National Center for Tuberculosis and Lung Diseases

Tbilisi, Georgia

National Center for Tuberculosis and Lung Diseases

Tbilisi, Georgia

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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.


Lomtadze N.,National Center for Tuberculosis and Lung Diseases | Kupreishvili L.,National Center for Tuberculosis and Lung Diseases | Salakaia A.,National Center for Tuberculosis and Lung Diseases | Vashakidze S.,National Center for Tuberculosis and Lung Diseases | And 5 more authors.
PLoS ONE | Year: 2013

Background: The country of Georgia has a high prevalence of tuberculosis (TB) and hepatitis C virus (HCV) infection. Purpose: To determine whether HCV co-infection increases the risk of incident drug-induced hepatitis among patients on first-line anti-TB drug therapy. Methods: Prospective cohort study; HCV serology was obtained on all study subjects at the time of TB diagnosis; hepatic enzyme tests (serum alanine aminotransferase [ALT] activity) were obtained at baseline and monthly during treatment. Results: Among 326 study patients with culture-confirmed TB, 68 (21%) were HCV co-infected, 14 (4.3%) had chronic hepatitis B virus (HBV) infection (hepatitis B virus surface antigen positive [HBsAg+]), and 6 (1.8%) were HIV co-infected. Overall, 19% of TB patients developed mild to moderate incident hepatotoxicity. In multi-variable analysis, HCV co-infection (adjusted Hazards Ratio [aHR]=3.2, 95% CI=1.6-6.5) was found to be an independent risk factor for incident anti-TB drug-induced hepatotoxicity. Survival analysis showed that HCV co-infected patients developed hepatitis more quickly compared to HCV seronegative patients with TB. Conclusion: A high prevalence of HCV co-infection was found among patients with TB in Georgia. Drug-induced hepatotoxicity was significantly associated with HCV co-infection but severe drug-induced hepatotoxicity (WHO grade III or IV) was rare. © 2013 Lomtadze et al.


PubMed | National Center for Tuberculosis and Lung Diseases, Autonomous University of Barcelona and CIBER ISCIII
Type: | Journal: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases | Year: 2016

Our aim was to retrospectively compare clinical data and characteristics of removed lesions of the cohort of patients undergoing therapeutical surgery for their tuberculosis.Demographic and epidemiological details, clinical data, data on the surgery performed, macroscopic characteristics of the TB lesions removed, and outcome were recorded retrospectively from the 137 patients who underwent therapeutical surgery for their TB in Tbilisi, Georgia during 2014 and 2015.Men represented 70% of the included patients, presented more comorbidities and underwent operation earlier in terms of days between diagnostic and surgery. Women underwent operation at younger ages, and in MDR/XDR-TB cases, showed higher percentages of sputum conversion at >2 months and of fresh necrosis in the surgical specimens, suggesting a worse evolution. Half of cases were MDR/XDR-TB cases. In spite of being considered microbiologically cured according to WHO, a non despricable percentage of cases showed viable bacilli in the surgical specimen. Even if no causality could be statistically demonstrated, differences could be encountered according to gender and drug susceptibility of the responsible strains.According to our results, host factors such as gender, type of necrosis found in the lesions, size of lesions and presence of viable bacilli in the surgical specimen, should be included in future studies on therapeutical surgery of TB. As most of studies are done in MDR/XDR-TB, more data on DS-TB operated cases are needed. Our results also highlight that, in spite of achieving the microbiologically cured status, sterilization might not occur, and thus new biomarkers and new methods to evaluate the healing process of TB patients are urgently needed and radiological assays should be taken into account.


Magee M.J.,Georgia State University | Magee M.J.,Emory University | Kempker R.R.,Emory University | Kipiani M.,National Center for Tuberculosis and Lung Diseases | And 6 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2015

SETTING: National tuberculosis (TB) treatment facility in the country of Georgia. OBJECTIVE: To determine the prevalence of diabetes mellitus (DM) and pre-DM among patients with TB using glycosylated-hemoglobin (HbA1c), and to estimate the association between DM and clinical characteristics and response to anti-tuberculosis treatment. DESIGN: A cohort study was conducted from 2011 to 2014 at the National Centre for TB and Lung Disease in Tbilisi. Patients aged ≥35 years with pulmonary TB were included. HbA1c was used to defineDM(≥6.5%), pre-DM (≥5.7-6.4%), and no DM (<5.7%). Interviews and medical chart abstraction were performed. Regression analyses estimated associations between DM and 1) baseline TB characteristics and 2) anti-tuberculosis treatment outcomes. RESULTS : A total of 318 newly diagnosed patients with TB were enrolled. The prevalence of DM and pre-DM was 11.6% and 16.4%, respectively. In multivariable analyses, patients with TB-DM had more cavitation (adjusted OR [aOR] 2.26), higher smear grade (aOR 2.37), and more multidrug-resistant TB (MDR-TB) (aOR 2.27) than patients without DM. The risk of poor anti-tuberculosis treatment outcomes was similar among patients with and those without DM(28.1%vs. 23.6%). CONCLUSION: DM and pre-DM were common among adults with newly diagnosed pulmonary TB in Tbilisi, Georgia, and DM was associated with more clinical symptoms, and MDR-TB, at presentation. © 2015 The Union.


