Experts at the Centers for Disease Control and Prevention have shown that a molecular change in the 1918 pandemic influenza virus stops its transmission in ferrets that were in close proximity, shedding light on the properties that allowed the 1918 pandemic virus to spread so quickly and potentially providing important clues that could help scientists assess emerging influenza viruses, such as H5N1.
The study, which is published in the Feb. 5 issue of Science, showed that a modest change of two amino acids in the main protein found on the surface of the 1918 virus did not change the virus's ability to cause disease, but stopped respiratory droplet transmission of the virus between ferrets placed in close proximity. The experiments were conducted with ferrets because their reaction to influenza viruses closely mimics how the disease affects humans.
The 1918 influenza strain killed tens of millons of people. The interest in studying the 1918 strain is driven in part by fear that the avian flu H5N1 might mutate to cause a similar big killer human pandemic.
But do not panic. This result does not mean that H5N1 bird flu is only 2 mutations away from causing a massive human pandemic. Bird flu probably has additional mutations that make it more suited to spead in birds than in humans.
To spread and cause illness, the influenza virus must first bind to host cells found in humans and animals. The Science study suggests that the hemagglutinin (HA), a type of protein found on the surface of influenza viruses, plays an important role in the 1918 virus's ability to transmit from one host to another efficiently. This research suggests that, for an influenza virus to spread efficiently, the virus's HA must prefer attaching to cells that are found predominately in the human upper airway instead of cells found predominately in the gastrointestinal tracts of birds. Other changes may be necessary as well. Current H5N1 viruses prefer attaching to avian cells, suggesting the virus would need to make genetic changes before it could pass easily between humans.
What I want to know: Will increased knowledge of what makes influenza strains more lethal get used more to reduce the spread of influenza than it will get used by crazies to make lethal strains? Initially I expect this knowledge to be more useful on the side of good. But in the longer run biotechnologies will make the creation of custom virus strains easy for amateurs.
Advances in microfluidics will enable the development of beneficial treatments including full body rejuvenation therapies. But as microfluidic chips become cheaper and the software for controlling these devices becomes more powerful and easier to use individuals in personal labs in their own bedrooms or cellars will be able to develop customized lethal pathogens.
Reasons for optimism? First off, most people do not want to die. The internet enables large numbers of people to contribute solutions to problem. If malicious biological script kiddies start tossing out killer pathogens into the world's population the number of people who will organize to develop defenses will far exceed the number generating killer pathogens. Also, those fighting for the defense will probably be much smarter than those who are malicious. I am expecting people who feel they have low status to tend toward malicious acts.
But will sheer numbers of smart brains be sufficient to defeat malicious makers of dangerous pathogens? Or will defense against designer pathogens run into difficult problems similar to the relative difficulties of stopping versus delivering nuclear bombs? My fear is that the defensive side will be the more difficult.
When it comes to natural pathogens I expect human brains controlling computer simulations and automated equipment to near totally defeat them. Biological evolution won't be able to keep up with computers and microfluidic devices. So we'll reach a point where most of the remaining big killer pathogens cease to rack up big death tolls..
Yoshiro Kawaoka and colleagues at University of Wisconsin in Madisonj have found that some strains of H5N1 bird influenza have mutations that increase their ability to bind to human cells.
Two mutations in the viral hemagglutinin surface protein independently enable H5N1 influenza A virus to bind to human receptors, researchers report in Nature this week.
That's not good news. Avian influenza is highly lethal for infected humans.
Two mutations found in human patients increase binding of the virus to human cells.
Whereas viruses from chickens and ducks could only recognize avian receptors, some viruses from human patients could recognize both human and avian cell receptors. "Once we identified the differences between the isolates, we narrowed down the specific changes that make avian H5N1 recognize the 2,6 receptors," Kawaoka explained. The changes were just two mutations, at positions 182 and 192 on the hemagglutinin sequence.
Half the 250 people known to have been infected by H5N1 have died. If the virus mutates into a form that is transmitted easily between humans while still retaining much of its current lethality you would be well advised to buy a lot of supplies and avoid contact with other humans for several months while a vaccine gets developed.
A highly lethal H5N1 would probably become less lethal with time since less sick people will get around more and spread the disease more widely. So you are also better off avoiding the disease in the early months in hopes that if eventually exposed you'll get a less lethal version.
It is also possible that antibodies taken from infected people who recover could be extracted and used as treatment for those who get it later. So, again, don't be the first one on your block to get a pandemic influenza virus.
In a few years the risk from H5N1 or any other influenza strain will go down due to development of faster means to scale up and produce vaccines. Also, better drugs will be found for suppressing the excess inflammation response by which more deadly influenza strains probably kill.
Bottom line: If you got a vaccine shot from one strain of H5N1 bird flu and then later got a different vaccine shot for a different strain of H5N1 bird flu you'll get a stronger immune response from the second shot. That means if you got vaccine to an old H5N1 strain now and then an avian flu pandemic happened and you get a vaccine shot for the killer pandemic strain you'll get a strong immune reaction and better resistance because you had the earlier shot of a different strain. Vaccination by one strain of bird flu increases the immune response to a later strain of bird flu.
Officials were able to track down 37 people who agreed to take part. Each had received two shots as part of the vaccine study in 1998 against the form of the virus that had emerged in Hong Kong. Earlier this year each was again vaccinated with another shot targeting a different form of bird flu, the variant that swept through Vietnam in 2004 and 2005. Their immune response to the second shot was compared to the response in people who received shots for the first time in 2005. More than twice as many people who also received the shot in 1998 developed a protective antibody response against bird flu compared to people who had never been immunized against bird flu previously.
