If this happens a super flu bug is sure to follow

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February 28, 2008

Panel Advises Flu Shots for Children Up to Age 18

By LAWRENCE K. ALTMAN

All children ages 6 months to 18 years in this country should receive an influenza shot every year, a federal advisory panel said on Wednesday.

The recommendation expands by about 30 million the number of children who should get annual flu shots. Current pediatric recommendations call for influenza vaccinations for children ages 6 months to about 5 years.

In expanding the new upper age limit to 18 years, the aim is to reduce both the time children and parents lose from visits to pediatricians and missing school and the need for antibiotics for complications, said Dr. Anne Schuchat, who directs the disease agency’s program on immunization and respiratory diseases.

An added expected benefit would be indirect — to reduce the number of influenza cases among parents and other household members, and possibly spread to the general community.

The recommendation, which is voluntary, was made by the Advisory Committee on Immunization Practice, which advises the Centers for Disease Control and Prevention in Atlanta. The C.D.C. and its parent, the Department of Health and Human Services, generally follow the advice of the committee, which is composed of vaccine experts from academia and the private sector.

The committee voted unanimously that the expanded immunization should start as soon as possible, but no later than the 2009-10 flu season. The centers expect that the vaccine industry, which made 132 million doses available this year, will be able to produce a sufficient supply in future years.

Every state but one has reported widespread influenza this winter. In Florida, activity is regional. Last week, the centers reported that 22 children had died in this influenza season.

The C.D.C. has long urged older adults and those with chronic ailments to get influenza shots each season.

In 2004, following the advisory committee’s recommendation, the centers urged that all infants ages 6 months to 23 months receive flu shots to protect them from serious complications of the viral illness. Hospitalization rates among the infant group rivals those among elderly Americans.

In 2006, the centers expanded the recommendation to include children ages 24 months to 59 months to provide them direct protection against influenza infection.

For initial protection, children ages 6 months to 9 years require two doses of flu vaccine, at least one month apart, the committee said. Then they should receive annual shots.

In a new study reported at Wednesday’s meeting, Dr. David K. Shay, who led a team from the C.D.C. and eight state health departments, found that full immunization against flu provided about a 75 percent effectiveness rate in preventing hospitalizations from influenza complications in the 2005-6 and 2006-7 influenza seasons. (The 75 percent rate could range, according to a standard statistical measure known as confidence intervals, from 41 percent to 91 percent.)

The study, which involved children ages 6 months to 23 months who had laboratory confirmed cases of influenza, will continue through this flu season. Because this season seems to be more severe than the last two, the researchers expect to have more cases to analyze and improve the statistical odds.

Vaccines are typically designed to protect against the three strains of influenza. Experts determine the strains based on data from current seasonal transmission and their judgment about future activity. Usually one or two strains are changed in each year’s vaccine.

But committees from the World Health Organization and the United States Food and Drug Administration voted earlier this month to change all three strains in next season’s vaccine. It is the first time that all three strains were changed at once, Dr. Nancy Cox, an influenza expert at the C.D.C., said in a news conference on Feb. 22.

The centers recommendations for annual flu shots for adults include all Americans ages 50 and older; people with chronic lung, heart and other ailments; health care workers; and women who will be pregnant during the influenza season.

New generation anti-depressants have little clinical benefit for most patients, research suggests.

Anti-depressants 'of little use'

The University of Hull reviewed published clinical trial data, and unpublished data secured under Freedom of Information legislation.

They found the drugs helped only a small group of the most severely depressed, and in most cases had no more effect than taking a dummy pill.

The Royal College of Psychiatrists said the findings were "very important".

In total, the Hull team, who published their findings in the journal PLoS Medicine, reviewed data on 47 clinical trials.

They focused on drugs in the class known as Selective Serotonin Reuptake Inhibitors (SSRIs), which work by increasing levels of the mood controlling chemical serotonin in the brain.

These included fluoxetine (Prozac), venlafaxine (Efexor) and paroxetine (Seroxat) - all commonly prescribed in the UK.

