Diagnosis Of Active Tuberculosis Research Articles

QuantiFERON-TB Gold In-Tube test in active tuberculosis patients and healthy adults.

ABSTRACTInterferon-gamma (IFN-γ) release assays have improved latent tuberculosis (TB) detection and have been considered promising for the diagnosis of TB disease. However, diagnosis efficacy data is limited in high burden countries. The aim of this study was to determine the diagnostic potential of the QuantiFERON-TB Gold In-Tube (QFT-GIT) test for the diagnosis of active TB in an endemic setting for TB. A cross-sectional study was conducted in a group of 102 Thai patients with clinical symptoms and chest x-ray findings suggesting of active pulmonary TB and a group of 112 healthy adults. Testing was carried out using sputum microscopy, mycobacterial culture and QFT-GIT test. Of these patients, QFT-GIT was positive in 73 (71.57%), negative in 27 (26.47%), and undetermined in 2 (1.96%) cases. Among healthy controls, QFT-GIT was positive in 18 (16.07%), negative in 93 (83.04%), and undetermined in 1 (0.89%) person. Based on TB culture results, the sensitivity of QFTGIT for diagnosing active TB was 84.21% (95% confidence interval (CI); 72.13-92.52). The positive and negative predictive values were 65.75% (95% CI; 59.26-71.70) and 66.67% (95% CI; 49.94-80.04), respectively. The median IFN-γ level in culture-confirmed TB patients was 3.91 compared to 0.03 IU/mL of the healthy group. QFT-GIT appears to be a useful indirect test for TB diagnosis in Thailand and its use is recommended in association with clinical and radiological assessments for identifying active or latent TB.

Phenotypic Changes on Mycobacterium Tuberculosis-Specific CD4 T Cells as Surrogate Markers for Tuberculosis Treatment Efficacy.

Background: The analysis of phenotypic characteristics on Mycobacterium tuberculosis (MTB)-specific T cells is a promising approach for the diagnosis of active tuberculosis (aTB) and for monitoring treatment success. We therefore studied phenotypic changes on MTB-specific CD4 T cells upon anti-tuberculosis treatment initiation in relation to the treatment response as determined by sputum culture.Methods: Peripheral blood mononuclear cells from subjects with latent MTB infection (n = 16) and aTB (n = 39) at baseline, weeks 9, 12, and 26 (end of treatment) were analyzed after intracellular interferon gamma staining and overnight stimulation with tuberculin. Liquid sputum cultures were performed weekly until week 12 and during 4 visits until week 26.Results: T cell activation marker expression on MTB-specific CD4 T cells differed significantly between subjects with aTB and latent MTB infection with no overlap for the frequencies of CD38pos and Ki67pos cells (both p < 0.0001). At 9 weeks after anti-TB treatment initiation the frequencies of activation marker (CD38, HLA-DR, Ki67) positive MTB-specific, but not total CD4 T cells, were significantly reduced (p < 0.0001). Treatment induced phenotypic changes from baseline until week 9 and until week 12 differed substantially between individual aTB patients and correlated with an individual's time to stable sputum culture conversion for expression of CD38 and HLA-DR (both p < 0.05). In contrast, the frequencies of maturation marker CD27 positive MTB-specific CD4 T cells remained largely unchanged until week 26 and significantly differed between subjects with treated TB disease and latent MTB infection (p = 0.0003).Discussion: Phenotypic changes of MTB-specific T cells are potential surrogate markers for tuberculosis treatment efficacy and can help to discriminate between aTB (profile: CD38pos, CD27low), treated TB (CD38neg, CD27low), and latent MTB infection (CD38neg, CD27high).

