Clinical application of a rapid lung-orientated immunoassay in individuals with possible tuberculosis

Breen, Ronan; Barry, Simon; Smith, Colette; Shorten, Robert J.; Dilworth, J P; Cropley, Ian; McHugh, Timothy D.; Gillespie, Stephen H.; Jánossy, G.; Lipman, Marc

doi:10.1136/thx.2007.078857

Cited by 30 publications

(41 citation statements)

References 20 publications

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“…Although the results of this study are not as clear cut as in the pilot trial, the sensitivity and specificity of the BAL ELISpot for the detection of sputum AFB smear-negative pulmonary TB were 91 and 80%, respectively. The diagnostic accuracy of this BAL ELISpot assay for the diagnosis of sputum AFB smear-negative pulmonary TB is comparable with results from a recent trial using a technically more demanding flow cytometry assay (30).…”

Section: Discussionsupporting

confidence: 63%

Bronchoalveolar Lavage Enzyme-linked Immunospot for a Rapid Diagnosis of Tuberculosis

Jafari¹,

Thijsen²,

Sotgiu³

et al. 2009

Am J Respir Crit Care Med

122

114

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Rationale: The rapid diagnosis of pulmonary tuberculosis (TB) is difficult when acid fast bacilli (AFB) cannot be detected in sputum smears. Objectives: Following a proof of principle study, we examined in routine clinical practice whether individuals with sputum AFB smearnegative TB can be discriminated from those with latent TB infection by local immunodiagnosis with a Mycobacterium tuberculosis-specific enzyme-linked immunospot (ELISpot) assay. Methods: Subjects suspected of having active TB who were unable to produce sputum or with AFB-negative sputum smears were prospectively enrolled at Tuberculosis Network European Trialsgroup centers in Europe. ELISpot with early-secretory-antigenic-target-6 and culture-filtrate-protein-10 peptides was performed on peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage mononuclear cells (BALMCs). M. tuberculosis-specific nucleic acid amplification (NAAT) was performed on bronchoalveolar lavage fluid. Measurements and Main Results: Seventy-one of 347 (20.4%) patients had active TB. Out of 276 patients who had an alternative diagnosis, 127 (46.0%) were considered to be latently infected with M. tuberculosis by a positive PBMC ELISpot result. The sensitivity and specificity of BALMC ELISpot for the diagnosis of active pulmonary TB were 91 and 80%, respectively. The BALMC ELISpot (diagnostic odds ratio [OR], 40.4) was superior to PBMC ELISpot (OR, 10.0), tuberculin skin test (OR, 7.8), and M. tuberculosis specific NAAT (OR, 12.4) to diagnose sputum AFB smear-negative TB. In contrast to PBMC ELISpot and tuberculin skin test, the BALMC ELISpot was not influenced by previous history of TB. Conclusions: Bronchoalveolar lavage ELISpot is an important advancement to rapidly distinguish sputum AFB smear-negative TB from latent TB infection in routine clinical practice.Tuberculosis (TB) is among the leading causes of morbidity and mortality worldwide (1). Pulmonary TB is the major manifestation of the disease (2). Despite constant diagnostic improvements, the rapid diagnosis of pulmonary TB is still difficult in a substantial proportion of cases (3). Identification of Mycobacterium tuberculosis by culture is the diagnostic gold standard for active TB, but culture growth of M. tuberculosis may take 2 or more weeks on average (4), and its sensitivity is only approximately 80% (5).Microscopy for the identification of acid-fast bacilli (AFB) is rapid and inexpensive (6), but AFB are undetectable from the sputum smear in 85 to 90% of children (7) and in approximately 50% of adults (8) with active pulmonary TB. In these cases, the decision to initiate anti-TB treatment can be difficult, especially because sensitivity estimates for the nucleic acid amplification technique (NAAT) to detect nucleic acids of M. tuberculosis from respiratory specimen are too variable and too low to be used to exclude the diagnosis of TB (9).If combined test results are negative, immunodiagnosis by peripheral blood IFN-g release assays (IGRAs) and tuberculin skin testing (TST) may be used as rule...

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Section: Discussionsupporting

confidence: 63%

Bronchoalveolar Lavage Enzyme-linked Immunospot for a Rapid Diagnosis of Tuberculosis

Jafari¹,

Thijsen²,

Sotgiu³

et al. 2009

Am J Respir Crit Care Med

122

114

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“…This procedure has the advantage of being able to sample specific sites (and hence in theory improve the recovery from, e.g., localized disease or a cavity) (Schoch et al 2007). A good-quality sample, which is promptly set up for mycobacterial culture, has a high diagnostic yield (Breen et al 2008b). This is important because the procedure is associated with significant up-front capital cost, and potential risk to both patients and health-care workers.…”