There seems little reason to prescribe anti-depressant medication to any but the most severely depressed patients Professor Irving Kirsch University of Hull

The number of prescriptions for anti-depressants hit a record high in England in 2006 - even though official guidance stresses they should not be a first line treatment for mild depression.

The researchers found that even the positive effects seen on severely depressed patients were relatively small, and open to interpretation.

The seemingly good result came from the fact that these patients' response to the placebo decreased, rather than any notable increase in their response to anti-depressants.

Lead researcher Professor Irving Kirsch said: "The difference in improvement between patients taking placebos and patients taking anti-depressants is not very great.

"This means that depressed people can improve without chemical treatments.

"Given these results, there seems little reason to prescribe anti-depressant medication to any but the most severely depressed patients, unless alternative treatments have failed to provide a benefit."

Flu shot formula off target this year

When are people going to wake up to the flu vaccine hoax?

By David Brown
Washington Post
Published on: 02/11/08

Washington —- Seasonal influenza is spreading widely throughout the United States, with nearly half the cases caused by strains of the virus that are not directly covered by this year's flu vaccine.

Whether the winter will end up being worse than usual remains to be seen. Flu mortality in adults has been higher than in the last two years, but deaths in children —- an important marker of severity —- have been rare.

Nevertheless, this winter is likely to be one of the few times that public health experts lose the bet they make each year when they devise the formula for the flu vaccine —- eight months before the virus starts circulating in the fall to allow time to produce mass quantities of the vaccine.

"Most years, the prediction is very good," said Joseph Bresee, an influenza epidemiologist at the Atlanta-based Centers for Disease Control and Prevention. "In 16 of the last 19 years, we have had a well-matched vaccine."

But probably not this time.

What happened

Each year, the vaccine contains representatives of the three huge families of flu virus that are currently circulating. They are two main types of influenza A, H1N1 and H3N2, and influenza B.

The viruses in each of these lineages are constantly changing through mutation. Inevitably, one appears that is different enough that a person protected against them is not protected against the new variant.

A version of this scenario apparently happened twice this year.

> A new strain of H3N2 virus was identified in Brisbane, Australia, last February, a few weeks after the components of this winter's vaccine were chosen.

But it was too late to substitute "Brisbane/10" for the H3N2 strain, called "Wisconsin," that had been in the vaccine since the 2006-07 season. From the start of flu season until the beginning of February, 34 percent of flu viruses taken from patients around the country were Brisbane strains.

> At the same time, a strain of influenza B called "Yamagata," which is significantly different from the "Victoria" B strain in the vaccine, was taking off.

About 16 percent of all flu samples this winter are influenza B, and of them 93 percent are Yamagata.

Together, the Brisbane and Yamagata strains are accounting for 48 percent of all flu samples this winter —- and neither is in the vaccine.

Any benefit?

That does not mean the vaccine is without benefit. The immunity conferred by the Wisconsin strain may protect somewhat against its Brisbane descendant. A vaccinated person may have milder symptoms. But the vaccine is unlikely to prevent infection altogether in lots of people.

A study done by the Department of Defense last year after Brisbane emerged found that it was 52 percent effective in preventing infection.

That is much lower than the 70 percent to 90 percent protection provided by a well-matched vaccine given to healthy, young adults. But it is not useless, either.

"It wouldn't be optimal, but there should be a measure of protection, based on our past experience," said Nancy Cox, the chief flu virologist at CDC.

Protection against the Yamagata strain by the vaccine is probably also poor. The best evidence that Yamagata is not well covered by the vaccine is that it is just about the only strain of influenza B around.

"That probably indicates that the effectiveness of the vaccine may be less than ideal," Bresee said.

Next year?

Influenza virologists from around the world will gather in Geneva, Switzerland, this week to decide the formula for next year's vaccine.

China Didn’t Check Drug Supplier, Files Show

By WALT BOGDANICH and JAKE HOOKER

A Chinese factory that supplies much of the active ingredient for a brand of a blood thinner that has been linked to four deaths in the United States is not certified by China’s drug regulators to make pharmaceutical products, according to records and interviews.