Adolescent tuberculosis associated with tuberculosis exposure in classrooms and dorm rooms in Guangxi, China

ObjectiveQuantify tuberculosis (TB) risk attributable to dorm room exposure in addition to classroom exposure. MethodsAdolescent school contact investigations were conducted for every reported index TB case, and similar contact investigations were conducted in selected community-control classes from November 2016 to October 2017 in Guangxi, China. ResultsA total of 6263 contacts of 112 index TB cases and 6130 classmates of 112 controls were investigated. There were 14, 12, and 2 new active TB cases detected among classmates/non-roommates of index cases, classmates/roommates of index cases, and control classmates, respectively. Compared with control contacts, the adjusted relative risk (95% confidence interval (CI)) and population attributable fraction (PAF) for being a classmate/non-roommate of the index case increased the risk of active TB diagnosis to 8.44 (95% CI: 1.31–54.48) and 44.1%. The adjusted RR and PAF for being a classmate/roommate of the index case was 29.37 (95% CI: 3.80, 227.11) and 41.4%. Being classmates/roommates significantly increased the risk of TB compared to a classmate/non-roommate of the index case (RR=3.48, 95% CI: 1.64, 7.40). ConclusionThe additional risk of TB due to exposure in the dorm room should be taken into account in planning of TB prevention and control in boarding schools.

Modeling the implementation of population-level isoniazid preventive therapy for tuberculosis control in a high HIV-prevalence setting.

Background:We model the epidemiological impact of providing isoniazid preventive therapy (IPT) to South African adolescents, among whom HIV prevalence is low, latent tuberculosis (TB) prevalence is high, and school-based programs may enable population-level coverage.Methods:We simulate a dynamic compartmental model of age-structured HIV and TB coepidemics in South Africa. HIV dynamics are modeled by infection status, CD4+ cell count, and antiretroviral therapy; TB dynamics are modeled by disease stage, diagnosis, treatment, and IPT status. We analyze the effects of continuous IPT coverage among adolescents from 5 (baseline) to 90%.Results:Our model is calibrated to WHO and the Joint United Nations Programme on HIV/AIDS epidemiological estimates. In simulations, increasing IPT coverage to 50% among adolescents reduced active TB incidence by 5–34%. Increasing coverage to 90% led to a 9–40% reduction in active TB incidence. Expanded IPT access causes TB incidence to decline in the general population of HIV-positive individuals, as well as in adult HIV-positive individuals.Conclusion:Targeting IPT to a secondary school population with high latent TB prevalence and low-HIV prevalence, in which risk of false-negative diagnosis of active TB is low and IPT benefits are more established, could have substantial benefits to adolescents and spillover benefits to the adult population.

Potential role for Rv2026c- and Rv2421c- specific antibody responses in diagnosing active tuberculosis

The current diagnostic methods for tuberculosis (TB) have several limitations. Although commercial serological tests based on antibody detection are available, their variable accuracies limit their roles in the clinic. The aim of this study was to discover the improved biomarkers for TB disease by investigating the serum profiles of IgG and IgM antibodies against nearly all Mycobacterium tuberculosis (MTB) antigens in 36 active TB patients and 18 healthy controls (HCs) using proteome microarrays. Our results revealed that multiple antigens could induce stronger serum IgG or IgM responses in TB patients compared to HCs, among them, Rv2026c and Rv2421c were further validated by ELISA with sera from 221 samples and showed the moderate performance in diagnosing TB by receiver operating characteristic analysis. Moreover, logistic regression analysis was performed to establish a combined panel that provided better sensitivity and specificity at 82.5% and 88.12%, respectively, than single antigens in the diagnosis of active TB. Furthermore, the antibody reactivity against Rv2026c and Rv2421c was correlated with clinical backgrounds. These results suggest that the combination of different antigens and classes of antibodies could provide promise and encouragement in developing an efficient serological test for the diagnosis of active TB.

The Diagnosis of Pulmonary Tuberculosis: Established and Emerging Approaches for Clinicians in High-income and Low-income Settings

Despite substantial improvements in global tuberculosis (TB) control over the past 2 decades, TB remains the ninth leading cause of death worldwide and the leading cause of death from a single infectious agent. From the perspective of both TB control programs and treating clinicians, rapid diagnosis of active pulmonary TB is crucial to identify potentially infectious persons, facilitate prompt initiation of treatment, and mitigate transmission. Although sputum smear microscopy and mycobacterial culture have traditionally been used for diagnosis, molecular diagnostic methods have evolved considerably over the past 2 decades, both in public health and clinical laboratory settings. Among these methods, Xpert MTB/RIF has revolutionized TB diagnosis in low-income and middle-income countries, enabling rapid initiation of treatment and infection control interventions. In parallel with continued optimization of their performance, increased access, implementation, and effectiveness evaluations of emerging diagnostic tools will be an important component of ongoing TB elimination strategies.

