Active Mycobacterium Tuberculosis Infection Research Articles

Combined Detection of IFN-γ and Lymphocyte Subsets with Activation Indicators in the Clinical Application of Mycobacterium Tuberculosis Infection at Different Times

The immune status of mycobacterium tuberculosis (MTB) infection is essential for the diagnosis and treatment of this disease. In this work, we aim to evaluate the clinical significance of the combination of serum IFN-γ, IGRAs (Interferon-Gamma Release Assay), lymphocyte subset with activation indicators detection in active and latent tuberculosis infection patients. For this study, anticoagulant whole blood were collected from 45 active tuberculosis (AT group), 44 latent tuberculosis (LT group) and 32 healthy controls (HCs group). The serum IFN-γ and IGRAs detected by chemiluminescence, and the percentage of lymphocyte subsets and activated lymphocytes detected by flow cytometry. The results showed combined IGRAs, serum IFN-γ and NKT cells not only has good diagnostic efficiency for the AT, but also provides a laboratory diagnostic method to distinguish AT from LT. Activation indicator of CD3+HLA-DR+T and CD4+HLA-DR+T can effectively distinguish LT from HCs. While combined CD3+T, CD4+T, CD8+CD28+T, Treg and CD16+CD56+CD69+ cells can distinguish AT from HCs. This study showed combined direct detection of serum IFN-γ and IGRAs as well as lymphocyte subsets with activation indicators which may provide laboratory basis for the diagnosis and differential diagnosis of active and latent MTB infection.

Treatment outcome of pediatric tuberculosis in eastern Ethiopia.

BackgroundChildren are more vulnerable to developing active Mycobacterium tuberculosis infection which causes significant morbidity and mortality. However, the contribution of childhood tuberculosis and its treatment outcomes have not been well documented, and no research has been conducted in eastern Ethiopia.ObjectiveThis study aimed to assess the treatment outcome and its predictors of pediatric tuberculosis in eastern Ethiopia from September 1, 2017 to January 30, 2018.MethodsA retrospective study was conducted in eight selected hospitals in eastern Ethiopia. Data on 2002 children with tuberculosis was extracted by using the standard checklist of the national tuberculosis treatment format. Treatment outcomes were determined according to the standard definitions of the National Tuberculosis and Leprosy Control Programme. Data were entered into Epi Data software version 3.1 and exported to Statistical Package for Social Science (SPSS) version 20 for analysis. Bivariable and multivariable regression analyses were carried out to examine the associations between dependent and independent variables. A P-value of <0.05 was considered statistically significant.ResultThe overall successful treatment rate was 1,774 (88.6%) [95% confidence interval (CI): (80.59–97.40)]. A total of 125 (6.2%), 1,648 (82.3%), 59 (2.9%), and 19 (0.9%) children with tuberculosis (TB) were cured, completed, defaulted, and died, respectively. A high number of defaulters and deaths were reported in the age group <10 years. More children with smear-positive pulmonary TB (74.4%) were cured, while smear-negative tuberculosis had higher treatment completion rates. Being male in sex (adjusted odds ratio (AOR): 0.71, 95% CI: 0.53, 0.96) and those with human immunodeficiency virus (HIV) positive sero status (AOR: 0.51, 95% CI: 0.29, 0.90) had a lower chance of a successful treatment outcome.ConclusionIn this study, thee treatment success rate was higher than the recent World Health Organization report. Those males and HIV seropositive status were less likely to have a successful treatment outcome. Therefore, efforts should be made by each health institution in eastern Ethiopia by giving emphasis on male and HIV-positive individuals.

Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection

Host cell chromatin changes are thought to play an important role in the pathogenesis of infectious diseases. Here we describe a histone acetylome-wide association study (HAWAS) of an infectious disease, on the basis of genome-wide H3K27 acetylation profiling of peripheral blood granulocytes and monocytes from persons with active Mycobacterium tuberculosis (Mtb) infection and healthy controls. We detected >2,000 differentially acetylated loci in either cell type in a Singapore Chinese discovery cohort (n = 46), which were validated in a subsequent multi-ethnic Singapore cohort (n = 29), as well as a longitudinal cohort from South Africa (n = 26), thus demonstrating that HAWAS can be independently corroborated. Acetylation changes were correlated with differential gene expression. Differential acetylation was enriched near potassium channel genes, including KCNJ15, which modulates apoptosis and promotes Mtb clearance in vitro. We performed histone acetylation quantitative trait locus (haQTL) analysis on the dataset and identified 69 candidate causal variants for immune phenotypes among granulocyte haQTLs and 83 among monocyte haQTLs. Our study provides proof-of-principle for HAWAS to infer mechanisms of host response to pathogens.

Coinfections with Other Respiratory Pathogens among Patients with COVID-19.

ABSTRACTEmerging evidence indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals are at an increased risk for coinfections; therefore, physicians need to be cognizant about excluding other treatable respiratory pathogens. Here, we report coinfection with SARS-CoV-2 and other respiratory pathogens in patients admitted to the coronavirus disease (COVID) care facilities of an Indian tertiary care hospital. From June 2020 through January 2021, we tested 191 patients with SARS-CoV-2 for 33 other respiratory pathogens using an fast track diagnostics respiratory pathogen 33 (FTD-33) assay. Additionally, information regarding other relevant respiratory pathogens was collected by reviewing their laboratory data. Overall, 13 pathogens were identified among patients infected with SARS-CoV-2, and 46.6% (89/191) of patients had coinfection with one or more additional pathogens. Bacterial coinfections (41.4% [79/191]) were frequent, with Staphylococcus aureus being the most common, followed by Klebsiella pneumoniae. Coinfections with SARS-CoV-2 and Pneumocystis jirovecii or Legionella pneumophila were also identified. The viral coinfection rate was 7.3%, with human adenovirus and human rhinovirus being the most common. Five patients in our cohort had positive cultures for Acinetobacter baumannii and K. pneumoniae, and two patients had active Mycobacterium tuberculosis infection. In total, 47.1% (90/191) of patients with coinfections were identified. The higher proportion of patients with coinfections in our cohort supports the systemic use of antibiotics in patients with severe SARS-CoV-2 pneumonia with rapid de-escalation based on respiratory PCR/culture results. The timely and simultaneous identification of coinfections can contribute to improved health of COVID-19 patients and enhanced antibiotic stewardship during the pandemic.IMPORTANCE Coinfections in COVID-19 patients may worsen disease outcomes and need further investigation. We found that a higher proportion of patients with COVID-19 were coinfected with one or more additional pathogens. A better understanding of the prevalence of coinfection with other respiratory pathogens in COVID-19 patients and the profile of pathogens can contribute to effective patient management and antibiotic stewardship during the current pandemic.

Mycobacterium tuberculosis (MTB) antigen-induced upregulation of interleukin-35 expression in patients with MTB infection: In vitro blockade of the effects of interleukin-35 on T lymphocyte subsets.

Immunosuppressive interleukin-35 (IL-35) serum concentrations were analyzed in patients with active pulmonary Mycobacterium tuberculosis (MTB) infections (PTB), PTB patients after two months treatment (stable PTB) and healthy controls. IL-35 concentrations were highest in active PTB followed by stable PTB cases and lowest in healthy control participants (all P <0.01). The same trents were found for supernatants of isolated blood mononuclear cells (PBMCs), with additional enhancements after MTB antigen stimulation only for PBMCs of active and stable PTB patients (P <0.001), for EBI3 and IL-12a transcriptions in PBMCs (P <0.001) and percentages of EBI3 expressing (CD4+CD25+Foxp3+) regulatory T cells (Treg) (P <0.001). IL-35 antibody applications significantly reversed MTB antigen stimulated IL-35 and IL-10 expression in PBMCs of active and stable PTB patients, and reduced Foxp3 expression in CD4+CD25+cells and EBI3 expression in Treg cells, but had no effects on healthy control cells. The percentages of Th1 and Th17 cells in CD4+cells were enhanced after MTB antigen stimulation of cells taken from active and stable PTB patients, which were partly increased only for Th1 cells after IL-35 antibody exposure. MTB antigen-driven upregulation of IL-35 may lead to reduced immune surveillance in PTB patients.

