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Tukvadze N.,National Center for Tuberculosis and Lung Diseases | Bablishvili N.,National Center for Tuberculosis and Lung Diseases | Apsindzelashvili R.,National Center for Tuberculosis and Lung Diseases | Blumberg H.M.,Emory University | Kempker R.R.,Emory University
International Journal of Tuberculosis and Lung Disease | Year: 2014

SETTING: The country of Georgia has a high burden of multi- (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). OBJECTIVE: To assess the performance of the Geno- Type® MTBDRsl assay in the detection of resistance to kanamycin (KM), capreomycin (CPM) and ofloxacin (OFX), and of XDR-TB. DESIGN: Consecutive acid-fast bacilli smear-positive sputum specimens identified as MDR-TB using the MTBDRplus test were evaluated with the MTBDRsl assay and conventional second-line drug susceptibility testing (DST). RESULTS: Among 159 specimens, amplification was adequate in 154 (97%), including 9 of 9 culture-negative and 2 of 3 contaminated specimens. Second-line DST revealed that 17 (12%) Mycobacterium tuberculosis isolates were XDR-TB. Compared to DST, the MTBDRsl had 41% sensitivity and 98% specificity in detecting XDR-TB and 81% sensitivity and 99% specificity in detecting OFX resistance. Sensitivity was low in detecting resistance to KM (29%) and CPM (57%), while specificity was respectively 99% and 94%. Median times from sputum collection to second-line DST and MTBDRsl results were 70-104 vs. 10 days. CONCLUSION: Although the MTBDRsl assay had a rapid turnaround time, detection of second-line drug resistance was poor compared to DST. Further genetic mutations associated with resistance to second-line drugs should be included in the assay to improve test performance and clinical utility. © 2014 The Union. Source


A. Whitaker J.,Emory University | A. Whitaker J.,Mayo Medical School | Mirtskhulava V.,Emory University | Mirtskhulava V.,National Center for Tuberculosis and Lung Diseases | And 6 more authors.
PLoS ONE | Year: 2013

Background: Tuberculosis is a major occupational hazard in low and middle-income countries. Limited data exist on serial testing of healthcare workers (HCWs) with interferon-γ release assays (IGRAs) for latent tuberculosis infection (LTBI), especially in low and middle-income countries. We sought to evaluate the rates of and risk factors for LTBI prevalence and LTBI test conversion among HCWs using the tuberculin skin test (TST) and QuantiFERON-TB Gold In-tube assay (QFT-GIT). Methods: A prospective longitudinal study was conducted among HCWs in the country of Georgia. Subjects completed a questionnaire, and TST and QFT-GIT tests were performed. LTBI testing was repeated 6-26 months after baseline testing. Results: Among 319 HCWs enrolled, 89% reported prior BCG vaccination, and 60% worked in TB healthcare facilities (HCFs). HCWs from TB HCFs had higher prevalence of positive QFT-GIT and TST than those from non-TB HCFs: 107/194 (55%) vs. 30/125 (31%) QFT-GIT positive (p<0.0001) and 128/189 (69%) vs. 64/119 (54%) TST positive (p = 0.01). There was fair agreement between TST and QFT-GIT (kappa = 0.42, 95% CI 0.31-0.52). In multivariate analysis, frequent contact with TB patients was associated with increased risk of positive QFT-GIT (aOR 3.04, 95% CI 1.79-5.14) but not positive TST. Increasing age was associated with increased risk of positive QFT-GIT (aOR 1.05, 95% CI 1.01-1.09) and TST (aOR 1.05, 95% CI 1.01-1.10). High rates of HCW conversion were seen: the QFT-GIT conversion rate was 22.8/100 person-years, and TST conversion rate was 17.1/100 person-years. In multivariate analysis, female HCWs had decreased risk of TST conversion (aOR 0.05, 95% CI 0.01-0.43), and older HCWs had increased risk of QFT-GIT conversion (aOR 1.07 per year, 95% CI 1.01-1.13). Conclusion: LTBI prevalence and LTBI test conversion rates were high among Georgian HCWs, especially among those working at TB HCFs. These data highlight the need for increased implementation of TB infection control measures. © 2013 Whitaker et al. Source


Magee M.J.,Emory University | Kempker R.R.,Emory University | Kipiani M.,National Center for Tuberculosis and Lung Diseases | Tukvadze N.,National Center for Tuberculosis and Lung Diseases | And 3 more authors.
PLoS ONE | Year: 2014

