Risk Factors For Active Tuberculosis Research Articles

Tuberculosis risk in patients with Crohn's disease on biologics: a retrospective analysis of the Japanese Medical Claims Database.

Treatment using tumor necrosis factor-α (TNF-α) inhibitors is one of the risk factors for active tuberculosis (TB) in patients with Crohn's disease (CD). Biologics, such as ustekinumab (UST) and vedolizumab (VDZ), are less likely to cause opportunistic infections. However, large-scale studies for active TB and biologics other than TNF-α inhibitors are limited. We aimed to investigate the association between biologics and active TB utilizing a Japanese medical claims database. We analyzed retrospectively the association of the risk of active TB development with treatment using TNF-α inhibitors and other biologics (UST and VDZ) in patients with CD using the Japanese Medical Data Vision (MDV) database between April 2008 and June 2022. The durations of each biologic and biologic-free treatment were calculated for each patient. Univariate and multivariate analyses were performed using the Cox proportional hazards model, with the utilization of biologics considered as time-dependent covariates. We included 28,811 patients with CD in MDV database. Finally, 17,169 patients were analyzed. In total, 7,064 patients were categorized as biologic-naïve, while 10,105 were classified as biologic-experienced. Seventeen patients developed active TB, including 7 on infliximab, 5 on adalimumab, and 5 on no biologics. None of the patients treated with UST and VDZ developed active TB. Multivariate analysis suggested that TNF-α inhibitors were the risk factors for active TB (hazard ratio, 3.66; P= 0.020). TNF-α inhibitors, but not UST or VDZ, are risk factors for active TB in Japanese patients with CD.

Risk factors of tuberculosis in children with adult household tuberculosis contact

Background Since children are more likely than adults to become infected with Mycobacterium tuberculosis or suffer from tuberculosis (TB), it is important to identify the risk factors of TB in children with adult household TB contacts. Objective To identify the risk factors of TB in children with adult household TB contacts. Methods This cross-sectional study was conducted at the Pediatric Respirology Inpatient Ward and Outpatient Clinic at Dr. Soetomo Hospital, Surabaya, Indonesia, using medical records of hospitalized patients from 2010 to 2018. Patients were children below 18 years of age who had a history of adult TB household contact(s). We analyzed age at TB diagnosis, nutritional status, BCG vaccination status, and HIV status as possible risk factors of TB. Results A total of 367 children with adult household TB contacts were included in our study. Age of <5 years (OR 8.38; 95%CI 3.78 to 18.21; P<0.001), severe malnutrition (OR 8.88; 95%CI 1.19 to 66.27, P<0.05), absence of BCG scar (OR 2.96; 95%CI 1.32 to 6.62, P<0.05), and positive HIV status (OR 6.72; 95%CI 1.72-38.49, P<0.05) were risk factors for contracting active TB. Conclusion Age of <5 years, severe malnutrition, absence of BCG scar, and positive HIV status are significant risk factors for active TB in children with adult household TB contacts.

Strong effect of demographic changes on Tuberculosis susceptibility in South Africa.

South Africa is among the world's top eight tuberculosis (TB) burden countries, and despite a focus on HIV-TB co-infection, most of the population living with TB are not HIV co-infected. The disease is endemic across the country, with 80-90% exposure by adulthood. We investigated epidemiological risk factors for (TB) in the Northern Cape Province, South Africa: an understudied TB endemic region with extreme TB incidence (926/100,000). We leveraged the population's high TB incidence and community transmission to design a case-control study with similar mechanisms of exposure between the groups. We recruited 1,126 participants with suspected TB from 12 community health clinics and generated a cohort of 774 individuals (cases = 374, controls = 400) after implementing our enrollment criteria. All participants were GeneXpert Ultra tested for active TB by a local clinic. We assessed important risk factors for active TB using logistic regression and random forest modeling. We find that factors commonly identified in other global populations tend to replicate in our study, e.g. male gender and residence in a town had significant effects on TB risk (OR: 3.02 [95% CI: 2.30-4.71]; OR: 3.20 [95% CI: 2.26-4.55]). We also tested for demographic factors that may uniquely reflect historical changes in health conditions in South Africa. We find that socioeconomic status (SES) significantly interacts with an individual's age (p = 0.0005) indicating that protective effect of higher SES changed across age cohorts. We further find that being born in a rural area and moving to a town strongly increases TB risk, while town birthplace and current rural residence is protective. These interaction effects reflect rapid demographic changes, specifically SES over recent generations and mobility, in South Africa. Our models show that such risk factors combined explain 19-21% of the variance (r2) in TB case/control status.

