A coalition of international organizations including the World Health Organization (WHO) will distribute in several developing countries a new test that quickly identifies multiple drug-resistant tuberculosis (MDR-TB). The assay, while not as sensitive or specific as some other methods, gives results in two days or less, which can be important in settings where the risk of infection with MDR-TB is high.

In developing countries, most tuberculosis (TB) patients are tested for MDR-TB only after they fail to respond to standard treatment. Often, patients with this resistant form of the disease die before they can receive second-line drugs, especially if the patients are infected with human immunodeficiency virus (HIV) in addition to TB.

While the incidence of TB in the United States has been steadily declining, it remains a health concern in much of the rest of the world, especially in areas that lack access to health care. The WHO estimates that one-third of the world’s population is currently infected with TB and, worldwide, it is still the leading cause of death due to infection, killing about 1.7 million people a year.

MDR-TB, which does not respond to standard treatment with the antibiotics rifampicin and isoniazid, comprises about 5% of TB cases worldwide. But fewer than 1 in 20 existing MDR-TB patients are actually diagnosed as having the resistant form of the disease. According to WHO, the main obstacle is lack of appropriate laboratory services. As a result, the vast majority of patients with MDR-TB get inappropriate treatment and drug resistant strains continue to spread.

Projects launched by WHO, the Stop TB Partnership, UNITAID (United to Aid), and the Foundation for Innovative New Diagnostics will make the rapid MDR-TB tests available in 16 countries over the next four years. Known as line probe assays, these tests identify the DNA of Mycobacterium tuberculosis that are resistant to both rifampicin and isoniazid. The projects will enhance lab facilities and staff training, while related programs will boost the supply of drugs needed to treat MDR-TB in 54 countries, including those receiving the new tests, and reduce the price of second-line TB drugs.

Prior to announcements about these projects, published research confirmed the speed, sensitivity, and specificity of the rapid MDR-TB line probe assay. Writing in the American Journal of Respiratory and Critical Care Medicine, researchers from Switzerland’s Foundation for Innovative New Diagnostics concluded that the test’s overall performance compares very well with conventional culture and drug susceptibility testing, adding it has the potential to “revolutionize” MDR TB diagnosis.

The researchers based their conclusion on analysis of 536 consecutive sputum specimens from patients at increased risk of MDR-TB and who tested positive for TB with an initial test called an AFB smear. The testing was conducted in a busy routine diagnostic laboratory in Cape Town, South Africa. In a comparison of the line probe assay results and those from conventional culture and drug susceptibility testing, 97% of smear-positive specimens gave interpretable results within 1-2 days using the line probe assay. However, some line probe assay results may be difficult for laboratorians to interpret due to the presence of multiple faint lines that may obscure a true positive or negative result. Interpretation of these equivocal results is subjective and may vary from laboratory to laboratory.

Versions of the test are marketed in certain European countries, Canada, Australia and Japan, but not in the United States, according to speakers at a recent teleconference about the assay and the WHO projects. The speakers noted that the new test for MDR-TB is not able to detect resistance to second-line drugs used to treat tuberculosis. Therefore, the line probe test can not classify M. tuberculosis isolates as extensively drug-resistant TB (XDR-TB), a form of the disease that responds to neither rifampicin and isoniazid nor three or more of the six classes of second-line drugs.

Sources

World Health Organization Press Release. New rapid tests for drug-resistant TB for developing countries. Available online at http://www.who.int/mediacentre/news/releases/2008/pr21/en/print.html. Issued June 30, 2008. Accessed July 22, 2008.

World Health Organization. Molecular Line Proble Assays for Rapid Screening of Patients at Risk of Multidrug-Resistant Tuberculosis (MDR-TB) Policy Statement. PDF available for download at http://www.who.int/tb/features_archive/policy_statement.pdf through http://www.who.int. Issued June 27, 2008. Accessed July 22, 2008.

Barnard, M. et al. Rapid molecular screening for multidrug-resistant tuberculosis in a high-volume public health laboratory in South Africa. Am J Respir Crit Care Med. 2008 Apr 1;177(7):787-9. Available online at http://ajrccm.at .org/cgi/content/abstract/177/7/787. Accessed July 22, 2008.

RESULTS. WHO Media Call on MDR-TB Diagnostics. June 30, 2008. Available online at http://www.results.org/website/article.asp?id=3510 through http://www.results.org. Accessed July 23, 2008.

World Health Organization Press Release. Emergence of XDR-TB. September 5, 2006. Available online at http://www.who.int/mediacentre/news/notes/2006/np23/en/index.html. Accessed July 23, 2008.

World Health Organinzation Tuberculosis Fact Sheet (2008) PDF available for download at http://www.who.int/tb/publications/2008/factsheet_april08.pdf through http://www.who.int. Accessed August 2008.

Centers for Disease Control and Prevention. Reported Tuberculosis in the United States, 2006. PDF available for download at http://www.cdc.gov/tb/surv/surv2006/pdf/FullReport.pdf through http://www.cdc.gov. Accessed August 2008.