Previous Article | Next Article 
Journal of Clinical Microbiology, October 1999, p. 3229-3232, Vol. 37, No. 10
0095-1137/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Evaluation of the Tuberculin Gamma Interferon
Assay: Potential To Replace the Mantoux Skin Test
Sudha
Pottumarthy,1
Arthur J.
Morris,1,*
Adrian
C.
Harrison,2 and
Virginia C.
Wells1
Departments of
Microbiology1 and Respiratory
Medicine,2 Green Lane Hospital, Auckland, New
Zealand
Received 19 January 1999/Returned for modification 6 March
1999/Accepted 10 July 1999
 |
ABSTRACT |
We evaluated an in vitro test of cell-mediated immunity, the
tuberculin gamma interferon assay, QuantiFERON-TB
(QIFN), in 455 individuals from three groups: group I, 237 immigrants
from high-risk countries; group II, 127 health care workers undergoing Mantoux testing; group III, 91 patients being investigated for possible
active tuberculosis (79 patients) or Mycobacterium
avium-Mycobacterium intracellulare complex infection (12 patients). The QIFN results were compared either to those of the
Mantoux test or to microbiological and clinical diagnosis, as
appropriate. In each group the correlation between the diameter of
induration for the skin test and the magnitude of QIFN response was
significant and of moderate strength (Spearman's rank correlation
coefficient; 
= 0.59 to 0.61; P < 0.001). For group I, the agreement between QIFN and Mantoux results was 89% for
Mantoux-negative and 64% for Mantoux-positive individuals. For group
II, when 
10-mm-diameter induration was taken as positive, the
agreement was 81% for Mantoux-negative and 67% for
Mantoux-positive individuals. For group III, agreement was 81% for
Mantoux-negative and 86% for Mantoux-positive patients. For
patients being evaluated for active tuberculosis, the performance of
the Mantoux test was not statistically different from that of the QIFN
assay. In patients with active tuberculosis, the assay had a
sensitivity of 77%, not significantly higher for extrapulmonary
than pulmonary cases (83% versus 74%). QIFN sensitivity was
not significantly different for smear-negative or smear-positive cases
(80% versus 71%). The QIFN assay is a potential replacement for
the Mantoux test. The acceptability of these performance values and
those of similar evaluations will determine the place this test
will have in detecting evidence of mycobacterial infection.
| |
INTRODUCTION |
Intradermal injection of tuberculin,
the Mantoux test (tuberculin skin test), is used worldwide to determine
whether an individual has immunological reactivity to mycobacterial
antigens. While the Mantoux test is a useful aid in identifying
tuberculous infection, it has a number of drawbacks, including the need
for a return visit to allow reading, problems in interpretation due to
cross-reactivity with other mycobacterial species, the booster effect,
and false-negative results because of intercurrent immunosuppression,
as well as the variability inherent in its application and
reading (3). The tuberculin gamma interferon (IFN-
)
assay, QuantiFERON-TB (QIFN), has recently been developed by
CSL Ltd Australia (5). Principally, this test involves
detection and quantitation of the cytokine IFN- produced by T
lymphocytes stimulated with tuberculin purified protein derivatives
(PPDs) obtained from either Mycobacterium tuberculosis
(human), Mycobacterium avium (avian), or Mycobacterium bovis (bovine). Due to the QIFN assay's ability to quantitate the
differential response to the tuberculin PPDs, e.g., human versus avian,
it has the potential to discriminate between M. tuberculosis
and M. avium-Mycobacterium intracellulare complex (MAC)
infections. The QIFN assay is an adaptation of the BOVIGAM test, which
is licensed as an official test for diagnosing bovine tuberculosis in
both Australia and New Zealand (13). QIFN overcomes some of
the shortcomings of the Mantoux test, namely, the need for return
visits and reader variability. Also, depending on specimen transport
time and laboratory efficiency, it has the potential to provide an
earlier result. Like the Mantoux test, the QIFN assay could have a role
in screening for M. tuberculosis infection, contact tracing,
and diagnosing tuberculosis, particularly when the acid-fast smear is
negative. We evaluated the performance of the QIFN assay with three
groups of individuals, immigrants, health care workers (HCWs), and
patients, and compared the results to either the Mantoux test results
or the microbiological and clinical diagnoses.
| |
MATERIALS AND METHODS |
Study population.