Incidence and risk factors of active tuberculosis among older individuals with latent tuberculosis infection: a cohort study in two high-epidemic sites in eastern China.

The influencing factors of the process from latent tuberculosis infection (LTBI) to the onset of active tuberculosis (TB) remain unknown among different population groups, especially among older individuals in high-incidence areas. This study aimed to investigate the development of active TB among older adults with LTBI and identify groups in greatest need of improved prevention and control strategies for TB. In 2021, we implemented an investigation among older individuals (≥ 65 years old) in two towns in Zhejiang Province with the highest incidence of TB. All participants underwent assessment using standardized questionnaires, physical examinations, interferon-gamma release assays, and chest radiography. All the participants with suspected TB based on the clinical symptoms or abnormal chest radiography results, as well as those with LTBI, were referred for diagnostic investigation in accordance with the national guidelines. Those with an initial diagnosis of TB were then excluded, whereas those with LTBI were included in a follow-up at baseline. Incident patients with active TB were identified from the Chinese Tuberculosis Management Information System, and a multivariate Cox regression model was used to estimate the incidence and risk of TB among those with LTBI. In total, 667 participants with LTBI were followed up for 1,315.3 person-years, revealing a disease density of 1,292.5 individuals/100,000 person-years (17/1,315.3). For those with LTBI, chest radiograph abnormalities had adjusted hazard ratios for active TB of 4.9 (1.6-15.3). The presence of abnormal chest radiography findings increased the risk of active TB among older individuals with LTBI in high-epidemic sites in eastern China.

Incidence and risk factors for HIV-tuberculosis coinfection in the Cologne-Bonn region: a retrospective cohort study.

The risk of developing active tuberculosis (TB) is considerably increased in people living with HIV/AIDS (PLWH). However, incidence of HIV/TB coinfection is difficult to assess as surveillance data are lacking in many countries. Here, we aimed to perform a quantitative analysis of HIV/TB coinfections within the Cologne/Bonn HIV cohort and to determine risk factors for active TB. We systematically evaluated data of patients with HIV/TB coinfection between 2006 and 2017. In this retrospective analysis, we compared HIV/TB-coinfected patients with a cohort of HIV-positive patients. The incidence density rate (IDR) was calculated for active TB cases at different time points. During 2006-2017, 60 out of 4673 PLWH were diagnosed with active TB. Overall IDR was 0.181 cases/100 patient-years and ranged from 0.266 in 2006-2009 to 0.133 in 2014-2017. Patients originating from Sub-Saharan Africa had a significantly (p < 0.001) higher IDR (0.694/100 patient-years of observation, 95% CI [0.435-1.050]) in comparison to patients of German origin (0.053/100 patient-years of observation, 95% CI [0.028-0.091]). In terms of TB-free survival, individuals originating from countries with a TB incidence higher than 10/100,000 exhibited a markedly reduced TB-free survival compared to those originating from regions with lower incidence (p < 0.001). In 22 patients, TB and HIV infection were diagnosed simultaneously. Overall, we observed a decline in the incidence density rate (IDR) of HIV/TB coinfections between 2006 and 2017. Patients originating from regions with high incidence bear a higher risk of falling ill with active TB. For PLWH born in Germany, the observed risk of active TB appears to be lower compared to other groups within the cohort. These findings should be considered when developing TB containment and screening strategies for PLWH in low-incidence countries.

Incidence and Risk Factors of Active Tuberculosis Among Hospitalized Patients with Latent Tuberculosis Infection in China: A Cohort Study.

