Screening for prevalence of current TB disease and latent TB infection in type 2 diabetes mellitus patients attending a diabetic clinic in an Indian tertiary care hospital.
ABSTRACT: BACKGROUND:Diabetes triples the risk of developing tuberculosis (TB). This study was designed to determine the prevalence of past and current TB disease and Latent TB infection (LTBI) in type 2 Diabetes Mellitus (NIDDM) patients. DESIGN:This was a prospective descriptive study on all NIDDM patients attending a Diabetic clinic. Detailed history, included details of previous history of TB (Past TB)and symptoms of active TB and a thorough physical exam was also done. When clinical suspicion of TB was present, appropriate investigations were carried out to diagnose 'Current TB'. Subsequently, 200 consecutive patients who were negative for Past and Current TB were screened for Latent TB infection (LTBI) by tuberculin skin test. RESULTS:Of 1000 NIDDM patients enrolled, 43(4.3%) had Past TB. Of remaining 957 patients, 50 were evaluated for New TB on the basis of suggestive symptoms and 10(1%) patients were confirmed to have Current TB. Risk factors for Past or Current TB 'DM-TB' in comparison with 'DM Only' group were; male sex (72% VS 57%; P = 0.033), manual laborer (28% VS 15%; P = 0.012), smoking (26% VS 14%; P = 0.015), alcohol consumption (23% VS 9%; P<0.001)& being on treatment with Insulin (40% VS 20%; P<0.001). There was a protective effect with being a home maker (17% VS 37%; P = 0.034&overweightstatus (53% VS 71%; P = 0.004). Of the 200 patient without Past or Current TB, who were screened for LTBI, 96(48%) patients were found to have LTBI. Male sex was the only significant risk factor for LTBI (72% VS 59%; P = 0.05). CONCLUSION:Past and Current TB was substantial in patients attending a Diabetic Clinic. Active symptom screening for TB in these clinics could lead to increase in case detection and earlier diagnosis.
Project description:OBJECTIVE:To investigate the association between diabetes and latent tuberculosis infections (LTBI) in high TB incidence areas. DESIGN:Community-based comparison study. SETTING:Outpatient diabetes clinics at 4 hospitals and 13 health centres in urban and rural townships. A community-based screening programme was used to recruit non-diabetic participants. PARTICIPANTS:A total of 2948 patients with diabetes aged older than 40 years were recruited, and 453 non-diabetic participants from the community were enrolled. PRIMARY AND SECONDARY OUTCOME MEASURES:The interferon-gamma release assay (IGRA) and the tuberculin skin test were used to detect LTBI. The IGRA result was used as a surrogate of LTBI in logistic regression analysis. RESULTS:Diabetes was significantly associated with LTBI (adjusted OR (aOR)=1.59; 95%?CI 1.11 to 2.28) and age correlated positively with LTBI. Many subjects with diabetes also had additional risk factors (current smokers (aOR=1.28; 95%?CI 0.95 to 1.71), comorbid chronic kidney disease (aOR=1.26; 95%?CI 1.03 to 1.55) and history of TB (aOR=2.08; 95%?CI 1.19 to 3.63)). The presence of BCG scar was protective (aOR=0.66; 95%?CI 0.51 to 0.85). Duration of diabetes and poor glycaemic control were unrelated to the risk of LTBI. CONCLUSION:There was a moderately increased risk of LTBI in patients with diabetes from this high TB incidence area. This finding suggests LTBI screening for the diabetics be combined with other risk factors and comorbidities of TB to better identify high-risk groups and improve the efficacy of targeted screening for LTBI.
