— Calls for Further Price Cuts to Ensure Global Access —
December 8, 2010
NEW YORK, NY, U.S.A. – A new rapid test for tuberculosis (TB) which was just recommended by the World Health Organization (WHO) for widespread use has the potential to revolutionize the world’s fight against the disease, said the Treatment Action Group today, but there are a number of obstacles that threaten to limit its impact, including cost.
“The new test, which yields results in two hours rather than the weeks to months it takes for standard TB culture to grow, has the potential to cause a paradigm shift in TB diagnosis and treatment, “said TAG Executive Director Mark Harrington. “The WHO has taken a bold step which if implemented by countries in TB and HIV programs has the potential to save millions of people from the ravages of HIV related and suspected multi-drug resistant (MDR) TB. But more actions are needed to make sure it reaches those most in need.”
Harrington noted that people with TB/HIV and MDR-TB are among those at greatest risk of death from the disease. Delayed diagnosis costs millions in undiagnosed or improperly treated TB, which sickened 20 million people and killed almost 2 million in 2009.
The test (called Xpert MTB/RIF) was developed by Cepheid of Sunnyvale, CA, with grant support from the U.S. National Institutes of Health, the Bill & Melinda Gates Foundation, the University of Medicine and Dentistry, New Jersey (UMDNJ), and the Foundation for Innovative New Diagnostics (FIND). While FIND has worked with Cepheid to reduce the cost of the test, TAG and other organizations have called for further price reductions to help ensure availability in resource-poor countries that are the most hard hit by TB.
“We desperately need tools like the Xpert MTB/RIF test so that we can get people on life-saving treatment. With the current TB tests, many people with HIV are either not diagnosed, misdiagnosed, or dead before TB is properly diagnosed and treated,” said Nelson Tom Otwoma, a TB/HIV activist from the Network of People Living with HIV/AIDS in Kenya.
The Xpert MTB/RIF is a cartridge based test which involves placing a small amount of sputum into a self-contained cartridge which decontaminates the sample, breaks open the cells, and copies their DNA to determine whether the Mycobacterium tuberculosis (Mtb) bacillus and mutations associated with resistance to rifampin—the anchor of first-line treatment for the disease—are present. The test takes two hours and successfully detects between 92-98% of culture confirmed cases. The test also detects up to 73% of smear negative pulmonary TB cases, demonstrating potential to identify HIV positive TB cases and 98% of TB cases with resistance to rifampin within hours rather than the weeks to months it currently takes using standard TB culture tests.
According to TAG’s TB/HIV Project Director, Javid Syed, “The test is a vast improvement over what is currently available. Even though it is expensive, at $19 per test and $17,000 per machine at the best current price for middle and low-income countries through the public sector, the test has major potential to reduce the burden on patients and on the health system. For the test to have a meaningful impact, we need to ensure that national TB programs and international donors such as the Global Fund to Fight AIDS, Tuberculosis and Malaria, and the U.S. government through the U.S. Agency for International Development (USAID) and the President’s Emergency Plan for AIDS Relief (PEPFAR) support urgent and accelerated roll out and implementation of the new test where it is most needed so that TB cases are detected rapidly and treated with the right course of antibiotic therapy.”
TAG expressed concern about the high cost of the test and the lack of U.S. Food and Drug Administration approval for its use in the United States. “The sponsor, Cepheid, deserves praise for working with FIND to develop a tiered pricing scheme to broaden access to the Xpert MTB/RIF test,” said Syed. “However, the test cost will need to come down further to maximize the availability and accessibility of the test where it is needed most.”
TAG’s Mark Harrington said, “Cepheid has received $3.3 million dollars in U.S. research contracts from the NIH to develop this TB test. The least it can do in return is to provide the test at an affordable price, and to submit the test for approval by the U.S. FDA so that the taxpayers who funded its development can benefit from its use. Though the numbers of TB cases are much smaller in the U.S., detecting TB is cumbersome everywhere, and FDA approval will further encourage global uptake. Only through innovations such as the Xpert MTB/RIF test will the world be able to reach the goal of eliminating TB as a public health threat by 2050.”
Blessina Kumar, a TB activist from India added, “We applaud WHO’s recommendation of Xpert MTB/RIF as a new rapid TB test, but caution that continued research is necessary to develop an accurate, rapid, and cheap ($1) point-of-care test for TB that does not require sophisticated instruments, electricity, and can diagnose TB in HIV positive individuals and in infants and children unable to produce sputum.”
Federal Tuberculosis Task Force (CDC, FDA, NIH, USAID)
December 8, 2010
Maximizing the Promise of Breakthrough Tuberculosis Test
The Federal TB Task Force* is collaborating to help ensure patients in the United States and around the world have access to a test that can revolutionize tuberculosis (TB) diagnosis and treatment. Xpert MTB/RIF is an automated test that can provide earlier and improved tuberculosis (TB) case detection. In studies, it has been shown to be an accurate and reliable test for diagnosing TB that does not require extensive laboratory safety measures.
