Risk Factors for Indeterminate Interferon-Gamma Release Assay for the Diagnosis of Tuberculosis in Children—A Systematic Review and Meta-Analysis

Meier, Noëmi; Volken, Thomas; Geiger, Marc; Heininger, Ulrich; Tebruegge, Marc; Ritz, Nicole

doi:10.3389/fped.2019.00208

Cited by 40 publications

(49 citation statements)

References 162 publications

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“…In addition, the participants' younger age likely affected our observed results. Because of the age-dependent maturation of the immune system, children's IFN-γ production tends to be lower and the contribution of T-cells producing IFN-γ is thought to be less compared to adults [4,27,28].…”

Section: Discussionmentioning

confidence: 99%

“…Screening for Mycobacterium tuberculosis complex (MTBC) infection is done by the widely implemented tuberculin skin test (TST) or the interferon gamma (IFN-γ) release assay (IGRA), both assessing the host's cell mediated immune response to tuberculous antigens [3]. Both tests have their limitations [4]. The TST -employing purified protein derivative (PPD) as antigen-has a low specificity due to cross reactivity with Bacillus Calmette-Guérin (BCG) vaccination and exposure to non-pathogenic environmental mycobacteria [5].…”

Section: Introductionmentioning

confidence: 99%

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Use of resuscitation promoting factors to screen for tuberculosis infection in household-exposed children in The Gambia

et al. 2020

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Background: Interferon-γ release assays (IGRA) with Resuscitation promoting factor (Rpf) proteins enhanced tuberculosis (TB) screening and diagnosis in adults but have not been evaluated in children. Children often develop paucibacillary TB and their immune response differs from that of adults, which together affect TB disease diagnostics and immunodiagnostics. We assessed the ability of Rpf to identify infection among household TBexposed children in The Gambia and investigated their ability to discriminate Mycobacterium tuberculosis complex (MTBC) infection from active TB disease in children. Methods: Detailed clinical investigations were done on 93 household TB-exposed Gambian children and a tuberculin skin test (TST) was administered to asymptomatic children. Venous blood was collected for overnight stimulation with ESAT-6/CFP-10-fusion protein (EC), purified protein derivative and RpfA, B, C, D and E. Interferon gamma (IFN-γ) production was measured by ELISA in supernatants and corrected for the background level. Infection status was defined by IGRA with EC and TB disease by mycobacterial confirmation and/or clinical diagnosis. We compared IFN-γ levels between infected and uninfected children and between infected and TB diseased children using a binomial logistic regression model while correcting for age and sex. A Receiver Operating Characteristics analysis was done to find the best cutoff for IFN-γ level and calculate sensitivity and specificity. Results: Interferon gamma production was significantly higher in infected (IGRA+, n = 45) than in uninfected (IGRA-, n = 20) children after stimulation with RpfA, B, C, and D (P = 0.03; 0.007; 0.03 and 0.003, respectively). Using RpfB and D-specific IFN-γ cutoffs (33.9 pg/mL and 67.0 pg/mL), infection was classified with a sensitivity-specificity combination of 73-92% and 77-72% respectively, which was similar to and better than 65-75% for TST. Moreover, IFN-γ production was higher in infected than in TB diseased children (n = 28, 5 bacteriologically confirmed, 23 clinically diagnosed), following RpfB and D stimulation (P = 0.02 and 0.03, respectively).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Use of resuscitation promoting factors to screen for tuberculosis infection in household-exposed children in The Gambia

et al. 2020

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“…In a systematic review and a meta‐analysis that was performed with paediatric TB cases, no statistically significant difference was noted in indeterminate results between different age groups. However, in studies performed in Africa and in non‐human immunodeficiency virus‐infected immunocompromised patients, analyses with T‐SPOT.TB were shown to have a lower frequency of indeterminate results compared to QuantiFERON‐TB analyses . In a study with 2173 subjects, 10 patients were found to have indeterminate QTF‐GIT results.…”

Section: Discussionmentioning

confidence: 95%

Evaluation of QuantiFERON tuberculosis Gold In‐Tube assay for diagnosis of active tuberculosis in children

