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ABTSRACTBackgroundWe aimed to determine the relationship between common pre-existing comorbidities in patients with tuberculosis (TB) (including human immunodeficiency virus [HIV], diabetes, and hepatitis C virus [HCV]) with rates of all-cause mortality after TB treatment.MethodsWe conducted a retrospective cohort study among patients treated for rifampicin-resistant and multi/extensively drug resistant (RR and M/XDR) TB in the country of Georgia during 2009-2017. Eligible participants were >15 years of age with newly diagnosed, laboratory-confirmed drug resistant TB who received second-line treatment. Exposures included HIV serologic status, diabetes, and HCV status. The primary outcome was post-TB treatment mortality determined by cross-validating vital status with Georgia’s national death registry through November 2019. We estimated hazard rate ratios (HR) and 95% confidence intervals (CI) of post-TB mortality among participants with and without pre-existing comorbidities using cause-specific hazard regressions.ResultsAmong 1032 eligible patients included in our analyses, 34 (3.3%) participants died during treatment and 87 (8.7%) died post-TB treatment. Among those who died post-TB treatment, the median time to death was 21 months (IQR 7–39) after TB treatment ended. After adjusting for potential confounders, the hazard rates of mortality post-TB treatment were higher among participants with HIV co-infection (adjusted hazard ratio [aHR]=3.74, 95%CI 1.77–7.91) compared to those without HIV co-infection.ConclusionsIn our cohort, post-TB mortality occurred most commonly in the first three years after TB treatment ended. Additional post-TB care and follow-up, especially among patients with TB and comorbidities (especially HIV co-infection), may reduce rates of mortality post-TB treatment.SummaryOur findings provide evidence that TB patients with comorbidities, especially HIV, may have a significantly increased risk of post-TB mortality compared to those without comorbidities. We also found that most post-TB mortality occurred within three years after TB treatment completion.

ObjectivesLatent Tuberculosis infection (LTBI) is marked by dynamic host-pathogen interactions with persistent low-grade inflammation and is associated with increased risk of cardiovascular diseases (CVD) including acute coronary syndrome, myocardial infarction, and stroke. However, few studies assess the relationship between LTBI and hypertension, an intermediate of CVD. We sought to determine the association between LTBI and hypertension using data representative of the adult US population.MethodsWe performed cross-sectional analyses using data from the 2011–2012 US National Health and Nutrition Examination Survey (NHANES). Eligible participants included adults with valid QuantiFERON-TB Gold In-Tube (QFT-GIT) test results who also had blood pressure measures and no history of TB disease. LTBI was defined by a positive QFT-GIT. We defined hypertension by either elevated measured blood pressure levels (i.e., systolic ≥130mmHg or diastolic ≥80mmHg) or known hypertension indications (i.e., self-reported previous diagnosis or use of antihypertensive medications). Analyses were performed using robust quasi-Poisson regressions and accounted for the stratified probability sampling design of NHANES.ResultsThe overall prevalence of LTBI was 5.7% (95%CI 4.7–6.7) and hypertension was present among 48.9% (95%CI 45.2–52.7) of participants. The prevalence of hypertension was higher among those with LTBI (58.5%, 95%CI 52.4–64.5) than those without LTBI (48.3%, 95%CI 44.5–52.1) (prevalence ratio [PR]=1.2, 95%CI 1.1–1.3). However, after adjusting for confounders, the prevalence of hypertension was similar for those with and without LTBI (adjusted PR=1.0, 95%CI 0.9 –1.1). Among individuals without CVD risk factors of elevated BMI (PRnormalBMI=1.6, 95%CI 1.2–2.0), hyperglycemia (PReuglycemia=1.3, 95%CI 1.1–1.5), or cigarette smoking (PRnon-smokers=1.2, 95%CI 1.1–1.4), the unadjusted prevalence of hypertension was higher among those with LTBI vs. no LTBI.ConclusionsMore than half of adults with LTBI in the US had hypertension. Importantly, we observed a relationship between LTBI and hypertension among those without established CVD risk factors.Strengths and limitationsStrengths-These analyses were conducted using data representative of civilian, non-institutionalized US adults, and thus, provide a robust population estimate of the prevalence of latent tuberculosis infection and hypertension in the US-Comprehensive definitions and different cut-offs of hypertension were used (i.e., measured blood pressure level, previous diagnosis hypertension by healthcare providers) to model the association between latent tuberculosis infection and hypertensionLimitationsOur findings may not be representative to other regions with higher burdens of tuberculosis-The cross-sectional study design of NHANES prevented us from assessing the temporal relationship between latent tuberculosis infection and hypertensionSummaryThe prevalence of hypertension was high (59%) among adults with tuberculosis infection in the U.S. In addition, we found that the prevalence of hypertension was significantly higher among adults with positive QFT without established hypertension risk factors.

Background Diabetes mellitus and human immunodeficiency virus (HIV) are independent risk factors for poor outcomes among people with tuberculosis (TB). To date, information on the joint impact of diabetes and HIV on TB outcomes is limited. We aimed to estimate (1) the association between hyperglycemia and mortality, and (2) the effect of joint exposure to diabetes and HIV on mortality. Methods We conducted a retrospective cohort study among people with TB in the state of Georgia between 2015-2020. Eligible participants were 16 or older, did not have a previous TB diagnosis, and were microbiologically confirmed or clinical cases. Participants were followed during TB treatment. Robust Poisson regression was used to estimate risk ratios for all-cause mortality. Interaction between diabetes and HIV was assessed on the additive scale using the attributable proportion and on the multiplicative scale with product terms in regression models. Results Of 1109 participants, 318 (28.7%) had diabetes, 92 (8.3%) were HIV-positive, and 15 (1.4%) had diabetes and HIV. Overall, 9.8% died during TB treatment. Diabetes was associated with an increased risk of death among people with TB (aRR = 2.59, 95% CI: 1.62, 4.13). We estimated that 26% (95% CI: -43.4%, 95.0%) of deaths among participants with DM and HIV were due to biologic interaction. Conclusions Diabetes alone and co-occurring diabetes and HIV were associated with an increased risk of all-cause mortality during TB treatment. These data suggest a potential synergistic effect between diabetes and HIV.

