Tuberculosis infection and hypertension: prevalence estimates from the US National Health and Nutrition Examination Survey.

OBJECTIVES: Tuberculosis infection (TBI) 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 TBI and hypertension, an intermediate of CVD. We sought to determine the association between TBI and hypertension using data representative of the adult US population. METHODS: We 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. TBI was defined by a positive QFT-GIT. We defined hypertension by either elevated measured blood pressure levels (ie, systolic ≥130 mm Hg or diastolic ≥80 mm Hg) or known hypertension indications (ie, 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. RESULTS: The overall prevalence of TBI was 5.7% (95% CI 4.7% to 6.7%) and hypertension was present among 48.9% (95% CI 45.2% to 52.7%) of participants. The prevalence of hypertension was higher among those with TBI (58.5%, 95% CI 52.4% to 64.5%) than those without TBI (48.3%, 95% CI 44.5% to 52.1%) (prevalence ratio (PR) 1.2, 95% CI 1.1 to 1.3). However, after adjusting for confounders, the prevalence of hypertension was similar for those with and without TBI (adjusted PR 1.0, 95% CI 1.0 to 1.1). The unadjusted prevalence of hypertension was higher among those with TBI versus no TBI, especially among individuals without CVD risk factors including those with normal body mass index (PR 1.6, 95% CI 1.2 to 2.0), euglycaemia (PR 1.3, 95% CI 1.1 to 1.5) or non-smokers (PR 1.2, 95% CI 1.1 to 1.4). CONCLUSIONS: More than half of adults with TBI in the USA had hypertension. Importantly, we observed a relationship between TBI and hypertension among those without established CVD risk factors. SUMMARY: The prevalence of hypertension was high (59%) among adults with TBI in the USA. In addition, we found that the prevalence of hypertension was significantly higher among adults with positive QFT without established hypertension risk factors.

HIV co-infection increases the risk of post-tuberculosis mortality among persons who initiated treatment for drug-resistant tuberculosis.

Little is known regarding the relationship between common comorbidities in persons with tuberculosis (TB) (including human immunodeficiency virus [HIV], diabetes, and hepatitis C virus [HCV]) with post-TB mortality. We conducted a retrospective cohort study among persons who initiated treatment for rifampicin-resistant and multi/extensively drug-resistant (RR and M/XDR) TB reported to the country of Georgia's TB surveillance during 2009-2017. Exposures included HIV serologic status, diabetes, and HCV status. Our outcome was all-cause post-TB mortality determined by cross-validating vital status with Georgia's death registry through November 2019. We estimated adjusted hazard rate ratios (aHR) and 95% confidence intervals (CI) of post-TB mortality among participants with and without comorbidities using cause-specific hazard regressions. Among 1032 eligible participants, 34 (3.3%) 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 (interquartile range 7-39) post-TB treatment. After adjusting for confounders, the hazard rates of post-TB mortality were higher among participants with HIV co-infection (aHR=3.74, 95%CI 1.77-7.91) compared to those without HIV co-infection. In our cohort, post-TB mortality occurred most commonly in the first three years post-TB treatment. Linkage to care for common TB comorbidities post-treatment may reduce post-TB mortality rates.

Pulmonary Function and Quality of Life in Adults with Cystic Fibrosis.

PURPOSE: People living with cystic fibrosis (CF) experience impaired quality of life, but the extent to which pulmonary function is associated with quality of life in CF remains unclear METHODS: Using baseline data from a trial of specialist palliative care in adults with CF, we examined the association between pulmonary obstruction and quality of life (measured with the Functional Assessment of Chronic Illness Therapy Total Score). RESULTS: Among 262 participants, median age was 33, and 78% were on modulator therapy. The median quality of life score was higher in those with mild obstruction (135, IQR 110-156) compared to moderate (125, IQR 109-146) and severe obstruction (120, IQR 106-136). In an unadjusted model, we observed a non-significant trend toward lower quality of life with increased obstruction-compared to participants with mild obstruction, those with moderate obstruction had quality of life score 7.46 points lower (95% CI -15.03 to 0.10) and those with severe obstruction had a score 9.98 points lower (95% CI -21.76 to 1.80). However, this association was no longer statistically significant in the adjusted model, which may reflect confounding due to sex, age, BMI, and modulator therapy. Comorbidities (depression and anxiety) and social determinants of health (financial insecurity and education) were also associated with quality of life. CONCLUSION: Advancing our understanding of patient-centered markers of quality of life, rather than focusing on pulmonary function alone, may help identify novel interventions to improve quality of life in this patient population.

Diabetes Mellitus and Tuberculosis Treatment Outcomes: Interaction Assessment Between Hyperglycemia and Human Immunodeficiency Virus in the State of Georgia, 2015-2020.