Over 16 months, November 1996 to February
1998, 455 individuals were evaluated. All were human immunodeficiency
virus negative except one patient in whom active tuberculosis was
excluded. Group I consisted of 237 immigrants from countries with a
high prevalence of tuberculosis. This group consisted of 191 New
Zealand quota refugees and 46 asylum seekers undergoing screening for
infectious diseases. They had a median age of 28 years (range, 1 to
72), and 151 were males. Group II consisted of 93 HCWs undergoing
employment screening at the occupational health clinics of Auckland
(AKH) and Green Lane (GLH) hospitals and 34 microbiology laboratory staff at these two hospitals and a community laboratory in Auckland. This group had a median age of 35 years (range, 20 to 56), and 16 were
males. No HCW was from a high-risk or high-prevalence group for
tuberculosis, was a close contact of a person with an active case of
tuberculosis, or had radiological evidence of tuberculosis. In groups I
and II QIFN assay results were compared to those of the Mantoux test.
The Centers for Disease Control and Prevention (CDC) interpretive
criteria for positive Mantoux test results were followed
(2). The chest X rays of individuals in group I with
discrepant Mantoux and QIFN results were reviewed by a respiratory
physician (A.C.H.) for radiological evidence of infection. Group III
consisted of 91 patients being evaluated for either tuberculosis
(n = 79) or MAC disease (n = 12). This
group had a median age of 44 years (range, 13 to 89), and 49 were
males. Among the 79 cases investigated for tuberculosis, active disease was excluded in 19. Sixty cases of active tuberculosis were detected, 42 (70%) pulmonary and 18 (30%) extrapulmonary. The extrapulmonary cases included lymphadenitis (eight), pleural (three), miliary (two),
and one each of disseminated, renal, skeletal, pericardial, and adrenal
gland infection. Forty-eight cases (80%) were culture proven, 28 smear
positive and 20 smear negative. The 12 culture-negative patients were
diagnosed on the basis of symptoms, exposure history, radiology and
histology findings, and response to antituberculous treatment. Mantoux
results were available for 51 of 79 (65%) patients evaluated for
tuberculosis, including 38 of 60 (63%) with active disease, 26 pulmonary and 12 extrapulmonary. In this group the QIFN assay results
were compared to those of the Mantoux test as well as to
microbiological and clinical diagnoses. Twelve patients were
investigated for active MAC infection: eight had recent positive cultures for MAC and were clinically thought to represent either colonization (n = 7) or MAC disease (n = 1). Four patients had been treated for MAC disease in the previous
4 years and did not have evidence of recurrence during the period of
study. In this group the results of the QIFN assay were compared to
microbiological and clinical diagnoses.
QIFN assay.
The QIFN assay was performed in accordance with
the manufacturer's instructions. In brief, testing was conducted in
two stages, overnight culture of blood with stimulation antigens and
the subsequent quantification of IFN- production by enzyme
immunoassay (EIA). In the first stage, 1-ml aliquots of heparinized
whole blood were incubated in tissue culture wells with different
tuberculin PPDs (human, avian, and bovine), sterile phosphate-buffered
saline (no-antigen control), and phytohemagglutinin (positive mitogen control). Following 18 h of incubation (range, 16 to 24 h) at 37°C in a humidified atmosphere, the supernatant plasma was
harvested. The IFN- in the plasma supernatant was subsequently
quantified by EIA.
The results were calculated and interpreted according to the
manufacturer's instructions: M. tuberculosis infection was
indicated by a percent human response (human PPD/mitogen response) of
>15% and a percent avian difference (human PPD 
avian
PPD/human PPD response) of >10%. MAC infection was indicated by a
percent avian response (avian PPD/mitogen response) of >20% and a
percent avian difference of <10%.
Statistical analysis.
The correlation between the degree of
QIFN response and the Mantoux induration diameter was assessed by
Spearman's rank correlation test. The kappa statistic was used to
measure the strength of agreement between the Mantoux and QIFN results,
with a kappa statistic value of >0.75 representing excellent
agreement, 0.40 to 0.75 representing good to fair agreement, and <0.40
representing poor agreement. Differences in the performance of the
test(s) were analyzed by the 
2 test.
| |
RESULTS |
Agreement between QIFN and Mantoux tests.
In all three groups
the correlation between the diameter of induration for the Mantoux test
and the magnitude of QIFN response was significant and of moderate
strength (Spearman's rank coefficient; = 0.59 to 0.61;
P < 0.001). For group III, the correlation between the
median percentage of QIFN response and the Mantoux result, stratified
as 0, 1 to 9, 10 to 19, and 20 mm, is shown in Fig. 1. Similar results were obtained for
groups I and II (data not shown).
