Doff Thy Gown-Shedding Contact Precautions for COVID-19.

SARS-CoV-2 is predominantly transmitted through aerosols (ie, airborne transmission); however, the US Centers for Disease Control and Prevention continue to recommend the use of contact precautions (a gown and gloves) for the care of patients with COVID-19. Infection-prevention guidelines should reflect the current science and eliminate this wasteful practice.

Association of Treated and Untreated Chronic Hepatitis C With the Incidence of Active Tuberculosis Disease: A Population-Based Cohort Study.

BACKGROUND: Hepatitis C virus (HCV) infection causes dysregulation and suppression of immune pathways involved in the control of tuberculosis (TB) infection. However, data on the role of chronic hepatitis C as a risk factor for active TB are lacking. We sought to evaluate the association between HCV infection and the development of active TB. METHODS: We conducted a cohort study in Georgia among adults tested for HCV antibodies (January 2015-September 2020) and followed longitudinally for the development of newly diagnosed active TB. Data were obtained from the Georgian national programs of hepatitis C and TB. The exposures of interest were untreated and treated HCV infection. A Cox proportional hazards model was used to calculate adjusted hazard ratios (aHRs). RESULTS: A total of 1 828 808 adults were included (median follow-up time: 26 months; IQR: 13-39 months). Active TB was diagnosed in 3163 (0.17%) individuals after a median of 6 months follow-up (IQR: 1-18 months). The incidence rate per 100 000 person-years was 296 among persons with untreated HCV infection, 109 among those with treated HCV infection, and 65 among HCV-negative persons. In multivariable analysis, both untreated (aHR = 2.9; 95% CI: 2.4-3.4) and treated (aHR = 1.6; 95% CI: 1.4-2.0) HCV infections were associated with a higher hazard of active TB, compared with HCV-negative persons. CONCLUSIONS: Adults with HCV infection, particularly untreated individuals, were at higher risk of developing active TB disease. Screening for latent TB infection and active TB disease should be part of clinical evaluation of people with HCV infection, especially in high-TB-burden areas.

Hepatitis C care cascade among patients with and without tuberculosis: Nationwide observational cohort study in the country of Georgia, 2015-2020.

BACKGROUND: The Eastern European country of Georgia initiated a nationwide hepatitis C virus (HCV) elimination program in 2015 to address a high burden of infection. Screening for HCV infection through antibody testing was integrated into multiple existing programs, including the National Tuberculosis Program (NTP). We sought to compare the hepatitis C care cascade among patients with and without tuberculosis (TB) diagnosis in Georgia between 2015 and 2019 and to identify factors associated with loss to follow-up (LTFU) in hepatitis C care among patients with TB. METHODS AND FINDINGS: Using national ID numbers, we merged databases of the HCV elimination program, NTP, and national death registry from January 1, 2015 to September 30, 2020. The study population included 11,985 adults (aged ≥18 years) diagnosed with active TB from January 1, 2015 through December 31, 2019, and 1,849,820 adults tested for HCV antibodies between January 1, 2015 and September 30, 2020, who were not diagnosed with TB during that time. We estimated the proportion of patients with and without TB who were LTFU at each step of the HCV care cascade and explored temporal changes. Among 11,985 patients with active TB, 9,065 (76%) patients without prior hepatitis C treatment were tested for HCV antibodies, of which 1,665 (18%) had a positive result; LTFU from hepatitis C care was common, with 316 of 1,557 (20%) patients with a positive antibody test not undergoing viremia testing and 443 of 1,025 (43%) patients with viremia not starting treatment for hepatitis C. Overall, among persons with confirmed viremic HCV infection, due to LTFU at various stages of the care cascade only 28% of patients with TB had a documented cure from HCV infection, compared to 55% among patients without TB. LTFU after positive antibody testing substantially decreased in the last 3 years, from 32% among patients diagnosed with TB in 2017 to 12% among those diagnosed in 2019. After a positive HCV antibody test, patients without TB had viremia testing sooner than patients with TB (hazards ratio [HR] = 1.46, 95% confidence intervals [CI] [1.39, 1.54], p < 0.001). After a positive viremia test, patients without TB started hepatitis C treatment sooner than patients with TB (HR = 2.05, 95% CI [1.87, 2.25], p < 0.001). In the risk factor analysis adjusted for age, sex, and case definition (new versus previously treated), multidrug-resistant (MDR) TB was associated with an increased risk of LTFU after a positive HCV antibody test (adjusted risk ratio [aRR] = 1.41, 95% CI [1.12, 1.76], p = 0.003). The main limitation of this study was that due to the reliance on existing electronic databases, we were unable to account for the impact of all confounding factors in some of the analyses. CONCLUSIONS: LTFU from hepatitis C care after a positive antibody or viremia test was high and more common among patients with TB than in those without TB. Better integration of TB and hepatitis C care systems can potentially reduce LTFU and improve patient outcomes both in Georgia and other countries that are initiating or scaling up their nationwide hepatitis C control efforts and striving to provide personalized TB treatment.

