Tuberculosis (TB) is a public health problem in Lithuania, among the 18 high-priority TB countries in the European region, and the most common AIDS-indicative disease with the highest proportion in ...the EU/EEA since 2015. The study aimed to identify socio-demographic, clinical characteristics and their relationship with TB outcomes in TB-HIV co-infected patients in Lithuania.
A retrospective chart review analysed the characteristics of TB-HIV co-infected adults registered in State Information System of Tuberculosis over 2008-2020. The factors associated with drug-resistant TB and unsuccessful treatment outcome were identified by multivariable logistic regression.
The study included 345 cases in 311 patients (239 new, 106 previously treated cases), median age 40 years (IQR 35-45), 80.7% male. 67.8% patients knew their HIV-positive status before TB diagnosis, median time to TB diagnosis was 8 years (IQR 4-12). 83.6% were unemployed, 50.5%-anytime intravenous drug users (IDU), 34.9% abused alcohol. Drug-resistant TB rates in new and previously treated TB cases were 38.1% and 61.3%, respectively. In multivariable analysis, higher risk of drug-resistant TB was associated with imprisonment in new (aOR 3.35; 95%CI 1.17-9.57) and previously treated (aOR 6.63; 95%CI 1.09-40.35) cases. In 52.3% of new TB cases and in 42.5% previously treated TB cases the treatment outcomes were unsuccessful. In multivariable analysis of new TB cases, current imprisonment (aOR 2.77; 95%CI 1.29-5.91) and drug-resistant TB (aOR 2.18; 95%CI 1.11-4.28) were associated with unsuccessful treatment outcome. In multivariable analysis of previously treated TB cases, female gender (aOR 11.93; 95%CI 1.86-76.69), alcohol abuse (aOR 3.17; 95%CI 1.05-9.58), drug-resistant TB (aOR 4.83; 95%CI 1.53-15.28) were associated with unsuccessful treatment outcome.
In the TB-HIV-infected adult cohort in Lithuania, unemployment, imprisonment, IDU, alcohol abuse, known to be risk factors for TB, were very frequent. Drug resistance was an undeniable risk factor for unsuccessful treatment outcome and imprisonment was associated with drug resistant TB.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lithuania remains one of the highest tuberculosis burden countries in Europe. Epidemiological studies have long pointed to infections as important factors of cancer aetiology, but the association ...between tuberculosis and the risk of non-pulmonary cancers has rarely been tested and results have been inconsistent. The aim of this population-based cohort study was to examine the risk of cancer among patients diagnosed with tuberculosis using data from Lithuanian Tuberculosis, Cancer and Resident's Registries.
The study cohort included 21,986 tuberculosis patients yielding 1583 cancers diagnosed during follow-up (1998-2012). Standardized incidence ratios (SIRs) and 95% confidence intervals (95% CIs) were calculated to compare the incidence of cancer among cohort participants with the general population for overall, non-pulmonary, site-specific cancers, as well as for subgroups of smoking-related, alcohol-related, hormone-related and haematological cancers.
The SIRs of all cancers combined were 1.89, 95% CI: 1.79-2.00 in men and 1.34, 95% CI: 1.19-1.50 in women. Risk was increased 3-fold within the first year following diagnosis; it decreased during later years, although remained significantly elevated for ≥5 years. Elevated long-term increased risks persisted for non-pulmonary cancers overall, and for cancers of mouth and pharynx, oesophagus, stomach, larynx, cervix uteri and leukaemias. Tuberculosis was associated with a decreased risk of melanoma. Increased risks were observed for smoking-related cancers in men (SIR 1.95, 95% CI: 1.79-2.13) and women (SIR 1.46, 95% CI: 1.22-1.73), alcohol-related cancers in men (SIR 2.40; 95% CI: 2.14-2.68) and haematological cancers in men (SIR 1.73, 95% CI: 1.33-2.23). The risk of hormone-related cancers was 18% lower (SIR = 0.82, 95% CI: 0.66-0.997) among women, the inverse association was weaker among men (SIR = 0.95, 95% CI: 0.84-1.07).
The risk of total and several non-pulmonary cancers was elevated in a cohort of tuberculosis patients. The recommendation for the awareness of this association among physicians is warranted. Analysis suggests a reduction in risk of hormone-related cancers and melanoma.