The population with latent tuberculosis infection (LTBI) represents a potential pool of patients with active tuberculosis (ATB). T-SPOT.TB is an important test tool for screening LTBI. Owing to the large population of LTBI patients in China, it is necessary to identify a high-risk group for LTBI and enlarge tuberculosis preventive treatment (TPT) to reduce the incidence of ATB. Hospitalized patients with positive T-SPOT.TB results were recruited from January 2013 to December 2016. Patients with ATB were excluded. Basic information was collected and the development of ATBs was examined during follow-up. The life-table method was used to calculate cumulative incidence rates. Potential risk factors were analyzed through Cox regression analysis. A total of 1680 patients with LTBI were recruited in the follow-up cohort, and 377 (22.44%) patients dropped out. With a median follow-up time of 81 months [interquartile range (IQR):61-93], 19 of 1303 patients with LTBI developed ATB. The 1-year incidence of ATB was 614 per 100,000 individuals [95%confidence interval (95% CI):584-644]. Over 5-year period, the cumulative incidence of ATB was 1496 per 100,000 [95% CI:1430-1570], and the incidence density was 240 per 100,000 person-years[95% CI:144-375]. In the Cox regression model, exposure of pulmonary tuberculosis (PTB) [adjusted hazard ratio (aHR)=10.557, 95% CI:2.273-49.031], maximum daily dosage of glucocorticoids (GCs)≥ 50 mg/d (aHR=2.948, 95% CI:1.122-7.748), leflunomide (LEF) treatment (aHR=8.572, 95% CI:2.222 -33.070), anemia (aHR=2.565, 95% CI:1.015-6.479) and T-SPOT.TB level≥300SFCs/106 PBMCs (aHR=4.195, 95% CI:1.365-12.892) were independent risk factors for ATB development in LTBI patients. The incidence of ATB is significantly higher in hospitalized patients with LTBI than in the general population. The exposure history of PTB, maximum daily dosage of GCs≥ 50 mg/day, LEF treatment, anemia, and T-SPOT.TB level≥300SFCs/106PBMCs, were the risk factors of tuberculosis reactivation. Hospitalized LTBI patients with the above factors may need TPT.

P1111 Prevalence and risk factors for active tuberculosis in Tunisian IBD patients

Abstract Background IBD patients are at risk of active tuberculosis,given the use of immunosuppressive treatments.Our country is an endemic region for tuberculosis,which may increase this risk. The aim of our study was to estimate the prevalence of active tuberculosis in IBD patients with prior screening and to investigate associated risk factors. Methods This was a retrospective and descriptive study,including all IBD patients admitted in the department,who had a screening for latent tuberculosis,over a 10-year period[2012-2022].Patients with less than 12 months' follow-up were excluded. Results We included 100 patients, 52 men and 48 women.Crohn's disease(CD)was present in 86% of cases,and ulcerative colitis in 14%.CD was predominantly ileocolic (47%).The phenotype of luminal CD was inflammatory, stenosing and fistulizing in 36.6%,28% and 35.4% of cases respectively.Anoperineal involvement was present in 41.9% of CD patients.At the time of screening, patients were on salicylates, steroids and thiopurines in 13%,27% and 22% of cases respectively.Body mass index median was 22.7kg/m².Two-thirds of patients(65%)were in a flare-up at the time of screening,with 50.8% in moderate severity, and 3.1% in severe acute colitis.Ninety patients had a negative TST.The quantiFERON test was positive in 9 patients and indeterminate in one,in four of them, the TST was also positive. There were no abnormalities on chest X-rays in all patients.Fifteen patients received chemoprophylaxis, mainly because of suspected latent tuberculosis, but also because of severe undernutrition despite a negative workup in 3 patients.Chemoprophylaxis was isoniazid monotherapy for 9 months,except for 3 patients who received isoniazid and rifampicin dual therapy for 3 months.The prevalence of active tuberculosis in our patients was 11%.The median time from onset of tuberculosis to screening was 12 months.Almost all patients were on anti-TNFα monotherapy(n=4) or combotherapy(n=6).One patient was on azathioprine only. Chest CT scans showed signs suggestive of tuberculosis in only 2 patients.Among patients who developed active tuberculosis, 2 had previously received chemoprophylaxis for a positive TST. In a univariate study,we analyzed all variables for risk factors associated with the occurrence of tuberculosis in our patients.Apart from the use of anti-TNF drugs(p=0.03),no statistically significant associations were found:severity of relapse during screening(p=0.3),undernutrition as evidenced by a low BMI(p=0.92),albuminemia(p=0.77),C reactive protein(p=0.8). Conclusion The median delay to onset of active tuberculosis suggests post-screening transmission.This is further evidence of the need to shorten the time required for systematic updating of the tuberculosis work-up in endemic countries.

