Performance of a T-cell-based diagnostic test for tuberculosis infection in HIV-infected individuals is independent of CD4 cell count

Dheda, Keertan; Lalvani, Ajit; Miller, R F; Scott, G.M.; Booth, Helen; Johnson, Margaret; Zumla, Alimuddin; Rook, G.A.W.

doi:10.1097/01.aids.0000191923.08938.5b

Cited by 114 publications

(71 citation statements)

References 23 publications

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“…It suggests that the T-SPOT.TB TM test maintains sensitivity and performance in immunosuppressed patients (a finding recently confirmed in HIV patients [24]) and can identify infected patients anergic to the tuberculin skin test. Further investigation is required to prove whether the present observations can be corroborated by larger-scale studies.…”

Section: Discussionmentioning

confidence: 73%

Use of a T-cell-based test for detection of tuberculosis infection among immunocompromised patients

Piana¹,

Codecasa

Cavallerio

et al. 2006

European Respiratory Journal

105

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The aim of this study was to compare the performance of the T-SPOT.TB TM test, a Tcell-based test, with the tuberculin skin test (TST) in the diagnosis of latent tuberculosis (TB) infection.The study was carried out in 138 immunosuppressed haematology patients who had been nosocomially exposed to a case of smear-positive TB.Overall, 44.2% of the contacts were positive by T-SPOT.TB TM test, and 17.4% by TST (concordance 67.8%). The apparent prevalence of infection fell from 25.9 to 14.5% with the TST with increasing immunosuppression, although this difference was not significant. In contrast, the apparent prevalence of infection with the T-SPOT.TB TM test was unaffected at 44.6 and 44.3%, respectively. The T-SPOT.TB TM test had an overall indeterminate rate of 4.3%, and this was also unaffected by the level of immunosuppression. This study suggests that the T-SPOT.TB TM test maintains its sensitivity and performance in immunocompromised patients, identifying a large number of truly infected patients anergic to the tuberculin skin test.

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Section: Discussionmentioning

confidence: 73%

Use of a T-cell-based test for detection of tuberculosis infection among immunocompromised patients

Piana¹,

Codecasa

Cavallerio

et al. 2006

European Respiratory Journal

105

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“…Prior reports examined T cell proliferation Naik et al, 2002;Pal et al, 2005;Srivastava et al, 2007) or flow cytometry (Srivastava et al, 2007) as a surrogate marker for CMI responses to HEV, however, the sensitivity and specificity of these assays were low. During the last ten years, highly sensitive IFN-γ ELISPOT assays have been used successfully for measuring the CMI responses in different diseases (Dheda et al, 2005;Liu et al, 2006;Sun et al, 2003). ELISPOT assays detect Agspecific T cells at frequencies as low as 1:100,000 (Lalvani et al, 1997;McCutcheon et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Characterization of hepatitis E-specific cell-mediated immune response using IFN-γ ELISPOT assay

Shata

Barrett

Shire

et al. 2007

Journal of Immunological Methods

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In developing countries, hepatitis E (HEV) and hepatitis A (HAV) are the major causes of acute viral hepatitis with similar fecooral modes of transmission. In contrast to the high seroprevalence of hepatitis A infection, a low seroprevalence of HEV among children in endemic areas has been reported. These data suggest the possibility that silent HEV infection is undiagnosed by the current available methods. Many of the serological tests used for HEV diagnosis have poor specificity and are unable to differentiate among different genotypes of HEV. Moreover, the RT-PCR used for HEV isolation is only valid for a brief period during the acute stage of infection. Cell-mediated immune (CMI) responses are highly sensitive, and long lasting after sub-clinical infections as shown in HCV and HIV. Our objective was to develop a quantitative assay for cell-mediated immune (CMI) responses in HEV infection as a surrogate marker for HEV exposure in silent infection. Quantitative assessment of the CMI responses in HEV will also help us to evaluate the role of CMI in HEV morbidity. In this study, an HEV-specific interferon-gamma (IFN-γ) ELISPOT assay was optimized to analyze HEV-specific CMI responses. We used peripheral blood mononuclear cells (PBMC) and sera from experimentally infected chimpanzees and from seroconverted and control human subjects to validate the assay. The HEV-specific IFN-γ ELISPOT responses correlated strongly and significantly with anti-HEV ELISA positive/negative results (rho=0.73, p=0.02). Moreover, fine specificities of HEV-specific T cell responses could be identified using overlapping HEV ORF2 peptides.

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“…In immunocompromised individuals, IGRAs might have a higher proportion of indeterminate results (mostly due to lack of T-cell response to mitogen), and this may indicate underlying anergy [46,47]. Recent studies suggest that IGRAs may be promising in individuals with HIV infection [30,48], contacts [36,37,[41][42][43], children [31,45] and healthcare workers [35,38], but this requires confirmation in larger studies. 38 In high-burden, developing countries, which patient or population subgroups are most likely to benefit from the use of IGRAs?…”

Section: Unresolved Issues and Agenda For Future Researchmentioning

confidence: 99%

New tools and emerging technologies for the diagnosis of tuberculosis: Part I. Latent tuberculosis

Pai

Kalantri²,

Dheda

2006

Expert Review of Molecular Diagnostics

Self Cite

220

157

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Nearly a third of the world's population is estimated to be infected with Mycobacterium tuberculosis. This enormous pool of latently infected individuals poses a major hurdle for global tuberculosis (TB) control. Currently, diagnosis of latent TB infection (LTBI) relies on the tuberculin skin test (TST), a century-old test with known limitations. In this review, the first of a two-part series on new tools for TB diagnosis, recent advances in the diagnosis of LTBI are described. The biggest advance in recent years has been the development of in vitro T-cell-based interferon-γ release assays (IGRAs) that use antigens more specific to M. tuberculosis than the purified protein derivative used in the TST. Available research evidence on IGRAs suggests they have higher specificity than TST, better correlation with surrogate markers of exposure to M. tuberculosis in low-incidence settings, and less cross-reactivity due to BCG vaccination than the TST. IGRAs also appear to be at least as sensitive as the purified protein derivative-based TST for active TB. In the absence of a gold standard for LTBI, sensitivity and specificity for LTBI are not well defined. Besides high specificity, other potential advantages of IGRAs include logistical convenience, avoidance of poorly reproducible measurements, such as skin induration, need for fewer patient visits and the ability to perform serial testing without inducing the boosting phenomenon. Overall, due to its high specificity, IGRAs may be useful in low-endemic, high-income settings where cross-reactivity due to BCG might adversely impact the utility of TST. However, despite the growing evidence supporting the use of IGRAs, several unresolved and unexplained issues remain. The review concludes by highlighting areas where evidence is lacking, and provides an agenda for future research. Active TB and drug resistance are discussed in Part II; 423-432 of this issue.

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Performance of a T-cell-based diagnostic test for tuberculosis infection in HIV-infected individuals is independent of CD4 cell count

Cited by 114 publications

References 23 publications

Use of a T-cell-based test for detection of tuberculosis infection among immunocompromised patients

Use of a T-cell-based test for detection of tuberculosis infection among immunocompromised patients

Characterization of hepatitis E-specific cell-mediated immune response using IFN-γ ELISPOT assay

New tools and emerging technologies for the diagnosis of tuberculosis: Part I. Latent tuberculosis

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