OBJECTIVE In cross-sectional U.S. studies, patients with diabetes had twice the prevalence of latent tuberculosis infection (LTBI) compared with those without diabetes. However, whether LTBI contributes to diabetes risk is unknown. We used longitudinal data to determine if LTBI is associated with increased diabetes incidence. RESEARCH DESIGN AND METHODS We conducted a retrospective cohort study among U.S. Veterans receiving care in the Veterans Health Administration from 2000 to 2015. Eligibility included all patients without preexisting diabetes who received a tuberculin skin test (TST) or interferon-γ release assay (IGRA). We excluded patients with a history of active TB and those diagnosed with diabetes before or within 2 years after LTBI testing. Patients were followed until diabetes diagnosis, death, or 2015. LTBI was defined as TST or IGRA positive. Incident diabetes was defined by use of ICD-9 codes in combination with a diabetes drug prescription. RESULTS Among 574,113 eligible patients, 5.3% received both TST/IGRA, 79.1% received TST only, and 15.6% received IGRA only. Overall, 6.6% had LTBI, and there were 2,535,149 person-years (PY) of follow-up after LTBI testing (median 3.2 years). The diabetes incidence rate (per 100,000 PY) was greater in patients with LTBI compared with those without (1,012 vs. 744; hazard ratio [HR] 1.4 [95% CI 1.3–1.4]). Increased diabetes incidence persisted after adjustment for covariates (adjusted HR [aHR] 1.2 [95% CI 1.2–1.3]) compared with those without LTBI. Among patients with LTBI, diabetes incidence was similar in those treated for LTBI compared with those who were not treated (aHR 1.0 [95% CI 0.9–1.1]). CONCLUSIONS Comprehensive longitudinal data indicate that LTBI is associated with increased diabetes incidence. These results have implications for people with LTBI, ∼25% of the global population.

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 (C(min)) and area under the curve from 0 to 24 hours (AUC(0–24)). 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 C(min) was 0.235 mg/L (interquartile range [IQR], 0.069 to 0.529), and median AUC(0–24) was 89.6 mg·h/L (IQR, 69.2 to 116.2). Cytopenias were associated with linezolid PK parameters (C(min) > 2 mg/L and AUC(0–24) > 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.

Background Hepatitis C virus (HCV) and hepatitis B virus (HBV) coinfection are associated with increased mortality in people with HIV (PWH), and hyperglycemia is a common comorbidity in PWH. In this study, we used routinely collected clinical data to assess the associations between HBV and HCV seropositivity with all-cause mortality and whether this relationship differs by hyperglycemia status. Methods Eligible participants included adult PWH (≥15 years) who initiated antiretroviral therapy between May 2005 and June 2016 in Myanmar. HBV and HCV serostatus and hyperglycemia were measured at enrollment to HIV care using HBV surface antigen, HCV antibody tests, and random blood glucose (≥140 mg/dL), respectively. Results Among 27 722 PWH, 2260 (8%) were HBV seropositive, 2265 (9%) were HCV seropositive, 178 (0.6%) were HBV-HCV seropositive, and 1425 (5%) had hyperglycemia. During the median follow-up (interquartile range) of 3.1 (1.5–5.1) years, 3655 (13%) PWH died, and the overall mortality rate was 3.8 (95% CI, 3.7–3.9) per 100-person-years (PY). The mortality rate (per 100 PY) among PWH who were HBV seropositive was 4.6, among PWH who were HCV seropositive it was 5.1, and among PWH who were HBV-HCV seropositive it was 7.1. When stratified by glycemic status, the mortality rate was higher among patients with hyperglycemia compared with those with euglycemia (5.4 vs 4.0 per 100 PY), and the difference in mortality rate between patients with hyperglycemia and euglycemia was highest among those with HCV seropositivity (9.8 vs 5.0 per 100 PY). Conclusions Increased mortality rates associated with HBV and HCV seropositivity in PWH differed by their glycemic status. PWH with HCV seropositivity and hyperglycemia had the highest mortality rates.

It is uncertain whether diabetes affects the risk of developing latent tuberculosis infection (LTBI) following exposure toIn this cross-sectional study, we performed interferon-γ release assays, TB symptom screening, and point-of-care glycolated hemoglobin (HbA1c) testing among HHCs of active TB cases. Diabetes status was classified into diabetes (HbA1c ≥6.5% or self-reported diagnosis), prediabetes (5.7%-6.4%), and euglycemia (≤5.6%). Multivariable logistic regression was used to determine the association of diabetes with LTBI.Among 597 study participants, 123 (21%) had dysglycemia including diabetes (n = 31) or prediabetes (n = 92); 423 (71%) participants were diagnosed with LTBI. Twelve of 31 (39%) HHCs with diabetes were previously undiagnosed with diabetes. The prevalence of LTBI among HHCs with diabetes, prediabetes, and euglycemia was 87% (27/31), 73% (67/92), and 69% (329/474), respectively. In multivariable analysis adjusted for age, sex, and HIV status, the odds of LTBI among HHCs with diabetes were 2.33 (95% confidence interval [CI], .76-7.08) times the odds of LTBI without diabetes. When assessing interaction with age, the association of diabetes and LTBI was robust among participants aged ≥40 years (adjusted odds ratio [aOR], 3.68 [95% CI, .77-17.6]) but not those40 years (aOR, 1.15 [95% CI, .22-6.1]).HHCs with diabetes may be more likely to have LTBI than those with euglycemia. Further investigations are needed to assess mechanisms by which diabetes may increase risk of LTBI after