This new test can detect TB and rifampicin resistance, a proxy for multidrug-resistant (MDR) TB, in less than 2 hours from a sample of respiratory fluid coughed up by a patient. Current laboratory tests for TB are skill intensive and require a minimum of 17 days for liquid culture and over 30 days for solid culture; drug-susceptibility testing requires an average of 75 days to get results. During this lag time, patients continue to suffer and can spread TB infection to others. Having TB test results within hours is an important step in improving patient-centered care and early case detection.
Xpert MTB/RIF is especially important for HIV-infected persons who are at greatest risk for rapid progression of TB disease, and in whom this disease is a leading cause of death. It is also important for persons at increased risk for MDR TB to prevent prolonged delays in diagnosis and to ensure appropriate treatment.
In 2009, the Federal TB Task Force released the Plan to Combat Extensively Drug-Resistant Tuberculosis (http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5803a1.htm), calling for enhanced laboratory capacity and evaluation of rapid tests for the diagnosis of TB and the detection of drug resistance, both in the United States and worldwide. The Federal TB Task Force has also issued an international strategy for U.S. support for the Global Plan to Stop TB through the President’s Emergency Plan for AIDS Relief (PEPFAR) and the Global Health Initiative.
Action Steps Being Taken
The Federal TB Task Force is aware of the global significance of a rapid and accurate tuberculosis test, and have been eager to accept and review data that would support the safety and effectiveness of such a test. However, the use of Xpert MTB/RIF has only been studied in countries with high rates of TB; thus, additional testing is needed in U.S. populations that have a low TB rate in order to secure Food and Drug Administration (FDA) approval and develop appropriate guidance for its use in our country. Recognizing the commitment other government agencies and support groups have made in the global fight against tuberculosis as well as the need to support medical device innovation, FDA, the National Institutes of Health (NIH), and the Centers for Disease Control and Prevention (CDC) recently held a public workshop on tuberculosis. Additionally, the FDA has been working with Cepheid, the manufacturer of Xpert MTB/RIF, on the pathway forward for seeking approval of their assay in the United States. Uptake of the Xpert MTB/RIF rapid diagnostic test will help both U.S. and global partners meet goals in reducing TB death and disease.
* The Federal Tuberculosis (TB) Task Force is a coalition composed of the federal agencies involved in U.S. TB research and control efforts. Established in 1991, it facilitates coordination of activities among these federal agencies. It was established under the leadership of the Director of the Centers for Disease Control and Prevention (CDC) (then William C. Roper, MD) to address the outbreaks of multidrug-resistant (MDR) TB occurring during the 1985-1992 surge in TB cases.
For additional information
• National Institute of Allergy and Infectious Diseases (NIAID):http://www.niaid.nih.gov/news/newsreleases/2010/Pages/TBdiagnostic.aspx
• World Health Organization: http://www.who.int/tb/features_archive/new_rapid_test/en/index.html
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PEPFAR — U.S. Global Health Programs Welcome World Health Organization Endorsement of Rapid Test for Tuberculosis
December 8, 2010
Following is the text of a joint statement by the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), U.S. Agency for International Development and U.S. Department of Health and Human Services.
The United States welcomes the policy statement and roadmap issued today by the World Health Organization (WHO) charting the rollout of the Xpert MTB/RIF rapid diagnostic test for tuberculosis (TB) and rifampicin resistance, a proxy for multidrug resistant tuberculosis (MDR-TB).
The limitations of traditional smear microscopy, along with the cost and long delays to receive culture results, have limited the ability to expeditiously diagnose and treat TB. The impact is witnessed daily in healthcare facilities and communities in the highest burden areas: increases in deaths that can be prevented, prolonged transmission of the TB bacteria, and delays in detecting drug resistance to the antibiotics we rely on to treat TB. The capacity to improve the diagnosis of TB has thus been a global priority, but the prospect of access to such a test was unthinkable just a few short years ago.
With today’s release of normative guidance and an implementation roadmap by WHO, we have reason to be hopeful. With funding from the U.S. National Institutes of Health and the Bill and Melinda Gates Foundation, FIND (Foundation for Innovative New Diagnostics) spearheaded a novel public-private partnership with Cepheid, Inc. and the University of Medicine and Dentistry of New Jersey to develop a TB-specific, automated nucleic amplification assay (Xpert MTB/RIF). This fully integrated and automated instrument has the capacity to detect the presence of TB disease and resistance to rifampicin in less than two hours. Of special importance to global health programs in rural areas, the tool can be decentralized to settings very close to where patients seek services in their communities.
The rapid test will be critical for programs supported by the U.S. Government, primarily through the bilateral programs of U.S. Agency for International Development (USAID) and in high HIV-prevalence contexts benefitting from PEPFAR support. The U.S. Government agencies contributing to global TB control, namely USAID, PEPFAR, and the U.S. Centers for Disease Control and Prevention (CDC), are committed to working together to support the rapid scale-up and appropriate use of this new technology.
