scholarly journals Analysis of Possible Factors Affecting the Specificity of the Gamma Interferon Test in Tuberculosis-Free Cattle Herds

2004 ◽  
Vol 11 (5) ◽  
pp. 952-956 ◽  
Author(s):  
M. Cagiola ◽  
F. Feliziani ◽  
G. Severi ◽  
P. Pasquali ◽  
D. Rutili
Keyword(s):  
Skin Test ◽  
Public Health Problem ◽  
Tuberculin Test ◽  
Gamma Interferon ◽  
Housing System ◽  
Factors Affecting ◽  
Purified Protein Derivative ◽  
Ifn Γ ◽  
Cattle Herds ◽  
Bovine Tuberculin

ABSTRACT Bovine tuberculosis (TB) is still a zoonotic problem in the world. Despite the fact that eradication programs for bovine TB are being implemented in many countries, it remains a public health problem. These programs are mainly based on a single intradermal tuberculin test using bovine tuberculin purified protein derivative (PPD), isolation, and slaughtering of infected animals. The aim of this study was to assess the specificity of the gamma interferon (IFN-γ) test in TB-free cattle herds, by using not only Australian tuberculins but also tuberculins produced at our institute, and to correlate the response with the type of production (beef cattle, dairy cattle, and a dual-purpose breed), the housing system, and the age of the animals. We studied 800 animals selected from 20 TB- and paratuberculosis-free herds. The animals were tested in parallel, after stimulation with Australian tuberculins and tuberculins produced at our institute, by using the skin test and two IFN-γ assays. The results of this trial showed that the specificity of the IFN-γ test is higher than that of the skin test (96.8%) and ranges from 97.3% (using only Australian tuberculins) to 98.6% (using tuberculins produced at our institute). We found that different categories of cattle could influence the specificity of the skin test but that these differences tended to be reduced in the IFN-γ assay, especially when Italian PPDs were used.

scholarly journals Development of a Human Gamma Interferon Enzyme Immunoassay and Comparison with Tuberculin Skin Testing for Detection ofMycobacterium tuberculosis Infection

1998 ◽  
Vol 5 (4) ◽  
pp. 531-536 ◽  
Author(s):  
Nuket Desem ◽  
Stephen L. Jones
Keyword(s):  
Enzyme Immunoassay ◽  
Skin Test ◽  
Skin Testing ◽  
Gamma Interferon ◽  
Tuberculin Skin Testing ◽  
In Vitro Test ◽  
Detection Range ◽  
Ifn Γ

ABSTRACT A sensitive two-step simultaneous enzyme immunoassay (EIA) for human gamma interferon (IFN-γ) has been developed and used as an in vitro test for human tuberculosis (TB) in comparison with tuberculin skin testing. The EIA was shown to be highly sensitive, detecting less than 0.5 IU of recombinant human IFN-γ per ml within a linear detection range of 0.5 to 150 IU/ml. The assay was highly reproducible and specific for native IFN-γ. In addition, the assay detected chimpanzee, orangutan, gibbon, and squirrel monkey IFN-γs. Cross-reactions with other human cytokines or with IFN-γs derived from mice, cattle, or Old World monkeys were not evident. The assay was used to detect TB infection by incubating whole blood overnight with human, avian, and bovine tuberculin purified protein derivatives (PPDs), as well as positive (mitogen)- and negative-control preparations. The levels of IFN-γ in plasma supernatants were then determined. Blood from 10 tuberculin skin test-positive individuals responded predominantly to the human tuberculin PPD antigen and to a lesser extent to bovine and avian PPD antigens. By contrast, blood from 10 skin test-negative individuals showed minimal responses or no response to any of the tuberculin PPDs. Detectable levels of IFN-γ were present in all blood samples stimulated with mitogen. In vivo tuberculin reactivity was correlated with IFN-γ responsiveness in vitro. These results support the further study of the blood culture–IFN-γ EIA system as an alternative to skin testing for the detection of human TB infection.