Plasma Circular RNAs hsa_circ_0001953 and hsa_circ_0009024 as Diagnostic Biomarkers for Active Tuberculosis.

Recent studies have demonstrated that circular RNAs (circRNAs) could serve as potential molecular markers for disease diagnosis; however, little is known about their diagnostic value in active tuberculosis (TB). This study first performed a microarray screening of circRNA changes in plasma samples from 3 patients with active pulmonary TB and 3 healthy controls. Then, candidate circRNAs were selected for validation on a quantitative real-time PCR system. Of the 61 differentially expressed circRNAs recorded, 43 and 18 were upregulated and downregulated in the TB group, respectively. Validation assays demonstrated that plasma levels of 6 circRNAs, including hsa_circ_0009024, hsa_circ_0001953, hsa_circ_0008297, hsa_circ_0003528, hsa_circ_0003524 and hsa_circ_0015879 were remarkably increased in TB patients. Plasma levels of hsa_circ_0001953 and hsa_circ_0009024 were correlated with TB severity. Next, hsa_circ_0001953 and hsa_circ_0009024 were assessed in an independent cohort consisting of 120 TB patients and 100 control individuals. An area under the receiver operating characteristic (ROC) curve of 0.915 (95% confidence interval 0.880-0.951; P < 0.001) was obtained for detecting TB, with hsa_circ_0001953 and hsa_circ_0009024 used in combination. Additionally, plasma levels of hsa_circ_0001953 and hsa_circ_0009024 were reduced significantly in patients after treatment (P < 0.001). The present findings indicate that the circRNAs hsa_circ_0001953 and hsa_circ_0009024 may represent novel plasma biomarkers for active TB diagnosis.

Evaluation of panels of Mycobacterium tuberculosis antigens for serodiagnosis of tuberculosis

To evaluate antibody responses to panels of Mycobacterium tuberculosis antigens for serological diagnosis of active tuberculosis (TB). We cloned, expressed and purified 10 M. tuberculosis recombinant proteins 38KD, MPT32 (M. tuberculosis protein 32), MPT64, EspC (ESX-1 secretion-associated protein), Mtb81, Rv3881, Rv3425, Rv0222, Rv3872 and CFP21 (culture filtrate protein 21), and obtained lipoarabinomannan (LAM) polysaccharide antigen from BEI Resources. The plasma immunoglobulin (Ig)G titre responses to the 11 antigens based on 45 patients with pulmonary TB (PTB) and 30 healthy controls (HCs) were first evaluated using enzyme-linked immunosorbent assays. Antigens with high sensitivities were then selected for further investigation in 200 PTB patients (121 smear- or culture-positive patients, 79 smear- or culture-negative patients) and 152 HCs. LAM, 38KD, MPT32, MPT64, EspC and Mtb81 were chosen. The LAM, 38KD, MPT32 and EspC IgG titres were significantly higher in Bacterium-negative TB patients than in HCs, except for MPT64 and Mtb81. The sensitivity of the individual antigens for detecting antibodies ranged from 21.5% to 67.0%, with 74.3-98.0% specificity. The sensitivity of MPT32 was higher than that of 38KD at a high level of specificity. The six-antigen combination reached a sensitivity of 69.6% in bacterium-negative TB patients, with 77.0% specificity. The combination panel had markedly improved sensitivity, but specificity requires further enhancement.

Cutaneous tuberculosis and HIV infection at a referral centre in Rio de Janeiro, Brazil.

