TUBERCULOSIS: India: Doctors express concern over wrong diagnosis

Apr 30, 2011,
LUCKNOW: Wrong diagnosis turned out to be a cause of concern for veteran doctors who gathered at Chhatrapati Shahuji Maharaj Medical University's pulmonary medicine department here on Friday.
"Roughly 25% diagnosis for tuberculosis is wrong, as physicians do not examine patients correctly. They go by what the tests reflect and as a result doctors get confused between TB, chronic obstructive pulmonary disease and other lung disease that are different from each other," said Prof Rajendra Prasad, head, pulmonary medicine department and member state task force on tuberculosis.
Acknowledging the fact, Dr P N Tandon, who set up neuro-surgery departments at AIIMS and CSMMU said, "The best diagnosis is done by the eyes and hands of the physicians." Padma awardee and former director of National Brain Research Institute, Dr Tandon added, "Machines may have become important for diagnosis but they can never replace humans."
http://articles.timesofindia.indiatimes.com/2011-04-30/lucknow/29490304_1_diagnosis-doctors-machines

TUBERCULOSIS: Rapid Tuberculosis Diagnostic Methods Inaccurate Alone

April 04, 2011.

Rapid microbial and immunological diagnostic methods are not accurate enough to diagnose or exclude pulmonary tuberculosis, according to a study published online March 21 in the Journal of Internal Medicine.

MONDAY, April 4 (HealthDay News) -- Rapid microbial and immunological diagnostic methods are not accurate enough to diagnose or exclude pulmonary tuberculosis, according to a study published online March 21 in the Journal of Internal Medicine.
Claudia Jafari, M.D., from the Research Center Borstel in Germany, and colleagues evaluated different methods used for an initial treatment decision in 135 individuals with suspected pulmonary tuberculosis. A specific algorithm including initial smear microscopy and M. tuberculosis-specific nucleic acid amplification from sputum, was used to enroll individuals with suspected tuberculosis. Tuberculin skin testing, bronchoscopy with transbronchial biopsies, and interferon-γ release assays (IGRAs) in peripheral blood and bronchoalveolar lavage (BAL) fluid were performed in cases of negative test results.
The researchers identified 42 cases of tuberculosis, 10 cases of non-tuberculous mycobacteria pulmonary infection/colonization, and 84 with a different diagnosis. Sputum microscopy had sensitivity of 41 percent and specificity of 99 percent. BAL nucleic acid amplification had sensitivity of 31 percent and specificity of 98 percent. M. tuberculosis-specific BAL fluid IGRAs had 92 percent sensitivity and 87 percent specificity for the tuberculosis diagnosis in patients with acid-fast bacilli smear-negative tuberculosis.
"The key finding of the study was that none of the evaluated methods alone was able to reliably diagnose or exclude tuberculosis," the authors write. "A stepwise diagnostic approach may yield the best results for a rapid preliminary diagnosis of tuberculosis, justifying treatment initiation while the results of M. tuberculosis cultures are pending."
http://www.doctorslounge.com/index.php/news/pb/19092

TUBERCULOSIS: Immediate treatment for drug resistant tuberculosis possible with “while you wait” test

Geoff Watts An instrument developed in the US after the country’s anthrax contaminated letters scare of 2001 has now been endorsed by the World Health Organization as a more effective means of testing for tuberculosis.
Manufactured by the Californian company Cepheid, the Xpert MTB/RIF uses a disposable cartridge containing all the reagents required to perform the test. Results are available in about 90 minutes.
Sputum smear microscopy, the method commonly used for detecting tuberculosis, was developed 125 years ago. It misses many cases, especially in children and people who are HIV positive. The diagnosis of drug resistant tuberculosis relies on bacterial culture and drug susceptibility testing. These findings are not available for weeks or even months during which time a drug resistant strain can continue to spread.
The new test is fully automated, poses few biosafety hazards, can be operated in a non-specialist laboratory, and detects the presence of rifampicin drug resistance, an indicator of multiple drug resistance. Patients can be offered the appropriate treatment immediately.
Demonstrated this week at press conferences held in London and Geneva, journalists were able to see for themselves how straightforward the instrument is to use.
The operator first scans the bar code on a small lidded cartridge, a few centimetres square. The addition to the sputum sample of a prepared solution renders it non-infectious within 15 minutes. Using a pipette, 2 mL of this mixture are put into the cartridge which, after closing its lid, is slipped into the instrument. The results are displayed on a laptop computer.
Giorgio Roscigno, chief executive of the Foundation for Innovative New Diagnostics (FIND), the not-for-profit organisation that helped to develop its application to tuberculosis, said, “By changing the cartridges you could also use this instrument for other diseases.”
Explaining WHO’s decision to endorse the instrument Karin Weyer, of its Stop TB department, pointed to the accumulated data. “An expert group reviewed the evidence from around 12 000 patients evaluated in a variety of settings,” she said. “We are now recommending that we move as quickly as possible to provide policy guidance and a road map to countries to get this test working in the field.”
Multiple drug resistance poses a severe challenge to national tuberculosis programmes according to a recent editorial in the New England Journal of Medicine (2010;363:1070-1). “Globally,” say the authors, “fewer than two per cent of the estimated cases of multi-drug resistant disease are reported to the WHO and managed according to international guidelines.”
The new instrument costs $17 000 (£10 800; €12 900) and can perform 16-20 tests in eight hours. Each test costs $16.86, but will drop to $10.72 by 2014 if uptake proceeds as intended. South Africa and India are among countries that have plans to use the system, and many non-governmental bodies active in fighting tuberculosis have also expressed interest or said they will promote it.
http://www.bmj.com/content/341/bmj.c7132.full

TUBERCULOSIS: U.S. Global Health Programs Welcome World Health Organization Endorsement of Rapid Test for Tuberculosis

 Dec. 8, 2010 /PRNewswire-USNewswire/ -- 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."