Because the plant, Changzhou SPL, has no drug certification, China’s drug agency did not inspect it. The United States Food and Drug Administration said this week that it had not inspected the plant either — a violation of its own policy — before allowing the company to become a major supplier of the blood thinner, heparin, to Baxter International in the United States.

Baxter announced Monday that it was suspending sales of its multidose vials of heparin after 4 patients died and 350 suffered complications. Why the heparin caused these problems — and whether the active ingredient in the drug, derived from pig intestines, was responsible — has not been determined.

The plant in Changzhou, west of Shanghai, appears to fall into the type of regulatory void that American and Chinese health officials are trying to close — in which chemical companies export pharmaceutical ingredients without a Chinese drug license.

China provides a growing proportion of the active pharmaceutical ingredients used in drugs sold in the United States. And Chinese drug regulators have said that all producers of those ingredients are required to obtain certification by the State Food and Drug Administration. However, some of the active ingredients that China exports are made by chemical companies, which do not fall under the Chinese drug agency’s jurisdiction.

In December, American and Chinese regulators signed an agreement under which China promised to begin registering at least some of the thousands of chemical companies that sell drug ingredients. Some of these companies are the source of counterfeit or diluted drugs, including those used to treat malaria.

Discussions that led to the accord began after an unlicensed chemical plant in China made a tainted drug ingredient that poisoned more than 170 people in Panama, killing at least 115.

The heparin plant in China has not been accused of providing a harmful product. The American majority owner of that plant, Scientific Protein Laboratories, also owns a plant in Wisconsin that produces the active ingredient in heparin for Baxter.

In response to questions, Scientific Protein issued a statement confirming that its Chinese plant had no license from the Chinese agency, but said that its raw ingredients come from a licensed supplier.

The statement added that an “independent private U.S. validation company” had found the plant to be in compliance with good manufacturing practices. And a spokeswoman for Baxter, which buys heparin’s active ingredient from Scientific Protein, said it had inspected the China plant less than six months ago.

A spokesman for China’s State Food and Drug Administration, Shen Chen, said Friday that “as far as we know, it is not a drug manufacturer — it is a producer of chemical ingredients.”

Eric S. Langer, managing partner of BioPlan Associates, which prepares and publishes reports on the biopharmaceutical and biotechnology industry, said he found it hard to believe that a company exporting the heparin ingredient would not be licensed by Chinese drug regulators.

“Being able to produce a pharmaceutical or a biologic in the U.S. or anywhere without having regulatory oversight really doesn’t happen,” Mr. Langer said, adding, “I find it surprising from a regulatory perspective, and I find it surprising from a business perspective.”

Karen Riley, a spokeswoman for the United States Food and Drug Administration, said inspectors from that agency would be visiting the Changzhou plant soon. Ms. Riley said she could not be more specific. Earlier in the week she described her agency’s failure to inspect the plant as a “glitch.”

Congress has criticized the oversight by the Food and Drug Administration of bulk pharmaceutical ingredients made by foreign manufacturers and sold in the United States. A growing number of those ingredients now come from China. Of the 700 approved Chinese drug plants, the United States agency has inspected only 10 to 20 each year.

Baxter makes roughly half of the United States supply of heparin, which is used widely for surgical and dialysis patients. Problems with Baxter’s heparin were first noticed late last year when four children undergoing dialysis in Missouri had severe allergic reactions minutes after being injected with the drug.

The F.D.A. then allowed Baxter to deliver heparin that it was in the midst of shipping, for fear that a total recall would lead to a shortage of the drug, but cautioned doctors to use as little of it as possible and to administer it very slowly.

The agency also suggested that doctors give steroids or antihistamines with the Baxter heparin to help prevent allergic reactions.

Erin Gardiner, a spokeswoman for Baxter, defended Scientific Protein, saying it had been making the heparin ingredient for more than 30 years. “They have been a good supplier,” she said.