Introduction Diabetes might confer a modestly increased risk of latent tuberculosis infection, which without treatment can progress to active tuberculosis disease. Three recent analyses of the National Health and Nutrition Examination Survey found a positive association between diabetes and a positive test for Mycobacterium tuberculosis infection. This study examines whether prevalence of a positive test still varies by diabetes status after stratifying by race/ethnicity. Methods This cross-sectional analysis used the public-use National Health and Nutrition Examination Survey 2011–2012 data sets and was conducted in 2018–2019. Interview and examination results for 5,560 adult participants yielded estimates for 219 million U.S. adults in the 4 largest race/ethnicity groups. The weighted prevalence of positive tuberculin skin test or interferon-gamma release assay by diabetes status was ascertained in each group. Results Among white and black adults, diabetes was associated with no difference in positive skin test prevalence and little difference in positive interferon-gamma release assay prevalence. The positive assay prevalence difference was +14.5% (95% CI=2.3%, 26.7%) among Hispanic and +9.9% (95% CI=1.2%, 18.6%) among Asian adults, when comparing those with diabetes with those with neither diabetes nor prediabetes. Based on assay results, 23.6% (95% CI=14.0%, 36.9%) of Hispanic and 27.2% (95% CI=19.6%, 36.5%) of Asian adults with diabetes also had latent tuberculosis infection. Conclusions Hispanic and Asian subpopulation results drove much of the previously reported positive association between diabetes and a positive test for M. tuberculosis infection. Hispanic and Asian adults with diabetes might particularly benefit from screening and treatment for latent tuberculosis infection.

Background Diabetes mellitus (DM) is a well-established risk factor for active tuberculosis (TB) infection. Despite the worldwide rapid increase in the prevalence of prediabetes, its impact on the risk of active TB remains largely unknown. This study aimed to investigate the relationship between prediabetes and risk of active TB in a large cohort study. Methods A total of 119 352 participants were screened from a community-based health screening programme in Northern Taiwan. Diabetes mellitus and prediabetes were defined by baseline fasting plasma glucose (FPG) and prescription of anti-diabetic drugs. Incident cases of active TB were identified from the National Tuberculosis Registry. Kaplan–Meier curves and Cox regression analysis were employed to estimate the hazard ratios for prediabetes and DM compared with normoglycaemia. Spline regression was performed to investigate the dose-response relationship between FPG level and risk of TB disease. Results At baseline, 27 404 (22.96%) participants had prediabetes and 10 943 (9.17%) participants had DM. After an average follow-up of 7.2 years, 322 TB cases occurred. The adjusted hazard ratio of developing active TB disease was 0.73 [95% confidence interval (CI) 0.55–0.97] for prediabetic and 1.48 (95% CI 1.11–1.98) for diabetic participants compared with normoglycaemic individuals. Spline regression revealed a U-shaped association between FPG level and risk of active TB disease, with the lowest risk at FPG around110 mg/dl. Sensitivity analyses were conducted to exclude factors such as potential confounders (including body mass index), misclassification of glycaemic level, and selection bias, and results showed that those factors could not explain the lower risk of active TB. Conclusions Prediabetes was associated with a 27% reduced risk of active TB disease compared with normoglycaemia. The biological mechanism of this inverse association and its implication for global nutrition transition and TB control should be further investigated.

There are limited data on post-hospital discharge clinic attendance rates and outcomes among patients with diabetic foot ulcers (DFUs).Retrospective study of patients hospitalized with a DFU from 2016 to 2019 in a large public hospital. We measured rates and predictors of clinic attendance with providers involved with DFU care within 30 days of hospital discharge ("30-day post-discharge clinic attendance"). Log-binomial regression was used to estimate risk ratios (RR) and 95 % confidence intervals (CI).Among 888 patients, 60.0 % were between 45 and 64 years old, 80.5 % were Black, and 24.1 % were uninsured. Overall, 478 (53.8 %) attended ≥1 30-day post-discharge clinic appointment. Initial hospital outcomes were associated with clinic attendance. For example, the RR of 30-day post-discharge clinic attendance was 1.39 (95%CI 1.19-1.61) among patients who underwent a major amputation compared to patients with DFUs without osteomyelitis and did not undergo an amputation during the initial hospitalization. Among 390 patients with known 12-month outcome, 71 (18.2 %) had a major amputation or died ≤12 months of hospital discharge.We found a low post-discharge clinic attendance and high post-discharge amputation and death rates among patients hospitalized with DFUs. Interventions to increase access to outpatient DFU care are needed and could prevent amputations.

OBJECTIVES: Low body mass index (BMI) and hyperglycemia are each important risk factors for tuberculosis (TB). However, the contribution of synergy between low BMI and hyperglycemia to risk of TB among people living with HIV (PLHIV) is unexplored. We compared TB incidence among PLHIV with different exposure profiles to low BMI (BMI

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.

Objectives: To estimate the incidence of diabetes, acute myocardial infarction (AMI), and stroke; and to determine factors associated with diabetes, AMI, and stroke incidence among patients previously treated for tuberculosis (TB) disease. Methods: A retrospective cohort study was conducted among non-pediatric TB patients registered in the Taiwan National Health Insurance Research Database (NHIRD) from 2002–2013. Diabetes, AMI, and stroke incidence were defined by International Classification of Diseases (ICD)-9 codes, drug prescriptions, and records of patient’s clinic visits. Cox proportional hazard models were used to estimate the hazard rate ratio (HR) of incident diabetes, AMI, and stroke. Results: From 2002–2013, there were 157,444 patients treated for TB registered in NHIRD. Among 129,453 patients with no prior history of diabetes, the age-adjusted incidence rate (IR) of diabetes was 3.85 (95%CI 3.70–4.01) per 1000 person-years. Among 143,646 patients with no prior history of AMI, the age-adjusted IR of AMI as 3.26 (95%CI 3.13–3.40). Among 118,774 patients with no prior history of stroke, the age-adjusted IR of stroke was 16.08 (95%CI 15.76–16.32). Conclusions: Chronic non-communicable disease risk factors like dyslipidemia, hypertension, and chronic kidney disease diagnosed before time of TB diagnosis were predictive of diabetes, AMI, and stroke incidence. Keywords: Tuberculosis, Diabetes, Myocardial infarction, Stroke, Incidence