BACKGROUNDCutaneous tuberculosis (CTB) is a rare extrapulmonary form of tuberculosis (TB). Despite the increase in the number of cases of TB and HIV, few cases of CTB have been reported.OBJECTIVE To describe CTB cases among patients with HIV infection from a cohort with tuberculosis.METHODS We describe a series of 15 CTB and HIV cases, based on secondary data from 2000 to 2016. Diagnosis was based on isolation of Mycobacterium tuberculosis in culture or clinical response to anti-tuberculous treatment associated with positive smear or histopathologic findings from affected skin or an adjacent lymph node.FINDINGS Scrofuloderma was present in 12 (80%) patients and solitary gumma in three (20%) patients. One case of scrofuloderma was associated with papulonecrotic tuberculid. Seven (46.6%) patients had pulmonary TB. Diagnosis was based on culture in nine patients (60%). The median CD4 cell count was 262 cells/µL. All patients were cured at the end of treatment (median time 6 months). Three patients presented with immune reconstitution inflammatory syndrome.CONCLUSIONS In this study, CTB associated with HIV infection presented as localised forms or in association with pulmonary TB. In patients with HIV who have subacute and chronic skin lesions, CTB should be considered in differential diagnosis, which may represent a good opportunity for early diagnosis of active TB.

Evaluation of the potential diagnostic value of cytotoxic T lymphocyte-associated antigen-4 in differentiation of active and latent tuberculosis infection

Objective To analyze the expressions of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) in the peripheral blood of patients with active tuberculosis (ATB) or latent tuberculosis infection (LTBI), and to evaluate its diagnostic value in differentiation of ATB and LTBI. Methods Forty-eight patients including 18 ATB cases and 30 LTBI cases were continuously enrolled from Wuxi No.5 People′s Hospital and Huashan Hospital affiliated to Fudan University from January 2011 to March 2013. Flow cytometry was applied to detect the CTLA-4 expression in CD4+ CD25+ FoxP3+ T cells in the peripheral blood of the 48 subjects. CTLA-4 levels were compared using non-parametric Mann-Whitney U test. Results The median percentage of CTLA-4+ Treg in CD4+ CD25+ Foxp3+ Treg cells of ATB patients was 18.95% (quantile range: 13.86%, 27.73%), and that in LTBI patients was 6.67% (quantile range: 5.74%, 9.59%), which was statistically significant (U=18.0, P<0. 01). Receiver operating curve (ROC) based on the CTLA-4 expression indicated that the area under the curve was 0.96, with the optimum cut-off value of 13.25%. Thus, the sensitivity and specificity for the diagnosis of ATB were 86.7% and 94.4%, respectively. Conclusion CTLA-4 has highly sensitivity and specificity for the differential diagnosis of ATB and LTBI whose interferon-gamma releasing assays are all positive, which may also provide meaningful clue for the study of pathogenesis of ATB. Key words: CTLA-4; Active tuberculosis; Latent tuberculosis infection; Differential diagnosis

Prevalence of tuberculosis infection and disease in children referred for tuberculosis medical surveillance in Ontario: a single-cohort study.

There are few data about the utility of the Canadian tuberculosis medical surveillance system for detecting tuberculosis in children and adolescents. We sought to assess the prevalence of tuberculosis infection and disease in children and adolescents referred by the tuberculosis medical surveillance program who were evaluated at The Hospital for Sick Children (SickKids) tuberculosis program. We retrospectively studied clinical records, radiographic findings and results of interferon-γ release assays (IGRAs) of all children less than 18 years of age referred by the tuberculosis medical surveillance program and evaluated at SickKids between November 2012 and June 2016. The median age of the 216 children was 10.0 years. Most were born in the Philippines (157 [72.7%]) or India (39 [18.0%]). Of the 216, 166 (76.8%) had a history of prior treatment for tuberculosis, and 34 (15.7%) were federal-sponsored refugees from settings with a high tuberculosis burden. Negative IGRA results were found in 110/130 (84.6%) of those with prior tuberculosis treatment. Thirty-one children (14.4%) had any chest radiographic abnormality, of whom 4 had changes thought to be due to tuberculosis. No child received a diagnosis of active tuberculosis at assessment or during follow-up; 3 (1.4%) were treated for latent tuberculosis infection following IGRA testing at SickKids. A positive IGRA result was associated with contact with infectious tuberculosis (odds ratio [OR] 5.97, 95% confidence interval [CI] 2.06-17.52) and older age at first clinic visit (OR 2.98, 95% CI 1.24-8.30) but not with radiographic abnormalities or history of prior tuberculosis treatment. Most children were referred because of a history of prior treatment for tuberculosis; few had clinical or laboratory evidence of infection or prior disease. The tuberculosis medical surveillance process did not identify any children who required treatment for active disease and requires improvement.