"We studied a relatively small group, so that certainly, this issue needs to be studied more thoroughly in a larger group of people," said John J. Treanor, M.D., professor of medicine and director of Rochester's Vaccine and Treatment Evaluation Unit. "If the findings hold up, then it might open up a number of options beneficial for planning. One might consider giving a priming shot to members of the community who would be a central part of the response if a pandemic were to occur, such as health care workers. You'd have people who were prepared as much as possible in advance."
The work is being presented at IDSA by research fellow Nega Ali Goji, M.D., who did the study with Treanor
The work addresses one of the features of bird flu that makes a potential pandemic so hard to fight: Like human flu viruses, bird flu mutates constantly, and by the time a vaccine has been produced to protect against one form of bird flu, it's very possible that another form, requiring a different vaccine, will have emerged that can move from person to person.
The results of the new study are similar to what doctors already know about giving "regular" flu shots. Every year millions of adults get an updated flu shot every year – one shot is enough, because their immune systems "remember" previous forms of the flu and help make the new shot each year effective. But small children who have never seen the flu before typically need two shots, a primer and a booster. The results from the new study indicate that, like small children who receive a regular flu shot, adults who have never encountered bird flu would benefit from a booster shot.
The two vaccines used in the study target viruses belonging to different "clades" or viral families. Both are H5N1 bird flu viruses, but the Hong Kong strain from 1997 belongs to clade 3, while the Vietnam strain from 2004 belongs to clade 1. Goji and Treanor found that the shot targeting clade 3 helps the body maximize the immunization against a virus in a different clade, clade 1. In other words, using the vaccines that are available now might help improve the response to the vaccines developed for a future strain of bird flu.
Very likely vaccination against some existing strain of H5N1 avian flu would also increase immune response to an infection by a future pandemic strain of avian flu. This means your odds of survival from a pandemic infection would be increased if you could only get yourself vaccinated against an existing known strain of bird flu.
These results argue for mass producing a bird flu vaccine using known strains. If such a vaccine was available I'd go get a shot. Partial immunity would be much better than boxes of N95 face masks.
H5N1 avian flu might have the potential to mutate into a killer epidemic. So an understanding of how the most lethal modern flu epidemic killed its victims may yield information that'll help protect us. Reconstructed 1918 Influenza viruses delivered into lab mice in biosafety level 3-enhanced laboratory at the CDC in Atlanta caused run-away inflammation that explains the lung damage seen in 1918 flu victims.
Unlike typical seasonal flu, which strikes hardest at the very young, the elderly and those with compromised immune function, the 1918 flu disproportionately killed young people in the prime of life. Modern analyses of 1918 flu victim autopsy samples show extreme and extensive damage to lung tissues. This observation gave rise to the hypothesis that the 1918 flu virus infection provoked an uncontrolled inflammatory response leading to rapid lung failure and death.
To test this idea, Dr. Tumpey infected mice intranasally with one of four types of flu virus: human seasonal flu virus from a strain that circulated in Texas in 1991; lab-made viruses containing either two or five of eight viral genes from the 1918 virus; or a reconstructed virus containing all eight 1918 flu virus genes. Lung tissue from three infected mice in each group was removed on days 1, 3 and 5 post-infection and processed to destroy any virus. The mouse genetic material (RNA) was then extracted from these lung samples and sent to the University of Washington team for analysis.
Drs. Katze and Kash and colleagues examined the mouse RNA using microarrays to determine which genes were activated when exposed to each of the four viruses. This analysis showed that the immune response to the reconstructed 1918 virus containing all eight flu genes was much greater than to any of the other viruses with all eight genes, says Dr. Katze. In particular, genes involved in promoting inflammation were strongly and immediately activated following infection by the reconstructed 1918 virus. "We clearly see a dramatic and uncontrolled immune response in the mouse lungs as early as one day following infection with the reconstructed 1918 virus," he says. A complete understanding of the host's response to the 1918 flu virus, adds Dr. Katze, requires use of a fully reconstructed virus.
If the H5N1 bird flu virus mutates into a form easily transmissible between humans it might cause death by the same general mechanism. If that turns out to be the case then many of those who get infected and manage to recover are probably going to live with some permanent damage to their bodies. Severe inflammation is going to leave behind damaged and scarred tissue.
If a highly lethal flu pandemic breaks out your best bet is to isolate yourself for months while vaccine production gets ramped up. Whether you go into solitary isolation or as part of a family, group of friends, or small job work team, cut yourself off from the chains of transmission of the virus. If you need to go to stores or meetings use N95, N100, or P100 face masks. Avoid touching surfaces. Try to avoid going in-doors with people who are not in your personal isolation group.
If you want to prepare for a pandemic here are my top suggestions:
If you can isolate yourself you won't get infected. It is as simple as that.
The longer we go without a flu pandemic the less the risk of an eventual pandemic killing any of us. Drugs that prevent extreme inflammation response will be found. Methods to scale up vaccine production more rapidly are on the way too. In 10 years I do not expect pandemic flu strains to pose a major threat to industrialized countries. We'll have the biotechnologies needed to protect ourselves pretty rapidly from deadly strains of influenza.
