Download Changing the way the world looks at TB

Changing the way the world looks at TB
QuantiFERON®-TB Gold
www.QuantiFERON.com
Identifying TB Infection is essential
Tuberculosis (TB) remains a significant threat to humanity. At least one billion people are thought to
be infected. A person who is infected with Mycobacterium tuberculosis, but who shows no symptoms
and is not sick with the disease, is regarded as having latent TB infection (LTBI).
Incidence of global TB
Importance of treating TB infection
Diagnose /treat
Latent TB only
Diagnose /treat
Active TB only
Although not everyone who becomes infected with TB
bacteria develops active TB disease, individuals with latent
TB and a compromised immune system are more likely to
progress to active TB. Certain communities remain at higher
risk of TB infection (CDC. Questions and Answers about
TB), including:
„„healthcare workers
„„the elderly
Diagnose /treat
Latent and Active TB
Increasing focus area over time to 2050
Theoretical graph of how treating latent and
active TB together can overcome global TB burden.
Model supported by data from Dye & Williams
(J R Soc Interface 2008).
„„immigrants
„„homeless
„„inmates
„„military personnel
„„
people taking certain medications (ie. TNF-blocker
medications)
„„people with a weakened immune system
„„public health officials working with TB control.
Approximately one in every 10 people with TB infection
will progress to active TB (CDC Fact Sheet: The Difference
Between Latent TB Infection and Active TB Disease). The key to
controlling TB is accurately and efficiently identifying the one
in 10. Global organizations are beginning to acknowledge
that to fight TB effectively, identifying and treating latent TB
infection—as well as active TB disease—are vital.
“…eliminating TB by the mid-century is most likely to be achieved if current treatment programmes
can be coupled with new approaches to reduce the vast reservoir of latent human [TB] infection.”
Dye & Williams (J R Soc Interface 2008).
2 Changing the way the world looks at TB
It’s time for a change
(per cumulative year)
500
400
300
200
100
20
10
08
20
06
20
04
20
02
20
20
00
0
98
A new paradigm in diagnosing TB infection is now
available: Interferon-gamma release assays (IGRAs). IGRAs
are blood tests that detect TB infection with significantly
higher specificity and sensitivity than the TST.
QFT peer-reviewed Clinical References
19
Previously, the only tool available for identifying TB
infection was the Tuberculin Skin Test (TST),or Mantoux. The
TST measures immune responses to tuberculin PPD, which is
made up of a multitude of bacterial proteins. Most of these
proteins are present in the TB vaccine, Bacille CalmetteGuérin (BCG), and shared with many environmental
mycobacteria. The TST has several limitations including
subjective results and frequent false positives often due
to cross-reactivity with BCG vaccination or responses to
environmental mycobacteria.
The most clinically tested and proven IGRA is the
QuantiFERON®-TB Gold In-Tube test (QFT®). QFT is a highlyspecific, controlled blood test for diagnosis of infection with
the bacteria responsible for TB. QFT provides results with a
high degree of accuracy. With over 450 published, peerreviewed clinical references, QFT is the most researched
IGRA. Its clinical value is now well-proven. Unlike the TST:
„„
QFT is unaffected by previous BCG vaccination and
most other environmental mycobacteria.
„„QFT requires only one patient visit.
„„QFT does not boost subsequent test results.
„„QFT is a controlled laboratory test.
„„
QFT provides an objective, reproducible result that is
unaffected by subjective interpretation.
„„QFT results can be available within 24 hours.
Changing the way the world looks at TB 3
QFT: the modern replacement for the TST
When evaluating the impact of a test on TB screening
programs, sensitivity and specificity are familiar
parameters. How they interact with prevalence to
influence negative and positive predictive values
(NPV, PPV) and overall test accuracy is important to
understanding the clinical significance of a test.
The relationship between sensitivity, specificity, NPV,
PPV, and accuracy is exemplified in the diagram
below. By applying QFT and TST sensitivity and
specificity estimates (Diel et al, Pai et al), QFT
delivers a significant improvement over the TST in
terms of both NPV and PPV at prevalence rates
between 0 % and 50+ %.
For example, when TB prevalence is 20%—a
realistic rate in contact investigations—QFT provides
close to 50% improvement in accuracy compared
with the TST.
QFT’s increased accuracy has significant and tangible
benefits for TB control programs—better outcomes for
patients, more confidence in correctly identifying TB
infection, and significant cost savings through fewer
false-positive results. Studies show that switching to
QFT provides significant program cost advantages—
over $64,000 saved per 1000 people tested, even
if investigation of false-positives includes only chest
X-rays and physician exams.
Significant savings through fewer QFT false-positives
200 people
1,000 people
800 people
True Negatives
False Positives
794
True negatives
per 1000 tests
False positives
per 1000 tests
176
624
6
QFT
TST
(1– 0.992)x800 (1– 0.78)x800
QFT
(0.992)x800
$64,000 savings with QFT
TST
(0.78)x800
TST
QFT
Sensitivity (Se)*: 71.5%
Sensitivity*: 84.5%
Specificity (Sp): 78.0%
Specificity*: 99.2%
TST
QFT
Cost Difference
(per 1000 tested)
Chest X-ray
176 x $300 = $52,800
6 x $300 = $1,800
$51,000
Physician exam
176 x $ 80 = $14,080
6 x $ 80 = $480
$13,600
Total savings with QFT vs TST based on false-positive results:
$64,600
*Data from Diel et al, Chest, 2010; `Calculated for a 50 % BCG vaccinated population, data from Pai et al, Annals Int Med, 2008.