Background: Post-treatment morbidity among subjects with drug-resistant tuberculosis (DR-TB) is unclear. Methods: This was a cross-sectional study of patients from Tbilisi, Georgia with cavitary DR-TB and an outcome of cure. Participants had a chest X-ray (CXR), St. George Respiratory Quality (SGRQ) survey, and pulmonary function tests (PFTs) performed. Correlations between SGRQ and PFT results and factors associated with pulmonary impairment were examined. Results: Among 58 subjects (median age 31 years), 40% used tobacco, 59% had prior TB, and 47% underwent adjunctive surgical resection. The median follow-up time was 41 months. Follow-up CXR revealed fibrosis in 30 subjects (52%) and bronchiectasis in seven (12%). The median forced expiratory volume (FEV1)/forced vital capacity (FVC) ratio was 0.72, with 24 subjects (41%) having a ratio of ≤0.70. Significant correlations existed between PFT measures and overall and component SGRQ scores. In linear regression, age, prior TB, and CXR fibrosis or bronchiectasis were significantly associated with decreased pulmonary function. Adjunctive surgery was significantly associated with a higher percent predicted FEV1 and FVC. Conclusions: A high proportion of DR-TB subjects had residual pulmonary impairment, particularly with recurrent TB and severe radiological disease. The association of surgical resection with improved lung function deserves further study. PFTs and SGRQ may both be useful to evaluate lung health. Keywords: St. George Respiratory Quality survey, Lung health, Tuberculosis, Impairment, Pulmonary function, Surgery

Setting Myanmar, a country with a high human immunodeficiency virus-tuberculosis (HIV-TB) burden, where the tuberculin skin test or interferon-gamma release assays are not routinely available for the diagnosis of latent tuberculous infection. Objective To assess the effect of isoniazid (INH) preventive therapy (IPT) on the risk of TB disease and mortality among people living with HIV (PLHIV). Design A retrospective cohort study of routinely collected data on PLHIV enrolled into care between 2009 and 2014. Results Of 7177 patients (median age 36 years, interquartile range 31-42; 53% male) included in the study, 1278 (18%) patients received IPT. Among patients receiving IPT, 855 (67%) completed 6 or 9 months of INH. Patients who completed IPT had a significantly lower risk of incident TB than those who never received IPT (adjusted hazard ratio [aHR] 0.21, 95%CI 0.12-0.34) after controlling for potential confounders. PLHIV who received IPT had a significantly lower risk of death than those who never received IPT (PLHIV who completed IPT, aHR 0.25, 95%CI 0.16-0.37; those who received but did not complete IPT, aHR 0.55, 95%CI 0.37-0.82). Conclusion Among PLHIV in Myanmar, completing a course of IPT significantly reduced the risk of TB disease, and receiving IPT significantly reduced the risk of death.

In the United States, multistate Salmonella outbreaks are most commonly linked to a food source; however, contact with live animals can also result in outbreaks of human illness. To characterize Salmonella outbreaks linked to animal contact and examine differences compared to foodborne outbreaks, we analysed data reported to the Centers for Disease Control and Prevention through the National Outbreak Reporting System (NORS) from 2009 to 2014 with a primary mode of transmission listed as “animal contact” or “food.” Four hundred and eighty-four outbreaks with animal contact or foodborne transmission were reported through NORS; of these outbreaks, 99 (20.5%) resulted from Salmonella transmission through animal contact and 385 (79.5%) resulted from foodborne transmission, which resulted in 3,604 (19.8%) and 13,568 (80.2%) illnesses, respectively. A higher proportion of illnesses among children aged

Objective The purpose of this study is to compare the prevalence of latent TB infection (LTBI) among patients with type-2 diabetes mellitus (T2DM) to healthy controls without T2DM. To achieve this objective, we conducted a case-control study in a large hospital in Atlanta from 2016 to 2019. Results We enrolled 98 cases; 119 potential controls were screened, 84 of which had HbA1c ≥ 5.7% and one did not have QFT result, leaving 34 (28.6%) individuals enrolled as controls. LTBI prevalence was 9.2% among cases and 14.7% among controls (crude odds ratio 0.59, 95% CI 0.19–2.04). After adjusting for age and sex, the adjusted odds of LTBI among patients with T2DM was 0.45 (95% CI 0.13, 1.71) times the controls. We did not observe a statistically significant association between LTBI and T2DM. However, we reported a positive correlation between HbA1c level and nil count among individuals with LTBI (R2 = 0.55, p

Background High rates of loss to follow-up (LFU) exist among patients with multidrug and extensively drug-resistant tuberculosis (M/XDR TB). We aimed to identify long-term clinical outcomes of patients who were LFU during second-line TB treatment. Methods We conducted a follow-up study among adults who received second-line TB treatment in the country of Georgia during 2011–2014 with a final outcome of LFU. We attempted to interview all LFU patients, administered a structured questionnaire, and obtained sputum samples. Active TB at follow-up was defined by positive sputum Xpert-TB/RIF or culture. Results Follow-up information was obtained for 461 patients. Among these patients, 107 (23%) died and 177 (38%) were contacted. Of those contacted, 123 (69%) consented to participate and 92 provided sputum samples. Thirteen (14%) had active TB with an estimated infectious time period for transmitting drug-resistant TB in the community of 480 days (interquartile range = 803). In multivariable analysis, positive culture at the time of LFU was associated with active TB at the time of our study (adjusted risk ratio = 13.3; 95% confidence interval, 4.2–42.2) Conclusions Approximately one quarter of patients on second-line TB treatment who were LFU died. Among those LFU evaluated in our study, 1 in 7 remained in the community with positive sputum cultures. To reduce death and transmission of disease, additional strategies are needed to encourage patients to complete treatment.

