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Published in: BMC Infectious Diseases 1/2018

Open Access 01-12-2018 | Research article

Predictors for false-negative QuantiFERON-TB Gold assay results in patients with extrapulmonary tuberculosis

Authors: Youn Jeong Kim, Ji Young Kang, Sang Il Kim, Mee Soo Chang, Yang Ree Kim, Yeon Joon Park

Published in: BMC Infectious Diseases | Issue 1/2018

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Abstract

Backgrounds

Extrapulmonary tuberculosis (EPTB) is a heterogeneous disease, and diagnosis is sometimes difficult. We investigated the diagnostic performance of the QuantiFERON-TB Gold assay (QFT-GIT) according to sites of EPTB and predictors for false-negative QFT-GIT results.

Methods

A total of 2176 patients were registered with active TB from January 2012 to December 2016 in Seoul St. Mary’s Hospital, a 1200-bed tertiary teaching hospital in Seoul, Korea. We retrospectively reviewed the medical records of 163 EPTB patients who underwent QFT-GIT.

Results

False negative QFT-GIT results were found in 28.8% (95% CI 0.22–0.36) of patients with EPTB. In the proven TB group, negative QFT-GIT results were found in 28.6% (95% CI 0.04–0.71) of pleural, 8.3% 0.002–0.38of lymph node, 8.3% (95% CI 0.002–0.38) of skeletal and 5.8% (95% CI 0.001–0.28) of gastrointestinal TB cases. Among probable TB cases, QFT-GIT negative results were identified in 46.2% (95% CI 0.19–0.75) of skeletal, 33.3% (95% CI 10–0.65) of pericardial, 30.8% (95% CI 0.09–0.61) of pleural and 17.2% (95% CI 0.10–0.56) of gastrointestinal TB cases. In the possible TB cases, central nervous system TB (n = 21) was most frequent, and 66.7% (95% CI 0.43–0.85) of those showed QFT-GIT negative results. By multivariate analysis, possible TB was independently associated with false-negative QFT-GIT results (OR 4.92, 95% CI 1.51–16.06, p = 0.008).

