Child ; Complement C3 ; metabolism ; Cytokinins ; analysis ; metabolism ; Female ; Humans ; Immunoglobulin A ; immunology ; Immunoglobulin G ; immunology ; Interferon-gamma ; immunology ; Interleukin-12 ; analysis ; immunology ; Interleukin-2 ; analysis ; immunology ; Male ; Peptide Fragments ; immunology ; Respiratory Tract Infections ; epidemiology ; immunology ; virology ; Secondary Prevention ; Tuberculin ; analysis

aboratory diagnosis of tuberculosis (TB) traditionally relies on smear microscopy and culture of Mycobacterium tuberculosis from clinical samples. With recent advances in technology, there have been numerous efforts to develop new diagnostic tests for TB that overcome the low sensitivity and specificity and long turnover time associated with current diagnostic tests. Molecular biological tests based on nucleic acid amplification have brought an unprecedented opportunity for the rapid and specific detection of M. tuberculosis from clinical specimens. With automated sequencing analysis, species identification of mycobacteria is now easier and more accurate than with conventional methods, and rapid detection of mutations in the genes associated with resistance to TB drugs provides early information on the potential drug resistance for each clinical isolate or for clinical samples. In addition, immunological tests for the detection of M. tuberculosis antigens and antibodies to the antigens have been explored to identify individuals at risk of developing TB or with latent TB infection (LTBI). The recent introduction of commercial IFN-gamma assay kits for the detection of LTBI provides a new approach for TB control even in areas with a high incidence of TB. However, these molecular and immunological tools still require further evaluation using large scale cohort studies before implementation in TB control programs.
Antigens, Bacterial/immunology ; DNA, Bacterial/chemistry/genetics ; Humans ; Immunologic Tests/*methods ; Interferon-gamma/analysis ; Mycobacterium tuberculosis/genetics/immunology ; Sequence Analysis, DNA ; Tuberculin Test ; Tuberculosis/*diagnosis/immunology/microbiology

aboratory diagnosis of tuberculosis (TB) traditionally relies on smear microscopy and culture of Mycobacterium tuberculosis from clinical samples. With recent advances in technology, there have been numerous efforts to develop new diagnostic tests for TB that overcome the low sensitivity and specificity and long turnover time associated with current diagnostic tests. Molecular biological tests based on nucleic acid amplification have brought an unprecedented opportunity for the rapid and specific detection of M. tuberculosis from clinical specimens. With automated sequencing analysis, species identification of mycobacteria is now easier and more accurate than with conventional methods, and rapid detection of mutations in the genes associated with resistance to TB drugs provides early information on the potential drug resistance for each clinical isolate or for clinical samples. In addition, immunological tests for the detection of M. tuberculosis antigens and antibodies to the antigens have been explored to identify individuals at risk of developing TB or with latent TB infection (LTBI). The recent introduction of commercial IFN-gamma assay kits for the detection of LTBI provides a new approach for TB control even in areas with a high incidence of TB. However, these molecular and immunological tools still require further evaluation using large scale cohort studies before implementation in TB control programs.
Antigens, Bacterial/immunology ; DNA, Bacterial/chemistry/genetics ; Humans ; Immunologic Tests/*methods ; Interferon-gamma/analysis ; Mycobacterium tuberculosis/genetics/immunology ; Sequence Analysis, DNA ; Tuberculin Test ; Tuberculosis/*diagnosis/immunology/microbiology

This study was performed to characterize the humoral immune responses with isotype profiles in Mycobacterium tuberculosis infection. PPD-Specific IgG and IgG subclasses were measured using ELISA in 212 patients with pulmonary tuberculosis. The values of PPD-specific IgG were significantly higher in pulmonary tuberculosis patients than those in the control group, and were correlated to the severity of illness (P < 0.01). The specificity and sensitivity of ELISA for IgG antibodies were 1.0 and 0.81, respectively as determined in 212 sera from tuberculosis patients and 44 from healthy controls. The positive predictive value was 1.0 (171/171), while negative predictive value was 0.52 (44/85). The values of PPD-specific IgG were significantly decreased after 2-4 months of treatment. Among the moderately and far advanced pulmonary tuberculosis patients, the values of PPD-specific IgG were significantly decreased in responders after 6 months of treatment. However, PPD-specific IgG in nonresponders was increased (P < 0.01). PPD-specific IgG subclass responses were evident to all four IgG subclasses. No changes of isotype response according to the severity of the disease were observed.
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunoglobulin G/*blood/classification ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Tuberculin/*immunology ; Tuberculosis, Pulmonary/*immunology

OBJECTIVETo study the prevalence of skin positivity to purified protein derivative (PPD) in human immunodeficiency virus (HIV)-infected patients in Hong Kong.

METHODSConsecutive clients of an HIV clinic were administered the PPD test and 2 units of PPD-RT23 were used. The area of induration was then measured in 48 to 72 h. Results were related to patient characteristics and HIV-related parameters.

RESULTSEight (17.0%) out of 47 clients tested positive to the administration of 2 units of PPD-RT23. If the cutoff were raised to 10 mm according to current practice, only two (4.3%) would test positive.

