Impact of Prior Tuberculosis Treatment With New/Companion Drugs on Clinical Outcomes in Patients Receiving Concomitant Bedaquiline and Delamanid for Multidrug- and Rifampicin-Resistant Tuberculosis.

BACKGROUND: There are scarce data on the clinical outcomes of persons retreated with new/companion anti-tuberculosis (TB) drugs for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB). We sought to evaluate the efficacy and safety of bedaquiline and delamanid containing regimens among patients with and without prior exposure to the new/companion drugs (bedaquiline, delamanid, linezolid, clofazimine, and fluoroquinolones). METHODS: We conducted a retrospective cohort study among patients with pulmonary MDR/RR-TB in Georgia who received bedaquiline and delamanid combination as a part of a salvage regimen from November 2017 to December 2020 in a programmatic setting. RESULTS: Among 106 persons with a median age of 39.5 years, 44 (41.5%) were previously treated with new/companion TB drugs. Patients with prior exposure to new/companion drugs had higher rates of baseline resistance compared to those without exposure to new/companion TB drugs (bedaquiline 15.2% vs 1.8%, linezolid 22.2% vs 16.7%). Sputum culture conversion rates among patients exposed and not exposed to new/companion drugs were 65.9% vs 98.0%, respectively (P < .001). Among patients with and without prior new/companion TB drug use, favorable outcome rates were 41.0% and 82.3%, respectively (P < .001). Treatment adherence in 32 (30.2%) patients was ≤80%. Five of 21 patients (23.8%) who had a baseline and repeat susceptibility test had acquired bedaquiline resistance. QTC/F prolongation (>500 ms) was rare (2.8%). CONCLUSIONS: Prior exposure to new/companion TB drugs was associated with poor clinical outcomes and acquired drug resistance. Tailoring the TB regimen to each patient's drug susceptibility test results and burden of disease and enhancing adherence support may improve outcomes.

Clinical Outcomes Among Patients With Drug-resistant Tuberculosis Receiving Bedaquiline- or Delamanid-Containing Regimens.

BACKGROUND: Bedaquiline and delamanid are newly available drugs for treating multidrug-resistant tuberculosis (MDR-TB); however, there are limited data guiding their use and no comparison studies. METHODS: We conducted a prospective, observational study among patients with MDR-TB in Georgia who were receiving a bedaquiline- or delamanid-based treatment regimen. Monthly sputum cultures, minimal inhibitory concentration testing, and adverse event monitoring were performed. Primary outcomes were culture conversion rates and clinical outcomes. Targeted maximum likelihood estimation and super learning were utilized to produce a covariate-adjusted proportion of outcomes for each regimen. RESULTS: Among 156 patients with MDR-TB, 100 were enrolled and 95 were receiving a bedaquiline-based (n = 64) or delamanid-based (n = 31) regimen. Most were male (82%) and the median age was 38 years. Rates of previous treatment (56%) and cavitary disease (61%) were high. The most common companion drugs included linezolid, clofazimine, cycloserine, and a fluoroquinolone. The median numbers of effective drugs received among patients on bedaquiline-based (4; interquartile range [IQR], 4-4) and delamanid-based (4; IQR, 3.5-5) regimens were similar. Rates of acquired drug resistance were significantly higher among patients receiving delamanid versus bedaquiline (36% vs 10%, respectively; P < .01). Adjusted rates of sputum culture conversion at 2 months (67% vs 47%, respectively; P = .10) and 6 months (95% vs 74%, respectively; P < .01), as well as more favorable clinical outcomes (96% vs 72%, respectively; P < .01), were higher among patients receiving bedaquiline versus delamanid. CONCLUSIONS: Among patients with MDR-TB, bedaquiline-based regimens were associated with higher rates of sputum culture conversion, more favorable outcomes, and a lower rate of acquired drug resistance versus delamanid-based regimens.

Impact of gyrB and eis Mutations in Improving Detection of Second-Line-Drug Resistance among Mycobacterium tuberculosis Isolates from Georgia.