Public Information: 202-712-4810: SOURCE U.S. Agency for International Development

http://www.prnewswire.com/news-releases/us-global-health-programs-welcome-world-health-organization-endorsement-of-rapid-test-for-tuberculosis-111546774.html

TUBERCULOSIS: WHO urges roll-out of new TB test despite worries over cost

A test that can detect TB, including drug-resistant forms, in less than two hours could revolutionise treatment of the disease, according to the World Health Organisation, which is urging its roll-out across the globe.
Tuberculosis killed 4,700 people every day last year. The annual death toll of 1.7 million includes 380,000 people who are at particular risk because they have HIV, the virus that depresses the immune system and causes Aids.
The current diagnostic test for TB has been used for 125 years. It involves microscopic examination of a sputum sample and is not ideal because it doesn’t easily detect the growing number of strains that are resistant to antibiotics, or TB where the patient is also infected with HIV.
Some patients have to wait as long as three months to be diagnosed, which means their treatment is delayed and their prospects of recovery are reduced. The long wait also increases the chances they will infect others and, if they are given the wrong antibiotics for their particular strain of TB, drug resistance can worsen.
The new test delivers a result in 100 minutes. Dr. Mario Raviglione, Director of the WHO’s Stop TB department, said, “This new test represents a 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.”
He added, “We have the scientific evidence, we have defined the policy, and now we aim to support implementation for impact in countries.” The number of TB cases is set to rise as the test is rolled out. The WHO says drug-resistant cases could increase threefold and the number of cases where the patient is co-infected with HIV could double.
Trials and demonstration studies have been carried out over 18 months in a number of different countries, involving more than 8,000 patients. The test is a fully-automated nucleic acid amplification test, which the WHO says is simple and safe to use. It incorporates modern DNA technology that can be used outside of conventional laboratories - although the need for a constant electricity supply may be a problem in rural settings.
The major issue will now be cost. The market price for the equipment is $55,000 to $62,000, with an additional $55 to $82 for the cartridges it uses. The makers, Cepheid, have agreed to cut the price by 75 per cent for the poorest countries. However, at $16.86 per test, the cost is higher than the current system and the roll-out will depend on donor funding.
http://www.thehindu.com/health/medicine-and-research/article941615.ece

TUBERCULOSIS: DNA test developed by UMDNJ researcher may revolutionize tuberculosis diagnosis, treatment

December 10, 2010,
Seth Augenstein


William Perlman/The Star-Ledger:  (L-R) Danielle Amisano, research teaching specialist V along with Padmapriya Banada, Ph.D., research teaching specialist III work with test spit samples using the revolutionary new test (developed by a UMDNJ doctor) endorsed this week by WHO, at the UMDNJ-NJ Medical School Center for Emerging and Reemerging Pathogena Division of Infectious Diseases in Newark.

 NEWARK — The test used to detect for tuberculosis is basically the same today as it was for the past 100 years — slow. So slow that while patients waited up to three months for the results they spread their disease to others and even died — particularly in impoverished countries.
But on Wednesday the World Health Organization endorsed a new weapon in the fight against the disease: a two-hour automated DNA test which could slow the creeping contagion, and simply "revolutionize" treatment across the world.
The new test was developed by David Alland, the chief of the division of infectious diseases from the University of Medicine and Dentistry of New Jersey — New Jersey Medical School. It uses DNA analysis to provide a diagnosis in as little as two hours.
"This new test represents a major milestone for global TB diagnosis and care," said Mario Raviglione, director of the WHO’s Stop TB Department. "It also represents new hope for the millions of people who are at the highest risk of TB and drug-resistant disease."
Under the old testing method, a sample of a patient’s saliva is taken and brought to culture then examined under a microscope — a tedious and time consuming process. The initial screening for the TB bacteria often involves a skin test which may show that a patient is carrying the disease but only the saliva test shows it’s progressed to disease.
The DNA test is simpler, does not present any risk of infection, is more accurate – particularly in identifying drug-resistant TB, while also bringing the quicker results, Alland said.
"The test will say whether TB is there or not, and whether the TB is drug-resistant," Alland said. "Overall, the test picks up 98 percent of all TB … It picks up strains the microscope misses."
Patients still spit into a cup, but now they are mixed and shaken up with an agent that renders the sample safe. Then the mixture is transferred to a test cartridge and inserted into the DNA analysis machine. About 100 minutes later, the results are in – and with only two minutes of total hands-on time for health workers. Gone are the hours over the microscope, and weeks or months of waiting – and infecting others.
Alland developed the quicker, more accurate test in 1996 but getting it a stage in which it could be widely used on took years.
He said developing the technology for the test took four years, then he had to get funding for to help perfect it and finally he had to find a private company to take on its deployment around the world. Various experts predicted Thursday that the new test could save millions of lives over decades to come.
The test machines, cartridges and technology are manufactured by Cepheid, a California-based genetic testing company, with help from the international non-profit Foundation for Innovative New Diagnostics. The start-up money for the research came from the National Institutes of Health and the Bill and Melinda Gates Foundation, but it also came with a catch: that the cost of the machines be made affordable to the neediest parts of the world.


William Perlman/The Star-Ledger:  Dr. Padmapriya Banada, PhD, Research Teaching Specialist III work with test spit samples using revolutionary new test (developed by UMDNJ doctor, endorsed this week by WHO) at the UMDNJ-NJ Medical School Center for Emerging and Reemerging Pathogena Division of Infectious Diseases.

The test is a bit more expensive than the old microscope method. The machines alone cost between $55,000 and $62,000 and cartridges cost $55 apiece. But there are 116 countries around the world which will be considered preferred customers because of their current infection rate. As such, their tests will be reduced by 75 percent, down to just $16 per test, and that cost will be decreased down to $10 after the first 3 million tests worldwide, Alland said.
"I think that’s a really good business model," the doctor said.
The WHO plans to test with the machine quickly, reaching that 3 million test threshold by 2014. The test comes at a crucial stalemate in the fight against HIV and TB co-infection, according to experts. Approximately 2 billion people worldwide still carry the baccilus of the disease. Nine million develop the disease each year — mostly in Southeast Asia and Africa — and about 1.6 million die from it annually, according to the World Health Organization.
A report written in the journal Nature in 2006 estimated that an automated, quicker and reliable test – such as the one developed by Alland and Cepheid – would save the lives of 392,000 people around the world annually.
Lee Reichman, the executive director of UMDNJ’s Global Tuberculosis Institute, and a colleague of Alland’s, said the new test would easily save that many patients — and more.
"It revolutionizes TB diagnosis and treatment," Reichman said. "The fact that the WHO endorsed it is dynamite."
http://www.nj.com/news/index.ssf/2010/12/innovative_dna_test_developed.html

TUBERCULOSIS: New diagnostics for tuberculosis: fulfilling patient needs first

Jean-Francois LemaireMartina Casenghi
Credits/Source: Journal of the International AIDS Society 2010, 13:40

