Tuberculin Skin Test Reversion following Isoniazid Preventive Therapy Reflects Diversity of Immune Response to Primary Mycobacterium tuberculosis Infection
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Date
2014
Journal Title
Journal ISSN
Volume Title
Publisher
Katalin Andrea Wilkinson
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-c) 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-c 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-c responses to MtbA85B or wMTB between groups. At conversion, stable converters demonstrated
significant increases in IFN-c responses to Ag85B and wMtb compared to enrollment (p = 0.001, p,0.001, respectively),
while there were no significant changes among reverters. Conclusions: TST reversion following IPT is common following primary Mtb infection and associated with unique patterns of Mtb-induced IFN-c production. We have demonstrated that immune responses to primary Mtb infection are heterogeneous, and submit that prospective longitudinal studies of cell mediated immune responses to Mtb infection be prioritized to identify immune phenotypes protective against development of TB disease.
Description
Keywords
Tuberculosis, Tuberculin, Skin Test, immunologic, public health
Citation
Citation: Johnson DF, Malone LL, Zalwango S, Mukisa Oketcho J, Chervenak KA, et al. (2014) Tuberculin Skin Test Reversion following Isoniazid Preventive Therapy Reflects Diversity of Immune Response to Primary Mycobacterium tuberculosis Infection. PLoS ONE 9(5): e96613. doi:10.1371/journal.pone.0096613