With an increase in survival rates among rheumatic patients, comorbidities and infections, in particular, have gained more importance, especially after the introduction of biologicals to the ...treatment algorithms. Tuberculosis (TB) infection has always been given a special attention in patients with rheumatic diseases (RD). Although Lithuanian population has one of the highest TB incidence rates among European countries, the incidence of TB in the rheumatic patients' population is still unknown. The aim of this study was to assess the incidence rate of TB in an inflammatory RD retrospective cohort and to compare that rate with a rate in a general population.
Patients with the first-time diagnosis of inflammatory RD during the period between 1 January 2012 and 31 December 2017 were identified from the Lithuanian Compulsory Health Insurance Information System database SVEIDRA. All cases were cross-checked with Health Information center at the Institute of Hygiene, for the vital status of these patients and date of death if the fact of death was documented, and with Tuberculosis Register operated by Vilnius University Hospital Santaros Klinikos, for the confirmation of TB cases. Sex and age standardized incidence ratios (SIR) were calculated by dividing the observed numbers of TB among rheumatic patients by the expected number of cases, calculated using national rates from Lithuanian Department of Statistics Official Statistics website.
Overall, 8779 patients with newly diagnosed RD were identified during the 2013-2017 period, these included 458 patients who used biological disease modifying drugs (bDMARDs). The mean duration of the follow-up period was 2.71 years. The cohort consisted mainly of women (70%) and a half of the cohort were rheumatoid arthritis (RA) patients (53%). Mean age of patients at the time of RD diagnosis was 56 years (range = 18-97 years). There were 9 TB cases identified during 23,800 person years of follow-up: 2 cases among them were treated with bDMARDs. The mean calculated annual TB incidence in RD cohort was 37.81 per 100,000 person years, which is consistent with the incidence rate predicted by national estimates, with a resultant SIR of 0.90 (0.41-1.70). The unadjusted hazard ratio for bDMARD use versus no bDMARD use was 4.54 (0.94; 21.87) in a total cohort and very similar in rheumatoid arthritis cohort; in both cohorts, it was not a statistically significant risk.
Here, we present the first nationwide cohort study to assess the incidence of TB in a broad spectrum of inflammatory RD. Although limited by short follow-up period, this study shows that TB incidence in RD cohort does not exceed TB incidence in the general Lithuanian population.
The whole-genome sequencing (WGS) is becoming an increasingly effective tool for rapid and accurate detection of drug resistance in Mycobacterium tuberculosis complex (MTBC). This approach, however, ...has still been poorly evaluated on strains from Central and Eastern European countries. The purpose of this study was to assess the performance of WGS against conventional drug susceptibility testing (DST) for the detection of multi-drug resistant (MDR) phenotypes among MTBC clinical strains from Poland and Lithuania.BACKGROUNDThe whole-genome sequencing (WGS) is becoming an increasingly effective tool for rapid and accurate detection of drug resistance in Mycobacterium tuberculosis complex (MTBC). This approach, however, has still been poorly evaluated on strains from Central and Eastern European countries. The purpose of this study was to assess the performance of WGS against conventional drug susceptibility testing (DST) for the detection of multi-drug resistant (MDR) phenotypes among MTBC clinical strains from Poland and Lithuania.The study included 208 MTBC strains (130 MDR; 78 drug susceptible), recovered from as many tuberculosis patients in Lithuania and Poland between 2018 and 2021. Resistance to rifampicin (RIF) and isoniazid (INH) was assessed by Critical Concentration (CC) and Minimum Inhibitory Concentration (MIC) DST as well as molecular-based techniques, including line-probe assay (LPA) and WGS. The analysis of WGS results was performed using bioinformatic pipeline- and software-based tools.METHODSThe study included 208 MTBC strains (130 MDR; 78 drug susceptible), recovered from as many tuberculosis patients in Lithuania and Poland between 2018 and 2021. Resistance to rifampicin (RIF) and isoniazid (INH) was assessed by Critical Concentration (CC) and Minimum Inhibitory Concentration (MIC) DST as well as molecular-based techniques, including line-probe assay (LPA) and WGS. The analysis of WGS results was performed using bioinformatic pipeline- and software-based tools.The results obtained with the CC DST were more congruent with those by LPA compared to pipeline-based WGS. Software-based tools showed excellent concordance with pipeline-based