The country of Georgia has a high burden of multi- and extensively drug-resistant tuberculosis (XDR-TB). To evaluate whether mutations in gyrB and eis genes increased the sensitivity of detection of phenotypic resistance to ofloxacin and kanamycin or capreomycin compared to use of the first-generation MTBDRsl assay alone, which tests for mutations in gyrA and rrs genes, a retrospective study of stored Mycobacterium tuberculosis isolates was performed. All isolates underwent DNA sequencing of resistance-determining regions. Among 112 M. tuberculosis isolates with DNA extraction data, targeted sequencing was successfully performed for each gene as follows: for gyrA, 98% sensitivity; for gyrB, 96%; for rrs, 93%; for the eis gene and its promoter, 93%. The specificity and hence the positive predictive value of gyrA and gyrB mutations for detecting ofloxacin resistance were 100%. The addition of gyrB mutations increased the sensitivity of phenotypic ofloxacin resistance detection by 13% (75% to 88%). All rrs resistance-conferring mutations were A1401G, and this mutation had low sensitivity (40% and 18%) and high specificity (95% and 100%) in predicting phenotypic capreomycin and kanamycin resistance, respectively. The eis C-14T mutation increased the sensitivity of phenotypic kanamycin resistance detection by 9% (18% to 27%) and was found solely in kanamycin phenotypic resistance isolates. Our data showed that the inclusion of eis C-14T and gyrB mutations in addition to rrs and gyrA mutations improves the sensitivity of detection of phenotypic ofloxacin and kanamycin resistance, respectively.

Diabetes mellitus and extrapulmonary tuberculosis: site distribution and risk of mortality.

Scarce data exist on the relationship between diabetes and extrapulmonary tuberculosis (EPTB). We evaluated whether diabetes impacts site of TB and risk of death in patients with EPTB. We evaluated a cohort of TB cases from the state of Georgia between 2009 and 2012. Patients aged ⩾16 years were classified by diabetes status according to medical records. Site of EPTB was determined by culture and/or state TB classification. Death was defined by all-cause mortality. Of 1325 eligible reported TB cases, 369 (27·8%) had any EPTB including 258 (19·5%) with only EPTB and 111 (8·4%) with pulmonary TB and EPTB. Of all TB cases, 158 had diabetes (11·9%). In multivariable analysis, the odds of any EPTB was similar in patients with and without diabetes [adjusted odds ratio 1·04, 95% confidence interval (CI) 0·70-1·56]. The risk of death was 23·8% in patients with EPTB and diabetes vs. 9·8% in those with no diabetes (P < 0·01); after adjusting for covariates the difference was not significant (aRR 1·19, 95% CI 0·54-2·63). Diabetes was common in patients with EPTB and risk of death was high. Improved understanding of the relationship between diabetes and EPTB is critical to determine the extent that diabetes affects TB diagnosis and clinical management.

Low BMI increases all-cause mortality rates in patients with drug-resistant TB.

BACKGROUND: Loss to follow-up (LTFU) is common among patients with drug-resistant TB (DR-TB) receiving second-line TB treatment; however, little is known about outcomes after LTFU, including mortality.OBJECTIVE: To determine rates of and factors associated with all-cause mortality among patients with DR-TB who were LTFU.METHODS: Retrospective cohort study of adult patients with DR-TB in Georgia who initiated second-line TB treatment during 2011-2014 and were LTFU. Survival analyses were used to estimate all-cause mortality rates and adjusted hazard ratios (aHR).RESULTS: During 2011-2014, 2,437 second-line treatment episodes occurred and 695 patients were LTFU. Among 695 LTFU patients, 143 (21%) died during 2,686 person-years (PY) post-LTFU (all-cause mortality rate 5.1%, 95% CI 4.3-6.0 per 100 PY). In multivariable analysis, low weight (BMI < 18.5 kg/m²) at treatment initiation (aHR 3.2, 95% CI 2.2-4.7), return to treatment after LTFU (aHR 3.1, 95% CI 2.2-4.4), <12 months of treatment (aHR 2.4, 95% CI 1.4-4.1) and a pre-LTFU positive culture (aHR 3.3, 95% CI 2.2-4.9) were associated with all-cause mortality.CONCLUSION: High all-cause mortality occurred among patients with DR-TB after LTFU despite a low HIV prevalence. Providing additional assistance for patients during DR-TB treatment to prevent LTFU and use of new and shorter treatment regimens may reduce mortality among LTFU.