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 and 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 (adjusted risk ratio [aRR] = 2.59; 95% confidence interval [CI], 1.62-4.13). We estimated that 26% (95% CI, -43.4% to 95.0%) of deaths among participants with diabetes mellitus 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.

Tuberculosis infection and hypertension: Prevalence estimates from the US National Health and Nutrition Examination Survey.

Objectives: Latent 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. Methods: We 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. Results: The 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 (PRnormal BMI=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. Conclusions: More 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.

Mapping digital health ecosystems in Africa in the context of endemic infectious and non-communicable diseases.

Investments in digital health technologies such as artificial intelligence, wearable devices, and telemedicine may support Africa achieve United Nations (UN) Sustainable Development Goal for Health by 2030. We aimed to characterize and map digital health ecosystems of all 54 countries in Africa in the context of endemic infectious and non-communicable diseases (ID and NCD). We performed a cross-national ecological analysis of digital health ecosystems using 20-year data from the World Bank, UN Economic Commission for Africa, World Health Organization, and Joint UN Programme on HIV/AIDS. Spearman's rank correlation coefficients were used to characterize ecological correlations between exposure (technology characteristics) and outcome (IDs and NCDs incidence/mortality) variables. Weighted linear combination model was used as the decision rule, combining disease burden, technology access, and economy, to explain, rank, and map digital health ecosystems of a given country. The perspective of our analysis was to support government decision-making. The 20-year trend showed that technology characteristics have been steadily growing in Africa, including internet access, mobile cellular and fixed broadband subscriptions, high-technology manufacturing, GDP per capita, and adult literacy, while many countries have been overwhelmed by a double burden of IDs and NCDs. Inverse correlations exist between technology characteristics and ID burdens, such as fixed broadband subscription and incidence of tuberculosis and malaria, or GDP per capita and incidence of tuberculosis and malaria. Based on our models, countries that should prioritize digital health investments were South Africa, Nigeria, and Tanzania for HIV; Nigeria, South Africa, and Democratic Republic of the Congo (DROC) for tuberculosis; DROC, Nigeria, and Uganda for malaria; and Egypt, Nigeria, and Ethiopia for endemic NCDs including diabetes, cardiovascular disease, respiratory diseases, and malignancies. Countries such as Kenya, Ethiopia, Zambia, Zimbabwe, Angola, and Mozambique were also highly affected by endemic IDs. By mapping digital health ecosystems in Africa, this study provides strategic guidance about where governments should prioritize digital health technology investments that require preliminary analysis of country-specific contexts to bring about sustainable health and economic returns. Building digital infrastructure should be a key part of economic development programs in countries with high disease burdens to ensure more equitable health outcomes. Though infrastructure developments alongside digital health technologies are the responsibility of governments, global health initiatives can cultivate digital health interventions substantially by bridging knowledge and investment gaps, both through technology transfer for local production and negotiation of prices for large-scale deployment of the most impactful digital health technologies.

Diabetes mellitus is associated with an increased risk of unsuccessful treatment outcomes among drug-susceptible tuberculosis patients in Ethiopia: A prospective health facility-based study.

Background: The impact of diabetes mellitus on tuberculosis (TB) treatment outcomes has not been well investigated in most sub-Saharan countries including Ethiopia. The current study aimed to determine the association between diabetes mellitus and unsuccessful TB treatment outcomes among drug-susceptible TB patients treated at selected health facilities in Addis Ababa, Ethiopia. Methods: This health facility-based prospective cohort study was conducted at six randomly selected public health centers in Addis Ababa, from August 2020 until November 2021. Clinically diagnosed adult pulmonary and extra pulmonary TB patients were recruited at the time of treatment initiation. A multivariable logistic regression analysis was used to estimate the association between diabetes and unsuccessful TB treatment outcomes. Results: Among the total 267 enrolled participants, 9.7% of patients with TB were identified to have diabetes comorbidity. Of patients with diabetes and TB, 9 (34.6%) were newly diagnosed based on glucose test results. Despite an overall high TB treatment success rate (94.0%), more than one-fourth (26.9%) of patients with diabetes had a poor TB treatment outcome (26.9%), which was remarkably higher compared to patients without diabetes (3.7%). In multivariable regression, the adjusted odds of poor TB treatment outcome among those with diabetes was 14.8 (95% CI 3.5 - 62.7) times the odds of poor outcome patients without diabetes. Conclusion: Diabetes was significantly associated with increased odds of poor TB treatment outcomes among patients in Addis Ababa, Ethiopia.

Increased All-cause Mortality in People With HIV and Comorbidities: Hepatitis B and C Virus Seropositivity and Hyperglycemia in Myanmar, 2005-2017.

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.

Longitudinal trends in glycated hemoglobin during and after tuberculosis treatment.