Background Among pediatric patients with multidrug-resistant tuberculosis (MDR-TB), limited data exist regarding treatment outcomes in the context of the new and repurposed second-line TB drugs (SLDs). We aimed to describe the treatment outcomes among pediatric MDR-TB patients receiving new and repurposed SLDs including the proportion who achieved favorable outcomes. Methods We conducted a retrospective cohort study among pediatric patients (age ≤18 years) treated for MDR-TB in the country of Georgia from 2009 to 2016. A “new and repurposed” SLD regimen was defined as a regimen that included linezolid, bedaquiline, and/or delamanid. Favorable treatment outcome was defined by treatment completion or documented microbial “cure” status at the end of treatment. We assessed the association between the use of the new and repurposed SLDs with MDR-TB treatment outcomes using bivariate analyses and log-binomial regression. Results There were 124 pediatric MDR-TB patients (median age: 13.7; interquartile range: 4.6-16.0) initiating treatment; 119 (96.0%) had a treatment outcome recorded and were included in our analyses. Eighteen (15.1%) patients received new and repurposed SLDs from 2015 or later. After adjusting for potential confounders, the proportion achieving favorable MDR-TB treatment outcomes was higher among patients treated with SLD regimens that included new and/or repurposed drugs when compared with those treated without (adjusted risk ratio: 1.17; 95% confidence interval: 0.51-2.72). Conclusions We observed a high proportion of favorable treatment outcomes among pediatric patients with MDR-TB receiving the new and repurposed SLDs. Further studies to evaluate the efficacy and children’s tolerability of the new and repurposed SLDs are still warranted.

Aims We aim to determine the association between prediabetes and diabetes with latent TB using National Health and Nutrition Examination Survey data. Methods We performed a cross-sectional analysis of 2011–2012 National Health and Nutrition Examination Survey data. Participants ≥20 years were eligible. Diabetes was defined by glycated hemoglobin (HbA1c) as no diabetes (≤5.6% [38 mmol/mol]), prediabetes (5.7–6.4% [39–46 mmol/mol]), and diabetes (≥6.5% [48 mmol/mol]) combined with self-reported diabetes. Latent TB infection was defined by the QuantiFERON®-TB Gold In Tube (QFT-GIT) test. Adjusted odds ratios (aOR) of latent TB infection by diabetes status were calculated using logistic regression and accounted for the stratified probability sample. Results Diabetes and QFT-GIT measurements were available for 4958 (89.2%) included participants. Prevalence of diabetes was 11.4% (95%CI 9.8–13.0%) and 22.1% (95%CI 20.5–23.8%) had prediabetes. Prevalence of latent TB infection was 5.9% (95%CI 4.9–7.0%). After adjusting for age, sex, smoking status, history of active TB, and foreign born status, the odds of latent TB infection were greater among adults with diabetes (aOR 1.90, 95%CI 1.15–3.14) compared to those without diabetes. The odds of latent TB in adults with prediabetes (aOR 1.15, 95%CI 0.90–1.47) was similar to those without diabetes. Conclusions Diabetes is associated with latent TB infection among adults in the United States, even after adjusting for confounding factors. Given diabetes increases the risk of active TB, patients with co-prevalent diabetes and latent TB may be targeted for latent TB treatment.

In 2004, there existed limited tuberculosis (TB) research capacity in the country of Georgia. In response, a collaborative research training program (RTP) supported by a National Institutes of Health Fogarty International Center Global Infectious Diseases grant was formed between a U.S. academic institution and the National Center for Tuberculosis and Lung Disease (NCTLD) and other institutions in Georgia. We sought to assess outcomes of this RTP. The TB RTP combined didactic and mentored research training for Georgian trainees. Long-term trainees were supported for a 2-year period and with posttrainee career development mentoring. Metrics used to measure program performance included publications, grants received, and career advancement. From 2004 to 2015, 20 trainees participated in the program with 15 (75%) authoring a total of 65 publications in PubMed-listed journals. The median number of publications per trainee was six (interquartile range 2–14). A total of 16 (80%) trainees remain working in the area of TB; nine were promoted to leadership positions and three to lead research units at Georgian institutions. Ten (50%) trainees were the principal investigator (PI) of a peer-reviewed external grant after Fogarty-supported training, and 40% served as research mentors. Annual TB-related research funding at the NCTLD increased from $5,000 in 2005 to ∼$1.5 million in 2017. A Georgian Fogarty trainee was either PI, site PI, or coinvestigator on > 90% of all research funding. We believe that the NIH Fogarty-funded TB research training grant has made critical contributions to increasing the TB-related research infrastructure and capacity in Georgia, particularly at the NCTLD.

Rationale: Isoniazid-monoresistant tuberculosis (INH-monoresistant TB) is the most common drug-resistant TB type in the United States; however, its impact on TB treatment outcomes is not clear. Objectives: This study aims to understand 1) factors associated with INH-monoresistant TB and 2) the association between INH monoresistance and response to TB treatment. Methods: We studied all patients with TB (age, ≥15 yr) reported to the Georgia State Electronic Notifiable Disease Surveillance System (SENDSS) from 2009 to 2014. INH-monoresistant TB was defined as a Mycobacterium tuberculosis isolate resistant to isoniazid only. Time to sputum culture conversion was defined as the time (measured in days) from TB treatment initiation to the date of the first consistently negative culture result reported to the SENDSS. Logistic regression and Cox proportional hazard models were used to estimate the odds and hazard rate of sputum culture conversion, all-cause mortality, and poor TB outcome among patients with INH-monoresistant TB. Results: Among 1,141 culture-confirmed patients with available drug susceptibility testing results, 998 (87.5%) were susceptible to TB first-line drugs, and 143 (12.5%) were patients with INH-monoresistant TB. In multivariable analysis, male sex (adjusted odds ratio [aOR], 1.62; 95% confidence interval [CI], 1.01–2.67) and homelessness (aOR, 5.55; 95% CI, 3.38–9.17) were associated with higher odds of INH-monoresistant TB. In the same multivariable model, older age (≥65 yr old) (aOR, 0.21; 95% CI, 0.07–0.55) and miliary disease (aOR, 0.19; 95% CI, 0.01–0.96) were associated with lower odds of INH-monoresistant TB. Among 1,116 patients with pulmonary TB, the median time to sputum culture conversion was 30 days (interquartile range, 13–58). The rate of culture conversion was similar among patients with and without INH monoresistance (adjusted cause-specific hazard ratio, 1.15; 95% CI, 0.95–1.40). INH-monoresistant TB was not significantly associated with poor TB treatment outcomes (aOR, 1.61; 95% CI, 0.67–3.70) or mortality during TB treatment (aOR, 1.72; 95% CI, 0.58–4.94). Conclusions: Our findings suggest that compared with drug-susceptible TB, patients in Georgia with INH-monoresistant TB have a similar response to TB treatment including culture conversion rate, final TB treatment outcome, and all-cause mortality.

