Serologic Responses in Childhood Pulmonary Tuberculosis

Bareng A.S. Nonyane, Mark P. Nicol, Nicholas J. Andreas, Stefanie Rimmele, Nicole Schneiderhan-Marra, Lesley J. Workman, Mark D. Perkins, Thomas Joos, Tobias Broger, Jerrold J. Ellner, David Alland, Beate Kampmann, Susan E. Dorman, Heather J. Zar

Research output: Research - peer-reviewArticle

Abstract

BACKGROUND:: Identification of the Mycobacterium tuberculosis immunoproteome and antigens associated with serologic responses in adults has renewed interest in developing a serologic test for childhood tuberculosis (TB). We investigated IgG antibody responses against M. tuberculosis antigens in children with well-characterized TB. METHODS:: We studied archived sera obtained from hospitalized children with suspected pulmonary TB, and classified as having confirmed TB (culture-confirmed), unlikely TB (clinical improvement without TB treatment), or unconfirmed TB (all others). A multiplexed bead-based assay for IgG antibodies against 119 M. tuberculosis antigens was developed, validated and used to test sera. The areas under the curves (AUC) of the empiric receiver-operator characteristic curves were generated as measures of predictive ability. A cross-validated generalized linear model was used to select the most predictive combinations of antigens. RESULTS:: For the confirmed TB versus unlikely TB comparison, the maximal single antigen AUC was 0.63, corresponding to sensitivity 0.60 and specificity 0.60. Older (age 60+ months) children’s responses were better predictive of TB status than younger (age 12-59 months) children’s, with a maximal single antigen AUC of -0.76. For the confirmed TB versus unlikely TB groups, the most predictive combinations of antigens assigned TB risk probabilities of 0.33 and 0.33, respectively, when all ages were considered, and 0.57 (IQR 0.48, 0.64) and 0.35 (IQR 0.32, 0.40) when only older children were considered. CONCLUSION:: An antigen-based IgG test is unlikely to meet the performance characteristics required of a TB detection test applicable to all age groups.

LanguageEnglish (US)
JournalPediatric Infectious Disease Journal
DOIs
StateAccepted/In press - Jul 15 2017

Fingerprint

Pulmonary Tuberculosis
Tuberculosis
Antigens
Area Under Curve
Immunoglobulin G
Mycobacterium tuberculosis antigens
Serum
Hospitalized Child
Serologic Tests
Antibody Formation
Linear Models
Age Groups
Sensitivity and Specificity
Antibodies
Therapeutics

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Nonyane, B. A. S., Nicol, M. P., Andreas, N. J., Rimmele, S., Schneiderhan-Marra, N., Workman, L. J., ... Zar, H. J. (2017). Serologic Responses in Childhood Pulmonary Tuberculosis. Pediatric Infectious Disease Journal. DOI: 10.1097/INF.0000000000001683

Serologic Responses in Childhood Pulmonary Tuberculosis. / Nonyane, Bareng A.S.; Nicol, Mark P.; Andreas, Nicholas J.; Rimmele, Stefanie; Schneiderhan-Marra, Nicole; Workman, Lesley J.; Perkins, Mark D.; Joos, Thomas; Broger, Tobias; Ellner, Jerrold J.; Alland, David; Kampmann, Beate; Dorman, Susan E.; Zar, Heather J.

In: Pediatric Infectious Disease Journal, 15.07.2017.

Research output: Research - peer-reviewArticle

Nonyane, BAS, Nicol, MP, Andreas, NJ, Rimmele, S, Schneiderhan-Marra, N, Workman, LJ, Perkins, MD, Joos, T, Broger, T, Ellner, JJ, Alland, D, Kampmann, B, Dorman, SE & Zar, HJ 2017, 'Serologic Responses in Childhood Pulmonary Tuberculosis' Pediatric Infectious Disease Journal. DOI: 10.1097/INF.0000000000001683
Nonyane BAS, Nicol MP, Andreas NJ, Rimmele S, Schneiderhan-Marra N, Workman LJ et al. Serologic Responses in Childhood Pulmonary Tuberculosis. Pediatric Infectious Disease Journal. 2017 Jul 15. Available from, DOI: 10.1097/INF.0000000000001683
Nonyane, Bareng A.S. ; Nicol, Mark P. ; Andreas, Nicholas J. ; Rimmele, Stefanie ; Schneiderhan-Marra, Nicole ; Workman, Lesley J. ; Perkins, Mark D. ; Joos, Thomas ; Broger, Tobias ; Ellner, Jerrold J. ; Alland, David ; Kampmann, Beate ; Dorman, Susan E. ; Zar, Heather J./ Serologic Responses in Childhood Pulmonary Tuberculosis. In: Pediatric Infectious Disease Journal. 2017
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abstract = "BACKGROUND:: Identification of the Mycobacterium tuberculosis immunoproteome and antigens associated with serologic responses in adults has renewed interest in developing a serologic test for childhood tuberculosis (TB). We investigated IgG antibody responses against M. tuberculosis antigens in children with well-characterized TB. METHODS:: We studied archived sera obtained from hospitalized children with suspected pulmonary TB, and classified as having confirmed TB (culture-confirmed), unlikely TB (clinical improvement without TB treatment), or unconfirmed TB (all others). A multiplexed bead-based assay for IgG antibodies against 119 M. tuberculosis antigens was developed, validated and used to test sera. The areas under the curves (AUC) of the empiric receiver-operator characteristic curves were generated as measures of predictive ability. A cross-validated generalized linear model was used to select the most predictive combinations of antigens. RESULTS:: For the confirmed TB versus unlikely TB comparison, the maximal single antigen AUC was 0.63, corresponding to sensitivity 0.60 and specificity 0.60. Older (age 60+ months) children’s responses were better predictive of TB status than younger (age 12-59 months) children’s, with a maximal single antigen AUC of -0.76. For the confirmed TB versus unlikely TB groups, the most predictive combinations of antigens assigned TB risk probabilities of 0.33 and 0.33, respectively, when all ages were considered, and 0.57 (IQR 0.48, 0.64) and 0.35 (IQR 0.32, 0.40) when only older children were considered. CONCLUSION:: An antigen-based IgG test is unlikely to meet the performance characteristics required of a TB detection test applicable to all age groups.",
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AU - Nonyane,Bareng A.S.

