What is qft-g test?

The interferon alpha release assay (QFT-G) is a new diagnostic test for latent tuberculosis infection (LTBI). QFT-G is similar to the Tuberculin Skin Test (TST), but cannot differentiate between LTBI and active TB.

Interferon-Gamma Release Assays (IGRAs) are whole-blood tests that can aid in diagnosing Mycobacterium tuberculosis infection. They do not help differentiate latent tuberculosis infection (LTBI) from tuberculosis disease. Two IGRAs that have been approved by the U.S. Food and Drug Administration (FDA) are commercially available in the U.S:

IGRAs measure a person’s immune reactivity to M. tuberculosis. White blood cells from most persons that have been infected with M. tuberculosis will release interferon-gamma (IFN-g) when mixed with antigens (substances that can produce an immune response) derived from M. tuberculosis.

To conduct the tests, fresh blood samples are mixed with antigens and controls. The antigens, testing methods, and interpretation criteria for IGRAs differ (see Table 1).

Table1: Differences in Currently Available IGRAs

Confirm arrangements for testing in a qualified laboratory, and arrange for delivery of the blood sample to the laboratory in the time the laboratory specifies to ensure testing of samples with viable blood cells.

IGRA interpretations are based on the amount of IFN-g that is released or on the number of cells that release IFN-g. Both the standard qualitative test interpretation (positive, negative, or indeterminate) and the quantitative assay measurements (Nil, TB, and Mitogen concentrations or spot counts) should be reported.

As with the tuberculin skin tests (TSTs), IGRAs should be used as an aid in diagnosing infection with M. tuberculosis. A positive test result suggests that M. tuberculosis infection is likely; a negative result suggests that infection is unlikely. An indeterminate result indicates an uncertain likelihood of M. tuberculosis infection. A borderline test result (T-Spot only) also indicates an uncertain likelihood of M. tuberculosis infection.

A diagnosis of LTBI requires that TB disease be excluded by medical evaluation. This should include checking for signs and symptoms suggestive of TB disease, a chest radiograph, and, when indicated, examination of sputum or other clinical samples for the presence of M. tuberculosis. Decisions about a diagnosis of M. tuberculosis infection should also include epidemiological and historical information.

Multiple negative results from any combination of these tests cannot exclude M. tuberculosis infection. Steps should be taken to minimize unnecessary and misleading testing of persons at low risk.

Selection of the most suitable test or combination of tests for detection of M. tuberculosis infection should be based on the reasons and the context for testing, test availability, and overall cost of testing.

As with TST, live virus vaccines might affect IGRA test results. However, the effect of live virus vaccination on IGRAs has not been studied. Until additional information is available, IGRA testing in the context of live virus vaccine administration should be done as follows:

If your TST (Mantoux) or Quantiferon blood test was found to be positive, this means you have a latent TB infection, but usually not the active disease.

No. Not everyone with the TB infection develops the active disease.

Tuberculosis infection occurs when you breathe in TB bacteria while you are exposed to someone who has active TB in their lungs. Usually, the body’s defences control the infection, but the bacteria can remain in the body for years in an inactive or ‘latent’ state. There is a small risk of developing TB disease (active TB) sometime later in life. About 90 per cent of people will not develop the active disease.

People with TB infection:

If taken correctly, preventative treatment can significantly reduce the risk of people with the latent TB infection developing the active TB disease.

At your doctor’s appointment, you will discuss your risk of developing the TB disease and also the treatment options available.

You must tell your doctor what medicine you are taking, your medical history and if you are pregnant or breastfeeding.

If it is decided that you should have preventative medication, the usual treatment is antibiotic tablets, taken once a day for 6 months. It is important to understand that, once you have started the medication, you should continue taking it without interruption.

Treatment taken irregularly or not completed fully may result in the treatment not being effective in reducing the risk of future disease.

