Studies confirm serological testing inadvisable option for TB detection

Recent findings from two studies published in PLoS Medicine outlined the basis of the WHO policy statement on advising against the use of serological testing for tuberculosis diagnosis published in July. According to the policy, serological tests should not be used in their present form.

“Despite expansion of the literature since 2006, commercial serological tests continue to produce inconsistent and imprecise estimates of sensitivity and specificity. Quality of evidence remains very low,” Karen R. Steingart, MD, of the department of health services at the University of Washington in Seattle, and colleagues wrote.

Serological testing for pulmonary, extrapulmonary TB

In an analysis of 67 studies (48% low- and middle-income countries; 5,147 participants), Steingart and colleagues conducted an updated systematic review and assessed the diagnostic accuracy of serological testing for pulmonary and extrapulmonary TB. The researchers focused on the relevance of these tests in low- and middle-income countries.

Sensitivity for serological testing was between 0% and 100% and between 31% and 100% for specificity for pulmonary TB cases. Sensitivity and specificity for extrapulmonary TB was between 0% and 100% and 59% and 100%, respectively.

“The WHO policy strongly encourages targeted further research to identify new/alternative point-of-care tests for TB diagnosis and/or serological tests with improved accuracy,” the researchers wrote.

Comparison of TB tests in India

In a second paper that utilized findings from the previous study, David W. Dowdy, MD, PhD, and colleagues said even though its sensitivity is limited, sputum smear microscopy continues to be the most cost-effective TB diagnostic test and is recommended for use in low- and middle-income countries, such as India

“Serological tests, when used to detect active TB, are not useful,” Dowdy, of the department of epidemiology at Johns Hopkins Bloomberg School of Public Health, told Infectious Disease News. “Using optimistic estimates of how well these tests perform, a person in India with a positive test is six times more likely to not have active TB than to have active TB.”

For the cost-effective analysis, Dowdy and colleagues pooled data from the public and private TB control sector of the health care system in India and compared the cost-effectiveness of serological testing ($20/test), sputum smear microscopy ($3.62/two smears) and microscopy plus automated liquid culture ($20/test) for active TB in India. Primary outcome measure was the incremental cost per disability-adjusted life-year (DALY) prevented.

Serological testing resulted in approximately 14,000 more TB diagnoses vs. sputum microscopy. However, when compared with microscopy, serology resulted in 121,000 more false-positive diagnoses, 102,000 fewer DALY’s prevented and 32,000 more secondary TB cases. Serology costs four times as much as microscopy ($47.5 million vs. $11.9 million).

The researchers said sensitivity analyses showed that, across a wide range of assumptions, sputum smear microscopy was cheaper and more effective than serology. Furthermore, where high-quality microscopy is already in place, adding automated liquid culture is consistently more cost-effective than adding serology.

“Just because our current serological tests are not useful does not mean there isn’t a similar test out there waiting to be developed,” Dowdy said. “The diagnostic tests we have right now — even though they are better than the current serological tests — are still far from perfect. The new WHO policy encourages further research to develop a simple, accurate point-of-care test for active TB. That is a big felt need.” – by Ashley DeNyse

For more information:

• Dowdy DW. PLoS Med. 2011;doi:10.1371/journal.pmed.1001074.
• Steingart KR. PLoS Med. 2011;doi:10.1371/journal.pmed.1001062.
• WHO. Commercial serodiagnostic tests for diagnosis of tuberculosis: policy statement. Available at: whqlibdoc.who.int/publications/2011/9789241502054_eng.pdf. Accessed on Aug. 10, 2011.

Disclosure: The research by Dowdy and colleagues was commissioned by the Stop TB Partnership’s New Diagnostics Working Group, via the subgroup on Evidence Synthesis. Dr. Madhukar Pai received support from the Canadian Institutes of Health Research. No funding bodies had any role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The research by Steingart and colleagues was commissioned by WHO with funding provided by USAID through a grant administered by the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases.

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