Risk Factors for False-Negative Interferon-γ Release Assay Results in Culture-Confirmed Childhood TB

Wang, Mao‐Shui; Liu, Xin-Jie

doi:10.4269/ajtmh.18-0684

Cited by 10 publications

(9 citation statements)

References 49 publications

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“…[ 22 ] This discrepancy may reflect inconsistencies in sample sizes, inclusion criteria and study populations; our study population originated from 5 provinces and municipalities of China and included a relatively high proportion of patients with hypoproteinemia that may have had false negative IGRA results. [ 23 ] Even so, the previous study also demonstrated a higher ESAT-6 positivity rate than that obtained for CFP-10 for active tuberculosis cases, suggesting that ESAT-6 had greater antigenic dominance than CFP-10 and triggered greater IFN-γ release, in accordance with other reported studies. [ 24 – 26 ] For example, 1 study conducted at nine locations assessed T cell reactivity to 59 MTB antigens and found that ESAT-6 showed higher immune-dominance than CFP-10.…”

Section: Discussionsupporting

confidence: 87%

Factors associated with differential T cell responses to antigens ESAT-6 and CFP-10 in pulmonary tuberculosis patients

Liu

Wu²,

Ertai³

et al. 2021

Medicine

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The T-SPOT.TB assay detects cellular immune responses to 2 core Mycobacterium tuberculosis antigens, early secreted antigenic target of 6-kDa protein (ESAT-6) and culture filtrate protein-10 (CFP-10). T-SPOT.TB has been recently used for auxiliary diagnosis of active pulmonary tuberculosis (PTB). However, testing can produce inconsistent results due to differential PTB patient immune responses to these antigens, prompting us to identify factors underlying inconsistent results. Data were retrospectively analyzed from 1225 confirmed PTB patients who underwent T-SPOT.TB testing at 5 specialized tuberculosis hospitals in China between December 2012 and November 2015. Numbers of spot-forming cells (SFCs) reflecting T cell responses to ESAT-6 and CFP-10 antigens were recorded then analyzed via multivariable logistic regression to reveal factors underlying discordant T cell responses to these antigens. The agreement rate of 84.98% (82.85%–86.94%) between PTB patient ESAT-6 and CFP-10 responses demonstrated high concordance. Additionally, positivity rates were higher for ESAT-6 than for CFP-10 (84.8% vs 80.7%, P < .001), with ESAT-6 and CFP-10 microwell SFC numbers for each single positive group not differing significantly (P > .99), while spot numbers of the single positive group were lower than numbers for the double positive group (P < .001). Elderly patients (aged ≥66 years) and patients receiving retreatment were most likely to have discordance results. ESAT-6 promoted significantly more positive T-SPOT.TB results than did CFP-10 in PTB patients. Advanced age and retreatment status were correlated with discordant ESAT-6 and CFP-10 results. Assessment of factors underlying discordance may lead to improved PTB diagnosis using T-SPOT.TB.

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Section: Discussionsupporting

confidence: 87%

Factors associated with differential T cell responses to antigens ESAT-6 and CFP-10 in pulmonary tuberculosis patients

Liu

Wu²,

Ertai³

et al. 2021

Medicine

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“…Although serum lymphocyte count and age were not statistically significant in our study, we also observed that the QFT-GIT-negative group tended to have lower serum lymphocyte count and be older than the QFT-GIT-positive group. Interestingly, the current study revealed that some other comorbidities such and decrease cell-mediated immunity (18,19). Also, coal workers pneumoconiosis is known to be vulnerable to pulmonary TB because coal dust is not a pure substance and usually contains 1-2% free silica (20).…”

Section: Discussionmentioning

confidence: 64%

“…On the other hand, the group with hypoproteinaemia <6.0 g/dL had a false-negative probability of QFT-GIT of more than seven times compared with the group with normal protein (P<0.001). Several studies have reported that hypoproteinaemia is associated with false-negative IGRA assay results (18,22,23). As hypoproteinaemia is an indicator of malnutrition, causing a decreased immune response, so too the protein status may lead to false-negative results of IGRA despite the presence of TB infection.…”

Section: Discussionmentioning

confidence: 99%

Clinical relevance of false-negative interferon-gamma release assays in patients with tuberculous pleurisy in an intermediate tuberculosis burden country