AIMS: To investigate the impact of pulmonary TB on glycemic status during and after TB treatment, and associations of glycemic trends with antidiabetic therapy and TB outcomes. METHODS: Data from two prospective cohort studies of adults in Chennai, India, with pulmonary TB were combined for this analysis. Participants were classified by baseline hemoglobin A1c (A1C) as having normoglycemia (NG; n = 74), prediabetes (pre-DM; n = 110), or diabetes (DM; n = 244). Repeat A1C measurements were performed at TB treatment months 3 and 6, and then 6 and 12 months after TB treatment completion. RESULTS: Median A1C at baseline declined after TB treatment initiation in all groups. No baseline NG or pre-DM participants progressed to DM by end of study, while 16.7% of baseline DM participants shifted to pre-DM or NG levels of A1C. In the baseline DM group, rising A1C after the intensive phase of TB treatment was significantly associated with adverse TB outcomes. CONCLUSIONS: Incident TB promotes transient glucose elevation but was not conclusively shown to promote chronic dysglycemia. Rising A1C during and after TB treatment may predict unfavorable treatment response in persons presenting with A1C ≥ 6.5 % at the time of TB diagnosis.

Prediabetes and risk of active tuberculosis: a cohort study from Northern Taiwan.

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.

The Impact of Diabetes and Prediabetes on Prevalence of Mycobacterium tuberculosis Infection Among Household Contacts of Active Tuberculosis Cases in Ethiopia.

Background: It is uncertain whether diabetes affects the risk of developing latent tuberculosis infection (LTBI) following exposure to Mycobacterium tuberculosis (Mtb). We assessed the relationship of diabetes or prediabetes and LTBI among close and household contacts (HHCs) of patients with active pulmonary tuberculosis (TB) disease in Addis Ababa, Ethiopia. Methods: In 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. Results: 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 those <40 years (aOR, 1.15 [95% CI, .22-6.1]). Conclusions: 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 Mtb exposure.

Outpatient clinic attendance and outcomes among patients hospitalized with diabetic foot ulcers.

BACKGROUND: There are limited data on post-hospital discharge clinic attendance rates and outcomes among patients with diabetic foot ulcers (DFUs). METHODS: 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). RESULTS: 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. CONCLUSION: 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.

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.

Increased Risk of Incident Diabetes Among Individuals With Latent Tuberculosis Infection.

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.

Synergy between low BMI and hyperglycemia at baseline increases tuberculosis incidence among people living with HIV.

OBJECTIVES: Low 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 (PWH) is unexplored. We compared TB incidence among PWH with different exposure profiles to low BMI (BMI < 18.5 kg/m2) and hyperglycemia (random blood glucose ≥140 mg/dl). DESIGN AND METHODS: We conducted a cohort study using data of PWH (≥15 years) who enrolled in Myanmar's Integrated HIV Care Program between 2011 and 2017. We used their follow-up data until 2018 to determine TB incidence. RESULTS: Among 20 865 PWH included in this study, 7610 (36%) had low BMI only, 1324 (6%) had hyperglycemia only, and 465 (2%) patients had concurrent low BMI and hyperglycemia (joint exposure) at baseline. During a median follow-up of 2.2 years (interquartile range: 0.5, 4.2), 3628 (17%) developed TB [6.7, 95% confidence interval (CI): 6.5,7.0 cases per 100 person-years (PY)]. TB incidence among PWH with joint exposure was 21.0 (95% CI: 18.0, 24.7), with low BMI only was 10.9 (95% CI: 10.4, 11.4), with hyperglycemia only was 5.2 (95% CI: 4.4, 6.3) and with no exposure was 4.6 (95% CI: 4.4, 4.9) cases per 100 PY. The attributable proportion of incident TB due to synergy between low BMI and hyperglycemia was 0.23 (95% CI: 0.06, 0.36). CONCLUSION: Synergy between low BMI and hyperglycemia was associated with increased excess TB incidence in PWH. TB preventive treatment, nutritional support, and hyperglycemia management should be evaluated as interventions to reduce TB risk in PWH with joint exposure.

Latent tuberculosis infection among patients with and without type-2 diabetes mellitus: results from a hospital case-control study in Atlanta.

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 < 0.01). In addition, we reported a high prevalence of LTBI among adults with T2DM and family members without T2DM.

Long-Term Mortality and Active Tuberculosis Disease Among Patients Who Were Lost to Follow-Up During Second-Line Tuberculosis Treatment in 2011-2014: Population-Based Study in the Country of Georgia.

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.

Treatment Outcomes Among Pediatric Patients With Highly Drug-Resistant Tuberculosis: The Role of New and Repurposed Second-Line Tuberculosis Drugs.

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.

Adults with Mycobacterium tuberculosis infection and pre-diabetes have increased levels of QuantiFERON interferon-gamma responses.

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.

Evaluation of the Host Genetic Effects of Tuberculosis-Associated Variants Among Patients With Type 1 and Type 2 Diabetes Mellitus.

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.