Antivirals & Vaccines

[bikerduck]

WASHINGTON - Don't count on a vaccine to protect against bird flu during the first six months of a pandemic. Health and Human Services Secretary Mike Leavitt said Monday it would take at least that long to produce a vaccine because the virus is changing and there's no way to know which strain might become capable of human-to-human transmissions
As a result, the government will have to maintain stockpiles of vaccine against each of the main H5N1 strains circulating the globe.

Once the particular strain is identified, it will take time to ensure that a vaccine is safe and to mass-produce it, he said.

"If we have a person-to-person, transmissible virus and we enter a pandemic condition, we will be operating without a vaccine for the first six months," Leavitt said. "We will be dependent upon traditional public health measures to contain and limit it."

Leavitt updated reporters Monday on what the federal government is doing to monitor and prepare for bird flu. A report he released noted that the virus has spread from 16 countries to about 37 in a span of about four months.

Leavitt said the federal government is operating under the assumption that an infected bird will be found in the United States by the fall. He stressed that people should not be overly concerned once a sick bird is found.

"As long as it is a bird disease, it is not a crisis," he said.

Scientists are concerned that the virus could mutate and become contagious among people. Currently, people have only been infected after close contact with sick birds. So far, 175 people have been infected and 96 of them have died.

HHS officials have held 23 bird flu summits throughout the country to emphasize the need for state and local communities to take the threat seriously, and to begin preparations for a pandemic.

Leavitt said his top bird flu concern was the ability of the government to get medicine quickly into the hands of people who need it.

"Doing anything millions of times is hard. Doing it fast makes it even more difficult," he said.

He also said he was worried about how the country would handle a surge in demand for health care.

"It will need to be the focus of individual community planning, because every community's surge will be handled differently," he said.

http://news.yahoo.com/s/ap/20060313/ap_on_he_me/bird_flu_leavitt_1

[bikerduck]

March 18 (Bloomberg) -- More studies are ``urgently'' needed to determine how bird flu patients can be best treated with oseltamivir, the antiviral drug marketed by Roche Holding AG as Tamiflu, the World Health Organization said.

Tamiflu is approved to treat seasonal flu. No direct clinical trial evidence shows the medicine is effective in treating people infected with the lethal H5N1 avian influenza virus because no such studies have been conducted, the Geneva- based United Nations health agency said yesterday.

``Because the optimal dosage has not been resolved by clinical trials, and because H5N1 infections continue to have a high mortality rate, prospective studies are needed urgently to determine optimal dosing and duration of treatment,'' the WHO said in a statement on its Web site.

The WHO and governments around the world are stockpiling Tamiflu for use as a prophylactic against any potential influenza pandemic. The medicine is also one of several drugs being used to treat patients with H5N1, which health officials worry may mutate into a form that's more contagious to humans.

Since 2003, H5N1 has killed at least 98 of 177 people infected, the WHO said on March 13.

There is limited evidence suggesting that some oseltamivir can reduce the duration of viral replication and improve prospects of survival, provided it is given within 48 hours following symptom onset, according to the WHO's fact sheet on avian flu, published on the Internet. Prior to an H5N1 outbreak in Turkey earlier this year, most patients were detected and treated late in the course of illness, it said.

Turkish Data

Roche said last week it has data from 21 patients in Turkey who took the drug after being infected with H5N1. Four of the patients were given the drug ``very, very late'' and died, David Reddy, head of Roche's pandemic task force, said. The remaining patients recovered and were discharged from the hospital.

``The evidence for effectiveness of oseltamivir in human H5N1 disease is based on virological data from in vitro, animal models, and limited human studies and extrapolation from the results of trials in patients with ordinary human influenza, '' the WHO said.

Optimal treatment of H5N1 cases using oseltamivir may be different than recommended for seasonal flu, the WHO said in the statement yesterday. For seasonal flu, it is recommended that adults take 75 milligrams of oseltamivir twice a day for five days.

In H5N1 cases, it is possible that severely ill patients might benefit from taking the medicine for seven to 10 days or given as much as 300 milligrams a day, the WHO said, adding that ``prospective studies are required.''

Higher Doses

Gastrointestinal side effects in particular may increase with higher doses, particularly above 300 milligrams a day, the WHO said. There is no adequate data on the use of oseltamivir in pregnant women, it said.

``Animal toxicology studies do not indicate direct or indirect harmful effects with respect to pregnancy or fetal development,'' the WHO said. ``Decisions to use oseltamivir in pregnant women should be made on a case by case basis where the potential benefit to the mother justifies the potential risk to the fetus.''