An effective tuberculosis (TB) control programme requires early diagnosis and immediate initiation of treatment. Any delays in diagnosing TB not only impair a patient's prognosis, but also increase the risks of transmitting the disease within the community.
Unfortunately, the most recent TB diagnostic tools still depend on high-infrastructure laboratories, making them poorly adapted for use in resource-limited settings. Additionally, existing tests show poor performance in diagnosing TB in children, people living with HIV/AIDS, and extrapulmonary forms of the disease.
As a consequence, TB patients are still to date left with either fair access to poor diagnostics or poor access to fair diagnostics.
Discussion
This article discusses recent efforts to identify the minimal test specifications for a new TB point-of-care diagnostic test through an approach based on medical and patient needs. As a first step, survey interviews with field practitioners were designed in order to identify the top-priority medical needs in resource-limited settings concerning new TB diagnostics.
Subsequently, an expert meeting convening field practitioners, laboratory experts, diagnostic test developers and researchers was held with the objective of defining the minimal test specifications for a new TB point-of-care test that would meet the identified medical needs. Finally, gaps in, as well as potential solutions for, enabling the development of adequate, patient needs-driven, low-cost new TB diagnostic tests specifically designed for vulnerable populations are discussed.SummaryAny new TB point-of-care diagnostic test should be designed to meet minimal specifications satisfying the most urgent medical needs in resource-poor settings.
The major gaps for developing a new TB point-of-care test include identification of new biomarkers, simplification of technological platforms, development of adequate and accessible specimen banks, and identification and definition of reference standards for diagnosis of childhood TB. Innovative research and development funding ensuring de-linkage of research and development costs from the price of the new product, such as a prize fund mechanism, could help focus these efforts towards the delivery of a much-needed point-of-care diagnostic test for TB.
http://7thspace.com/headlines/361287/new_diagnostics_for_tuberculosis_fulfilling_patient_needs_first.html

TUBERCULOSIS: Patient Friendly Research To Fight Tuberculosis (TB)

by bobbyramakant September 1, 2010

The present diagnosis and treatment regimen for tuberculosis is almost 40 years old. According to the WHO, with the currently available diagnostic tools, we are able to diagnose just 61% of TB cases globally. This means that 40% of the cases go undetected and inadvertently help in further transmission of the disease in healthy people. Dr Christian Lienhardt, who heads the Research Movement of the Stop TB Partnership, gave exclusive interview to CNS during the recently concluded “Open Forum 4: Critical Path to TB Regimen: New Hope of Life for TB Patients” in Addis Ababa, Ethiopia (18-19 August 2010).The current drug regimen comprises 4 different drugs/tablets which have to be taken daily for a period of 6 months. It has a fairly good success rate of 80%. But the treatment is very cumbersome. The patient has to take the drugs, which are available at the Directly Observed Treatment Shortcourse (DOTS)/ health centres, usually every day. This is easier said than done. It has been seen that many patients discontinue treatment before the stipulated 6 months period. They may have to trudge long distances to reach the clinic, and/or have to take leave from work, or might just be unable to bear the severe side effects. This discontinuation of the treatment midway could result in a relapse or drug resistant TB, which is still more difficult to cure. Even the existing TB vaccine (Bacillus Calmette Guerin - BCG) has a variable efficacy which is waning with time. According to the WHO, "BCG vaccine has a documented protective effect against meningitis and disseminated TB in children. It does not prevent primary infection and, more importantly, does not prevent reactivation of latent pulmonary infection, the principal source of bacillary spread in the community. The impact of BCG vaccination on transmission of Mtb is therefore limited."It is true that after reaching a peak in 2004, the incidence of the disease has shown a decline. But this is very slight—a mere 1% per year. With this slow pace it would be almost impossible to reach either the Millennium Development Goal (MDG) of halting and reversing the incidence of TB by 2015. So we need better tools for early detection and efficient treatment to cure 100% of the patients and also control the spread of the disease. All this requires extensive basic research in all allied fields. Researchers have to come up with new vaccines for prevention, better diagnostic equipment/tests, and shorter treatment regimens which are more patient friendly. Research in all these fields is of utmost importance. Researchers from various facilities –be they bio chemical labs, or pharmaceutical companies or PDPs (product development partnerships) -- will have to join hands for the discovery of better drugs.It is very important that there is enough funding to put all this basic research in place for new discoveries to happen as soon as possible. The next phase involves a long drawn out period of clinical trials to test the efficacy of the new tools in real life situations. Then comes the implementation part of research which ensures that the new vaccines/ drugs/ diagnostics are adopted where needed most. This is very important, especially at the diagnostic stage, as the diagnosis of TB will vary according to the level where it can be applied. If the patient has access to a modern hospital with trained personnel, then he/she can undergo more sophisticated and reliable tests. In peripheral labs we need simpler tests which allow one to identify TB cases with the help of easily available instruments which do not require professionals to operate them. Dr Christian Lienhardt mentioned some existing modern diagnostic tools, some of which can shorten the time of diagnosis to as less as 2 hours. One of them is LED Microscopy which gives far better and quicker results than the normal sputum testing done by an ordinary microscope. Another method is the culture base method. This method allows the bacteria, in a culture of sputum, to grow for better identification. Then the effect of the drugs on these germs is tested. If a drug kills them they are sensitive to it; if not then it is established that they are drug-resistant. The latest in this line is the Interferon Gamma Release Assay (IGRA) test which involves taking a blood sample to test for dormant as well as active TB. But these are not cost effective, and currently not being used commercially on a general basis, and are available only in a few select hospitals. The WHO recommends the use of these tools as they can dramatically shorten the time taken for TB diagnosis, which is a crucial factor in TB treatment.As for the availability of new drug regimens which will make the TB treatment simpler and shorter, Dr Lienhardt feared that we may have to wait for a couple of years. Despite best efforts of like minded partners like TB Alliance, the proverbial magic cure will not come about over night. However, there is greater excitement on the front of new drugs for MDR-TB (multi drug resistant TB). There are two new drugs for MDR-TB which have shown very encouraging results and are in the second phase of clinical trials. They show the promise of better efficacy and shorter treatment duration, and hope to be used in the foreseeable future.The first step forward has been taken with active support from the TB Alliance which has been working to spearhead the testing of new TB drug candidates in combination with one another. This has lead to a revolutionary cross-sector initiative called the Critical Path to TB Regimens (CPTR), which is a collaboration of pharmaceutical companies; government/ regulatory agencies; donors; academia; advocates— all having the common aim to accelerate the development of new, safe, and highly effective tuberculosis (TB) treatment regimens with shorter therapy durations. This is an urgent public need for saving millions of lives. http://www.nowpublic.com/health/patient-friendly-research-fight-tuberculosis-tb

