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The new WHO policy on TB diagnostics

Providing the evidence for its development

TDR news item
5 August 2011

In the best interests of patients and caregivers in the private and public health sectors, the World Health Organization (WHO) is calling for an end to using serological tests to diagnose tuberculosis (TB)," said Dr Mario Raviglione, Director of WHO Stop TB Department, in a 20 July WHO statement. "A blood test for diagnosing active TB disease is bad practice. Test results are inconsistent, imprecise and put patients' lives in danger."

This is the first time WHO has issued an explicit "negative" policy recommendation against a practice that is widely used in tuberculosis care. Tuberculosis kills 1.7 million people every year, and is the major killer of people living with HIV. The failure to diagnose TB accurately and rapidly is a key challenge in controlling the epidemic.

Testing for active TB disease by detecting antibodies 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.

This issue has been studied by TDR and partners (including the University of California San Francisco, McGill University and the University of Washington) for the last 5 years. In 2006, TDR commissioned the first in a series of systematic reviews that have shown the dangers in using these tests. The first systematic reviews were published in 2007. In 2008, TDR published the results of a collaborative study with the Institute of Tropical Medicine in Antwerp, which showed that none of the 19 commercially-available rapid tests for TB should be used to diagnose TB. This information was provided to WHO's Stop TB Department. In 2010, at the request of WHO, TDR commissioned the updating of the systematic reviews. In September 2010, TDR and the WHO Stop TB Dept co-convened an Expert Group Meeting to discuss the policy and research implications of all the evidence. TDR's Dr Andy Ramsay presented the findings and recommendations of this meeting to the WHO's Strategic and Technical Advisory Group on Tuberculosis, which advised WHO to issue a recommendation against their use.

"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."

"It is clear that stronger regulatory oversight is needed if bad tests like these are to be removed from the market," says Ramsay. "Perhaps this assessment of the human and health service costs of using poor TB diagnostics will encourage governments to act".

 The updated systematic review commissioned by TDR, and led by Dr Karen Steingart of the University of Washington, is due for publication in PLoS Medicine on 9 August. Also published that day by PLoS will be a study led by Dr David Dowdy of the John Hopkins University and supported by the New Diagnostics Working Group, describing the human and financial costs of poor TB diagnostics in India.

For more information, contact Dr Andrew Ramsay

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Full research reports

  • Commercial serological antibody detection tests for the diagnosis of pulmonary tuberculosis: a systematic review.
    KR Steingart, M Henry, PC Hopewell, S Laal, A Ramsay, R Menzies, K Weldingh, J Cunningham, M Pai. PLoS Medicine, 2007. 4(6): e202.
  • Laboratory-based evaluation of 19 commercially-available rapid diagnostic tests for tuberculosis.
    UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases. World Health Organization, 2008.
  • Performance of Purified Antigens for Serodiagnosis of Pulmonary Tuberculosis: a meta-analysis.
    KR. Steingart, N Dendukuri, M Henry, I Schiller, P Nahid, PC Hopewell, A Ramsay, M Pai, S Laal. Clinical and Vaccine Immunology. 2009. 16(2): 260-76.
  • The TDR Tuberculosis Specimen Bank: A resource for diagnostic test developers
    C-M Nathanson, LE Cuevas, J Cunningham, M Perkins, M Guillerm, R Peeling, F Moussy, A Ramsay. International Journal of Tuberculosis and Lung Diseases. 2010. 14(11): 1461-67.
  • A comprehensive new resource for evidence-based TB diagnosis.
    M Pai, A Ramsay, R O'Brien. Expert Review of Molecular Diagnostics. 2009. 9(7): 637-9.

Related links

  • The WHO Policy Statement on TB testing
  • New findings could make TB testing more accessible in poor countries
  • Editorial in Expert Reviews calls for more data on patient-important outcomes, cost-effectiveness and impact of new diagnostics for tuberculosis (2009)

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