Rapid TB blood tests fail to perform as well as smear microscopy
Rapid blood tests for TB now on the market generally perform poorly in diagnosing active disease, and cannot be recommended for use. This is the conclusion emerging from the results of TDR laboratory evaluations of 19 of the many rapid TB blood tests commercially available in low- and middle-income countries, published in October.
The rapid TB tests were evaluated at the Prince Leopold Institute of Tropical Medicine using 355 well-characterized archived serum samples. The evaluation considered performance, reproducibility and operational characteristics, and was conducted with the agreement of the manufacturers. Evaluations showed that none of the TB rapid assays perform well enough to replace sputum smear microscopy, the diagnostic technique used for the past 100 years, and the one most available in developing countries. When rapid tests were used together with smear microscopy, overall diagnostic sensitivity went from 75% for smear alone, to 89% for the combination of smear and a rapid test. However, use of the combination technique, had an associated, unacceptably high false-positive rate of 42%.
It also appeared that HIV co-infection diminishes the performance of existing assays. “These tests are sold and used in disease-endemic countries, without evidence of effectiveness,” said Dr Rosanna Peeling, who heads TDR’s diagnostic research effort. “But now we have the evidence that can be used to develop regulatory oversight that can guide both procurement and clinical practice.”
The sensitivity of the rapid tests ranged from 0.97% to 59.7%; specificity ranged from 53% to 98.7%, compared to a combined reference standard of mycobacterial culture and clinical follow-up. Test performance was significantly poorer in patients with sputum smear-negative TB and in HIV-positive patients. The average difference in test sensitivity between the HIV-negative (n=198) and the HIV-positive population (n=157) was +22%; the maximum difference was +43%.
This evaluation did not include an analysis of how specific antigen or antigen combinations in the test kits performed because of the proprietary nature of this information. However, the next stage of research on rapid tests, said Peeling, should be a review of the literature targeting the utility of specific antigens or a cocktail of antigens, in addition to activities supporting the discovery of new antigens with immunodiagnostic potential.
On the plus side, the majority of rapid TB tests on the market today have very low technical complexity. So if a more reliable and accurate rapid test was developed, it would be appropriate for use in primary health-care settings in developing countries, where more sophisticated diagnostic tools are both too expensive or too technically complex for use. Peeling said that the evaluation was undertaken in response to repeated requests from public health ministries and countries for information on the performance of rapid serologic TB tests and their potential for use in primary health-care settings in developing countries.
Currently, it is estimated that fewer than 20% of active TB patients receive a microbiologically confirmed diagnosis. Sputum smear microscopy, the tool most widely available, fails to identify 30-40% of active TB cases – and is even less reliable when used in populations with high rates of HIV infection.