and similar clinical and chest X-ray picture. Laboratory detection of NTM is complicated and does not always mean presence of the disease, but can be attributed to colonization or sample contamination. Molecular tests, such as Genotype Mycobacterium CM/AS, allow quick and reliable detection of NTM. OBJECTIVE: To assess the NTM identification rate, to estimate the incidence of pulmonary NTM disease and to report the treatment outcomes among patients with NTM disease. DESIGN: Retrospective cohort design. RESULTS: NTM were detected among 92 (0.98 per 100,000 population) presumptive pulmonary TB patients in Arkhangelsk region in 2010-2017 among who 39 (0.42 per 100,000 population) patients were diagnosed with NTM disease. The most prevalent species found in our study were M. avium (33%) and M.intracellulare (11%). 69% of patients with NTM disease completed their treatment, 15% died, 13% were lost to follow up and 3% failed treatment. CONCLUSION: A system of diagnostics and treatment for NTM disease was set up in the Arkhangelsk region in Russia. Average NTM identification rate and incidence of pulmonary NTM disease were 0.98 per 100,000 and 0.42 per 100,000 population accordingly and were lower than reported in other studies. Treatment success rate in our study was 69% encouraging further improvements in diagnostics and treatment of patients with NTM.
Subject(s)
Lung Diseases/diagnosis , Lung Diseases/drug therapy , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/drug therapy , Nontuberculous Mycobacteria/drug effects , Female , Humans , Incidence , Lung/drug effects , Lung Diseases/microbiology , Male , Middle Aged , Mycobacterium/drug effects , Retrospective Studies , Russia , Sputum/microbiology , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/microbiologyABSTRACT
BACKGROUND: In the Arkhangelsk region of Northern Russia, multidrug-resistant (MDR) tuberculosis (TB) rates in new cases are amongst the highest in the world. In 2014, MDR-TB rates reached 31.7% among new cases and 56.9% among retreatment cases. The development of new diagnostic tools allows for faster detection of both TB and MDR-TB and should lead to reduced transmission by earlier initiation of anti-TB therapy. STUDY AIM: The PROVE-IT (Policy Relevant Outcomes from Validating Evidence on Impact) Russia study aimed to assess the impact of the implementation of line probe assay (LPA) as part of an LPA-based diagnostic algorithm for patients with presumptive MDR-TB focusing on time to treatment initiation with time from first-care seeking visit to the initiation of MDR-TB treatment rather than diagnostic accuracy as the primary outcome, and to assess treatment outcomes. We hypothesized that the implementation of LPA would result in faster time to treatment initiation and better treatment outcomes. METHODS: A culture-based diagnostic algorithm used prior to LPA implementation was compared to an LPA-based algorithm that replaced BacTAlert and Löwenstein Jensen (LJ) for drug sensitivity testing. A total of 295 MDR-TB patients were included in the study, 163 diagnosed with the culture-based algorithm, 132 with the LPA-based algorithm. RESULTS: Among smear positive patients, the implementation of the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 50 and 66 days compared to the culture-based algorithm (BacTAlert and LJ respectively, p<0.001). In smear negative patients, the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 78 days when compared to the culture-based algorithm (LJ, p<0.001). However, several weeks were still needed for treatment initiation in LPA-based algorithm, 24 days in smear positive, and 62 days in smear negative patients. Overall treatment outcomes were better in LPA-based algorithm compared to culture-based algorithm (p = 0.003). Treatment success rates at 20 months of treatment were higher in patients diagnosed with the LPA-based algorithm (65.2%) as compared to those diagnosed with the culture-based algorithm (44.8%). Mortality was also lower in the LPA-based algorithm group (7.6%) compared to the culture-based algorithm group (15.9%). There was no statistically significant difference in smear and culture conversion rates between the two algorithms. CONCLUSION: The results of the study suggest that the introduction of LPA leads to faster time to MDR diagnosis and earlier treatment initiation as well as better treatment outcomes for patients with MDR-TB. These findings also highlight the need for further improvements within the health system to reduce both patient and diagnostic delays to truly optimize the impact of new, rapid diagnostics.
Subject(s)
Algorithms , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/therapy , Adult , Female , Humans , Male , Middle Aged , Russia/epidemiology , Tuberculosis, Multidrug-Resistant/epidemiologyABSTRACT
Acquired resistance to antituberculosis drugs decreases effective treatment options and the likelihood of treatment success. We identified risk factors for acquisition of drug resistance during treatment for multidrug-resistant tuberculosis (MDR TB) and evaluated the effect on treatment outcomes. Data were collected prospectively from adults from Arkhangelsk Oblast, Russia, who had pulmonary MDR TB during 2005-2008. Acquisition of resistance to capreomycin and of extensively drug-resistant TB were more likely among patients who received <3 effective drugs than among patients who received >3 effective drugs (9.4% vs. 0% and 8.6% vs. 0.8%, respectively). Poor outcomes were more likely among patients with acquired capreomycin resistance (100% vs. 25.9%), acquired ofloxacin resistance (83.6% vs. 22.7%), or acquired extensive drug resistance (100% vs. 24.4%). To prevent acquired drug resistance and poor outcomes, baseline susceptibility to first- and second-line drugs should be determined quickly, and treatment should be adjusted to contain >3 effective drugs.
Subject(s)
Antitubercular Agents/pharmacology , Drug Resistance, Multiple, Bacterial , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/microbiology , Adult , Antitubercular Agents/therapeutic use , Cohort Studies , Female , Humans , Male , Middle Aged , Risk Factors , Russia/epidemiology , Treatment Outcome , Tuberculosis, Multidrug-Resistant/drug therapy , Young AdultABSTRACT
BACKGROUND: Tuberculosis (TB) is a major problem in Russia, particularly regarding multidrug-resistant tuberculosis (MDR-TB). Rapid drug susceptibility testing methods are therefore needed. OBJECTIVES: To perform epidemiological analyses of TB in the Archangelsk region and to evaluate the molecular method GenoType®MTBDRplus in this type of setting. MATERIALS AND METHODS: Clinical and microbiological data of all TB patients in Archangelsk were collected in 2010. Smear-positive sputa were analysed by MTBDRplus and Bactec MGIT 960. RESULTS: The number of TB cases was 812 (incidence 65/105) and among these patients, 151 cases were registered in the penitentiary system (incidence 1162/105). Most patients were men, 94% had pulmonary TB and 22% were relapses. Out of all cases, 341 (42%) were smear positive and thus contagious and 176 (22%) had MDR-TB, among which one had extensively drug resistant tuberculosis (XDR-TB). Furthermore, two TB patients had strains being resistant to rifampicin, but susceptible to isoniazid. The number of cases being both contagious and MDR-TB was 128 representing 15.8% of all TB cases (incidence 10.2/105). Among these 128 TB patients 37 were relapses representing 25.7% of all the relapse cases. The results of MTBDRplus and Bactec MGIT analyses corresponded in 98.8%. CONCLUSIONS: In Archangelsk many TB patients had contagious MDR-TB thus being hazardous in society and relapsing pulmonary TB was common. The TB situation in the prisons was particularly severe. The analyses showed furthermore that MTBDRplus is of major value in this setting.