In countries with low and moderate incidence of tuberculosis (TB), the disease tends to concentrate in specific high-risk populations such as people with diabetes mellitus (DM). We review the updated evidence on the association between 1) DM and active TB, and 2) DM and latent tuberculous infection (LTBI), and 3) we summarize the findings on the population-level impact of DM on TB epidemiology, with particular focus on low- and moderate-incidence settings. We conducted an updated review of studies on DM and active TB, and found 11 more cohort studies published after the previous systematic review from 2008. The updated pooled relative risk (RR) (2.03, 95%CI 1.62-2.55) of all the studies was substantially lower than the three-fold risk increase in the previous review. Substantial heterogeneity of RR across studies was found. Possible reasons for such heterogeneity include different levels of residual confounding, the effect of modification by age, and different levels of glycemic control in the population. In a recently published systematic review on DM and LTBI, one cohort study and 12 cross-sectional studies were identified. The results from cross-sectional studies suggest a significant but modestly increased risk of LTBI among patients with DM (pooled odds ratio 1.18, 95%CI 1.06-1.30). We reviewed evidence on the population-level impact of DM on TB epidemiology in studies using population-attributable fraction analysis and infectious disease modelling. Those studies revealed that DM accounted for a substantial TB burden in low- and moderate-incidence countries. Finally, we discussed the complex association of obesity, DM and TB risk and the impact of the global obesity pandemic on TB epidemiology.

IMPACT: This work examines the association between diabetes mellitus and latent tuberculosis infection among a cohort of household contacts exposed to active tuberculosis in Ethiopia, focusing attention on the need for further translational research to determine the mechanisms of susceptibility to Mycobacterium tuberculosis infection among individuals with diabetes and pre-diabetes. OBJECTIVES/GOALS: Diabetes mellitus (DM) is an established risk factor for active TB disease, but there is limited understanding of the relationship of DM and latent tuberculosis (LTBI). We sought to determine the relationship between DM or pre-DM with LTBI among household or close contacts (HHCs) of active TB cases in Ethiopia. METHODS/STUDY POPULATION: We conducted a cross-sectional study of the HHCs of index active TB cases enrolled in an ongoing TB Research Unit (TBRU) study in Addis Ababa, Ethiopia. HHCs of individuals with laboratory-confirmed TB had QuantiFERON ®-TB Gold Plus (QFT) and glycated hemoglobin (HbA1c) tests performed. LTBI was defined as a positive QFT and lack of symptoms. HbA1C results were used to define no DM (HbA1c 6.5% or prior history of diabetes). Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) after adjustment for age, sex and HIV status as potential confounders. RESULTS/ANTICIPATED RESULTS: Among 466 HHCs, the median age was 29 years (IQR 23-38), 58.8% were female, 3.4% were HIV-positive, and median BMI was 20.9 kg/m^2 (IQR 18.9-23.8). Overall, 329 HHCs (70.6%) had LTBI, 26 (5.6%) had DM and 73 (15.7%) had pre-DM. Compared to HHC without DM, the prevalence of LTBI was higher in those with pre-DM (68.9% vs. 72.6%; OR 1.19, 95% CI 0.69-2.13) and those with DM (88.5%; OR 3.45, 95% CI 1.17-14.77). In multivariable analysis, there was a trend towards increased LTBI risk among HHCs with DM vs. without DM (OR 2.16, 95% CI 0.67-9.70) but the difference was not statistically significant. Among HHCs with LTBI, the median IFN-? response to TB1 antigen was modestly greater in those with DM (5.3 IU/mL; IQR 3.0-7.8) and pre-DM (5.4 IU/mL; IQR 2.0-8.4) compared to HHCs without DM (4.3 IU/mL; IQR 1.4-7.7). DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results suggest that DM may increase the risk of LTBI among HHCs recently exposed to active TB. Among those with LTBI, increased IFN-? antigen response in the presence of DM and pre-DM may indicate an exaggerated but ineffectual response to TB. Further investigation is needed to assess how dysglycemia impacts susceptibility to M. tuberculosis.

Background Understanding the link between tuberculosis (TB) and diabetes is increasingly important as public health responds to the growing global burden of noncommunicable diseases. Genetic association studies have identified numerous host genetic variants linked to TB; however, potential host genetic mechanisms linking TB and diabetes remain unexplored. Methods We used genetic and phenotypic data from the UK Biobank to evaluate the association of 6 previously reported TB-related host genetic variants (genome-wide significant associations from published studies) with diabetes. The study included 409 692 adults of European ancestry including 2177 with type 1 diabetes mellitus (T1DM) and 13 976 with type 2 diabetes mellitus (T2DM), defined by ICD-10 diagnosis codes. Results Of the 6 TB-associated single nucleotide polymorphisms (SNPs), 2 were associated with T1DM and 3 with T2DM, after adjusting for age, sex, body mass index, smoking, alcohol use, and population structure. After correction for multiple testing, SNPs rs2894257 and rs3135359 (HLA-DRA-DQA1) were associated with T1DM (rs2894257: odds ratio [OR], 1.32; 95% confidence interval [CI], 1.21–1.45; rs3135359: OR, 1.72; 95% CI, 1.57–1.88) and T2DM (rs2894257: OR, 1.11; 95% CI, 1.08–1.15; rs3135359: OR, 1.06; 95% CI, 1.025–1.096). The associations with T2DM weakened for rs2894257 and rs3135359 after further exclusion of probable T1DM cases defined by International Statistical Classification of Diseases and Related Health Problems (ICD-10) codes. SNP rs4733781 on chromosome 8 (ASAP1 gene) was associated with T2DM after exclusion of T1DM cases. Conclusions Our findings suggest that common host genetic effects may play a role in the molecular mechanism linking TB and diabetes. Future large genetic studies of TB and diabetes should focus on developing countries with high burdens of infectious and chronic diseases.