Section: Postprimary Pulmonary Tbmentioning

confidence: 99%

Clinical Aspects of Adult Tuberculosis

Loddenkemper

Lipman

Zumla

2015

Cold Spring Harb Perspect Med

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Tuberculosis (TB) in adults can present in a large number of ways. The lung is the predominant site of TB. Primary pulmonary TB should be distinguished from postprimary pulmonary TB, which is the most frequent TB manifestation in adults (70%-80% cases). Cough is common, although the chest radiograph often raises suspicion of disease. Sputum sampling is a key step in the diagnosis of TB, and invasive procedures such as bronchoscopy may be necessary to achieve adequate samples for diagnosis. Extrapulmonary involvement, which may present many years after exposure, occurs in a variable proportion of cases (20%-45%). This reflects the country of origin of patients and also the frequency of associated human immunodeficiency virus (HIV) coinfection. In the latter case, the presentation of TB is often nonspecific, and care needs to be taken to not miss the diagnosis. Anti-TB therapy should be given in line with proven (or assumed) drug resistance. In extrapulmonary TB, adjunctive therapeutic measures may be indicated; although in all cases, support is often required to ensure that people are able to complete treatment with minimal adverse events and maximal adherence to the prescribed regimen, and so reduce risk of future disease for themselves and others.

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“…Recently, it has been shown that mononuclear cells (MCs) compartmentalized in infected sites such as pleural fluid (8,14) or bronchoalveolar lavage fluid (3,5) have higher gamma interferon responses than peripheral blood mononuclear cells (PBMCs). We aimed to demonstrate the proof of concept for the ability of the enzyme-linked immunospot (ELISPOT) assay to differentiate active TB from latent TB using compartmentalized lymphocytes.…”

mentioning

confidence: 99%

Diagnosis of Central Nervous System Tuberculosis by T-Cell-Based Assays on Peripheral Blood and Cerebrospinal Fluid Mononuclear Cells

Kim

Chu

Choi

et al. 2008

Clin Vaccine Immunol

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In active tuberculosis (TB), Mycobacterium tuberculosis-specific T cells are compartmentalized more to the site of infection than to the circulating blood. Therefore, an M. tuberculosis-specific enzyme-linked immunospot (ELISPOT) assay with samples from the site of infection may permit a more sensitive or specific diagnosis of active central nervous system (CNS) TB than that achieved by the assay with blood alone. Therefore, we prospectively evaluated the usefulness of circulating and compartmentalized mononuclear cell (MC; i. and 25 (68%) were classified as not having active TB. The sensitivity and specificity of the PBMC ELISPOT assay were 91% (95% confidence interval [CI], 59% to 100%) and 63% (95% CI, 41% to 81%), respectively. By comparison, the sensitivity and specificity of the CSF MC ELISPOT assay were 75% (95% CI, 19% to 99%) and 75% (95% CI, 43% to 95%), respectively. When the ratio of the CSF MC ELISPOT assay results to the PBMC ELISPOT results was 2 or more, the sensitivity and specificity were 50% (95% CI, 7% to 93%) and 100% (95% CI, 74% to 100%), respectively. The ELISPOT assay with PBMCs and CSF MCs is a useful adjunct to the current tests for the diagnosis of CNS TB.The diagnosis of central nervous system (CNS) tuberculosis (TB) remains a serious clinical problem (1). The signs and symptoms, the results of routine analyses of cerebrospinal fluid (CSF), and the radiologic findings for patients with CNS TB are often inadequate as a guide to the initiation of empirical therapy (1). Therefore, a rapid, sensitive, and specific test for the diagnosis of CNS TB is urgently required. Several newly developed assays for the diagnosis of TB based on Mycobacterium tuberculosis-specific antigens encoded by genes in the RD1 region gave promising results for the detection of latent TB infection and active pulmonary TB (10). However, data on the usefulness of these assays for the diagnosis of CNS TB in actual clinical practice are limited.The clinical use of the immunodiagnosis of TB is limited in regions where TB has intermediate to high levels of endemicity because it cannot differentiate active TB from latent TB infection (6). Recently, it has been shown that mononuclear cells (MCs) compartmentalized in infected sites such as pleural fluid (8,14) or bronchoalveolar lavage fluid (3, 5) have higher gamma interferon responses than peripheral blood mononuclear cells (PBMCs). We aimed to demonstrate the proof of concept for the ability of the enzyme-linked immunospot (ELISPOT) assay to differentiate active TB from latent TB using compartmentalized lymphocytes. Therefore, we prospectively evaluated the usefulness of circulating and compartmentalized MC-based ELISPOT assays for the diagnosis of active TB in patients with suspected CNS TB. MATERIALS AND METHODSAll adult patients with suspected CNS TB were prospectively enrolled at the Seoul National University Hospital, Seoul, Republic of Korea, and the Seoul National University Bundang Hospital in Gyunggi Province, Republic of Korea, between September 2006 and Augu...

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Clinical application of a rapid lung-orientated immunoassay in individuals with possible tuberculosis

Cited by 30 publications

References 20 publications

Bronchoalveolar Lavage Enzyme-linked Immunospot for a Rapid Diagnosis of Tuberculosis

Bronchoalveolar Lavage Enzyme-linked Immunospot for a Rapid Diagnosis of Tuberculosis

Clinical Aspects of Adult Tuberculosis

Diagnosis of Central Nervous System Tuberculosis by T-Cell-Based Assays on Peripheral Blood and Cerebrospinal Fluid Mononuclear Cells

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