Conclusions

Prudent interpretation of QFT-GIT results might be needed according to anatomic site of involvement and diagnostic criteria in patients with high suspicion of EPTB.
Literature
3.
go back to reference Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med. 2008;149(3):177–84.CrossRefPubMedPubMedCentral Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med. 2008;149(3):177–84.CrossRefPubMedPubMedCentral
4.
go back to reference Sester M, Sotgiu G, Lange C, Giehl C, Girardi E, Migliori GB, Bossink A, Dheda K, Diel R, Dominguez J, et al. Interferon-gamma release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2011;37(1):100–11.CrossRefPubMed Sester M, Sotgiu G, Lange C, Giehl C, Girardi E, Migliori GB, Bossink A, Dheda K, Diel R, Dominguez J, et al. Interferon-gamma release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2011;37(1):100–11.CrossRefPubMed
5.
go back to reference Bennett JE, Raphael D, Blaser MJ. Mandell Douglas, and Bennett's principles and practice of infectious diseases. 8th ed. Canada: Saunders; 2015. Bennett JE, Raphael D, Blaser MJ. Mandell Douglas, and Bennett's principles and practice of infectious diseases. 8th ed. Canada: Saunders; 2015.
6.
go back to reference Kim YJ, Kim SI, Kim YR, Wie SH, Park YJ, Kang MW. Predictive value of interferon-gamma ELISPOT assay in HIV 1-infected patients in an intermediate tuberculosis-endemic area. Aids Res Hum Retrov. 2012;28(9):838–43.CrossRef Kim YJ, Kim SI, Kim YR, Wie SH, Park YJ, Kang MW. Predictive value of interferon-gamma ELISPOT assay in HIV 1-infected patients in an intermediate tuberculosis-endemic area. Aids Res Hum Retrov. 2012;28(9):838–43.CrossRef
7.
go back to reference Kim SH, Choi SJ, Kim HB, Kim NJ, Oh MD, Choe KW. Diagnostic usefulness of a T-cell based assay for extrapulmonary tuberculosis. Arch Intern Med. 2007;167(20):2255–9.CrossRefPubMed Kim SH, Choi SJ, Kim HB, Kim NJ, Oh MD, Choe KW. Diagnostic usefulness of a T-cell based assay for extrapulmonary tuberculosis. Arch Intern Med. 2007;167(20):2255–9.CrossRefPubMed
8.
go back to reference Thwaites G, Fisher M, Hemingway C, Scott G, Solomon T, Innes J, British Infection S. British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children. J Inf Secur. 2009;59(3):167–87. Thwaites G, Fisher M, Hemingway C, Scott G, Solomon T, Innes J, British Infection S. British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children. J Inf Secur. 2009;59(3):167–87.
9.
go back to reference Peto HM, Pratt RH, Harrington TA, LoBue PA, Armstrong LR. Epidemiology of extrapulmonary tuberculosis in the United States, 1993-2006. Clin Infect Dis. 2009;49(9):1350–7.CrossRefPubMed Peto HM, Pratt RH, Harrington TA, LoBue PA, Armstrong LR. Epidemiology of extrapulmonary tuberculosis in the United States, 1993-2006. Clin Infect Dis. 2009;49(9):1350–7.CrossRefPubMed
10.
go back to reference Pai M, Denkinger CM, Kik SV, Rangaka MX, Zwerling A, Oxlade O, Metcalfe JZ, Cattamanchi A, Dowdy DW, Dheda K, et al. Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Clin Microbiol Rev. 2014;27(1):3–20.CrossRefPubMedPubMedCentral Pai M, Denkinger CM, Kik SV, Rangaka MX, Zwerling A, Oxlade O, Metcalfe JZ, Cattamanchi A, Dowdy DW, Dheda K, et al. Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Clin Microbiol Rev. 2014;27(1):3–20.CrossRefPubMedPubMedCentral
11.
go back to reference Menzies D, Pai M, Comstock G. Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research. Ann Intern Med. 2007;146(5):340–54.CrossRefPubMed Menzies D, Pai M, Comstock G. Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research. Ann Intern Med. 2007;146(5):340–54.CrossRefPubMed
12.
go back to reference Lu P, Chen X, Zhu LM, Yang HT. Interferon-gamma release assays for the diagnosis of tuberculosis: a systematic review and meta-analysis. Lung. 2016;194(3):447–58.CrossRefPubMed Lu P, Chen X, Zhu LM, Yang HT. Interferon-gamma release assays for the diagnosis of tuberculosis: a systematic review and meta-analysis. Lung. 2016;194(3):447–58.CrossRefPubMed
13.
go back to reference Kobashi Y, Shimizu H, Ohue Y, Mouri K, Obase Y, Miyashita N, Oka M. Comparison of T-cell interferon-gamma release assays for Mycobacterium tuberculosis-specific antigens in patients with active and latent tuberculosis. Lung. 2010;188(4):283–7.CrossRefPubMedPubMedCentral Kobashi Y, Shimizu H, Ohue Y, Mouri K, Obase Y, Miyashita N, Oka M. Comparison of T-cell interferon-gamma release assays for Mycobacterium tuberculosis-specific antigens in patients with active and latent tuberculosis. Lung. 2010;188(4):283–7.CrossRefPubMedPubMedCentral
14.
go back to reference Clifford V, He Y, Zufferey C, Connell T, Curtis N. Interferon gamma release assays for monitoring the response to treatment for tuberculosis: a systematic review. Tuberculosis (Edinb). 2015;95(6):639–50.CrossRef Clifford V, He Y, Zufferey C, Connell T, Curtis N. Interferon gamma release assays for monitoring the response to treatment for tuberculosis: a systematic review. Tuberculosis (Edinb). 2015;95(6):639–50.CrossRef
15.
go back to reference Lee YM, Kim SM, Park SJ, Lee SO, Choi SH, Kim YS, Woo JH, Kim SH. Factors associated with a strong response to the T-SPOT.TB in patients with Extrapulmonary tuberculosis. Infect Chemother. 2014;46(4):248–52.CrossRefPubMedPubMedCentral Lee YM, Kim SM, Park SJ, Lee SO, Choi SH, Kim YS, Woo JH, Kim SH. Factors associated with a strong response to the T-SPOT.TB in patients with Extrapulmonary tuberculosis. Infect Chemother. 2014;46(4):248–52.CrossRefPubMedPubMedCentral