Different preventative medication can cause side effects in some people. If side effects occur it is important to report them to your TB case manager or doctor immediately. Some of the potential side effects to be aware of when taking TB medication are:

While you are taking TB medication a monthly visit to a TB clinic is usually required. The purpose of this visit is to:

All medications for tuberculosis treatment are supplied free of charge from the WA Tuberculosis Control Program.

Interferon-gamma release assays (IGRAs) are diagnostic tools for latent tuberculosis infection (LTBI). They are surrogate markers of Mycobacterium tuberculosis infection and indicate a cellular immune response to M. tuberculosis if the latter is present.

IGRAs cannot distinguish between latent infection and active tuberculosis (TB) disease, and should not be used as a sole method for diagnosis of active TB, which is a microbiological diagnosis. A positive IGRA result may not necessarily indicate TB infection, but can also be caused by infection with non-tuberculous mycobacteria. A 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 results.

Because IGRAs are not affected by Bacille Calmette–Guérin (BCG) vaccination status, IGRAs are useful for evaluation of LTBI in BCG-vaccinated individuals, particularly in settings where BCG vaccination is administered after infancy or multiple (booster) BCG vaccinations are given. In contrast, the specificity of tuberculin skin test (TST) varies depending on timing of BCG and whether repeated (booster) vaccinations are given.

QuantiFERON, also known as QFT, is the registered trademark of an interferon gamma release assay (IGRA) for tuberculosis diagnosis manufactured by QIAGEN. 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 result is reported as quantification of IFN-gamma in international units (IU) per mL. An individual is considered positive for M. tuberculosis infection if the IFN-gamma response to TB antigens is above the test cut-off (after subtracting the background IFN-gamma response in the negative control).

Since IGRAs are more costly and technically complex to do than the Mantoux test, in their 2011 policy statement, the WHO did not recommend replacing the Mantoux test by IGRAs as a public health intervention in low- and middle-income countries.[1]

QuantiFERON-TB Gold In-Tube (QFT-GIT), the third generation test, has replaced QuantiFERON-TB (QFT) and QuantiFERON-Gold, which are no longer marketed.

According to the U.S. Centers for Disease Control,[2] in 2001, the QuantiFERON-TB test (QFT) was approved by the Food and Drug Administration (FDA) as an aid for detecting latent Mycobacterium tuberculosis infection. This test is an in vitro diagnostic aid that measures a component of cell-mediated immune reactivity to M. tuberculosis. The test is based on the quantification of interferon-gamma (IFN-γ) released from sensitized lymphocytes in whole blood incubated overnight with purified protein derivative (PPD) from M. tuberculosis and control antigens.

Tuberculin skin testing (TST) has been used for years as an aid in diagnosing latent tuberculosis infection (LTBI) and includes measurement of the delayed type hypersensitivity response 48–72 hours after intradermal injection of PPD. TST and QFT do not measure the same components of the immunologic response and are not interchangeable. Assessment of the accuracy of these tests is limited by lack of a standard for confirming LTBI.[citation needed]

As a diagnostic test, QFT:

Compared with TST, QFT results are less subject to reader bias and error. In a CDC-sponsored multicenter trial, QFT and TST results were moderately concordant (overall kappa value = 0.60). The level of concordance was adversely affected by prior bacille Calmette-Guérin (BCG) vaccination, immune reactivity to nontuberculous mycobacteria (NTM), and a prior positive TST.[3] In addition to the multicenter study, two other published studies have demonstrated moderate concordance between TST and QFT.[4][5] However, one of the five sites involved in the CDC study reported less agreement.[6] Although there have been studies confirming the increased future risk of active TB in individuals with positive TST, the same was not true for those with a positive IGRA result. A recently published study[7] demonstrated that a positive IGRA result is predictive of future active TB risk. Moreover, IGRA was at least as sensitive and was more specific compared to traditional TST. In this study of immunocompetent recently exposed close contacts of active TB cases, the progression rate to active disease among untreated QFT positive individuals was significantly greater than for untreated TST positives (14.6% versus 2.3%). Although the numbers were small, all of the close contacts who went on to develop active TB were QFT positive, but only 83% were TST positive.[citation needed]

As noted above, prior BCG vaccination can produce false positive TST results. In a study of military personnel returning from missions, about one-half of the positive TSTs were falsely positive.[8] In a more recent study of military returning from missions, Franken et al.[9] reported evidence suggesting false positive TST results are common and that QFT testing could guide more targeted treatment and alleviate unnecessary anti-tuberculous treatment.