Introduction: Diabetes mellitus (DM) is a risk factor for active tuberculosis (TB) but little is known about the effect of DM on culture conversion among patients with multidrug-resistant (MDR)-TB. The primary aim was to estimate the association between DM and rate of TB sputum culture conversion. A secondary objective was to estimate the association between DM and the risk of poor treatment outcomes among patients with MDR-TB. Materials and Methods: A cohort of all adult patients starting MDR-TB treatment in the country of Georgia between 2009-2011 was followed during second-line TB therapy. Cox proportional models were used to estimate the adjusted hazard rate of sputum culture conversion. Log-binomial regression models were used to estimate the cumulative risk of poor TB treatment outcome. Results: Among 1,366 patients with sputum culture conversion information, 966 (70.7%) had culture conversion and the median time to conversion was 68 days (interquartile range 50-120). The rate of conversion was similar among patients with MDR-TB and DM (adjusted hazard ratio [aHR] 0.95, 95%CI 0.71-1.28) compared to patients with MDR-TB only. The rate of culture conversion was significantly less in patients that currently smoked (aHR 0.82, 95%CI 0.71-0.95), had low body mass index (aHR 0.71, 95%CI 0.59-0.84), second-line resistance (aHR 0.56, 95%CI 0.43-0.73), lung cavities (aHR 0.70, 95%CI 0.59-0.83) and with disseminated TB (aHR 0.75, 95%CI 0.62-0.90). The cumulative risk of poor treatment outcome was also similar among TB patients with and without DM (adjusted risk ratio [aRR] 1.03, 95%CI 0.93-1.14). Conclusions: In adjusted analyses, DM did not impact culture conversion rates in a clinically meaningful way but smoking did. © 2014 Magee et al. Source


Rabin A.S.,Emory University | Kuchukhidze G.,National Center for Tuberculosis and Lung Diseases | Sanikidze E.,National Center for Tuberculosis and Lung Diseases | Kempker R.R.,Emory University | Blumberg H.M.,Emory University
International Journal of Tuberculosis and Lung Disease | Year: 2013

SETTING: Georgia has a high burden of tuberculosis (TB), including multidrug-resistant TB. Enhancing early diagnosis of TB is a priority to reduce transmission. OBJECTIVE: To quantify delays in TB diagnosis and identify risk factors for delay in the country of Georgia. DESIGN: In a cross-sectional study, persons with newly diagnosed, culture-confirmed pulmonary TB were interviewed within 2 months of diagnosis and medical and laboratory records were abstracted. RESULTS: Among 247 persons enrolled, the mean and median total TB diagnostic delay was respectively 89.9 and 59.5 days. The mean and median patient delay was 56.2 and 23.5 days, while health care system delay was 33.7 and 14.0 days. In multivariable analysis, receipt of a medication prior to TB diagnosis was associated with increased overall diagnostic delay (adjusted odds ratio [aOR] 2.28, 95%CI 1.09-4.79); antibiotic use prior to diagnosis increased the risk of prolonged health care delay (aOR 4.16, 95%CI 1.97-8.79). TB cases who had increased patient-related diagnostic delay were less likely to have prolonged health care diagnostic delay (aOR 0.38, 95%CI 0.19-0.74). CONCLUSION: Prolonged delays in detecting TB are common in Georgia. Interventions addressing the misuse of antibiotics and targeting groups at risk for prolonged delay are warranted to reduce diagnostic delays and enhance TB control. © 2012 The Union. Source


Kempker R.R.,Emory University | Vashakidze S.,National Center for Tuberculosis and Lung Diseases | Solomonia N.,National Center for Tuberculosis and Lung Diseases | Dzidzikashvili N.,National Center for Tuberculosis and Lung Diseases | Blumberg H.M.,Emory University
The Lancet Infectious Diseases | Year: 2012

The global emergence and spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis has led to the re-examination of surgery as a possible adjunctive treatment. We present the case of a 26-year-old HIV-seronegative patient with XDR pulmonary tuberculosis refractory to medical therapy. Surgical resection of the patient's solitary cavitary lesion was done as adjunctive treatment, and a successful outcome with a combination of surgery and drug therapy was achieved. We review the history of surgical therapy for tuberculosis and reports of its role in treatment of MDR and XDR tuberculosis. 26 case series and cohort studies were included, and together showed that surgical resection is beneficial in the treatment of drug-resistant tuberculosis. However, the results might not be applicable in all settings because investigations were observational and typically included patients with less severe disease, and all surgeries were done at specialised thoracic-surgery centres. Well designed studies are needed to establish the efficacy of surgery in treatment of drug-resistant tuberculosis. © 2012 Elsevier Ltd. Source

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