CONCLUSIONThe prevalence of PPD positivity in HIV-infected patients in Hong Kong is 17%, when a cutoff of 5 mm is used. This figure may form the basis for further studies on the utility of isoniazid preventive therapy in this group of patients.

Adult ; Aged ; BCG Vaccine ; immunology ; Female ; HIV Infections ; complications ; immunology ; Humans ; Isoniazid ; therapeutic use ; Male ; Middle Aged ; Prevalence ; Tuberculin Test ; Tuberculosis ; prevention & control

BACKGROUNDPrompt diagnosis of Mycobacterium tuberculosis (MTB) infection is an essential step in tuberculosis control and elimination. However, it is often difficult to accurately diagnose pediatric tuberculosis (TB). The tuberculin test (TST) may have a low specificity because of cross-reactivity with antigens present in Mycobacterium bovis bacillus Calmette-Guerin (BCG) and other mycobacteria, especially in China with a predominantly BCG-vaccinated population. Early-secreted antigenic target 6-kDa protein (ESAT-6) and culture filtrate protein 10 (CFP-10), stand out as suitable antigens that induce an interferon-gamma (IFN-γ) secreting, T-cell-mediated immune response to infection. While, considered the higher costs and complexity of the IFN-γ release assay (TSPOT), we aimed to evaluate the TSPOT and TST test in the clinical diagnosis of pediatric tuberculosis and to establish a diagnostic process suitable for China.

METHODSThe sensitivity and specificity of the assay were evaluated in total seventy four children with active tuberculosis and fifty one nontuberculous children with other disease, and then the results were compared with TST. Logistic regression models were used to identify variables that were associated with positive results for each assay. The independent variables included sex, age, birth place, vaccination history, close contract with an active TB patient.

RESULTSThe sensitivity of TSPOT was higher than TST in active TB children with or without BCG vaccination, as well as in children with culture-confirmed TB. But the difference was not significant statistically. Combining results of the TSPOT and TST improved the sensitivity to 94.6%. Agreement of the TST and TSPOT was low (77.0%, κ = 0.203) in active TB patients. The difference in specificity between TSPOT and TST test was statistically significant (94.1% vs. 70.6%, P = 0.006). Specificity of the two tests in patients without prior BCG vaccination history was similar (80.0% vs. 60.0%). The concordance between the two tests results in BCG vaccinated subjects was low (71.7%, κ = 0.063). For TSPOT, none of the included risk factors was significantly associated with positive results. For TST, BCG vaccination (OR: 1.78; 95%CI: 1.30 - 2.00) was significantly associated with positive results.

CONCLUSIONSAlthough IFN-γ release assay had relatively high sensitivity and specificity, we also should consider the higher costs and complexity of this test. Therefore, TSPOT could be used as the complementary tool of TST in circumstances when a suspected patient with negative TST results, or to exclude a positive TST result caused by BCG vaccination.

BCG Vaccine ; immunology ; Child ; Child, Preschool ; Female ; Humans ; Interferon-gamma ; secretion ; Logistic Models ; Male ; Sensitivity and Specificity ; Tuberculin Test ; methods ; Tuberculosis ; diagnosis ; Vaccination

Radiographic lesions suggesting old healed tuberculosis (TB) is considered a risk factor for the subsequent development of active TB. The aim of this study was to estimate the positive rates of tuberculin skin test (TST) and interferon-gamma release assay (IGRA) in persons with old healed TB. Participants with lesions suggesting old healed TB on chest images and controls without such lesions were prospectively enrolled between January 1, 2010, and January 31, 2011. TST and the QuantiFERON-TB Gold In-Tube test (QFT-GIT) were performed. In total, 193 participants with old healed TB and 126 controls were recruited. The rates of positive TST and QFT-GIT among patients with old healed TB were 54.6% and 77.7%, respectively. The rates of positive TST and QFT-GIT among patients without old healed TB were 38.9% and 61.9%. Sixteen percent of participants with old healed TB showed negative results by both TST and QFT-GIT. The positive rate of TST waned among participants with old healed TB who were older than 60 yr, whereas QFT-GIT positivity was unaffected by age. The positive rates of TST and IGRA among participants with radiographic lesions suggesting old healed TB was higher than without those lesions. In addition, IGRA may be more accurate than TST for the detection of latent TB infection, especially in populations of individuals older than 60 yr.
Adult ; Age Factors ; Aged ; Aged, 80 and over ; Female ; Humans ; Interferon-gamma Release Tests ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; Tuberculin Test ; Tuberculosis/*diagnosis/immunology/radiography

BACKGROUNDThe health-care workers (HCWs) are at high risk of acquiring infection with Mycobacterium tuberculosis. The objectives of this study were to compare the performance of the T-SPOT.TB and tuberculin skin test (TST) for latent tuberculosis infection (LTBI), evaluate diagnostic concordance and risk factors for LTBI, and observe the progression to active tuberculosis (TB) disease among HCWs in a general hospital in Beijing.