scholarly journals Assessment of the specificity of a gamma-interferon test performed with specific antigens to detect bovine tuberculosis, after non-negative results to intradermal tuberculin testing

2019 ◽  
Vol 6 (1) ◽  
pp. e000335 ◽  
Author(s):  
Anne Praud ◽  
Clémence Bourély ◽  
Maria-Laura Boschiroli ◽  
Barbara Dufour
Keyword(s):  
Bovine Tuberculosis ◽  
Gamma Interferon ◽  
Skin Tests ◽  
Negative Results ◽  
In Series ◽  
Specific Antigens ◽  
Ifn Γ ◽  
Tuberculin Testing ◽  
Cattle Herds ◽  
Higher Sensitivity

In cattle herds in France, cervical skin tests (STs) using simple intradermal tuberculin (SIT) are performed to detect bovine tuberculosis (bTB). When positive results are found on ST screening, the herd is considered to be ‘under suspicion’ and confined, raising economic issues. The suspicion can be lifted by carrying out a single intradermal cervical comparative test (SICCT) at least six weeks later.The authors conducted an experimental study in France between 2013 and 2015 to assess the accuracy of the gamma-interferon test (IFN-γ), used in series after a non-negative result to ST screening, and to study the possibility of replacing the SICCT performed six weeks later by an IFN performed within a few days. Data were collected concerning 40 infected and 1825 bTB-free animals from herds with non-negative results to ST screening. This study showed that the IFN-γ test based on specific antigens and performed within a few days of a non-negative result to the ST has higher sensitivity than the SICCT performed six weeks later and equal specificity. The IFN test is more convenient to perform; however, it is more expensive. The IFN-γ test based on MIX antigens may be a useful alternative to the SICCT, to shorten the confinement period of suspect herds without underdetecting bTB.

scholarly journals Distinct Response Kinetics of Gamma Interferon and Interleukin-4 in Bovine Tuberculosis

2000 ◽  
Vol 68 (9) ◽  
pp. 5393-5400 ◽  
Author(s):  
S. G. Rhodes ◽  
N. Palmer ◽  
S. P. Graham ◽  
A. E. Bianco ◽  
R. G. Hewinson ◽  
...  
Keyword(s):  
Bovine Tuberculosis ◽  
Gamma Interferon ◽  
Interleukin 4 ◽  
Early Increase ◽  
Onchocerca Ochengi ◽  
Ifn Γ ◽  
Bovine Tuberculin ◽  
Kinetics Of ◽  
Experimental Challenge

ABSTRACT This study shows that gamma interferon (IFN-γ) and interleukin-4 (IL-4) cytokine responses are produced by peripheral blood cells in cattle infected with Mycobacterium bovis. The different kinetics of the IFN-γ and IL-4 responses to bovine tuberculin and to ESAT-6 following experimental intratracheal infection with M. bovis are described. An early increase in IFN-γ was observed that was maintained throughout the period studied. In contrast, the IL-4 response was delayed and confined to a peak of activity lasting 6 to 8 weeks. Interestingly, an experimental challenge of cattle with a lower dose of M. bovis which did not result in the development of lesions, positive DTH skin test, or substantial IFN-γ responses nevertheless generated strong specific IL-4 responses. Investigation of naturally infected M. bovis field reactors showed increased IFN-γ and IL-4 responses compared to uninfected cattle and that both of these cytokines were equally able to differentiate infected from uninfected animals. The magnitude of theM. bovis-induced IL-4 responses were found to be similar to the antigen-specific IL-4 responses of cattle infected with the parasitic nematode Onchocerca ochengi, further supporting the presence of this type 2 cytokine in bovine tuberculosis.

scholarly journals Increased Numbers of ESAT-6- and Purified Protein Derivative-Specific Gamma Interferon-Producing Cells in Subclinical and Active Tuberculosis Infection