Weissella confusa bacteremia in a liver transplant patient with hepatic artery thrombosis.

A 54-year-old man with a history of nonalcoholic steatohepatitis and hepatocellular carcinoma presented 2 months after an orthotopic liver transplant with fever and abdominal pain. Two weeks earlier, he had an hepatic artery thrombosis and a biliary stricture, for which an hepatic artery stent and a biliary stent were placed. Laboratory workup was significant for leukocyte count of 7800/mcL with 92% segmented neutrophils, hemoglobin 9.4 g/dL, alanine aminotransferase 98 U/L, aspartate aminotransferase 72 U/L, alkaline phosphatase 358 U/L, albumin 2.8 mg/dL, and total bilirubin 1.6 mg/dL. A computed tomography scan of the abdomen and pelvis revealed multiple small fluid collections in the liver consistent with bilomas, and an hepatic angiogram showed complete occlusion of the common hepatic artery. Two sets of blood cultures were positive for an organism initially identified by MicroScan(®) analysis as an α-hemolytic Streptococcus species that was resistant to vancomycin. Further testing confirmed the organism as Weissella confusa 2 days later. W. confusa is a gram-positive coccobacillus that may be misidentified as a Lactobacillus when cultured. It is commonly found in sewage, carrots, sugar cane, fermented foods, and intestinal flora. Although only 4 cases of clinical infection with W. confusa have been described previously, W. confusa has been isolated from the stool of liver transplant patients, and may be an underreported cause of infection owing to improper identification. As it can cause clinical infection in these immunosuppressed hosts, identification of this organism is paramount because it is vancomycin resistant, and incorrect identification could lead to improper antimicrobial selection and ultimately worsened patient morbidity or mortality.

Clinical outcomes among patients with tuberculous meningitis receiving intensified treatment regimens.

SETTING: National Center for Tuberculosis and Lung Diseases (NCTLD), Tbilisi, Georgia.OBJECTIVE: To determine clinical outcomes of patients with tuberculous meningitis (TBM) treated with an intensified regimen including a fluoroquinolone (FQ) and an injectable agent.DESIGN: Prospective cohort of patients aged ≥16 years initiating treatment for TBM at the NCTLD from January 2018 to December 2019. Treatment outcomes and neurologic disability at 1, 6 and 12 months after treatment initiation were assessed.RESULTS: Among 77 patients with median follow-up time of 363 days (IQR 269-374), 97% received a FQ, 62% an injectable agent, 44% linezolid and 39% a carbapenem. Fifty-seven patients (74%) successfully completed treatment, 2 (2.6%) had treatment failure, 6 (7.8%) died, and the remainder (12%) were lost to follow up. Among 11 patients treated for multidrug-resistant TBM, the median follow-up time was 467 days and one patient (8%) died. Regarding neurologic outcomes, 14/76 (18%) patients had Modified Rankin Scores of 0 at baseline, improving to 85% (56/66) and 94% (47/50) at 6 and 12 months, respectively.CONCLUSION: Intensified multidrug treatment regimens including a FQ and an injectable agent in all patients and newly implemented drugs in patients with multidrug-resistant TBM resulted in low mortality and favorable neurologic outcomes.

Linezolid use for drug-resistant tuberculosis in Georgia: a retrospective cohort study.

