The interferon-gamma release test (IGRAs) is a diagnostic tool for latent tuberculosis (LTBI) infection. They are markers of infection of Mycobacterium tuberculosis and show cellular immune response to M. tuberculosis . IGRAs can not distinguish between latent infection and active tuberculosis (TB) disease, and should not be used as a single method for the diagnosis of active TB, which is a microbiological diagnosis. Positive IGRA outcomes may not always indicate TB infection, but can also be caused by infection with non-tuberculous mycobacteria. Negative IGRA does not rule out active TB disease; a number of studies have shown that up to a quarter of patients with active TB have negative IGRA outcomes.
Because IGRA is not affected by the vaccination status of Bacille Calmette-GuÃÆ' Â © rin (BCG), the IGRA is useful for the evaluation of LTBI in individuals who are vaccinated against BCG, especially in settings where BCG vaccination is given after a baby or multiple (booster) BCG vaccinations are given. In contrast, the specificity of the tuberculin skin test (TST) varies depending on BCG time and whether recurrent vaccinations (boosters) are given.
QuantiFERON , also known as QFT, is a registered trademark of the test for tuberculosis or latent tuberculosis infection. It's manufactured by QIAGEN. QFT is interferon-? release assay (IGRA) is used in the diagnosis of tuberculosis. The QFT-GIT assay is an ELISA-based whole-blood test that uses peptides from three TB antigens (ESAT-6, CFP-10, and TB7.7) in an in-tube format. The results are reported as IFN-gamma quantification in international units (IU) per mL. A person is considered positive for M. tuberculosis if the IFN-gamma response to TB antigen is above the cut-off test (after subtracting the IFN-gamma response of the background on the negative control).
Video QuantiFERON
QuantiFERON-TB (QFT)
QuantumFERON-TB Gold In-Tube (QFT-GIT), a third-generation test, has replaced QuantiFERON-TB (QFT) and QuantiFERON-Gold, which is no longer marketed.
According to the US Centers for Disease Control, in 2001, the QuantiFERON-TB (QFT) test was approved by the Food and Drug Administration (FDA) as an aid to detect latent infection Mycobacterium tuberculosis . This test is an in vitro diagnostic aid that measures the component of cell-mediated immune reactivity for M. tuberculosis . This test is based on the quantification of interferon-gamma (IFN-?) Which is released from sensitive lymphocytes in all blood incubated overnight by purified the derivative protein (PPD) of M. tuberculosis and controlling the antigen.
Tuberculin skin testing (TST) has been used for many years as an aid in diagnosing latent tuberculosis (LTBI) infections and includes measurement of delayed hypersensitivity response 48-72 hours after intradermal injection of PPD. TST and QFT do not measure the same immunological response component and can not be interchanged. Assessment of the accuracy of this test is limited by the lack of standards to confirm LTBI.
As a diagnostic test, QFT:
- needs a blood-clearing process
- can be completed after one patient visit
- rate response to multiple antigens simultaneously
- does not improve the immune response of anamnesa (see Latent tuberculosis # Boosting).
Compared with TST, QFT results are less subject to bias and reader error. In CDC-sponsored multicenter trials, QFT and TST results are quite appropriate (overall kappa value = 0.60). The degree of concordance is influenced by previous vaccinations of bacille Calmette-GuÃÆ' Â © rin (BCG), immune reactivity to nontuberculous myobobia (NTM), and previous positive TST. In addition to multicenter studies, two other published studies have demonstrated a moderate concordance between TST and QFT. However, one of the five sites involved in the CDC study reported a lack of agreement. Although there are studies that confirm the increased risk of active TB in the future in individuals with positive TST, the same does not apply to those with positive IGRA outcomes. A recently published study shows that positive IGRA outcomes are predictive of the risk of active TB in the future. In addition, IGRA is at least sensitive and more specific than traditional TST. In this study of immunocompetent that recently exposed close contact of active TB cases, the rate of progression to active disease in untreated positive QFT individuals was significantly greater than for untreated positive TST (14.6% versus 2.3 %). Although the numbers are small, all the close contacts that develop active TB are positive QFT, but only 83% are positive TST.
As mentioned above, previous BCG vaccination can produce false positive TST results. In a study of military personnel returning from the mission, about half of the positive TST were false positives. In a more recent study of the military returning from the mission, Franken et al. the reported evidence showing false-positive TST results is common and that QFT testing can guide more targeted treatment and relieve unnecessary anti-tuberculosis treatment.
FDA Cutpoint for positive results established at & gt; 0.34 International/Milliliter (IU/ml) units, although these have proven functionally functional in low prevalence areas, such as among US and Canadian health workers. In areas with low risk and low prevalence, the positive predictive value of each test is reduced. In the case of radiant North American healthcare workers, the QFT results just above this cutpoint resulted in false-positive test results that were re-examined back to negative, where TB checkups were often mandated on an annual basis (MMWR June 2010, https://www. cdc.gov/mmwr/pdf/rr/rr5905.pdf). Research at Stanford University and the Veterans Administration has reported the use of retesting zones (or limits) below 1.1 IU/ml reduces 76% of the positive-error, or returns.