In a clinical trial, 80% of volunteers who received two vaccine doses containing 3.8 mcg of antigen with an adjuvant (a chemical that stimulates the immune system) had a strong immune response, the British-based company said in a news release. A typical dose of seasonal flu vaccine is 15 mcg.
"This is the first time such a low dose of H5N1 vaccine has been able to stimulate this level of strong immune response," GSK Chief Executive Officer J.P. Garnier said in the news release.
By comparison, an H5N1 vaccine developed by Sanofi Pasteur induced a good immune response in 67% of volunteers who received two 30-mcg doses with an adjuvant, according to findings reported in May. The US government is stockpiling the Sanofi vaccine.
Garnier called the GSK vaccine a breakthrough because, with the effectiveness of the low dose, a given amount of antigen will go much further than it would otherwise.
"The meaning of this is that we are going to be in a position, starting later this year, to produce hundreds of millions of doses of an effective pandemic vaccine, so this is a big breakthrough," Garnier said on BBC Radio, as reported today by Agence France-Presse (AFP).
World influenza vaccine production capacity is too low in event of a deadly pandemic flu outbreak. A vaccine that is potent in such a small dose greatly expands the number of doses of vaccine that could be made in a year in response to a deadly pandemic.
Other vaccines against H5N1 are much less potent.
Previous attempts to produce a low dose vaccine had been unsuccessful, with required doses as high as 180 micrograms. Companies then tried adding an adjuvant – a chemical which stimulates the immune system and increases the potency of a vaccine. But, again, results were disappointing.
We need newer and far more easily scaled vaccine production technologies. The lead time for vaccine production is several months. The production capacity is low because only a small fraction of the world's population gets vaccinated for the flu in typical years. A better vaccine production method would be faster and scale up rapidly with easily produceable capital equipment.
As humans face the growing possibility of a deadly flu pandemic our four legged friends demonstrate just how much they have in common with us. A deadly influenza strain that has jumped from horses to dogs is producing headlines similar to what we can expect to see when the next human influenza pandemic hits. The horse influenza H3N8 has mutated and jumped to dogs and killed greyhounds in 7 states.
The virus, which scientists say mutated from an influenza strain that affects horses, has killed racing greyhounds in seven states and has been found in shelters and pet shops in many places, including the New York suburbs, though the extent of its spread is unknown.
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The virus is an H3N8 flu closely related to an equine flu strain. It is not related to typical human flus or to the H5N1 avian flu that has killed about 100 people in Asia.
Fido, Spot, and Rover are in danger. But humans can control the spread of a canine influenza outbreak a lot more easily than they can control a human outbreak. Humans travel greater distances and congregate together a lot more. While Rover is at home in the backyard waiting for people to come home and barking plaintively through the fence at dogs getting walked Johnnie is at grade school fighting with Billy, Bobby, Biff, and Brett on the playground and passing pathogens around in the process. His sister Jill is playing pattie cakes with Suzie and Taylor and passing along germs too. Johnnie's Dad is flying back from a business meeting in Singapore with regional manangers from Thailand, Canton, and Indonesia. Mom is at Pilates with a bunch of other women all touching the same floors, door knobs, and railings with their sweaty skin. Or maybe Mom is carrying on an affair with another law firm partner. Oh, and Mom's sister is waitressing at a busy packed restaurant to work through law school.
There is no evidence that it has spread to humans, or that it ever will. But at a Monday press conference, federal officials said they are monitoring the health of exposed dog owners -- because a virus that jumps species once could do it again.
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"We have never been able to document a single case of human infection with this virus,'' said Ruben Donis, a researcher with the federal Centers for Disease Control and Prevention and principal author of the study.
But a virus that has managed to hop into dogs might now be closer to human compatibility. Anyone have scientific reasons to think this might be the case?
The CDC says don't panic even though it appears to kill 5% to 8% of dogs..
"We are going to monitor all cases of human exposure, but at this point there is no reason to panic," said Ruben Donis of the federal Centers for Disease Control and Prevention in Atlanta. Donis noted that it has been known for about 40 years that the virus causes the flu in horses, with no reports of its infecting humans. Tests also indicate it is sensitive to antiviral drugs.
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Although the mortality rate from the new flu virus remains unclear, so far it appears to kill 5 to 8 percent of infected dogs.
Well, what a human-centric attitude. Don't panic? Imagine a pandemic flu virus that killed 8% of humans was in the lose. Oh wait, the CDC would still say there is no reason to panic. But that only makes sense. There's never any reason to panic. Panic is a maladaptive response. But sometimes desperate measures are called for. Just stay level headed.
Since the dog flu is responsive to Tamiflu and amantadine I see this as yet another reason to stockpile Tamiflu. Fido's life might depend on it. What if a human pandemic breaks out, you stay totally healthy, but Fido comes down with a bad case of the flu? I can tell you right now that those human-centric public health authorities aren't going to let you get any Tamiflu for Spot or Scooby Do. No way. You have to stock up ahead of time if you want to protect your dog during a human flu pandemic.
Continue to walk your dog and let neighborhood packs congregate.
The C.D.C., which is tracking the disease, issued no official recommendations. But Dr. Crawford urged pet owners to continue to walk healthy dogs, visit dog runs, use boarding kennels and otherwise let animals congregate.
But, Dr. Crawford added, owners should "use common sense," including isolating dogs with any symptoms of respiratory disease for up to two weeks and alerting a veterinarian's office before taking in a sick dog for treatment.
