Flu season is coming, and with it is a raft of diagnostics that aims to track and diagnose the virus including its lethal H5N1 strain. The field is heading more toward personalized medicine every year.
The field of influenza diagnostics is mostly composed of traditional pathology procedures and virus-detection tests, such as Rockeby Biomed's rapid antibody-based test and Qiagen's PCR-based detection test, both of which can now help detect the H5N1 virus in birds.
But there could be more valuable clinical information to be found in the viruses' genes. Initially, products like the two different strain-typing microarrays made by Combimatrix and a University of Colorado at Boulder research team will be useful only as epidemiological tools, but as scientists learn more about flu strains, and as pharma creates new drugs to combat them, the pharmacogenomic applications become obvious.
"Certainly if someone has a strain that is not H5N1, you may not want to waste precious amounts of things like [Roche's] Tamiflu, because there is a limited supply," Amit Kumar, Combimatrix' president and CEO, told Pharmacogenomics Reporter this week.
"It is only a matter of time before an avian-flu virus most likely H5N1" sparks "the outbreak of human pandemic influenza."
In addition to serving as a way to help conserve Roche's limited stores of Tamiflu, influenza strain-typing diagnostics have the potential to become pharmacogenomic tools similar to HIV strain-typing diagnostics. Some strains of avian flu are resistant to Tamiflu, so "using our chip, we can tell if an individual has a resistant strain, and so in that case, a physician would know that Tamiflu is not going to have an impact, and so there may be other drugs that people would want to try," said Kumar.
Coincidentally, preliminary evidence emerged this week at a World Health Organization meeting in Geneva that older drugs, in particular amantadine and rimantadine, may be useful in treating some types of H5N1, even though scientists believed that this strain of the virus was resistant to such treatment, according to the Wall Street Journal. The WHO has not yet decided whether to publicize the information, the article said. Amantadine and rimantadine have long been used for treating seasonal influenza, and both are cheaper than Tamiflu.
However, with what is currently known about influenza, if Tamiflu is taken off the table as a possible treatment, "there is not much that can be done, unfortunately," Kumar said.
Combimatrix will probably file for FDA approval for its flu chip toward the end of 2005 or early next year, Kumar said. "Filing for FDA approval is something that we plan to do for the influenza chip in general, which will include H5N1 [probes] now if one of these [strains] gets out of hand, it's not clear whether FDA is going to accelerate approval processes" for that particular strain, he said. But when and if the chip is approved, it will be a general influenza-typing diagnostic, he added.
Until Combimatrix is awarded FDA clearance, the company will be selling the flu chip to international health organizations and government entities primarily those in East Asia interested in disease monitoring and surveillance, which is a difficult market to estimate, Kumar said. Combimatrix is currently selling its diagnostic to an undisclosed US military agency, which is evaluating its possible uses in the event of an epidemic, he said.
It is not yet known how funding for influenza-pandemic prevention will be allocated, said Qiagen spokesperson Solveigh Mähler. "How much money will go into diagnostics, testing, treatment, and all the other things? It could also go into bird caging, for example, just to make sure birds are not infecting each other," she said. The company is marketing its flu-identification tests to research laboratories and clinical molecular diagnostics.
"H5N1, right now, has only been transmitted to humans through birds, and so there's really not a lot of epidemiological work to be done" in humans, Kumar said. "I think if there is a case where there's human-to-human disease movement, then I think you're going to see products like ours fly off the shelves, because people are going to be concerned," since H5N1 has the potential to kill as many as one of every two victims, he added.
In remarks made to a group of health experts and government officials at the World Health Organization's Geneva headquarters, Lee Jong-wook, the organization's director-general said this week that "it is only a matter of time before an avian-flu virus most likely H5N1" sparks "the outbreak of human pandemic influenza."
The advantage of a strain-typing microarray to epidemiology lies mainly in its ability to rapidly differentiate between different virus types, and to identify new mutations and new combinations of viral genes. Approximately 200 laboratories worldwide perform detailed strain analysis, and that data is used to predict which vaccines will be necessary for the next flu season, Kathy Rowlen, a professor in the University of Colorado at Boulder chemistry and biochemistry department, said this week in a statement.
With the Combimatrix array, results are available in about four hours. Using the array developed by CU researchers led by Rowlen, results can be available in about 11 hours, while traditional microbiological techniques take about four days, she said in the statement.
The CU flu array exhibited 90-percent accuracy when it was tested last month by the US Centers for Disease Control and Prevention using three primary subtypes of the virus, and it will be tested against traditional strain-typing methods in December, said Rowlen. The CU team may make the DNA sequences on its flu array freely available to interested researchers, she said.
Both the CU team and Combimatrix plan to produce small, portable flu strain-typing devices for use in the field.
The advantage of rapid antibody-based tests and PCR based tests, such as Qiagen's new H5N1 test and its existing influenza-A and -B tests, is that they are more portable, simpler, and more rapid. Antibody-based testing can take about an hour after sample preparation, and the more-sensitive PCR testing can take about two hours. These tests provide yes-or-no answers for infection by specific strains, but they offer no further information.
Rapid tests are generally used in epidemiology, said Qiagen spokesperson Solveigh Mähler. In avian flu trouble spots, "it is very, very important if there is a [human] flu infection to make sure that he's not infected with avian flu, just to make sure that this epidemic is not spreading out," she said.
"Qiagen is the only company that has an approved [avian flu] test already in its portfolio," with its PG Biotech test, which is approved by the Chinese food and drug regulatory agency for detecting the strain in birds, said Mähler.
Chris Womack ([email protected])