Tuberculosis detection in nonhuman primates is enhanced by use of testing algorithms that include an interferon-γ release assay

Abstract OBJECTIVE To develop a testing algorithm that incorporates multiple assays to evaluate host cellular and humoral immunity and antigen detection concerning Mycobacterium tuberculosis complex (MTBC) infection in captive nonhuman primates. ANIMALS Cohorts of captive-bred and wild-caught macaques from 5 different geographic regions. PROCEDURES Macaques were tested for MTBC infection by use of a γ interferon tuberculosis (GIFT) assay, an interferon-γ release assay, and other assays. In the first 2 cohorts (n = 15 and 181), initial validation of the GIFT assay was performed by use of experimentally infected and unexposed control macaques. In the next 3 cohorts (n = 59, 42, and 11), results were obtained for opportunistically collected samples from macaques exposed during spontaneous outbreaks. RESULTS Sensitivity and specificity of the GIFT assay in the control cohorts were 100% and 97%, respectively, and were variable but enhanced by incorporating results from multiple assays in spontaneous outbreaks. CLINICAL RELEVANCE The detection and management of MTBC infection in captive nonhuman primate populations is an ongoing challenge, especially with animal imports and transfers. Despite standardized practices of initial quarantine with regular intradermal tuberculin skin testing, spontaneous outbreaks continue to be reported. Since infection encompasses a range of disease manifestations over time, a testing algorithm that incorporates multiple assays, such as the GIFT assay, to evaluate host cellular and humoral immunity in addition to agent detection is needed. Testing a combination of samples from controlled studies and spontaneous outbreaks of MTBC infection in nonhuman primates would advance the development and validation of a functional algorithm that incorporates promising tools such as the GIFT assay.

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Comparison between a Whole Blood Interferon‐γ Release Assay and Tuberculin Skin Testing for the Detection of Tuberculosis Infection among Patients at Risk for Tuberculosis Exposure

The Journal of Infectious Diseases ◽

10.1086/314707 ◽

1999 ◽

Vol 179 (5) ◽

pp. 1297-1300 ◽

Cited By ~ 31

Author(s):

Moriyo Kimura ◽

Paul J. Converse ◽

Jacqueline Astemborski ◽

James S. Rothel ◽

David Vlahov ◽

...

Keyword(s):

At Risk ◽

Whole Blood ◽

Skin Testing ◽

Interferon Γ ◽

Tuberculosis Infection ◽

Tuberculin Skin Testing ◽

Patients At Risk ◽

Release Assay

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Comparison of an Interferon-γ 947; Release Assay with Tuberculin Skin Testing in HIV-infected Individuals

Yearbook of Pulmonary Disease ◽

10.1016/s8756-3452(08)79207-7 ◽

2009 ◽

Vol 2009 ◽

pp. 343-346

Author(s):

L.T. Tanoue

Keyword(s):

Skin Testing ◽

Interferon Γ ◽

Tuberculin Skin Testing ◽

Release Assay

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Comparison of an Interferon-γ Release Assay with Tuberculin Skin Testing in HIV-infected Individuals

American Journal of Respiratory and Critical Care Medicine ◽

10.1164/rccm.200608-1088oc ◽

2007 ◽

Vol 175 (7) ◽

pp. 737-742 ◽

Cited By ~ 129

Author(s):

Annie F. Luetkemeyer ◽

Edwin D. Charlebois ◽

Laura L. Flores ◽

David R. Bangsberg ◽

Steven G. Deeks ◽

...

Keyword(s):

Skin Testing ◽

Interferon Γ ◽

Tuberculin Skin Testing ◽

Release Assay

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Interferon-γ Release Assay vs. Tuberculin Skin Test for Tuberculosis Screening in Exposed Healthcare Workers: A Longitudinal Multicenter Comparative Study

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2015.19 ◽

2015 ◽

Vol 36 (5) ◽

pp. 569-574 ◽

Cited By ~ 6

Author(s):

Jean-Christophe Lucet ◽

Dominique Abiteboul ◽

Candice Estellat ◽

Carine Roy ◽

Sylvie Chollet-Martin ◽

...