Zübarioğlu

Bayraktar

Dalgıç

et al. 2019

J Paediatrics Child Health

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Aim: Tuberculin skin test (TST) is still used in diagnostic algorithms of childhood tuberculosis (TB). QuantiFERON TB Gold In-Tube assay (QFT-GIT) is an alternative test to TST based on the detection of interferon-gamma release upon in vitro induction of peripheral mononuclear cells by TB antigens. In this study, we aimed to determine the diagnostic value and performance of QFT-GIT for active childhood TB. Methods: This retrospective study was conducted between January 2005 and December 2011 in three referral hospitals in Turkey with 124 children who were diagnosed with definite active TB. Sensitivity values of TST and QFT-GIT were determined by accepting the microbiological confirmation as the gold standard of diagnosis of TB. Results: In our study, sensitivity of QFT-GIT and TST was found to be 65 and 66% respectively. However, combined usage of QFT-GIT and TST was found to be more sensitive (85%) than TST or QFT-GIT alone (P < 0.0001). Although negative results of QFT-GIT or TST did not exclude the diagnosis of active TB in children, their positivity supported the diagnosis. Specificity could not be measured as only microbiologically confirmed cases of Mycobacterium tuberculosis disease were enrolled in the study. Conclusion: Although sensitivities of TST and QFT-GIT are too low to exclude active TB, their positivity supports diagnosis of active TB in children concomitant with signs and symptoms. QFT-GIT and TST should be used together to enhance diagnostic sensitivity and could help exclude a diagnosis of TB if the pretest probability is low.

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“…Screening for Mycobacterium tuberculosis complex (MTBC) infection is done by the widely implemented tuberculin skin test (TST) or the interferon gamma (IFN-γ) release assay (IGRA), both assessing the host's cell mediated immune response to tuberculous antigens [3]. Both tests have their limitations [4]. The TST -employing puri ed protein derivative (PPD) as antigen-has a low speci city due to cross reactivity with Bacillus Calmette-Guérin (BCG) vaccination and exposure to nonpathogenic environmental mycobacteria [5].…”

Section: Introductionmentioning

confidence: 99%

Use of Resuscitation promoting factors to screen for tuberculosis infection in household-exposed children in The Gambia

Loon

Gomez

Jobe

et al. 2020

Preprint

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Abstract Background Interferon-γ release assays (IGRA) with Resuscitation promoting factor (Rpf) proteins enhanced tuberculosis (TB) screening and diagnosis in adults but have not been evaluated in children. Children often develop paucibacillary TB and their immune response differs from that of adults, which together affect TB disease diagnostics and immunodiagnostics. We assessed the ability of Rpf to identify infection among household TB-exposed children in The Gambia and investigated their ability to discriminate Mycobacterium tuberculosis complex (MTBC) infection from active TB disease in children. Methods Detailed clinical investigations were done on 93 household TB-exposed Gambian children and a tuberculin skin test (TST) was administered to asymptomatic children. Venous blood was collected for overnight stimulation with ESAT-6/CFP-10-fusion protein (EC), purified protein derivative and RpfA, B, C, D and E. Interferon gamma (IFN-γ) production was measured by ELISA in supernatants and corrected for the background level. Infection status was defined by IGRA with EC and TB disease by mycobacterial confirmation and/or clinical diagnosis. We compared IFN-γ levels between infected and uninfected children and between infected and TB diseased children using a binomial logistic regression model while correcting for age and sex. A Receiver Operating Characteristics analysis was done to find the best cut-off for IFN-γ level and calculate sensitivity and specificity. Results Interferon gamma production was significantly higher in infected (IGRA+, n=45) than in uninfected (IGRA-, n=20) children after stimulation with RpfA, B, C, and D (P = 0.03; 0.007; 0.03 and 0.003, respectively). Using RpfB and D-specific IFN-γ cut-offs (33.9 pg/mL and 67.0 pg/mL), infection was classified with a sensitivity-specificity combination of 73%-92% and 77%-72% respectively, which was similar to and better than 65%-75% for TST. Moreover, IFN-γ production was higher in infected than in TB diseased children (n=28, 5 bacteriologically confirmed, 23 clinically diagnosed), following RpfB and D stimulation (P = 0.02 and 0.03, respectively). Conclusion RpfB and RpfD show promising results for childhood MTBC infection screening, and both performed similar to and better than the TST in our study population. Additionally, both antigens appear to discriminate between infection and disease in children and thus warrant further investigation as screening and diagnostic antigens for childhood TB.

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Risk Factors for Indeterminate Interferon-Gamma Release Assay for the Diagnosis of Tuberculosis in Children—A Systematic Review and Meta-Analysis

Cited by 40 publications

References 162 publications

Use of resuscitation promoting factors to screen for tuberculosis infection in household-exposed children in The Gambia

Use of resuscitation promoting factors to screen for tuberculosis infection in household-exposed children in The Gambia

Evaluation of QuantiFERON tuberculosis Gold In‐Tube assay for diagnosis of active tuberculosis in children

Use of Resuscitation promoting factors to screen for tuberculosis infection in household-exposed children in The Gambia

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