Although the cause of the adverse reactions has yet to be determined, she said tests performed by her company had detected unspecified differences between some lots of the ingredient. She did not say whether the lots had come from China or from the Wisconsin plant, which Scientific Protein also owns.

Those differences had not turned up in routine testing that the company does on active ingredients, Ms. Gardiner said, but she said Baxter had used “advanced testing techniques” to find the differences. She added that it was unclear whether the finding was significant.

Two Congressional committees have asked the Food and Drug Administration for more information about inspections of plants making the active ingredient of heparin.

Andrew W. Lehren contributed reporting.

Tamiflu-Resistant Flu Found in Nine European Nations

By Jason Gale

Feb. 1 (Bloomberg) -- Influenza strains resistant to Roche Holding AG's Tamiflu were found in a samples from five more countries, indicating the mutant bug is more widespread than health officials reported earlier this week.

Tests on 437 virus specimens from patients with the H1N1 flu strain in 18 countries found 59 that harbored resistance to the pill, the European Centre for Disease Prevention and Control said in a statement yesterday. Resistant viruses were found in nine European countries, with Norway accounting for almost half.

Emerging resistance to Tamiflu, also known as oseltamivir, has led doctors to consider GlaxoSmithKline Plc's Relenza and other treatments for a disease the World Health Organization estimates causes 250,000 to 500,000 deaths globally each year. Experts are assessing the significance of the data and will release an interim assessment in the coming days, ECDC said.

``At this stage, it is impossible to say what the level of resistance is in influenza across Europe,'' the Stockholm-based health agency said. ``However from the limited data, the proportion of influenza viruses exhibiting resistance to oseltamivir must be significant, but not as high as in Norway.''

The H1N1 viruses identified in Europe that aren't susceptible to Tamiflu carry a so-called H274Y gene mutation that confers ``high-level resistance,'' Frederick Hayden, a researcher with the WHO's Global Influenza Program in Geneva, said in a Jan. 28 interview.

U.S. Strains

Of 109 H1N1 viral samples tested in the U.S. during the 2007-2008 flu season, 5.5 showed the same resistance-inducing mutation, according to the Centers for Disease Control and Prevention in Atlanta.

Recent tests on samples from Europe found viruses with the H274Y mutation in Germany, Netherlands, Portugal, Sweden and Finland, scientists from the U.K.'s Health Protection Agency said in a report published yesterday in Eurosurveillance, a newsletter on communicable diseases.

Earlier sampling found the mutant strain in France, the U.K., Denmark, France and Norway, the ECDC said in a Jan. 27 risk assessment report. Of 37 samples from Norway tested, 26 harbor resistance, the agency said yesterday.

``The oseltamivir resistance investigation is still in its early stages,'' researchers from the ECDC's Influenza Project Team wrote in a separate report in yesterday's Eurosurveillance. ``A more accurate picture will only emerge when many more specimens have been tested and more epidemiological information is available.''

Tests so far show that the mutated viruses are susceptible to Relenza and an older class of antiviral drugs known as adamantanes, the researchers said. There's insufficient evidence for authorities to consider changes to clinical guidelines, the researchers said.

No More Virulent

People who become ill with the Tamiflu-resistant H1N1 strain don't appear to become any more sick than people infected with ``normal'' seasonal flu, ECDC said.

Tamiflu, which generated 2.09 billion francs ($1.9 billion) in sales for Basel, Switzerland-based Roche in 2007, is the company's fifth-best-selling drug. Relenza, an inhaled medicine, had sales of 91 million pounds ($181 million) in 2006 for London-based Glaxo.

The medicines are being stockpiled by the Geneva-based WHO and governments around the world for use in the event of a pandemic, and to treat the H5N1 avian flu strain that's spread to more than 60 countries, infecting people in 14 of them.

The H5N1 bird flu strain could trigger a global outbreak if it adopts some of the characteristics of seasonal flu that enable it to be spread easily through coughing and sneezing.

To contact the reporter on this story: Jason Gale in Singapore at j.gale@bloomberg.net

Last Updated: February 1, 2008 00:53 EST