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.


Shubladze N.,National Center for Tuberculosis and Lung Diseases | Tadumadze N.,National Center for Tuberculosis and Lung Diseases | Bablishvili N.,National Center for Tuberculosis and Lung Diseases
International Journal of Mycobacteriology | Year: 2013

Background: Tuberculosis (TB) infections caused by multidrug-resistant Mycobacterium tuberculosis (MDR MTB) remain a significant public health concern worldwide. Georgia has a high prevalence of MDR MTB. The genetic mechanisms underlying the emergence of MDR MTB strains in this region are poorly understood and need to be determined for developing better strategies for TB control. This study investigated the frequency of major drug resistance mutations across rpoB, katG and inhA loci of Georgian MDR MTB strains and explored differences between new and previously treated patients. Methods: A total of 634 MTB strains were examined for which an MDR phenotype had been previously determined by the proportions method. The GenoType®MTBDRplus system was applied to screen the strains for the presence of rpoB (S531L, H526D, H526Y, and D516V), katG (S315T) and inhA promoter region (C15T and T8C) mutations. The target loci were amplified by PCR and then hybridized with the respective site-specific and wild type (control) probes. Results: Out of the 634 isolates tested considered by phenotypic testing to be resistant to RIF and INH, this resistance was confirmed by the GenoType®MTBDRplus assay in 575 (90.7%) isolates. RIF resistance was seen in 589 (92.9%) and INH resistance was seen in 584 (92.1%); 67.2% and 84.3% of MDR strains harbored respectively rpoB S531L and katG S315T mutations (generally known as having low or no fitness cost in MTB). The inhA C15T mutation was detected in 22.6% of the strains, whereas rpoB H526D, rpoB H526Y, rpoB D516V and inhA T8C were revealed at a markedly lower frequency (≤5.2%). The specific mutations responsible for the RIF resistance of 110 isolates (17.4%) could not be detected as no corresponding mutant probe was indicated in the assay. There was no specific association of the presence of mutations with the gender/age groups. All types of prevailing mutations had higher levels in new cases. Conclusions: A great majority of the Georgian MDR MTB strains have a strong preference for the drug resistance mutations carrying no or low fitness cost. Thus, it can be suggested that MDR MTB strains with such mutations will continue to arise in Georgia at a high frequency even in the absence of antibiotic pressure. © 2013 Asian-African Society for Mycobacteriology.


Kempker R.R.,Emory University | Rabin A.S.,Emory University | Nikolaishvili K.,National Center for Tuberculosis and Lung Diseases | Kalandadze I.,National Center for Tuberculosis and Lung Diseases | And 3 more authors.
Clinical Infectious Diseases | Year: 2012

The pathogenesis of increasing drug resistance among patients with multidrug-resistant or extensively drug-resistant tuberculosis undergoing treatment is poorly understood. Increasing drug resistance found among Mycobacterium tuberculosis recovered from cavitary isolates compared with paired sputum isolates suggests pulmonary cavities may play a role in the development of worsening tuberculosis drug resistance. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.


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.


Tukvadze N.,National Center for Tuberculosis and Lung Diseases | Kempker R.R.,Emory University | Kalandadze I.,National Center for Tuberculosis and Lung Diseases | Kurbatova E.,Emory University | And 5 more authors.
PLoS ONE | Year: 2012

Background: The WHO has recommended the implementation of rapid diagnostic tests to detect and help combat M/XDR tuberculosis (TB). There are limited data on the performance and impact of these tests in field settings. Methods: The performance of the commercially available Genotype MTBDRplus molecular assay was compared to conventional methods including AFB smear, culture and drug susceptibility testing (DST) using both an absolute concentration method on Löwenstein-Jensen media and broth-based method using the MGIT 960 system. Sputum specimens were obtained from TB suspects in the country of Georgia who received care through the National TB Program. Results: Among 500 AFB smear-positive sputum specimens, 458 (91.6%) had both a positive sputum culture for Mycobacterium tuberculosis and a valid MTBDRplus assay result. The MTBDRplus assay detected isoniazid (INH) resistance directly from the sputum specimen in 159 (89.8%) of 177 specimens and MDR-TB in 109 (95.6%) of 114 specimens compared to conventional methods. There was high agreement between the MTBDRplus assay and conventional DST results in detecting MDR-TB (kappa = 0.95, p<0.01). The most prevalent INH resistance mutation was S315T (78%) in the katG codon and the most common rifampicin resistance mutation was S531L (68%) in the rpoB codon. Among 13 specimens from TB suspects with negative sputum cultures, 7 had a positive MTBDRplus assay (3 with MDR-TB). The time to detection of MDR-TB was significantly less using the MTBDRplus assay (4.2 days) compared to the use of standard phenotypic tests (67.3 days with solid media and 21.6 days with broth-based media). Conclusions: Compared to conventional methods, the MTBDRplus assay had high accuracy and significantly reduced time to detection of MDR-TB in an area with high MDR-TB prevalence. The use of rapid molecular diagnostic tests for TB and drug resistance should increase the proportion of patients promptly placed on appropriate therapy. © 2012 Tukvadze et al.


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.

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