Communities of practice
The scandal of TB misdiagnosis
13 Nov 2010
It is well known that many cases of infectious diseases go undiagnosed, with the result that people who need treatment often fail to get it. Not so often discussed are the problems that arise when patients are incorrectly diagnosed as having an infectious disease and then receive inappropriate treatment. A major article published in the New Yorker magazine, has performed a great service by drawing attention to the situation in India, where inaccurate and misleading tests for tuberculosis are conducted on an estimated 1.5 million people every year.
The inadequacies of the tests available to diagnose TB constitute one of the greatest barriers holding back efforts to improve the control of this disease, which kills nearly 5,000 people worldwide every day. The most widely used method of TB diagnosis (sputum smear microscopy) misses more than half of all cases and is largely ineffective in patients with HIV co-infection; while the most sensitive test (culture testing) takes weeks to provide a result, is costly and can only be carried out by highly-trained staff in specialist laboratories.
The new kids on the block are the commercially available rapid tests, which detect the presence of antibodies to TB. But half of the world’s population have TB antibodies, though only about 10% of them go on to develop the active form of the disease. The tests therefore have a very low specificity – i.e. they give a high proportion of false-positive results. Based on reviews of the evidence [1,2], it has been concluded that they do not have a useful role to play in TB diagnosis. These findings were supported by a TDR evaluation  of 19 of the tests. Nevertheless, the tests are in widespread use in many countries.
The New Yorker article starts with the tale of a poor Indian woman that provides an excellent illustration of what happens in situations where the tests are in common use. The patient paid for a test privately, was incorrectly diagnosed as having active TB and went on (with some difficulty) to complete a six-month course of multi-drug therapy. Such unnecessary treatment encourages the development of drug resistance and patients like this woman may find that, if they do later develop active TB, the drugs available will no longer work for them.
TropIKA.net spoke to TB specialist Madhu Pai at Canada’s McGill University, one of the authors of the two systematic reviews of the effectiveness of commercial TB antibody tests [1,2]. He said that an estimated $15 million were wasted on “these inaccurate and useless serological tests” every year in India alone. “In addition to the obvious economic costs to poor patients, there is the problem of misdiagnosis and its consequences for patients, and the community (in terms of TB transmission)”.
“What is particularly scandalous,” Dr Pai continued, “is that serological kits made in countries like France and UK are dumped in poor countries, when these tests are not used in the countries that make them! Everyone is aware of the consequences of bad drugs and vaccines, but nobody really thinks about bad diagnostics and what impact they can have.
Diagnostics remains the most neglected area in the fight against neglected diseases. Research to develop improved diagnostics tests has been very poorly funded. In the case of TB, there was good news recently with the publication  of excellent findings in the evaluation of a new molecular test, Xpert MTB/RIF, developed by a public–private partnership – see TropIKA.net article. But the greater challenge will be to bring the benefits of such effective new diagnostic tests to those who need them. The New Yorker article makes it clear that the way in which the private and public health sectors in India presently function will add to the difficulties that must be overcome.
1. Steingart KR, Henry M, Laal S, Hopewell PC, Ramsay A, Menzies D, Cunningham J, Weldingh K, Pai M (2007). Commercial serological antibody detection tests for the diagnosis of pulmonary tuberculosis: a systematic review. PLoS Med; 4(6):e202. Available freom: http://www.ncbi.nlm.nih.gov/pubmed/17564490
2. Steingart KR, Henry M, Laal S, Hopewell PC, Ramsay A, Menzies D, Cunningham J, Weldingh K, Pai M (2007). A systematic review of commercial serological antibody detection tests for the diagnosis of extrapulmonary tuberculosis. Thorax.; 62(10):911-918. Available fom: http://www.ncbi.nlm.nih.gov/pubmed/17675320
3. WHO/TDR (2010). Laboratory-based evaluation of 19 commercially available rapid diagnostic tests for tuberculosis. Geneva, World Health Organization. Available from: http://apps.who.int/tdr/publications/tdr-research-publications/diagnostics-evaluation-2/pdf/diagnostic-evaluation-2.pdf
4. Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, Allen J, Tahirli R, Blakemore R, Rustomjee R, Milovic A, Jones M, O’Brien SM, Persing DH, Ruesch-Gerdes S, Gotuzzo E, Rodrigues C, Alland D, Perkins MD (2010). Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med; 363(11):1005-1015. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20825313
5. Morris K (2010). Xpert TB diagnostic highlights gap in point-of-care pipeline. Lancet; 10(11):742-743. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21053414
The issue of bad diagnostics for TB also came up at the 41st Union World Conference on Lung Health in Berlin, as discussed in the following blog: http://sciencespeaksblog.org/2010/11/12/the-urgent-need-for-new-tb-diagnostics/
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