2000 ◽  
Vol 68 (10) ◽  
pp. 6073-6076 ◽  
Author(s):  
Timo Ulrichs ◽  
Peter Anding ◽  
Steven Porcelli ◽  
Stefan H. E. Kaufmann ◽  
Martin E. Munk
Keyword(s):  
Mycobacterium Bovis ◽  
Synthetic Peptides ◽  
Gamma Interferon ◽  
Active Tuberculosis ◽  
Tuberculosis Infection ◽  
Potential Candidate ◽  
Tuberculosis Patients ◽  
Purified Protein Derivative ◽  
Healthy Donors ◽  
Ifn Γ

ABSTRACT Numbers of gamma interferon (IFN-γ)-producing cells reactive to ESAT-6 antigen were increased in recent converters to purified protein derivative positivity and in tuberculosis patients but not in unvaccinated or Mycobacterium bovis BCG-vaccinated healthy donors. ESAT-6-reactive IFN-γ-producing cells in recent converters and tuberculosis patients recognized similar synthetic peptides. Thus, ESAT-6 is a potential candidate for use in detection of early, as well as active, tuberculosis and for control of the disease.

scholarly journals Evaluation of Gamma Interferon Immune Response Elicited by the Newly Constructed PstS-1(285-374):CFP10 Fusion Protein To Detect Mycobacterium tuberculosis Infection

2014 ◽  
Vol 21 (4) ◽  
pp. 552-560 ◽  
Author(s):  
Leonardo Silva de Araujo ◽  
Fernanda Carvalho de Queiroz Mello ◽  
Nidai de Bárbara Moreira da Silva ◽  
Janaina Aparecida Medeiros Leung ◽  
Silvia Maria Almeida Machado ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tuberculin Skin Test ◽  
Skin Test ◽  
Positive Tuberculin Skin Test ◽  
Gamma Interferon ◽  
Preventative Treatment ◽  
Mycobacterium Tuberculosis Infection ◽  
Content Type ◽  
Ifn Γ ◽  
First Time

ABSTRACTThe PstS1 antigen is highly immunogenic, principally when combined with CFP10 during both latent and active TB infection. In the present study, a selectedpstS1gene fragment was cloned, fused with CFP10, and expressed inEscherichia coli. The product [PstS-1(285-374):CFP10] was compared to the recombinant fused RD1 (region of deletion 1) protein (ESAT-6:CFP10) in detectingMycobacterium tuberculosisinfection in 108 recent contacts of pulmonary tuberculosis (TB) cases, considering a positive tuberculin skin test (TST) to be the baseline. The release of gamma interferon (IFN-γ) in 22-h whole-blood and 5-day lymphocyte stimulation assays primed with each antigen was determined. All contacts were clinically followed for up to 1 year, and 87% of the tuberculin skin test-positive (TSTpositive) patients accepted preventative treatment. Concerning the IFN-γ response to PstS-1(285-374):CFP10 in the 22-h and 5-day assays, a slight increase in contact-TSTpositivedetection was observed (23/54 and 26/54) compared to the level seen with the RD1 protein (18/54 and 24/54) whereas in the TSTnegativegroup, similarly lower numbers (≤5/48) of responders were achieved for both antigens, except for RD1 in the 5-day assay (8/48). By combining the IFN-γ responders to both antigens in the 5-day assays, slightly higher increases in positivity were found in the TSTpositive(32/54) and TSTnegative(10/48) groups. Two of 12 untreated TSTpositivecontacts progressed to active TB and were concordantly positive in all assays, except for one contact who lacked positivity in the RD1 5-day assay. We demonstrated for the first time that PstS-1(285-374):CFP10 slightly increased contact positivity and detection of active disease progression, suggesting its potential application as a TB infection marker.

scholarly journals Comparison of a New ESAT-6/CFP-10 Peptide-Based Gamma Interferon Assay and a Tuberculin Skin Test for Tuberculosis Screening in a Moderate-Risk Population