Cytokine Biosignature of Active and Latent Mycobacterium Tuberculosis Infection in Children.

None of the currently used diagnostic tools are efficient enough in diagnosing Mycobacterium tuberculosis (M.tb) infection in children. The study was aimed to identify cytokine biosignatures characterizing active and latent tuberculosis (TB) in children. Using a multiplex bead-based technology, we analyzed the levels of 53 Th17-related cytokines and inflammatory mediators in sera from 216 BCG-vaccinated children diagnosed with active TB (TB) or latent TB (LTBI) as well as uninfected controls (HC). Children with active TB, compared to HC children, showed reduced serum levels of IL-17A, MMP-2, OPN, PTX-3, and markedly elevated concentrations of APRIL/TNFSF13. IL-21, sCD40L, MMP-2, and IL-8 were significantly differentially expressed in the comparisons between groups: (1) HC versus TB and LTBI (jointly), and (2) TB versus LTBI. The panel consisting of APRIL/TNFSF13, sCD30/TNFRSF8, IFN-α2, IFN-γ, IL-2, sIL-6Rα, IL-8, IL-11, IL-29/IFN-λ1, LIGHT/TNFSF14, MMP-1, MMP-2, MMP-3, osteocalcin, osteopontin, TSLP, and TWEAK/TNFSF12 possessed a discriminatory potential for the differentiation between TB and LTBI children. Serum-based host biosignatures carry the potential to aid the diagnosis of childhood M.tb infections. The proposed panels of markers allow distinguishing not only children infected with M.tb from uninfected individuals but also children with active TB from those with latent TB.

Is the New Interferon-Gamma Releasing Assay Beneficial for the Diagnosis of Latent and Active Mycobacterium tuberculosis Infections in Tertiary Care Setting?

Interferon-Gamma Release Assays (IGRAs) are widely used in the laboratory diagnosis of Mycobacterium tuberculosis (MTB) infections, particularly in the latent form. We compared the performance of a newly developed IGRA, the Standard E TB-Feron ELISA (TBF) with the currently used QuantiFERON-TB Gold Plus assay (QFT-Plus) for the detection of latent tuberculosis infections (LTBIs) in tertiary care settings. We also investigated interferon-gamma (IFN-γ) released by T cell subsets via intracellular cytokine staining (ICS) and flow cytometry. A total of 335 subjects including 40 patients with active tuberculosis (ATB), 75 immunocompromised patients with LTBIs (P-LTBI), 70 health care workers with LTBIs (H-LTBI), and 150 healthy controls (HC) were studied. Overall, 168 subjects (50.1%) and 178 subjects (53.1%) displayed IGRA-positive results in the QFT-Plus and TBF, respectively. The overall concordance rate was 94.0%. The sensitivity and specificity of TBF were 88% and 95%, respectively, while the sensitivity and specificity of QFT-Plus were 90% and 100%, respectively. Twenty discordant results (6.0%) were observed in simultaneously performed QFT-Plus and TBF. Particularly, 13 LTBI subjects previously positive QFT-Plus showed negative results in QFT-Plus performed after enrollment. In TBF, six subjects showed positive results while five were negatively concordant with QFT-plus and two were indeterminate. The overall proportion of IFN-γ releasing CD8+ T lymphocytes was significantly higher in TBF compared to those of QFT-Plus TB1 and TB2 (0.21% vs. 0.01% and 0.02%; p-value < 0.05). The recombinant protein antigens in the TBF stimulated TB-specific CD8+ T cells more efficiently. Therefore, TBF would be a useful alternative to current IGRAs such as the QFT-Plus, particularly in tertiary care settings where the immunocompromised patients are subjected to IGRA tests to differentiate MTB infection. Further strategies to analyze the implications of the discrepancies, particularly near the cutoff values between different IGRAs, are needed.

