Officials fear the virus could eventually morph into a strain that can jump between humans and become a global pandemic. But for now the few dozen human deaths from the avian flu have resulted from direct contact with infected birds.
Other strains of the flu virus, meanwhile, are likely to kill more than 35,000 U.S. residents this winter, assuming it is a typical year. And that's not the half of it.
Here are some hard-to-pronounce bugs that may well be on a doorknob near you: metapneumovirus; rhinoviruses; coronaviruses, parainfluenza; respiratory syncytial virus (RSV).
RSV kills 14,000 elderly people and high-risk adults every year, said scientists at the University of Rochester Medical Center. It is also the leading cause of bronchiolitis and pneumonia among infants, especially those under 6 months. In most cases, it goes away untreated.
After a decade of effort, no RSV vaccine exists.
"A lot of cases that people think are from flu aren't really the flu at all, but other respiratory viruses like RSV," said Ann Falsey, who works in the university's Infectious Disease Unit. "At least with the flu, we have something to control it — a vaccine."
The flu tends to spread when someone coughs, and the airborne virus lands on another person, or they cough and then touch the faucet or doorknob, Falsey and her colleagues say. Symptoms typically include fever and body aches.
RSV is more likely to produce a runny nose, a cough with mucus, and wheezing.
Like the common cold, RSV spreads mainly via large droplets on hard surfaces and even towels, and by shaking hands.
"RSV lives on objects including faucets, door handles, and change from the coffee shop, for quite awhile, for at least a day," said William Hall, a University of Rochester researcher who studies how diseases spread. "If you put your finger in your mouth, or touch your eye, or pick your nose, you're a spreader, to put it bluntly."
Same old advice
Your best defense hasn't changed for decades: Wash your hands.
"We've known for more than 100 years that hand washing prevents infection, but we still can't get people to wash their hands," said Falsey. "Hand washing is the simplest, most effective way to keep from getting sick and making others sick."
Falsey's advice was confirmed last year by a study that showed regular soap and a few seconds of scrubbing is the most effective way to rid your hands of germs. Yet another study revealed that only 83 percent of Americans wash their hands before leaving public restrooms.
The Center for Disease Control and Prevention also recommends that everyone else over age 50 be vaccinated.
And if you think you have the flu?
Rest, drink lots of fluids and call a doctor immediately, the researchers say, because the flu can be treated effectively with new medications if caught within the first 48 hours.
Tuesday, December 13, 2005, Fox News
NEW YORK — The "chicken and the egg" approach to mass-producing influenza vaccines may soon fly the coop.
Although the tried-and-true — yet slow — process of making vaccines from flu viruses grown in fertilized chicken eggs is currently the only method approved in the United States, various drug companies and other corners are working on the next generation of vaccines using what's called "cell-culture technology."
The hope is that cell culture can help create vaccines faster, especially in the face of a pandemic flu — whether it be the H5N1 bird flu virus or another strain.
Making vaccine has sometimes been compared to farming," Dr. James Matthews, senior director for science and health policy at Sanofi Pasteur U.S., a division of the pharmaceutical giant Aventis Pasteur, told FOXNews.com.
"Like a farmer cultivating a crop, the inactivated influenza virus must first be grown before being harvested," explained Matthews. "Each virus has its own growth characteristics — some grow quickly, others slowly; some produce a large amount of virus, others a small amount."
In laying out his national plan to protect America against pandemic avian influenza, President Bush encouraged the use of cell-culture techniques, which could bring vaccines to the U.S. market faster. He's requested $2.8 billion from Congress for a crash program using the technology.
Using chicken eggs, it takes about nine months to make a flu vaccine, from the moment a new strain is identified to the day the vials ship out to health-care providers.
The current approach, which has been used for over 50 years, requires about 270 million eggs to make the roughly 90 million doses of flu vaccine in a given year, according to the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. Hundreds of thousands of chickens need to be cooped up year-round just to lay those eggs.
"Basically we haven't really advanced much in new tech for the last 60 years," said Dr. Paul Offit, chief of the division of infectious diseases at the Children's Hospital of Philadelphia. "The problem with eggs is [that] only chickens grow eggs, so you're limiting steps."
Cell culture, on the other hand, can create a theoretically limitless amount of vaccine.