METHODSThe prospective cohort study enrolled HCWs in a tertiary general hospital in Beijing, China, to evaluate LTBI with T-SPOT.TB and TST. The subjects were evaluated every 12 months during the 60-month follow-up.

RESULTSOf 101 participating HCWs, 96 and 101 had valid TST and T-SPOT.TB results, respectively. Twenty-nine (28.7%, 95% confidence interval (CI), 19.9% - 37.5%) were defined as positive by T-SPOT.TB and 53 (55.2%, 95%CI, 45.2% - 64.9%) were defined as positive by TST (using a ≥ 10 mm cutoff). An agreement between the two tests was poor (57.3%, κ = 0.18, 95%CI, 0.01% - 0.52%). In multivariate analysis, direct exposure to sputum smear-positive TB patients was a significant risk factor for a positive T-SPOT.TB (OR 5.76; 95%CI 1.38 - 24.00). Pooled frequency of antigen-specific IFN-γ secreting T-cells for subjects who reported direct contact with sputum smear-positive TB patients was significantly higher than that for participants without direct contact (P = 0.045). One of 20 participants with positive result of T-SPOT.TB and TST developed active TB at 24-month follow-up.

CONCLUSIONT-SPOT.TB is a more accurate, targeted method of diagnosing LTBI than TST.

Adult ; Female ; Health Personnel ; Hospitals, General ; Humans ; Latent Tuberculosis ; diagnosis ; etiology ; immunology ; Longitudinal Studies ; Male ; Pilot Projects ; Prospective Studies ; Risk Factors ; Tuberculin Test

Recent increase in the incidence of lung cancer often makes it difficult to differentiate between lung cancer and tuberculosis (TB), due to their radiologic similarities. Fine needle aspiration biopsy (FNAB) has been widely employed for the diagnosis of lung cancer and TB, but the diagnostic accuracy of TB is not high enough. As a rapid screening test for tuberculosis, we evaluated serological tests using Mycobacterium tuberculosis PPD and lipoarabinomannan (LAM) antigens. A total of 95 patients with indication of FNAB cytology from initial CT findings were enrolled. 25 patients had TB, 76 thoracic malignancy, and six (7.9%) of the lung cancer patients also had TB, indicating much higher prevalence of TB in thoracic tumor patients. Antibodies to PPD were elevated in 18 (72.0%) of 25 TB patients and in 22 (31.4%) of 70 patients with thoracic malignancy. In contrast, only 3 (4.7%) of 64 healthy controls aged 40 or above were seropositive to PPD antigen. The prevalence of anti-PPD antibodies in thoracic tumor patients was therefore significantly greater than that amongst the healthy controls (p 0.001, chi-square test). However, no significant difference in the prevalence of anti-LAM antibodies was found between study subjects and controls. This study demonstrates that thoracic tumor patients have significantly elevated antibodies to PPD; therefore, high anti-PPD seroreactivity in thoracic tumor patients should be cautiously interpreted. A longitudinal investigation on seropositive thoracic tumor patients is required to determine the role of the serological test for TB in lung cancer patients.
Adult ; Aged ; Aged, 80 and over ; Antibodies, Bacterial/*analysis ; Biopsy, Needle ; Female ; Human ; Lipopolysaccharides/*immunology ; Lung Neoplasms/complications/diagnosis/*microbiology ; Male ; Middle Age ; Mycobacterium tuberculosis/*immunology ; Seroepidemiologic Studies ; Tuberculin/*immunology ; Tuberculosis, Pulmonary/complications/diagnosis

Regulatory T cells, which stimulate or inhibit the effector functions of distinct T cell subsets, are critical in the control of the immune response. We investigated the effect of TGF-beta and IL-10 on T cell subsets according to the Th1/Th2 immune status. Sixty-two patients with asthma and 38 patients with pulmonary tuberculosis were included. Allergy skin tests, tuberculin tests, and chest radiography were performed. The levels of circulating IL-4, IFN-gamma, TGF-beta1, and IL-10 were measured using ELISA. The level of TGF-beta1 was higher in patients with asthma than in those with tuberculosis, but the IL-10 levels were the same between the asthma and tuberculosis groups. Atopy was unrelated to the tuberculin response. The IFN-gamma level was correlated with the IL-10 level, and the level of IL-4 was unrelated to the IL-10 or TGF-beta1 level. The level of IL-10 was higher in the negative tuberculin reactors than in the positive tuberculin reactors among patients with asthma, and TGF-beta1 was higher in the positive tuberculin reactors than in the negative tuberculin reactors among patients with tuberculosis. These results demonstrate that the regulatory effects of circulating TGF-beta and IL-10 on T cell cytokines may be different between Th2-type asthma and Th1 tuberculosis.
Adult ; Asthma/*blood/immunology ; Cytokines/*blood ; Female ; Humans ; Interferon Type II/blood ; Interleukin-10/blood ; Interleukin-4/blood ; Male ; Research Support, Non-U.S. Gov't ; Respiratory Function Tests ; Skin Tests ; Th1 Cells/*metabolism ; Th2 Cells/*metabolism ; Transforming Growth Factor beta/blood ; Tuberculin Test ; Tuberculosis/*blood/immunology