Multifocal skeletal tuberculosis with mycobacteremia after kidney transplantation: A case report

Solid organ transplant recipients have a higher risk of active Mycobacterium tuberculosis infection (TB) compared to the general population. Recognized risk factors are immunosuppressant use, graft dysfunction, diabetes mellitus, liver disease caused by the hepatitis C virus, and co-infections by other opportunists. Most of the active TB cases reported in solid organ transplant recipients occur in kidney transplant patients, especially if they come from M tuberculosis-endemic areas. Extrapulmonary and disseminated TB are among the wide spectrum of clinical presentations found, but the lungs are the most common organ affected. Disseminated disease occurs in up to a third of the affected population, however, multifocal osteoarticular TB with mycobacteremia is unusual. We report the case of a kidney transplant patient with disseminated M tuberculosis infection, who presented with multifocal skeletal TB.

Urine lipoarabinomannan as a marker for low-risk of NTM infection in the CF airway

BackgroundIndividuals with Cystic fibrosis (CF) are the most vulnerable population for pulmonary infection with nontuberculous mycobacteria (NTM). Screening, diagnosis, and assessment of treatment response currently depend on traditional culture techniques, but sputum analysis for NTM in CF is challenging, and associated with a low sensitivity. The cell wall lipoarabinomannan (LAM), a lipoglycan found in all mycobacterial species, and has been validated as a biomarker in urine for active Mycobacterium tuberculosis infection. MethodsUrine from a CF cohort (n = 44) well-characterized for NTM infection status by airway cultures was analyzed for LAM by gas chromatography/mass spectrometry. All subjects with positive sputum cultures for NTM had varying amounts of LAM in their urine. No LAM was detected in subjects who never had a positive culture (14/45). One individual initially classified as NTM sputum negative subsequently developed NTM disease 657 days after the initial urine LAM testing. Repeat urine LAM testing turned positive, correlating to her positive NTM status. Subjects infected with subspecies of M. abscessus had greater LAM quantities than those infected with M. avium complex (MAC). There was no correlation with disease activity or treatment status and LAM quantity. A TB Capture ELISA using anti-LAM antibodies demonstrated very poor sensitivity in identifying individuals with positive NTM sputum cultures. ConclusionThese findings support the conclusion that urine LAM related to NTM infection may be a useful screening test to determine patients at low risk for having a positive NTM sputum culture, as part of a lifetime screening strategy in the CF population.

Is Takayasu arteritis the result of a Mycobacterium tuberculosis infection? The use of TNF inhibitors may be the proof-of-concept to demonstrate that this association is epiphenomenal.

Although the association between Takayasu arteritis (TA) and latent or active Mycobacterium tuberculosis infection has been suggested for a long time, studies conducted in recent years are challenging this notion. Until recently, the possibility of a pathogenic relationship between TA and tuberculosis (TB) was considered a medical curiosity, but the advent of tumor necrosis factor (TNF) inhibitors as therapy for recalcitrant TA cases, as well as the widespread use of Bacille Calmette-Guérin (BCG) for vaccination purposes, has relocated this association as a top priority issue. In an attempt to define whether both diseases are pathogenically linked or if their association is only epiphenomenal in nature, we conduct a thorough literature search on the development of TB in patients with TA receiving TNF inhibitors. From a total of 13 studies that included 214 patients, the occurrence of TB was observed only in two individuals exposed to infliximab. This frequency of 0.93% is similar to that encountered in patients with other rheumatic diseases exposed to TNF inhibitors. Finally, we propose a novel pathogenic model that could reconcile the epidemiological, clinical, and immunological evidence that links TA and TB, while providing rationality for the use of TNF inhibitors in patients with TA.