The FDA's cutpoint for a positive result was established at >0.34 International Units/millilitre (IU/ml), though this has proven functionally problematic in low prevalence areas, such as among US and Canadian healthcare workers. In areas of low risk and low prevalence, the positive predictive value of any test is diminished. In the case of serially screened North American healthcare workers, QFT results just above this cutpoint produce false-positive test results that upon repeat testing revert to negative,[10] where tuberculosis screening is often mandated on an annual basis.[11] Research at Stanford University and the Veterans Administration has reported the use of a retesting (or borderline) zone below 1.1 IU/ml mitigates 76% of the false-positives, or reversions.[12][13]

Limitations of QFT include the need to draw blood and process it within 16 hours after collection and limited laboratory and clinical experience with the assay. There is need for further study of the utility of QFT in predicting the progression to active tuberculosis, particularly in children and immunocompromised hosts.[12]

To its disadvantage, QFT can yield false positive results with Mycobacterium szulgai, Mycobacterium kansasii, and Mycobacterium marinum.[14]

The QuantiFERON-TB Gold test (QFT-G) is a whole-blood test for use as an aid in diagnosing Mycobacterium tuberculosis infection, including latent tuberculosis infection (LTBI) and tuberculosis (TB) disease.[15] This test was approved by the U.S. Food and Drug Administration (FDA) in 2005.

Blood samples are mixed with antigens (substances that can produce an immune response) and controls. For QFT-G, the antigens include mixtures of synthetic peptides representing two M. tuberculosis proteins, ESAT-6 and CFP-10. After incubation of the blood with antigens for 16 to 24 hours, the amount of interferon-gamma (IFN-gamma) is measured.

If the patient is infected with M. tuberculosis, their white blood cells will release IFN-gamma in response to contact with the TB antigens. The QFT-G results are based on the amount of IFN-gamma that is released in response to the antigens.

Clinical evaluation and additional tests (such as a chest radiograph, sputum smear, and culture) are needed to differentiate between a diagnosis of latent TB or active TB.

Advantages of the test are:

Disadvantages and limitations of the test are:

On 10/10/2007 the US FDA[19] gave approval for the Quantiferon TB Gold In Tube to be marketed in the US

The FDA states:

According to the FDA approved package insert[20] Quantiferon TB Gold In Tube has a consistent specificity of >99% in low risk individuals and a sensitivity as high as 92% in individuals with active disease, depending on setting and extent of disease. The specificity in two studies of a few hundred people is 96-98% in a health immunised population.

The package insert also advises that the kit provides three collection tubes which have had antigens dried onto their walls and that these tubes must be transferred to an incubator within 16 hours of blood collection.

On 25 June 2010, the US Centers for Disease Control and Prevention (CDC) updated the tuberculosis (TB) testing guidelines providing guidance to US public health officials, clinicians, and laboratory workers regarding screening for and diagnosis of TB infection. The updated guidelines provide new direction for TB control in the US.[11]

Previously, QuantiFERON®-TB Gold was able to be used in any situation in which the Tuberculin Skin Test (TST) was used, without preference. The 2010 guidelines establish a new benchmark because they recommend IGRAs as the preferred TB testing method in many patients, including those who are BCG vaccinated or are unlikely to return for TST reading.[citation needed]

In the United States, the test is widely available from state public health laboratories, hospitals, and commercial laboratories.

In January 2008 the CDC advised - via their TB Notes Newsletter[21] - TB controllers and others of a link[22] to a list of laboratories in the US and Canada offering to perform the Quantiferon Gold test.

The California Tuberculosis Controllers Association have also provided a list of public health laboratories[23] in California that are testing with Quantiferon.