Tuberculin skin test reversion following isoniazid preventive therapy reflects diversity of immune response to primary Mycobacterium tuberculosis infection

Denise F. Johnson, LaShaunda L. Malone, Sarah Zalwango, Joy Mukisa Oketcho, Keith A. Chervenak, Bonnie Thiel, Harriet Mayanja-Kizza, Catherine M. Stein, W. Henry Boom, Christina Lancioni

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Rationale: Healthy household contacts (HHC) of individuals with Tuberculosis (TB) with Tuberculin Skin Test (TST) conversions are considered to harbor latent Mycobacterium tuberculosis (Mtb), and at risk for TB. The immunologic, clinical, and public health implications of TST reversions that occur following Isoniazid preventive therapy (IPT) remain controversial. Objectives: To measure frequency of TST reversion following IPT, and variation in interferon-gamma (IFN-γ) responses to Mtb, in healthy Ugandan TB HHC with primary Mtb infection evidenced by TST conversion. Methods: Prospective cohort study of healthy, HIV-uninfected, TST-negative TB HHC with TST conversions. Repeat TST was performed 12 months following conversion (3 months following completion of 9 month IPT course) to assess for stable conversion vs. reversion. Whole blood IFN-γ responses to Mtb antigen 85B (MtbA85B) and whole Mtb bacilli (wMtb) were measured in a subset (n = 27 and n = 42, respectively) at enrollment and TST conversion, prior to initiation of IPT. Results: Of 122 subjects, TST reversion was noted in 25 (20.5%). There were no significant differences in demographic, clinical, or exposure variables between reverters and stable converters. At conversion, reverters had significantly smaller TST compared to stable converters (13.7 mm vs 16.4 mm, respectively; p = 0.003). At enrollment, there were no significant differences in IFN-γ responses to MtbA85B or wMTB between groups. At conversion, stable converters demonstrated significant increases in IFN-γ responses to Ag85B and wMtb compared to enrollment (p = 0.001, p

Original languageEnglish (US)
Article numbere96613
JournalPLoS One
Volume9
Issue number5
DOIs
StatePublished - May 5 2014

Fingerprint

isoniazid
Tuberculin Test
Mycobacterium Infections
tuberculin
skin tests
Tuberculin
Isoniazid
Mycobacterium tuberculosis
Skin Tests
Skin
immune response
therapeutics
infection
interferon-gamma
tuberculosis
Interferon-gamma
Tuberculosis
Therapeutics
households
Bacilli

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Tuberculin skin test reversion following isoniazid preventive therapy reflects diversity of immune response to primary Mycobacterium tuberculosis infection. / Johnson, Denise F.; Malone, LaShaunda L.; Zalwango, Sarah; Oketcho, Joy Mukisa; Chervenak, Keith A.; Thiel, Bonnie; Mayanja-Kizza, Harriet; Stein, Catherine M.; Boom, W. Henry; Lancioni, Christina.

In: PLoS One, Vol. 9, No. 5, e96613, 05.05.2014.

Research output: Contribution to journalArticle

Johnson, DF, Malone, LL, Zalwango, S, Oketcho, JM, Chervenak, KA, Thiel, B, Mayanja-Kizza, H, Stein, CM, Boom, WH & Lancioni, C 2014, 'Tuberculin skin test reversion following isoniazid preventive therapy reflects diversity of immune response to primary Mycobacterium tuberculosis infection', PLoS One, vol. 9, no. 5, e96613. https://doi.org/10.1371/journal.pone.0096613
Johnson, Denise F. ; Malone, LaShaunda L. ; Zalwango, Sarah ; Oketcho, Joy Mukisa ; Chervenak, Keith A. ; Thiel, Bonnie ; Mayanja-Kizza, Harriet ; Stein, Catherine M. ; Boom, W. Henry ; Lancioni, Christina. / Tuberculin skin test reversion following isoniazid preventive therapy reflects diversity of immune response to primary Mycobacterium tuberculosis infection. In: PLoS One. 2014 ; Vol. 9, No. 5.
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abstract = "Rationale: Healthy household contacts (HHC) of individuals with Tuberculosis (TB) with Tuberculin Skin Test (TST) conversions are considered to harbor latent Mycobacterium tuberculosis (Mtb), and at risk for TB. The immunologic, clinical, and public health implications of TST reversions that occur following Isoniazid preventive therapy (IPT) remain controversial. Objectives: To measure frequency of TST reversion following IPT, and variation in interferon-gamma (IFN-γ) responses to Mtb, in healthy Ugandan TB HHC with primary Mtb infection evidenced by TST conversion. Methods: Prospective cohort study of healthy, HIV-uninfected, TST-negative TB HHC with TST conversions. Repeat TST was performed 12 months following conversion (3 months following completion of 9 month IPT course) to assess for stable conversion vs. reversion. Whole blood IFN-γ responses to Mtb antigen 85B (MtbA85B) and whole Mtb bacilli (wMtb) were measured in a subset (n = 27 and n = 42, respectively) at enrollment and TST conversion, prior to initiation of IPT. Results: Of 122 subjects, TST reversion was noted in 25 (20.5{\%}). There were no significant differences in demographic, clinical, or exposure variables between reverters and stable converters. At conversion, reverters had significantly smaller TST compared to stable converters (13.7 mm vs 16.4 mm, respectively; p = 0.003). At enrollment, there were no significant differences in IFN-γ responses to MtbA85B or wMTB between groups. At conversion, stable converters demonstrated significant increases in IFN-γ responses to Ag85B and wMtb compared to enrollment (p = 0.001, p",
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