Archive for July 2011
20 July 2011 | GENEVA – The use of currently available commercial blood (serological) tests to diagnose active tuberculosis often leads to misdiagnosis, mistreatment and potential harm to public health, says the World Health Organization (WHO) in a policy recommendation issued today. WHO is urging countries to ban the inaccurate and unapproved blood tests and instead rely on accurate microbiological or molecular tests, as recommended by WHO.
Testing for active TB disease through antibodies or antigens found in the blood is extremely difficult. Patients can have different antibody responses suggesting that they have active TB even when they do not. Antibodies may also develop against other organisms which again could wrongly indicate they have active TB. In addition, different organisms share the same antigens, making tests results unreliable. These factors can result in TB disease not being identified or wrongly diagnosed.
“In the best interests of patients and caregivers in the private and public health sectors, WHO is calling for an end to the use of these serological tests to diagnose tuberculosis,” said Dr Mario Raviglione, Director of WHO Stop TB Department. “A blood test for diagnosing active TB disease is bad practice. Test results are inconsistent, imprecise and put patients’ lives in danger.”
Today’s policy recommendation applies to blood tests for active TB. Blood tests for inactive TB infection (also known as dormant or latent TB) are currently under review by WHO.
The new recommendation comes after 12 months of rigorous analysis of evidence by WHO and global experts. Ninety-four studies were evaluated – 67 for pulmonary tuberculosis (TB in the lungs) and 27 for extrapulmonary tuberculosis (TB elsewhere in other organs). Overwhelming evidence showed that the blood tests produced an unacceptable level of wrong results – false-positives or false-negatives – relative to tests endorsed by WHO.
The research revealed “low sensitivity” in commercial blood tests which leads to an unacceptably high number of patients wrongly being given the ‘all clear’ (i.e. a false-negative when in reality they have active TB). This can result in the transmission of the disease to others or even death from untreated tuberculosis. It also revealed “low specificity”, which leads to an unacceptably high number of patients being wrongly diagnosed with TB (i.e. a false-positive when in reality they do not have active TB). Those patients may then undergo unnecessary treatment, while the real cause of their illness remains undiagnosed, which may then also result in premature death.
More than a million of these inaccurate blood tests are carried out annually to diagnose active TB, often at great financial cost to patients. Many patients pay up to US$30 per test. There are at least 18 of these blood tests available on the market. Most of these tests are manufactured in Europe and North America, even though the blood tests are not approved by any recognized regulatory body.
“Blood tests for TB are often targeted at countries with weak regulatory mechanisms for diagnostics, where questionable marketing incentives can override the welfare of patients,” said Dr Karin Weyer, Coordinator of TB Diagnostics and Laboratory Strengthening for the WHO Stop TB Department. “It’s a multi-million dollar business centred on selling substandard tests with unreliable results.”
This is the first time WHO has issued an explicit “negative” policy recommendation against a practice that is widely used in tuberculosis care. It underscores the Organization’s determination to translate strong evidence into clear policy advice to governments.
Tuberculosis kills 1.7 million people every year, and is the major killer of people living with HIV. Improving the early and effective diagnosis of TB to ensure more lives are saved is a priority action for WHO and the international TB community. TB research is currently underway to bring better and more rapid tests that are easy to administer, effective and accurate.
First published in Deccan Herald on 22 June 2011 to coincide with the 30th anniversary of AIDS. Reproduced in JATB unedited
The week that has passed has been significant for the HIV/AIDS sector. It marked the 30th anniversary of the AIDS epidemic. World leaders gathered for a high level meeting on AIDS in New York and according to reports, a scientific blueprint for interventions that will enable us to save a million more lives by 2015 was unveiled.
The Stop TB Partnership released new scientific modelling at the meeting, which shows that with aggressive use of existing technology and tested interventions, TB-HIV deaths can be reduced by 80 per cent by 2015. In 2010 the Stop TB Partnership and UNAIDS set the joint goal of reducing by half the number of deaths among people living with HIV, compared to 2004 levels, between 2011 and 2015. With the new model, they have agreed to aim for the one million mark.
These are great achievements indeed, considering AIDS is only 30 years old. Let’s juxtapose that against TB, which is more that 125 years old. We have had practically no new developments on diagnosis, prevention or treatment. The most commonly used test for TB is still the smear microscopy which is as old as TB itself, and misses half of all cases. Prevention and treatment are not much better.
India’s directly observed treatment short-course (DOTS) programme has been counted among more successful ones in the world. But it will not be far-fetched to say that TB has come under a special spotlight largely by piggy-backing on HIV. Increasingly, TB is spoken of in the same breath as HIV as there is evidence to prove that TB is responsible for one in four AIDS-related deaths and therefore deserves more aggressive attention.
It’s time to pause and ask some questions here. What about those who are TB infected but not HIV positive? Who speaks for them? According to revised national tuberculosis control programme (RNTCP) India has around 1.8 million new cases of TB every year and and more than 3.7 lakh people die of TB every year in India How many of these are not HIV positive? What do health systems have in place to save these lives? These are questions that we desperately need to find answers to, even as we save a million precious lives that will suffer from the co-infections of HIV/TB. It is time to give TB the same attention that HIV gets, and take it to international forums with the same vigour and activism that HIV has managed to do.