TCA cycle remodeling drives proinflammatory signaling in humans with pulmonary tuberculosis.

The metabolic signaling pathways that drive pathologic tissue inflammation and damage in humans with pulmonary tuberculosis (TB) are not well understood. Using combined methods in plasma high-resolution metabolomics, lipidomics and cytokine profiling from a multicohort study of humans with pulmonary TB disease, we discovered that IL-1ß-mediated inflammatory signaling was closely associated with TCA cycle remodeling, characterized by accumulation of the proinflammatory metabolite succinate and decreased concentrations of the anti-inflammatory metabolite itaconate. This inflammatory metabolic response was particularly active in persons with multidrug-resistant (MDR)-TB that received at least 2 months of ineffective treatment and was only reversed after 1 year of appropriate anti-TB chemotherapy. Both succinate and IL-1ß were significantly associated with proinflammatory lipid signaling, including increases in the products of phospholipase A2, increased arachidonic acid formation, and metabolism of arachidonic acid to proinflammatory eicosanoids. Together, these results indicate that decreased itaconate and accumulation of succinate and other TCA cycle intermediates is associated with IL-1ß-mediated proinflammatory eicosanoid signaling in pulmonary TB disease. These findings support host metabolic remodeling as a key driver of pathologic inflammation in human TB disease.

Cycloserine and Linezolid for Tuberculosis Meningitis: Pharmacokinetic Evidence of Potential Usefulness.

BACKGROUND: The ability of antituberculosis drugs to cross the blood-brain barrier and reach the central nervous system is critical to their effectiveness in treating tuberculosis meningitis (TBM). We sought to fill a critical knowledge gap by providing data on the ability of new and repurposed antituberculosis drugs to penetrate into the cerebrospinal fluid (CSF). METHODS: We conducted a clinical pharmacology study among patients treated for TBM in Tbilisi, Georgia, from January 2019 until January 2020. Serial serum and CSF samples were collected while patients were hospitalized. CSF was collected from routine lumbar punctures with the timing of the lumbar puncture alternating between 2 and 6 hours to capture early and late CSF penetration. RESULTS: A total of 17 patients treated for TBM (8 with confirmed disease) were included; all received linezolid, with a subset receiving cycloserine (5), clofazimine (5), delamanid (4), and bedaquiline (2). All CSF measurements of bedaquiline (12), clofazimine (24), and delamanid (19) were below the limit of detection. The median CSF concentrations of cycloserine at 2 and 6 hours were 15.90 and 15.10 µg/mL with adjusted CSF/serum ratios of 0.52 and 0.66. CSF concentrations of linezolid were 0.90 and 3.14 µg/mL at 2 and 6 hours, with adjusted CSF/serum ratios of 0.25 and 0.59, respectively. CSF serum linezolid concentrations were not affected by rifampin coadministration. CONCLUSIONS: Based on moderate to high CSF penetration, linezolid and cycloserine may be effective drugs for TBM treatment, whereas the utility of bedaquiline, delamanid, and clofazimine is uncertain given their low CSF penetration.