Cytokine and chemokine profiles in pulmonary tuberculosis with pre-diabetes.

Tuberculosis (TB) remains a significant health concern in India, and its complexity is exacerbated by the rising occurrence of non-communicable diseases such as diabetes mellitus (DM). Recognizing that DM is a risk factor for active TB, the emerging comorbidity of TB and PDM (TB-PDM) presents a particular challenge. Our study focused on the impact of PDM on cytokine and chemokine profiles in patients with pulmonary tuberculosis TB) who also have PDM. We measured and compared the cytokine (GM-CSF, IFN-γ, IL-1α/IL-1F1, IL-1β/IL-1F2, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-17/IL-17A, IL-18/IL-1F4, TNF-α) and chemokine (CCL1, CCL2, CCL3, CCL4, CCL11, CXCL1, CXCL2, CXCL9, CXCL10, and CXCL11) levels in plasma samples of TB-PDM, only TB or only PDM using multiplex assay. We observed that PDM was linked to higher mycobacterial loads in TB. Patients with coexisting TB and PDM showed elevated levels of various cytokines (including IFNγ, TNFα, IL-2, IL-17, IL-1α, IL-1β, IL-6, IL-12, IL-18, and GM-CSF) and chemokines (such as CCL1, CCL2, CCL3, CCL4, CCL11, CXCL1, CXCL9, CXCL10, and CXCL11). Additionally, cytokines such as IL-18 and GM-CSF, along with the chemokine CCL11, were closely linked to levels of glycated hemoglobin (HbA1c), hinting at an interaction between glycemic control and immune response in TB patients with PDM. Our results highlight the complex interplay between metabolic disturbances, immune responses, and TB pathology in the context of PDM, particularly highlighting the impact of changes in HbA1c levels. This emphasizes the need for specialized approaches to manage and treat TB-PDM comorbidity.

A retrospective study of tuberculosis prevalence and associated factors among HIV-positive key populations in Nigeria.

HIV is a major risk factor for active Tuberculosis (TB.) This raises patients' risk of original infection, reinfection, and TB reactivation. Providing healthcare to KPLHIV in developing countries requires TB prevalence research. This study aims to determine the prevalence of TB and HIV co-infection and associated factors among KPLHIV. This is a retrospective cross-sectional study among KP's living with HIV enrolled on care in One Stop Shop (OSS) of Heartland Alliance Ltd/GTE across six states in Nigeria. Data were analysed using IBM SPSS version 25.0. Secondary data analysis of client's records from the RADET files of the KPCARE 1 project from 6 states was conducted. Means with standard deviations were computed for continuous variables like age, and frequency tables were generated for categorical variables. Chi-square tests and t-tests were used for the bivariate analysis of variables. All tests were done at a 5% level of statistical significance (p = 0.05).TB prevalence was 19.1% among KP's living with HIV, with variations observed in age groups, geographic locations, target populations, marital status, educational backgrounds, clinical characteristics, and antiretroviral therapy (ART) history. KPs aged 51 and above exhibited the highest TB prevalence (21.0%), while those aged below 20 years had the lowest (18.2%). Jigawa KPs recorded the highest TB prevalence (38.4%), and Niger had the least (13.3%). TB was more prevalent among People who inject drugs (20.3%), divorced (32.3%), and those who attained Qur'anic education (29.7%). KPs who had to restart ART exhibited the highest TB prevalence (22.0%), whereas those who experienced Interruption in treatment (IIT) reported the lowest at 10.0%. Immune-suppressed KPs (CD4 counts < 200 cells/m3) had a higher TB prevalence of 26.6%. TB prevalence among KPs living with HIV varies greatly, underlining the need for targeted treatments, especially for high-risk categories, to improve HIV treatment outcomes and reduce TB prevalence.