But we need continued press coverage of this problem. Dog owners need to know when H3N8 comes to their neighborhoods.
Update: Dr. Brad Fenwick thinks the mortality rate is lower than Crawford's estimate.
Dr. Brad Fenwick, vice president for research at the College of Veterinary Medicine at Virginia Polytechnic Institute, said he thinks mortality from this flu is even less than estimated by Crawford. If infected dogs are treated, mortality can be much lower, Fenwick said in a telephone interview.
From the CDC press conference: Dr. Ruben Donis:
So what about the implications for public health? We must keep in mind that this H3N8 equine influenza virus has been in horses for over 40 years. In all these years, we have never been able to document and single case of human infection with this virus. So that is something that I want everybody to take note of so to dispel, you know, major panic. That's not to say that there isn't any risk. We are going to monitor all cases of possible human exposure, but, this point, there is no reason to panic.
Dr. Cynda Crawford:
Only a minority of dogs, a small number of dogs, experience complications such as pneumonia, just like the humans infected with influenza, certain populations of humans are more prone to development of pneumonia. And it's a small number of humans compared to everyone else.
So that is the same with canine influenza virus. It's a small population of dogs that will develop complications, most likely bacterial complications and these dogs do need to be--have their treatment supervised by a veterinarian.
In addition, since not all dogs will show a clinical syndrome, showing that they have a respiratory infection, there is a minority that are infected with the virus, but will not show clinical signs to announce to everybody that “I am sick.” And it is very difficult to find these dogs in the dog population. And we're working on a more rapid means of identification.
If bacterial infection sets in as a complication that obviously can get treated by antibiotics. Also, Tamiflu and amantadine can slow the virus itself.
George W. Bush has decided to order an experimental French avian flu vaccine.
At the United Nations on Wednesday, President Bush proposed an "international partnership" to combat the disease, and the United States announced last week that it had placed orders for $100 million worth of a promising but technically unlicensed vaccine that is under development by the French drug maker Sanofi-Aventis.
If it was up to me I'd take money away from Bush's massive Gulf Coast mini-Great Society boondoggle (why subsidize rebuilding in a flood plain where hurricanes will hit again and again?) and use it instead to develop better influenza vaccine production technologies and other measures to protect against the inevitable next influenza pandemic. Why subsidize the movement of people back into harm's way when we could instead fund research that would remove people from harm's way? But my knee jerk use of rational analysis keeps placing me outside of the emotional mainstream.
We are overdue for the next big influenza pandemic and it is just a matter of time till the pandemic happens.
"We know we're overdue for an influenza pandemic strain, and we know it will occur, but we don't know when or even exactly what virus will cause it," said Dick Thompson, a WHO spokesman. "It is possible that the virus won't be H5N1 at all or that this virus will change in a way so that the vaccine under development doesn't work against it."
Thompson added that government orders for unproven vaccines still are worthwhile because they provide incentives for companies to do vaccine development work against H5N1. That makes sense. The companies will be further up the learning curve on H5N1 and will also have more vaccine production facilities in place available to switch over to a different vaccine variant once the exact pandemic strain emerges.
The backdrop to these statements is the avian flu news from Indonesia. Indonesia has 4 dead from the H5N1 avian flu strain and birds all over the Indonesian islands have the flu.
The developments highlighted Indonesia's continuing struggle against bird flu, which is endemic in chicken flocks across the sprawling island nation and has killed four humans since July, the most recent being a 37-year-old woman who died nine days ago.
3 Indonesian children have suspected cases of H5N1 avian influenza.
Three Indonesian children are suspected of having been infected with bird flu, a health official said, while the Jakarta zoo remains closed over an outbreak of the disease.
'There are now three suspected cases of bird flu infection, all children,' said Sumardi, the health ministry's acting spokesman.
Apriyantono later told reporters his ministry had requested more funds to handle the outbreak, but said the government had little money to conduct a mass slaughter of poultry or birds.
"Depopulation will need a huge amount of funds. This year, we need more funds for avian influenza to do research, surveillance and selective depopulation."
The WHO would support recommendations by the World Organisation for Animal Health and by the U.N. Food and Agriculture Organisation (FAO) for a mass cull in Indonesia, Petersen said.
I'd love to know what the cost of a huge domestic bird depopulation would cost in Indonesia. Suppose the US withdrew from Iraq and used some of the money against domestic avian flu in poor countries. How many weeks of fighting in Iraq would yield enough money to pay for a cull of infected birds in Indonesia, Cambodia, and Laos?
The WHO regional director for Western Pacific, Shigeru Omni, said at the opening of a WHO conference in New Caledonia that poor Asian farmers are a weak link in the fight to contain the disease. He said these farmers are reluctant to report bird flu outbreaks because of a lack of financial incentives to do so.
WHO says countries should hold a mass culling when an outbreak occurs, but some nations refuse. Indonesia has launched a vaccination drive for poultry, but has carried out only limited culling because it lacks the money to compensate farmers.
When the pandemic comes it will cost industrialized countries trillions of dollars. Why not spend a small fraction of that up front to reduce the odds of the pandemic in the first place? As one of the B-52s women singers once sang "I'm just asking!".
World Health Organization (WHO) Indonesia country representative Georg Petersen says that farmers living in close proximity to their chickens makes the spread of avian flu to humans hard to control. At the same time an Indonesian government official says Indonesians should just accustom themselves to getting sick from H5N1 avian influenza.
