New Test Speeds Diagnosis of Lethal Avian Flu Strain

By DONALD G. McNEIL Jr.
Published: August 29, 2006
http://www.nytimes.com/2006/08/29/health/29flu.html?_r=1&ref=health&oref=slogin

In an advance that speeds up diagnosis of the most dangerous avian flu, scientists have developed a detailed influenza test that takes less than 12 hours, federal health officials said yesterday.

The new technology, a microchip covered with bits of genetic material from many different flu strains, cuts the typical time needed for diagnosis of the A(H5N1) flu to less than a day from a week or more. In addition, rather than giving just a yes-or-no result, it usually reveals which flu a human or an animal has.

That means that public health officials investigating, for example, a flu outbreak in poultry or in humans in a remote Asian or African village will be able to decide quickly whether to kill thousands of birds or to treat hundreds of potentially exposed people with expensive antiviral drugs.

Right now, ascertaining whether a flu is of the lethal A(H5N1) strain requires that a sample be frozen and shipped to a highly secure laboratory, usually in a major city like Atlanta or Hong Kong, where the virus can be grown in eggs, isolated and genetically sequenced. That process takes four to five days plus shipping time and runs the risk of samples defrosting in transit and being ruined.

The new test, called FluChip, can be performed in any laboratory that can amplify bits of genetic material; many countries have such laboratories in their national capitals, if not in provincial hospitals. Samples need not be frozen, and because only bits of genetic material are multiplied rather than whole viruses, the work can be done in laboratories with lower biosecurity levels.

Nancy J. Cox, chief of the influenza branch of the Centers for Disease Control and Prevention in Atlanta, said the chip “really allows us to get a lot of information about a virus in a short time.”

Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, which announced the creation of the test, called it an “encouraging advance” that could be “invaluable to international flu surveillance efforts.”

Dr. William B. Karesh, chief field veterinarian for the Wildlife Conservation Society, who led a 2005 expedition to Mongolia to track the lethal avian flu virus as it first moved out of Asia in migrating wild birds, said the new test “sounds fabulous.”

“It could be an incredibly powerful tool,” Dr. Karesh said.

A more advanced version to be used in the field may be ready within two years, said Kathy L. Rowlen, a University of Colorado chemistry professor who led the team that developed the test.

At present, animal and human health experts trying to fight avian flu in remote areas are forced to make important decisions based largely on guesses because it is too risky to wait a week for a laboratory to confirm that a highly dangerous virus is loose.

A dipstick test done on the spot, which a veterinarian working in Indonesia said was as quick and as simple as a home pregnancy test, can tell only if a flu is type A.

Getting more information requires polymerase chain reaction amplification, which Dr. Rowlen described as “separating the genetic material of the virus itself from all the other things you find in a nasal swab, and then making a million copies of it, like using a photocopier.”

That requires a machine costing about $20,000, which can be found in most countries’ national laboratories and in some provincial hospitals, Dr. Karesh said. One he saw in Mongolia was “a kitchen-tabletop-type thing,” he said.

Currently, such machines and follow-up tests can tell in about four hours whether a flu is an H5 strain.

The FluChip, sometimes called a microarray, or gene chip, greatly enhances that technology.

It is coated with 55 short stretches of RNA selected from 5,000 samples of human, bird, pig and horse flus provided by the C.D.C., and including H5N1 and routine human flus of the H3N2 and H1N1 strains. The broken-up DNA in the amplified sample is, in effect, poured across the chip, and fragments stick to the matching bits of RNA. By noting the matches, scientists can deduce which flu it is.

In recent tests, the technology correctly identified 72 percent of samples and partly identified an additional 13 percent, according to the disease centers.

Moreover, as the flu mutates, Dr. Cox said, stretches of RNA from newly emerging strains could be added.

Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, called the chip “good news, because it clearly moved ahead the diagnostic tools we have.” It also has the potential to speed up mass testing because dozens of samples can be tested on dozens of chips at once.

But if a flu pandemic were to erupt, Dr. Osterholm warned, the test could quickly be rendered useless because most of the chemicals needed for the preliminary DNA-amplification steps come from abroad, and the chaos that a pandemic would cause would interrupt supplies.

“You can have all the guns you want,” he said, “but if the bullets are offshore, you can’t shoot very much.”