Neutrophil Surface CD64 Stimulation Index Detection Assay in Diagnosing Mycobacterium tuberculosis Infection.

This study aimed to develop a method for assessing the sensitivity and diagnostic performance of the neutrophil surface CD64 stimulation index (SI) in tuberculosis infection. A total of 149 samples were divided into three groups (tuberculosis group, n = 51; nontuberculosis infection group, n = 50; and healthy control group, n = 48). Flow cytometry was used to detect the sensitivity of CD64 SI on the surface of neutrophils. The sensitivities of CD64 SI before and after stimulation with ESAT-6 and CFP-10 antigens were compared using interferon-gamma release assay-enzyme-linked immunosorbent assay (IGRA-ELISA). The diagnostic threshold for CD64 SI based on the receiver operating characteristic curve was found to be 2.025, which is the standard for judging tuberculosis infection. The IGRA-ELISA and the CD64 SI assays were highly consistent with a kappa value of 0.635 (p < 0.003, 95% CI: 0.002 - 0.003). The neutrophil surface CD64 SI value detection method may serve as one of the new diagnostic methods for active Mycobacterium tuberculosis infection.

Reprogramming of Small Noncoding RNA Populations in Peripheral Blood Reveals Host Biomarkers for Latent and Active Mycobacterium tuberculosis Infection.

In tuberculosis (TB), as in other infectious diseases, studies of small noncoding RNAs (sncRNA) in peripheral blood have focused on microRNAs (miRNAs) but have neglected the other major sncRNA classes in spite of their potential functions in host gene regulation. Using RNA sequencing of whole blood, we have therefore determined expression of miRNA, PIWI-interacting RNA (piRNA), small nucleolar RNA (snoRNA), and small nuclear RNA (snRNA) in patients with TB (n = 8), latent TB infection (LTBI; n = 21), and treated LTBI (LTBItt; n = 6) and in uninfected exposed controls (ExC; n = 14). As expected, sncRNA reprogramming was greater in TB than in LTBI, with the greatest changes seen in miRNA populations. However, substantial dynamics were also evident in piRNA and snoRNA populations. One miRNA and 2 piRNAs were identified as moderately accurate (area under the curve [AUC] = 0.70 to 0.74) biomarkers for LTBI, as were 1 miRNA, 1 piRNA, and 2 snoRNAs (AUC = 0.79 to 0.91) for accomplished LTBI treatment. Logistic regression identified the combination of 4 sncRNA (let-7a-5p, miR-589-5p, miR-196b-5p, and SNORD104) as a highly sensitive (100%) classifier to discriminate TB from all non-TB groups. Notably, it reclassified 8 presumed LTBI cases as TB cases, 5 of which turned out to have features of Mycobacterium tuberculosis infection on chest radiographs. SNORD104 expression decreased during M. tuberculosis infection of primary human peripheral blood mononuclear cells (PBMC) and M2-like (P = 0.03) but not M1-like (P = 0.31) macrophages, suggesting that its downregulation in peripheral blood in TB is biologically relevant. Taken together, the results demonstrate that snoRNA and piRNA should be considered in addition to miRNA as biomarkers and pathogenesis factors in the various stages of TB.IMPORTANCE Tuberculosis is the infectious disease with the worldwide largest disease burden and there remains a great need for better diagnostic biomarkers to detect latent and active M. tuberculosis infection. RNA molecules hold great promise in this regard, as their levels of expression may differ considerably between infected and uninfected subjects. We have measured expression changes in the four major classes of small noncoding RNAs in blood samples from patients with different stages of TB infection. We found that, in addition to miRNAs (which are known to be highly regulated in blood cells from TB patients), expression of piRNA and snoRNA is greatly altered in both latent and active TB, yielding promising biomarkers. Even though the functions of many sncRNA other than miRNA are still poorly understood, our results strongly suggest that at least piRNA and snoRNA populations may represent hitherto underappreciated players in the different stages of TB infection.