``The problem with this country, as in many Asian countries is that a large portion of the chickens are raised by farmers in their backyard and even within the cities, people are raising chickens and this is very difficult to control,'' Petersen said.
Indonesians ``will have to be prepared to live together with bird flu, as it has with dengue,'' agriculture minister Anton Apriantono told reporters while visiting Pasar Cempaka Putih, a traditional market that sells live poultry in central Jakarta today. Dengue, which causes, fevers, rashes, headaches, muscle pain and sometimes death, is an annual occurrence in Indonesia.
Bottom line? Your own considerable future risk of getting killed by an H5N1 avian influenza pandemic comes from an attitude prevalent in Third World countries that lots of disease sicken and kill people so why get worked up about just one more infectious disease?
French newspaper Liberation said the government had already acquired 5 million doses of the antiviral drug Tamiflu, produced by Swiss pharmaceutical giant Roche, and was planning to raise the level to 14 million by the year end.
France has a population of over 60 million people. Not all the population would get sick. 14 million Tamiflu doses might be enough if many steps were taken to reduce the rate of transmission of the flu virus.
The French government is also negotiating contracts to produce large stocks of flu vaccines. But pre-stocking flu vaccines might not work since the avian H5N1 viruses in birds are still mutating. If a viable strain emerges in humans it might look antigenically very different than any strain used now to base a vaccine on.
The French government is also purchasing a couple hundred million face masks.
The number of protective face masks in stock would be increased to 200 million by the start of next year from 50 million.
One wonders how long these masks would last. The 3M N100 and P100 masks last for 150 hours. However, most masks last for about an order of magnitude less time. Therefore individuals out in public all day would need many masks to get through the length of time of a pandemic.
Cambridge, UK and Cambridge, Massachusetts – 4 August 2005 – Acambis plc (“Acambis") (LSE: ACM, NASDAQ: ACAM) has commenced development of a potentially breakthrough new influenza vaccine that could offer permanent protection against influenza and may also offer protection against influenza pandemics. Influenza vaccines are currently administered annually.
Acambis has entered into a research collaboration and licensing agreement with the Flanders Interuniversity Institute for Biotechnology (“VIB"), a Belgian research institute.
Acambis and VIB will work together to develop a vaccine against both A and B strains of influenza, using Acambis' influenza A vaccine candidate that it acquired from Apovia earlier in the year and additional technology licensed from VIB. Apovia is a US biotechnology company and started development of the influenza A vaccine candidate in 2000, having originally licensed the technology from VIB. Walter Fiers, emeritus professor of Molecular Biology at the University of Ghent, is an inventor of the patent rights licensed from VIB.
The aim of the research collaboration would be to generate a ‘universal' vaccine candidate that would protect against both A and B strains of influenza and, more importantly, would not require annual changes to the formulation. This contrasts with current influenza vaccines that need to be changed, generally each year, to cope with genetic drift, mutations that occur in influenza strains circulating in nature, as well as major genetic shifts that can result in influenza pandemics. The need to change vaccine formulations each year results in delays in initiating vaccine coverage.
Unforunately it sounds like they are not far enough along to offer anything against the H5N1 avian flu strains should avian flu manage to mutate into a form that spreads easily between humans in the next few years.
The appeal here is not just the universality of the vaccine. Their use of baterial fermentation technology addresses the big problem of slow production and poor scaling of today's chicken egg-based influenza vaccine production technology.
The initial vaccine candidate against influenza A is currently in pre-clinical development. It is manufactured using recombinant bacterial fermentation technology, which aims to provide time and cost efficiencies compared with traditional egg-based production methods.
They haven't yet proven their vaccine will be universal but they are hopeful.
Walter Fiers, Professor emeritus, University of Ghent and VIB, said:
“The research and pre-clinical development carried out so far supports the promising potential of a universal, M2e-based influenza vaccine. In view of the conservation of the M2e structure, vaccination against all human influenza virus strains may become possible, even before new epidemics or pandemics have started to spread. Moreover, the vaccine is a recombinant protein with a defined chemical structure which can be rigorously characterised and produced on a large scale. We are pleased to collaborate with Acambis in the further development of this promising vaccine."
Could this vaccine save us from avian flu? If avian flu breaks out into a pandemic could this approach be scaled up rapidly without clinical trials? Even if the vaccine would be risky in an emergency where the alternative is a decent chance of dying from a killer flu a rapid deployment of this vaccine might be worth the risk.
We have some bad news and we have some possibly good news.
If Asian bird flu mutates into a form that spreads easily between humans, an outbreak of just 40 infected people would be enough to cause a global pandemic. And within a year half of the world’s population would be infected with a mortality rate of 50%, according to two studies released on Wednesday.
And yet, the models show, if targeted action is taken within a critical three-week window, an outbreak could be limited to fewer than 100 individuals within two months.
This result comes out in a pair of papers published in Nature and Science by teams of British and American researchers.
Neil Ferguson, a professor at the Imperial College in London and lead author of the Nature paper says that if the pandemic happens half the world's population could be infected within a year.
Prof Ferguson said if nothing was done, half the world could be infected within a year. But a stockpile of Tamiflu, along with a policy of closing schools and workplaces, could have more than a 90 per cent chance of stopping a pandemic virus.
Bummer dudes. If I survive I'll probably have a much smaller readership. Could all my readers please plan in advance and buy provisions to allow themselves to flee to isolated cabins for a year? I don't have a big marketing budget to attract new readers. So you guys and gals have got to be careful and stay alive. Oh, and stop smoking, get more exercise, eat better food, lose weight, and don't drink and drive.
