TRENDS & PERSPECTIVES
In an unprecedented partnership, the Centers for Disease Control and Prevention (CDC; Atlanta) and the Office of Public Health and Emergency Preparedness at the Department of Health and Human Services (HHS) are working together to comanage the development of diagnostic tests for avian influenza (H5N1).
Last month, CDC announced that it had awarded $11.4 million in new contracts to four IVD companies for developing rapid diagnostic tests for avian influenza: $2.4 million to Cepheid (Sunnyvale, CA); $3.8 million to Iquum Inc. (Marlborough, MA); $706,241 to Meso Scale Discovery (Gaithersburg, MD); and $4.5 million to Nanogen Inc. (San Diego). This follows last year’s announcement by the Bush administration of its plan to prepare the United States for a possible influenza pandemic. Despite the fact that there have been no documented cases of avian influenza in the United States, its high fatality rate makes it a prime target for IVD test development.
There have been 258 confirmed cases and 153 human deaths resulting from avian influenza since 2003 in Southeast Asia, Africa, and Europe, most resulting from contact with contaminated poultry. Developing IVD products that will help to ensure appropriate treatment at the bedside is of paramount importance, and CDC says that it hopes to see commercialization of avian influenza diagnostic products in less than three years.
The contract awardees will work during the next year with the goal of creating tests that will successfully differentiate avian influenza from seasonal and other influenza viruses within 30 minutes of collecting respiratory samples. Currently, no tests can make such distinctions at the point of care.
At this stage, companies have received contracts for phase one and two development (out of five phases) over a 12-month time frame and will later be reevaluated for phase three through five funding. Shuqi Chen, PhD, Iquum’s chief executive officer, says the purpose of the contracts according to CDC is “to support advanced development and commercialization of clinical influenza point-of-care diagnostic tests, which must have high sensitivity and specificity, high reproducibility, ease of use, and high biosafety.” Iquum will lead a team of molecular diagnostic industry leaders and biotechnology innovators to develop nucleic acid tests for influenza based on the company’s innovative lab-in-a-tube, or Liat, technology.
“CDC and HHS want a test that will allow appropriate treatment at the point of care,” says David
Persing, MD, PhD, Cepheid’s chief medical and technical officer and executive vice president. “You don’t want to admit patients with influenza into a hospital if possible, because introducing that into an immune-compromised population becomes a serious infectious-disease problem for the hospital. But you also want to make sure patients have appropriate antiviral treatment when you release them.”
Persing continues, “CDC’s and HHS’s goals are for a test that doesn’t require a professional to administer it.” Cepheid believes it can meet the challenge with its GeneXpert Flu assay, which allows for PCR-based testing in a CLIA-waived test format. “Likewise, the agencies are skeptical about using antigen–antibody-based testing for avian influenza since specificity and sensitivity have been low historically.”
In fact, high false-positive and false-negative rates for seasonal influenza have led to admission errors and could be catastrophic if avian influenza becomes an imminent problem in the United States.
CDC and HHS have also placed a strong emphasis on the adaptability of the diagnostic tests because the mutation rate of H5N1 is high, which might increase its human-to-human transmissibility over time. The contract awardees must focus on the ability of their companies to adapt the diagnostic test rapidly in case a new strain arises. Persing emphasizes that the adaptability of PCR technology would also allow adaptation to a new strain in weeks rather than months.
Nanogen, the recipient of the greatest funding for the first two phases, is working to develop a high-sensitivity lateral-flow test using the underlying technology employed in its current cardiac infarction products. According to Suzanne Clancy, PhD, Nanogen’s director of corporate communications, “We plan to capitalize on current technology to develop a readily adaptable test that can provide results at the point of care in as few as 15 minutes.”
