Cellestis’ Goals Cellestis (CST) has the following goals: (i) To...

Cellestis’ Goals

Cellestis (CST) has the following goals:

(i) To have its unique Quantiferon TB Gold (QFTG) blood test replace the 115 year old Tuberculin TB Skin Test (TST or Mantoux test) and become the preferred and most widely used test for TB infection worldwide.

(ii) To commercially exploit its Quantiferon (QFT) breakthrough technology platform measuring the cellular immune response, as a rapid diagnostic for various diseases. Cellestis’ first application of Quantiferon is for diagnosing TB.

5. Latent & Active TB

“Medical thinking now largely accepts that QFTG is a superior test [to the TST]”.
- Cellestis Annual Report - September 2005.

“All these studies point to the fact that the standard of TB diagnosis is now QFTG and the use of skin testing is an inferior medical practice.”

- Cellestis – February 2005

“QFTG and QFTG In-Tube represent the best TB diagnostic products that are currently available. They are highly specific, sensitive, robust, relatively inexpensive and logistically simple to perform.”

- Cellestis – December 2004

TB has afflicted humans for thousands of years; signs of the disease are found in Egyptian mummies. In the 19th century TB killed an estimated one-quarter of the adult population of Europe. For many people, a diagnosis of TB was considered a slow death sentence. The discovery of antibiotics curtailed the disease in industrial countries by the 1950’s. Today with migration, immunosuppression and drug resistance, TB is making a comeback.

To analyse the potential of CST it is first necessary to understand the difference between latent and active TB.

Latent TB

The World Health Organisation (WHO) estimates that around two billion people – one third of the world’s population – are infected with latent TB infection (LTBI). Persons with LTBI are not sick or contagious and the TB may lie dormant for years. However, 10% of these people will progress to active TB in their lifetime because a lowering of their immune system due to illness, HIV or old age will trigger active TB.

Treatment of LTBI greatly reduces the risk of progression to active TB, and is considerably cheaper and easier than treatment of active TB. Identifying people with LTBI is therefore crucial to the goal of TB eradication.

TB control programs in the US, Japan and Europe test an estimated 33 to 38 million people for TB each year. Up until QFTG, the only test available for latent TB has been the very inaccurate TST. QFTG is a highly accurate test for both latent and active TB and has significant advantages over the TST.

In latent TB, QFTG has at least 89% sensitivity and 99.8% specificity. The TST has only 66% sensitivity and 35% specificity. (Sensitivity of a test is the percentage of people reliably classified as having the disease. Specificity of a test is the percentage of people reliably classified as not having the disease).

QFTG’s sensitivity in LTBI is in fact likely to be higher than 89% for two reasons. First, clinical trial results currently being processed indicate that QFTG In-Tube has enhanced sensitivity. Second, the immune response is lower in active TB patients than in healthy but latently infected individuals, and thus the sensitivity of QFTG for latent TB infection is likely to be higher than 89%. In the absence of a gold standard definitive test for LTBI, the sensitivity of QFTG can only be measured in active TB patients.

The TST has been the front line TB test, however it is notoriously unreliable due to false-positive and false-negative results. In a major report in 2000, the US Institute of Medicine recorded the failings of the TST as the single largest problem for TB control in the USA.

“The only reason the tuberculin is still around is because it was introduced before the US Food & Drug Administration was formed. It would never be approved by the FDA today. Unfortunately, it has been the only test available for 100 years”.

- Professor Peter Barnes, November 2005.

The TST requires physical examination of the skin reaction, which is highly subjective, and can be easily misinterpreted even by trained TST readers. (It is for this reason that on 30/12/2005 the US Centers for Disease Control issued new Health Care Workers TB guidelines specifying onerous and costly ongoing annual training for TST administrators). The TST has poor reproducibility and requires two patient encounters; one to inject the subject and a second to read the inflammation it may produce. Commonly, up to 30% of placed tests are never read because the patient fails to return for the second appointment.

Of major significance, the TST is confounded by previous TB vaccination with BCG (Bacillus Calmette-Guerin), as well as by exposure to non-tuberculosis mycobacteria, resulting in a high rate of people with TST false-positive results in certain populations.