New data indicate metformin and statin use reduce incidence of active TB, but if they prevent TB infection (LTBI) is unknown. We used national data to report LTBI prevalence was highest among participants with diabetes who did not use statins or metformin.http://ow.ly/W21v30nehnt

Aims To develop and pilot test a taxonomy that empirically estimates health intervention effectiveness from efficacy data. Methods We developed a taxonomy to score health interventions across 11 items on a scale from 0–100. The taxonomy was pilot-tested in efficacy and effectiveness diabetes prevention studies identified in two separate systematic reviews; here, the face validity, inter-rater reliability and factor structure of the taxonomy were established. Random effects meta-analyses were used to obtain weight loss and diabetes incidence pooled effects across studies. These effects and taxonomy scores were used to down calibrate efficacy estimates to effectiveness estimates as follows: Efficacy effect*[Efficacy score/highest possible score]. Results We scored 82 effectiveness lifestyle modification studies (mean score 49.2), 32 efficacy lifestyle modification studies (mean score 69.8) and 20 efficacy studies testing medications (mean score 77.4). The taxonomy had face validity and good inter-rater reliability (ICC = 0.9 [0.87, 0.93]). The between-groups down calibrated weight loss estimate was similar to that observed in the effectiveness meta-analysis (1.7 and 1.8 kg, respectively). The down calibrated diabetes relative risk reduction was also similar to that observed in the effectiveness meta-analysis (30.6% over 2.7 years and 29% over 2 years, respectively). Conclusions The taxonomy is a promising tool to estimate the real-world impact of health interventions.

SUMMARYScarce 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.

Background Diabetes is associated with increased prevalence of TB infection in the US. We assessed associations between diabetes and interferon-gamma (IFN-γ) TB antigen response among adults with TB infection using US representative data. Methods National Health and Nutrition Examination (NHANES) participants >19 years from 2011 to 2012 with positive QuantiFERON®-TB Gold-In-Tube (QFT) results were eligible. Diabetes was defined by combination of self-report and glycated hemoglobin (HbA1c). Quantitative IFN-γ TB antigen was classified as high ( ≥ 10 IU/mL), intermediate (1.01–9.99 IU/mL), or low (0.35–1.00 IU/mL). Analyses accounted for NHANES weighted design. Results Among NHANES participants >19 years, n = 513 had positive QFT (5.9%). Among those with positive QFT, diabetes prevalence was 22.2% and pre-diabetes was 25.9%. Overall, 16.7% of positive QFT participants had high IFN-γ TB antigen levels including 21.7% among those with diabetes, 20.8% among those with pre-diabetes, and 12.6% among euglycemic participants. In adjusted analyses, high IFN-γ TB antigen response was more common among those with pre-diabetes (aOR 1.9, 95%CI 1.0, 3.6) compared to euglycemic participants. Conclusion Higher antigen responses may reflect immunopathy consistent with an exaggerated inflammatory but ineffectual response to TB or a reflection of more Mtb replication in participants with pre-diabetes or diabetes.

Importance Antihypertension medications have been associated with prevention of cardiovascular events, although less is known about the comparative effectiveness of different medication classes. Objective To compare contemporary aggregated first-in-trial cardiovascular events among patients with hypertension and no substantial comorbidities. Data Sources The PubMed, Embase, and Cochrane Library databases were systematically searched for articles published between January 1, 1990, and October 24, 2017. Study Selection Randomized clinical trials that tested commonly used antihypertension medications (angiotensin-converting enzyme inhibitors, dihydropyridine calcium channel blockers, nondihydropyridine calcium channel blockers, β-blockers, angiotensin receptor blockers, and diuretics) and that reported selected cardiovascular outcomes for at least 6 months of follow-up. Data Extraction and Synthesis The analysis was conducted from October 2017 to December 2019. Two reviewers extracted the number of cardiovascular events at the end of treatment for all study groups. For each outcome, a frequentist network meta-analysis was used to compare risk reductions between medication classes (random-effects models weighted by the inverse variance). The dose-response association between a 10–mm Hg reduction of systolic blood pressure and a 5–mm Hg reduction of diastolic blood pressure and the risk of first-in-trial cardiovascular events was estimated. Main Outcomes and Measures First-in-trial cardiovascular events, including cardiovascular death, myocardial infarction, stroke, and revascularization. Results In this systematic review and network meta-analysis, data were pooled from 46 eligible clinical trials (248 887 total participants with a mean [SD] age of 65.6 [5.8] years; 52.8% men). In the network meta-analysis, compared with placebo, angiotensin-converting enzyme inhibitors, dihydropyridine calcium channel blockers, and thiazide diuretics were reported to be similarly effective in reducing overall cardiovascular events (25%), cardiovascular death (20%), and stroke (35%); angiotensin-converting enzyme inhibitors were reported to be the most effective in reducing the risk of myocardial infarction (28%); and diuretics were reported to be the most effective in reducing revascularization (33%). In the metaregression analyses, each 10–mm Hg reduction in systolic blood pressure and 5-mm Hg reduction in diastolic blood pressure was significantly associated with a lower risk of cardiovascular death, stroke, and overall cardiovascular events. Conclusions and Relevance In this network meta-analysis of clinical trials of patients with hypertension and no substantial comorbidities, different classes of antihypertension medications were associated with similar benefits in reducing cardiovascular events. Future studies should compare the effectiveness of combinations of antihypertension medications in reducing cardiovascular events.