TUBERCULOSIS: Tuberculosis Diagnosis — Time for a Game Change

Peter M. Small, M.D., and Madhukar Pai, M.D., Ph.D.
The effective treatment of tuberculosis is a lifesaving intervention. The global scale-up of tuberculosis therapy has averted 6 million deaths over the past 15 years, making it one of the greatest public health interventions of our lifetime. Unfortunately, by the time most patients are treated, they have already infected many others. This failure to interrupt transmission fuels the global epidemic so that every year there are more new cases of tuberculosis than in the previous year.
National tuberculosis programs are particularly challenged by multidrug-resistant tuberculosis. Globally, fewer than 2% of the estimated cases of multidrug-resistant disease are reported to the World Health Organization (WHO) and managed according to international guidelines. The vast majority of the remaining cases are probably never properly diagnosed or treated, further propagating the epidemic of multidrug-resistant tuberculosis.
The situation is further worsened by the epidemic of human immunodeficiency virus (HIV), especially in Africa. For decades there has been little effort to improve techniques for diagnosing tuberculosis. Consequently, tuberculosis tests are antiquated and inadequate. The most widely used test (smear microscopy) is 125 years old and routinely misses half of all cases. These inadequacies are particularly problematic since such tests are generally performed in underfunded and dysfunctional health care systems.4,5 The problem is exacerbated
by the widespread use of inaccurate and inappropriate diagnostic tools, such as serologic assays, in many countries. Fortunately, in the past few years, several improved tuberculosis tests have received WHO endorsement for widespread use. In this issue of the Journal, Boehme and colleagues8 describe a new automated nucleic acid–amplification test that may allow a relatively unskilled health care worker to diagnose tuberculosis and detect resistance to a key antibiotic within 90 minutes. This test and others that are likely to follow have the potential
to revolutionize the diagnosis of tuberculosis. Thus, in the coming years, rapid diagnosis and targeted treatment will provide the greatest opportunity for stopping the tuberculosis epidemic.
In a large, well-conducted, multicountry study, Boehme et al. evaluated an automated tuberculosis assay (Xpert MTB/RIF) for the presence of Mycobacterium tuberculosis (MTB) and resistance to rifampin (RIF). With a single test, this assay identified 98% of patients with smear-positive and culture-positive tuberculosis (including more than 70% of patients with smear-negative and culturepositive disease) and correctly identified 98% of bacteria that were resistant to rifampin.
The assay has several critical advantages over conventional nucleic acid–amplification tests, which have been licensed for nearly 20 years and yet have not had a substantial effect on tuberculosis control. The MTB/RIF assay is simple to perform with minimal training, is not prone to cross-contamination, requires minimal biosafety facilities, and has a high sensitivity in smear-negative tuberculosis (the last factor being particularly relevant in patients with HIV infection). However promising these findings, issues involving the MTB/RIF assay may limit its global utility. These issues include its high cost, limitations in testing only for rifampin resistance, a platform that detects a relatively small number of mutations, and inability to indicate which patients are “sputum smear–positive” for reporting purposes, infection-control intervention, and treatment monitoring.
On the plus side, the MTB/RIF assay promises to decentralize molecular diagnosis, since it potentially can be used at the point of treatment in
a microscopy center or in a tuberculosis or HIV clinic. However, because Boehme et al. used the test at reference laboratories, their study offers only indirect proof of concept for use in such settings.
Critical to a rapid scale-up of the test will be the results of additional studies to determine how it performs in such settings and whether its use improves outcomes for patients in a cost-effective manner.
If an improved rapid nucleic acid–amplification test is adopted globally, it could help avert more than 15 million tuberculosis-related deaths by 2050.9 However, even the most promising diagnostic test will have only limited impact if it
does not reach the patients who need it. As with any diagnostic test or intervention, its actual impact will depend on the system in which it is used.
Health systems must be strengthened so that patients do not delay in seeking care and have prompt access to appropriate treatment once they receive a diagnosis. Health-system barriers to the use of improved technologies must be anticipated and addressed. Although the burden on health systems will be reduced by a simple dipsticklike, point-of-care assay, such tests are not likely to be available in the short term.7
To realize the potential of improved technologies, a diverse set of stakeholders need to support large-scale innovation and delivery. Scientists and industry need to develop radically improved tools, including drugs and vaccines, while offering
reasonable pricing that reflects public health needs and economic realities in resource-limited countries. Operational and implementation researchers need to quickly identify and respond to the full spectrum of issues that form the critical
path to improving the prevention and control of tuberculosis. Policymakers and regulators must turn scientific evidence into permissive policies and regulations that allow national programs to rapidly incorporate new tools. Funders must increase and reprogram resources to become conduits for innovation and not fund decades-old technologies for years into the future. Programs must maintain focus on the basics of tuberculosis control while quickly modifying delivery systems
to take advantage of the benefits of improved tools. Lastly, patient advocates and activists should hold everyone accountable and ensure that communities
drive demand for improved systems and tools.
Despite these challenges, it is clear that improvements in diagnostics are driving a virtuous cycle in care: the promise of improved tests drives their uptake, their uptake results in better health outcomes, improved outcomes attract more unding for health care systems, and better-funded systems are an incentive to the development of even better technologies. We are particularly optimistic
about the potential role of governments, product developers, and companies in emerging economies with high tuberculosis burdens, such as China, India, Brazil, and South Africa. These countries now have the capacity to develop lowcost
generic or novel assays adapted to local contexts and incorporate their scale-up in both national tuberculosis-control programs and private laboratories, supported by successful public–private partnerships. Emerging economies have the potential to become global leaders in innovative product development and delivery. If these countries successfully tackle their own tuberculosis problems, the limination of tuberculosis by 2050 might become a reality.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
From the Global Health Program, Bill and Melinda Gates Foundation,
and the Institute for Systems Biology, Seattle (P.M.S.);
and the Department of Epidemiology and Biostatistics, McGill
University, and Montreal Chest Institute, Montreal (M.P.).
This article (10.1056/NEJMe1008496) was published on September
1, 2010, at NEJM.org.
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and elimination 2010-50: cure, care, and social development.
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of tuberculosis. Science 2010;328:856-61.
3. Perkins MD, Small PM. Partnering for better microbial diagnostics.
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4. Small PM. Strengthening laboratory services for today and
tomorrow. Int J Tuberc Lung Dis 2008;12:1105-9.
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diagnosis of tuberculosis in the HIV era. J Infect Dis 2007;
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6. Pai M, Minion J, Steingart K, Ramsay A. New and improved
tuberculosis diagnostics: evidence, policy, practice, and impact.
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7. Wallis RS, Pai M, Menzies D, et al. Biomarkers and diagnostics
for tuberculosis: progress, needs, and translation into practice.
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detection of tuberculosis and rifampin resistance. N Engl J Med
2010. DOI: 10.1056/NEJMoa0907847.
9. Abu-Raddad LJ, Sabatelli L, Achterberg JT, et al. Epidemiological
benefits of more-effective tuberculosis vaccines, drugs,
and diagnostics. Proc Natl Acad Sci U S A 2009;106:13980-5.
Copyright © 2010 Massachusetts Medical Society.