Basel, Switzerland-based Roche said on March 16 it will use 15 partners, including Sanofi-Aventis SA and Clariant AG, to increase production of Tamiflu by 33 percent by year's end.

Based on the current manufacturing capacity, it will take a decade to produce enough oseltamivir to treat a fifth of the world's population, according to the WHO.

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

http://www.bloomberg.com/apps/news?pid=10000087&sid=aI8r6k310BL4

[bikerduck]

ATLANTA - The bird flu vaccine currently being manufactured fought at least two forms of the virus in mice, but it's unclear whether the drug would be equally effective in humans, a health official said Monday.
The vaccine was designed to combat a version of bird flu identified in Vietnam in 2003. Scientists have wondered whether it also offers protection against a version seen later in Indonesia, Europe and Africa.

Experiments have shown that in mice, the vaccine for the first version prevented proliferation of the second, said Dr. Nancy Cox, director of the influenza branch of the federal Centers for Disease Control and Prevention.

But the results can't necessarily be applied to humans, she said. And in an another test that did not involve a vaccine, the immune defenses developed by a ferret against the first version of the bird flu did not work against the second, Cox said.

The test results were discussed Monday at an international conference in Atlanta on emerging infectious diseases.

The H5N1 virus has killed or forced the slaughter of tens of millions of chickens and ducks across Asia since 2003. It has spread more recently with migrating birds to Europe, Africa and the Middle East.

Worldwide, 177 human cases of bird flu have been reported, including 98 deaths, according to researchers at the conference. No cases have been found in the U.S.

Health officials fear the virus could evolve into a version that could easily be transmitted between people, potentially triggering a global pandemic. So far, there has been no evidence of such a mutation.

But more and more versions of H5N1 are being identified, according to research presented Monday.

Scientists must keep a close watch, and it may be necessary to develop additional vaccines as the virus mutates, said Rebecca Garten, a CDC researcher.

The U.S. government is spending $250 million on vaccine doses to fight the Vietnamese version of bird flu and has plans for enough to protect 20 million Americans.

This month, U.S. Health and Human Services Secretary Mike Leavitt authorized work to begin on a second vaccine based on the later form of the virus.

http://news.yahoo.com/s/ap/20060321/ap_on_he_me/bird_flu_vaccine_1

Dr. Henry Niman of Recombinomix, recently the out-of-the-box star that was the focus of last week's Wall St. Journal article, published last July info about the Indonesian family cluster whose virus genetics now form the basis of the vaccine development that was just announced by HHS's Leavitt:

Dr. Niman wrote on July 13, 2005 why this family cluster was so significant. They had just returned from a trip to India and Hong Kong.

Recombinomics Commentary
July 13, 2005

A father and his little daughter have died at a hospital in the western Java town of Tangerang from suspected avian influenza, local media reports said Wednesday.

Iwan Siswara Rafei, a staff with the Supreme Audit Body (BPK), died at the Siloam Gleneagles Hospital Tuesday afternoon after showing bird flu symptoms, reported the Detikcom online news service.

His daughter Thalita Nurul Azizah died earlier Saturday with similar symptoms, it said. Another daughter Sabrina Nurul Aisyah, who was first detected with the symptoms, is still under intensive treatment at the same hospital, around 20 km south of Jakarta.

She suffers high fever and respiratory problems.

The reports were first released by Metro TV, which reported that the family suffered the disease after their trip to Hong Kong and India.

The above familial cluster of bird flu is of concern for many reasons. Since a family of three has symptoms, human-to-human transmission is a major consideration. In addition, the return from a trip abroad highlights the potential of H5N1 being just one flight away, as well as the possibility of spread via other passengers, assuming the family had been flying. If linked to International airports, it would be the first reported H5N1 transmission linked to air travel.

The report leaves many questions unanswered, but two deaths will likely spur intense investigation and a combination of epidemiological and genetic investigations should provide answers.

The first questions simply focuses on disease onset dates. If all three family members developed symptoms at the same time, then a common source is likely. If disease onset dates were bimodal, the index case probably infected other family members. Since the index case is alive, but two family members have died, the initial reports sound like human-to-human transmission within the family.

Symptoms usually appear 2-4 days after exposure, so the dates would help determine if the infection originated in India, Hong Kong, or Indonesia. Since none of the three suspect areas have reported fatal human H5N1 cases recently, the potential for infection at airports cannot be excluded by the public data.

