Novel Approaches to TB Diagnosis
line decor
  HOME  ::  Diagnostics and TB Control
line decor
 
 
Diagnostics and TB Control

QFT-Gold vs. TST: Application to TB Control Programs

The TST has been the standard in TB diagnostics for over one hundred years, and the introduction of a novel system like QFT-gold has naturally recieved much scrutiny.

Test Administration and Results While the TST may seem like a relatively simple test to administer, there are many practical limitations in use of TST at a programmatic level. The test itself is very subjective, and many nurses and practitioners are liscenced but not adequetly trained to interpret test results. Furthermore, a positive result depends on the health and exposure status of the individual, and must be determined on a case by case basis. [Kawamura] The potential for significant varaiability between readers and improper administration of the test becomes particularly problematic at a large sacle programmatic level, analysis of such variable and subjective responses does not allow for efficient and precise TB control efforts. [Smith] Quantification and automation are two key factors lacking in current TB diagnostic techniques. Results for the QFT-Gold test are in most cases categoprical, and can easily be read and quantified. Automation is also quite feasible, allowing for standardization and ease of large scale analysis. [Kawamura]

Operational Viability

The TST requires multiple visits, and results are available after 48 to 72 hours. Results from the QFT-Gold test can be obtained within 24 hours, and only a single patient visit is required. In itself, reduction in number of visits required will result in far fewer missed appointments, allowing for more complete screening [Smith]. On the other hand, the QFT-Gold requires blood samples to be taken from each patient, and neccesitates laboratory analysis of results. Sample blood must reach the testing laboratory and be stimulated within 12 hours of testing. The TST in comparison is a relatively simple test to administer and requires few associated materials. Operationally, drawing blood can be and ensuring safe storage and transport to the laboratory within the 12 hour time frame can be difficult, especially where field investigations are used for extensive screening programms. [Smith]

Cost

At a basic level, the TST is cheaper - each test costs under $8 to administer, compared with a per-test cost of about $25 for the QFT-Gold. However, the QFT-Gold test provides the potential of significant long term reductions in expenditures. Currently, the highest costs in TST based TB control programmes lies in the number of health care workers required; expenditure on the actual TST test material represents under 2% of the total costs of the program. WIth reduction of medical visits from single visit test administration, a lower false positive rate reducing unneccsary dedication of medical practitioners, tests such as chest xrays, drugs to non-infected patients, and the potential for automation of large portions of the testing process, TB control programs employing QFT-Gold may significantly reduce costs of TB control. Nevertheless, implementation of a QFT-Gold programme at a large scale will require significant up front costs in testing materials,laboratory equipment and infrastructure. Moreover, many of the "extra" costs of TST programs are not borne by TB Control Programs but by private and public clinics, other County Departments, and so on. Costs of a QFT-Gold based program would require heavy investment by TB Control Departments. [Smith, San Francisco Guidelines, ]

Sensitivity and Specificty

While issues such as cost effectiveness and ease of use become significant in implementing changes to a TB control program, what has first been of primary interest among health care practitioners and public health officials is the actual specificity and sensitivity of the QFT-Gold test. IFN-Gamma Assays such as QFT-Gold appear are certianly more specific; refined antigen selection specific for M. tuberculosis rather than the more general PPD ensures that the test will not react to BCG vaccine or to most common non-tubercular strains of mycobacterium. However, actual research on the relative sensitivity of the test is limited. Studies thus far have been unable to categorically prove that the test is more sensitive in all population groups, due primarily to the wide range of patient populations in which large scale trials are conducted. [Smith, Pai] While the test is clearly valuable in detecting LTBI in general screening programs (at 80-89% sensitivity, an average of ten points above TST sensitivity, Kawamura), its sensitivity may not be as high in diagnosis of active TB. Further research is required to truely determine relative sensitivity, especially through the use of long term cohort studies. However, in countries with low endemicity of Tuberculosis, use of QFT-Gold and other IFN-Gamma release assays will certainly be valuable in evaluation of close contacts, broad screeing for LTBI, and evaluation of health care workers and employee groups. Further research may demonstrate its value in a broader range of population groups as well.If it is ultimately determined that a new diagnostic test is more effective than the TST in certain settings, the mos significant obstacke to its implementation will be convincing the range of officials and practitioners that phasing out an old and ineffective test is indeed a neccesary step for TB control programs.

It is important to remember that no current diagnositic test is perfect, and all of the existing immune-response based tests do have certain limitations. The tests have very low sensitivity in cases of patient anergy or immunocompromised state (caused for example by HIV+, a range of drugs including TNF-alpha blockers for diabetes and corticosteroids, as well as a range of other conditions), and newborns or young children with undeveloped immune systems. They are not sensitive enough to be used in following the effects of a course of drug therapy in LTBI patients, or for detecting very recent infection (within 2 to 8 weeks). However, these limitations are inherent to both the TST and current IFN-gamma assays. Further developments and enhancements in diagnostic technology may help to address these limitations.

 
QFT-Gold
TST

Antigens used will not react with strains used in the BCG vaccine or common strains of non-tubercular mycobacterium.

Can give false positive results with recent BCG vaccine ormany strains of non-tubercular mycobacteria.
Requires only one clinic visit with results within 24 hours.
Requires multiple visits; results available after 48 to 72 hours.
Quantifiable results are more easily categorized and automatable. Results are categorical and easy to read.
Test reading incredibly subjective, especially given lack of training of many practictitioners.
Requires the collection of blood, which must reach the lab within 12 hours for stimulation.
Relatively simple test with few required materials.
No boosting effect
Boosting can be a problem

Increased up front costs, but potential for long term reduction in costs.

Very cheap test, but inefficient use of resources.
May be more sensitive than TST.
May be less sensitive than QFT-Gold.
Tests not effective in certain cases: immunocompromised, very young children and new borns, recently infected individuals.
BCG Vaccine: Live attenuated vaccine using one of several strains of M. Bovis. The vaccine is not used in the United States but is used extensively in parts of the world. The BCG will usually only cause positive TST results if vaccination was recent, and reactions of over 10-15mm are almost always the result of TB infection.
Boosting: Individuals with LTBI may have a negative result with an initial TST if Tcelll memory has waned sufficiently. Subsequent TSTs may then give positive result if the immune response is boosted by the initial test.