Search Results: Displaying all Interpretation of Test Results (10)

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How are QFT test results interpreted? 2013 Proper assessment of patients suspected of infection with TB takes into consideration a combination of epidemiological, historical, medical and diagnostic findings, of which the QFT result is an essential component. In some situations results are provided numerically (a value of 0.35 IU/mL and above is defined as a positive result), however the QFT test is a qualitative test of infection. Some pathology providers will choose to report QFT results as positive, negative, or indeterminate whereas others will also report IU/mL values. „„- A positive QFT result suggests that current M. tuberculosis infection is likely. The result does not differentiate between recently acquired or old infection, or between LTBI and active tuberculosis. „„- A negative QFT result suggests that M. tuberculosis infection is unlikely but cannot be excluded, especially when the illness is consistent with tuberculosis disease or the likelihood of progression to disease is increased (e.g. because of immune suppression). - „„I n rare cases results cannot be interpreted as the blood cells have not responded to a positive control stimulant. This indicates the sample may have been mishandled (delays in sending samples or over/under filling of specimen tubes) or may be related to the immune system of the individual being tested. These results are called ‘indeterminate’; TB infection can neither be excluded nor confirmed. Such persons are usually TST negative.
How was the cut-off value of ≥ 0.35 IU/mL established? 2013 As expected for any diagnostic test, there is a trade-off between sensitivity and specificity, so that if one is increased under a different cut-off, then the other is decreased at the same time. Thus a cut-off was selected that gave the best combination of sensitivity and specificity. The primary test cut-off for QFT (TB antigen response – Nil ≥ 0.35 IU/mL) was established through Receiver Operator Characteristic (ROC) curve analysis of data from low risk BCG-vaccinated individuals for specificity, and from patients with culture confirmed M. tuberculosis infection for sensitivity.
Can the amount of IFN-gamma measured be correlated to the stage or degree of TB infection? 2013 Individuals displaying a response to the TB Antigen greater than or equal to 0.35 IU/mL above the Nil control, are likely to be infected with M. tuberculosis. No definitive correlation between their response to these antigens and the stage or degree of infection, their level of immune responsiveness, or their likelihood for progression to active disease can currently be made.
What constitutes a QFT conversion? 2013 QFT is highly specific—thus a change from Negative to Positive in a person with known exposure to tuberculosis is likely to be indicative of M. tuberculosis infection, especially when there is a significant increase in quantitative values. Existing CDC guidelines define a QFT conversion as a ‘change from negative to positive’. This definition is routinely used in situations where populations are serially screened with QFT (such as HCW screening programs in the USA). However, as is always the case, a positive result should be interpreted in light of all available information. In regards to using the 0.35 IU/mL (TB Ag minus Nil) dichotomous cut-point to define QFT conversion, the CDC guidelines state specifically that ‘using this lenient criterion to define IGRA conversion might produce more conversions than are observed with the more stringent criteria applied to TSTs.’ It should also be noted that the specificity of QFT—although much higher than for the TST—is not absolute and, therefore, there is the possibility of an occasional false-positive result. As suggested in the Package Insert, for anyone with an unexpected positive QFT result (ie. no apparent risk factors), it is recommended to confirm the result by retesting the plasma samples in duplicate in the QFT ELISA and use the consensus from the 3 test results. From a medical management perspective, the CDC guidelines state ‘repeat testing, with either the initial test or a different test, may be considered on a case-by-case basis’, especially when there is a low probability of TB infection and risk of disease progresssion.