Project description:BACKGROUND: Interferon gamma release assays, including the QuantiFERON TB Gold In Tube (QFT) have been shown to be accurate in diagnosing Mycobacterium tuberculosis infection. These assays however, do not discriminate between latent TB infection (LTBI) and active TB disease. METHODS: We recruited twenty-three pulmonary TB patients and 34 household contacts from Cape Town, South Africa and performed the QFT test. To investigate the ability of new host markers to differentiate between LTBI and active TB, levels of 29 biomarkers in QFT supernatants were evaluated using a Luminex multiplex cytokine assay. RESULTS: Eight out of 29 biomarkers distinguished active TB from LTBI in a pilot study. Baseline levels of epidermal growth factor (EGF) soluble CD40 ligand (sCD40L), antigen stimulated levels of EGF, and the background corrected antigen stimulated levels of EGF and macrophage inflammatory protein (MIP)-1beta were the most informative single markers for differentiation between TB disease and LTBI, with AUCs of 0.88, 0.84, 0.87, 0.90 and 0.79 respectively. The combination of EGF and MIP-1beta predicted 96% of active TB cases and 92% of LTBIs. Combinations between EGF, sCD40L, VEGF, TGF-alpha and IL-1alpha also showed potential to differentiate between TB infection states. EGF, VEGF, TGF-alpha and sCD40L levels were higher in TB patients. CONCLUSION: These preliminary data suggest that active TB may be accurately differentiated from LTBI utilizing adaptations of the commercial QFT test that includes measurement of EGF, sCD40L, MIP-1beta, VEGF, TGF-alpha or IL-1alpha in supernatants from QFT assays. This approach holds promise for development as a rapid diagnostic test for active TB.
Project description:BACKGROUND:Because of the high global prevalence of latent TB infection (LTBI), a key challenge in endemic settings is distinguishing patients with active TB from patients with overlapping clinical symptoms without active TB but with co-existing LTBI. Current methods are insufficiently accurate. Plasma proteomic fingerprinting can resolve this difficulty by providing a molecular snapshot defining disease state that can be used to develop point-of-care diagnostics. METHODS:Plasma and clinical data were obtained prospectively from patients attending community TB clinics in Peru and from household contacts. Plasma was subjected to high-throughput proteomic profiling by mass spectrometry. Statistical pattern recognition methods were used to define mass spectral patterns that distinguished patients with active TB from symptomatic controls with or without LTBI. RESULTS:156 patients with active TB and 110 symptomatic controls (patients with respiratory symptoms without active TB) were investigated. Active TB patients were distinguishable from undifferentiated symptomatic controls with accuracy of 87% (sensitivity 84%, specificity 90%), from symptomatic controls with LTBI (accuracy of 87%, sensitivity 89%, specificity 82%) and from symptomatic controls without LTBI (accuracy 90%, sensitivity 90%, specificity 92%). CONCLUSIONS:We show that active TB can be distinguished accurately from LTBI in symptomatic clinic attenders using a plasma proteomic fingerprint. Translation of biomarkers derived from this study into a robust and affordable point-of-care format will have significant implications for recognition and control of active TB in high prevalence settings.
Project description:Studies addressing the association between diabetes mellitus (DM) and tuberculosis (TB) in sub-Saharan Africa are limited. We assessed the prevalence of active TB among DM patients at a primary care clinic, and identified risk factors for prevalent TB.A cross-sectional study was conducted in adult DM patients attending a clinic in Khayelitsha, Cape Town. Participants were screened for active TB (symptom screening and microbiological diagnosis) and HIV.Among 440 DM patients screened, the active TB prevalence was 3.0% (95% CI 1.72-5.03). Of the 13 prevalent TB cases, 53.9% (n?=?7; 95% CI 27.20-78.50) had no TB symptoms, and 61.5% (n?=?8; 95% CI 33.30-83.70) were HIV-1 co-infected. There were no significant differences in either fasting plasma glucose or HbA1c levels between TB and non-TB participants. On multivariate analysis, HIV-1 infection (OR 11.3, 95% CI 3.26-39.42) and hemoptysis (OR 31.4, 95% CI 3.62-273.35) were strongly associated with prevalent active TB, with no differences in this association by age or gender.The prevalence of active TB among DM patients was 4-fold higher than the national prevalence; suggesting the need for active TB screening, particularly if hemoptysis is reported. Our results highlight the importance of HIV screening in this older population group. The high prevalence of sub-clinical TB among those diagnosed with TB highlights the need for further research to determine how best to screen for active TB in high-risk TB/HIV population groups and settings.