TUBERCULOSIS: Molecular profiling

Thanks to molecular profiling, scientists now have a better idea about how a mass killer selects its victims. And the new analysis suggests that the killer, TB, may use a different murder weapon than researchers previously believed.
Mycobacterium tuberculosis infects one-third of people worldwide. But only about 10 percent of people infected will actually get sick with a debilitating lung disease. Until now, scientists had no way to predict who would become ill.
Now, an international consortium of researchers has compiled profiles of genetic activity in the blood of people with dormant TB infections, people with active infections, and healthy people. Those profiles show how the immune system deals with tuberculosis and point to some surprising culprits responsible for awakening a slumbering infection. Such profiles may help predict who will succumb to TB, the researchers report in the Aug. 19 Nature.
“This is literally the way to tell who is going to get sick,” says Clifton Barry, chief of the tuberculosis research section at the U.S. National Institute of Allergy and Infectious Diseases in Bethesda, Md. This study could revolutionize TB diagnosis in the same way that breast cancer treatments were forever changed by the discovery that some tumor cells make molecules that respond to estrogen, and that those molecules can serve as targets for chemotherapy, Barry says.
In the new study, researchers drew blood from TB patients and from healthy people in London and analyzed gene activity in the blood cells. People who had active infections had 393 genes with activity different from that seen in healthy people. The team could classify people into groups—no infection, latent infection or active illness—just by looking at the gene activity profiles in their blood. The findings were replicated in a separate group of patients from Cape Town, South Africa. The TB signature disappeared as people were treated with antibiotics.
About 10 to 25 percent of people with latent infections had signatures similar to those of people with active infections, indicating that people with the active profile may go on to develop the disease even if their infection is currently dormant, says study coauthor Matthew Berry of the MRC National Institute for Medical Research in London. The researchers are planning to follow people with latent infections to see if those with the signature really are the same ones who develop active infections later. If the results hold up, the blood profiles could be the first means of predicting who is likely to get sick from TB.
That could spare people from developing a lung-damaging infection, but may also mean that people who aren’t likely to get sick won’t need to take anti-TB drugs that can damage the liver.
Blood cells called neutrophils also appeared in the new study to be important for spreading the disease. Previously, researchers didn’t think that short-lived neutrophils could play any role in such a long-term infection as tuberculosis. The dogma in the field was that the bacterium infected only immune cells called macrophages, says study leader Anne O’Garra, also of the MRC National Institute for Medical Research. The new study indicates that genes turned on by a protein known as type 1 interferon become active in the neutrophils of people with full-blown TB. Interferon helps to fight off viral infections but may actually make bacterial infections such as TB even worse, O’Garra says.
These findings fit well with recent data from mouse studies implicating both neutrophils and interferon in serious disease caused by tuberculosis, says Andrea Cooper, an infectious disease immunologist at the Trudeau Institute in Saranac Lake, N.Y.
“We’re at a watershed here in changing what we think the disease is about,” she says.
TB’s molecular signature was distinct from the profiles of blood taken from people with autoimmune diseases, such as lupus, and from those with other infectious diseases like Streptococcus or Staphylococcus infections, the researchers found. The discovery was unexpected, as most researchers thought that different types of bacteria might change the activity of specific genes at the site of the infection but that those differences would not show up in the blood, Cooper says. The variety of signatures indicates that the immune system has developed multiple ways of dealing with infectious organisms.
“It highlights the beauty of the immune response and its finesse in dealing with different pathogens,” Cooper says.
http://www.usnews.com/science/articles/2010/08/19/gene-profiles-may-predict-tb-prognosis.html

TUBERCULOSIS: Test offers hope of tuberculosis breakthrough

A blood test that can tell doctors whether someone is likely to develop the active and dangerous form of tuberculosis has become a realistic possibility.
Scientists believe they have finally found a way that could distinguish the 10 per cent of people infected with TB who will go on to develop the full-blown disease from the 90 per cent of healthy carriers who have the latent form of the lung infection.
It would mean that doctors could concentrate on treating the one in 10 infected people who are at high risk of becoming seriously ill, rather than attempting to give potent anti-TB drugs to everyone who is shown to be infected with the TB bacterium.
About two million people worldwide die each year from TB, mostly in the developing world, but the disease has also made a come-back in developed countries. In Britain 9,153 cases were recorded in 2009, the largest annual increase (5.5 per cent) since 2005, with nine out of 10 cases occurring in ethnic minorities.
The researchers, led by Anne O'Garra of the Medical Research Council's National Institute for Medical Research in London, found a "genetic signature" in the blood of people with active TB which could be used as the basis of a diagnostic test.
The study in the journal Nature also found the same genetic signature – evidence of certain infection-related genes being activated – in 10 per cent of people with the latent form of the disease. However, further work needs to be done to assess whether this 10 per cent will be the same 10 per cent of latent patients who go on to develop active TB, Dr O'Garra said.
"As an immunologist, what most intrigued me was that approximately a third of the world has been exposed or infected with the TB bacterium but only 10 per cent of these people get sick and the question is why – what determines when people get active tuberculosis?" Dr O'Garra said.
"What we've described is a distinct blood gene signature in active TB patients, and intriguingly this is absent in other infectious diseases and also in healthy individuals. But it is present in latent TB individuals, but only in 10 per cent of these individuals," she said.
The study involved a wide range of ethnic groups in London, where 3,500 cases of TB were diagnosed last year, about 40 per cent of all UK cases. More than 400 participants took part in the study, which also involved analysing the blood of TB patients in Cape Town in South Africa.
"By doing the study in London we were able to involve individuals with a really wide range of backgrounds and diverse ethnicity and thus make our findings more widely available to this global disease," said Matthew Berry, a consultant in respiratory medicine.
The blood signature found in active TB patients is independent of ethnicity, age and sex, and appears to reflect the severity and extent of the disease. The signature also disappears after successful treatment, Dr Berry said.
"What such a test would enable is very targeted treatment. Instead of trying to treat everyone with latent TB you could focus all of your efforts on that 10 per cent who would develop the disease," he said.
The genetic signature shows that certain genes in specialised blood cells called neutrophils have been turned on by the action of a molecule in the immune system known as type-1 interferon, which can aggravate bacterial infections, Dr O'Garra said. "Finding these molecules expressed in TB suggests that they may be contributing to make the disease worse," she said.
Robert Wilkinson of the University of Cape Town said that the existing diagnostic test for TB has not changed for 125 years. "We're excited by the study because it gives us greater insight into how tissue damage might occur in tuberculosis. It also raises the prospect of developing a diagnostic test or a way of learning who is most at risk of TB," he said.
http://www.independent.co.uk/news/science/test-offers-hope-of-tuberculosis-breakthrough-2056374.html