View larger version (13K):
[in this window]
[in a new window]
|
FIG. 1.
Correlation between percent QIFN response and Mantoux
induration diameter in patients being evaluated for active
tuberculosis. The percent QIFN response versus the Mantoux induration
diameter is stratified as either 0, 1 to 9, 10 to 19, or 20 mm of
induration. The solid bars represent medians, the boxes indicate the
interquantile ranges, and the lines show the most extreme observations
within 1.5 times the interquantile range. There was one extreme outlier
with a value of 1,043% QIFN response in the 0-mm Mantoux group. The
correlation between the QIFN result and Mantoux induration diameter was
significant and of moderate strength (Spearman's rank correlation
coefficient = 0.61; P < 0.001).
|
|
For the 237 immigrants in group I, for whom a positive Mantoux reaction
was defined as a
10-mm-diameter induration (
2),
the
agreement was 89 and 64% for Mantoux-negative and -positive
individuals, respectively, with a kappa statistic of 0.55 (Table
1). None of the 47 immigrants with
discrepant Mantoux and QIFN
results, i.e., Mantoux positive and QIFN
negative (
n = 31) or
Mantoux negative and QIFN positive
(
n = 16), had radiological
evidence of active
tuberculosis. Only one immigrant who was Mantoux
positive but QIFN
negative had minor radiological evidence of
old tuberculosis.
For the 127 HCWs in group II, if
10-mm-diameter induration was
defined as a positive Mantoux test result, the agreement was
81 and
67% for Mantoux-negative and -positive individuals, respectively,
with
a kappa statistic of 0.48 (Table
1). When the CDC guidelines
for the
interpretation of Mantoux reactions were followed, i.e.,
15-mm-diameter induration was considered positive (
2), the
agreement was 70 and 68% in the Mantoux-negative and -positive
individuals, respectively, with a kappa statistic of 0.26.
For the 51 patients in group III for whom a Mantoux test result was
obtained, the agreement between the two tests was 81 and
86% for
Mantoux-negative and -positive individuals, respectively,
with a kappa
statistic of 0.65 (Table
1).
Agreement between QIFN assay and clinical diagnosis.
The
sensitivity of the QIFN assay to detect M. tuberculosis
disease is shown in Table 2. The QIFN
results were not statistically different for pulmonary versus
extrapulmonary disease, for culture-positive versus clinically
diagnosed cases, or for smear-positive versus smear-negative cases.
None of the patients with active tuberculosis tested positive for MAC
by the QIFN assay.
For the 38 patients with evaluable Mantoux test results, the
sensitivities of the Mantoux and QIFN tests to detect
M. tuberculosis disease are shown in Table
3. Mantoux test results were not
different
from those of the QIFN assay. Similarly, there was no
significant
difference between the sensitivities of the assays when the
patients
were stratified by pulmonary or extrapulmonary disease (Table
3).
The QIFN assay was positive for MAC in three of seven cases of MAC
colonization. One patient with active MAC disease, who
was clinically
suspected to have concurrent MTB disease and had
a positive blistering
Mantoux test result, had a positive
M. tuberculosis response
in the QIFN assay. Two of the four cases of previously
treated MAC
disease had a positive
M. tuberculosis QIFN response;
one of
these had been treated for tuberculosis in the
past.
| |
DISCUSSION |
The resurgence of tuberculosis and the increase in
multidrug-resistant strains has intensified the need for rapid and
accurate screening and case finding. Despite the widely acknowledged
limitations of the Mantoux test, due to the lack of an effective
alternative, it remains the "gold standard" for identifying
tuberculous infection (9). The sensitivity of the Mantoux
test in patients with culture-positive tuberculosis has been estimated
to be 87%, with a specificity of 80% in a nonvaccinated healthy
population and a 13 to 15% variability in reading of the skin test
(3). In comparison, the sensitivity of the QIFN assay was
recently determined to be 83% in individuals with active tuberculosis
and 90% in individuals with tuberculous infection (Mantoux positive
but no disease) (12). Its specificity was estimated to be
98% in nonvaccinated Australian-born military recruits with low
tuberculosis exposure (12).