SETTING: Data on the long-term use of linezolid (LZD) in the treatment of drug-resistant pulmonary tuberculosis (DR-PTB) are limited.OBJECTIVE: To assess safety, tolerability and efficacy of LZD-containing regimens for the treatment of DR-PTB in the country of Georgia.DESIGN: A retrospective study was conducted among DR-PTB patients receiving LZD 600 mg/day as part of newly implemented regimens (bedaquiline or delamanid, repurposed and second-line drugs) from July 2014 to October 2015 in programmatic conditions and following WHO recommendations.RESULTS: One hundred mostly male (82%) patients with a median age of 33 years received LZD. Most patients (77%) had previously been treated for TB; 57% had extensively drug-resistant TB. The median duration of LZD use was 503 days (interquartile range 355-616). LZD-associated adverse events occurred in 12 patients, leading to discontinuation in 4 (2 each due to peripheral neuropathy and cytopenias), and dose reduction to 300 mg/day in 6 cases (4 due to peripheral neuropathy and 2 for cytopenias). Almost all patients (95%) achieved culture conversion and 79% had a successful treatment outcomes.CONCLUSION: Treatment regimens including lengthy LZD use showed fairly good safety and tolerability and were associated with high rates of culture conversion and favorable outcomes.

Evaluation of a comprehensive diabetic foot ulcer care quality model.

AIMS: Diabetes-related amputations are typically preceded by a diabetic foot ulcer (DFU) but models to assess the quality of care are lacking. We investigated a model to measure inpatient and outpatient quality. METHODS: Cohort study among adults hospitalized with a DFU to a safety-net hospital during 2016. We measured adherence to DFU-related quality metrics based on guidelines during and 12 months following hospitalization. Inpatient metrics included ankle-brachial index measurement during or 6 months prior to hospitalization, receiving diabetes education and a wound offloading device prior to discharge. Outpatient metrics included wound care ≤30 days of discharge, in addition to hemoglobin A1c (HbA1c) ≤8%, tobacco cessation, and retention in care (≥2 clinic visits ≥90 days apart) 12 months following discharge. RESULTS: 323 patients were included. Regarding inpatient metrics, 8% had an ankle brachial index measurement, 37% received diabetes education, and 20% received offloading prior to discharge. Regarding outpatient metrics, 33% received wound care ≤30 days of discharge. Twelve months following discharge, 34% achieved a HbA1c ≤8%, 13% quit tobacco, and 52% were retained in care. Twelve-month amputation-free survival was 71%. CONCLUSIONS: Our model demonstrated large gaps in DFU guideline-adherent care. Implementing measures to close these gaps could prevent amputations.

Rates and risk factors for nephrotoxicity and ototoxicity among tuberculosis patients in Tbilisi, Georgia.

SETTING: Treatment of multidrug-resistant tuberculosis (MDR-TB) is lengthy and utilizes second-line anti-TB drugs associated with frequent adverse drug reactions (ADRs).OBJECTIVE: To evaluate the prevalence of and risk factors for ADRs among patients with MDR- and extensively drug-resistant TB (XDR-TB).DESIGN: A retrospective chart review of patients initiating treatment for M/XDR-TB in 2010-2012 in Tbilisi, Georgia.RESULTS: Eighty (54%) and 38 (26%) of 147 patients developed nephrotoxicity per RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) classification and ototoxicity, respectively. Twenty-five (17%) patients required permanent interruption of injectables due to an ADR. Median hospital stay, total treatment duration and number of regimen changes were higher among those with nephrotoxicity and/or ototoxicity, compared to those without (P < 0.01). Multinomial logistic regression analysis identified increasing age (per year) as a risk factor for nephrotoxicity (aOR 1.08, 95%CI 1.03-1.12) and for both, nephro- and ototoxicity (aOR 1.11, 95%CI 1.05-1.17). Low baseline creatinine clearance (CrCl) was a significant risk factor for developing nephrotoxicity (aOR 1.05, 95%CI 1.02-1.07).CONCLUSION: Second-line injectable drug-related ADRs are common among M/XDR-TB patients. Patients with increasing age and low baseline CrCl should be monitored closely for injectable-related ADRs. Notably, our findings support WHO's latest recommendations on introduction of injectable free anti-TB treatment regimens.

A survey of the tuberculosis physician workforce in the country of Georgia.