"To get it to mass scale where you make tens of millions of doses [of vaccines] is a big deal," Offit added.
Currently, the three flu strains identified by the World Health Organization as those most likely to spread around the world in any given year are injected into separate fertilized eggs, where the viruses multiply.
Vaccine makers then "split" the viruses using a detergent, releasing each strain's surface antigens. Fluids containing the dead viruses and their antigens are mixed together to make one dose of seasonal flu vaccine.
When the vaccine is injected into a recipient, the surface antigens trigger his immune system to make antibodies against them, conferring at least partial immunity to the original viruses.
With the cell-culture method, the virus is grown on specially selected cell lines instead of eggs. This can reduce the start-up time to get a vaccine into production from four weeks to two. Furthermore, people with egg allergies, barred from getting regular flu shots, can tolerate cell-culture vaccines.
Placing viruses in mammalian cells such as monkey or dog kidney cells allows vaccine makers to produce more pure doses in less time; they aren't limited in how much vaccine they can grow by the number of eggs they have to work with.
"We need to be able to bring our ability to manufacture [vaccines] into the 21st century. Egg-based cultures work, and they're reliable but they have a major disadvantage of lack of surge capacity," NIAID Director Anthony Fauci said Monday.
Several companies, including Sanofi Pasteur, Chiron and Protein Sciences Corp., are working on cell-based vaccine technology. ID Biomedical Corporation of Northborough, Mass., was awarded a $9.5 million contract from the NIAID to study cell culture.
But Bush doesn't anticipate a complete switch to cell-based technology until at least 2010. Some companies agree that timeline may be accurate.
"We view cell culture as being a longer-term prospect that will take years before it is approved for actual manufacturing in the U.S.," said Matthews of Sanofi Pasteur. "It is a promising technology but one still in development. Until then, we must rely on egg-based manufacture. There is no quick fix for improving current influenza vaccine manufacturing methods."
Sanofi Pasteur was awarded a $97 million contract from the U.S. Department of Health and Human Services to speed up the production process of cell-culture flu vaccines and the design of a manufacturing facility in the United States that could facilitate the production of 300 million flu vaccines annually. The majority of that contract is expected to be completed by 2008.
Chiron is conducting clinical trials of its seasonal flu vaccine in Europe, where they will file for approval for that product next year. That company has also begun studies of its cell-culture flu vaccine in the United States; Chiron produces those vaccines from viruses propagated in the Madin-Darby Canine Kidney cell line. Company representatives say vaccines made for the H5N1 strain via the traditional egg method will be available in the United States the first half of 2006.
Snipping a Little Genetic Code Here and There
Protein Sciences Corp. of Meriden, Conn., already has a cell-culture vaccine based on a flu strain's genetic code, one that's nearly ready for market.
"We're way ahead of the field," Protein Sciences President Daniel Abrams told FOXNews.com. "Making a pandemic vaccine for us is no different than making scrambled eggs … There's no danger working with a genetic code, and in the age of genomics, we can use the genetic code much faster than you can get a virus out of CDC that they feel comfortable releasing."
The cells are later "infected" with the genetic code for the protein that is characteristic of the harmful virus. The company doesn't work with the actual pandemic flu virus.
"We take the virus that only infects these fall armyworms. … We isolate that virus, and then what we do is, we snip off the genetic code that the virus carries normally in nature and we substitute for it the code we get from the CDC, which codes for the protein that is characteristic for the virus," Abrams explained.
The maximum amount of protein for the virus is produced in two to three days. The infected cells die off, and the remaining three proteins are further purified. A little salt water is added, and the substance is put into a vaccine. This method results in purer proteins in less time than with the chicken-egg technique.
"It's a very pure, very straightforward vaccine. We use the ovary cells to make the protein because they don't know any different. They don't know they shouldn't be making the protein," Abrams said.
Protein Sciences has been granted accelerated approval status by the Food and Drug Administration to use its vaccines in clinical trials. The company's goal is to have the vaccine ready for market by 2006.
Many in the medical community say it's not whether more modern-day techniques can more effectively make vaccines, but whether there's the will in Washington and in the pharmaceutical industry to do it.