The epidemiological data can be supported by sequence data. Although there are no reported H5N1 cases in India, the Qinghai sequences include those from bar headed geese migrating from India. These sequences have the PB2 E627K polymorphism, which had not been previously reported and the sequences have an unusual constellation of genes with 3 related to Shantou sequences and 5 related to Hong Kong sequences. Prior sequences from Indonesia also contain sequences unique to Indonesia and Indonesia has a confirmed positive poultry worker, although symptoms were mild.

If the infections are linked to travel, then the number of actual cases is likely to be significantly higher than the reported number.

Transmission linked to international airports is a considerable concern.

http://www.recombinomics.com/News/07130502/H5N1_Export_India_Indonesia.html

[bikerduck]

Researchers claimed only partial success Thursday in the largest human trial of an avian flu vaccine. (Related video: Vaccine needs boost)
They showed the vaccine is safe and generates what appears to be a protective immune response. But it worked just half the time and only when given in a total dose that is 12 times the amount used in seasonal flu vaccine, study leader John Treanor of the University of Rochester says.

"Every journey starts with the first step," Treanor says, saying researchers hope to use chemicals called adjuvants to boost the vaccine's effectiveness.

The study, in Thursday's New England Journal of Medicine, marks a milestone in the joint government-private sector push to guard against avian flu by developing new vaccines and better ways of producing them. Without an effective vaccine, the Congressional Budget Office estimates, a flu pandemic in the USA could kill 2 million people.

So far, the avian flu virus, H5N1, has mainly killed birds. As of March 24, the World Health Organization reported 186 human cases and 105 deaths.

The virus's lethality, and its ongoing mutations, make it unlikely that any one vaccine will be enough, experts say.

"If this virus evolves to a point of being able to spread person to person, and we hope it never does, it will be different than the strain" used in this vaccine, possibly limiting its effectiveness, says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, the study's main sponsor.

Although the vaccine is not a perfect match, "we would hope there would be some benefit from deploying it."

The vaccine, made by Sanofi-Aventis, carries inactivated genes from an H5N1 virus taken from a patient in Vietnam. It was given to 451 healthy adults ages 18 to 64 who were broken into four groups. Each group received a different dose ranging from 7.5 micrograms to 90 micrograms. Just more than half of those who got two 90-microgram doses 28 days apart made enough protective antibody to match the levels that occur after standard flu shots.

Standard flu shots contain vaccines against three types of virus and are 75% to 90% effective in the age group studied in the trial. Each of the three doses totals just 15 micrograms.

The amount of vaccine needed to provide protection will be crucial in a pandemic. As the dose increases, the number of people who can be vaccinated shrinks, because there are limits to how much vaccine manufacturers can make.

Current global manufacturing capacity is about 900 million 15-microgram doses. At the high dose used in the trial, only 1.2% of the world's population, 75 million people, could be vaccinated, Gregory Poland of the Mayo Clinic Foundation wrote in an NEJ editorial.

The biotech firm Chiron also has produced an avian flu vaccine that is now in human trials.

And Thursday, officials at GlaxoSmithKline were to announce the launch of two studies of the company's vaccine. About 30 other avian flu vaccines are in early testing stages, Fauci says.

http://www.usatoday.com/news/health/2006-03-29-bird-flu-vaccine_x.htm?csp=34

Case Western Reserve University in Cleveland, my alma mater, is conducting a pioneering effort in a 2-day conference to bring together engineers, scientists and vaccine mfrs from around the world to lay out a framework to come up with a technology to dramatically up scale vaccine production for a pandemic.

With current technology, it takes 10 billion eggs (that would almost fill my refrigerator) to ensure 2 billion vaccine doses. The logistics of the traditional method are mind-boggling.
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The National Academy of Engineering, the Institute of Medicine, and other governmental and nongovernmental organizations have organized a Topical Meeting devoted to possible engineering responses to critical vaccine needs that might arise in the event of a worldwide, viral pandemic.

The goals of the meeting are to:

Identify challenges to manufacturing influenza vaccines, including rapid production for pandemic influenza.

Discuss specific approaches for increasing influenza vaccine production using both existing and "next generation" technologies.

Provide a venue where a "community" of interested academic and industrial engineers, government regulators, and other scientists and physicians can bring an engineering perspective to critical demand situations.

Identify research opportunities for young researchers and others new to the field.