How reproducible are QFT results? 2013 Reproducibility has been studied in low risk individuals, those at high risk of infection, and in HIV infected subjects. Reproducibility of the test system from plasma to plasma and with multiple blood samples is part of the test validation for regulatory approval, and has been demonstrated as very high. Comparison of results obtained at 3 different laboratories, over 3 different days and with 3 different operators found variations of less than 8.7% CV (co-efficent of variation), on average in the IFN‑γ response between testing sites, day of performance, between ELISA plates, and within ELISA plates. An equally important clinical question is the reliability of the result when subjects are tested sequentially. Data from low risk individuals shows that reproducibility in such situations is very high (> 98%). In an unpublished but FDA-reviewed study (see QFT Package Insert USA), of 530 Navy recruits, who were retested 4 to 5 weeks after initial QFT and TST testing, QFT reproducibility was 98.5% (522/530). Five (0.9%) individuals changed from positive to negative, while 3 (0.6%) changed from negative to positive and there was no evidence of the TST inducing positive QFT responses. In this same study TST reproducibility was lower—94.7% (520/549) if using a 5 mm cut-off and 97.4% (535/549) using a 10 mm cut-off, however there were 8 and 14 reversions, respectively. Additionally in HIV infected individuals, QFT results are highly reproducible. In a US study, only 1.5% (3/206) of specimens run in duplicate, yielded discordant results. A complicating factor in sequential testing is the period between testing. Short periods (a few weeks) and low TB risk environments allow less chance of infection in the intervening period or for natural or drug induced resolution of the infection, which may decrease IFN‑γ response to the TB antigens. Leyten et al demonstrated that reproducibility of results for both QFT positive and negative individuals was high when retested three days after having a skin test placed.
Why would I see false negative results in patients with active TB? 2013 Individuals who progress to active TB do so because their immune system cannot control their infection. This can result from a large infectious exposure to M. tuberculosis. It may also be due to individuals having an impaired immune response—typical for malnourished individuals, those with advanced TB, those who are severely immune suppressed or whose immune function has altered. Some individuals may develop active TB as a result of a genetic deficiency in their immune system—such as an inability to produce sufficient IFN-γ and/or IL‑12. Others may develop active TB as a result of iatrogenic immune suppression, for example individuals taking anti‑TNF‑α medications. Studies evaluating the sensitivity of QFT in developed world settings demonstrate a higher sensitivity for QFT than when evaluated in developing world populations. It is likely this reflects the variables mentioned above, almost all of which are more prevalent in the developing world. It is important to note that QFT is a test for M. tuberculosis infection and is approved as a diagnostic aid for detection of M. tuberculosis infection (whether active TB disease or LTBI). Clinicians may use QFT to assist in the diagnosis or active TB (in conjunction with risk assessment, radiography and other medical and diagnostic evaluations). A negative QFT result in a person with obvious symptoms of active TB should by no means be considered definitive. Culture of M. tuberculosis remains the gold standard for confirming a diagnosis of active TB.
Are the results affected by pregnancy? 2013 There is no clinical evidence to show that results of IGRA tests are affected by pregnancy. Studies show that IGRAs perform equally well in each trimester with comparable results to non-pregnant women. When compared with the TST, QFT is more specific, and at least as sensitive in crosssectional or longitudinal studies.
What should I do if the QFT result is indeterminate? 2013 When presented with an indeterminate result, physicians may choose to redraw a specimen or perform other procedures as appropriate. However, an indeterminate QFT is meaningful, suggesting possible error in performing the test or immune suppression - particularly in patients with known or suspected immunosuppression, chronic disease, malnutrition, or on medications known to decrease immunity. By including an internal positive control (Mitogen tube), QFT can enable the distinction between indeterminate results in those prone to immunosuppression and that are truly QFT negative. In contrast, a negative TST does not differentiate between those individuals who cannot respond to the test due to immune suppression or incorrect test performance and those who have a truly negative TST.
How often does QFT yield an indeterminate result? 2013 QFT indeterminate results generally occur very infrequently in healthy individuals. In clinical studies submitted to the FDA for approval of QFT, the indeterminate rate was less than 2%. However, in populations where the level of immune suppression is high, indeterminate rates can be correspondingly higher. An indeterminate response in a highly immune suppressed individual is appropriate as it indicates a measureable immune response is not present. In contrast, the TST would likely be negative in such individuals—thus not providing any real measure of their infection status.
What is the meaning of Mitogen negative responses in healthy individuals? 2013 In a very small proportion of individuals, indeterminate QFT results may be obtained despite the subject being apparently healthy and immune competent. In most instances, repeating the QFT test with a new blood sample will result in a non-indeterminate QFT result, suggesting that the initial result may have been due to operational difficulties. However, for a very small proportion of subjects, the repeat test may also be indeterminate. In these rare cases the reason for the indeterminate result is unclear if immune suppression and/or technical error are ruled out. However, such a response may be transient and retesting the individual after a period of a few weeks may result in a non-indeterminate test result.


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