Tuberculosis diagnosis using immunodominant, secreted antigens of Mycobacterium tuberculosis

Bekmurzayeva, Aliya; Sypabekova, Marzhan; Kanayeva, Damira

doi:10.1016/j.tube.2013.03.003

Cited by 74 publications

(51 citation statements)

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“…The main disadvantage for this diagnosis method is low specificity (20). Recently, M. tuberculosis-secreted antigens serving as TB skin test reagents have attracted a lot of interest in the diagnosis of TB (21).These antigens, including ESAT6, CFP10, PE13, PE5, MPB70, TB10.4, and TB27.4, have been tested. ESAT6 and CFP10 are powerful antigens that elicit humoral and cellular immunity, so they are considered the most promising antigens as skin test reagents (22).…”

Section: Discussionmentioning

confidence: 99%

Safety of Recombinant Fusion Protein ESAT6-CFP10 as a Skin Test Reagent for Tuberculosis Diagnosis: an Open-Label, Randomized, Single-Center Phase I Clinical Trial

Zhou

et al. 2016

Clin Vaccine Immunol

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cThis trial was conducted to explore the safety of recombinant fusion protein ESAT6-CFP10 as a skin test reagent for the diagnosis of Mycobacterium tuberculosis infection. Twenty-four healthy adult volunteers were recruited and randomized into four groups (groups A to D) to study four increasing doses of ESAT6-CFP10. All subjects in each dose group received an intradermal injection of reagent (0.1 ml) via the Mantoux technique. Then, the vital signs of all subjects were monitored, and skin reactions around injection sites and adverse events were recorded at different detection time points after the skin test. No serious adverse events were observed in this study. A total of 3 subjects had unexpected events. One subject in group A developed subcutaneous hemorrhage 24 h after the skin test, one subject in group B was found with red spots 15 min after the skin test, and another subject in group A showed abnormity during a chest X-ray after the skin test without affecting her health. One of three adverse events (red spots) was probably related to the recombinant ESAT6-CFP10 reagent. A single dose of 1, 5, 10, or 20 g/ml of recombinant ESAT6-CFP10 as a skin test reagent for M. tuberculosis infection diagnosis is well tolerated and safe in China. (This study has been registered at ClinicalTrials.gov under registration no. NCT01999231.)A lthough tuberculosis (TB) has been a curable disease, it still remains a major global problem that seriously threatens human health. According to the WHO Global TB report 2015, there were 9.6 million new cases and nearly 1.5 million TB-related deaths in 2014 (1). Thus, exploring diagnostic techniques with high sensitivity and specificity is crucial for controlling TB development and its drug resistance.TB is caused by infection with Mycobacterium tuberculosis, an intracellular pathogen transmitted by air (2). Several in vitro assay systems based on the detection of immune reactivity against an M. tuberculosis-specific antigen have been established and widely accepted in recent years. Early secreted antigenic target 6-kDa protein (ESAT6) and culture filtrate protein of 10 kDa (CFP10), two major M. tuberculosis-specific antigens, have been reported to play key roles in the virulence of M. tuberculosis and elicit strong T-cell responses (3, 4). Interferon gamma release assays (IGRAs) based on immune recognition against ESAT6 and CFP10 have been used to help diagnose activated and latent M. tuberculosis infection (5). IGRAs have an increased specificity compared to the conventional tuberculin skin test (TST) because the antigens included in IGRAs, namely, ESAT6 and CFP10, have been selected based on their absence in many environmental nontuberculous mycobacteria and the vaccine strain Mycobacterium bovis Bacillus Calmette-Guérin (BCG), which can only be detected in a number of pathogenic mycobacteria species, including M. tuberculosis, and a minority of nontuberculous mycobacteria (Mycobacteria kansasii, Mycobacteria szulgai, Mycobacteria marinum, and Mycobacteria riyadhense), altogether l...

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Section: Discussionmentioning

confidence: 99%

Safety of Recombinant Fusion Protein ESAT6-CFP10 as a Skin Test Reagent for Tuberculosis Diagnosis: an Open-Label, Randomized, Single-Center Phase I Clinical Trial

Zhou

et al. 2016

Clin Vaccine Immunol

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“…The widely used tuberculin skin test (TST) assesses local immunological responses elicited by mycobacterial antigens (Bekmurzayeva et al 2013) and is primarily used to show prior sensitization and latent infection. Subcutaneous injection of an extract of heatkilled Mtb proteins evokes a delayed-type hypersensitivity (DTH) reaction, causing transient swelling and reddening of the skin.…”

Section: Single Biomarkers In Tb Diagnostics-a Matter Of Sensitivity mentioning

confidence: 99%

“…Subcutaneous injection of an extract of heatkilled Mtb proteins evokes a delayed-type hypersensitivity (DTH) reaction, causing transient swelling and reddening of the skin. Although of low cost, the test has profound limitations for detecting latent infections both with respect to sensitivity and specificity, which range widely depending on the population tested and can be affected by HIV infection and Bacillus Calmette -Guérin (BCG) vaccination (Bekmurzayeva et al 2013).…”

