Correction Appended
A strain of avian flu that is resistant to the antiviral drug oseltamivir has been isolated from two family members in Egypt, the World Health Organization said yesterday.
The development is potentially dangerous because oseltamivir, commonly sold under the name Tamiflu, is the chief weapon against the flu strain, H5N1, which many worry could mutate into a strain that could set off a worldwide pandemic.
The health organization emphasized that it was too early to tell whether the resistant strain had developed independently in the two patients, who were both under treatment with the drug, or whether they had picked it up from birds or from each other. The resistant strain did not spread to anyone else, including a third family member who also had avian flu.
“Given the information we have, we don’t see any broad public health implications,” said Dick Thompson, a spokesman for the organization.
Mr. Thompson was unsure which Egyptian cluster of flu infections the patients were part of. But another source said it was one in Gharbiya Province, roughly 50 miles north of Cairo, in which flu killed three people last month in a 33-member family living in one compound.
Oseltamivir-resistant strains were found in three unrelated patients in Vietnam in 2005 but did not spread.
The development “is not a big surprise, but it certainly is disheartening,” said Dr. Anne Moscona, an expert on flu treatment at Weill Cornell Medical College.
The oseltamivir-resistant strain in Egypt was susceptible to zanamivir, which is sold as Relenza, and to amantadine, which is from an older, cheaper and easier-to-use class of drugs but is not normally used as a first-line treatment because many avian flu strains are resistant to it.
The development, Dr. Moscona said, suggested that doctors might have to consider switching to a cocktail of drugs as first-line treatment, as is done with AIDS medications and sometimes with antibiotics.
Dr. Andrew T. Pavia, chairman of the pandemic influenza task force of the Infectious Diseases Society of America, said it was theoretically possible that resistant strains of the flu had developed simultaneously in two related patients, especially if they were very sick and had been treated with doses of oseltamivir that were too low.
But if one transmitted it to the other, “it would be very worrisome,” he said, because previous resistant strains had been very weak at infecting new victims.
Scientists do not know exactly which mutations or how many of them would make the avian flu virus more dangerous, but they have some clues.
The virus now circulating in birds does not attach easily to cells inside human noses or throats. It reproduces more slowly at human temperatures than at bird temperatures, which are slightly higher. It does not detach easily from cells to infect new ones, and it is usually killed by oseltamivir.
Scientists are keeping an eye on the genes that code for those aspects of the virus — for example, the shape of the spikes on its outer coating, where it binds to cells.
If an oseltamivir-resistant strain spreads, it will complicate the public health response. Governments have been stockpiling oseltamivir, not zanamivir. Zanamivir is more expensive and also harder to use and to ship, because it is typically sold not as a pill but as a powder that comes in an inhaler resembling a small hockey puck.
An intravenous form exists but has not been approved for use in some countries, including the United States, Dr. Moscona said.
A mutation in the H5N1 avian flu or bird flu virus has been found in two humans infected with the virus located in the Gharbiyah Province of Egypt which is located about 50 miles outside of Egypt's capital Cairo.

The victims, a 16 year-old girl and her 26 year-old uncle both died in December of 2006 and both patients were administered the Bird Flu treatment oseltamivir (Tamiflu®), had shown to be less effective against their illnesses. The virus was also tested against the drugs zanamivir (Relenza®) and amantadine, and is was found that these drugs were still effective against the mutated form of this virus.

A sister of the 26 year-old also died of Bird Flu in December of 2006, but health officials have yet to determine if she died from the mutated form of the virus.

The World Health Organization is also stating that the three cases may be human to human transmission, but further tests are needed. The three cases are being treated as an outbreak and officials have yet to determine if the victims received the illness from chickens, or from one another.

"Based on the information we have, we can't yet rule out human-to-human transmission. We need to better understand the dynamics of this outbreak," said Bird Flu antivirals expert for the WHO, Doctor Fred Hayden. "It would be very worrisome" if human to human transmission did occur.

The WHO however is not concerned that this outbreak may be the start of a world-wide pandemic and it is unknown how many times Bird Flu will need to mutate before it becomes more dangerous to humans.

"Given the information we have, we don’t see any broad public health implications," said a spokeman for the WHO, Dick Thompson.

Egypt was added to the list of countries where the H5N1 virus has been found just last year. Since then the virus has only infected 18 people. Of those people, 10 have died so far, including these three cases in December.

The WHO reports that 267 people have been infected with Bird Flu in the entire world and that of those people, 161 have been confirmed to have died from the H5N1 virus.

Mutated Strains of Bird Flu have been found in Vietnam in 2005 and in Turkey in 2006.