Association between Takayasu arteritis and latent or active Mycobacterium tuberculosis infection: a systematic review

Takayasu arteritis (TA) is a granulomatous vasculitis of large vessels with unknown aetiopathogenesis. An association between TA and tuberculosis (TB) has been suggested by several authors. The objective of this study was to perform a systematic review of the literature on the association of Mycobacterium tuberculosis (MT) infection in patients with TA. The research was conducted using the PUBMED/Medline and LILACS databases including studies published until June 2019 and using the descriptors "takayasu arteritis", "tuberculosis", "mycobacterium tuberculosis", "purified protein derivate" (PPD), "mantoux test", "quantiferon tb gold", and "interferon gamma release assay" (IGRA). A total of 113 publications were found, but only 38 publications were included after the pre-established criteria were applied. The results were divided into (1) active TB in adolescents with TA: 13 cases; (2) active TB in adults with TA: 116 cases, with a prevalence ranging from 6.3 to 20%, including a South Korean study of 267 cases of TA that found a prevalence of active TB of 17.7%; (3) latent TB in TA patients: the most widely used method was PPD, and only one study compared PPD with IGRA; the prevalence ranged from 20 to 82%; (4) findings that indicate TB in arterial biopsy or autopsies: 5 studies, with different results ranging from an absence of MT DNA in the aortic tissue to 70% positivity; and (5) immunological studies that evaluated the presence of antimycobacterial antibodies and heat shock proteins in TA patients. Although most of the studies show a high prevalence of TB, it is not possible to establish a causal relationship. We suggest that greater care be taken with latent TB screening in patients who are TA candidates for immunosuppressive therapy.

Active Mycobacterium tuberculosis infection at a comprehensive cancer center, 2006\u20132014

BackgroundMorbidity and mortality from Mycobacterium tuberculosis (Mtb) infection remain significant in cancer patients. We evaluated clinical characteristics, management, and outcomes in patients with active Mtb infection at our institution who had cancer or suspicion of cancer.MethodsWe retrospectively examined medical records of all patients with laboratory-confirmed active Mtb infection diagnosed between 2006 and 2014.ResultsA total of 52 patients with laboratory-confirmed active Mtb infection were identified during the study period, resulting in an average rate of 6 new cases per year. Thirty-two (62%) patients had underlying cancer, while 20 (38%) patients did not have cancer but were referred to the institution because of suspicion of underlying malignancy. Among patients with cancer, 18 (56%) had solid tumors; 8 (25%) had active hematologic malignancies; and 6 (19%) had undergone hematopoietic-cell transplantation (HCT). Patients with and without cancer were overall similar with the exception of median age (61 years in cancer patients compared to 53 years in noncancer patients). Pulmonary disease was identified in 32 (62%) patients, extrapulmonary disease in 10 (19%) patients, and disseminated disease in 10 (19%) patients. Chemotherapy was delayed in 53% of patients who were to receive such treatment. Eleven patients (all of whom had cancer) died; 3 of these deaths were attributable to Mtb infection.ConclusionsAlthough not common, tuberculosis remains an important infection in patients with cancer. Approximately one-third of patients were referred to our institution for suspicion of cancer but were ultimately diagnosed with active Mtb infection rather than malignancy.

Microbiological and Clinical Aspects of Cervicofacial Actinomyces Infections: An Overview.