Risk factors and treatment outcome of smear positive pulmonary tuberculosis patients: A five-year study in the North of Iran.

It is essential to constantly review the risk factors and treatment outcomes of tuberculosis (TB). This study evaluated some important risk factors of TB over five years. Between 2013 and 2018, all available information and possible risk factors related to TB patients were analyzed from the TB registry program of the health district of Gorgan, Iran. Among 349 TB patients, 194 (55.59%) were males and 167 (47.85%) had at least a comorbidity. The death rate was higher in the age group more than 65 years (p < 0.001), the low-educated group (P = 0.012), and patients with underlying diseases, especially diabetes (p < 0.001). In total, univariate and multivariate statistical analyzes showed that having comorbidity (OR = 4.34; 95% CI 1.49 - 13.49), as well as, being jobless (OR = 3.07; 95% CI 1.19 - 8.59) were the main factors influencing the adverse events. According to the study, aging, underlying diseases, and cultural poverty include a higher share of the main risk factors for active TB and/or treatment outcomes. By considering these risk factors and training the medical staff continually, we can reduce the time of TB diagnosis, and prevent it from spreading.

Incidence of and Risk Factors for Active Tuberculosis Disease in Individuals With Glomerular Disease: A Canadian Cohort Study

Kidney failure is an established risk factor for active tuberculosis (TB) but the risk of TB has not been reported in specific kidney diseases. We sought to determine the incidence of and risk factors for active TB in patients with glomerular disease. Observational cohort study. A provincial kidney pathology registry (2000-2012) was used to identify 3,079 adult patients with IgA nephropathy, focal segmental glomerulosclerosis (FSGS), antineutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis, lupus nephritis, membranous nephropathy, minimal change disease, or "other" glomerular diseases in British Columbia, Canada. Predictors included demographics, immigration status, comorbidities, immunosuppression use, estimated glomerular filtration rate (eGFR), and proteinuria. A diagnosis of active TB was ascertained using administrative data linkages and defined based on (1) the dispensation of 1 or more unique combinations of medications used to treat active TB, or (2) physician or hospital visits for active TB. The definition of TB was validated in an external cohort linked to the Provincial TB registry at the BC Centre for Disease Control (BCCDC). Standardized incidence ratios were calculated using the age-matched general population. Risk factors for active TB were identified using Cox proportional hazards regression analysis. The sensitivity and specificity of the outcome definition of active TB were 87.6% and 99.5%, respectively. During a median follow-up of 6.2 years, 41 patients developed active TB with an incidence of 197 of 100,000 person-years, approximately 23 times as high as the general population and>6 times higher than the threshold of 30 per 100,000 used to define high TB incidence. A high incidence was observed in all glomerular diseases (range, 110-403 per 100,000), in both Canadian- and foreign-born patients (range, 124-424 per 100,000), and in patients exposed or not to immunosuppression (282 vs 147 per 100,000). Factors associated with higher TB risk included immigration from a high-incidence country (HR, 3.90 [95% CI, 1.75-8.68]), diminished eGFR (HR, 2.81 [95% CI, 1.18-6.69]), higher levels of proteinuria (HR, 1.15 [95% CI, 1.04-1.27]), lupus nephritis (HR, 2.79 [95% CI, 1.37-5.68]), and immunosuppression use (HR, 2.13 [95% CI, 1.13-4.03]). A relatively low number of events contributed to uncertainty in risk estimates. Patients with glomerular disease have a high incidence of active TB irrespective of disease type, demographics, or use of immunosuppression. Prospective studies are needed to evaluate the utility of screening for latent TB infection in this population. Patients with kidney failure are at high risk of developing tuberculosis (TB), a major infection that can be prevented by identifying and treating patients who have had prior exposure to TB. The risk of TB in specific kidney diseases is unknown. In this Canadian study of 3,079 patients with glomerular disease, a group of autoimmune kidney conditions, the rate of TB was 23 times higher than in the general population. The rate was high irrespective of the use of immunosuppressive drugs or whether patients had immigrated to Canada from another country. These findings suggest that screening patients with glomerular disease for prior TB exposure may be beneficial; however, this needs to be evaluated in a prospective study.

