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Hijikata M.,The Research Institute of Tuberculosis | Hijikata M.,National Center for Global Health and Medicine | Matsushita I.,The Research Institute of Tuberculosis | Hang N.T.L.,Medical Collaboration Center | And 8 more authors.
Human Immunology | Year: 2014

Mannose-binding lectin (MBL) binds to pathogens and induces complement-mediated opsonophagocytosis. Although the association between MBL2 polymorphisms and tuberculosis (TB) has been studied in various populations, the results are controversial. We explored the stages of TB associated with MBL2 polymorphisms. X/. Y (rs7096206) and A/. B (rs1800450) were genotyped in 765 new patients with active pulmonary TB without HIV infection and 556 controls in Hanoi, Viet Nam. The MBL2 nucleotide sequences were further analyzed, and plasma MBL levels were measured in 109 apparently healthy healthcare workers and 65 patients with TB. Latent TB infection (LTBI) was detected by interferon-gamma release assay (IGRA). The YA/. YA diplotype, which exhibited high plasma MBL levels, was associated with protection against active TB in younger patients (mean age = 32). ≦. 45. years old (odds ratio, 0.61; 95% confidence interval, 0.46-0.80). The resistant diplotype was less frequently found in the younger patients at diagnosis (P= 0.0021). MBL2 diplotype frequencies and plasma MBL levels were not significantly different between the IGRA-positive and -negative groups. MBL2 YA/. YA exhibited a protective role against the development of TB in younger patients, whereas the MBL2 genotype and MBL levels were not associated with LTBI. High MBL levels may protect against the early development of pulmonary TB after infection. © 2014 American Society for Histocompatibility and Immunogenetics. Source

Matsushita I.,The Research Institute of Tuberculosis | Hang N.T.L.,Medical Collaboration Center | Hong L.T.,Hematology and Blood Transfusion | Tam D.B.,Hematology and Blood Transfusion | And 9 more authors.
International Journal of Infectious Diseases | Year: 2015

Objectives: In the performance of interferon gamma release assays (IGRA) for the diagnosis of tuberculosis (TB) infection, false-negative results are a major obstacle. In active TB patients, treatment-dependent changes of the negative test results remain unknown. Methods: The treatment course of 19 smear-positive/culture-confirmed TB patients who had IGRA-negative results by QuantiFERON-TB in-tube (QFT-IT) method at the time of diagnosis (month 0) in a previous study, were monitored in the present study. Blood was further collected at months 2 and 7, and the concentrations of 27 immune molecules were measured in the plasma supernatants remaining after performing the IGRA, using a suspension array system. Results: After initiating treatment, eight of the 19 QFT-IT-negative patients showed positive conversion, whereas the remaining 11 (58%) did not; the interferon gamma (IFN-γ) response was restored to levels higher than 1 IU/ml in only three of the eight patients with positive conversion. Plasma concentrations of interleukin 1 receptor antagonist, interleukin 2, and interferon gamma-induced protein 10 remained low after Mycobacterium tuberculosis-specific antigen stimulation at months 2 and 7 in the continuously QFT-IT-negative group, whereas the parameters were elevated only in the transiently QFT-IT-negative group. Conclusions: It was demonstrated that a majority of active TB patients showing negative IGRA results did not regain sufficient levels of immune responsiveness despite successful treatment. © 2015 The Authors. Source

Le Hang N.T.,Medical Collaboration Center | Lien L.T.,Hanoi Lung Hospital | Kobayashi N.,National Center for Global Health and Medicine | Shimbo T.,International Clinical Research Center | And 10 more authors.
PLoS ONE | Year: 2011