Similarly to other non-spore-forming Gram-positive anaerobes, members of the Actinomyces genus are important saprophytic constituents of the normal microbiota of humans. Actinomyces infections are considered to be rare, with cervicofacial infections (also known as ‘lumpy jaw syndrome’) being the most prevalent type in the clinical practice. Actinomycoses are characterized by a slowly progressing (indolent) infection, with non-specific symptoms, and additionally, the clinical presentation of the signs/symptoms can mimic other pathologies, such as solid tumors, active Mycobacterium tuberculosis infections, nocardiosis, fungal infections, infarctions, and so on. The clinical diagnosis of actinomycosis may be difficult due to its non-specific symptoms and the fastidious, slow-growing nature of the pathogens, requiring an anaerobic atmosphere for primary isolation. Based on 111 references, the aim of this review is to summarize current advances regarding the clinical features, diagnostics, and therapy of cervicofacial Actinomyces infections and act as a paper for dentistry specialists, other physicians, and clinical microbiologists.

The Gut Microbiome Signatures Discriminate Healthy From Pulmonary Tuberculosis Patients.

Cross talk occurs between the human gut and the lung through a gut-lung axis involving the gut microbiota. However, the signatures of the human gut microbiota after active Mycobacterium tuberculosis infection have not been fully understood. Here, we investigated changes in the gut microbiota in tuberculosis (TB) patients by shotgun sequencing the gut microbiomes of 31 healthy controls and 46 patients. We observed a dramatic changes in gut microbiota in tuberculosis patients as reflected by significant decreases in species number and microbial diversity. The gut microbiota of TB patients were mostly featured by the striking decrease of short-chain fatty acids (SCFAs)-producingbacteria as well as associated metabolic pathways. A classification model based on the abundance of three species, Haemophilus parainfluenzae, Roseburia inulinivorans, and Roseburia hominis, performed well for discriminating between healthy and diseased patients. Additionally, the healthy and diseased states can be distinguished by SNPs in the species of B. vulgatus. We present a comprehensive profile of changes in the microbiota in clinical TB patients. Our findings will shed light on the design of future diagnoses and treatments for M. tuberculosis infections.

Evaluation of the Diagnostic Efficacy of Monocyte Parameters and MCP-1 to Distinguishing Active Tuberculosis from Latent Tuberculosis.

It is important to distinguish those with active Mycobacterium tuberculosis infection (ATB) from latent tuberculosis infection (LTBI) for monitoring and treating the disease. Monocytes play an important role and may undergo morphological changes against active TB infection. The aim of this study is to investigate the clinical usefulness of the monocyte morphometric parameters and monocyte chemoattractant protein-1 (MCP-1) to distinguish active tuberculosis (ATB) from latent tuberculosis infection (LTBI) and healthy controls (HC). Peripheral blood was collected from 97 ATB patients, 113 LTBI patients, and 101 healthy controls. The monocyte morphometric parameters were obtained using a UniCel Coulter DxH800 system. MCP-1 level was determined by enzyme-linked immunosorbent assay method. Cutoff values were established based on receiver operator characteristic (ROC) curve analysis. Mean monocyte volume with its standard deviation, mean monocyte conductivity, and MCP-1 were significantly increased in ATB compared with LTBI and HC. ROC curve analyses showed that simultaneous measurements of mean monocyte volume with its standard deviation, mean monocyte conductivity and MCP-1 achieved good sensitivity and specificity (93.8% and 93.1%), which may be clinically useful. The findings using monocyte morphometric parameters and MCP-1 to distinguish ATB from LTBI with high sensitivity and specificity may be a potential parameter for clinical.

Hyperglycaemia is inversely correlated with live M. bovis BCG-specific CD4+ T cell responses in Tanzanian adults with latent or active tuberculosis.