The Prophit Survey showed a direct relationship between a strong
reaction on Mantoux conversion and development of tuberculosis: 11% of
the strong converters developed active disease versus 3% of regular
converters (10). Thus, the ability to quantitate the
reaction to tuberculin may help estimate the risk of developing active
disease. Our findings (Fig. 1) support those of Converse et al., which
also showed a correlation between the Mantoux induration diameter and
the magnitude of the QIFN response, i.e., the assay is able to be
quantified in a manner similar to the Mantoux test (4). This
is desirable, as it could allow for different cutoff values to be
applied to different groups, based on the risk of tuberculosis, just as
different induration diameters are used in Mantoux testing
(2). This possibility requires further evaluation.
In the present study the agreement between the Mantoux test and the
QIFN assay was good to fair, with kappa statistics of 0.55 and 0.65 for
group I (immigrants) and group III (patients), respectively. None of
the 47 immigrants with discrepant test results had radiological
evidence of active disease. It may be speculated that the discrepancies
could be accounted for in Mantoux-positive and QIFN-negative
participants by the cross-reactivity of the Mantoux test due to
exposure to nontuberculous mycobacteria, and in Mantoux-negative and
QIFN-positive participants it could be accounted for by a greater
sensitivity of the QIFN assay in detecting M. tuberculosis
infection compared to that of the Mantoux test, as suggested by others
(4, 12). One method of resolving this issue would be
long-term follow-up of those persons with discrepant results to
determine if there is any difference in the rates of developing active
disease according to either the Mantoux or QIFN result.
For group II (HCWs), the agreement between the tests was good to fair,
with a kappa statistic of 0.48 when a positive Mantoux test result was
defined as a 10-mm-diameter induration. The kappa statistic decreased
to 0.26, indicating poor agreement, when the CDC interpretive criterion
of 15-mm-diameter was used. Due to the antigens shared across
mycobacterial species and the lack of specificity of the tuberculin
used, both the Mantoux test and the QIFN assay can suffer from
cross-reactivity in M. bovis BCG-vaccinated individuals. For
the Mantoux test this is compensated for in the New Zealand guidelines
by increasing the cutoff from 10-mm to 15-mm diameter for
BCG-vaccinated people, to increase its specificity (8). A
corresponding modification in interpretation of QIFN assay results is
not recommended by the manufacturer for BCG-vaccinated individuals.
However, newer antigens, such as ESAT-6 and MTP-64, may increase the
specificity of the QIFN assay in these situations. ESAT-6, a
low-molecular-weight secreted antigen, and the gene encoding it,
esat-6, are absent in BCG strains (7).
Preliminary studies indicate that immunological response to ESAT-6 is
not influenced by previous BCG vaccination, in that 11 of 54 (20%) individuals tested QIFN positive 5 months after BCG vaccination with tuberculin PPD (human), but none were positive when ESAT-6 was used in its place in the QIFN assay (5a).
A positive acid-fast smear remains the most rapid diagnostic test for
tuberculosis. However, smear-positive cases only comprise about 50% of
patients with pulmonary disease and are less frequent in cases of
extrapulmonary disease and pediatric tuberculosis (1). If
the QIFN assay was equivalent to or better than the Mantoux test at
detecting active tuberculosis, it would be useful in cases where
conventional laboratory means of diagnosis fail. Our results show that
the sensitivity of the QIFN assay in detecting various forms of
M. tuberculosis disease was 70 to 80%. This difference from
the performance of the Mantoux test was not statistically significant,
and therefore the assay could potentially replace the Mantoux test in
clinical situations where tuberculosis is suspected.
By virtue of its ability to quantitate a differential response to the
human and avian PPDs, the QIFN assay has the potential to discriminate
between M. tuberculosis and MAC disease. The QIFN assay
correctly differentiated 50 culture-confirmed M. tuberculosis cases from 10 cases of MAC cervical lymphadenitis in
children (6). The present study showed that all cases of
active tuberculosis detected by the QIFN assay had a predominant
response to human PPD and were identified as M. tuberculosis
infection. None had a predominant MAC response. The assay also
accurately detected three of the seven cases of MAC colonization. Too
few cases of MAC disease were tested to draw any conclusions about the
discriminatory power of the QIFN assay for adult patients with
respiratory MAC disease or colonization. More data are required for
patients with sputum cultures containing MAC to determine if the QIFN
assay can help differentiate colonization from disease in this
difficult to evaluate patient group.