4 Changing the way the world looks at TB
Highly-specific
in vitro blood test
Quantification of
interferon-gamma
levels stimulated by
TB-specific antigens,
ESAT-6, CFP-10,
TB7.7(p4)
Non-specific
in vivo skin test
Measurement of
induration caused
by a non-specific
response to tuberculin PPD
Presentation of
mycobacterial
antigens
Antigen
Presenting
Cell
IFN-γ
Effector
Cell
QFT contains TB mycobacterial proteins which are not found in the BCG vaccine.
Because of this highly-specific composition, QFT overcomes virtually all of the
shortcomings of the TST, with the added benefit of providing a laboratory-based,
objective result.
„„QFT is significantly more precise than TST in identifying people who will
progress to active TB disease.
„„
QFT is significantly more sensitive, nearly halving the number of infected
people missed by the TST.
„„QFT is >99% specific, virtually eliminating false-positive readings (false
positives by TST range from 3% to 65% of all persons tested, dependent upon
the population).
(Diel, et al. Am J Respir Crit Care Med, 2011; Diel, et al. Chest, 2010; Diel, et al. Am J Respir Crit
Care Med, 2008; Pai, et al. Annals Int Med, 2008; Mori, et al. Am J Respir Crit Care Med, 2004)
Changing the way the world looks at TB 5
IGRAs: Endorsed around the world
Many countries around the world recognize IGRA technology for detecting TB infection. A considerable
diversity of strategies exists: some countries have multiple guidelines regarding IGRAs, some have
“official” government mandates while other institutions such as universities, hospitals, and medical
professional societies provide policy and recommendations for TB infection testing.
IGRAs preferred
Other test preferred
The CDC guidelines establish a new benchmark, recommending IGRAs as the preferred TB testing
method for many patients, including BCG vaccinated and those unlikely to return for TST reading.
“Updated guidelines for using Interferon-Gamma Release Assays to detect Mycobacterium tuberculosis infection—United
States, 2010.” by CDC, MMWR.
QFT / IGRA Guidelines and Recommendations
Australia ASID 2009. NTAC 2007.
Norway Folkehelseinstituttet 2010, 2009, 2007.
Bulgaria 2011
Poland Kucharz et al. 2008.
Canada CTC 2008, 2007.
Portugal DGS 2011, 2010.
Czech Republic CTS 2006.
Romania NHIH 2010.
Denmark DLHA 2010.
Saudi Arabia Al Jahdali et al. 2010.
EU ECDC 2011. EuroTB 2007.
South Korea KCDC 2009.
France HAS 2006.
Spain SEPAR 2008.
Germany DZK 2011, 2009, 2007.
Switzerland SUVA 2010, 2007. Beglinger et al. 2007.
Italy SIGE 2011. AIPO 2009.
UK NICE 2011, 2006. HPA 2008.
Japan Kekkaku 2010, 2008. JST 2006.
USA CDC 2010, 2005, 2003. CDC Global Migration
& Quarantine 2009, 2007. CDC/NIH/ISDA 2009. AAP
2009. ATS/CDC/IDSA 2009. US Armed Forces 2009.
Netherlands KNCV 2007.
New Zealand MOH 2010.
Contact your local Cellestis representative for full reference listings.
6 Changing the way the world looks at TB
QFT Procedure: Simple, reliable, reproducible
QFT Procedure
Blood collection
Nil
TB Antigen Mitogen
Collect
1 ml
of of
Blood
into
Collect
1 ml
Blood
intoNil,
Nil,
Antigen,
Antigen,and
andMitogen
Mitogentubes
tubes
Shake tubes
tubes 10
10 times at room temperature.
Shake
temperature.
Tubes
can
either
incubated
thentransported
transported
Tubes
can
either
bebe
incubated
then
to
lab
or
sent
directly
to
lab
for
incubation.
to lab or sent
for incubation.
Shake
10x
Manual
Automated
Centrifuge
tubes
separate
plasma. Centrifuge
tubes
to to
separate
plasma.
Complete
Completethe
theELISA
ELISAand
andobtain
obtain
absorbance
values values
absorbance
Results
Calculate
results
using QFT software
Calculate
results
using QFT software
These images are for illustrative purposes only. For full
instructions, please refer to the QFT Package Insert on
www.QuantiFERON.com.
Changing the way the world looks at TB 7
QFT has been CE marked. QFT is approved by the US FDA
QFT is approved by FDA as an in vitro diagnostic aid for detection of Mycobacterium tuberculosis infection.
It uses a peptide cocktail simulating ESAT-6, CFP-10 and TB7.7(p4) proteins to stimulate cells in heparinized
whole blood. Detection of IFN-γ by ELISA is used to identify in vitro responses to these peptide antigens
that are associated with M. tuberculosis infection. FDA approval notes that QFT is an indirect test for
M. tuberculosis infection (including disease) and is intended for use in conjunction with risk assessment,
radiography and other medical and diagnostic evaluations. QFT Package Inserts, available in up to 25
different languages, can be found at www.cellestis.com.
Cellestis, a QIAGEN Company
World Headquarters
Cellestis Limited
Email: [email protected]
Tel: +61 3 8527 3500
Europe/Middle East /Africa
Cellestis GmbH
Email: [email protected]
Tel: +49 6151 428 590
Japan/Korea
QIAGEN KK
Email: [email protected]
Tel: +81 3 6890 7300
Australia/New Zealand
Cellestis International
Email: [email protected]
Tel: +61 3 8527 3500
Asia/Pacific
QIAGEN Singapore PTE Ltd
Email: [email protected]
Tel: +65 6854 8100
North America/South America
Cellestis Inc.
Email: [email protected]
Tel: +1 661775 7480 (outside USA)
Toll free: 800 519 4627 (USA only)
QM05995192D
www.QuantiFERON.com