Ambassador Eric Goosby, M.D., U.S. Global AIDS Coordinator commented, “WHO’s endorsement is welcome news to PEPFAR given the real impact this new rapid test will have on saving lives. With this endorsement, PEPFAR now has validation of the evidence base for this tool as well as a roadmap for implementation and field-level evaluations to be accelerated in 2011. HIV-associated TB is the leading cause of death among people living with HIV in the Africa region. During the early years of PEPFAR, the U.S. has partnered with Ministries of Health, strengthening and expanding laboratory services to support HIV testing, care of opportunistic infections (including TB diagnosis and treatment), and monitoring of antiretroviral treatment. We look forward to further partnering with Ministries of Health, WHO, FIND and other partners to ensure that we use the platform established through PEPFAR to facilitate the rapid uptake of this critical new technology.”
Dr. Raj Shah, USAID Administrator said, “Rapid diagnosis, coupled with improved health delivery systems and stronger community awareness, is critical to the early detection and treatment of TB. To win the fight against TB we must slow the growth of drug resistance by providing quality basic TB control, investing in the rapid and appropriate uptake of Xpert MTB/RIF and other new technologies and continuing to support the research and development of new tools. USAID stands ready to support the roll-out of this new technology, including the advancement of sound international policy, training and impact monitoring.”
Dr. Thomas Frieden, CDC Director said, “Having a reliable test that can detect TB and MDR-TB in less than two hours from a patient’s sputum specimen is a great tool. This is especially important in caring for HIV-infected persons who are at greatest risk for rapid progression of TB disease, and in whom this disease is a leading cause of death. It is also important to prevent prolonged delays in diagnosis and to ensure appropriate treatment in areas where multidrug resistant TB is common. Xpert MTB/RIF rapid diagnostic test for TB and MDR TB, in conjunction with effective tuberculosis diagnosis, treatment, and monitoring, will help reduce disease and death from TB.”
WHO ENDORSES NEW RAPID TUBERCULOSIS TEST
8 December 2010 | LONDON | GENEVA |
Today, WHO endorsed a new and novel rapid test for tuberculosis (TB), especially relevant in countries most affected by the disease. The test could revolutionize TB care and control by providing an accurate diagnosis for many patients in about 100 minutes, compared to current tests that can take up to three months to have results.
A major milestone
“This new test represents a major milestone for global TB diagnosis and care. It also represents new hope for the millions of people who are at the highest risk of TB and drug-resistant disease.” said Dr Mario Raviglione, Director of WHO’s Stop TB Department. “We have the scientific evidence, we have defined the policy, and now we aim to support implementation for impact in countries.”
WHO’s endorsement of the rapid test, which is a fully automated NAAT (nucleic acid amplification test) follows 18 months of rigorous assessment of its field effectiveness in the early diagnosis of TB, as well as multidrug-resistant TB (MDR-TB) and TB complicated by HIV infection, which are more difficult to diagnose.
Increase in diagnosis
Evidence to date indicates that implementation of this test could result in a three-fold increase in the diagnosis of patients with drug-resistant TB and a doubling in the number of HIV-associated TB cases diagnosed in areas with high rates of TB and HIV.
Many countries still rely principally on sputum smear microscopy, a diagnostic method that was developed over a century ago. But this new ‘while you wait’ test incorporates modern DNA technology that can be used outside of conventional laboratories. It also benefits from being fully automated and therefore easy and safe to use.
WHO is now calling for the fully automated NAAT to be rolled out under clearly defined conditions and as part of national plans for TB and MDR-TB care and control. Policy and operational guidance are also being issued based on findings from a series of expert reviews and a global consultation held last week in Geneva. The consultation was attended by more than a hundred representatives from national programmes, development aid agencies and international partners.
Affordability has been a key concern in the assessment process. Co-developer FIND (the Foundation for Innovative and New Diagnostics) is announcing today it has negotiated with the manufacturer, Cepheid, a 75% reduction in the price for countries most affected by TB, compared to the current market price. Preferential pricing will be granted to 116 low- and middle- income countries where TB is endemic, with additional reduction in price once there is significant volume of demand.
“There has been a strong commitment to remove any obstacles, including financial barriers, that could prevent the successful roll-out of this new technology,” said Dr Giorgio Roscigno, FIND’s Chief Executive Officer. “For the first time in TB control, we are enabling access to state-of-the-art technology simultaneously in low, middle and high income countries. The technology also allows testing of other diseases, which should further increase efficiency.”
WHO is also releasing recommendations and guidance for countries to incorporate this test in their programs. This includes testing protocols (or algorithms) to optimize the use and benefits of the new technology in those persons where it is needed most.
Though there have been major improvements in TB care and control, tuberculosis killed an estimated 1.7 million people in 2009 and 9.4 million people developed active TB last year.
For more information please contact:
World Health Organization (WHO)
Mobile: +41 79 509 0677
Foundation for Innovative New Diagnostics (FIND)
Mobile +41 79 935 6419
All related material is available at www.who.int/tb