TUBERCULOSIS: new $240 microscope

A new $240 microscope that runs on AA batteries is as effective for diagnosing tuberculosis as $40,000 professional laboratory models.
The microscope, described online in the journal PLoS ONE, weighs just two and a half pounds and could be used in developing countries that lack expensive lab equipment and reliable electricity.
"The World Health Organization estimates that 1.3 million people died from tuberculosis in 2008," study researcher Rebecca Richards-Kortum, a professor of bioengineering at Rice University, said in a statement. The microscope, "which is portable, durable and inexpensive, could be used to diagnose tuberculosis in community or rural health centers with limited infrastructure in the developing world, promoting early detection and successful treatment of the disease."
The microscope was developed by Andrew Miller, then a Rice undergraduate and now a designer for San Francisco-based medical device firm Thoratec.
To test the microscope's reliability, Miller and his colleagues used 64 slides of saliva samples, some of which were contaminated with tuberculosis. Each sample was stained and examined under Miller's portable Global Focus microscope and under a standard laboratory microscope worth thousands of dollars. The person examining the slides did not know which were contaminated. In 98.4 percent of cases, the examiner's conclusions using both microscopes were identical.
The researchers have filed a patent on the microscope and have contracted with the medical device company 3rd Stone Design to produce 20 models that will be field tested next month, according to Rice University.
"This is hugely significant as a point-of-care tool clinicians can use for tuberculosis patients, whether they're in Asia or Africa or even in West Texas," study co-author Edward Graviss of the Methodist Hospital Research Institute in Houston said in the statement.
"The first identification of TB is usually made with a smear, and it will be good to know that in the field instead of having to wait three or four days to get the smear to a lab."
http://www.msnbc.msn.com/id/38645474/ns/technology_and_science-innovation/

TUBERCULOSIS: Singapore invests in tuberculosis research

Aug. 12 -- An investment of 3 million Singapore dollars (about 2.2 million U.S. dollars) is being pumped into tuberculosis (TB) research in Singapore, the country's Agency for Science, Technology and Research (A*STAR) said on Thursday.
The project, joined by A*STAR's Singapore Immunology Network and bioindustrial group Institut Merieux, involves setting up a joint laboratory in Singapore to investigate and identify novel biomarkers that could allow early identification of individuals at risk of TB disease development and disease reactivation.
At the shared lab, researchers will study the immune cells in the blood of infected individuals without active TB, and compare them with those in individuals with active TB, as well as non- infected healthy controls. Any change in gene expression and behavior of the immune cells will then be analyzed to identify biomarkers associated with TB infection and/or TB re-activation.
This information would be pertinent to clinicians and researchers as current tests cannot reliably detect if the individual is at risk of developing the disease. This will lead to early and accurate assessment of the effectiveness of treatment in TB patients.
http://news.xinhuanet.com/english2010/health/2010-08/12/c_13441629.htm

Jul. 29, 2010
Often causing no symptoms in carriers of the disease, worldwide tuberculosis (TB) infects eight to ten million people every year, kills two million, and it is highly contagious as it is spread through coughing and sneezing. “It’s a global health disaster waiting to happen, even here in Canada, but this new paradigm in TB research may offer an immediate opportunity to improve vaccination and treatment initiatives,” explains Dr. Maziar Divangahi of McGill University and of the Research Institute of the McGill University Health Centre.
The ability of TB bacteria to persist in individuals with apparently normal immune systems implies that they have developed strategies to avoid, evade, and even subvert immunity. The bacteria mainly enter the body through inhalation into the respiratory tract. Alveolar macrophages, a type of white blood cell residing in our lungs, initially recognize the bacteria and engulf them. This process is one of our immune system’s defense mechanisms. However, TB has evolved into a parasite that can survive and replicate inside the macrophages until they burst out, spreading the infection.
The way infected macrophages die is a determining factor in the development of immunity to TB. Macrophages can induce apoptosis, a type of cell death which keeps their membrane intact, trapping and reducing bacterial viability. However, TB bacteria induce another type of cell death called necrosis. Necrosis causes cell death by disrupting the cell membranes, which enables the bacteria to escape the cell. It may help to visualize a box with broken walls.
The key to the fate of the macrophages is the balance between two kinds of eicosanoids. Eicosanoids are molecules that contribute to the control of our immune system. The genetic code of TB bacteria enables it to tip this balance in favor of necrosis, and human genetic analysis revealed that modification in eicosanoids production is associated with susceptibility or resistance to TB. Fortunately, drugs that target the production of eicosanoids are already in use for treating other inflammatory diseases, such as rheumatoid arthritis.
“The next steps will be to see exactly how these drugs can be used to treat TB,” said Divangahi. The research received funding from the Fonds de la Recherche en Santé du Québec and was published in Nature Immunology. Divangahi is affiliated with the Departments of Medicine and Microbiology/Immunology of McGill’s Faculty of Medicine, with the Research Institute of the McGill University Health Centre, and with the Meakins-Christie Laboratory.
http://www.mcgill.ca/newsroom/news/item/?item_id=165121

TUBERCULOSIS: India: The outcasts of Tuberculosis

July 10, 2010
Mumbai: It may be curable but Tuberculosis (TB) remains a stigma in our country especially for women. Over a lakh Indian women are thrown out of their homes each year because they have TB.NDTV brings you the story of a woman who was deserted by her husband one year after marriage because she was diagnosed with TB.The 21-year-old woman's only fault was that she was infected with tuberculosis."I had been married for a year. Three months after the wedding I started coughing and was admitted to a clinic. An X-Ray showed I had TB. My husband and his family insisted my mother take me home. After that my husband has not come to see me even once. When the doctor told them I had TB my husband said he did not want me. He told my mother I would infect everyone in the family," said TB patient.
She is not alone in her isolation. Every year, one lakh women in India are thrown out of their homes because they have tuberculosis.India accounts for one third of the world's TB cases but it's women who bear the brunt of the social stigma.It's a curable disease and yet every year one million women die of tuberculosis worldwide. One of the main reasons experts say, is because women delay seeking diagnosis afraid of rejection.At the government TB hospital in Mumbai, one of the largest facilities in the country, of the 200 women admitted for treatment most have been abandoned by their families."In our country when women get the infection they are largely ill-treated by the family. Often the husbands leave them here and go away. They don't take them back home," said Dr Vijay Jumar Narvengkar, Dean, Government TB Hospital, Mumbai.The disease may have a cure but the stigma doesn't
http://origin-netmg.ndtv.com/article/india/the-outcasts-of-tb-tuberculosis-36625?cp

TUBERCULOSIS: Misindentification of Mycobacterium kumamotonense as M. tuberculosis