Background There is limited empirical evidence on the relationship between hyperglycemia, tuberculosis (TB) comorbidity, and mortality in the context of HIV. We assessed whether hyperglycemia at enrollment in HIV care was associated with increased risk of all-cause mortality and whether this relationship was different among patients with and without TB disease. Methods We conducted a retrospective analysis of adult (≥15 years) HIV-positive patients enrolled into HIV care between 2011 and 2016 who had random blood glucose (RBG) measurements at enrollment. We used hazards regression to estimate associations between RBG and rate of all-cause mortality. Results Of 25 851 patients, 43% were female, and the median age was 36 years. At registration, the median CD4 count (interquartile range [IQR]) was 162 (68–310) cell/mm3, the median RBG level (IQR) was 88 (75–106) mg/dL, and 6.2% (95% confidence interval [CI], 6.0%–6.5%) had hyperglycemia (RBG ≥140 mg/dL). Overall 29% of patients had TB disease, and 15% died during the study period. The adjusted hazard of death among patients with hyperglycemia was significantly higher (adjusted hazard ratio [aHR], 1.2; 95% CI, 1.1–1.4) than among those with normoglycemia without TB disease, but not among patients with TB disease (aHR, 1.0; 95% CI, 0.8–1.2). Using 4 categories of RBG and restricted cubic spline regression, aHRs for death were significantly increased in patients with RBG of 110–140 mg/dL (categorical model: aHR, 1.3; 95% CI, 1.2–1.4; restricted spline: aHR, 1.1; 95% CI, 1.0–1.1) compared with those with RBG Conclusions Our findings highlight an urgent need to evaluate hyperglycemia screening and diagnostic algorithms and to ultimately establish glycemic targets for PLHIV with and without TB disease.

The intersection of tuberculosis (TB) with non-communicable disease, including diabetes mellitus, chronic pulmonary disease, and cardiovascular disease has emerged as a critical clinical and public health challenge. Rapidly expanding non-communicable disease epidemics threaten TB control in low- and middle-income countries, where the prevention and treatment of TB disease remains a great burden. However, to date, the notion that TB may adversely impact non-communicable disease risk and severity has not been well explored. This review summarizes biomedical hypotheses, findings from animal models, and emerging epidemiologic data related to the progression of diabetes mellitus, chronic lung disease and cardiovascular disease during and after active TB disease. We conclude that there is sufficient empirical evidence to justify a greater research emphasis on the syndemic interaction between TB and non-communicable disease.

Purpose The purpose of this study was to determine if a negative tuberculin skin test (TST) result is associated with increased risk of mortality during tuberculosis (TB) treatment. Methods We conducted a retrospective cohort study among patients aged ≥15 years with culture-positive TB reported to the Georgia State Electronic Notifiable Disease Surveillance System from 2009 to 2014. TST positivity was defined by the US Centers for Disease Control guidelines. All-cause mortality during TB treatment as well as HIV, diabetes, and end-stage renal disease status were collected from surveillance data. Log-binomial regression was used to estimate adjusted risk ratios and 95% confidence intervals. Results Among 1186 culture-confirmed TB patients, 780 (65.8%) with a valid TST and TB treatment outcomes were eligible. Nearly one-third (242/780) had a negative TST result, and 5.6% died during treatment. The highest risk of death was observed among patients with a negative TST and HIV (12.5%) and a negative TST and diabetes (15.4%). Adjusting for confounders, the risk of death among patients with a negative TST was significantly greater compared with those with a positive TST (adjusted risk ratio 2.33 95% confidence interval 1.23–4.43). Conclusions A negative TST was associated with more than twice the risk of mortality during TB treatment after adjusting for immunosuppressive conditions.

PURPOSE OF REVIEW: The intersection of tuberculosis (TB) disease and type 2 diabetes mellitus is severely hindering global efforts to reduce TB burdens. Diabetes increases the risk of developing TB disease and negatively impacts TB treatment outcomes including culture conversion time, mortality risk, and TB relapse. Recent evidence also indicate plausible mechanisms by which TB disease may influence the pathogenesis and incidence of diabetes. We review the epidemiology of stress hyperglycemia in patients with TB and the pathophysiologic responses to TB disease that are related to established mechanisms of stress hyperglycemia. We also consider clinical implications of stress hyperglycemia on TB treatment, and the role of TB disease on risk of diabetes post-TB. RECENT FINDINGS: Among patients with TB disease, the development of stress hyperglycemia may influence the clinical manifestation and treatment response of some patients, and can complicate diabetes diagnosis. SUMMARY: Research is needed to elucidate the relationship between TB disease and stress hyperglycemia and determine the extent to which stress hyperglycemia impacts TB treatment response. Currently there is insufficient data to support clinical recommendations for glucose control among patients with TB disease, representing a major barrier for efforts to improve treatment outcomes for patients with TB and diabetes.

Mentoring is a critical component of career development for research scientists and is related to mentee success both in terms of career selection and advancement. However, there are limited data on the role of mentoring in low- and middle-income countries (LMICs). Cross-cultural mentorship programs have the potential to foster the transfer of knowledge and the development of capacity to resource-poor settings. This formative evaluation explores the cultural context of mentoring in the countries of Georgia and Ethiopia. Results were used to build culturally relevant mentor training programs for two Global Infectious Disease Research Training Programs focused on tuberculosis funded by the Fogarty International Center at the US National Institutes of Health. Four focus group discussions were conducted with research trainees and mentors to explore the perceptions of mentorship, identify obstacles for successful mentoring, and generate recommendations to strengthen mentoring in each program situated in a LMIC. Data revealed the barriers to mentoring in Ethiopia and Georgia included gaps in knowledge about mentoring roles and responsibilities, lack of knowledge about the responsibilities of the trainee in a mentoring relationship, and the need to set clear expectations between mentors and trainees. All of the focus group participants desired formal mentor training. These data informed six key components of the development and implementation of the mentor training programs in both countries. The topics included the following: a foundation in mentoring, establishing expectations between mentees and mentors, increasing interactions between mentees and mentors, additional mentor training, a case study curriculum, and methods of evaluating mentoring relationships.