Project description:BACKGROUND:The early and accurate diagnosis of tuberculosis (TB) is critical for controlling the global TB epidemic. Although early studies have supported the potential role of cytokine biomarkers in blood for the diagnosis of TB, this method requires further investigation and validation in different populations. A set of biomarkers that can discriminate between active TB (ATB) and latent TB infection (LTBI) remains elusive. METHODS:In the current study, we organized two retrospective cohorts and one prospective cohort to investigate the immune responses at different clinical stages of TB infection, as determined by candidate cytokine biomarkers detected with a multiplex cytokine platform. Using a pre-established diagnostic algorithm, participants were classified as ATB, LTBI, and TB uninfected controls (CON). Based on our multiplex cytokine assay, a multi-cytokine biosignature was modelled for the optimal recognition of the different TB infection status. RESULTS:Our analysis identified a six-cytokine biosignature of TB-antigen stimulated IFN-?, IP-10, and IL-1Ra, and unstimulated IP-10, VEGF, and IL-12 (p70) for a biomarker screening group (n?=?88). The diagnostic performance of the biosignature was then validated using a biomarker validation cohort (n?=?216) and resulted in a sensitivity of 88.2% and a specificity of 92.1%. In a prospectively recruited clinical validation cohort (n?=?194), the six-cytokine biosignature was further evaluated, and displayed a sensitivity of 85.7%, a specificity of 91.3% and an overall accuracy of 88.7%. CONCLUSIONS:We have identified a six-cytokine biosignature for accurately differentiating ATB patients from subjects with LTBI and CON. This approach holds promise as an early and rapid diagnostic test for ATB.
Project description:The study aimed to define transcriptional signatures for detection of active TB (TB) compared to latent TB infection (LTBI) as well as to other diseases (OD) with similar clinical phenotypes in patients with and without HIV in two African adult populations. Transcriptional signatures were identified that distinguished active TB from LTBI, active TB from other diseases, and active TB from both LTBI and other diseases in HIV+/- patients. Adults were recruited from Cape Town, South Africa (n=300) and Karonga, Malawi (n=237) who were either HIV+ or HIV - with either active TB, LTBI or OD. Blood was collected into PAX gene tubes (PreAnalytiX). Total RNA integrity was assessed using an Agilent 2100 Bioanalyzer (Agilent, Palo Alto, CA). Labeled cRNA was hybridized to Illumina Human HT-12 Beadchips. Data were analysed in R.
Project description:<h4>Background</h4>The present study was designed to investigate the utility of Quantiferon TB gold (QFT-G) and Tuberculin skin test (TST) for diagnosis of latent TB infection (LTBI) in high crowding TB endemic zone of Nagpur, India and their comparison with associated risk factors.<h4>Methods</h4>Out of 342 eligible participants, QFT-G and TST were performed in 162 participants.<h4>Results</h4>The prevalence of LTBI observed according to QFT-G and TST was 48% and 42% respectively, with an agreement of 52.47%. QFT-G positivity was associated with age while TST positivity was associated with body mass index (BMI). Duration of exposure emerged as a key risk factor significantly associated with both the tests.<h4>Conclusion</h4>The prevalence of LTBI was quite high in the studied zone as detected by both the evaluated tests and thus, the combination of both the tests will be best predictive for LTBI in such high TB endemic regions.