QIFN assay works on the same principles as the Mantoux test but, being
an in vitro test, has several inherent advantages: it only requires a
single patient visit, it lacks a booster effect, and its interpretation
is more objective. The inclusion of a phytohemagglutin as a positive
mitogen control allows the identification of those who are negative
because they cannot mount an in vitro response. This is not possible in
routine Mantoux testing, where a negative result due to
immunosuppression is not detected. Furthermore, it has been suggested
that by showing a reduction in human PPD response the QIFN assay could
also be useful in monitoring the response to treatment (11).
Sodhi et al. showed that reduced IFN- production by peripheral blood
mononuclear cells stimulated by heat-killed MTB is a marker of severe
tuberculosis in both HIV-negative and -positive patients with
tuberculosis (11). Whether the QIFN assay could be used
similarly to assess the severity of tuberculosis requires investigation.
Conclusion.
We evaluated the QIFN assay in three different
settings, immigrant and HCW screening and evaluation of cases of
M. tuberculosis and MAC disease. The QIFN results showed a
correlation with Mantoux test results. When CDC interpretive guidelines
were used, the agreement between the QIFN assay and Mantoux test was
good to fair for immigrants and patients but poor for the HCW group.
The sensitivity of the assay was not significantly different from that
of the Mantoux test in cases of active tuberculosis, and it detected
three of the seven cases of MAC colonization. The QIFN assay seems to
be a promising new approach to detect evidence of mycobacterial
infection. In some situations it may have the potential to replace the
Mantoux skin test. The assay does, however, require laboratory
facilities to stimulate viable lymphocytes and EIA to quantify IFN-.
More experience is needed from long-term studies to determine whether
the management of contacts of individuals with infectious tuberculosis,
based in part on Mantoux results, can be extrapolated to the QIFN assay
results. The acceptability of the performance values observed in this
study and those of similar evaluations will determine the place this
test will have in detecting evidence of mycobacterial infection, either
as a screening test or for those suspected of having active disease.
| |
ACKNOWLEDGMENTS |
We thank Lester Calder, Martin Reeves, Alison McCleod, Tony
Wansborough, Chris Walls, the staff of the tuberculosis ward (GLH) and
the occupational health clinics (GLH & AKH), and the staff of the
Mangere Refugee Resettlement Centre for their help with the study and
the immigrants, the Microbiology staff at GLH, AKH, and Diagnostic
laboratories, and the staff attending occupational health clinics at
GLH and AKH for their participation. We also thank Jim Rothel, Gavin
Horrigan, and Judy Woodard of CSL Biosciences for their technical
advice and assistance with the statistical analysis.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: Microbiology
Laboratory, Green Lane Hospital, Green Lane West, Auckland 1003, New
Zealand. Phone: (649) 638-9909. Fax: (649) 630-9785. E-mail:
arthurm{at}ahsl.co.nz.
| |
REFERENCES |
| 1.
|
Bothamley, G. H.
1995.
Serological diagnosis of tuberculosis.
Eur. Respir. J.
8(Suppl. 20):676-688.
|
| 2.
|
Centers for Disease Control and Prevention.
1994.
Guidelines for preventing the transmission of Mycobacterium tuberculosis in healthcare facilities.
Morbid. Mortal. Weekly Rep.
43(RR-13):59-64.
|
| 3.
|
Chaparas, S. D.,
H. M. Vandiviere,
I. Melvin,
G. Koch, and C. Becker.
1985.
Tuberculin test. Variability with the Mantoux procedure.
Am. Rev. Respir. Dis.
132:175-177[Medline].
|
| 4.
|
Converse, P. J.,
S. L. Jones,
J. Astemborski,
D. Vlahov, and N. M. H. Graham.
1997.
Comparison of a tuberculin interferon- assay with the tuberculin skin test in high-risk adults: effect of human immunodeficiency virus infection.
J. Infect. Dis.
176:144-150[Medline].
|
| 5.
|
Desem, N., and S. L. Jones.
1998.
Development of a human gamma interferon enzyme immunoassay and comparison with tuberculin skin testing for detection of Mycobacterium tuberculosis infection.
Clin. Diagn. Lab. Immunol.
5:531-536[Abstract/Free Full Text].
|
| 5a.
| Johnson, P. D. R. Personal communication.
|
| 6.
|
Mukherjee, S.,
R. Lumb,
P. Robinson, and R. Stapledon.
1995.
Evaluation of gamma interferon (IFN-) assay in human mycobacterial infection.