Participants will review current technologies of vaccine production and explore alternative technologies, including unconventional approaches capable of scale-up in the event of a pandemic. Both current egg-based and alternative cell culture-based production technologies will be covered. Particular attention will be given to identifying novel approaches, including those currently used in non-pharmaceutical industries for other purposes.

There is a web cast of the 2-day event going on now.

http://www.vaccine2006.org

Replikins, Ltd. has discovered of a group of virus peptides that predict whether a virus is rapidly replicating and whether it is likely to spread. The company has designed software which can now detect and count these proteins which may allow scientists to better predict viral epidemics, such as the H5N1 (avian) flu.

To date, no protein or other biological phenomenon has been known to correlate with viral epidemics. Researchers have had no objective quantitative protein based means to predict if, and what, strain of a given viral organism will become a public health threat. The current concern over when, or if, there will be an avian flu epidemic has drawn attention to the need for improved measures to help predict, prevent and prepare for emerging health threats.

"We have identified a group of viral peptides we call 'Replikins' whose concentration correlates with rapid viral replication, and can give advance notice of virus epidemics," said Samuel Bogoch, M.D., PhD, a former faculty member of Harvard and Boston University School of Medicine who with his wife and colleague Dr. Elenore Bogoch discovered this new group of peptides.

Groups of Replikins can now be categorized and counted, using computerized software programs, providing a forecasting method. The FluForecast(TM) program analyzes the peptide sequences of a virus and can indicate by the virus's strain-specific Replikins concentration in viral proteins which strains are replicating rapidly, thereby creating the potential for an epidemic. The FluForecast(TM) program has quantitatively analyzed historical data on Replikins (from 1917 to the present) in protein sequences in strains of influenza viruses saved by agencies such as the World Health Organization and The U.S. Centers for Disease Control and Prevention. The FluForecast(TM) program has shown that higher concentrations of Replikins correlate with the emergence of epidemics and lower concentrations of Replikins correlate with dormancy in the three great flu pandemics of the past century and in the H5N1 outbreaks of recent years (see data in Figures 1 and 2 attached below).

"Combined with the software that analyzes viral strains, we now -- for the first time -- have an objective means of determining the threat level of a virus," said Dr. Sam Bogoch. "To our knowledge, there is no other product which provides this predictive information."


Full article:

http://www.medicalnewstoday.com/medicalnews.php?newsid=42091

[Deepwater]

Companies and global governments open their pocketbooks to prevent a pandemic

May 1, 2006
By: Brian O'Connell
BioPharm International


You can't swing a dead yellow-bellied sapsucker without running into an investment speculator whooping it up over the impending bird flu bonanza. Sure, there's been a big potful of money earmarked for avian bird flu vaccines, both public and private. In March, Health and Human Services Secretary Michael Leavitt announced that the federal government plans to spend $3.3 billion on bird flu initiatives, about half of that on a vaccine.

States are getting into the act, too. In Maryland, Governor Robert Erlich broke ground on a new bird flu vaccine laboratory in Rockville. The lab is capable of producing 150 million doses of flu vaccine annually.

That's not an isolated incident. Novavax, the flu vaccine manufacturer based in Malvern, Pa., saw its stock climb to a 52-week high last October after media reports that the bird flu epidemic had escalated in countries like Turkey, Rumania, and Russia; and even Great Britain (where a lone parrot shipped from South Africa was found to have the disease).

http://www.birdflubreakingnews.com/templates/birdflu/window.php?url=http%3A%2F%2Fwww.biopharm-mag.com%2Fbiopharm%2Farticle%2FarticleDetail.jsp%3 Fid%3D321954

[Deepwater]

Glaxo's Relenza Is Less Likely to Cause Resistant Flu Strains
Aug. 18 (Bloomberg) -- GlaxoSmithKline Plc's Relenza antiviral treatment is less likely to lead to drug-resistant flu strains than Roche Holding AG's Tamiflu, giving the product an edge against a feared pandemic, a Glaxo-sponsored study found.

Tamiflu is recommended by the World Health Organization as the first choice for doctors treating human cases of avian influenza. A Tamiflu-resistant strain of the H5N1 virus killed at least three people in Vietnam, raising concern about the drug's potency should H5N1 spark a pandemic.

Human flu strains created to be resistant to Relenza were weakened and less viable when studied test tubes in the laboratory. The study, to be published in this month's edition of the Journal of Antimicrobial Chemotherapy, was undertaken by Glaxo's Medicine Research Centre in Stevenage, England, and an Australian government scientific organization.