analysis in prediction of RIF/INH resistance. The RIF-resistant strains demonstrated a relatively homogenous MIC distribution with the mode at the highest tested MIC value. The most frequent RIF-resistance conferring mutation was rpoB S450L. The mode MIC for INH was two-fold higher among double katG and inhA mutants than among single katG mutants. The overall rate of discordant results between all methods was calculated at 5.3%. Three strains had discordant results by both genotypic methods (LPA and pipeline-based WGS), one strain by LPA only, three strains by MIC DST, two strains by both MIC DST and pipeline-based WGS, and the remaining two strains showed discordant results with all three methods, compared to CC DST.RESULTSThe results obtained with the CC DST were more congruent with those by LPA compared to pipeline-based WGS. Software-based tools showed excellent concordance with pipeline-based analysis in prediction of RIF/INH resistance. The RIF-resistant strains demonstrated a relatively homogenous MIC distribution with the mode at the highest tested MIC value. The most frequent RIF-resistance conferring mutation was rpoB S450L. The mode MIC for INH was two-fold higher among double katG and inhA mutants than among single katG mutants. The overall rate of discordant results between all methods was calculated at 5.3%. Three strains had discordant results by both genotypic methods (LPA and pipeline-based WGS), one strain by LPA only, three strains by MIC DST, two strains by both MIC DST and pipeline-based WGS, and the remaining two strains showed discordant results with all three methods, compared to CC DST.Considering MIC DST results, current CCs of the first-line anti-TB drugs might be inappropriately high and may need to be revised. Both molecular methods demonstrated 100% specificity, while pipeline-based WGS had slightly lower sensitivity for RIF and INH than LPA, compared to CC DST.CONCLUSIONSConsidering MIC DST results, current CCs of the first-line anti-TB drugs might be inappropriately high and may need to be revised. Both molecular methods demonstrated 100% specificity, while pipeline-based WGS had slightly lower sensitivity for RIF and INH than LPA, compared to CC DST.
Delamanid is one of two recently approved drugs for the treatment of multidrug-resistant tuberculosis. We aimed to evaluate the safety and efficacy of delamanid in the first 6 months of treatment.
...This randomised, double-blind, placebo-controlled, phase 3 trial was done at 17 sites in seven countries (Estonia, Latvia, Lithuania, Moldova, Peru, the Philippines, and South Africa). We enrolled eligible adults (>18 years) with pulmonary multidrug-resistant tuberculosis to receive, in combination with an optimised background regimen developed according to WHO and national guidelines, either oral delamanid (100 mg twice daily) for 2 months followed by 200 mg once daily for 4 months or placebo (same regimen). Patients were centrally randomised (2:1) and stratified by risk category for delayed sputum culture conversion. Primary outcomes were the time to sputum culture conversion over 6 months and the difference in the distribution of time to sputum culture conversion over 6 months between the two groups, as assessed in the modified intention-to-treat population. The trial is registered at ClinicalTrials.gov, number NCT01424670.
Between Sept 2, 2011, and Nov 27, 2013, we screened 714 patients, of whom 511 were randomly assigned (341 to delamanid plus optimised background regimen delamanid group and 170 to placebo plus optimised background regimen placebo group) and formed the safety analysis population. 327 patients were culture-positive for multidrug-resistant tuberculosis at baseline and comprised the efficacy analysis population (226 in the delamanid group and 101 in the placebo group). Median time to sputum culture conversion did not differ between the two groups (p=0·0562; modified Peto-Peto), with 51 days (IQR 29-98) in the delamanid group and 57 days (43-85) in the placebo group; the hazard ratio was 1·17 (95% CI 0·91-1·51, p=0·2157). 501 (98·0%) of 511 patients had at least one treatment-emergent adverse event. 136 (26·6%) of 511 patients had at least one serious treatment-emergent adverse event; the incidence was similar between treatment groups (89 26·1% of 341 patients for delamanid and 47 27·6% of 170 for placebo). Deaths related to treatment-emergent adverse events were similar between groups (15 4·4% of 341 for delamanid and six 3·5% of 170 for placebo). No deaths were considered to be related to delamanid.
The reduction in median time to sputum culture conversion over 6 months was not significant in the primary analysis. Delamanid was well tolerated with a highly characterised safety profile. Further evaluation of delamanid is needed to determine its role in a rapidly evolving standard of care.
Otsuka Pharmaceutical.