Linezolid Exposure Is Associated with Cytopenias in Patients Treated for Multidrug-Resistant Tuberculosis.

Although linezolid is effective for multidrug-resistant TB (MDR-TB) tuberculosis treatment, it is associated with cytopenias after 4 weeks of administration. Data on toxicities with long-term use of linezolid and drug pharmacodynamics in MDR-TB treatment are limited, and concerns about toxicity present barriers to wider implementation. This was a secondary analysis of a prospective cohort study of patients treated for MDR-TB in the country of Georgia from 2015 to 2017. Intensive blood sampling 4 to 6 weeks after treatment initiation with linezolid 600 mg daily was performed for pharmacokinetic (PK) analysis, including linezolid trough concentration (Cmin) and area under the curve from 0 to 24 hours (AUC0-24). Linezolid exposure was defined using literature-reported thresholds. Cytopenias were defined using an NIH adverse event (AE) scale. Logistic regression was used to evaluate the relationship between linezolid exposure and cytopenias. Among 76 patients receiving linezolid in their baseline treatment regimen and who had PK data available, cytopenia AEs occurred in 30 (39.5%) for an incidence rate of 46 per 100 person-years. The median duration of linezolid therapy was 526 days. No patients required dose reduction or interruption due to cytopenias. Median linezolid Cmin was 0.235 mg/L (interquartile range [IQR], 0.069 to 0.529), and median AUC0-24 was 89.6 mg·h/L (IQR, 69.2 to 116.2). Cytopenias were associated with linezolid PK parameters (Cmin > 2 mg/L and AUC0-24 > 160 mg·h/L). Cytopenias occurred frequently with long-term use of linezolid 600 mg/day and were associated with PK parameters but did not result in the need for treatment interruption in the management of a cohort of patients with MDR-TB.

Prevalence of Latent Tuberculosis Infection Among Non-US-Born Persons by Country of Birth-United States, 2012-2017.

BACKGROUND: Most tuberculosis (TB) disease in the United States (US) is attributed to reactivation of remotely acquired latent TB infection (LTBI) in non-US-born persons who were likely infected with Mycobacterium tuberculosis in their countries of birth. Information on LTBI prevalence by country of birth could help guide local providers and health departments to scale up the LTBI screening and preventive treatment needed to advance progress toward TB elimination. METHODS: A total of 13 805 non-US-born persons at high risk of TB infection or progression to TB disease were screened for LTBI at 16 clinical sites located across the United States with a tuberculin skin test, QuantiFERON Gold In-Tube test, and T-SPOT.TB test. Bayesian latent class analysis was applied to test results to estimate LTBI prevalence and associated credible intervals (CrIs) for each country or world region of birth. RESULTS: Among the study population, the estimated LTBI prevalence was 31% (95% CrI, 26%-35%). Country-of-birth-level LTBI prevalence estimates were highest for persons born in Haiti, Peru, Somalia, Ethiopia, Vietnam, and Bhutan, ranging from 42% to 55%. LTBI prevalence estimates were lowest for persons born in Colombia, Malaysia, and Thailand, ranging from 8% to 13%. CONCLUSIONS: LTBI prevalence in persons born outside the US varies widely by country. These estimates can help target community outreach efforts to the highest-risk groups.

Isoniazid and Rifapentine Treatment Eradicates Persistent Mycobacterium tuberculosis in Macaques.