"From a scientific basis, the prospect of cell-culture technology replacing chicken-embryo egg techniques is really within grasp," said Dr. Brian Currie, vice president and senior medical director at Montefiore Medical Center in the Bronx, N.Y. "It's a real likelihood that can be developed in short order … The problem is not the technology, but implementing the technology."
One problem is that the FDA, which is currently heavily invested in egg technology, needs to approve any new vaccine-making method, and that method's side effects, before the vaccine can be used.
There is also little incentive for pharmaceutical companies to pay the up-front production costs to mass-produce vaccines. And if the U.S. government stockpiles vaccines, companies can't count them as being sold for a profit until they are actually distributed.
What isn't sold to governments to be stockpiled is left to be sold by the industry at marginal prices.
Another problem, Currie said, is getting academia, government and industry together to churn out vaccines.
"When you look at drug development, [something] like 90 to 95 percent of new drugs come out of pharmaceutical companies, not academia," Currie said. "All of the new technology for vaccine production seems to be coming out of academia, not the pharmaceutical industry. I think we keep disincentivizing the pharmaceutical industry from wanting to invest in new technology and research."
Thursday, January 26, 2006, Fox News
The study focused on the influenza A virus — the type responsible for most flu outbreaks, including the infamous 1918 pandemic.
Researchers used a technique called electron tomography to generate three-dimensional images of the virus and its insides. They then dissected their virtual model to see how various viral parts were put together.
They found that the genetic material for the influenza virus is divided into eight column-like segments, with seven of the columns arranged in a circle around one central column.
The finding raises the possibility of developing a drug that interferes with RNA segment assembly.
"As these segments get incorporated into the [virus] as a set, it suggests these elements could be a target for disruption," said study co-author Yoshihiro Kawaoka from the University of Wisconsin-Madison School of Veterinary Medicine and the University of Tokyo.
There must be a genetic element in each of the eight segments that allow them to interact."
The work is detailed in today's issue of the journal Nature.
Friday, January 13, 2006, Fox News.
"We assume this could be one small step in the virus' attempt to adapt to humans," said WHO virologist Mike Perdue. "But it's only seen in one isolate and it's difficult to make sweeping conclusions. We just have to wait and see what the rest of the viruses [from Turkey] look like."
Turkey has seen an unusually high number of cases in a short period of time. Experts are investigating why.
Health authorities there raised the number of people infected with H5N1 from 15 to 18 on Thursday, after the virus turned up in preliminary tests on two people hospitalized in southeastern Turkey and in a lung of an 11-year-old girl who died last week in the same region.
All the victims are thought to have close contact with infected poultry. Samples from several of those cases are being sent to a laboratory in Britain for analysis.
Perdue said the U.N. health agency is not alarmed by the finding in a single virus sample because this exact genetic change has been seen before, in samples from southern China in 2003, and it had no impact on the course of the disease, the behavior of the virus or the pattern of human infections.
"If we saw it in more than 50 percent of samples, it would suggest the virus is really trying to adapt to humans and it would be problematic," he said.
Even if the mutation is confirmed in more samples, that does not necessarily mean it is an important enough change on its own to make the virus easily transmissible between humans, Perdue said.
The 1918 flu pandemic, the biggest in recorded history, became a global killer only after the virus slowly made a series of genetic mutations.
Influenza viruses are notoriously volatile, and experts expect to see mutations frequently. Many mutations are meaningless, or happen in only a minority of the virus samples, but specialists are watching the H5N1 virus carefully to pick up any important changes as early as possible.
Although nothing can be done to stop the mutations, tracking them is considered the best way to anticipate the next human flu pandemic.
Scientists Make Breakthrough in Bird Flu Genetic Code
Thursday, January 26, 2006, Fox News.
St. Jude Children's Research Hospital in Memphis, Tenn., is home to a remarkable viral library, samples of about 11,000 influenza viruses that Dr. Robert Webster has gathered from around the world since 1976. They're not just flu viruses that have infected people over the years, but ones from pigs and other animals — including about 7,000 bird flu viruses, gathered from poultry, ducks, gulls and other flocks.
Thursday, St. Jude researchers reported in the journal Science that they have completed the first large genetic analysis of more than 300 of these bird flu viruses. They identified 2,196 bird flu genes and 160 complete genomes, doubling the amount of genetic information available for scientists to study how these viruses evolve and spread over time.