During the pandemic using cellular broadband on broadcast towers you'd still be able to read me from your mountain cabins while I hole up in a cabin of my own. Note to self: Buy a cabin with a water well and a bunch of solar panels and batteries and in sight of a cellular internet modem tower. Stock it with lots of pop corn, Total cereal, and other vital necessities.
Another team from Emory University in Atlanta, the US, led by Dr Ira Longini, simulated an outbreak in a population of 500,000 in rural Thailand, where people mixed in a variety of settings, including households, schools, workplaces and a hospital.
Provided targeted use of antiviral drugs was adopted within 21 days it would be possible to contain an outbreak, they found, as long as each infected person was not likely to infect more than an average of 1.6 people.
If it was more infective than this, household quarantines would also be necessary, they said.
But among the many reasons such a strategy might fail is the possibility that the outbreak strain could develop esistance to the anti-viral drug Tamiflu (chemical name oseltamivir).
Another problem is that the earliest victims must be identified promptly.
Professor Ferguson then considered what would happen if Tamiflu were given rapidly to everybody within a 5km (3.1m) or 10km radius of an infected person, and measures were taken to reduce contact by closing schools and workplaces.
These approaches will contain an outbreak, but only if Tamiflu is given swiftly, preferably within 48 hours of a case being diagnosed. Prevention must begin before more than 30 to 40 people are infected, and 90 per cent must take the drugs they are given.
Well, imagine that the early victims are in Laos or Cambodia or Burma (all quite plausible) and since large areas of those places are pretty primitive what if nobody of importance notices for weeks? Also, to enforce household quarantines and other measures one needs a fully functional government with plenty of public health workers. Well, in some parts of the world government is dysfunction or effectively non-existent.
Even with prompt response we'd still have to get lucky.
"If we end up with a pandemic like [previous catastrophic pandemics], we'll have a lot of people dead," said study team member Elizabeth Halloran, professor of biostatistics at Emory University in Atlanta, Georgia.
Halloran added that the simulations show that it should be possible to contain an outbreak at its source. But the results are unpredictable. "We have shown in these simulations that—even given the same [hypothetical] situation—sometimes when we intervene it's successful and sometimes it's not," Halloran added.
Bottom line: Do not count on this approach working even if the political will and resources are available to execute the containment strategy.
The experts are aware that success of a prompt containment strategy depends on many "ifs".
"The models show that if you combine well-directed, targeted treatment with some social interventions like closing schools, ideally together with some vaccination, it's conceivable you'd be able to stop the epidemic," said Anthony S. Fauci, chief of infectious diseases at the National Institutes of Health, which funded much of the work through its National Institute of General Medical Sciences.
But the odds of success are tempered by many "ifs," Fauci and others warned.
Here's one problem with this strategy: A reluctance to commit resources. They assume a few million doses of Tamiflu available and some panel or person authorized to employ it. Well, as it stands now the WHO is reluctant to raise the warning level for a pandemic because raising the level causes stuff like the use of Tamiflu stocks. They know if they use it prematurely they will basically shoot their guns but without ammo to reload. So there is going to be a bias against committing resources until absolutely certain. Well, how to determine that a strain that has pandemic capability has finally emerged and how to do that very quickly?
Suppose that the WHO and national governments got together 10 million or 20 million Tamiflu doses. Then public health officials could afford to commit resources against each potential outbreak before being absolutely sure. Would this work? Maybe. But then again, maybe widespread use of Tamiflu would help select for Tamiflu-resistant strains.
But there's another problem: The H5N1 strains that are popping around in animal populations could mutate into a human pandemic capable form more than once. We might need to stop it 2, 3, 4, or 5 times. Are we going to get that lucky? Heck if I know. But I'm not optimistic.
I think governments and public health officials ought to consider the rapid development and widescale delivery of vaccines to populations in Southeast Asia right now. Even if the vacines would be only partially effective against some future avian flu strain the ability to slow the spread of a new strain using partial immunity might give the containment strategy a much better chance of working.
My joking aside, this is serious business. Lots of us could die. We ought to be doing orders of magnitude more to avoid getting killed by an avian flu pandemic. Think about it. Complain to your elected representatives. Buy the sorts of supplies you'd need to survive a major societal disruption.
Update: Even a slowing of the pandemic would provide more time for vaccine development and production.
"Our findings indicate that we have reason to be somewhat hopeful. If -- or, more likely, when -- an outbreak occurs in humans, there is a chance of containing it and preventing a pandemic. However, it will require a serious effort, with major planning and coordination, and there is no guarantee of success," said coauthor Elizabeth Halloran of Emory University.
"Early intervention could at least slow the pandemic, helping to reduce morbidity until a well-matched vaccine could be produced," she said.
The danger of avian flu is that the virus could develop into a new strain that could be transmitted among humans. The virus might mutate, or it might jump over to a human already infected with the flu and then mix, or "reassort," with the human flu virus. Because humans would have little or no immune protection against this strain, it could potentially cause a massive pandemic.
"There were three influenza pandemics in the 20th century alone. The threat of another pandemic, related to avian influenza, is real and very serious. Fortunately, as the new study shows, for the first time in human history, we have a chance of stopping the spread of a new influenza strain at the source through good surveillance and aggressive use of public health measures," said Katrina Kelner, Deputy Editor, Life Sciences, at Science.
