A tuberculosis test, called Xpert® MTB/RIF, can successfully identify 98% of all culture-confirmed TB cases, including more than 90% of those with smear-negative disease, a study published in NEJM (New England Journal of Medicine) reveals. The test is highly sensitive for tuberculosis as well as drug resistance to the powerful anti-TB drug rifampicin (RIF) in low resource settings, the authors write. The study revealed that the Xpert® MTB/RIF was accurate in more than 97% of patients with drug resistance.

The Xpert® MTB/RIF was co-developed by FIND (Foundation for Innovative New Diagnostics), Switzerland, Cepheid, California, and the University of Medicine and Dentistry of New Jersey. It is a cartridge-based, fully-automatic molecular diagnostic TB test. FIND researchers inform that it uses the Cepheid GeneXpert system - " a fully-automated technology platform based on real-time polymerase chain reaction amplification with integrated sample preparation." There was also collaboration and help from by the NIAID (U.S. National Institute of Allergy and Infectious Diseases), Cepheid and the Bill & Melinda Gates Foundation.

In a press release, FIND informs that tuberculosis is still one of the deadliest infectious diseases on the planet, even though it is rare in industrialized nations. 1.8 million people die annually from tuberculosis (TB), the vast majority of them in developing countries. The threat of drug-resistance is becoming an increasingly serious health concern.

In order to stop the TB epidemic early detection is vital. The average undiagnosed patient who is infected with TB may pass the infection on to 10-15 other people each year.

Dr Mario Raviglione, Director of the World Health Organization's Stop TB Department, said:

The search for faster and more effective means to diagnose TB, which is the second greatest infectious killer of adults worldwide, is a top priority for the global health community. Over the next few days, WHO will convene independent experts to review the full evidence about the field effectiveness of this novel technology and propose it to country programs. These results suggest that it has the potential to revolutionize TB care, and WHO will treat it as a top priority.

Sputum smear microscopy is the most widely used method to diagnose TB - this diagnostic procedure is over 125 years also and is less than 50% accurate, does not detect drug resistance, and is fairly useless when HIV-positive patients have TB. A significant percentage of TB patients worldwide are also HIV positive.

Culture testing, the currently most sensitive tool for detecting TB or drug resistant, is very slow and expensive - results take weeks to come back. Culture testing requires significant capital investment, specialized training, as well as bio-safety facilities which are often not available in endemic areas.

Dr L.S. Chauhan, Manager of the National Tuberculosis Program, India, said:

The results of the study show that this innovative tool has the potential to revolutionize TB care for our patients. The new test enables health workers in the field to give patients a reliable on-the-spot diagnosis of TB and drug resistance during clinic visits, allowing for prompt diagnosis and early initiation of appropriate treatment.

Molecular amplification TB tests have been around for over ten years. However, the advantage of the Xpert® MTB/RIF test is that it can be used by relatively unskilled personnel in areas where TB is widespread. To run the test, the health workers need the minimal of technical skills and there is no need for sophisticated laboratory equipment. FIND writes that "it has the potential to be used outside reference laboratories, at local diagnostic centres or clinics, where the need is greatest."

The Xpert® MTB/RIF test inactivates the TB bacteria in the sputum sample, and requires no additional equipment, making it possible to decentralize diagnosis and give rapid, accurate results to patients, without the use of bio-safety facilities.

Dr Giorgio Roscigno, Chief Executive Officer of FIND, said:

Quick and accurate TB diagnosis is critical to break the chain of disease transmission and prevent new TB infections. and the results of this study confirm that the Xpert® MTB/RIF test provides a faster, more accurate result than the standard tests used today. Once WHO has issued a recommendation on the use of the test, FIND will work with international partners and national health programmes to accelerate global access to this potentially lifesaving technology.

In the study, investigators examined 1,730 patients with suspected drug-sensitive or multidrug-resistant (MDR) pulmonary tuberculosis in Azerbaijan, India, Peru and South Africa between July 2008 and March 2009.

The authors say that the Xpert® MTB/RIF test was able to detect a significantly greater fraction of all cases using a single sample than did the current gold standard solid culture method. Additionally, the test was 99.2% specific, showing positive results in only 5 of 609 culture-negative patients, all of whom were symptomatic with pulmonary disease.

Out of 205 patients with rifampicin resistance, the test identified 200 (97.6%) of them - and is was more than 98% specific in rifampicin-susceptible patients. Dr Peter Small, Senior Program Officer for TB at the Bill & Melinda Gates Foundation, said:

The Xpert® MTB/RIF test is a ground-breaking advance, which is great to see coming from a product development partnership. We also need additional support from many partners to ensure that new technologies reach those in need, and truly disrupt the spread of TB.

Dr. Small also wrote an Editorial (link at below).

Source: FIND (Foundation for Innovative New Diagnostics), Switzerland

"Rapid Molecular Detection of Tuberculosis and Rifampin Resistance"
Catharina C. Boehme, M.D., Pamela Nabeta, M.D., Doris Hillemann, Ph.D., Mark P. Nicol, Ph.D., Shubhada Shenai, Ph.D., Fiorella Krapp, M.D., Jenny Allen, B.Tech., Rasim Tahirli, M.D., Robert Blakemore, B.S., Roxana Rustomjee, M.D., Ph.D., Ana Milovic, M.S., Martin Jones, Ph.D., Sean M. O'Brien, Ph.D., David H. Persing, M.D., Ph.D., Sabine Ruesch-Gerdes, M.D., Eduardo Gotuzzo, M.D., Camilla Rodrigues, M.D., David Alland, M.D., and Mark D. Perkins, M.D.
NEJM September 1, 2010 (10.1056/NEJMoa0907847)

EDITORIAL
"Tuberculosis Diagnosis - Time for a Game Change"
Peter M. Small, M.D., and Madhukar Pai, M.D., Ph.D.
NEJM September 1, 2010 (10.1056/NEJMe1008496)



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