NEW YORK ─ BioMérieux recently launched an interferon gamma release assay with a desktop immunoassay analyzer to detect Mycobacterium tuberculosis in blood samples, marking its entry into the IVD market for tuberculosis testing.
BioMérieux's new assay, running on its Vidas 3 immunoassay platform, automates several steps of the IGRA testing process, an advance that can make the Vidas TB-IGRA the go-to test for hospitals looking to diagnose and treat latent TB, said Mark Miller, its executive VP and chief medical officer.
The test, which requires one whole-blood sample, is fully automated from sample-to-answer and eliminates manual sample preparation, signifying the "the biggest difference" between it and other competitive assays in the market, Miller said.
Blood sample preparation steps such as centrifugation and external incubation required by current IGRA tests run the risk of introducing variability in test results, Miller said, adding that with its automated IGRA immunoassay, clinicians can reduce the potential for error.
BioMérieux has launched the test for use by hospitals in their testing labs on the back of CE marking in March. The firm is preparing to submit Vidas TB-IGRA to the US Food and Drug Administration for clearance and is evaluating potential regulatory approval in parts of Asia, Miller said.
Overall, the Vidas TB-IGRA test automates several testing steps, including whole-blood pipetting, the introduction of stimulants, incubation, plasma separation, measurements of interferon gamma, and the analysis of results.
The test provides a result in about 16 hours from the initiation of testing. To do so, it conducts three separate measurements using one test cartridge that slots into the Vidas 3 analyzer. The system completes a baseline measurement of interferon gamma in the blood sample, and then runs a separate test to measure the level of interferon gamma following the addition of a nonspecific stimulant to the blood. It runs a third test to measure the level of interferon gamma after adding TB-specific antigens to the sample. A mathematical calculation reveals differences in the levels of interferon gamma among the three steps.
For patients with latent TB, "the white cells in the blood sample will release a substantially higher volume of interferon gamma upon the introduction of the TB stimulant," Miller said.
IGRA test providers
BioMérieux will face competition from established companies in the market for latent TB testing. IGRA tests developed by Qiagen and Oxford Immunotec already have regulatory clearances, including FDA clearance, and have been growing in popularity as an alternative to skin tests.
Oxford Immunotec, based in Oxford, UK, and recently acquired by PerkinElmer, produces the T-Spot.TB test, which has been approved for sale in more than 50 countries. It is based on the principle that the T cells of an infected patient respond to specific antigens and secrete interferon-gamma. In its documents filed with the FDA to obtain clearance, Oxford Immunotec said that its test had a sensitivity of 95.6 percent and a specificity of 97.1 percent in its pivotal clinical study. In the US, the T-Spot.TB test is sold by Secaucus, New Jersey-based Quest Diagnostics and regional laboratories.
According to Qiagen, its QuantiFeron-TB Gold Plus test, marketed in more than 75 countries, combines a flexible blood collection workflow with CD4/CD8 T-cell technology, and the test has a sensitivity of 89 percent in samples from patients with culture-confirmed M. tuberculosis infection and 99.1 percent specificity in samples from individuals with no reported risk for M. tuberculosis infection.
In 2019, it teamed up with DiaSorin, and both firms announced FDA approval for the Liaison QuantiFeron-TB Plus test. A more automated workflow pairs Qiagen's standard QuantiFeron-TB Gold Plus (QFT-Plus) Blood Collection Tubes with DiaSorin's Liaison QuantiFeron-TB Plus detection assay, which runs on the DiaSorin Liaison laboratory analyzer, the firms said.
The alternative to IGRA tests for detecting latent TB infection is a skin test, also known as a tuberculin sensitivity test, which requires two visits to a healthcare provider — one to take the test and another to read the result. A person given the tuberculin skin test must return within 48 to 72 hours to have a trained healthcare worker look for a reaction on the arm.
During a recent presentation about the Vidas TB-IGRA test, Maria Laura Gennaro, a professor of medicine and epidemiology at Newark, New Jersey-based Rutgers Biomedical and Health Sciences, said Qiagen and Oxford Immunotec's IGRA tests "have constituted a tremendous advance over the tuberculin skin test."