Preparing the blueprint
The government is currently in the process of preparing the blueprint for the next phase of RNTCP phase 3 which will run from 2012-2017. Having crossed WHO’s targets of new case-detection of 70 per cent and treatment success rate of 85 per cent, the RNTCP is being expanded to ensure early detection and treatment of at least 90 per cent of estimated TB cases in the community.
Achieving the targets would mean better diagnosis as the currently used smear microscopy test is as old as TB itself and routinely misses half of all cases of TB.
Additionally, as Dr Madhukar Pai, associate professor, Dept of Epidemiology and Biostatistics, McGill University says: “Universal access, which is what is being aimed at, will mean that RNTCP alone cannot do it as more than 50 per cent of all TB patients in India are managed in the private sector. So, without a massive effort to engage private sector, universal access is impossible to reach. But RNTCP has done very little to engage the private sector so far.”
New diagnostic tools such as the GeneXpert hold great promise of being robust point-of-care (P-O-C) tools that are simple to use, and give immediate and reliable results. This means timely diagnosis and treatment. But there is a down side to this. With the depth and reach that a P-O-C such as GeneXpert will have, the number of patients diagnosed (both sensitive and MDR) is almost certainly going to increase dramatically. Once diagnosed, the patients must have access to treatment. This would mean a considerable increase in the need for and the cost of drugs (both first line and second line drugs) and also the infrastructure and systems to manage patients, particularly those with MDR TB.
Implementation of RNTCP 3 will involve huge resources and this brings us to the question of whether the government is committed to providing these funds. A back of the envelope calculation reveals it would involve tripling of the current annual budget of $65 million. Are we geared up for better diagnosis and the requirements thereafter? Do we have the funds required for this? Questions we must find answers to because a failure to do so means failing so many people who are entitled to health. Whether they are HIV positive or not.
JATB was begun to direct media focus towards TB. In what can be seen as a very encouraging trend, we have had requests from several organisations working on TB to feature their news in JATB. We are happy to accommodate all these requests because ultimately getting news across is what matters and as journalists against TB, we see this as fitting in very well with our objective. This week, we feature news from TBVI on a request from them, and thank them for choosing this platform. Jojanneke Nieuwenhuis, who has consistently provided content for JATB reports yet again.
TB vaccine research is moving forward steadily. In their 2010 annual report, the TuBerculosis Vaccine Initiative (TBVI) looks back at a scientifically successful year. Researchers within TBVI’s network are progressing towards new, safer and more effective tuberculosis vaccines. However, in order to successfully deliver these live-saving vaccines to the market, both political support and innovative investment are crucial.
Worldwide, 12 vaccine candidates are now in various phases of clinical trials and several more are on their way. Many of these candidates received support through one of TBVI’s research projects. “Good reason to be positive,” said Prof. Kaufmann, chair of TBVI’s research project NEWTBVAC. “Having 12 candidates in clinical trials is a breakthrough that nobody would have thought of 20 years ago.” In 2010, existing challenges remained though, one of them being a lack of validated biomarkers, indicators that could for example predict levels of protection. Finding these biomarkers is one of TBVI’s research priorities and research carried out over the past year has certainly led to a better idea of what to look for.
Developing new tuberculosis vaccines is scientifically challenging, but the progress that has been made over the past ten years is tremendous. TBVI ties together a network of more than 40 research institutes, universities and industries with the aim to develop more effective tuberculosis vaccines. TBVI calculated a critical financing gap of 560 million euros, needed to bring the first, most advanced vaccines out of its portfolio to the market. In order to close this gap, the organisation has proposed an innovative funding model. In this plan, European governments are asked to provide guarantees to make it possible for TBVI to finance clinical trials through a loan. The loan can then be repaid through the sales of marketed vaccines. “New vaccines can be developed at no cost for the tax-payer and with minimal risk for state budgets,” explains TBVI’s vice president Joris Vandeputte.
New, more effective and safe tuberculosis vaccines are within sight. However, some promising projects are close to being put on hold because of a lack of funding. New vaccines could be available within a decade. It’s now up to decision makers, politicians and industries to join forces with scientists and make this happen.
The views expressed here are entirely of TBVI
JATB has strongly advocated for activism of the kind that HIV has, in order that greater focus can be directed to people suffering from TB. We have also at various times emphasized that TB needs to move out of labs and clinics and that people suffering from TB need to speak out and voice their demands more strongly instead of leaving TB care entirely to the medical fraternity. We are glad to feature an initiative by Medicins sans Frontieres (MSF) which promises that a direction towards this has been set.
MSF is launching ‘TB and me’, a citizen journalism project for TB patients. TB&ME is an MSF blogging platform, created to help patients suffering from multidrug-resistant tuberculosis (MDR TB) share their stories. Over the coming months and years MSF will campaign for better treatment/services for TB sufferers. TB&ME enables MSF, and others, to learn where improvement is most needed and provides a much-needed support network for patients.
Madan Mishra is 36 and has been on treatment for MDR-TB for 9 months and for HIV for 3 years and 4 months. This is the fourth time he has been on treatment for TB – first in the private sector, twice in the public sector, and now with MSF. He will need to be on treatment until at least December 2011. JATB salutes the spirit and courage he has displayed by coming out and speaking about his experiences.