Dysregulated circRNAs in plasma from active tuberculosis patients.

Endogenous circular RNAs (circRNAs) have been reported in various diseases. However, their role in active TB remains unknown. The study was aimed to determine plasma circRNA expression profile to characterize potential biomarker and improve our understanding of active TB pathogenesis. CircRNA expression profiles were screened by circRNA microarrays in active TB plasma samples. Dysregulated circRNAs were then verified by qRT‐PCR. CircRNA targets were predicted based on analysis of circRNA‐miRNA‐mRNA interaction. GO and KEGG pathway analyses were used to predict the function of circRNA. ROC curve was calculated to evaluate diagnostic value for active TB. A total of 75 circRNAs were significantly dysregulated in active TB plasma. By further validation, hsa_circRNA_103571 exhibited significant decrease in active TB patients and showed potential interaction with active TB‐related miRNAs such as miR‐29a and miR‐16. Bioinformatics analysis revealed that hsa_circRNA_103571 was primarily involved in ras signalling pathway, regulation of actin cytoskeleton, T‐ and B‐cell receptor signalling pathway. ROC curve analysis suggested that hsa_circRNA_103571 had significant value for active TB diagnosis. Circulating circRNA dysregulation may play a role in active TB pathogenesis. Hsa_circRNA_103571 may be served as a potential biomarker for active TB diagnosis, and hsa_circRNA_103571‐miRNA‐mRNA interaction may provide some novel mechanism for active TB.

MPT64 patch test for the diagnosis of active pulmonary tuberculosis: a randomised controlled trial in Peru.

SETTING:There remains a lack of effective and inexpensive diagnostic tools for active tuberculosis (TB) disease. Testing immune responses to proteins secreted by Mycobacterium tuberculosis, such as MPT64, may be a diagnostic option.OBJECTIVE:To evaluate the sensitivity and specificity of a patch test using MPT64 for the diagnosis of active TB disease.DESIGN:This randomised, double-blind, placebo-controlled, prospective study in Lima, Peru, involved 55 healthy controls and 457 symptomatic individuals referred for routine TB testing by the National TB Control Programme. All subjects underwent a comprehensive diagnostic workup, and received an active patch on one arm and a placebo patch on the opposite arm, which were read after 4 days.RESULTS:Eighty-one (18%) of the symptomatic participants were classified as having definite TB, while an additional 98 (21%) had probable TB. The patch tests performed the same in both groups, with a sensitivity of 27% and specificity of 74%. The area under the receiver operating characteristic curve was 0.495 (95%CI 0.425–0.565).CONCLUSIONS:Contrary to existing literature, the MPT64 patch was not sensitive and specific to detect active TB. Given the potential of the test, understanding possible differences in the protein source or underlying genetic factors should be explored further.

Clinical Evaluation of a Blood Assay to Diagnose Paucibacillary Tuberculosis via Bacterial Antigens.