Project description:The incidence rate of active tuberculosis (TB) disease in the Canadian Territory of Nunavut has shown a rising trend over the past 10 years. In 2010 it was 60 times greater than the national incidence rate. The objective of the Taima (translates to "stop" in Inuktitut) TB study was to implement and evaluate a public health campaign to enhance existing TB prevention efforts in Nunavut.A TB awareness campaign followed by a door-to-door screening campaign was carried out in Iqaluit, Nunavut. The aim of the campaign was to raise awareness about TB, and to provide in-home screening and treatment for people living in residential areas at high risk for TB. Screening was based on geographic location rather than on individual risk factors.During the general awareness campaign an increase in the number of people who requested TB testing at the local public health clinic was observed. However, this increase was not sustained following cessation of the awareness campaign. Targeted TB screening in high risk residential areas in Iqaluit resulted in 224 individuals having TSTs read, and detection of 42 previously unidentified cases of latent TB, (overall yield of 18.8% or number needed to screen?=?5.3). These cases of latent TB infection (LTBI) were extra cases that had not been picked up by traditional screening practices (34% relative increase within the community). This resulted in a 33% relative increase in the completion of LTBI treatment within the community. The program directly and indirectly identified 5/17 new cases of active TB disease in Iqaluit during the study period (29.5% of all incident cases).While contact tracing investigations remain a cornerstone of TB prevention, additional awareness, screening, and treatment programs like Taima TB may contribute to the successful control of TB in Aboriginal communities.
Project description:The study aimed to define transcriptional signatures for detection of active TB (TB) compared to latent TB infection (LTBI) as well as to other diseases (OD) with similar clinical phenotypes in patients with and without HIV in a paediatric cohort from Kenya Transcriptional signatures were identified that distinguished active TB from LTBI, active TB from other diseases, and active TB from both LTBI and other diseases in HIV+/- patients. Children were recruited from 2 hospitals in Coast Province, Kenya (n=157) who were either HIV+ or HIV - with either active TB (culture confirmed), active TB (culture negative), LTBI or OD. Blood was collected into PAX gene tubes (PreAnalytiX). Total RNA integrity was assessed using an Agilent 2100 Bioanalyzer (Agilent, Palo Alto, CA). Labeled cRNA was hybridized to Illumina Human HT-12 Beadchips. Data were analysed in R.
Project description:<h4>Background</h4>QuantiFERON-TB Gold In-Tube (QFT-GIT) is considered an alternative to the tuberculin skin test (TST) for the diagnosis of tuberculosis (TB) infection, but the programmatic impact of QFT-GIT implementation is largely unknown. In March, 2010, the Baltimore City Health Department (BCHD) introduced routine QFT-GIT testing for individuals referred to the TB program for suspected latent TB infection (LTBI).<h4>Design</h4>Retrospective study comparing LTBI diagnosis and treatment during the 13 months before and after QFT-GIT implementation at the BCHD TB clinic.<h4>Results</h4>607 and 750 individuals were referred by community-providers for suspected LTBI in the pre- and post-QFT-GIT periods, respectively. Most individuals in the pre- and post-QFT-GIT periods were referred on the basis of a positive TST (597/607 [98%] vs. 690/750 [92%], respectively) and were foreign-born (363/607[59%] vs. 507/750[68%], respectively). BCHD performed QFT-GIT testing for 375/543 (69%) eligible individuals in the post-QFT-GIT period, of which 185 (49%) were positive, 178 (47%) were negative, 1 (0.25%) was indeterminate, and 11 (3%) did not yield results. Concordance of QFT-GIT with TST was low (183/352[52%]). Foreign-born individuals had higher proportions of QFT-GIT positivity (57%) than US-born individuals (36%; AOR 3.3 [95%CI 1.7-6.2]). Significantly fewer individuals received a final diagnosis of LTBI in the post-QFT-GIT period (397/567 [70%]) compared to the pre-QFT-GIT period (445/452 [98%], p<0.001). In the post-QFT-GIT period, only 230/399 (58%) of those receiving QFT-GIT testing had a final diagnosis of LTBI, while 167/168 (99%) of those without QFT-GIT testing were diagnosed with LTBI (p<0.001). There was no difference in treatment initiation between those with and without QFT-GIT testing (175/230 [76%]) vs. 133/167 [80%], respectively) in the post-QFT-GIT period.<h4>Conclusion</h4>QFT-GIT implementation for LTBI evaluation in a public health clinic significantly reduced the proportion of referred individuals in whom LTBI was diagnosed. QFT-GIT testing had no impact on treatment initiation or completion among those diagnosed with LTBI.