Methylprednisolone Promotes Mycobacterium smegmatis Survival in Macrophages through NF-κB/DUSP1 Pathway

Mycobacterium tuberculosis (M. tuberculosis) is the causative agent of tuberculosis. As an important component of host immunity, macrophages are not only the first line of defense against M. tuberculosis but also the parasitic site of M. tuberculosis in the host. Glucocorticoids can cause immunosuppression, which is considered to be one of the major risk factors for active tuberculosis, but the mechanism is unclear. To study the effect of methylprednisolone on the proliferation of mycobacteria in macrophages and try to find key molecules of this phenomenon. The macrophage line RAW264.7 infected by M. smegmatis was treated with methylprednisolone, and the intracellular bacterial CFU, Reactive Oxygen Species (ROS), cytokine secretion, autophagy, and apoptosis were measured. After the cells were treated with NF-κB inhibitor BAY 11-7082 and DUSP1 inhibitor BCI, respectively, the intracellular bacterial CFU, ROS, IL-6, and TNF-α secretion were detected. After treatment with methylprednisolone, the CFU of intracellular bacteria increased, the level of ROS decreased, and the secretion of IL-6 and TNF-α decreased in infected macrophages. After BAY 11-7082 treatment, the CFU of M. smegmatis in macrophages increased, and the level of ROS production and the secretion of IL-6 by macrophages decreased. Transcriptome high-throughput sequencing and bioinformatics analysis suggested that DUSP1 was the key molecule in the above phenomenon. Western blot analysis confirmed that the expression level of DUSP1 was increased in the infected macrophages treated with methylprednisolone and BAY 11-7082, respectively. After BCI treatment, the level of ROS produced by infected macrophages increased, and the secretion of IL-6 increased. After the treatment of BCI combined with methylprednisolone or BAY 11-7082, the level of ROS produced and the secretion of IL-6 by macrophages were increased. methylprednisolone promotes the proliferation of mycobacteria in macrophages by suppressing cellular ROS production and IL-6 secretion through down-regulating NF-κB and up-regulating DUSP1 expression. BCI, an inhibitor of DUSP1, can reduce the level of DUSP1 in the infected macrophages and inhibit the proliferation of intracellular mycobacteria by promoting cellular ROS production and IL-6 secretion. Therefore, BCI may become a new molecule for host-directed therapy of tuberculosis, as well as a new strategy for the prevention of tuberculosis when treated with glucocorticoids.

Thiopurines are an independent risk factor for active tuberculosis in inflammatory bowel disease patients.

The use of thiopurines is an independent risk factor for active tuberculosis in patients with inflammatory bowel disease.

Active tuberculosis in inflammatory bowel disease patients: a case–control study

Background/Aims: Anti-tumor necrosis factor (anti-TNF) drugs have been the mainstay therapy for moderate to severe inflammatory bowel disease (IBD) over the past 25 years. Nevertheless, these drugs are associated with serious opportunistic infections like tuberculosis (TB). Brazil is ranked among the 30 countries with the highest incidence of TB in the world. This study aimed at identifying risk factors for the development of active TB and describing clinical characteristics and outcomes in IBD patients followed at a tertiary referral center in Brazil. Methods: We conducted a retrospective, case–control study between January 2010 and December 2021. Active TB cases in IBD patients were randomly matched 1:3 to controls (IBD patients with no previous history of active TB) according to gender, age, and type of IBD. Design: This was a retrospective, case–control study. Results: A total of 38 (2.2%) cases of TB were identified from 1760 patients under regular follow-up at our outpatient clinics. Of the 152 patients included in the analysis (cases and controls), 96 (63.2%) were male, and 124 (81.6%) had Crohn’s disease. Median age at TB diagnosis was 39.5 [interquartile range (IQR) 30.8–56.3]. Half of the active TB cases were disseminated (50%). Overall, 36 patients with TB (94.7%) were being treated with immunosuppressive medications. Of those, 31 (86.1%) were under anti-TNF drugs. Diagnosis of TB occurred at a median of 32 months after the first dose of anti-TNF (IQR 7–84). In multivariate analysis, IBD diagnosis older than 17 years and anti-TNF therapy were significantly associated with the development of TB ( p &lt; 0.05). After the TB treatment, 20 (52.7%) patients received anti-TNF therapy, and only one developed ‘de novo’ TB 10 years after the first infection. Conclusions: TB remains a significant health problem in IBD patients from endemic regions, especially those treated with anti-TNFs. In addition, age at IBD diagnosis (&gt;17 years old) was also a risk factor for active TB. Most cases occur after long-term therapy, suggesting a new infection. The reintroduction of anti-TNFs agents after the anti-TB treatment seems safe. These data highlight the importance of TB screening and monitoring in IBD patients living in endemic areas.