Simply having that new trove of gene information — posted in a public genetic database so that any scientist can mine it — in itself is a huge step, said Dr. Maria Giovanni of the National Institutes of Health, which has launched a major project to map influenza genomes and helped to fund the St. Jude's work. So far, most of the complete influenza genomes available are from human viruses.
Until now, scientists trying to decode flu genetics have mostly focused on specific genes involved in making flu vaccines, such as hemagglutinin — the H in H5N1 — on the virus' surface that triggers the immune system to mount an attack. Encounter a brand new hemagglutinin variation, like when H5 strains first infected people in 1997, and the body doesn't know how to defend itself.
But unique hemagglutinin alone doesn't explain why H5N1 is so dangerous to people.
Decoding all the influenza genes instead of select ones will help scientists learn how these constantly evolving viruses change and spread, and why some are so much more virulent than others.
Enter the new clue, a protein called NS1 produced inside flu-infected cells. In bird flus, the NS1 protein harbors a molecular feature that seems to help the virus latch onto and disrupt certain important cellular processes — a feature that influenza strains common in humans don't seem to have, the researchers concluded.
"It's likely to be important in virulence, but we don't have any evidence that it's the case yet," cautioned St. Jude's Dr. Clayton Naeve, who led the new research.
But if the finding pans out, it might provide a marker of virulence. That would be very useful for scientists who collect samples of emerging flu viruses and today struggle to predict which might prove unusually dangerous, explained Dr. Karen Lacourciere, a flu specialist with NIH's National Institute of Allergy and Infectious Disease.
Probably there will be multiple factors that determine a virus' virulence, she stressed.
"If you can help detect factors that correlate with virulence, it helps us in ... understanding when we see a virus whether it's one we should be more concerned about," she said.
Study Reveals How Virus Harpoons Your Cells
Thursday, January 05, 2006, Fox News.
Researchers have deciphered the structure of a harpoon-like protein some viruses use to enter cells and begin infection.
The protein is known as fusion (F) protein and is found on the outer surface of parainfluenza virus 5, a so-called "enveloped" virus that fuses its membrane with the membrane of its host cell before infection.
Once the membranes are fused, the virus dumps its genetic content into the healthy human cell's interior, hijacking the cell's replication machinery to clone itself.
Enveloped viruses are responsible for a wide variety of human diseases, including mumps, measles, HIV, SARS and Ebola. The finding could help researchers develop drugs that prevent infection by blocking viral entry into cells.
The researchers crystallized the F protein and used x-ray crystallography to determine its three-dimensional structure.
Doing so revealed a hydrophobic (meaning water-repellent) tip that allows the viral harpoon to latch on more securely to the cell membrane, which is also hydrophobic.
It also provided researchers with more insight into the dramatic structural change that the F protein undergoes while performing its task.
When not in use, the F protein looks like a mushroom, and its hydrophobic tip is folded into a compact form, safely hidden inside the cap.
When the virus comes into contact with a target cell, the cap unfurls and the hydrophobic tip is hurled like a harpoon into the cell's outer membrane.
The F protein then brings the virus and the cell together so their two membranes can merge. It does this by collapsing back on itself like a metal rod bent so that its ends meet.
"The collapse of the protein acts like a hairpin that snaps together and brings the two membranes together to make them fuse," said Theodore Jardetzky, a structural biologist from Northwestern University and the study's principle investigator.
The research, led by Hsien-Sheng Yin of Northwestern University, is detailed in the Jan. 5 issue of the journal Nature.
Swedish Newspaper Prints First Photos of H5N1 Virus
Stockholm.
The first high-resolution close-up photographs of the H5N1 avian flu virus to be taken by a scanning electro microscope appeared in the Swedish daily Dagens Nyeter (DN), in what the newspaper said was a world exclusive.
The photos, taken by science photographer Lennart Nilsson, show the virus as a string of blue balls attacking and destroying healthy pink cells.
Scientists fear that avian flu could cause a world pandemic if it crosses with human strains and mutates into a form easily passed between people. The H5N1 strain, which has killed over 60 people in southeast Asia since 2003, has spread as far west as Croatia, apparently carried by migratory birds.
