The study, conducted by the Foundation for Innovative New Diagnostics (FIND), showed that the Xpert(R) MTB/RIF test successfully identified 98% of all culture-confirmed TB cases, including over 90% of those with smear-negative disease.
It also accurately detected resistance to the powerful anti-TB drug rifampicin (RIF) in more than 97% of patients, providing results in less than two hours.
The Xpert(R) MTB/RIF test is a cartridge-based, fully automated molecular diagnostic test for TB co-developed by FIND and its partners Cepheid and the University of Medicine and Dentistry of New Jersey (UMDNJ).
The test uses the Cepheid GeneXpert(R) system–a fully-automated technology platform based on real-time polymerase chain reaction amplification with integrated sample preparation.
Development of the assay was also supported by the U.S. National Institute of Allergy and Infectious Diseases (NIAID), Cepheid and the Bill & Melinda Gates Foundation.
This public-private partnership effort successfully demonstrates that combining the resources and expertise of diverse stakeholders, from fundamental science through translational research and product development to clinical evaluation, can lead to the rapid development of novel TB diagnostic tools.
Although rare in developed countries, TB remains one of the world’s deadliest infectious diseases. TB kills approximately 1.8 million people each year, mainly in developing countries, and drug-resistant TB is a growing threat.
Early detection of TB is crucial to stop the TB epidemic, because undiagnosed and untreated patients with active TB–including drug-resistant TB–can infect 10-15 other people each year.
“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,” said Dr Mario Raviglione, Director of the World Health Organization’s Stop TB Department. “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 programmes. These results suggest that it has the potential to revolutionize TB care, and WHO will treat it as a top priority.”
The most widely used method of TB diagnosis, sputum smear microscopy, is more than 125 years old and misses more than half of all TB cases. It cannot detect drug resistance and is largely ineffective in patients with HIV co-infection–a major driver of the global TB epidemic. At the same time, the most sensitive tool available for detecting TB or drug resistance is culture testing, which takes weeks to provide a result, is costly, requires capital intensive equipment, highly trained personnel and the construction of bio-safety facilities.
“The results of the study show that this innovative tool has the potential to revolutionize TB care for our patients,” said Dr L.S. Chauhan, Manager of the National Tuberculosis Programme in India. “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.”
Although molecular amplification tests for TB have been licensed for diagnostic use for over a decade, the Xpert(R) MTB/RIF test is the first in its class specifically designed for use by relatively unskilled health workers in endemic areas. Running the test requires little hands-on time and minimal technical skills or laboratory facilities. As such, it has the potential to be used outside reference laboratories, at local diagnostic centres or clinics, where the need is greatest.
The Xpert(R) 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.
“Quick and accurate TB diagnosis is critical to break the chain of disease transmission and prevent new TB infections,” said Dr Giorgio Roscigno, Chief Executive Officer of FIND, “and the results of this study confirm that the Xpert(R) 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.”
The study examined some 1,730 patients with suspected drug-sensitive or multidrug-resistant (MDR) pulmonary tuberculosis across five trial sites in Peru, Azerbaijan, South Africa and India between July 2008 and March 2009.
The Xpert(R) MTB/RIF test detected a greater fraction of all cases using a single sample than did conventional solid culture, the current “gold standard”. In addition, 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.
The test detected 200 of the 205 patients with rifampicin resistance (97.6% sensitive) and was over 98% specific in rifampicin-susceptible patients.
“The Xpert(R) MTB/RIF test is a ground-breaking advance, which is great to see coming from a product development partnership,” said Dr Peter Small, Senior Program Officer for TB at the Bill & Melinda Gates Foundation, whose accompanying editorial was published today.
“We also need additional support from many partners to ensure that new technologies reach those in need, and truly disrupt the spread of TB.”
FIND is a non-profit Swiss organization established in 2003, with offices in Switzerland, Uganda and India. Its mission is to develop, evaluate, demonstrate, and accelerate the roll out of new diagnostic tests and platforms for diseases of poverty, including TB, malaria and human African trypanosomiasis.
FIND’s approach is to address diagnostic needs across disease areas so that tests can also be implemented at levels of the health care system closer to where patients first seek care. FIND has active collaborations with over 100 partners, including Ministries of Health, bilateral and multilateral organizations, such as WHO, research institutes/academia, commercial partners and clinical trial sites.
In addition to its contribution to diagnostic advances for TB (with four diagnostic tools endorsed by WHO into global policy since 2007), and malaria (with the completion of the first-ever product testing program for rapid diagnostic tests), FIND has a significant program targeted at neglected diseases.
Current donors include the Bill & Melinda Gates Foundation, the Government of the Netherlands, the European Union, UNITAID, the UK Department for International Development, National Institutes of Health (USA) and others. FIND is ISO 9001:2008 and ISO 13485:2003 certified.
(1) Boehme et al., Rapid Molecular Detection of Tuberculosis and Rifampin Resistance.