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Active and Latent tuberculosis infection Diagnosis of infection Tuberculin skin test (TST) vs. Interferon-Gamma Release Assays (IGRAs) Principles of T-SPOT.TB test (1 type of IGRAs) Advantages and disadvantages of IGRAs
-May be infectious -Have TB symptoms -TST or IGRA result usually positive -Chest radiograph is usually abnormal.
(However, may be normal in persons with advanced immunosuppression or extrapulmonary disease.)
-Respiratory specimens are usually (but not always) smear or culture positive. (However, may
be negative in persons with extrapulmonary disease or minimal or early pulmonary disease.)
The number of people with active TB at a given time is just the tip of the iceberg, as many more are infected with TB and are therefore at a risk of developing the disease.
Most of the cases of active disease occur through the conversion of LTBI to active disease. tuberculosis control and elimination strategies must aim at diminishing the incidence and prevalence of latent infection.
Diagnostics for Tuberculosis: Global Demand and Market Potential/TDR, FIND SA. WHO 2006: p. 21.
Detect antibodies to pathogen (e.g. ELISA) If the immune system recognises antigens from the pathogen, the person must have been infected by the pathogen.
T-cell responses to pathogens Immune response = antibodies + T cells T cells control intracellular pathogens Many diseases where antibodies dont work. T cells are key in these diseases (e.g. HIV, Cancer, Allergy, Autoimmune disease, HPV, Hepatitis)
TST is administered by injection Tuberculin is made from proteins derived from inactive tubercle bacilli Most people who have TB infection will have a reaction at injection site Relates to delayed hypersensitivity reaction (delayed hypersensitivity T cells)
One of the major drawbacks of the Tuberculin Skin Test is the cross reaction that it has with BCG vaccination.
Why ?
The Purified Protein Derivative that is injected in the skin test is a crude mixture of around 200 peptides extracted from dead MTB cells. Many of these proteins have common epitopes to BCG (and environmental mycobacteria) so the skin test will cross react with these.
IGRAs measure a persons 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 derived from M. tuberculosis.
Types of IGRAs
QuantiFERON-TB Gold (QFT-G) CDC guidelines published in 2005 QuantiFERON-TB Gold In-Tube (QFT-GIT) Approved 10/2007 T-Spot.TB test (T-SPOT) Type of ELISpot assay Approved 7/2008
.TB T-SPOT
test
TB Skin Test Vs
.TB T-SPOT
The accuracy of the TB skin test varies and can be affected by a previous BCG vaccination, a weakened immune system and by other illnesses or medical treatments.
Both tests identify LTBI by using the body's immune response to TB proteins, whether the person is showing signs and symptoms of TB disease or not.
TB Skin Test
T-SPOT.TB
Very specific: Specificity approaching 100% Not affected by BCG vaccination Does not cross-react with common environmental mycobacterium
Very sensitive: Sensitivity ~95% Identifies infected subjects missed by TST Immunosuppression has little effect Performance maintained in infants High sensitivity in active TB, including extrapulmonary TB
False Negatives Skin reaction is a mixed immune response (problem in immunosuppressed patients) Often negative in active disease (7590% sensitivity, lower in immunosuppressed).
.TB T-SPOT
test bases on
the presence of memory T cells would only indicate that someone had been infected with the pathogen at some point in the past
Interferon gamma
Released by T cells Fights the infecting organism which has been recognized as foreign. Specific epitopes on the infecting organism have to be recognized by the T cells to initiate this release. the T-SPOT.TB test uses very specific antigens (ESAT-6 and CFP 10) to stimulate the effector T cells.
BCG vaccine (and most environmental mycobacteria) lose an area from M. bovis, which is known as the Region of Difference 1 (RD1). Nine proteins are made by this genomic area including ESAT-6 and CFP 10.
Requires single patient visit to conduct test Results can be available in 24 hours Very few false negative results (sensitivity ~95%)
Improving reliable detection of truly infected individuals Can be used in HIV, very young children,anti-TNF , transplant, renal dialysis, malnourished and other immunocompromised patient groups, as well as in pregnancy
No patient exclusions
Blood samples must be processed within 8-30 hours after collection while white blood cells are still viable. Errors in running and interpreting test can decrease accuracy Limited data on its use in certain populations
Children younger than 5 years of age Persons recently exposed to M. tuberculosis; Immunocompromised persons; and Serial testing.
Tests may be expensive. Limited data on the use of IGRAs to predict who will progress to TB disease in the future.
References
Benh hoc lao Y Ha Noi www.oxfordimmunotec.com www.cdc.gov/tb And some other websites