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

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. 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. 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. 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.

Prevalence of proximate risk factors of active tuberculosis in latent tuberculosis infection: A cross-sectional study from South India.

The prevalence of proximate risk factors for active tuberculosis (TB) in areas of high prevalence of latent tuberculosis infection (LTBI) is not clearly understood. We aimed at assessing the prevalence of non-communicable multi-morbidity focusing on diabetes mellitus (DM), malnutrition, and hypertension (HTN) as common risk factors of LTBI progressing to active TB. In a cross-sectional study, 2,351 adults (45% male and 55% female) from villages in the Kancheepuram district of South India were enrolled between 2013 and 2020. DM was defined as HbA1c >6.4%, undernutrition was defined as low body mass index (LBMI) <18.5 kg/m2, obesity was classified as BMI ≥25 kg/m2, HTN was reported as systolic pressure >130 mmHg, and LTBI was defined as positive (≥ 0.35 international units/ml) by QuantiFERON Gold In-Tube assay. A total of 1,226 individuals (52%) were positive for LTBI out of 2351 tested individuals. The prevalence of DM and pre-diabetes mellitus (PDM) was 21 and 35%, respectively, HTN was 15% in latent tuberculosis (LTB)-infected individuals. The association of DM [odds ratio (OR)]; adjusted odds ratio (aOR) (OR = 1.26, 95% CI: 1.13–1.65; aOR = 1.19, 95% CI: 1.10–1.58), PDM (OR = 1.11, 95% CI: 1.0–1.35), and HTN (OR = 1.28, 95% CI: 1.11–1.62; aOR = 1.18, 95% CI: 1.0–1.56) poses as risk factors of LTBI progression to active TB. The prevalence of LBMI 9% (OR = 1.07, 95% CI: 0.78–1.48) and obesity 42% (OR = 0.85, 95% CI: 0.70–1.03) did not show any statistically significant association with LTB-infected individuals. The present evidence of a high burden of multi-morbidity suggests that proximate risk factors of active TB in LTBI can be managed by nutrition and lifestyle modification.

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

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

Hypovitaminosis D among newly diagnosed pulmonary TB patients and their household contacts in Uganda

An estimated one billion people globally live with hypovitaminosis D. Studies have indicated that vitamin D deficiency is a risk factor for active tuberculosis (TB) disease. The aim of this study was to determine the association between vitamin D deficiency and TB status among patients with active TB, latent TB infection (LTBI) and those without TB infection. In a cross-sectional study of active TB patients, LTBI, QuantiFERON GOLD testpositive and (QFN+TST+) household contact and controls QuantiFERON GOLD testnegative (QFN−TST−) samples vitamin D levels were compared. Vitamin D status was determined by measurement of total vitamin D levels with 56 samples of active TB patients, 17 with LTBI, and 22 without TB infection using electrochemiluminescence. The median interquartile range (IQR) age of the study participants was 28 (20–35) years, and the majority (63%) were females. The median (IQR) vitamin D levels were 18 ng/ml (14–24). All groups had vitamin D hypovitaminosis with significantly lower levels among active TB patients (17 ng/ml, 13, 2) than among LTBI individuals (23 ng/ml 16–29) and those without TB infection (22 ng/ml, 17–28).