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AU - Andreas,Nicholas J.

AU - Rimmele,Stefanie

AU - Schneiderhan-Marra,Nicole

AU - Workman,Lesley J.

AU - Perkins,Mark D.

AU - Joos,Thomas

AU - Broger,Tobias

AU - Ellner,Jerrold J.

AU - Alland,David

AU - Kampmann,Beate

AU - Dorman,Susan E.

AU - Zar,Heather J.

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N2 - BACKGROUND:: Identification of the Mycobacterium tuberculosis immunoproteome and antigens associated with serologic responses in adults has renewed interest in developing a serologic test for childhood tuberculosis (TB). We investigated IgG antibody responses against M. tuberculosis antigens in children with well-characterized TB. METHODS:: We studied archived sera obtained from hospitalized children with suspected pulmonary TB, and classified as having confirmed TB (culture-confirmed), unlikely TB (clinical improvement without TB treatment), or unconfirmed TB (all others). A multiplexed bead-based assay for IgG antibodies against 119 M. tuberculosis antigens was developed, validated and used to test sera. The areas under the curves (AUC) of the empiric receiver-operator characteristic curves were generated as measures of predictive ability. A cross-validated generalized linear model was used to select the most predictive combinations of antigens. RESULTS:: For the confirmed TB versus unlikely TB comparison, the maximal single antigen AUC was 0.63, corresponding to sensitivity 0.60 and specificity 0.60. Older (age 60+ months) children’s responses were better predictive of TB status than younger (age 12-59 months) children’s, with a maximal single antigen AUC of -0.76. For the confirmed TB versus unlikely TB groups, the most predictive combinations of antigens assigned TB risk probabilities of 0.33 and 0.33, respectively, when all ages were considered, and 0.57 (IQR 0.48, 0.64) and 0.35 (IQR 0.32, 0.40) when only older children were considered. CONCLUSION:: An antigen-based IgG test is unlikely to meet the performance characteristics required of a TB detection test applicable to all age groups.

AB - BACKGROUND:: Identification of the Mycobacterium tuberculosis immunoproteome and antigens associated with serologic responses in adults has renewed interest in developing a serologic test for childhood tuberculosis (TB). We investigated IgG antibody responses against M. tuberculosis antigens in children with well-characterized TB. METHODS:: We studied archived sera obtained from hospitalized children with suspected pulmonary TB, and classified as having confirmed TB (culture-confirmed), unlikely TB (clinical improvement without TB treatment), or unconfirmed TB (all others). A multiplexed bead-based assay for IgG antibodies against 119 M. tuberculosis antigens was developed, validated and used to test sera. The areas under the curves (AUC) of the empiric receiver-operator characteristic curves were generated as measures of predictive ability. A cross-validated generalized linear model was used to select the most predictive combinations of antigens. RESULTS:: For the confirmed TB versus unlikely TB comparison, the maximal single antigen AUC was 0.63, corresponding to sensitivity 0.60 and specificity 0.60. Older (age 60+ months) children’s responses were better predictive of TB status than younger (age 12-59 months) children’s, with a maximal single antigen AUC of -0.76. For the confirmed TB versus unlikely TB groups, the most predictive combinations of antigens assigned TB risk probabilities of 0.33 and 0.33, respectively, when all ages were considered, and 0.57 (IQR 0.48, 0.64) and 0.35 (IQR 0.32, 0.40) when only older children were considered. CONCLUSION:: An antigen-based IgG test is unlikely to meet the performance characteristics required of a TB detection test applicable to all age groups.

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