2 Studies Find Flu Treatments Fall Far Short
By ELISABETH ROSENTHAL
International Herald Tribune
September 22, 2005
http://www.nytimes.com/2005/09/22/health/22flu.html?oref=login&pagewanted=print  (Must register to NY Times to view original article)

ROME, Sept. 21 - Just as governments around the world are stockpiling millions of doses of flu vaccine and antiviral drugs in anticipation of a potential influenza pandemic, two new surprising research papers to be published Thursday have found that such treatments are far less effective than previously thought.

"The studies published today reinforce the shortcomings of our efforts to control influenza," wrote Dr. Guan Yi, a virologist at the University of Hong Kong, in an editorial that accompanied the papers. The two studies were published early online by The Lancet, the London-based medical publication, because of their important implications for the coming flu season.

In one paper, international researchers analyzed all the data from patient studies on the flu vaccine performed worldwide in the last 37 years and discovered that vaccines showed at best a "modest" ability to prevent influenza or its complications in elderly people.

"The runaway 100 percent effectiveness that's touted by proponents was nowhere to be seen," said Tom Jefferson, a researcher in Rome with the Cochrane Vaccine Fields project, an international consortium of scientists who perform systematic reviews of research data.

"There is a wild overestimation of the impact of these vaccines in the community," he said. "In the case of a pandemic, we are unsure from the data whether these vaccines would work on the elderly."

In the second paper, researchers from the Centers for Disease Control and Prevention in Atlanta found that influenza viruses, particularly those from the dreaded bird flu strain, had developed high rates of resistance to the only class of cheap antiviral drugs available - drugs mainly used to treat flu once patients have caught it. These resistance rates have increased rapidly since 2003, particularly in Asia.

"We were alarmed to find such a dramatic increase in drug resistance in circulating human influenza viruses in recent years," said Dr. Rick Bright of the disease control centers. "Our report has broad implications for agencies and governments planning to stockpile these drugs for epidemic and pandemic strains of influenza."

Before 2000, almost no virus was resistant to the drug Amantadine. By 2004, 15 percent of influenza A viruses collected in South Korea, 70 percent in Hong Kong and 74 percent in China were impervious. During the first six months of 2005, 15 percent of the influenza A viruses in the United States were resistant, up from 2 percent the year before. All human cases of the bird flu A(H5N1) strain - which is still extremely rare in humans - have been resistant, the researchers said.

The immediate implications of these finding are most ominous for the developing world, because wealthier nations have been stockpiling newer and vastly more expensive antiviral medicines, like Tamiflu, which are effective against the disease but still under patent.

Even so, the research is alarming because it demonstrates how quickly and unexpectedly flu viruses can become impervious to medicines once they are put into common use, as they would be in the case of a pandemic. Also, at their best, antiviral medicines do not cure influenza. They reduce transmission of the disease and lessen somewhat the symptoms and complications in people already infected, including the high rate of associated pneumonias.

Called for comment, Dick Thompson, a spokesman for the World Health Organization, said that the group could neither support nor deny the findings of the analysis of vaccine studies at this point, noting only that some specialists criticized the researchers for "not including some important past studies" in their sample.

But the problem of resistance "is a finding that is being discussed widely within the flu world and will bear careful monitoring," he said, noting that he was not aware of any country in the developing world that had been able to stockpile the newer drugs.

Anticipating a possible flu pandemic caused by a variant of the bird flu virus - which belongs to the influenza A group - countries have been aggressively buying antiviral medicines and contracting to purchase a flu vaccine against that strain, even though it is still under development. The United States has ordered $100 million worth of vaccine, and Italy $43 million worth, for example.

The current bird flu virus does not spread easily - if at all - from human to human, and so has little potential to become a worldwide human scourge. But the World Health Organization has warned that it could acquire that potential through a couple of common biological processes, and that countries should prepare for a possible wave of serious influenza.

The fact that the vaccine study showed that inoculations have had only a modest effect in the elderly is particularly worrisome, because this is a group that tends to suffer high rates of complications and deaths from the disease and vaccination is the standard practice. In people over 65, the vaccines "are apparently ineffective" in the prevention of influenza, pneumonia and hospital admissions, although they did reduce deaths from pneumonia a bit, by "up to 30 percent," the study says.

"What you see is that marketing rules the response to influenza, and scientific evidence comes fourth or fifth," Dr. Jefferson said. "Vaccines may have a role, but they appear to have a modest effect. The best strategy to prevent the illness is to wash your hands."

In terms of antiviral drugs, 30 countries have placed huge orders for Tamiflu, the most popular newer more expensive antiviral medicine, said Martina Rupp, a spokesman for Roche, the Swiss company that makes it. The Dutch Health Ministry has ordered five million doses, enough to treat one-third of the population. Britain has ordered supplies to treat 15 million.

Researchers speculate that one reason resistance rates to the older, cheaper antiviral drugs jumped so much starting in 2000 - and skyrocketed after 2002 - is that doctors in Asia started prescribing the drugs far more widely after the advent of bird flu in 1997 and sudden acute respiratory syndrome, or SARS, in 2002.

No Mutation Seen in Fatal Virus

The New York Times

HONG KONG, Sept. 21 - A woman's death from avian influenza in Jakarta, the capital of Indonesia, has caused alarm there, but genetic tests here on virus samples from the woman showed on Wednesday that the virus had not mutated in ways likely to make it more of a threat to people.

The virus in the woman, who died early this month, "seems like a virus that has gone directly from birds," rather than from person to person, said Dr. Georg Petersen, the World Health Organization representative in Jakarta. The deaths of two girls with flulike symptoms this week in Jakarta have fed public concern there. But Dr. Petersen said that laboratory tests would be needed to conclude whether the girls had been infected with the A(H5N1) virus.