SETTING: A well-trained and sufficient tuberculosis (TB) workforce is essential for disease control, especially in an era of newly implemented diagnostics and medications. However, there are few reports on the status of the TB workforce in many endemic countries. OBJECTIVE: To evaluate the demographics, salary, career satisfaction, and attitudes towards the field of TB among the physician TB workforce in the country of Georgia. DESIGN: A cross-sectional study of physicians in the current Georgian National TB Programme (NTP) using an anonymous 31-item questionnaire. RESULTS: Among 184 NTP physicians countrywide, 142 (77%) were contacted and 138 (75%) completed questionnaires. The median age was 56 years (interquartile range 50-64); most (81%) were female. The monthly salary from TB work was USD205 for 50% of respondents. Nearly half (47%) received an additional salary from another source. Many physicians (65%) indicated that they were satisfied with their work, but over half (55%) were unsatisfied with reimbursement. While most physicians (78%) were concerned about the lack of interest in TB, only 36% would recommend a career in TB care. CONCLUSION: While the current TB workforce in Georgia finds their work fulfilling, an ageing workforce, low salaries and perceived lack of interest in the field are a matter of concern for future TB control.

A population-based tuberculosis contact investigation in the country of Georgia.

Setting: Identification and screening of contacts of patients with active tuberculosis (TB) is infrequent in low- and middle-income countries. Objective: To estimate the incidence, prevalence and risk factors of latent tuberculous infection (LTBI) and active TB among contacts of newly reported smear-positive TB patients. Design: A population-based contact investigation of sputum smear-positive pulmonary TB (PTB) cases diagnosed between April and December 2012 in Georgia was conducted. LTBI was assessed using the tuberculin skin test (TST). Contacts with active TB were identified from the National TB Program surveillance database. Results: Among 896 index patients with active TB, 3133 contacts were identified and 1157 (37%) underwent a TST, 34% of whom were positive. Most contacts were household contacts (86%) and female (58%). Among contacts, the 1-year period prevalence of active TB was 3.3% (95%CI 2.70-3.98); the incidence rate was 1101 per 100 000 person-years (95%CI 822-1443). In multivariable analysis, household contacts were more likely to have LTBI (adjusted OR [aOR] 2.28, 95%CI 1.49-3.49) than close contacts. Conclusions: A high prevalence of both LTBI and active TB was identified among contacts of PTB cases. Efforts aimed at active case finding among TB contacts should improve early case detection and enhance TB control efforts.

Contexte : Identifier et dépister les contacts des patients atteints de tuberculose (TB) active n'est pas souvent réalisé dans les pays à revenu faible et moyen.Objectif : Estimer l'incidence, la prévalence et les facteurs de risque d'infection tuberculeuse latente (LTBI) et de TB active parmi les contacts de patients TB nouveaux à frottis positif.Schéma : Une investigation en population a été réalisée à la recherche des contacts de cas de TB pulmonaire à frottis positif diagnostiqués entre avril et décembre 2012 en Géorgie ; la LTBI a été évaluée grâce à un test cutané à la tuberculine (TST). Les contacts atteints de TB active ont été identifiés à partir de la base de données de surveillance du Programme National TB.Résultats : Parmi 896 patients index atteints de TB active, 3133 contacts ont été identifiés et 1157 (37%) ont eu un TST, dont 34% ont été positifs. La majorité des contacts ont été des contacts domiciliaires (86%) et des femmes (58%). Parmi les contacts, la prévalence sur un an de la TB active a été de 3,3% (IC95% 2,70­3,98) tandis que le taux d'incidence a été de 1101 par 100 000 années-personne (IC95% 822­1443). En analyse multivariée, les contacts domiciliaires ont été plus susceptibles d'avoir une LTBI (OR ajusté [ORa] 2,28 ; IC95% 1,49­3,49) comparés aux contacts étroits.Conclusion : Une prévalence élevée à la fois de LTBI et de TB active a été identifiée parmi les contacts des cas de TB pulmonaire. Les efforts visant à une recherche active de cas parmi les contacts de TB devraient améliorer une détection précoce des cas et renforcer les efforts de lutte contre la TB.