Rationale: Direct evidence for persistence of Mycobacterium tuberculosis (Mtb) during asymptomatic latent tuberculosis infection (LTBI) in humans is currently lacking. Moreover, although a 12-week regimen of once-weekly isoniazid and rifapentine (3HP) is currently recommended by the CDC as treatment for LTBI, experimental evidence for 3HP-mediated clearance of persistent Mtb infection in human lungs has not been established.Objectives: Using a nonhuman primate (NHP) model of TB, we sought to assess 3HP treatment-mediated clearance of Mtb infection in latently infected macaques.Methods: Sixteen NHPs were infected via inhalation with ∼10 cfu of Mtb CDC1551, after which asymptomatic animals were either treated with 3HP or left untreated. Pharmacokinetics of the 3HP regimen were measured. Following treatment, animals were coinfected with simian immunodeficiency virus to assess reactivation of LTBI and development of active TB disease.Measurements and Main Results: Fourteen NHPs remained free of clinical signs or microbiological evidence of active TB following infection with Mtb and were subsequently either treated with 3HP (n = 7) or left untreated (n = 7). Untreated NHPs were asymptomatic for 7 months but harbored persistent Mtb infection, as shown by reactivation of latent infection following simian immunodeficiency virus coinfection. However, none of the treated animals developed TB reactivation disease, and they remained without clinical or microbiological evidence of persistent bacilli, suggesting treatment-mediated clearance of bacteria.Conclusions:Mtb can persist in asymptomatic macaques for at least 7 months. Furthermore, 3HP treatment effectively cleared bacteria and prevented reactivation of TB in latently infected macaques.

A High Throughput Whole Blood Assay for Analysis of Multiple Antigen-Specific T Cell Responses in Human Mycobacterium tuberculosis Infection.

Antigen-specific CD4 and CD8 T cells are important components of the immune response to Mycobacterium tuberculosis, yet little information is currently known regarding how the breadth, specificity, phenotype, and function of M. tuberculosis-specific T cells correlate with M. tuberculosis infection outcome in humans. To facilitate evaluation of human M. tuberculosis-specific T cell responses targeting multiple different Ags, we sought to develop a high throughput and reproducible T cell response spectrum assay requiring low blood sample volumes. We describe here the optimization and standardization of a microtiter plate-based, diluted whole blood stimulation assay utilizing overlapping peptide pools corresponding to a functionally diverse panel of 60 M. tuberculosis Ags. Using IFN-γ production as a readout of Ag specificity, the assay can be conducted using 50 µl of blood per test condition and can be expanded to accommodate additional Ags. We evaluated the intra- and interassay variability, and implemented testing of the assay in diverse cohorts of M. tuberculosis-unexposed healthy adults, foreign-born adults with latent M. tuberculosis infection residing in the United States, and tuberculosis household contacts with latent M. tuberculosis infection in a tuberculosis-endemic setting in Kenya. The M. tuberculosis-specific T cell response spectrum assay further enhances the immunological toolkit available for evaluating M. tuberculosis-specific T cell responses across different states of M. tuberculosis infection, and can be readily implemented in resource-limited settings. Moreover, application of the assay to longitudinal cohorts will facilitate evaluation of treatment- or vaccine-induced changes in the breadth and specificity of Ag-specific T cell responses, as well as identification of M. tuberculosis-specific T cell responses associated with M. tuberculosis infection outcomes.

Moxifloxacin target site concentrations in patients with pulmonary TB utilizing microdialysis: a clinical pharmacokinetic study.

Background: Moxifloxacin is a second-line anti-TB drug that is useful in the treatment of drug-resistant TB. However, little is known about its target site pharmacokinetics. Lower drug concentrations at the infection site (i.e. in severe lung lesions including cavitary lesions) may lead to development and amplification of drug resistance. Improved knowledge regarding tissue penetration of anti-TB drugs will help guide drug development and optimize drug dosing. Methods: Patients with culture-confirmed drug-resistant pulmonary TB scheduled to undergo adjunctive surgical lung resection were enrolled in Tbilisi, Georgia. Five serum samples per patient were collected at different timepoints including at the time of surgical resection (approximately at Tmax). Microdialysis was performed in the ex vivo tissue immediately after resection. Non-compartmental analysis was performed and a tissue/serum concentration ratio was calculated. Results: Among the seven patients enrolled, the median moxifloxacin dose given was 7.7 mg/kg, the median age was 25.2 years, 57% were male and the median creatinine clearance was 95.4 mL/min. Most patients (71%) had suboptimal steady-state serum Cmax (total drug) concentrations. The median free moxifloxacin serum concentration at time of surgical resection was 1.23 µg/mL (range = 0.12-1.80) and the median free lung tissue concentration was 3.37 µg/mL (range = 0.81-5.76). The median free-tissue/free-serum concentration ratio was 3.20 (range = 0.66-28.08). Conclusions: Moxifloxacin showed excellent penetration into diseased lung tissue (including cavitary lesions) among patients with pulmonary TB. Moxifloxacin lung tissue concentrations were higher than those seen in serum. Our findings highlight the importance of moxifloxacin in the treatment of MDR-TB and potentially any patient with pulmonary TB and severe lung lesions.