Section: Single Biomarkers In Tb Diagnostics-a Matter Of Sensitivity mentioning

confidence: 99%

“…The more recent approach in this group of diagnostic tests, the interferon-g release assays (IGRAs), such as the Quantiferon test, rely on ex vivo activation of T lymphocytes secreting interferon-g (IFN-g) on stimulation with defined Mtb-specific proteins (Bekmurzayeva et al 2013). Although a positive test result indicates previous exposure of a person's cellular immune response to Mtb, it is not a measure of bacterial activity or even persistence of the bacillus.…”

Section: Single Biomarkers In Tb Diagnostics-a Matter Of Sensitivity mentioning

confidence: 99%

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Toward a Unified Biosignature for Tuberculosis

Maertzdorf

Kaufmann

Weiner

2014

Cold Spring Harbor Perspectives in Medicine

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Accurate and rapid diagnosis of active tuberculosis (TB) disease is still hampered by inadequate tools. Although current assays relying on single-marker readouts mostly display inadequate sensitivity and/or specificity, host-related multimarker signatures are especially poorly developed. As a consequence, research programs have been initiated to search for combinations of markers-so-called biosignatures with superior performance. Many such investigations harness high-throughput platforms to analyze the host response during infection and disease. A major challenge for these activities is the analysis of vast amounts of data produced. Specialized bioinformatic tools are being applied to identify the most robust biosignatures for classification of exposed and diseased individuals and prognosis of risk of disease in endemic areas. Validation of the most promising biosignatures in ongoing multicohort studies will bring us a step closer to the identification of an accurate unified signature.

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“…It has also been proven that MPT64 antigen is found only in viable and actively dividing cells of M. tuberculosis. 9 Subjects of this study were pulmonary tuberculosis and TB meningitis because pulmonary tuberculosis account for 85% of all TB cases while TB meningitis was the most severe TB manifestation. 10,11 The aim of this study was to determine the validity of TB antigen cocktail (ESAT-6, CFP-10 and MPT64) for the diagnosis of pulmonary tuberculosis and TB meningitis.…”

Section: Introductionmentioning

confidence: 99%

The Validity of Mycobacterium Tuberculosis Antigens Cocktail: Esat-6, CFP-10 and Mpt64 in Sputum and Cerebrospinal Fluid for Pulmonary Tuberculosis and Tuberculous Meningitis Diagnosis

Turbawat¹,

Gustiani²,

Noviani³

et al. 2015

IJIHS

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Objective: To determine the validity of tuberculosis (TB) antigen cocktail (ESAT-6, CFP-10 and MPT64) for pulmonary tuberculosis and TB meningitis diagnosis.Methods: This is a descriptive observational study design. The study was conducted at the Clinical Pathology Laboratory of Dr. Hasan Sadikin General Hospital during September 2012 until March 2013 for the pulmonary tuberculosis study and from January 2014 to May 2014 for the TB meningitis study. The TB antigen cocktail rapid immunochromatography (ICT) test was conduncted on all samples. The sputum and cerebrospinal fluid (CSF) were cultured as gold standards.Results: There were 149 pulmonary and 41 TB meningitis subjects. The sensitivity of rapid ICT TB antigen cocktail for diagnosing pulmonary tuberculosis was 95.7% with a specificity of 87.2%. Of 41 TB meningitis subjects, based on Marais criteria, there were 6 (16%) subjects with a definite TB meningitis, 26 (63%) subjects with probable TB meningitis, and 9 (21%) subjects with possible TB meningitis. The sensitivity and specificity of TB antigen cocktail rapid ICT for TB meningitis diagnosis were 83.3% and 68.5%, respectively. Conclusions:In this study, rapid ICT TB antigen cocktail (ESAT-6, CFP-10 and MPT64) from sputum sample has good validity for diagnosing a pulmonary tuberculosis. Cerebrospinal fluid sample has moderate validity to diagnose TB meningitis.

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Tuberculosis diagnosis using immunodominant, secreted antigens of Mycobacterium tuberculosis

Cited by 74 publications

References 68 publications

Safety of Recombinant Fusion Protein ESAT6-CFP10 as a Skin Test Reagent for Tuberculosis Diagnosis: an Open-Label, Randomized, Single-Center Phase I Clinical Trial

Safety of Recombinant Fusion Protein ESAT6-CFP10 as a Skin Test Reagent for Tuberculosis Diagnosis: an Open-Label, Randomized, Single-Center Phase I Clinical Trial

Toward a Unified Biosignature for Tuberculosis

The Validity of Mycobacterium Tuberculosis Antigens Cocktail: Esat-6, CFP-10 and Mpt64 in Sputum and Cerebrospinal Fluid for Pulmonary Tuberculosis and Tuberculous Meningitis Diagnosis

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