The effectiveness of containment depends on quick decisions to do targeted antiviral drug use, a fairly low multiplier for how many others each infected person passes the virus on to, a high level of use of antiviral drugs, and effective quarantine measures.
They found that targeted use of antiviral drugs could be effective for containment as long as the intervention occurred within 21 days and the virus' reproductive number (which represents the average number of people within a population someone with the disease is able to infect) had a relatively moderate value of roughly 1.6.
A process of administering antiviral drugs to the people in the same mixing groups as the infected person, called TAP for "targeted antiviral prophylaxis," could contain the outbreak as long as it reached 80 percent of the people targeted. A related strategy, GTAP, for "geographically targeted antiviral prophylaxis," which targets people within a certain geographic range of the initial case, produced similar results as long as it achieved coverage of 90 percent.
Vaccination before the outbreak, even with a vaccine that is poorly matched to the actual virus strain, increased the effectiveness of TAP and GTAP.
For even higher viral reproductive numbers, household quarantines would also be necessary to contain the virus. A combination of TAP, prevaccination and quarantine could contain strains with a reproductive number around 2.4. A value of 2.4 is relatively contagious, though some other viruses such as measles are substantially higher. In all cases, early intervention would be essential.
We can't have a wonderful long future if we die first. Future rejuvenation therapies are useless to anyone who dies from bird flu next year.
Would the United States, Europe and Japan be willing to donate their precious vaccine supply to mount this long-shot defense? This is perhaps the biggest unanswered question in pandemic flu planning -- and one likely to be answered only at the moment of truth.
Officially, it is a possibility.
"If it was done in consultation with the WHO [World Health Organization] -- and with other governments that would make contributions, as well -- we would be more likely to consider it," said Gellin at HHS. But observers both in and out of the government said, not for quotation, that they doubt the U.S. government would ever send a significant amount of its vaccine stockpile overseas.
Production of a sufficient supply of vaccine could take years. The economic disruption of a pandemic will be enormous. I am expecting an economic depression. The threat of terrorism will seem tiny by comparison.
Also see my previous posts "Yet Another Avian Flu Preparedness Warning Report" and "More Warnings On Avian Flu Danger To Humanity".
WASHINGTON, June 24, 2005 – Trust for America’s Health (TFAH) today released state-by-state projections that found over half a million Americans could die and over 2.3 million could be hospitalized if a moderately severe strain of a pandemic flu virus hits the U.S. Additionally, based on the model estimates, 66.9 million Americans are at risk of contracting the disease. The study also found that the U.S. currently only has stockpiled 2.3 million courses and has placed orders for an additional three million courses of antiviral pharmaceuticals (produced as Tamiflu by Roche Pharmaceuticals), which would likely be available in 2006. This would be enough to cover 5.3 million Americans, leaving over 60 million who could be infected and would not be able to receive medication before an effective vaccine to combat the flu strain is identified and produced.
TFAH’s numerical projections are included in a new report, “A Killer Flu? ‘Inevitable’ Epidemic Could Kill Millions.”
“This is not a drill. This is not a planning exercise. This is for real,” said Shelley A. Hearne, DrPH, Executive Director of TFAH. “Americans are being placed needlessly at risk. The U.S. must take fast and furious action to prepare for a possible pandemic outbreak here at home.”
“The Government Reform Committee has held several hearings over the last few years to let people know that the flu is not something to take lightly,” said U.S. Congressman Tom Davis (R-VA), Chairman of the House Government Reform Committee. “TFAH's report clearly demonstrates that the emergence of a pandemic flu could exact a tremendous toll on U.S. health and economic stability. In order to identify problem areas and prioritize planning and response efforts, the Committee will hold a hearing next week on the threats posed by a potential flu pandemic.”
Dr. Hearne will be testifying Thursday, June 30th, before the House Government Reform Committee on U.S. preparedness for pandemic and annual flu. Some of the TFAH report’s other findings include:
- While estimates find that over two million Americans may need to be hospitalized during a pandemic outbreak, the U.S. currently only has approximately 965,256 staffed hospital beds.
- The U.S. has not adequately planned for the disruption a flu pandemic could cause to the economy, daily life, food and supply distributions, or homeland security.
- The U.S. lags in pandemic preparations compared to Great Britain and Canada based on an examination of leadership, vaccine development, vaccine and antiviral planning, health care system surge capacity planning, coordination between public and private sectors, and emergency communications planning.
TFAH provides a series of detailed recommendations to help ensure the U.S. is better prepared regardless of whether a pandemic occurs as soon as this year or in several years. With a crisis looming, the U.S. plan for the pandemic should be finalized and the President should designate an official with authority to coordinate the U.S. response across federal agencies. Other top level recommendations include taking:
- Immediate steps of outbreak tracking, stockpiling medical supplies, and developing emergency communications plans;
- Intermediate steps of stockpiling additional antivirals and developing surge capacity plans for hospitals and health care providers; and
- Longer range steps to increase vaccine production and the development of new technologies for vaccines.
I figure, humans being humans, we'll have a big pandemic and millions will die and only afterwards all the recommendations about building more rapid vaccine production technologies, stockpiling of medical supplies, and better methods of reducing human-to-human transmission will be implemented. The warnings coming from infectious disease experts and others are being discounted as the standard exaggerated doom and gloom fare of coming disasters.