Because of slow growth of mycobacteria, use of rapid tests to identify them is strongly recommended; rapid tests are widely used as an advanced diagnostic tool in clinical laboratories (1,2). These tests are particularly useful for diagnosing extrapulmonary mycobacterioses and identifying unusual mycobacteria as etiologic agents (3). Commercial probes are frequently used for rapid and specific identification of mycobacteria, especially Mycobacterium tuberculosis complex. However, cross-reactivity of DNA probes between mycobacterial species could result in incorrect diagnosis and treatment of patients (4,5). Misidentification could be a problem if a newly described species, such as M. kumamotonense (6), were an etiologic agent of a disease.
In July 2006, we obtained a fine-needle, puncture aspiration biopsy specimen from a cervical lymph node of a 30-year-old man at Doce de Octubre Hospital (Madrid, Spain). The patient was a recent immigrant from Paraguay and was HIV positive (C2 stage of infection). A biopsy specimen from a cervical lymph node showed necrotizing granulomatous lymphadenopathy. A computed tomographic scan showed cervico-thoraco-abdominal, multiple cervical, supraclavicular, axillar, paratracheal, and mediastinal lymphadenopathies. The patient had a CD4 cell count of 219 cells/mm3 and an HIV viral load of 197,181 copies/mL.
The aspiration sample was positive for acid-fast bacilli by fluorescent staining. The clinical isolate (designated 1369) obtained from the aspirate sample was grown in liquid media (MGIT Diagnostic Kit; Becton Dickinson Diagnostics, Sparks, MD, USA) and identified as M. tuberculosis complex by using the AccuProbe System (bioMérieux, Marcy l'Etoile, France).
A diagnosis of lymphoid tuberculosis was made, and the patient was treated with isoniazid, rifampin, ethambutol, and pyrazinamide. After 1 month, rifampin was withdrawn because of a cutaneous exanthem. Three months later, the clinical status of the patient had improved, fever had disappeared, and sizes of cervical and axillary lymph nodes had decreased. Treatment with tenofovir, emtricitabine, and lopinavir/ritonavir was started. Two weeks later, an immune reconstitution syndrome and adenopathies developed, but these resolved in 1 month.
Five months after treatment was started, susceptibility testing in a reference laboratory showed that isolate 1369 was M. kumamotonense. The isolate showed 100% identity with the 16S rRNA gene sequence of M. kumamotonense (GenBank accession no. AB239925). Results of PCR restriction analysis of heat shock protein 65 gene (7) (http://app.chuv.ch/prasite/index.html) were consistent with those for M. kumamotonense. The isolate was susceptible to ethambutol, rifampin, cycloserine, and ethionamide and resistant to isoniazid, streptomycin, pyrazinamide, and kanamycin.
http://www.cdc.gov/eid/content/16/7/1178.htm

TUBERCULOSIS: Nigeria, new diagnostic centre

ZARIA, Nigeria — The United States on Monday donated a multi-million dollar facility for the detection and treatment of tuberculosis to Nigeria, where around 400,000 people suffer from the disease.
Located on the outskirts of the northern city of Zaria, the facility includes a state-of-the-art bio-safety laboratory and a medical staff training centre as well as clinics for people living with HIV and AIDS.
"This facility can train large numbers of people to diagnose tuberculosis," Thomas Frieden, director of the US Centres for Disease Control and Prevention (CDC) said on the ocassion.
"It can also improve the quality of the testing done for people with HIV around the country," he told AFP after a tour of the four-block facility.
"For Nigeria, this is a new facility to increase its ability to diagnose and treat those with tuberculosis and HIV," added Frieden, who is on a five-day visit to the country.
Nigeria, Africa's most populous nation, is ranked fourth among the 22 countries with the world?s highest tuberculosis prevalence, with around 400,000 sufferers.
It also has one of the world?s highest HIV burden with a prevalence rate of 4.5 percent and more than three million people infected with HIV, according to official figures.
The project was executed with funds from the US president?s Emergency Programme for AIDS Relief initiated in 2003 to curb the ravaging effects of HIV in 15 countries in the world including Nigeria, Frieden said.
Germfree, the US-based firm that built the facility, will maintain the laboratory for the next five years and train local personnel.
For this year, the US government has provided Nigeria with more than 533 million dollars to support health-related programmes and services, a statement by the US embassy in Nigeria said.
http://www.google.com/hostednews/afp/article/ALeqM5ijpzYuCAvImUoQ8eVAUo_vJ91hCQ

TUBERCULOSIS: New CDC Guidelines Prefer Use of Blood Tests, Including QuantiFERON®-TB, to Diagnose Tuberculosis Infection in Certain Populations