Keyword(s):

High Risk ◽

Healthcare Workers ◽

Skin Testing ◽

Interferon Γ ◽

Tuberculin Skin Testing ◽

Tuberculosis Screening ◽

Clinical Trial Registration ◽

Current Function ◽

History Of ◽

Release Assay

OBJECTIVEHealthcare workers (HCWs), especially those caring for patients with tuberculosis (TB), are at high risk of acquiring that disease. The poor specificity of tuberculin skin testing (TST) prompted us to evaluate the effectiveness of the interferon-γ release assay (IGRA) in comparison with TST in a large prospective, multicenter, 1-year study of HCWs with occupational exposure to TB.METHODSHCWs from high-risk units at 14 university hospitals were invited to participate and underwent both TST and IGRA (first Quantiferon TB Gold-IT®, QFT-G, then T-SPOT.TB® if QFT-G was indeterminate) at baseline and after 1 year. We collected demographic characteristics, country of birth, history of TB, immunosuppression, past exposure to TB, history of BCG vaccination, results of most recent TST, job category, and duration of current function.RESULTSAmong 807 HCWs enrolled, current or past TST at baseline was positive (≥15 mm) in 282 (34.9%); the IGRA was positive in 113 (14.0%) and indeterminate in 3 (0.4%). After 1 year, 594 HCWs had both an IGRA and TST (or prior TST≥15 mm) at baseline and an IGRA and TST (if indicated). The conversion rate was 2.5% (9 of 367) with TST and 7.6% (45 of 594) with IGRA, with poor agreement between the 2 tests. Using only QFT-G, conversion (9.9%) and reversion (17.8%) rates were higher for baseline QFT-G positive quantitative values <1 IU/mL.CONCLUSIONTST and the IGRA yielded discordant results. The value of IGRA in addition to TST remains undetermined; the two should be jointly interpreted in decision-making (clinical trial registration NCT00797836).Infect Control Hosp Epidemiol 2015;00(0): 1–6

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Distribution and expression of esat-6 and cfp-10 in non-tuberculous mycobacteria isolated from lymph nodes of slaughtered cattle in Switzerland

Journal of Veterinary Diagnostic Investigation ◽

10.1177/1040638718824074 ◽

2019 ◽

Vol 31 (2) ◽

pp. 217-221 ◽

Cited By ~ 1

Author(s):

Simone Scherrer ◽

Patricia Landolt ◽

Ute Friedel ◽

Roger Stephan

Keyword(s):

Lymph Nodes ◽

Skin Testing ◽

Control Program ◽

Interferon Γ ◽

Immune Reactivity ◽

Tuberculin Skin Testing ◽

Tuberculosis Control ◽

Release Assay ◽

Positive Results

The most commonly used tools for tuberculosis testing in cattle, the tuberculin skin test and the interferon-γ release assay, detect immune reactivity to various antigens of Mycobacterium bovis, including ESAT-6 and CFP-10. However, some non-tuberculous mycobacteria (NTM) can also harbor the cfp-10 and/or esat-6 genes, which can lead to false-positive results. We tested 77 NTM isolates belonging to 22 different species from lymph nodes of healthy slaughtered cattle for the occurrence of cfp-10 and esat-6. Most isolates did not harbor cfp-10 and esat-6. However, M. gordonae, ‘M. lymphaticum’, M. kansasii, and M. persicum were cfp-10 positive. The esat-6 gene was found in M. kansasii and M. persicum. Protein expression of cfp-10 and esat-6 could be detected for M. kansasii and M. persicum. An effective tuberculosis control program based on interferon-γ release assays and tuberculin skin testing is dependent on further monitoring and characterization of NTM in a cattle population.

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