DN's science correspondent Karin Bojs told AFP that the 83-year-old photographer had initially approached US laboratories for a sample of the virus but was turned down.
In the end he obtained samples from the World Health Organisation (WHO) which were then cultivated at Stockholm's Institut Karolinska in Stockholm, which awards the annual Nobel science prize, she explained.
Nilsson then photographed the virus using images from a powerful microscope. The H5N1 sample had come from a father and daughter who died from the virus in Hong Kong two years ago.
It was Nilsson who first photographed the moment of human conception, published in a book in 1965 called "A child is born."
Nilsson is the Institut Karolinska's official science photographer.
Cases of Influenza A (H5N1)
Thailand
The 1997 outbreak of influenza A (H5N1) in Hong Kong established that highly pathogenic avian influenza viruses can infect humans directly, with resulting illness that was fatal in six (33%) of 18 patients. The viruses were not transmitted efficiently from person to person, and human infections stopped after the culling of poultry (2). The 2003--2004 avian outbreak is more widespread, with poultry disease reported across much of east and southeast Asia. Direct infection of humans with H5N1 viruses has been confirmed in Thailand and Vietnam. However, no evidence of sustained person-to-person transmission has been identified.
Despite the antigenic and genetic differences in the H5N1 viruses causing the current Asian outbreaks, certain clinical features of the five human cases described in this report are similar to those of severely affected patients from the 1997 outbreak in Hong Kong (3). In all five cases, disease was severe, with pneumonia progressing to respiratory failure and death. Early distinguishing features included fever, sore throat, cough, and lymphopenia. Other organ involvement included mild-to-moderate hepatitis and later cardiac and renal impairment. In contrast with the cases reported from Hong Kong, gastrointestinal symptoms were not prominent features.
Because of the severity of disease and the concern for the safety of health-care personnel, the Ministry of Public Health in Thailand recommends that hospitalized patients with suspected avian influenza be cared for by using precautions to minimize the risk for airborne transmission. Broad-spectrum antibacterial drugs should be used as empiric treatment for the major causes of pneumonia (e.g., Streptococcus pneumoniae), including possible superinfection with Staphylococcus aureus. Testing of a limited number of human isolates demonstrates resistance to amantadine and rimantadine (4). For this reason, treatment with neuraminidase inhibitors should be initiated early. The effectiveness of antiviral drugs against H5N1 infections and the period after which these drugs will provide little or no benefit is not known. A more detailed understanding of the pathogenesis is needed to direct therapeutic approaches such as the use of immunomodulating drugs. Updated recommendations for hospital infection control and treatment are available from the World Health Organization at http://www.who.int/csr/disease/avian_influenza/en.
The epidemiology of influenza A (H5N1) in Thailand and neighboring countries remains incompletely described, but the confirmed human infections have occurred in geographic areas with recognized avian disease, and two patients reported direct physical contact with ill or dead chickens. Of the five laboratory-confirmed cases in Thailand, four were in boys aged 6--7 years, which suggests that boys in this age group might be subject to particular high-risk exposures. Case-control studies in Thailand and Vietnam should help define specific risk factors for infection and allow for the development of evidence-based public health interventions.
Control of highly pathogenic avian influenza should include surveillance for affected flocks, aggressive culling on the basis of international guidelines to eradicate foci of infection, careful protection of cullers through the use of personal protective equipment, and use of the currently licensed human trivalent influenza vaccine to reduce the risk for co-infection in poultry workers and cullers, which might lead to genetic reassortment of avian and human influenza viruses (2,3). In recent weeks, Thailand has moved aggressively to 1) identify geographic areas with confirmed H5N1 disease in poultry (e.g., cull-affected flocks and flocks within a 5-kilometer radius), 2) establish controls on the transport of poultry and poultry products out of affected areas, and 3) promote safe food-handling practices.
Clinicians should be aware of the clinical features of the current human influenza A (H5N1) disease and the potential risk factors for infection so that health-care workers are protected and patients can be identified quickly and managed appropriately. Interim U.S. recommendations for infection-control precautions and the diagnostic evaluation of persons with specific epidemiologic and clinical criteria have been developed (4). Additional information is available from CDC at http://www.cdc.gov/flu/avian/index.htm.