pncA Gene Mutations Associated with Pyrazinamide Resistance in Drug-Resistant Tuberculosis, South Africa and Georgia.

Although pyrazinamide is commonly used for tuberculosis treatment, drug-susceptibility testing is not routinely available. We found polymorphisms in the pncA gene for 70% of multidrug-resistant and 96% of extensively drug-resistant Mycobacterium tuberculosis isolates from South Africa and Georgia. Assessment of pyrazinamide susceptibility may be prudent before using it in regimens for drug-resistant tuberculosis.

Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis.

Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary (n = 6 patients), mass-like (n = 3 patients), or consolidative (n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 µg/ml. The median lung tissue free pyrazinamide concentration was 20.96 µg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis (R = -0.66, P = 0.04) and acid-fast bacilli (R = -0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens.

Student and faculty perceptions on the rapid scale-up of medical students in Ethiopia.

BACKGROUND: Ethiopia is a country of over 94 million people that has a severe physician shortage with approximately only 2.5 physicians per 100,000 persons. Recently, the Ethiopian government implemented a "flood and retain" initiative to rapidly increase the quantity of physicians in Ethiopia. Consequently, medical student enrollment at Addis Ababa University (AAU) School of Medicine increased from 100 to approximately 300-400 students per class. This study evaluated the impact of the rapid scale-up in the number of medical students on the quality of medical education at AAU and the impact of the U.S. government-funded Medical Education Partnership Initiative (MEPI) grant awarded to AAU to provide resources to strengthen the quality of medical education at AAU. METHODS: Qualitative, semi-structured, in-depth interviews were conducted with 22 key informants including faculty members, administrators and medical students at AAU. The audio recordings were transcribed verbatim and interview data were analyzed with thematic analysis. RESULTS: Four key themes emerged from the data. Overall, participants perceived a decrease in the quality of medical education at AAU due to challenges created by the rapid scale-up in the number of medical students. Positive learning environments were described as difficult to achieve due to overcrowding in classrooms and the limited numbers of textbooks. Overall, participants stated that infrastructure improvement is needed to provide adequate medical student training. The medical education initiatives implemented and funded by MEPI have provided significant resources to support the medical student curriculum but additional resources are required to accommodate a large student body. CONCLUSIONS: The unprecedented rapid scale-up of medical students has impacted multiple facets of medical education at AAU. It is important to consider the perspectives of students and faculty in order to focus future medical education policies, MEPI programming and the allocation of resources.

Efficacy and Safety of Glutamine-supplemented Parenteral Nutrition in Surgical ICU Patients: An American Multicenter Randomized Controlled Trial.

