Changing the way the world looks at TB

Transcription

1 Changing the way the world looks at TB QuantiFERON -TB Gold

2 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). Importance of treating TB infection Incidence of global TB Diagnose/treat Latent TB only Diagnose/treat Active TB only 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). 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 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

3 It s time for a change 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 Calmette- Guérin (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. 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. 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. QFT peer-reviewed Clinical References (per cumulative year) Changing the way the world looks at TB 3

4 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 even if investigation of false-positives includes only chest X-rays and physician exams. Significant savings through fewer QFT false-positives 1,000 people 200 people 800 people False Positives True Negatives False positives per 1000 tests 6 True negatives per 1000 tests 624 QFT TST ( )x800 (1 0.78)x800 QFT (0.992)x800 TST (0.78)x TST QFT Sensitivity (Se)*: 71.5% Sensitivity*: 84.5% Specificity (Sp) : 78.0% Specificity*: 99.2% *Data from Diel et al, Chest, 2010; Calculated for a 50 % BCG vaccinated population, data from Pai et al, Annals Int Med, Changing the way the world looks at TB

5 Non-specific in vivo skin test Measurement of induration caused by a non-specific response to tuberculin PPD Presentation of mycobacterial antigens IFN-γ Highly-specific in vitro blood test Quantification of interferon-gamma levels stimulated by TB-specific antigens, ESAT-6, CFP-10, TB7.7(p4) Antigen Presenting Cell 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

6 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. Countries with IGRA Guidelines / Recommendations 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, by CDC, MMWR. QFT / IGRA Guidelines and Recommendations Australia ASID NTAC Bulgaria Canada CTC 2008, Czech Republic CTS Denmark DLHA EU ECDC EuroTB France HCSP HAS Germany DZK 2011, 2009, Italy SIGE AIPO Japan Kekkaku 2010, JST Netherlands KNCV 2011, New Zealand MOH Contact your local Cellestis representative for full reference listings. Norway Folkehelseinstituttet 2010, 2009, Poland Kucharz et al Portugal DGS 2011, Romania NHIH Saudi Arabia Al Jahdali et al South Korea KCDC Spain SEPAR Switzerland SUVA 2010, Beglinger et al UK NICE 2011, HPA USA CDC 2010, 2005, CDC Global Migration & Quarantine 2009, CDC/NIH/ISDA AAP ATS/CDC/IDSA US Armed Forces Changing the way the world looks at TB

7 QFT Procedure: Simple, reliable, reproducible Blood collection Nil TB Antigen Mitogen Collect 1 ml of Blood into Nil, Antigen, and Mitogen tubes Shake 10x Shake tubes 10 times at room temperature. Tubes can either be incubated then transported to lab or sent directly to lab for incubation. Manual Automated Centrifuge tubes to separate plasma. Complete the ELISA and obtain absorbance values Results Calculate results using QFT software These images are for illustrative purposes only. For full instructions, please refer to the QFT Package Insert on Changing the way the world looks at TB 7

8 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 Cellestis, a QIAGEN Company World Headquarters Cellestis Limited info@cellestis.com Tel: Australia/New Zealand Cellestis International anz@cellestis.com Tel: Europe/Middle East/Africa Cellestis GmbH Europe@cellestis.com Tel: Asia/Pacific QIAGEN Singapore PTE Ltd asiapac@cellestis.com Tel: Japan/Korea QIAGEN KK jp.kr@cellestis.com Tel: North America/South America Cellestis Inc. customer.service@cellestis.com Tel: (outside USA) Toll free: (USA only) QM D