Lena Ronge1, Rosa Sloot1, Karen Du Preez1, Alexander W Kay2, H Lester Kirchner3, Harleen M S Grewal4,5, Anna M Mandalakas2, Anneke C Hesseling1. 1. From the Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa. 2. The Global Tuberculosis Program, Texas Children's Hospital, Department of Pediatrics, Baylor College of Medicine, Houston, Texas. 3. Department of Population Health Sciences, Geisinger Clinic, Danville, Pennsylvania. 4. Department of Clinical Science, BIDS Group, Faculty of Medicine, University of Bergen. 5. Department of Microbiology, Haukeland University Hospital, Bergen, Norway.
Abstract
BACKGROUND: The clinical utility of the magnitude of interferon gamma (IFNγ) in response to mycobacterial antigens is unknown. We assessed the association between quantitative IFNγ response and degree of Mycobacterium tuberculosis exposure, infection and tuberculosis (TB) disease status in children. METHODS: We completed cross-sectional analysis of children (≤15 years) exposed to an adult with bacteriologically confirmed TB, 2007-2012 in Cape Town, South Africa. IFNγ values were reported as concentrations and spot forming units for the QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB, respectively. Random-effects linear regression was used to investigate the relation between the M. tuberculosis contact score, clinical phenotype (TB diseased, infected, uninfected) and IFNγ▪response as outcome, adjusted for relevant covariates. RESULTS: We analyzed data from 669 children (median age, 63 months; interquartile range, 33-108 months). A 1-unit increase in M. tuberculosis contact score was associated with an increase of IFNγ 0.60 international unit/mL (95% confidence interval [CI], 0.44-0.76 international unit/mL), and IFNγ spot forming unit 2 counts (95% CI, 1-3). IFNγ response was significantly lower among children with M. tuberculosis infection compared with children with TB disease (β = -1.42; 95% CI, -2.80 to -0.03) for the QFT-GIT, but not for the T-SPOT.TB. This association was strongest among children 2-5 years (β = -2.35 years; 95% CI, -4.28 to -0.42 years) and absent if <2 years. CONCLUSIONS: The magnitude of IFNγ response correlated with the degree of recent M. tuberculosis exposure, measured by QFT-GIT and T-SPOT.TB, and was correlated with clinically relevant TB phenotypes using the QFT-GIT. IFNγ values are not only useful in estimating the risk of M. tuberculosis infection but may also support the diagnosis of TB disease in children. DISCUSSION: The magnitude of IFNγ response correlated with the degree of recent M. tuberculosis exposure, measured by QFT-GIT and T-SPOT.TB, and was correlated with clinically relevant TB phenotypes using the QFT-GIT. IFNγ values are not only useful in estimating the risk of M. tuberculosis infection but may also support the diagnosis of TB disease in children.
BACKGROUND: The clinical utility of the magnitude of interferon gamma (IFNγ) in response to mycobacterial antigens is unknown. We assessed the association between quantitative IFNγ response and degree of Mycobacterium tuberculosis exposure, infection and tuberculosis (TB) disease status in children. METHODS: We completed cross-sectional analysis of children (≤15 years) exposed to an adult with bacteriologically confirmed TB, 2007-2012 in Cape Town, South Africa. IFNγ values were reported as concentrations and spot forming units for the QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB, respectively. Random-effects linear regression was used to investigate the relation between the M. tuberculosis contact score, clinical phenotype (TB diseased, infected, uninfected) and IFNγ▪response as outcome, adjusted for relevant covariates. RESULTS: We analyzed data from 669 children (median age, 63 months; interquartile range, 33-108 months). A 1-unit increase in M. tuberculosis contact score was associated with an increase of IFNγ 0.60 international unit/mL (95% confidence interval [CI], 0.44-0.76 international unit/mL), and IFNγ spot forming unit 2 counts (95% CI, 1-3). IFNγ response was significantly lower among children with M. tuberculosis infection compared with children with TB disease (β = -1.42; 95% CI, -2.80 to -0.03) for the QFT-GIT, but not for the T-SPOT.TB. This association was strongest among children 2-5 years (β = -2.35 years; 95% CI, -4.28 to -0.42 years) and absent if <2 years. CONCLUSIONS: The magnitude of IFNγ response correlated with the degree of recent M. tuberculosis exposure, measured by QFT-GIT and T-SPOT.TB, and was correlated with clinically relevant TB phenotypes using the QFT-GIT. IFNγ values are not only useful in estimating the risk of M. tuberculosis infection but may also support the diagnosis of TB disease in children. DISCUSSION: The magnitude of IFNγ response correlated with the degree of recent M. tuberculosis exposure, measured by QFT-GIT and T-SPOT.TB, and was correlated with clinically relevant TB phenotypes using the QFT-GIT. IFNγ values are not only useful in estimating the risk of M. tuberculosis infection but may also support the diagnosis of TB disease in children.
Authors: Christina Lancioni; Melissa Nyendak; Sarah Kiguli; Sarah Zalwango; Tomi Mori; Harriet Mayanja-Kizza; Stephen Balyejusa; Megan Null; Joy Baseke; Deo Mulindwa; Laura Byrd; Gwendolyn Swarbrick; Christine Scott; Denise F Johnson; LaShaunda Malone; Philipa Mudido-Musoke; W Henry Boom; David M Lewinsohn; Deborah A Lewinsohn Journal: Am J Respir Crit Care Med Date: 2011-10-27 Impact factor: 21.405
Authors: Anna M Mandalakas; H Lester Kirchner; Gerhard Walzl; Robert P Gie; H Simon Schaaf; Mark F Cotton; Harleen M S Grewal; Anneke C Hesseling Journal: Am J Respir Crit Care Med Date: 2015-04-01 Impact factor: 21.405
Authors: Edhyana Sahiratmadja; Bachti Alisjahbana; Tjitske de Boer; Iskandar Adnan; Anugrah Maya; Halim Danusantoso; Ronald H H Nelwan; Sangkot Marzuki; Jos W M van der Meer; Reinout van Crevel; Esther van de Vosse; Tom H M Ottenhoff Journal: Infect Immun Date: 2006-12-04 Impact factor: 3.441
Authors: C S Hirsch; Z Toossi; C Othieno; J L Johnson; S K Schwander; S Robertson; R S Wallis; K Edmonds; A Okwera; R Mugerwa; P Peters; J J Ellner Journal: J Infect Dis Date: 1999-12 Impact factor: 5.226
Authors: A M Mandalakas; H L Kirchner; C Lombard; G Walzl; H M S Grewal; R P Gie; A C Hesseling Journal: Int J Tuberc Lung Dis Date: 2012-06-11 Impact factor: 2.373
Authors: Ben J Marais; Robert P Gie; H Simon Schaaf; Nulda Beyers; Peter R Donald; Jeff R Starke Journal: Am J Respir Crit Care Med Date: 2006-02-16 Impact factor: 21.405
Authors: James Ayieko; Lisa Abuogi; Brett Simchowitz; Elizabeth A Bukusi; Allan H Smith; Arthur Reingold Journal: BMC Infect Dis Date: 2014-02-20 Impact factor: 3.090