Dataset Information

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

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-?) 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-? 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-? responses to MtbA85B or wMTB between groups. At conversion, stable converters demonstrated significant increases in IFN-? 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-? 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.

SUBMITTER: Johnson DF

PROVIDER: S-EPMC4010490 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

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

Johnson Denise F DF Malone LaShaunda L LL Zalwango Sarah S Mukisa Oketcho Joy J Chervenak Keith A KA Thiel Bonnie B Mayanja-Kizza Harriet H Stein Catherine M CM Boom W Henry WH Lancioni Christina L CL

PloS one 20140505 5

<h4>Rationale</h4>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.<h4>Objectives</h4>To measure frequency of TST reversion following IPT, and variation in interferon-gamma (IFN-γ) responses to M ...[more]

PMID: 24796677

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Project description:National guidelines recommend screening for latent tuberculosis infection (LTBI) in all HIV-infected patients. Thus, the objective of this study was to measure protocol adherence to national guidelines regarding LTBI screening for HIV-infected patients entering care at an urban primary care clinic specializing in HIV care, identify clinical and other characteristics associated with adherence, and determine whether transitioning from the tuberculin skin test (TST) to the interferon-gamma release assay (IGRA) improved adherence. We conducted a retrospective study using protocol adherence to LTBI screening guidelines within twelve months of entering care at an HIV clinic as the primary outcome. Successful protocol adherence was defined as the placement and reading of a TST, performance of an IGRA, or a note in study clinic records documenting prior testing or treatment for tuberculosis in an outside setting. Multivariable modified Poisson regression models were used in analyses. Overall, 32% (n?=?118/372) of patients received LTBI screening within twelve months of entering care. Protocol adherence to LTBI screening guidelines increased from 28% to 37% following the transition from TST to IGRA screening. IGRA screening [adjusted prevalence ratio: 1.45, 95% confidence limits: (1.07, 1.96)], male sex [1.47 (1.05, 2.07)], transfer patient status [1.51 (1.05, 2.18)], and greater than one year of clinic attendance [1.62 (1.06, 2.48)] were independently associated with protocol adherence. Among patients without prior LTBI screening or treatment, patients entering the clinic in 2013 under the IGRA screening protocol were more likely to be screened for LTBI compared to patients entering under the TST screening protocol (34.3% vs. 9.7%, p?<?0.001). In conclusion, transitioning from TST to IGRA-based screening improved adherence to screening guidelines. However, further work on improving adherence to LTBI screening guidelines among HIV-infected patients is needed.

Dataset Information

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

Rationale

Objectives

Methods

Results

Conclusions

Publications

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

Similar Datasets

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