Aust. N. Z. J. Med.
25:436.
|
| 7.
|
Pollock, J. M., and P. Anderson.
1997.
The potential of the ESAT-6 antigen secreted by virulent mycobacteria for specific diagnosis of tuberculosis.
J. Infect. Dis.
175:1251-1254[Medline].
|
| 8.
|
Public Health Group.
1996.
Guidelines for tuberculosis control in New Zealand, p. 18-22.
Ministry of Health, Wellington, New Zealand.
|
| 9.
|
Reichman, L. B.
1998.
A scandalous incompetence ... continued.
Chest
113:1153-1154[Free Full Text].
|
| 10.
|
Sepkowitz, K. A.
1996.
Tuberculin skin testing and the health care worker: lessons of the Prophit Survey.
Tuber. Lung Dis.
77:81-85[Medline].
|
| 11.
|
Sodhi, A.,
J. Gong,
C. Silva,
D. Qian, and P. F. Barnes.
1997.
Clinical correlates of Interferon production in patients with tuberculosis.
Clin. Infect. Dis.
25:617-620[Medline].
|
| 12.
|
Streeton, J. A.,
N. Desem, and S. L. Jones.
1998.
Sensitivity and specificity of a gamma interferon blood test for tuberculosis infection.
Int. J. Tuber. Lung Dis.
2:443-450.
|
| 13.
|
Wood, P. R.,
L. A. Corner,
J. S. Rothel,
C. Baldock,
S. L. Jones,
D. B. Cousins,
B. S. McCormick,
B. R. Francis,
J. Creeper, and N. E. Tweddle.
1991.
Field comparison of the interferon-gamma assay and the intradermal tuberculin test for the diagnosis of bovine tuberculosis.
Aust. Vet. J.
68:286-290[Medline].
|
Journal of Clinical Microbiology, October 1999, p. 3229-3232, Vol. 37, No. 10
0095-1137/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Hu, W. P., Lu, Y., Precioso, N. A., Chen, H. Y., Howard, T., Anderson, D., Guan, M.
(2008). Double-Antigen Enzyme-Linked Immunosorbent Assay for Detection of Hepatitis E Virus-Specific Antibodies in Human or Swine Sera. CVI
15: 1151-1157
[Abstract]
[Full Text]
-
Perry, S., Sanchez, L., Yang, S., Agarwal, Z., Hurst, P., Parsonnet, J.
(2008). Reproducibility of QuantiFERON-TB Gold In-Tube Assay. CVI
15: 425-432
[Abstract]
[Full Text]
-
Kim, C.-M., Blanco, L. B. C., Alhassan, A., Iseki, H., Yokoyama, N., Xuan, X., Igarashi, I.
(2008). Development of a Rapid Immunochromatographic Test for Simultaneous Serodiagnosis of Bovine Babesioses Caused by Babesia bovis and Babesia bigemina. Am J Trop Med Hyg
78: 117-121
[Abstract]
[Full Text]
-
Kaushik, V. V., Ambalavanan, S., Binymin, K.
(2007). Comment on: Use of the QuantiFERON TB Gold test as part of a screening programme in patients with RA under consideration for treatment with anti-TNF-{alpha} agents: the Newcastle (UK) experience. Rheumatology (Oxford)
46: 1863-1864
[Full Text]
-
Koo, H. C., Park, Y. H., Ahn, J., Waters, W. R., Palmer, M. V., Hamilton, M. J., Barrington, G., Mosaad, A. A., Park, K. T., Jung, W. K., Hwang, I. Y., Cho, S.-N., Shin, S. J., Davis, W. C.
(2005). Use of rMPB70 Protein and ESAT-6 Peptide as Antigens for Comparison of the Enzyme-Linked Immunosorbent, Immunochromatographic, and Latex Bead Agglutination Assays for Serodiagnosis of Bovine Tuberculosis. J. Clin. Microbiol.
43: 4498-4506
[Abstract]
[Full Text]
-
Ampel, N. M., Nelson, D. K., Chavez, S., Naus, K. A., Herman, A. B., Li, L., Simmons, K. A., Pappagianis, D.
(2005). Preliminary Evaluation of Whole-Blood Gamma Interferon Release for Clinical Assessment of Cellular Immunity in Patients with Active Coccidioidomycosis. CVI
12: 700-704
[Abstract]
[Full Text]
-
Chen, H. Y., Lu, Y., Howard, T., Anderson, D., Fong, P. Y., Hu, W.-P., Chia, C. P., Guan, M.
