Rapid TB tests need more refinement

U.S. company developing serum-based test

Two new rapid diagnostic tests for tuberculosis can provide results weeks earlier than traditional culture tests. However, they are still too unreliable for routine health care settings, according to the American Lung Association (ALA) in New York City.

A report on the new tests, published recently in the ALA’s publication, the American Journal of Respiratory and Critical Care Medicine, points out that the RNA- and DNA-based diagnostics have been tested only in clinical trials and should not be used on patients with either a very high or very low likelihood of having TB.

"In these patients, the current tests, combined with a doctor’s clinical judgment, are quite accurate, and results of the new tests will not change patient management but will increase health care costs," said Peter Barnes, MD, associate professor of medicine at the University of Southern California in Los Angeles, in an editorial accompanying the study.

Manufacturers of the two approved tests — Gen-Probe MTD and Amplicor M tuberculosis — are developing more accurate, second-generation refinements of the tests. They point out that while the tests cost more than traditional screening, they are justified for screening certain patient populations and for ruling out suspected cases. (See TB Monitor, December 1996, pp. 133-135.) So far, the tests are indicated for sputum-positive patients only, and as Barnes points out, the tests are not 100% sensitive and cannot replace culture testing to determine if a patient’s strain is drug-resistant.

A diagnostic test with a novel approach

In what could prove to be a viable alternative to traditional TB testing, researchers at Boston University and ImmunoDiagnostics in Buffalo, NY, have developed a novel serum or plasma-based test for TB. The test, called TB AccuScreen, uses a strip format similar to a pregnancy test but uses blood instead of urine to produce results within 45 minutes, says company President Wayne Bacon. Unlike the Gen-Probe and Amplicor tests, AccuScreen requires no special equipment; a small cartridge to hold the serum and chemicals is all that’s needed, he adds.

"This is an antigen test, and the beauty of it is that by using blood, you get a consistent sample," he tells TB Monitor. "Sputum, on the other hand, is a terrible thing to work with; it’s infectious, and it’s hard to get a good sample."

While other biomedical researchers interested in TB have focused on proteins, ImmunoDiagnostics focused on carbohydrates. Its research led to a novel complex carbohydrate or antigen that allowed them to develop an antibody test. The test can detect antibodies for patients who have active disease with M. tuberculosis, M. avium, and M. kansassi. The test doesn’t respond to patients with latent or old infection or with BCG (bacille Calmette-Guerin) vaccine.

How long the test would detect antibodies after successful treatment requires more study, Bacon says. The best estimate is that the test would not be reactive six or more months after a person is cured, he adds.

As for its accuracy, Bacon says the test is more than 90% sensitivity and specificity. "It’s a much more accurate and less expensive test than the PCR," he says, referring to the polymerase chain reaction technique used in the Genprobe test. (The Genprobe test reportedly has a 95% sensitivity and specificity rate and sells for about $35.)

Bacon says the test could be sold to the World Health Organization for less than $5, making it affordable in countries where TB rates are highest, and special equipment and training are not available. The test would be priced at about $35 in the United States, he adds.

Because ImmunoDiagnostics is a small company and venture capitalists are not excited about investing in diagnostics, the company doesn’t have the resources for the large clinical trials needed for FDA approval, Bacon says. However, the Centers for Disease Control and Prevention in Atlanta has asked the company to participate in two large pediatric TB studies.

Outside the United States, the test is being considered for an eight-country HIV/TB trial in West Africa and already has been tested in Russia, which recently approved $50 million to combat TB and expressed strong interest in using the test on a massive scale, he says. The company also plans to register the test soon in Canada, where extensive clinical trials are not required before a medical test goes to market.

While the WHO expressed interest in the test as the type of screening format well suited for poor countries, the agency could not help fund development, Bacon says. "They said they have lots of money for HIV and none for TB, even though TB kills about 30 times as many people."