Full Article:

http://www.bloomberg.com/apps/news?pid=20601102&sid=apT0bMPgell0&refer=uk

[Deepwater]

WHO changes H5N1 strains for pandemic vaccines, raising concern over virus evolution
Lisa Schnirring Contributing Writer


Aug 18, 2006 (CIDRAP News) – The World Health Organization (WHO) today changed the H5N1 avian influenza strains recommended for candidate vaccines for the first time since 2004, causing some experts to question how far the virus has evolved.

The WHO's new prototype strains, prepared by reverse genetics, include three new H5N1 subclades.

The hemagglutinin sequences of most of the H5N1 avian influenza viruses circulating in the past few years fall into two genetic groups, or clades. Clade 1 includes human and bird isolates from Vietnam, Thailand, and Cambodia and bird isolates from Laos and Malaysia. Clade 2 viruses were first identified in bird isolates from China, Indonesia, Japan, and South Korea before spreading westward to the Middle East, Europe, and Africa. The clade 2 viruses have been primarily responsible for human H5N1 infections that have occurred during late 2005 and 2006, according to WHO.

http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/aug1806vaccines.html

[David_Lohr]

JAPANESE COMPANIES STRIVE TO FIND CURE FOR BIRD FLU

Bahrain News Agency

OCT. 22, 2006

TOKYO -- THE JAPANESE GOVERNMENT ANNOUNCED THAT IT WAS STORING 10 MILLION ANTIDOTES AGAINST BIRD FLU IN ORDER TO PROTECT CITIZENS AGAINST ANY NEW TYPE OF HUMAN FLU.

JAPANESE EXPERTS IN A STATEMENT TRANSMITTED BY TOKYO RADIO EXPRESSED THEIR FEAR FROM THE SPREAD OF A DANGEROUS EPIDEMIC IF BIRD FLU IS TRANSFERRED FROM HUMAN TO ANOTHER HUMAN.

Full Story:
http://english.bna.bh/?ID=51791

[David_Lohr]

Measures Fail to Stop Spread of New H5N1 Virus

eMaxHealth.com
By St. Jude Children's Research Hospital
Oct 31, 2006

A new variant of the bird flu virus H5N1 emerged in late 2005 and replaced most of the previous variants of the bird flu virus across a large part of southern China, despite an ongoing program to vaccinate poultry, according to researchers at the University of Hong Kong in collaboration with scientists at St. Jude Children's Research Hospital.

Read the full story here:
http://www.emaxhealth.com/39/8094.html

[David_Lohr]

New drug to boost defence against bird flu pandemic

The Times
November 25, 2006
By: Mark Henderson, Science Editor

A new flu drug that can kill deadly strains of bird flu is promising to transform global preparations for an influenza pandemic.
Peramivir, an antiviral agent, could provide the world with a critical new line of defence against flu viruses with the potential to cause millions of deaths, such as the H5N1 avian strain, research has suggested.

Studies in the United States show that it should be more powerful and easier to give to seriously ill patients than either Tamiflu or Relenza, the two existing drugs for H5N1 flu.

Full Story:
http://www.timesonline.co.uk/article/0,,2-2471200,00.html

[David_Lohr]

Bird flu virus 'still smoldering,' U.S. expert says

CNN
December 6, 2006
By Caleb Hellerman

A year ago, headlines were screaming about a looming disaster: the rapid spread of bird flu across two-thirds of the globe. The H5N1 strain of the virus was killing more than half its human victims. Experts were urging the government to stockpile medicine and experimental vaccines.

Dr. Robert Webster, whose vaccine the U.S. government plans to use in case of an outbreak, told CNN at the time, "If this virus learns to transmit human to human and maintains that level of killing, we've got a global catastrophe."

That worldwide pandemic hasn't yet materialized, and bird flu has been out of the headlines for a while. But we may be in for another round of news.

Last week South Korea announced two new outbreaks in poultry. And Dr. Timothy Uyeki of the U.S. Centers for Disease Control and Prevention said he's bracing for another surge in human infections. "When the temperature drops and the humidity drops, that's when you start seeing more poultry outbreaks. And when you see poultry outbreaks, that's when you see human cases."

"It's still smoldering," said Dr. Anthony Fauci, who heads U.S. scientific efforts to combat bird flu. "What it hasn't done, much to our relief, is to become more virulent or better able to transmit from person to person."

Full Story:
http://edition.cnn.com/2006/HEALTH/12/06/bird.flu/