(2005). Comparison of a New Immunochromatographic Test to Enzyme-Linked Immunosorbent Assay for Rapid Detection of Immunoglobulin M Antibodies to Hepatitis E Virus in Human Sera. CVI
12: 593-598
[Abstract]
[Full Text]
-
Avgustin, B., Kotnik, V., Skoberne, M., Malovrh, T., Skralovnik-Stern, A., Tercelj, M.
(2005). CD69 Expression on CD4+ T Lymphocytes after In Vitro Stimulation with Tuberculin Is an Indicator of Immune Sensitization against Mycobacterium tuberculosis Antigens. CVI
12: 101-106
[Abstract]
[Full Text]
-
Taggart, E. W., Hill, H. R., Ruegner, R. G., Martins, T. B., Litwin, C. M.
(2004). Evaluation of an In Vitro Assay for Gamma Interferon Production in Response to Mycobacterium tuberculosis Infections. CVI
11: 1089-1093
[Abstract]
[Full Text]
-
Scarpellini, P., Tasca, S., Galli, L., Beretta, A., Lazzarin, A., Fortis, C.
(2004). Selected Pool of Peptides from ESAT-6 and CFP-10 Proteins for Detection of Mycobacterium tuberculosis Infection. J. Clin. Microbiol.
42: 3469-3474
[Abstract]
[Full Text]
-
Guan, M., Chan, K. H., Peiris, J. S. M., Kwan, S. W., Lam, S. Y., Pang, C. M., Chu, K. W., Chan, K. M., Chen, H. Y., Phuah, E. B., Wong, C. J.
(2004). Evaluation and Validation of an Enzyme-Linked Immunosorbent Assay and an Immunochromatographic Test for Serological Diagnosis of Severe Acute Respiratory Syndrome. CVI
11: 699-703
[Abstract]
[Full Text]
-
Guan, M., Chen, H. Y., Foo, S. Y., Tan, Y.-J., Goh, P.-Y., Wee, S. H.
(2004). Recombinant Protein-Based Enzyme-Linked Immunosorbent Assay and Immunochromatographic Tests for Detection of Immunoglobulin G Antibodies to Severe Acute Respiratory Syndrome (SARS) Coronavirus in SARS Patients. CVI
11: 287-291
[Abstract]
[Full Text]
-
Jungersen, G., Huda, A., Hansen, J. J., Lind, P.
(2002). Interpretation of the Gamma Interferon Test for Diagnosis of Subclinical Paratuberculosis in Cattle. CVI
9: 453-460
[Abstract]
[Full Text]
-
Hersh, A., von Reyn, C. F., Herzmann, C., Mazurek, G. H.
(2002). Interferon Assay Compared to Tuberculin Skin Testing for Latent Tuberculosis Detection. JAMA
287: 450-452
[Full Text]
-
Mazurek, G. H., LoBue, P. A., Daley, C. L., Bernardo, J., Lardizabal, A. A., Bishai, W. R., Iademarco, M. F., Rothel, J. S.
(2001). Comparison of a Whole-Blood Interferon {gamma} Assay With Tuberculin Skin Testing for Detecting Latent Mycobacterium tuberculosis Infection. JAMA
286: 1740-1747
[Abstract]
[Full Text]
-
Small, P. M., Fujiwara, P. I.
(2001). Management of Tuberculosis in the United States. NEJM
345: 189-200
[Full Text]
-
Barnes, P. F.
(2001). Diagnosing Latent Tuberculosis Infection . The 100-year Upgrade. Am. J. Respir. Crit. Care Med.
163: 807-808
[Full Text]
-
Katial, R. K., Hershey, J., Purohit-Seth, T., Belisle, J. T., Brennan, P. J., Spencer, J. S., Engler, R. J. M.
(2001). Cell-Mediated Immune Response to Tuberculosis Antigens: Comparison of Skin Testing and Measurement of In Vitro Gamma Interferon Production in Whole-Blood Culture. CVI
8: 339-345
[Abstract]
[Full Text]
-
Pottumarthy, S., Wells, V. C., Morris, A. J.
(2000). A Comparison of Seven Tests for Serological Diagnosis of Tuberculosis. J. Clin. Microbiol.
38: 2227-2231
[Abstract]
[Full Text]
Top
Abstract
Introduction
