Two articles that went live on the PLoS Medicine journal website Tuesday afternoon further explain the reasoning behind the World Health Organization’s (WHO) July 20th statement urging countries to ban blood tests for active tuberculosis (TB) and instead rely on accurate microbiological or molecular tests, as they recommend.
The key components of the WHO policy statement on serological diagnostic tests for TB include:
- A strong recommendation that these commercial tests not be used for the diagnosis of active pulmonary or extra-pulmonary TB, regardless of a person’s HIV status.
- Currently available commercial serodiagnostic tests (also referred to as serological tests) provide inconsistent and imprecise findings.
- There is no evidence that existing commercial serological assays improve patient outcomes, and high proportions of false-positive and false-negative results may have an adverse impact on the health of patients.
- A strong recommendation to continue research to develop accurate serological tests that can be used at the point-of-care
Originally thought to be a small problem confined to few countries, further research has found that the inaccurate and unapproved blood tests for active TB are much more widely used, making the potential risk of false negatives and false positives much higher than anticipated. Moreover, the tests are not cost-effective as compared to other available TB tests.
“Our research found that at least 1.5 million TB serological tests are estimated to be done in India every year at an expenditure conservatively estimated at US $15 million per year, not to mention the cost of TB drugs wasted on treating hundreds of thousands of patients with false-positive results. When compared to the entire Indian TB control program annual budget of $65 million, this is a potentially overwhelming expense,” said Madhukar Pai, MD, PhD, professor and TB researcher McGill University in Montreal, Canada in a Speaking of Medicine blog post. Pai is the senior author of the article, “Commercial Serological Tests for the Diagnosis of Active Pulmonary and Extrapulmonary Tuberculosis: An Updated Systematic Review and Meta-Analysis,” led by Karen Steingart (University of Washington, Seattle) and published today on PLoS, which found no shortage of studies discounting the accuracy of these tests since 2006, and the quality of evidence for the use of serological tests very low.
According to a PLoS press release, the systemic review found of the literature found that “the sensitivity of serological tests (the proportion of patients with confirmed TB with a positive serological test) ranged from 0 to 100 percent, and their specificities (the proportion of patients who did not have confirmed TB with a negative serological test) ranged from 31 to 100 percent.” Great variance was also found for extrapulmonary TB, with sensitivities ranging from 0 to 100 percent, and specificities ranging from 59 to 100 percent.
“We also found that every major private laboratory in India offers TB serological tests, mostly ELISA kits imported from countries like France, the United Kingdom, USA, Germany, Canada and Australia – countries that do not approve these same tests for clinical use on their own TB patients,” said Pai, who also serves as co-chair of the STOP TB Partnership’s New Diagnostics Working Group.
Although only used in the private medical sector, the study team found that commercial serological tests are available in at least 17 of 22 countries with the highest TB burden, including India, China, South Africa, Brazil, Indonesia, Thailand, Vietnam, Cambodia, Nigeria, Bangladesh, Kenya, Uganda, Afghanistan, Myanmar, Pakistan, the Russian Federation and the Philippines.
The second article released Tuesday, entitled “Serological Testing Versus Other Strategies for Diagnosis of Active Tuberculosis in India: A Cost-Effectiveness Analysis,” by David Dowdy at Johns Hopkins University as lead author, found that sputum smear microscopy is still the most cost-effective diagnostic test available for active TB. “In areas where high-quality microscopy exists and resources are sufficient, [the Mycobacteria Growth Indicator Tube or] MGIT culture is more cost-effective than serology as an additional diagnostic test for TB,” according to the article.
Both articles are publicly available on the PLoS website.