2006 ◽  
Vol 13 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Emaeil Porsa ◽  
Lee Cheng ◽  
Michael M. Seale ◽  
George L. Delclos ◽  
Xin Ma ◽  
...  
Keyword(s):  
African American ◽  
Tuberculin Skin Test ◽  
Skin Test ◽  
The United States ◽  
Gamma Interferon ◽  
Test Results ◽  
Bcg Vaccination ◽  
Ifn Γ ◽  
Foreign Birth ◽  
American Ethnicity

ABSTRACT Screening for latent tuberculosis infection (LTBI) with Mantoux tuberculin skin test (TST) has many limitations, including false-positive results due to exposure to Mycobacterium other than tuberculosis (TB) and BCG vaccination. A total of 474 adult inmates in a county jail were screened for LTBI using TST and a new ESAT-6/CFP-10 peptide-based whole-blood gamma interferon (IFN-γ) assay. LTBI prevalence was 9.0 and 5.4% as determined by TST and IFN-γ assay, respectively. Overall, agreement between test results was 90% (κ = 0.25). Positive TST results were significantly associated with increased age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01 to 1.08), African-American ethnicity (OR, 4.97; 95% CI, 1.58 to 15.68), foreign birth (OR, 20.20; 95% CI, 4.21 to 97.02) and prior incarceration (OR, 6.19; 95% CI, 1.48 to 25.95). Positive IFN-γ assay results were significantly associated with African-American ethnicity (OR, 5.58; 95% CI, 1.16 to 26.74). Factors associated with statistically significant discordance between TST and IFN-γ assay results were African-American ethnicity (OR, 0.29; 95% CI, 0.11 to 0.77), foreign birth (OR, 0.23; 95% CI, 0.07-0.80), and prior incarceration (OR, 0.06; 95% CI, 0.01-0.50). Among subjects born in the United States, African-American ethnicity was the only variable significantly associated with positive test results for both TST (OR, 4.26; 95% CI, 1.38 to 13.16) and IFN-γ assay (OR, 5.74; 95% CI, 1.19 to 27.75) and remained associated with statistically significant discordance between TST and IFN-γ assay results. The reactivity of the new IFN-γ assay is unaffected by prior BCG vaccination or serial TSTs but may be diminished in African-Americans. Future longitudinal studies are needed to assess the sensitivity and specificity of this new assay in detecting LTBI.

scholarly journals Evaluation of Gamma Interferon (IFN-γ)-Induced Protein 10 Responses for Detection of Cattle Infected with Mycobacterium bovis: Comparisons to IFN-γ Responses

2012 ◽  
Vol 19 (3) ◽  
pp. 346-351 ◽  
Author(s):  
W. R. Waters ◽  
T. C. Thacker ◽  
B. J. Nonnecke ◽  
M. V. Palmer ◽  
I. Schiller ◽  
...  
Keyword(s):  
Mycobacterium Bovis ◽  
Similar Pattern ◽  
Gamma Interferon ◽  
Content Type ◽  
Purified Protein Derivative ◽  
Testing Protocol ◽  
Archived Samples ◽  
Ifn Γ ◽  
Highly Correlated ◽  
Mycobacterial Antigens

ABSTRACTGamma interferon (IFN-γ)-induced protein 10 (IP-10) has recently shown promise as a diagnostic biomarker ofMycobacterium tuberculosisinfection of humans. The aim of the current study was to compare IP-10 and IFN-γ responses uponMycobacterium bovisinfection in cattle by using archived samples from two aerosol inoculation studies. In the first study (104CFUM. bovisby aerosol,n= 7),M. bovispurified protein derivative (PPDb)-specific IP-10 and IFN-γ gene expression was detected as early as 29 days after challenge. PPDb-specific IP-10 and IFN-γ mRNA responses followed a similar pattern of expression over the course of this study and were highly correlated (r= 0.87). In the second study (105CFUM. bovisby aerosol,n= 5), IP-10 and IFN-γ (protein) responses to mycobacterial antigens were compared following challenge. IFN-γ responses to mycobacterial antigens were detected at 29 days after challenge and were sustained during the remainder of the study. IFN-γ responses to mycobacterial antigens exceeded corresponding responses in nonstimulated cultures. IP-10 responses to mycobacterial antigens exceeded preinfection responses at 7, 29, and 63 days after challenge. In contrast to IFN-γ responses, IP-10 responses to mycobacterial antigens generally did not exceed the respective responses in nonstimulated cultures. IP-10 responses to medium alone and to mycobacterial antigens followed a similar pattern of response. Correlations between IP-10 and IFN-γ (protein) responses were modest (r≈ 0.50 to 0.65). Taken together, these findings do not support the use of IP-10 protein as a biomarker for bovine tuberculosis using the current testing protocol and reagents; however, mRNA-based assays may be considered for further analysis.