Background: Imperfect sensitivity of interferon-γ release assay (IGRA) is a potential problem to detect tuberculosis. We made a thorough investigation of the factors that can lead to false negativity of IGRA. Methods: We recruited 543 patients with new smear-positive pulmonary tuberculosis in Hanoi, Viet Nam. At diagnosis, peripheral blood was collected and IGRA (QuantiFERON-TB Gold In-Tube) was performed. Clinical and epidemiological information of the host and pathogen was collected. The test sensitivity was calculated and factors negatively influencing IGRA results were evaluated using a logistic regression model in 504 patients with culture-confirmed pulmonary tuberculosis. Results: The overall sensitivity of IGRA was 92.3% (95% CI, 89.6%-94.4%). The proportions of IGRA-negative and -indeterminate results were 4.8% (95% CI, 3.1%-7.0%) and 3.0% (95% CI, 1.7%-4.9%). Age increased by year, body mass index <16.0, HIV co-infection and the increased number of HLA-DRB1*0701 allele that patients bear showed significant associations with IGRA negativity (OR = 1.04 [95% CI, 1.01-1.07], 5.42 [1.48-19.79], 6.38 [1.78-22.92] and 5.09 [2.31-11.22], respectively). HIV co-infection and the same HLA allele were also associated with indeterminate results (OR = 99.59 [95% CI, 15.58-625.61] and 4.25 [1.27-14.16]). Conclusions: Aging, emaciation, HIV co-infection and HLA genotype affected IGRA results. Assessment of these factors might contribute to a better understanding of the assay. © 2011 Hang et al. Source

Hang N.T.L.,Medical Collaboration Center | Matsushita I.,Research Institute of Tuberculosis JATA | Shimbo T.,Research Institute of Tuberculosis JATA | Shimbo T.,Clinical Research Center | And 13 more authors.
Journal of Infection | Year: 2014

Objectives: We investigated the relationship between tuberculosis recurrence and Mycobacterium tuberculosis antigen-stimulated interferon-gamma (IFN-γ) responses during treatment. Methods: Plasma IFN-γ levels in active pulmonary tuberculosis patients (. n=407) were analyzed using QuantiFERON-TB Gold In-Tube™ (QFT-IT) at 0, 2, and 7 months of the 8-month treatment received from 2007 to 2009 and the patients were followed up for another 16 months after treatment. Risk factors for recurrence were assessed using the log-rank test and Cox proportional hazard models. Random coefficient models were used to compare longitudinal patterns of IFN-γ levels between groups. Results: QFT-IT showed positive results in 95.6%, 86.2%, and 83.5% at 0, 2, and 7 months, respectively. The antigen-stimulated IFN-γ responses varied significantly during the treatment course (. P<0.0001). Unexpectedly, positive-to-negative conversion of QFT-IT results between 0 and 2 months was significantly associated with earlier recurrence (adjusted hazard ratio, 5.57; 95% confidence interval, 2.28-13.57). Time-dependent changes in IFN-γ levels were significantly different between the recurrence and nonrecurrence groups (P<0.0001). Conclusions: Although the IGRA response varies individually, early response during the treatment course may provide an insight into host immune responses underlying tuberculosis recurrence. © 2014 The British Infection Association. Source

Gaggin H.K.,Massachusetts General Hospital | Do L.D.,Cardiology | Defilippi C.R.,University of Maryland, Baltimore | Christenson R.H.,University of Maryland, Baltimore | And 9 more authors.
Clinical Chemistry | Year: 2014

Background: Reference intervals of high-sensitivity troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been determined from Western populations. No data are available regarding expected values in Asian populations. methods: A total of 1157 age- and sex-matched healthy individuals (mean age, 41.2 years; 48.0% male) were prospectively enrolled from the US (n = 565) and Vietnam (n = 592). Blood samples were analyzed for hs-cTnT and NT-proBNP. Median values were determined for each country and compared in unadjusted analyses and in analyses adjusted for age, sex, body mass index, study site, race, and vital signs. results: Median hs-cTnT concentrations were slightly higher for individuals from the US than for those from Vietnam, but both were below the limit of detection (3.7 vs 3.0 ng/L, respectively; P = 0.03). More US participants had an hs-cTnT concentration above the limit of detection (57.2% vs 47.3%; P = 0.001), but the 99th percentile concentration was slightly higher for Asians (US 15.1 vs Vietnam 19.0 ng/L). Concentrations for >98% of both populations were below the standard hs-cTnT 99th percentile of 14.0 ng/L (P = 0.54). Median NT-proBNP concentrations were slightly higher for US participants compared with Vietnamese participants (28 vs 16 ng/L, respectively; P < 0.001). Following adjustment, differences in concentrations of NT-proBNP between healthy US and Vietnamese populations remained significant, whereas for hs-cTnT the differences were no longer significant. Inclusion of hs-cTnT values down to the limit of blank did not change the result. CONCLUSIONS: The differences in hs-cTnT and NT-proBNP between healthy individuals from the US and Vietnam are small. Previously derived reference intervals for both analytes may be applied in Asian populations. © 2014 American Association for Clinical Chemistry. Source

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