Kim

Jeong²,

Lim

et al. 2022

J Thorac Dis

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Background: There have been few studies to verify factors associated with a false-negative interferongamma release assay (IGRA) in patients with tuberculous pleurisy. We investigated the clinical relevance of false-negative results of the blood QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and its risk factors in patients diagnosed with pleural tuberculosis (TB).Methods: Medical records of 650 pleural TB patients in a tertiary hospital between January 2009 and December 2020 were reviewed retrospectively. Patients who underwent the blood QFT-GIT assay and pleural fluid analysis before starting anti-TB medication were included.Results: Of 199 patients with pleural TB who were performed QFT-GIT assay, 36 (18.1%) were falsenegative results. These patients tended to be older than those with a positive result (P=0.060). The QFT-GIT-false-negative group of had significantly more comorbidities such as end-stage renal disease (ESRD), haematological cancer or pneumoconiosis than the QFT-GIT-positive group. Hypoproteinaemia and pH >6 in pleural fluid were associated with a false-negative QFT-GIT. Of the 199 patients, 163 (81.9%) were cured or completed anti-TB treatment; 13 patients (6.5%) died. The QFT-GIT-negative patients had significantly worse outcomes including mortality [unfavourable outcome: 33.3% (12/36 patients) in QFT-GIT-negative groups vs. 14.7% (24/163 patients) in QFT-GIT-positive groups, P<0.017; overall mortality: 16.7% (6/36 patients) vs. 4.3% (7/163 patients), respectively, P<0.015]. Conclusions:In pleural TB, a false-negative QFT-GIT result was 18.1% in a country of intermediate TB incidence. This discordant result in GFT-GIT was associated with ESRD, pneumoconiosis, hypoproteinaemia and a poor outcome. Clinicians should keep in mind the possibility of false-negativity in the blood IGRA test, especially in specific situations and its impact on TB outcome in managing patients with pleural TB.

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“…Besides, these tests could facilitate the diagnosis of TBM [ 7 ]. Unfortunately, false-negative results of IGRA remain a concern among childhood TB, and approximately 15% of culture-confirmed TB children were IGRA-negative [ 8 ], and children with an age of < 2 years were more likely to have a negative IGRA response [ 9 ]. Therefore, the actual performance of IGRA and Mantoux tests require to be investigated, especially in infant TB.…”

Section: Introductionmentioning

confidence: 99%

Interferon-γ release assay and mantoux response in infants with tuberculous meningitis in low and intermediate burden countries

Yang¹,

Hou

et al. 2023

BMC Infect Dis

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Aim Until now, the performance of interferon-γ release assay (IGRA) and Mantoux tests remains unclear in infant tuberculous meningitis (TBM). Therefore, a systematic review is performed to evaluate the sensitivity of IGRA and Mantoux tests for the diagnosis of infant TBM in low and intermediate tuberculosis (TB) burden countries, while following PRISMA. Methods Several databases, including PubMed, EBSCO, Embase, Scopus, Web of Science, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials, were searched. Articles describing the results of IGRA or Mantoux tests among infant TBM were included for analysis. Data, such as age, sex, Mantoux test or IGRA, and cerebrospinal fluid (CSF) microbiological examinations (such as acid-fast bacilli (AFB) smear, TB PCR, and TB culture), were extracted from each study. Results A total of 31 articles were enrolled for further analysis, including 48 cases. The mean age was 9.4 ± 5.8 months and boys accounted for 57.1% of infants (24/42). Mantoux test was positive in 57.4% (27/47) of tested infants and IGRA was positive in 77.8% (7/9) of infants. In addition, among the infants with confirmed TB, 18 (52.9%, 18/34) of them have positive Mantoux responses and 7 (20.0%, 7/35) have positive IGRA results. Conclusions In low or intermediate TB burden countries, the Mantoux test has a poor performance for diagnosing TBM among infants, and IGRAs appear to have a moderate sensitivity for the diagnosis of infant TBM.

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Risk Factors for False-Negative Interferon-γ Release Assay Results in Culture-Confirmed Childhood TB

Cited by 10 publications

References 49 publications

Factors associated with differential T cell responses to antigens ESAT-6 and CFP-10 in pulmonary tuberculosis patients

Factors associated with differential T cell responses to antigens ESAT-6 and CFP-10 in pulmonary tuberculosis patients

Clinical relevance of false-negative interferon-gamma release assays in patients with tuberculous pleurisy in an intermediate tuberculosis burden country

Interferon-γ release assay and mantoux response in infants with tuberculous meningitis in low and intermediate burden countries

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