TB Remains a Major Public Health Threat in Both Developing and Developed Countries
June 24 -- Today the United States (U.S.) Centers for Disease Control and Prevention (CDC) issued new and important guidelines on the detection of Mycobacterium tuberculosis infections, the causative agent of tuberculosis (TB). In these landmark guidelines, CDC advises that Interferon Gamma Release Assay (IGRA) blood tests are now preferred over the 100+-year-old tuberculin skin test (TST) for diagnosing TB infection in certain populations, including people who typically do not return for the necessary reading of TST results, and those who have received Bacille Calmette-Guerin (BCG) as a vaccine or for cancer therapy. Typically the TST or IGRAs, such as QuantiFERON®-TB Gold (QFT), manufactured by Cellestis Limited, should be used as aids to diagnose infection with M. tuberculosis.
"In the U.S., up to 14 million Americans may be infected with TB bacteria and are at risk of developing full-blown, highly contagious TB. With these sobering numbers, complacency about TB's public health impact is not an option," said Antonino Catanzaro, M.D., professor of medicine, University of California San Diego, and Non-Executive Independent Director, Cellestis Limited. "These guidelines encapsulate the enormous body of clinical evidence on the performance of the QFT test and reflect the significant benefits this test is bringing to TB control worldwide."
The CDC report, "Updated Guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium tuberculosis Infection — United States, 2010" along with a companion implementation guide, appears in the June 25, 2010, Volume 59, No. RR-5 issue of the CDC's Morbidity & Mortality Weekly Report (MMWR). TST's drawbacks – which include a higher risk for false positives, especially in people who have been BCG-vaccinated; irritating TB-extract that must be injected under the skin; and the need for a second doctor's visit – were evaluated by the CDC and factored into their recommendations.
Approximately one person dies of TB every 17 seconds. Each infected person represents a potential yet preventable future outbreak. Convenient and trustworthy testing for TB infection is vital in order to efficiently identify the appropriate persons for treatment and thereby prevent its spread.
The populations specified by CDC in these guidelines, represent a majority of those being screened for TB infection. "With a specificity of more than 99 percent, QFT virtually eliminates false positive results and is simple to administer," said Tony Radford, chief executive officer, Cellestis Limited. "With more than 400 peer-reviewed, published clinical studies, QFT is a modern, scientifically–validated solution for reliable diagnosis of TB infection, and offers significant economic and public health advantages."
Specific highlights from the recommendations with regards to IGRAs include:
IGRAs are preferred over the TST for testing persons who have received BCG (as a vaccine or for cancer therapy).
IGRAs are preferred over the TST for diagnosing TB infection for persons from groups that historically have low rates of returning to have TSTs read.
IGRAs may be used in place of (not in addition to) TST in all situations in which CDC recommends testing, and is considered acceptable medical and public health practice.
IGRAs may be used in place of TST (without preference) to test recent contacts of persons with infectious tuberculosis.
IGRAs may be used in place of TST (without preference) for periodic screening to address occupational exposure to TB.
A TST is preferred for testing children aged <5 years. Use of an IGRA in conjunction with TST has been advocated by some experts to increase diagnostic sensitivity in this age group. Recommendations regarding use of IGRAs in children have also been published by the American Academy of Pediatrics.
About Tuberculosis
Tuberculosis (TB) is a contagious disease caused by a bacterium called Mycobacterium tuberculosis. TB bacteria usually attack the lungs, but can affect any part of the body such as the kidney, spine, and brain. If not treated properly, TB can be fatal. TB bacteria is spread through the air when a person with TB disease of the lungs or throat coughs, sneezes, speaks, or sings, which may lead people in close proximity to become infected.
According to the World Health Organization, about one person dies of TB every 17 seconds, causing nearly 2 million deaths annually. TB continues to be a contagious scourge in developing countries, and with the world shrinking rapidly due to global migration, it is a major public health threat in developed nations as well, including the United States. Each infected person represents a potential yet preventable future outbreak. Convenient and trustworthy testing for TB infection is necessary in order to quickly identify the appropriate persons for treatment and thereby prevent its spread.
About QuantiFERON®-TB Gold (QFT)
QuantiFERON®-TB Gold (QFT) is a simple blood test that accurately identifies people infected with Mycobacterium tuberculosis, the causative agent of Tuberculosis (TB). As a modern alternative to the 110 year old Tuberculin Skin Test (TST), also known as the Mantoux, QFT offers unmatched specificity, high sensitivity and simplicity. QFT enables focused TB therapy by providing clinicians with an accurate, reliable and convenient TB diagnostic tool. QFT is unaffected by previous BCG vaccination and most other environmental mycobacteria. Unlike the TST, it requires only one patient visit, is a controlled laboratory test and provides an objective, reproducible result that is unaffected by subjective interpretation. Results can be available within 24 hours.
QFT is available for use in all clinical settings in which TST is commonly used. Examples include contact tracing, regular employee testing, for example for health care workers, as well as screening programs for prisoners and immigrants. QFT's application in the screening of immunosuppressed patients prior to anti-TNF-alpha therapy initiation and in patients with HIV, cancer or organ transplants offers distinct advantages over the TST.
QFT® is sold directly in the U.S. by Cellestis Inc. and through Quest Diagnostics, Inc. and other commercial laboratories. In Europe QFT is provided by Cellestis GmbH (Germany); and in Australia/New Zealand by Cellestis International Pty. Ltd. (Australia). QFT is also available through Cellestis Commercial Partners in Japan, Europe, the Middle East, Africa, South America and Asia.
About Cellestis Limited
Cellestis Limited, a listed Australian biotechnology company founded in 2000 in Melbourne, Australia, develops and manufactures the QuantiFERON-TB Gold In-Tube (QFT) test, a breakthrough blood test for the detection and control of tuberculosis. The QuantiFERON technology is a patented method for detecting cell mediated immune (CMI) responses of T-cell lymphocytes using whole blood samples. In comparison to existing methods of measuring CMI, this unique technology provides accuracy and sensitivity along with major savings in operator time, labor and reagents. Using its patented QuantiFERON technology, Cellestis develops diagnostics tests that measure immune function for diseases with an unmet medical need.
Cellestis is proud to be exploring opportunities to enhance the global effort to eliminate TB. Cellestis is an industry partner of FIND (the Foundation for Innovative New Diagnostics) and the Stop-TB Partnership.
For more information, please visit www.cellestis.com.
http://www.prnewswire.com/news-releases/new-cdc-guidelines-prefer-use-of-blood-tests-including-quantiferon-tb-to-diagnose-tuberculosis-infection-in-certain-populations-97100554.html

TUBERCULOSIS: SOUTH AFRICA: TB patients not getting HIV counselling

DURBAN, 11 June 2010 (PLUSNEWS) - Too many tuberculosis patients are not receiving counselling about the link between TB and HIV, according to new research. A study by South Africa's University of the Free State (USF), involving 600 TB patients, found that about 40 percent had never received HIV counselling, and 75 percent did not understand the relationship between HIV and TB. The findings were part of a broader study into safer sex practices among TB patients, presented by USF Associate Professor Christo Heunis at the South African TB Conference in the east-coast city of Durban. South Africa's TB epidemic, one of the world's worst according to the World Health Organization (WHO), has been fuelled by a high HIV prevalence rate of 18 percent. Globally, TB is the leading killer of people living with HIV, whose weakened immune systems make them particularly susceptible to the airborne disease. In the part of Free State Province where the USF study was conducted, the HIV/TB co-infection rate was 62 percent, which is below the national average of 73 percent. The South African government made giving TB patients better access to HIV care and services a priority in its 2007 National TB Strategic Plan, but implementation has lagged behind policy. The study noted that about half the TB patients surveyed had used a condom during their last sexual encounter, and that patients who reported using condoms were more likely to have received counselling. However, female patients who understood the relationship between HIV and TB were less likely to have used a condom than their male counterparts. Heunis attributed this discrepancy to women's fear of HIV-related stigma.

TUBERCULOSIS: Failure to integrate AIDS and Tbc diagnostic centers

DURBAN, 3 June 2010 (PLUSNEWS) - A consortium of AIDS organizations has given the South African government three months to deliver on promises to integrate TB and HIV services. A local AIDS lobby group, the Treatment Action Campaign (TAC), international medical charity Medicines Sans Frontiers (MSF), and the AIDS and Rights Alliance for Southern Africa (ARASA), a regional partnership of non-governmental organisations, were among civil society groups that issued the deadline at the South African TB Conference in the port city of Durban. MSF spokesperson Lesley Odendal called the three-month deadline "generous" because TB and HIV care should have been integrated by 1 April 2010, according to newly adopted national antiretroviral (ARV) treatment guidelines, but the Department of Health has yet to issue an implemention plan. "Patients are still going to different sites, and healthcare workers still have not been trained on new guidelines," said TAC Deputy Secretary General Lihle Dlamini. "One patient who has both diseases should be seen by one healthcare worker with one file." Dlamini noted that integrating TB and HIV care would lead to earlier diagnosis of TB, especially strains of the disease occurring outside the lungs, which are common in co-infected patients. It would also help health workers become more familiar with the potentially severe interactions between antiretroviral (ARV) and TB drugs. Krista Dong, of the Integration of TB in Education & Care for HIV/AIDS (iTEACH) Programme, based at Edendale Hospital in KwaZulu-Natal Province, said proper training of healthcare workers was crucial. She cited recent research by Health Systems Trust, a non-profit health research organization, which found that nurses' knowledge of potentially dangerous HIV and TB drug interactions continued to be problematic, even with training.