OBJECTIVE: To determine whether glutamine (GLN)-supplemented parenteral nutrition (PN) improves clinical outcomes in surgical intensive care unit (SICU) patients. SUMMARY BACKGROUND DATA: GLN requirements may increase with critical illness. GLN-supplemented PN may improve clinical outcomes in SICU patients. METHODS: A parallel-group, multicenter, double-blind, randomized, controlled clinical trial in 150 adults after gastrointestinal, vascular, or cardiac surgery requiring PN and SICU care. Patients were without significant renal or hepatic failure or shock at entry. All received isonitrogenous, isocaloric PN [1.5 g/kg/d amino acids (AAs) and energy at 1.3× estimated basal energy expenditure]. Controls (n = 75) received standard GLN-free PN (STD-PN); the GLN group (n = 75) received PN containing alanyl-GLN dipeptide (0.5 g/kg/d), proportionally replacing AA in PN (GLN-PN). Enteral nutrition (EN) was advanced and PN weaned as indicated. Hospital mortality and infections were primary endpoints. RESULTS: Baseline characteristics, days on study PN and daily macronutrient intakes via PN and EN, were similar between groups. There were 11 hospital deaths (14.7%) in the GLN-PN group and 13 deaths in the STD-PN group (17.3%; difference, -2.6%; 95% confidence interval, -14.6% to 9.3%; P = 0.66). The 6-month cumulative mortality was 31.4% in the GLN-PN group and 29.7% in the STD-PN group (P = 0.88). Incident bloodstream infection rate was 9.6 and 8.4 per 1000 hospital days in the GLN-PN and STD-PN groups, respectively (P = 0.73). Other clinical outcomes and adverse events were similar. CONCLUSIONS: PN supplemented with GLN dipeptide was safe, but did not alter clinical outcomes among SICU patients.

Acquired Drug Resistance in Mycobacterium tuberculosis and Poor Outcomes among Patients with Multidrug-Resistant Tuberculosis.

Rates and risk factors for acquired drug resistance and association with outcomes among patients with multidrug-resistant tuberculosis (MDR TB) are not well defined. In an MDR TB cohort from the country of Georgia, drug susceptibility testing for second-line drugs (SLDs) was performed at baseline and every third month. Acquired resistance was defined as any SLD whose status changed from susceptible at baseline to resistant at follow-up. Among 141 patients, acquired resistance in Mycobacterium tuberculosis was observed in 19 (14%); prevalence was 9.1% for ofloxacin and 9.8% for capreomycin or kanamycin. Baseline cavitary disease and resistance to >6 drugs were associated with acquired resistance. Patients with M. tuberculosis that had acquired resistance were at significantly increased risk for poor treatment outcome compared with patients without these isolates (89% vs. 36%; p<0.01). Acquired resistance occurs commonly among patients with MDR TB and impedes successful treatment outcomes.

Cavitary penetration of levofloxacin among patients with multidrug-resistant tuberculosis.

A better understanding of second-line drug (SLD) pharmacokinetics, including cavitary penetration, may help optimize SLD dosing. Patients with pulmonary multidrug-resistant tuberculosis (MDR-TB) undergoing adjunctive surgery were enrolled in Tbilisi, Georgia. Serum was obtained at 0, 1, 4, and 8 h and at the time of cavitary removal to measure levofloxacin concentrations. After surgery, microdialysis was performed using the ex vivo cavity, and levofloxacin concentrations in the collected dialysate fluid were measured. Noncompartmental analysis was performed, and a cavitary-to-serum levofloxacin concentration ratio was calculated. Twelve patients received levofloxacin for a median of 373 days before surgery (median dose, 11.8 mg/kg). The median levofloxacin concentration in serum (Cmax) was 6.5 µg/ml, and it was <2 µg/ml in 3 (25%) patients. Among 11 patients with complete data, the median cavitary concentration of levofloxacin was 4.36 µg/ml (range, 0.46 to 8.82). The median cavitary/serum levofloxacin ratio was 1.33 (range, 0.63 to 2.36), and 7 patients (64%) had a ratio of >1. There was a significant correlation between serum and cavitary concentrations (r = 0.71; P = 0.01). Levofloxacin had excellent penetration into chronic cavitary TB lesions, and there was a good correlation between serum and cavitary concentrations. Optimizing serum concentrations will help ensure optimal cavitary concentrations of levofloxacin, which may enhance treatment outcomes.

Tobacco smoking and tuberculosis treatment outcomes: a prospective cohort study in Georgia.