Abstract Introduction Drug-resistant tuberculosis (TB) is an important public health problem in Lithuania with MDR rates in new cases reaching 11% in 2012. Currently available diagnostic tools are ...not fully adequate for an accurate and rapid result for diagnosis of TB and MDR-TB. Objectives To evaluate the performance of Xpert® MTB/RIF assay for an early diagnosis of TB and detection of rifampicin (RIF) resistance in routine settings in Lithuania. Methods A total of 833 individual respiratory samples obtained from patients previously treated for TB and MDR-TB contacts were tested using the Xpert MTB/RIF assay. Performance characteristics of the assay for TB and RIF resistance detection were calculated using culture and phenotypical DST results as a gold standard. Results The overall sensitivity and specificity of the Xpert MTB/RIF assay for TB detection were 93.7% and 91.7%, respectively with the sensitivity for smear-negative specimens reaching 82.5%. Resistance to RIF was detected in 81 (20.7%) primary specimens with no false negative results; there were 4/225 (1.8%) false-positives among strains sensitive to rifampicin. Overall sensitivity and specificity of the molecular assay for detection of RIF resistance calculated against phenotypic DST results were 100% and 98.2%, respectively. Conclusions Our results demonstrate very good performance of the Xpert MTB/RIF assay for the detection of TB and RIF resistance on primary respiratory specimens. It provides strong evidence that implementation of the assay for routine laboratory diagnosis in high drug-resistance settings may improve and facilitate TB diagnosis.
WHO recently recommended the use of a shorter multidrug-resistant TB (MDR-TB) regimen under programmatic conditions. We assessed eligibility for this regimen in a cohort of 737 adult patients with ...MDR-TB from Latvia, Lithuania, Estonia and Bucharest city recruited in 2007 and 2009. Only 4.2% of the patients were eligible for this regimen. Ethambutol (64%), pyrazinamide resistance (58%) and previous exposure to second-line TB drugs were major reasons for non-eligibility. High-level resistance to isoniazid is expected due to widespread prevalence of
mutations. In Eastern Europe, the use of the shorter regimen might be an exception rather than a rule.
The quality of care for patients with TB in Eastern Europe has improved significantly; nevertheless drug resistance rates remain high. We analysed survival in a cohort of patients with ...multidrug-resistant and extensively drug-resistant (MDR-/XDR-) TB from Latvia, Lithuania, Estonia and Bucharest city.
Consecutive adult new and retreatment patients with culture-confirmed pulmonary MDR-TB registered for treatment in 2009 (and in 2007 in Latvia) were enrolled; prospective survival information was collected.
A total of 737 patients were included into the cohort. Of all MDR-TB cases, 46% were newly diagnosed; 56% of all MDR-TB cases had no additional resistance to fluoroquinolones or injectable agents, 33% had pre-XDR-TB and 11% XDR-TB. Median survival was 5.9 years in patients with MDR-TB and XDR-TB; 1.9 years in patients coinfected with HIV. Older age, male gender, alcohol abuse, retirement, co-morbidities, extrapulmonary involvement and HIV coinfection independently worsened survival. Inclusion of fluoroquinolones and injectable agents improves survival in patients with MDR-TB. Pre-XDR and XDR status did not significantly shorten survival as long as fluoroquinolones and injectable agents were part of the regimen. Moxifloxacin seems to improve survival in ofloxacin-susceptible patients when compared with older generation fluoroquinolones.
The burden of additional resistances in patients with MDR-TB is high likely due to primary transmission of resistant strains. Social and programmatic factors including management of alcohol dependency, expansion of HIV testing and antiretroviral treatment need to be addressed in order to achieve cure and to interrupt transmission. The role of last generation fluoroquinolones and injectable agents in treatment of patients with pre-XDR and XDR-TB needs to be further investigated.
Rifapentine, a synthetic derivate of rifampicin which was developed in 1965, has interesting pharmacological properties, including a long terminal half-life (13 h, compared to 2-3 h for rifampicin) ...and promising bactericidal activity against Mycobacterium tuberculosis. Despite being approved in 1998 by the US Food and Drug Administration (FDA) for the treatment of pulmonary tuberculosis, its global use has been limited by unavailability. In the past decade, new evidence has emerged to define rifapentine as a key component for treatment of active disease and latent infection with M. tuberculosis (LTBI).
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