The limitations of QFT include the need to take blood and process it within 16 hours of collection and limited laboratory and clinical experience with the test. There is a need for further study of QFT utility in predicting progression to active tuberculosis, especially in children and immunocompromised hosts. {Thanassi, 2012 # 6}
For the disadvantage, QFT can produce false positive results with Mycobacterium szulgai , Mycobacterium kansasii , and Mycobacterium marinum .
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Gold QuantiFERON-TB
The QuantiFERON-TB Gold (QFT-G) test is a complete blood test to be used as an aid in diagnosing Mycobacterium tuberculosis infection, including latent tuberculosis (LTBI) infection and tuberculosis (TB) disease. This test was approved by the US Food and Drug Administration (FDA) in 2005.
Blood samples are mixed with antigens (substances that can produce immune responses) and controls. For QFT-G, antigens include a mixture of synthetic peptides representing two proteins M. tuberculosis, ESAT-6 and CFP-10. After incubation of blood with antigen for 16 to 24 hours, the amount of interferon-gamma (IFN-gamma) was measured.
If the patient is infected with M. tuberculosis, their white blood cells will release IFN-gamma in response to contact with the TB antigen. The QFT-G results are based on the amount of IFN-gamma released in response to the antigen.
Clinical evaluations and additional tests (such as chest radiographs, AFB sputum, and culture) are needed to differentiate between the diagnosis of latent TB or active TB.
The advantages of this test are:
- It takes one patient visit to take a blood sample.
- Results can be available in 24 hours.
- Does not increase the response as measured by subsequent tests, which can occur with tuberculin skin test (TST).
- Not subject to reader bias that can happen with TST.
- Not affected by previous BCG vaccination (bacille Calmette-GuÃÆ' Â © rin).
The shortcomings and limitations of the test are:
- Blood samples should be processed within 16 hours after the temporary collection of white blood cells is still feasible.
- There is limited data on the use of QFT-G in children younger than 17 years, among people who have recently been exposed to M. tuberculosis, and in people with impaired immunity (eg, impaired immune function caused by HIV infection or acquired immunodeficiency syndrome [AIDS], current treatment with immunosuppressive drugs, selected haematological disorders, certain malignancies, diabetes, silicosis, and chronic renal failure).
- Errors in collecting or transporting blood specimens or in running and interpreting tests may decrease QFT-G accuracy.
- Limited data about using QFT-G to determine who is at risk for developing TB disease.
In-Tube Gold QuantiFERON-TB
On 10/10/2007, the United States FDA approved for Inox Quantiffon Gold Tube that will be marketed in the US
The FDA states:
Approval for the modification of the quantifon-tb gold to the collection system inside the tube consisting of three collecting tubes of blood, nil, tb antigen, and mitogen. This tool, as modified, will be marketed under the trade name gold in in-tube quantiferon-tb and is indicated for use as an in vitro diagnostic test using cocktail peptide simulates the 6th, cfp-10 and tb 7,7 (p4) protein to stimulate blood cells that are in heparin directly into special blood-collection tubes. Interferon-y detection by enzyme-linked immunosorbent assay (elisa) is used to identify in vitro responses to peptide antigens associated with mycobacterium tuberculosis infection.
According to FDA approved packages, Quantiferon TB Gold In Tube has a consistent specificity & gt; 99% in low-risk individuals and as high as 92% sensitivity in individuals with active disease, depending on the setting and level of the disease. The specificity in two studies of several hundred individuals was 96-98% in health-immunized populations.
The package inserts also suggest that the kit provides three collection tubes that have dry antigens to their walls and that these tubes must be transferred to the incubator within 16 hours of blood collection.
On June 25, 2010, the US Centers for Disease Control and Prevention (CDC) updated tuberculosis (TB) testing guidelines (MMWR June 2010, https://www.cdc.gov/mmwr/pdf/rr/rr5905.pdf) providing guidance for US public health officials, doctors and laboratory workers on screening for and diagnosing TB infection. Updated guidelines provide new direction for TB control in the US.
Previously, QuantiFERONÃ,®-TB Gold could be used in any situation where Tuberculin Skin Tests (TSTs) were used, without preference. The 2010 guidelines set a new benchmark because they recommend IGRA as a preferred TB testing method in many patients, including those who are vaccinated with BCG or are unlikely to return to read the TST.
Medical facilities in the US using QFT can be found at http://www.quantiferon.com/irm/content/contact-us1.aspx?RID=342.
Availability
In the United States, these tests are widely available from state public health laboratories, hospitals, and commercial laboratories.
In January 2008, the CDC recommends - through their TB Note Newsletter - TB and other controllers from links to laboratory lists in the US and Canada offering to perform the Quantiferon Gold test.
The California Tuberculosis Controllers Association has also provided a list of public health laboratories in California that are tested with Quantiferon.
References
Source of the article : Wikipedia
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