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[Characteristics of a diagnostic method for tuberculosis infection based on whole blood interferon-gamma assay]

Nobuyuki Harada
Kekkaku: [Tuberculosis] 2006, 81 (11): 681-6
It is assumed that about 10% of individuals infected with M. tuberculosis (Mtb) develop tuberculosis (Tb), and the remaining 90% suppress contain Mtb through their immune systems, but have a latent tuberculosis infection (LTBI). To effectively control Tb, it is essential to detect individuals with LTBI in a Tb outbreak and provide chemoprophylaxis for them. Until recently, the tuberculin skin test (TST) has been the only diagnostic method for LTBI. However, the specificity of TST is low, because the purified protein derivative (PPD) used for TST contains numerous Mtb antigens that are almost identical to BCG antigens or similar to non-tuberculous mycobacterium (NTM) antigens. For this reason, TST may produce positive results in BCG-vaccinated individuals or NTM-infected individuals without Mtb infection. Therefore, it is very difficult to diagnose LTBI in Japan, where BCG vaccination is widely administered. In addition to this, TST has other defects, such as technical variations for injecting PPD or measuring the TST response, the necessity of a return visit to the doctor to measure the TST response 2 days after PPD injection, and the booster effect through reinjection of PPD. More recently, a new diagnostic method that can overcome these defects in TST, QuantiFERON TB-2G (QFT-2G), has been developed. In QFT-2G, two Mtb-specific antigens, ESAT-6 and CFP-10, are used to stimulate whole blood, and based on produced interferon-gamma (IFN-gamma), Mtb infection is diagnosed. Since ESAT-6 and CFP-10 are absent from all M. bovis BCG substrains and most of NTM including M. avium, M. intracellulare, but are present in tuberculosis complex (M. tuberculosis, M. bovis, M. africanum) and only a few strains of NTM, QFT-2G is not affected by prior BCG vaccination nor most of NTM infections. Moreover, as measurement of IFN-gamma can be carried out by machines on the next day following the blood draw, more objective results are obtained more quickly than with TST. It is not necessary to consider the booster effect in QFT-2G as PPD is not injected, nor to revisit the doctor. Thus, QFT-2G overcomes the defects of TST described here. From a clinical trial of QFT-2G in which the subjects were smear-positive, untreated Tb patients and BCG-vaccinated healthy individuals, it has been demonstrated that the specificity and sensitivity of QFT-2G are 98.1% and 89.0%, respectively, and QFT-2G is an excellent diagnostic method. Furthermore, many contact investigations have shown that QFT-2G detects not only active Tb but also LTBI. Several data indicate that frequency of contact with Tb patients correlates well with QFT-2G positive rates in contact investigations. The validity and usefulness of diagnosing LTBI by QFT-2G have been suggested in other countries. In many contact investigations, it has been shown that most contacts who had been diagnosed as LTBI based on TST results were QFT-2G negative, suggesting that as a result, many unnecessary chemoprophylaxes were indicated. On the contrary, many QFT-2G positives were identified in those who were diagnosed to be uninfected with Mtb based on TST. Therefore, as the wide spread of QFT-2G testing in contact investigations would prevent unnecessary chemoprophylaxes and detect true infected individuals more accurately, we hope that more effective Tb control could be performed. Although QFT-2G is an excellent diagnostic method, it is still new, and some questions remain to be answered. For example, the period of converting QFT-2G positive after Mtb infection, alteration of long-term QFT-2G responses after Mtb infection, and the effects of treatment for Tb or LTBI are not fully understood. The behavior of QFT-2G in infants or children is not understood either. Especially in infants, the problem of the blood volume required for the QFT-2G test is the major issue. We are working on these issues to provide more appropriate directions for QFT-2G users, and hope that we can contribute to Tb control.


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