Nov. 20 (Bloomberg) -- Swine flu infections in which the virus mutated to a form that’s more severe or less sensitive to drug treatment are being investigated by European and U.S. public health officials.

Five patients at a hospital in Wales contracted swine flu that resisted treatment with Roche Holding AG’s Tamiflu, and three more infections are being analyzed, the U.K. Health Protection Agency said today. Four patients had resistance in a North Carolina hospital. A separate mutation that may trigger more severe illness was found in Norway among two patients who died of the flu and one who was severely ill.

While there is little risk posed by the mutations, investigators are monitoring the new clusters closely, according to health officials from the U.S. Centers for Disease Control and Prevention and the World Health Organization. Influenza activity decreased last week in the U.S. and was widespread in 43 states compared with 46 states the week earlier, the CDC’s Anne Schuchat said today in a briefing. Since swine flu was identified in April, there have been 57 U.S. cases of Tamiflu resistance and “sporadic” reports of mutations similar to those in Norway, she said.

“We take this development seriously, but the HPA currently considers that the risk to the general healthy population is low,” the U.K. officials said in a statement about the Wales cases. “The Tamiflu-resistant virus has emerged in a group of particularly vulnerable individuals. These patients are known to be at increased risk of developing resistance to the drug.”

Spread Since April

Swine flu, also known as H1N1, infected about 22 million people in the U.S. and killed 3,900 people from April to Oct. 17, according to the CDC’s most recent estimate. Norway has had an estimated 700,000 infections, with 21 reported deaths. The disease has killed at least 6,770 people worldwide, according to an estimate today from the Geneva-based WHO. The agency no longer keeps an up-to-date count of global cases.

In the U.S., patient visits to doctors for flu-like symptoms declined the week of Nov. 8 to Nov. 14 from the week earlier as did the rate of influenza hospitalizations, said Schuchat, head of the CDC’s National Center for Immunization and Respiratory Diseases.

“We are beginning to see some declines in influenza activity,” she said. “But it is still much greater than we would ever see at this time of year” compared with typical seasonal flu that runs from November to March.

Difficult to Transmit

The swine flu mutation discovered in Norway is difficult to pass from person to person, said David Mercer, acting head of the communicable diseases unit of the WHO’s European region, and Geir Stene-Larsen, the head of the Oslo-based Institute of Public Health. The mutation was found in 3 of 70 patients tested, the institute said.

The infections in Wales may have passed from a person using Tamiflu to patients who haven’t taken the drug, raising the possibility that a hard-to-treat form of the disease may spread, according to the U.K. health agency. The U.S. cases occurred in October and November, according to the Atlanta-based CDC.

The patients in Wales had blood diseases that weakened their immune systems, either because of the condition itself or the chemotherapy used to treat it, according to the U.K. agency. Resistance to Tamiflu is known to occur in patients with weak immune systems. All the Welsh patients remain sensitive to GlaxoSmithKline Plc’s Relenza, another antiviral treatment, the agency said.

In Norway, the changes seen in the virus may allow it to penetrate deeper into the airways and cause more severe disease.

“It seems that the mutated virus does not circulate in the population but might be a result of spontaneous changes which have occurred in these three patients,” Stene-Larsen said in a statement. “There is no indication that this change in the virus is of any importance for the effect of the vaccine or the effect of antiviral treatment.”

Sensitive to Drugs

The virus in Norway appears to be sensitive to Tamiflu and the vaccine now being offered in some areas to prevent swine flu infection, said Mercer of the WHO.

“I don’t think it yet has the public health implications that we would wonder about,” said Schuchat of the CDC. Similar mutations have been seen elsewhere and haven’t necessarily led to a more virulent disease, she said.

“It’s most likely that the virus’ capability to mutate is not just specific to Norway, it will occur in other countries as well,” Stene-Larsen said in an interview on broadcaster TV2.

To contact the reporters on this story: Michelle Fay Cortez in London at mcortez@bloomberg.netMarianne Stigset in Oslo at mstigset@bloomberg.net

Last Updated: November 20, 2009 19:23 EST