The diagnosis of active tuberculosis (TB) cases primarily relies on methods that detect Mycobacterium tuberculosis (Mtb) bacilli or their DNA in patient samples (e.g., mycobacterial culture and Xpert MTB/RIF assays), but these tests have low clinical sensitivity for patients with paucibacillary TB disease. Our goal was to evaluate the clinical performance of a newly developed assay that can rapidly diagnose active TB cases by direct detection of Mtb-derived antigens in patients' blood samples. Nanoparticle (NanoDisk)-enriched peptides derived from the Mtb virulence factors CFP-10 (10-kDa culture factor protein) and ESAT-6 (6-kDa early secretory antigenic target) were analyzed by high-throughput mass spectrometry (MS). Serum from 294 prospectively enrolled Chinese adults were analyzed with this NanoDisk-MS method to evaluate the performance of direct serum Mtb antigen measurement as a means for rapid diagnosis of active TB cases. NanoDisk-MS diagnosed 174 (88.3%) of the study's TB cases, with 95.8% clinical specificity, and with 91.6% and 85.3% clinical sensitivity for culture-positive and culture-negative TB cases, respectively. NanoDisk-MS also exhibited 88% clinical sensitivity for pulmonary and 90% for extrapulmonary TB, exceeding the diagnostic performance of mycobacterial culture for these cases. Direct detection and quantification of serum Mtb antigens by NanoDisk-MS can rapidly and accurately diagnose active TB in adults, independent of disease site or culture status, and outperform Mycobacterium-based TB diagnostics.

The value of T cell spot test of tuberculosis infection and inflammatory indicators for diagnosis of active tuberculosis in patients with fever of unknown origin

Objective To evaluate the value of T cell spot test of tuberculosis infection(T-SPOT.TB) and inflammatory indicators for diagnosis of active tuberculosis in patients with fever of unknown origin (FUO). Methods Patients with FUO in Tongji Hospital from Jan 1st 2014 to Feb 28th 2015 were retrospectively enrolled, and general condition, laboratory examination including T-SPOT.TB, blood routine test, procalcitonin (PCT), high sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), serum ferritin (SF) and final diagnosis were collected and analyzed. Results A total of 395 hospitalized patients with FUO were retrospectively enrolled into this study, among which there were 36 (9.11%) confirmed active tuberculosis (including 7 pulmonary cases and 29 extra-pulmonary cases), 189 (47.85%) bacterial infections, 50 (12.66%) viral infections, 4 (6.32%) fungal infections, 20 (5.06%) neoplastic diseases, 51(12.91%) autoimmune diseases, 25 (6.32%) other diseases. While 20 (5.06%) patients remained un-diagnosed. The sensitivity of T-SPOT.TB for the diagnosis of active TB in patients with FUO was 80.56% (95%CI: 63.43%-91.20%), and the specificity was 83.57% (95%CI: 79.23%-87.16%). The positive predictive value was 32.95% (95%CI: 23.52%-43.89%), and the negative predictive value was 97.72% (95%CI: 95.16%-99.00%). There were significant differences in positive LDH levels (187[141, 255] U/L vs 209[160, 343] U/L) and SF levels (296.2[191.3, 494.8] g/L vs 528.1[281.1, 1 022.0] μg/L) between active tuberculosis group and bacterial infection group (χ2=77.692, H=13.442, H=16.142, all P<0.05). The combination of T-SPOT.TB and multiple inflammatory indicators obtained most valuable efficiency (AUC=0.866) for TB diagnosis. Similarly, there were significant differences in positive ESR (31[15, 78] mm/1 h vs 10[6, 19] mm/1 h), ratio of neutrophil granulocytes ([71.17±12.59]% vs [57.08±20.38]%) between active tuberculosis group and viral infection group (H=32.797, F=6.171, all P<0.05). The combination acquired most valuable efficiency (AUC=0.929). Conclusions For patients with FUO, T-SPOT.TB combined with inflammatory indicators are valuable for the diagnosis of active tuberculosis. Key words: Fever of unknown origin; T-SPOT.TB test; Inflammatory indicators; Active tuberculosis

Prospective Comparison of QFT-GIT and T-SPOT.TB Assays for Diagnosis of Active Tuberculosis