Marco de referencia: La localización y la investigación de contactos de pacientes con tuberculosis (TB) activa rara vez se siguen en los países con ingresos bajos y medianos.Objetivo: Estimar la incidencia, la prevalencia y los factores de riesgo de contraer la infección tuberculosa latente (LTBI) y la TB activa en los contactos de los casos nuevos de TB con baciloscopia positiva notificados.Método: Se llevó a cabo una investigación de base poblacional de los contactos de casos de TB pulmonar con baciloscopia positiva diagnosticados de abril a diciembre del 2012 en Georgia; se investigó la LTBI mediante la prueba cutánea de la tuberculina (TST). Los contactos con TB activa se localizaron en la base de datos de vigilancia del Programa Nacional contra la Tuberculosis.Resultados: Se reconocieron 3133 contactos de los 896 casos iniciales con TB activa y se practicó la TST en 1157 (37%), de los cuales el 34% obtuvo un resultado positivo. La mayoría de los contactos fueron contactos domiciliarios (86%) y de sexo femenino (58%). En los contactos, la prevalencia a un año de TB activa fue 3,3% (IC95% 2,70­3,98) y la tasa de incidencia fue 1101 por 100 000 años-persona (IC95% 822­1443). El análisis multivariante reveló que la probabilidad de padecer la ITL era mayor en los contactos domiciliarios (cociente de posibilidades ajustado 2,28; IC95% 1,49­3,49) que los contactos directos (no domiciliarios).Conclusiones: Se encontró una alta prevalencia de LTBI y de TB activa en los contactos de los casos de TB pulmonar. Las iniciativas de búsqueda activa de casos en los contactos de los pacientes con TB deberían mejorar la detección temprana y reforzar los esfuerzos de control de la TB.

High utility of active tuberculosis case finding in an Ethiopian prison.

SETTING: Hawassa Prison, Southern Region of Ethiopia. OBJECTIVE: To determine the burden of pulmonary tuberculosis (TB) using active case finding among prisoners. DESIGN: In this cross-sectional study, prisoners were screened for TB using a symptom screen. Those with cough of 2 weeks had spot and morning sputum samples collected for acid-fast bacilli (AFB) smear microscopy and molecular diagnostic testing (Xpert® MTB/RIF). RESULTS: Among 2068 prisoners, 372 (18%) had a positive cough screen. The median age of these 372 persons was 23 years, 97% were male and 63% were from urban areas. Among those with a positive symptom screen, 8 (2%) were AFB sputum smear-positive and 31 (8%) were Xpert-positive. The point prevalence of pulmonary TB at the prison was 1748 per 100 000 persons. In multivariate analysis, persons with cough >4 weeks were more likely to have TB (OR 3.34, 95%CI 1.54-7.23). CONCLUSION: A high prevalence of TB was detected among inmates at a large Ethiopian prison. Active case finding using a cough symptom screen in combination with Xpert had high utility, and has the potential to interrupt transmission of Mycobacterium tuberculosis in correctional facilities in low- and middle-income, high-burden countries.

Smoking behavior and beliefs about the impact of smoking on anti-tuberculosis treatment among health care workers.

SETTING: Tuberculosis (TB) health care facilities throughout Georgia. OBJECTIVE: To describe smoking behaviors among health care workers (HCWs) at TB facilities and determine HCWs' knowledge and beliefs regarding the impact of tobacco use on anti-tuberculosis treatment. DESIGN: Cross-sectional survey from May to December 2014 in Georgia. Adult HCWs (age 18 years) at TB facilities were eligible. We administered a 60-question anonymous survey about tobacco use and knowledge of the effect of smoking on anti-tuberculosis treatment. RESULTS: Of the 431 HCWs at TB facilities who participated, 377 (87.5%) were female; the median age was 50 years (range 20-77). Overall, 59 (13.7%) HCWs were current smokers and 35 (8.1%) were past smokers. Prevalence of current smoking was more common among physicians than among nurses (18.6% vs. 7.9%, P < 0.0001). Among HCWs, 115 (26.7%) believed smoking does not impact anti-tuberculosis treatment, and only 25.3% of physicians/nurses received formal training in smoking cessation approaches. Physicians who smoked were significantly more likely to believe that smoking does not impact anti-tuberculosis treatment than non-smoking physicians (aOR 5.11, 95%CI 1.46-17.90). CONCLUSION: Additional education about the effect of smoking on TB treatment outcomes is needed for staff of TB health care facilities in Georgia. Nurses and physicians need more training about smoking cessation approaches for patients with TB.