Gennaro was a participant on a virtual presentation in May prior to the 31st European Congress of Clinical Microbiology and Infectious Diseases and hosted on the ECCMID web platform.
IGRA testing, in general, is more convenient for patients because it requires one instead of two visits to the clinic, and it has better specificity than skin testing, noted Gennaro, who is an adviser to BioMérieux.
Because of its level of automation, the Vidas TB-IGRA test has advantages over the current tests in the market, she noted. The T-Spot.TB test requires centrifugation of peripheral blood mononuclear cells and is consequently done in a central laboratory rather than a hospital laboratory, she said. Additionally, the QuantiFeron test is not fully automated and requires a manual step in which "the supernatant is taken from the blood that has been incubated with antigen, and the release of interferon is read by ELISA," Gennaro added.
Oxford Immunotec and Qiagen did not respond to requests for comments.
Vidas TB-IGRA Validation
BioMérieux said that overall, it has validated the performance of its IGRA test in the blood samples of more than 1,600 patients in six countries, involving internal and independent testing.
In its validation testing, the firm included samples from individuals who have an extremely low risk of having latent TB. Some were healthy blood donors with no TB history, live in countries with a low latent TB disease prevalence, and have no record of previous exposure, Miller said.
The second group of individuals included in its validation testing were confirmed positive for active TB by culture methods, and represent "the only individuals we know for sure that have been infected," Miller said. "In those two groups, our test has a better sensitivity and better specificity than the current predicate tests on the market," he added.
Camille Pease, a BioMérieux R&D immunoassays and biosciences manager, said during the presentation prior to ECCMID that in a study involving 198 blood samples from patients with TB confirmed by culture, the Vidas TB-IGRA test had two indeterminate results and a comparator IGRA test currently on the market had 19 indeterminate results.
The Vidas test had a sensitivity of 97.5 percent while the comparator assay had a sensitivity of 80.7 percent in the study, she said, without naming the comparator assay.
The firm also conducted a "specificity-like" comparison of its assay's performance compared to the comparator test. It uses the term "specificity-like" because no gold standard method is available to confirm with certainty that an individual does not have latent TB. For specificity-like validation, BioMérieux used blood samples from healthy blood donors who had no history of having contracted TB. The Vidas TB-IGRA assay had a specificity of 97.6 percent and the comparator assay had a specificity of 95.2 percent on tests of 125 samples, Pease said.
The IGRA test has been designed to differentiate individuals who have latent infection from those who do not have a latent TB infection, but detecting active TB is not an intended use.
To detect individuals with active infection, IVD companies are seeking rapid means of detection. For example, the Xpert MTB/RIF test, developed by Danaher's Cepheid, detects both active tuberculosis and Rifampin-resistant mutations in three hours.
The Vidas TB-IGRA test "can help" in detecting active TB infection, "but it is not the only tool and should not be the only tool used to detect active disease," Miller said. That's why hospital laboratories doing blood testing for latent tuberculosis are the primary targets for the Vidas TB-IGRA, he said.
"We are aiming at those labs that are sending out blood samples for testing," Miller said. Many hospitals wait to accumulate batches of samples before sending them to a reference laboratory, which delays the time to results and has the potential to introduce errors into testing because of the manual handing of samples, he noted. With BioMérieux's IGRA test, hospital labs will be able to do testing on-site by providing minimal technician training.
BioMérieux is also evaluating where the test can provide the best clinical utility. "Right now, most people with latent TB live in low-income countries," Miller said. "In a perfect world and to eradicate tuberculosis, those countries would be [conducting broad scale] latent TB testing … finding people who have latent infection, and giving them a chemoprophylaxis that prevents them from getting the disease."
However, low-income countries rarely have the budgets or resources to conduct that level of testing, he said. As a result, BioMérieux is mainly targeting hospitals in developed countries "where the IGRA test can be a powerful tool," and middle-income countries "where TB is also a problem, but they have the budgets, the means, and the personnel to do the testing, follow up with patients, and provide a chemoprophylaxis," Miller said.