Analysis of Some Risk Factors of Active Tuberculosis in Three South Florida Counties.

BackgroundWith tuberculosis (TB) being among the top 13 leading cause of death and second leading infectious disease killer next to COVID-19 globally, there is a need for continued study and a better understanding of the risk factors and management approaches. One in five tuberculosis (TB) deaths occurs in individuals who have contracted human immunodeficiency virus (HIV). However, other risk factors play a role in its morbidity pattern. Therefore, descriptions of these comorbidities between TB, HIV, and other risk factors such as diabetes are needed.MethodA retrospective, descriptive study was conducted to evaluate the prevalence of TB and its relationship with some risk factors (HIV, diabetes, race, ethnicity, end-stage renal disease, post-organ transplant, recent contact with active TB, and other non-HIV immunosuppressive conditions) using data from three South Florida counties (Dade, Broward, and Palm Beach) from 2010 to 2019 retrieved from the CDC’s Report of Verified Case of Tuberculosis (RVCT).ResultsA total of 2437 cases of TB were reported between 2010 and 2019. There was approximately a 14% positive rate among the three counties for HIV. In contrast, 47% of the individuals with active TB in all three counties were also diagnosed with diabetes mellitus. An average of 25% of the active TB cases in these counties had a concurrent immunosuppressive condition other than HIV. Known contact with another active TB case was an identified risk factor in 18%, 17%, and 29% of reported TB cases in Dade, Broward, and Palm Beach counties, respectively.DiscussionThe HIV status of patients with TB in these three counties was predominantly negative, in contrast to initial theories. The presence of diabetes mellitus was associated with a diagnosis of TB or latent tuberculosis infection (LTBI) within the studied population.ConclusionScreening for latent tuberculosis infection (LTBI), compliance, and promotion of LTBI management in newly diagnosed and uncontrolled diabetics may be a successful prevention strategy for this high-risk group.

Study of clinical characteristics, risk factors and outcomes for tuberculosis post allogeneic stem cell transplant: never count it out.

Background:Allogeneic stem cell transplant (AlloSCT) recipients remain at a higher risk of developing tuberculosis (TB), especially in endemic populations. We conducted a retrospective study to identify the incidence, clinical presentation, and risk factors for active TB among our alloSCT recipients.Methods:Records of all patients transplanted between 1 January 2012 and 31 July 2020 were reviewed. Patients were followed up for outcome until 30 September 2020. None of the patients received prophylactic anti-tubercular drugs. Proven diagnosis of active TB was considered if Mycobacterium tuberculosis (MTB) was cultured from clinical samples or acid-fast bacilli (AFB) or MTB demonstrated on Ziehl-Neelsen (ZN) staining or histopathology or XPERT MTB, while probable diagnosis of TB was considered if histopathology findings were suggestive of caseation necrosis/epithelioid cell granulomas without any evidence of malignancy or lymphocyte rich exudative effusions (pleural/pericardial) without an alternative cause.Results:Among 381 alloSCT recipients, 15 patients (3.9%) developed TB at median of 246 (74–279) days post AlloSCT, after being symptomatic for a median of 22 (7–60) days, amounting to a cumulative incidence of 4.9%. All patients were started on four-drug anti tubercular therapy, ATT [Rifampicin, Isoniazid, Ethambutol, Pyrazinamide (RHEZ)], of which five patients developed hepatotoxicity at a median of 12 days after start of ATT, leading to drug modification. At last follow up, TB was cured in 13 (86.67%) patients, one succumbed to disease relapse, while others are still on treatment. Age ⩾ 30 years, immunosuppression for graft versus host disease (GvHD) > 6 months, prior use of tyrosine kinase inhibitors (TKI) and chronic GvHD on univariate analysis and immunosuppression for GvHD > 6 months on multivariate analysis were found to be associated with development of TB.Conclusion:A high index of suspicion with timely workup and treatment of TB is the key in AlloSCT recipients, especially in endemic TB populations.