T-SPOT.TB and QuantiFERON-TB Gold In-Tube (QFT-GIT) tests, as two commercial blood assays for diagnosing active tuberculosis (ATB), are not yet fully validated. Especially, there are no reports on comparing the efficacy between the two tests in the same population in China. A multicenter, prospective comparison study was undertaken at four hospitals specializing in pulmonary diseases. A total of 746 suspected pulmonary TB were enrolled and categorized, including 185 confirmed TB, 298 probable TB and 263 non-TB. Of 32 patients with indeterminate test results (ITRs), age and underlying disease were associated with the rate of ITRs. Furthermore, the rate of ITRs determined by T-SPOT.TB was lower than QFT-GIT (0.4% vs. 4.3%, P < 0.01). When excluding ITRs, the sensitivities of T-SPOT.TB and QFT-GIT were 85.2% and 84.8%, and specificities of 63.4% and 60.5%, respectively in the diagnosis of ATB. The two assays have an overall agreement of 92.3%, but exhibited a poor linear correlation (r2 = 0.086) between the levels of interferon-γ release detected by the different assays. Although having some heterogeneity in detecting interferon-γ release, both the QFT-GIT and T-SPOT.TB demonstrated high concordance in diagnosing ATB. However, neither of them showed suitability in the definitive diagnosis of the disease.

18F FDG PET-CT Imaging in Tuberculosis

&lt;p&gt;Tuberculosis (TB) is the second highest infective cause of death worldwide and the global impact of TB is very important. Among all the TB burden WHO regions, 40% TB cases accounts in the South East Asian region. It has become a medical emergency not only in developing countries but also in some high-income countries. The rising incidence of multidrug resistance (MDR) TB and HIV co-infection has increased the morbidity and mortality of TB despite the availability of cheap and effective treatment. The diagnosis of active TB is almost similar over the world. Conventional radiography and Computed Tomography (CT) imaging play a crucial role in the diagnosis of TB. But these conventional imaging are often nonspecific and unable to provide a definitive diagnosis in cases of atypical and heterogeneous presentation. The signs of TB may mimic other diseases in conventional imaging. The introduction of new imaging tool Fluorine18 Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography (18F FDG PET-CT) opens the door to evaluate its potentiality application in TB. The role of this new imaging tool in TB imaging has been well documented. 18F FDG PET-CT may assist in early diagnosis, facilitate differentiation between malignancies and TB, identification of extrapulmonary TB, staging of TB, and in assessment of treatment response. Therefore, familiarity with the spectrum of imaging features and understanding the use of 18F FDG PET-CT in diagnosis and management of TB is important, especially for referring clinicians and the reporting nuclear medicine specialists in TB burden country like Bangladesh. This article reviews the main applications, pattern of imaging spectrum with limitations of 18F FDG PET-CT in TB.&lt;/p&gt;&lt;p&gt;Bangladesh J. Nuclear Med. 19(2): 135-140, July 2016&lt;/p&gt;

Evaluation of risk factors for false-negative results with an antigen-specific peripheral blood-based quantitative T cell assay (T-SPOT®. TB) in the diagnosis of active tuberculosis: A large-scale retrospective study in China.

ObjectiveTo investigate the diagnostic efficacy of an interferon-γ release assay, T-SPOT®.TB, for diagnosing active tuberculosis (TB) and to identify risk factors for false-negative results.MethodsThis retrospective study enrolled consecutive patients with active TB and with non-TB respiratory diseases to evaluate the risk factors for false-negative results when using the T-SPOT®.TB assay for the diagnosis of active TB. Patients with active TB were categorized as having confirmed pulmonary TB, clinically diagnosed pulmonary TB or extrapulmonary TB (EPTB).ResultsThis study analysed 4964 consecutive patients; 2425 with active TB and 2539 with non-TB respiratory diseases. Multivariate logistic regression analyses identified the following five factors that were all associated with an increased false-negative rate with the T-SPOT®.TB assay: increased age (odds ratio [OR] 1.018; 95% confidence interval [CI] 1.013, 1.024); decreased CD8+ count (OR 0.307; 95% CI 0.117, 0.803); negative sputum acid-fast bacilli (AFB) smear staining (OR 1.821; 95% CI 1.338, 2.477); negative mycobacterial cultures (OR 1.379; 95% CI 1.043, 1.824); and absence of EPTB (OR 1.291; 95% CI 1.026, 1.623).ConclusionsIncreased age, decreased CD8+ count, negative sputum AFB smear results, negative sputum mycobacterial cultures and absence of EPTB might lead to an increased false-negative rate when using the T-SPOT®.TB assay.