Increased risk of latent tuberculous infection among persons with pre-diabetes and diabetes mellitus.

SETTING: Although diabetes mellitus (DM) is an established risk factor for active tuberculosis (TB) disease, little is known about the association between pre-DM, DM, and latent tuberculous infection (LTBI). OBJECTIVE: To estimate the association between DM and LTBI. DESIGN: We conducted a cross-sectional study among recently arrived refugees seen at a health clinic in Atlanta, GA, USA, between 2013 and 2014. Patients were screened for DM using glycosylated-hemoglobin (HbA1c), and for LTBI using the QuantiFERON(®)-TB (QFT) test. HbA1c and QFT results, demographic information, and medical history were abstracted from patient charts. RESULTS: Among 702 included patients, 681 (97.0%) had HbA1c and QFT results. Overall, 54 (7.8%) patients had DM and 235 (33.8%) had pre-DM. LTBI was prevalent in 31.3% of the refugees. LTBI prevalence was significantly higher (P < 0.01) among patients with DM (43.4%) and pre-DM (39.1%) than in those without DM (25.9%). Refugees with DM (adjusted OR [aOR] 2.3, 95%CI 1.2-4.5) and pre-DM (aOR 1.7, 95%CI 1.1-2.4) were more likely to have LTBI than those without DM. CONCLUSION: Refugees with DM or pre-DM from high TB burden countries were more likely to have LTBI than those without DM. Dysglycemia may impair the immune defenses involved in preventing Mycobacterium tuberculosis infection.

A comparison of the Xpert(®) MTB/RIF and GenoType(®) MTBDRplus assays in Georgia.

Few studies have directly compared the performance of rapid molecular diagnostic tests for tuberculosis (TB). We found that the commercially available molecular diagnostic tests Xpert(®) MTB/RIF and GenoType(®) MTBDRplus both provided timely and accurate results compared to conventional phenotypic tests in detecting TB and rifampicin resistance.

Intensified tuberculosis case finding among HIV-infected persons using a WHO symptom screen and Xpert(®) MTB/RIF.

SETTING: Human immunodeficiency virus (HIV) clinic in Addis Ababa, Ethiopia. The World Health Organization (WHO) recommends active tuberculosis (TB) case-finding among people living with HIV (PLHIV) in high-burden settings. OBJECTIVE: To evaluate the effectiveness of combining a WHO-recommended symptom screen and the Xpert(®) MTB/RIF test to enhance TB case finding. DESIGN: In this cross-sectional study, PLHIV were screened for TB using a WHO-recommended symptom-based algorithm (cough, fever, night sweats, weight loss). Those with a positive symptom screen (⩾1 symptom) underwent diagnostic testing with smear microscopy, culture, and Xpert. RESULTS: Of 828 PLHIV (89% on antiretroviral therapy), 321 (39%) had a positive symptom screen. In multivariate analysis, an unscheduled clinic visit (aOR 3.78, 95%CI 2.69-5.32), CD4 count <100 cells/µl (aOR 2.62, 95%CI 1.23-5.59) and previous history of TB (aOR 1.62, 95%CI 1.12-2.31) were predictors of a positive symptom screen. Among those with a positive symptom screen, 6% had active pulmonary TB. Smear microscopy sensitivity for TB was poor (30%) compared to culture and Xpert. CONCLUSIONS: A positive symptom screen was common among PLHIV, creating a substantial laboratory burden. Smear microscopy had poor sensitivity for active TB disease. Given the high rate of positive symptom screen, substantial additional resources are needed to implement intensified TB case finding among PLHIV in high-burden areas.

Diabetes mellitus is associated with cavities, smear grade, and multidrug-resistant tuberculosis in Georgia.

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 define DM (⩾ 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.

Performance of the MTBDRsl assay in Georgia.

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 GenoType® 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.