16.
go back to reference Erdem H, Ozturk-Engin D, Elaldi N, Gulsun S, Sengoz G, Crisan A, Johansen IS, Inan A, Nechifor M, Al-Mahdawi A, et al. The microbiological diagnosis of tuberculous meningitis: results of Haydarpasa-1 study. Clin Microbiol Infect. 2014;20(10):O600–8.CrossRefPubMed Erdem H, Ozturk-Engin D, Elaldi N, Gulsun S, Sengoz G, Crisan A, Johansen IS, Inan A, Nechifor M, Al-Mahdawi A, et al. The microbiological diagnosis of tuberculous meningitis: results of Haydarpasa-1 study. Clin Microbiol Infect. 2014;20(10):O600–8.CrossRefPubMed
17.
go back to reference Pai M, Flores LL, Pai N, Hubbard A, Riley LW, Colford JM Jr. Diagnostic accuracy of nucleic acid amplification tests for tuberculous meningitis: a systematic review and meta-analysis. Lancet Infect Dis. 2003;3(10):633–43.CrossRefPubMed Pai M, Flores LL, Pai N, Hubbard A, Riley LW, Colford JM Jr. Diagnostic accuracy of nucleic acid amplification tests for tuberculous meningitis: a systematic review and meta-analysis. Lancet Infect Dis. 2003;3(10):633–43.CrossRefPubMed
18.
go back to reference Leonard JM. Central nervous system tuberculosis. Microbiol Spectr. 2017;5(2) Leonard JM. Central nervous system tuberculosis. Microbiol Spectr. 2017;5(2)
19.
go back to reference Kim CH, Lim JK, Yoo SS, Lee SY, Cha SI, Park JY, Lee J. Diagnostic performance of the QuantiFERON-TB gold in-tube assay and factors associated with nonpositive results in patients with miliary tuberculosis. Clin Infect Dis. 2014;58(7):986–9.CrossRefPubMed Kim CH, Lim JK, Yoo SS, Lee SY, Cha SI, Park JY, Lee J. Diagnostic performance of the QuantiFERON-TB gold in-tube assay and factors associated with nonpositive results in patients with miliary tuberculosis. Clin Infect Dis. 2014;58(7):986–9.CrossRefPubMed
20.
go back to reference Lai CC, Tan CK, Lin SH, Liao CH, Huang YT, Hsueh PR. Diagnostic performance of whole-blood interferon-gamma assay and enzyme-linked immunospot assay for active tuberculosis. Diagn Microbiol Infect Dis. 2011;71(2):139–43.CrossRefPubMed Lai CC, Tan CK, Lin SH, Liao CH, Huang YT, Hsueh PR. Diagnostic performance of whole-blood interferon-gamma assay and enzyme-linked immunospot assay for active tuberculosis. Diagn Microbiol Infect Dis. 2011;71(2):139–43.CrossRefPubMed
21.
go back to reference Telisinghe L, Amofa-Sekyi M, Maluzi K, Kaluba-Milimo D, Cheeba-Lengwe M, Chiwele K, Kosloff B, Floyd S, Bailey SL, Ayles H. The sensitivity of the QuantiFERON(R)-TB gold plus assay in Zambian adults with active tuberculosis. Int J Tuberc Lung Dis. 2017;21(6):690–6.CrossRefPubMedPubMedCentral Telisinghe L, Amofa-Sekyi M, Maluzi K, Kaluba-Milimo D, Cheeba-Lengwe M, Chiwele K, Kosloff B, Floyd S, Bailey SL, Ayles H. The sensitivity of the QuantiFERON(R)-TB gold plus assay in Zambian adults with active tuberculosis. Int J Tuberc Lung Dis. 2017;21(6):690–6.CrossRefPubMedPubMedCentral
22.
go back to reference Choi JC, Jarlsberg LG, Grinsdale JA, Osmond DH, Higashi J, Hopewell PC, Kato-Maeda M. Reduced sensitivity of the QuantiFERON((R)) test in diabetic patients with smear-negative tuberculosis. Int J Tuberc Lung Dis. 2015;19(5):582–8.CrossRefPubMed Choi JC, Jarlsberg LG, Grinsdale JA, Osmond DH, Higashi J, Hopewell PC, Kato-Maeda M. Reduced sensitivity of the QuantiFERON((R)) test in diabetic patients with smear-negative tuberculosis. Int J Tuberc Lung Dis. 2015;19(5):582–8.CrossRefPubMed
23.
go back to reference Jang JY, Park IW, Choi BW, Choi JC. The usefulness of the tuberculosis skin test and the interferon-gamma release assay in the diagnosis of latent tuberculosis infection in South Korea. Osong Public Health Res Perspect. 2014;5(Suppl):S18–23.CrossRefPubMedPubMedCentral Jang JY, Park IW, Choi BW, Choi JC. The usefulness of the tuberculosis skin test and the interferon-gamma release assay in the diagnosis of latent tuberculosis infection in South Korea. Osong Public Health Res Perspect. 2014;5(Suppl):S18–23.CrossRefPubMedPubMedCentral
24.
go back to reference Kim YJ, Chi YH, Lee JY, Lee HJ, Kang JY, Kim YR, Kim SI. In-hospital contact investigation among health care workers after exposure to pulmonary tuberculosis in an intermediate tuberculosis prevalence area: a prospective study. Arch Environ Occup H. 2017;72(5):272–8.CrossRef Kim YJ, Chi YH, Lee JY, Lee HJ, Kang JY, Kim YR, Kim SI. In-hospital contact investigation among health care workers after exposure to pulmonary tuberculosis in an intermediate tuberculosis prevalence area: a prospective study. Arch Environ Occup H. 2017;72(5):272–8.CrossRef
25.
go back to reference Mori T, Harada N, Higuchi K, Sekiya Y, Uchimura K, Shimao T. Waning of the specific interferon-gamma response after years of tuberculosis infection. Int J Tuberc Lung Dis. 2007;11(9):1021–5.PubMed Mori T, Harada N, Higuchi K, Sekiya Y, Uchimura K, Shimao T. Waning of the specific interferon-gamma response after years of tuberculosis infection. Int J Tuberc Lung Dis. 2007;11(9):1021–5.PubMed
Metadata
Title
Predictors for false-negative QuantiFERON-TB Gold assay results in patients with extrapulmonary tuberculosis
Authors
Youn Jeong Kim
Ji Young Kang
Sang Il Kim
Mee Soo Chang
Yang Ree Kim
Yeon Joon Park
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2018
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-018-3344-x

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