IntroductionThe rising prevalence of Diabetes mellitus (DM) in high TB‐endemic countries may adversely affect sustainability of TB control since DM constitutes a risk factor for development of active tuberculosis (TB). The impact of DM on TB specific adaptive immune responses remains poorly addressed, particularly in people living in Sub‐Saharan countries. We performed a functional characterization of TB specific cellular immune response in Tanzanian subjects with active or latent Mycobacterium tuberculosis (Mtb) infection stratified by their diabetic status.MethodsHIV negative active TB patients (≥18 years) with Xpert MTB/RIF positive pulmonary TB were included before starting TB treatment in Dar es Salaam, Tanzania between April and December 2013. HIV negative healthy controls latently infected with TB but without past TB history were also included. Active and latent TB patients were stratified in two groups according to their diabetic status. Peripheral Blood Mononuclear cells were stimulated with either live M. bovis BCG or Mtb‐specific peptide pools and analyzed by intracellular cytokine staining and polychromatic flow cytometry.ResultsOur results show a lower frequency of IFN‐γ CD4+ T cells in patients with active TB and DM compared to patients with active TB only after live M. bovis BCG (p = 0.04) but not after Mtb peptide pools re‐stimulation. Irrespective of TB status, level of glycaemia is selectively inversely correlated with IFN‐γ and TNF‐α CD4+ T cell production (p = 0.02 and p = 0.03) after live M. bovis BCG stimulation.ConclusionsThese results support the hypothesis that hyperglycaemia negatively impacts antigen processing and/or presentation of whole mycobacteria delaying secretion of key cytokines involved in TB immunity.

An update on the management of latent tuberculosis infection and active disease in patients with chronic kidney disease.

In 2010, the British Thoracic Society published guidelines on the management of tuberculosis (TB) infection and disease in patients with chronic kidney disease (CKD), in response to physicians' concerns about the challenges encountered in treating this complex patient group. Later, in 2010, we summarized the main messages from these guidelines for readers of this journal. The purpose of this review is an update on the current management of latent and active Mycobacterium tuberculosis infection in patients with CKD. Patients with CKD have an increased risk of both infection and disease with Mycobacterium tuberculosis, and practice varies between renal units. Since 2010, the majority of published data have focused on screening for TB infection in immunosuppressed patients, including those with CKD and transplant recipients. While there is currently no perfect screening test, the evidence suggests that we should be using the available interferon‑γ release assays, with or without the tuberculin skin test, to try and reduce the undoubted risk of active TB in these patients. While we are not aware of any new evidence to change the recommended treatment regimens, we have reiterated some of the important recommendations outlined in the original guidelines.

Multiplex analysis of plasma cytokines/chemokines showing different immune responses in active TB patients, latent TB infection and healthy participants

Interferon gamma release assays (IGRAs) have been widely used to diagnose Mycobacterium tuberculosis (MTB) infection. However, IGRAs cannot discriminate between active TB patients and latent TB infection (LTBI), and the sensitivity of IGRAs for MTB infection is suboptimal. Here, we analyzed cytokines/chemokines in MTB antigen-stimulated and -unstimulated plasma samples to identify host biomarkers that are associated with active TB and MTB infection. Active TB patients, subjects with LTBI and healthy participants were recruited. Seventy-one soluble cytokines and chemokines were tested using Luminex liquid array-based multiplexed immunoassays. For the 71 examined factors, our results indicated that the unstimulated levels of IL-8 Nil, IP-10 Nil, MIP-1a Nil, and sIL-2Ra Nil and the antigen stimulated levels of IL-8 (Ag-Nil), VEGF (Ag-Nil), and MCP-3 (Ag-Nil) were potential biomarkers for differentiating between active TB and LTBI, with AUCs of 0.8, 0.86, 0.755, 0.845, 0.825, 0.812 and 0.75, respectively. The G-CSF (Ag-Nil), GM-CSF (Ag-Nil), IL-1a (Ag-Nil), IL-2 (Ag-Nil), IP-10 (Ag-Nil), BCA-1 (Ag-Nil) and Eotaxin-1 (Ag-Nil) responses were significantly higher in patients with active TB and LTBI compared with healthy participants (p < 0.05), with AUCs of 0.922, 0.902, 0.908, 1.0, 0.937, 0.919 and 0.935, respectively. Our preliminary data suggest that unstimulated or stimulated levels of cytokines and chemokines could be used as host biomarkers for diagnosing active TB as well as additional biomarkers, except IFN-γ, for MTB infection.