scholarly journals Frequencies of Region of Difference 1 Antigen-Specific but Not Purified Protein Derivative-Specific Gamma Interferon-Secreting T Cells Correlate with the Presence of Tuberculosis Disease but Do Not Distinguish Recent from Remote Latent Infections

2009 ◽  
Vol 77 (12) ◽  
pp. 5486-5495 ◽  
Author(s):  
Timothy S. C. Hinks ◽  
Davinder P. S. Dosanjh ◽  
John A. Innes ◽  
Geoffrey Pasvol ◽  
Sarah Hackforth ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Latent Infection ◽  
Clinical Status ◽  
Asymptomatic Infection ◽  
Gamma Interferon ◽  
Latent Infections ◽  
Purified Protein Derivative ◽  
Ifn Γ ◽  
Active Disease

ABSTRACT The majority of individuals infected with Mycobacterium tuberculosis achieve lifelong immune containment of the bacillus. What constitutes this effective host immune response is poorly understood. We compared the frequencies of gamma interferon (IFN-γ)-secreting T cells specific for five region of difference 1 (RD1)-encoded antigens and one DosR-encoded antigen in 205 individuals either with active disease (n = 167), whose immune responses had failed to contain the bacillus, or with remotely acquired latent infection (n = 38), who had successfully achieved immune control, and a further 149 individuals with recently acquired asymptomatic infection. When subjects with an IFN-γ enzyme-linked immunospot (ELISpot) assay response to one or more RD1-encoded antigens were analyzed, T cells from subjects with active disease recognized more pools of peptides from these antigens than T cells from subjects with nonrecent latent infection (P = 0.002). The T-cell frequencies for peptide pools were greater for subjects with active infection than for subjects with nonrecent latent infection for summed RD1 peptide pools (P ≤ 0.006) and culture filtrate protein 10 (CFP-10) antigen (P = 0.029). Individuals with recently acquired (<6 months) versus remotely acquired (>6 months) latent infection did not differ in numbers of peptide pools recognized, proportions recognizing any individual antigen or peptide pool, or antigen-specific T-cell frequencies (P ≥ 0.11). The hierarchy of immunodominance for different antigens was purified protein derivative (PPD) > CFP-10 > early secretory antigenic target 6 > Rv3879c > Rv3878 > Rv3873 > Acr1, and the hierarchies were very similar for active and remotely acquired latent infections. Responses to the DosR antigen α-crystallin were not associated with latency (P = 0.373). In contrast to the RD1-specific responses, the responses to PPD were not associated with clinical status (P > 0.17) but were strongly associated with positive tuberculin skin test results (≥15-mm induration; P ≤ 0.01). Our results suggest that RD1-specific IFN-γ-secreting T-cell frequencies correlate with the presence of disease rather than with protective immunity in M. tuberculosis-infected individuals and do not distinguish recently acquired asymptomatic infection from remotely acquired latent infection.

scholarly journals Evaluation of Gamma Interferon and Antibody Tuberculosis Tests in Alpacas