OBJECTIVE: To assess the effect of tobacco smoking on the outcome of tuberculosis treatment in Tbilisi, Georgia. METHODS: We conducted a prospective cohort study of adults with laboratory-confirmed tuberculosis from May 2011 to November 2013. History of tobacco smoking was collected using a standardized questionnaire adapted from the global adult tobacco survey. We considered tuberculosis therapy to have a poor outcome if participants defaulted, failed treatment or died. We used multivariable regressions to estimate the risk of a poor treatment outcome. FINDINGS: Of the 591 tuberculosis patients enrolled, 188 (31.8%) were past smokers and 271 (45.9%) were current smokers. Ninety (33.2%) of the current smokers and 24 (18.2%) of the participants who had never smoked had previously been treated for tuberculosis (P < 0.01). Treatment outcome data were available for 524 of the participants, of whom 128 (24.4%) - including 80 (32.9%) of the 243 current smokers and 21 (17.2%) of the 122 individuals who had never smoked - had a poor treatment outcome. Compared with those who had never smoked, current smokers had an increased risk of poor treatment outcome (adjusted relative risk, aRR: 1.70; 95% confidence interval, CI: 1.00-2.90). Those who had ceased smoking more than two months before enrolment did not have such an increased risk (aRR: 1.01; 95% CI: 0.51-1.99). CONCLUSION: There is a high prevalence of smoking among patients with tuberculosis in Georgia and smoking increases the risk of a poor treatment outcome.

Significant clinical impact of a rapid molecular diagnostic test (Genotype MTBDRplus assay) to detect multidrug-resistant tuberculosis.

BACKGROUND: There are limited data on the clinical impact of rapid diagnostic tests to detect multidrug-resistant tuberculosis (MDR-TB). We sought to determine whether the use of a molecular diagnostic test to detect MDR-TB improves clinical outcomes. METHODS: A quasi-experimental study was conducted to analyze the impact of the Genotype MTBDRplus assay on clinical outcomes among patients with culture-confirmed pulmonary MDR-TB. Patients received treatment at the National Center for Tuberculosis and Lung Diseases in Tbilisi, Georgia. Time to MDR-TB treatment initiation, culture conversion, and infection control measures were compared to a time period prior to the implementation of the molecular test. RESULTS: Of 152 MDR-TB patients, 72 (47%) were from prior to and 80 (53%) following implementation of the MTBDRplus assay ("post-implementation group"). Patients in the post-implementation group initiated a second-line treatment regimen more rapidly than those in the pre-implementation group (18.2 vs 83.9 days, P < .01). Among patients admitted to a "drug-susceptible" tuberculosis ward, those from the post-implementation group spent significantly fewer days on the drug-susceptible ward compared to patients in the pre-implementation group (10.0 vs 58.3 days, P < .01). Among patients with 24 weeks follow-up (n = 119), those in the post-implementation group had a higher rate of culture conversion at 24 weeks (86% vs 63%, P < .01) and a more rapid rate of time to culture conversion (adjusted hazard ratio [aHR] 4.15, 95% confidence interval [CI], 2.5-6.9). CONCLUSIONS: The implementation of a rapid molecular diagnostic test led to significant clinical improvements including reduced time to initiation of MDR-TB treatment, culture conversion, and improved infection control practices.

Recruitment Strategies To Improve Gender Equity in Clinical and Translational Research Training in Ethiopia.

Women from sub-Saharan Africa, including Ethiopia, are underrepresented in biomedical research due in part to limited access to high-quality research training and mentorship. Tuberculosis (TB) is a major public health problem in Ethiopia, with a limited number of female Ethiopian scientists engaged in TB-related research. To improve access to TB-related research training among junior women scientists, our NIH Fogarty International Center-funded D43 program released an all-women request for applications (RFA), which substantially increased the number of women applying for research training and the number of women trained in our program. The impact of the all-women cohort was also bolstered by prominent female representation in mentor teams, program leadership, and program alumnae. Sustained increases in applications from women were seen in subsequent RFAs that included both women and men. Targeted leadership, mentorship, and recruitment efforts were effective in promoting improved gender equity in biomedical research training.