New tools for detecting latent tuberculosis infection: evaluation of RD1-specific long-term response View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-11-21

AUTHORS

Ornella Butera, Teresa Chiacchio, Stefania Carrara, Rita Casetti, Valentina Vanini, Serena Meraviglia, Giuliana Guggino, Francesco Dieli, Marco Vecchi, Francesco N Lauria, Almerico Marruchella, Patrizia Laurenti, Mahavir Singh, Nadia Caccamo, Enrico Girardi, Delia Goletti

ABSTRACT

BACKGROUND: Interferon-gamma (IFN-gamma) release assays (IGRAs) were designed to detect latent tuberculosis infection (LTBI). However, discrepancies were found between the tuberculin skin test (TST) and IGRAs results that cannot be attributed to prior Bacille Calmètte Guerin vaccinations. The aim of this study was to evaluate tools for improving LTBI diagnosis by analyzing the IFN-gamma response to RD1 proteins in prolonged (long-term response) whole blood tests in those subjects resulting negative to assays such as QuantiFERON-TB Gold In tube (QFT-IT). METHODS: The study population included 106 healthy TST+ individuals with suspected LTBI (recent contact of smear-positive TB and homeless) consecutively enrolled. As controls, 13 healthy subjects unexposed to M. tuberculosis (TST-, QFT-IT-) and 29 subjects with cured pulmonary TB were enrolled. IFN-gamma whole blood response to RD1 proteins and QFT-IT were evaluated at day 1 post-culture. A prolonged test evaluating long-term IFN-gamma response (7-day) to RD1 proteins in diluted whole blood was performed. RESULTS: Among the enrolled TST+ subjects with suspected LTBI, 70/106 (66.0%) responded to QFT-IT and 64/106 (60.3%) to RD1 proteins at day 1. To evaluate whether a prolonged test could improve the detection of LTBI, we set up the test using cured TB patients (with a microbiologically diagnosed past pulmonary disease) who resulted QFT-IT-negative and healthy controls as comparator groups. Using this assay, a statistically significant difference was found between IFN-gamma levels in cured TB patients compared to healthy controls (p < 0.006). Based on these data, we constructed a receiver operating characteristic (ROC) curve and we calculated a cut-off. Based on the cut-off value, we found that among the 36 enrolled TST+ subjects with suspected LTBI not responding to QFT-IT, a long term response to RD1 proteins was detected in 11 subjects (30.6%). CONCLUSION: These results indicate that IFN-gamma long-term response to M. tuberculosis RD1 antigens may be used to detect past infection with M. tuberculosis and may help to identify additional individuals with LTBI who resulted negative in the short-term tests. These data may provide useful information for improving immunodiagnostic tests for tuberculosis infection, especially in individuals at high risk for active TB. More... »

PAGES

182-182

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1471-2334-9-182

DOI

http://dx.doi.org/10.1186/1471-2334-9-182

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1039383870

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19930588


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22 schema:description BACKGROUND: Interferon-gamma (IFN-gamma) release assays (IGRAs) were designed to detect latent tuberculosis infection (LTBI). However, discrepancies were found between the tuberculin skin test (TST) and IGRAs results that cannot be attributed to prior Bacille Calmètte Guerin vaccinations. The aim of this study was to evaluate tools for improving LTBI diagnosis by analyzing the IFN-gamma response to RD1 proteins in prolonged (long-term response) whole blood tests in those subjects resulting negative to assays such as QuantiFERON-TB Gold In tube (QFT-IT). METHODS: The study population included 106 healthy TST+ individuals with suspected LTBI (recent contact of smear-positive TB and homeless) consecutively enrolled. As controls, 13 healthy subjects unexposed to M. tuberculosis (TST-, QFT-IT-) and 29 subjects with cured pulmonary TB were enrolled. IFN-gamma whole blood response to RD1 proteins and QFT-IT were evaluated at day 1 post-culture. A prolonged test evaluating long-term IFN-gamma response (7-day) to RD1 proteins in diluted whole blood was performed. RESULTS: Among the enrolled TST+ subjects with suspected LTBI, 70/106 (66.0%) responded to QFT-IT and 64/106 (60.3%) to RD1 proteins at day 1. To evaluate whether a prolonged test could improve the detection of LTBI, we set up the test using cured TB patients (with a microbiologically diagnosed past pulmonary disease) who resulted QFT-IT-negative and healthy controls as comparator groups. Using this assay, a statistically significant difference was found between IFN-gamma levels in cured TB patients compared to healthy controls (p < 0.006). Based on these data, we constructed a receiver operating characteristic (ROC) curve and we calculated a cut-off. Based on the cut-off value, we found that among the 36 enrolled TST+ subjects with suspected LTBI not responding to QFT-IT, a long term response to RD1 proteins was detected in 11 subjects (30.6%). CONCLUSION: These results indicate that IFN-gamma long-term response to M. tuberculosis RD1 antigens may be used to detect past infection with M. tuberculosis and may help to identify additional individuals with LTBI who resulted negative in the short-term tests. These data may provide useful information for improving immunodiagnostic tests for tuberculosis infection, especially in individuals at high risk for active TB.
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29 schema:keywords Bacille Calmètte Guerin vaccinations
30 Calmètte Guerin vaccinations
31 Guerin vaccinations
32 IFN-gamma levels
33 IFN-gamma long-term response
34 IFN-gamma responses
35 IFN-gamma whole blood response
36 IGRAs results
37 LTBI diagnosis
38 QFT
39 QFT-IT
40 QuantiFERON-TB Gold
41 RD1 antigens
42 RD1 proteins
43 RD1-specific long-term response
44 TB
45 TB patients
46 active TB
47 additional individuals
48 aim
49 antigen
50 assays
51 blood
52 blood response
53 blood tests
54 characteristic curve
55 comparator group
56 control
57 curves
58 cut
59 data
60 day 1
61 detection
62 detection of LTBI
63 diagnosis
64 differences
65 diluted whole blood
66 discrepancy
67 evaluation
68 gold
69 group
70 healthy controls
71 healthy subjects
72 high risk
73 immunodiagnostic tests
74 individuals
75 infection
76 information
77 interferon-gamma release assays
78 latent tuberculosis infection
79 levels
80 long-term IFN-gamma response
81 long-term response
82 new tool
83 past infection
84 patients
85 population
86 prior Bacille Calmètte Guerin vaccinations
87 prolonged (long-term response) whole blood tests
88 prolonged test
89 protein
90 pulmonary TB
91 receiver
92 release assays
93 response
94 results
95 risk
96 short-term tests
97 significant differences
98 skin test
99 study
100 study population
101 subjects
102 term response
103 test
104 tool
105 tube
106 tuberculin skin test
107 tuberculosis
108 tuberculosis RD1 antigens
109 tuberculosis infection
110 useful information
111 vaccination
112 values
113 whole blood
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115 whole blood test
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