2012 ◽  
Vol 19 (10) ◽  
pp. 1677-1683 ◽  
Author(s):  
Shelley Rhodes ◽  
Tom Holder ◽  
Derek Clifford ◽  
Ian Dexter ◽  
Jacky Brewer ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Gamma Interferon ◽  
Enzyme Linked Immunosorbent Assay ◽  
Content Type ◽  
South American Camelids ◽  
Purified Protein Derivative ◽  
History Of ◽  
Similar Range ◽  
Ifn Γ ◽  
Antibody Tests

ABSTRACTWe describe the performance of cell-based and antibody blood tests for the antemortem diagnosis of tuberculosis (TB) in South American camelids (SAC). The sensitivity and specificity of the gamma interferon (IFN-γ) release assay, two lateral flow rapid antibody tests (Stat-Pak and Dual Path Platform [DPP]), and two enzyme-linked immunosorbent assay (ELISA)-based antibody tests (Idexx and Enferplex) were determined using diseased alpacas fromMycobacterium bovisculture-confirmed breakdown herds and TB-free alpacas from geographical areas with no history of bovine TB, respectively. Our results show that while the sensitivities of the IFN-γ and antibody tests were similar (range of 57.7% to 66.7%), the specificity of the IFN-γ test (89.1%) was lower than those of any of the antibody tests (range of 96.4% to 97.4%). This lower specificity of the IFN-γ test was at least in part due to undisclosedMycobacterium microtiinfection in the TB-free cohort, which stimulates a positive purified protein derivative (PPD) response. The sensitivity of infection detection could be increased by combining two antibody tests, but even the use of all four antibody tests failed to detect all diseased alpacas. These antibody-negative alpacas were IFN-γ positive. We found that the maximum sensitivity could be achieved only by the combination of the IFN-γ test with two antibody tests in a “test package,” although this resulted in decreased specificity. The data from this evaluation of tests with defined sensitivity and specificity provide potential options for antemortem screening of SAC for TB in herd breakdown situations and could also find application in movement testing and tracing investigations.

scholarly journals Interpretation of the Gamma Interferon Test for Diagnosis of Subclinical Paratuberculosis in Cattle

2002 ◽  
Vol 9 (2) ◽  
pp. 453-460 ◽  
Author(s):  
G. Jungersen ◽  
A. Huda ◽  
J. J. Hansen ◽  
P. Lind
Keyword(s):  
Bovine Tuberculosis ◽  
Preventive Measures ◽  
Clinical Signs ◽  
Cross Reactivity ◽  
Gamma Interferon ◽  
Test Results ◽  
Young Stock ◽  
Purified Protein Derivative ◽  
Interpretation Criteria ◽  
Ifn Γ

ABSTRACT A group of 252 cattle without clinical signs of paratuberculosis (paraTB) in 10 herds infected with paraTB and a group of 117 cattle in 5 herds without paraTB were selected. Whole-blood samples were stimulated with bovine, avian, and johnin purified protein derivative (PPD) and examined for gamma interferon (IFN-γ) release. For diagnosis of paraTB, satisfactory estimated specificities (95 to 99%) could be obtained by johnin PPD stimulation irrespective of interpretation relative to bovine PPD or no-antigen stimulation alone, but numbers of test positives in the infected herds varied from 64 to 112 with different interpretation criteria. For a limited number of test-positive animals, no change in the test results could be observed with increasing antigen concentrations but IFN-γ responses were significantly reduced (P < 0.0001) and four out of seven reactors tested negative when stimulation was performed on day-old samples. Denmark is free of bovine tuberculosis, but cross-reactivity with paraTB could be documented for cattle more than 14 months old in paraTB-infected herds compared with those in non-paraTB-infected herds. In both paraTB-free and paraTB-infected herds, false positives were observed when the test was applied to calves less than 15 months of age. Until novel antigen formulations more specific for these diseases are available, interpretation of the IFN-γ test must be individually adjusted to fit specific needs and the context within which the test is applied and, for paraTB, the test seems most appropriate for use as a supportive tool for evaluation of disease-preventive measures in young stock.

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