Addressing tuberculosis among Inuit in Canada.

The average annual rate of tuberculosis (TB) among Inuit in Canada is now more than 290 times higher than Canadian born non-Indigenous people. How did this happen? Using the Territory of Nunavut as a case example, the roots of this situation can largely be traced back to social determinants of health and challenges in access to health care. Half (52%) of all Nunavut residents live in social housing, often under overcrowded conditions. Many experience food insecurity, with food prices in Nunavut that are twice those in southern Canada. Sixty percent of Nunavut residents smoke. Challenges in health care delivery include the small isolated communities, with few roads and difficult weather conditions during the long winters, which impede the ability to reach or provide healthcare, staff that arrive with little TB experience or cultural knowledge, multiple competing health care demands, limited resources and high staff turnover. The housing shortage is not only a social determinant of health, it also impacts the ability to hire new staff or mount an effective response in the event of an outbreak. Yet despite these challenges, progress has been made. Tuberculosis care in Nunavut includes active case finding, contact tracing for all cases of infectious TB, and screening of school age children. Rapid testing with the GeneXpert© platform has resulted in a quicker diagnosis of active TB, earlier treatment (preventing progression of disease) and less transmission. Progressively, there has been a switch from plain film to digital x-rays reducing x-ray turnaround time from as long as two to three weeks to one or two days. Standard treatment protocols include quadruple therapy until sensitivities are known, the use of home isolation for active cases and directly observed treatment (DOT) for both latent and active TB. Special access to rifapentine (Priftin), and its use in combination therapy (3HP), requires only once weekly treatments that can be completed in 12 visits instead of 78 visits for isoniazid (INH) or 120 visits for rifampin, which increases adherence and greatly reduces the health care resources needed to treat TB. In October 2017, the Honourable Jane Philpott, then Minister of Health and now Minister of Indigenous Services, and Natan Obed, president of Inuit Tapiriit Kanatami (ITK) announced the establishment of a Task Force to develop an Inuit TB Elimination Action Framework, accompanied by regional action plans. It is hoped that the task force, and current efforts in Nunavut, will lead to the long term changes needed to ultimately eliminate TB among Inuit in Canada.

Update on tuberculosis biomarkers: From correlates of risk, to correlates of active disease and of cure from disease.

Tuberculosis (TB) remains a devastating disease, yet despite its enormous toll on global health, tools to control TB are insufficient and often outdated. TB Biomarkers (TB-BM) would constitute extremely useful tools to measure infection status and predict outcome of infection, vaccination or therapy. There are several types of TB-BM: Correlate of Infection; Correlate of TB Disease; Correlate of Increased Risk of Developing Active TB Disease; Correlate of the Curative Response to Therapy; and Correlate of Protection (CoP). Most TB-BM currently studied are host-derived BM, and consist of transcriptomic, proteomic, metabolomic, cellular markers or marker combinations ('signatures'). In particular, vaccine-inducible CoP are expected to be transformative in developing new TB vaccines as they will de-risk vaccine research and development (R&D) as well as human testing at an early stage. In addition, CoP could also help minimizing the need for preclinical studies in experimental animals. Of key importance is that TB-BM are tested and validated in different well-characterized human TB cohorts, preferably with complementary profiles and geographically diverse populations: genetic and environmental factors such as (viral) coinfections, exposure to non-tuberculous mycobacteria, nutritional status, metabolic status, age (infants vs children vs adolescents vs adults) and other factors impact host immune set points and host responses across different populations. In this study, we review the most recent advances in research into TB-BM for the diagnosis of active TB, risk of TB development and treatment-induced TB cure.