The full report projects a high economic cost from a pandemic. (PDF format)
The estimated economic impact of a pandemic flu outbreak in the U.S. today, based on projections from the relatively mild 1968 flu epidemic, would be $71.3 to $166.5 billion due to death and lost productivity, excluding other “disruptions to commerce and society.”6
Note the real possibility that the avian flu could have a higher lethality rate than the 1918 flu. So the economic costs, number of hospitalizations, and total deaths could be much greater than the estimates provided above.
Some countries could be politically destabilized by the effects of a flu pandemic. Though I'm going to go out on a limb here and guess that in Africa with so much disease already a flu pandemic might seem like nothing out of the ordinary.
The U.S. would be impacted by the global implications as soon as a pandemic outbreak occurred in any part of the world due to the interdependence of economies. Sectors, such as hospitals and the health care system, which rely on supplies manufactured in other parts of the world, including Asia, would feel immediate repercussions and supply shortages. Travel restrictions, possible limitations on public gatherings and events, and other measures taken to limit the spread of disease would also have rapid and far reaching repercussions. Since a pandemic could likely result in political and economic destabilization, particularly in developing countries, it poses serious national security concerns for the U.S.
Those who think the threat of the avian flu is overblown need to learn about the larger historical context: Influenza pandemics have occurred regularly in human history and statistically speaking we are overdue for the next one.
Based on historical trends and projections, virologists and epidemiologists predict a new flu pandemic will emerge three to four times each century.8 Health officials around the world are troubled by the severity of the “avian flu” circulating in Asia, which scientists refer to as the H5N1 flu strain. They fear this avian flu could become the next pandemic for humans. The regional director of the WHO for the Western Pacific region stated in February 2005 that the “world is now in the gravest possible danger of a pandemic.”9
We currently run the risk that the avian flu will not only be the next pandemic but that it will be much more lethal than the average pandemic.
The economic disruptions of a pandemic would reach the United States rapidly due to the interdependent nature of economies.
The U.S. has not assessed or planned for the disruption a flu pandemic could cause both to the economy and society as a whole. This includes daily life considerations, such as potential school and workplace closures, potential travel and mass transit restrictions, and the potential need to close stores resulting in complications in the delivery of food and basic supplies to people. Daily life and economic problems would likely emerge in the U.S. even before the pandemic flu hit the country due to the global interdependence of the world economy.
Put aside for the moment the medical issues (e.g. virus manufacture, acute patient care, drug production, medical supplies shortages, and so on). Think about the problem at the level of human organization to reduce pathogen transmission in ways that minimize economic disruption. We have the potential to develop and find ways to carry out economic functions with less human-to-human exposure. The development of procedures and products, the training of work forces, and the purchase of key pieces of capital equipment could reduce the amount of human contact involved in most types of economic activity. This would simultaneously reduce the rate and extent of spread of the pandemic virus and reduce the size of the economic disruption caused by the virus.
The rate of infection of the population might be between 25% and 50%. But with better economic organization and practices human-to-human contacts and transmission could be greatly decreased.
For Americans who become infected their odds of getting anti-viral medication will be less than 1 in 12. For people on most other countries their odds will be much lower. For anyone who has stockpiled your own personal Tamiflu supply your odds of getting anti-viral treatment are excellent - unless you tell too many people about your stockpile and someone steals it.
As of May 2005, the U.S. has stockpiled 2.3 million courses of the antiviral medication Tamiflu, which could be used as a treatment in the event of an outbreak, and intends to order approximately three million more with funds recently appropriated by Congress to total 5.3 million. The WHO is currently estimating that an avian flu epidemic could impact 25 percent of countries’ populations.
In the U.S., this means it could affect nearly 67 million individuals, based on FluAid projections and population numbers. With the current level of the U.S. Tamiflu order, over 61.5 million Americans who could be infected would not receive antiviral medication. If the U.S. orders additional courses of Tamiflu, they would not be available until 2007, unless production capacity significantly changes.
The Brits have ordered enough Tamiflu anti-viral drug to cover a quarter of their population. If the US government decided to do so it would have to wait till 2007 to have the needed number of doses.
Several other countries have already ordered enough Tamiflu to protect between 20-25 percent of their populations in case of an outbreak. The U.S. is already behind in the queue to place an order for the medication, for which there is a single manufacturer worldwide -- Roche Pharmaceutical, which is located in Switzerland. In testimony before the U.S. House of Representatives Health Subcommittee of the Energy and Commerce Committee, the medical director for Tamiflu of the Roche company explained that historically they have not produced the levels of Tamiflu required for global stockpiling. To help accommodate the growing concerns and orders, they have increased production of the antiviral nearly eight-fold since 2003.42
On March 1, 2005, the British government announced that it was taking steps to procure 14.6 million courses of Tamiflu.43 This procurement would cover 25 percent of the British population, the rate WHO has recommended.
Given the current and projected production capacity, if the U.S. did place a large order for Tamiflu, Roche has testified before Congress that it could be the end of 2007 before they could deliver enough to the national stockpile for 25 percent of the population. Thus, antiviral treatment will only be an effective part of the U.S. response if a pandemic does not occur for several years and, of course, if the pandemic strain is responsive to antiviral medications.
This wll create a real problem for the British: People from other countries will try to sneak into Britain in order to be better protected in case they get sick.
The $58 million the US Congress has appropriated for avian flu preparedness is chump change.
The recently enacted emergency supplemental appropriations legislation made available $58 million for the purchase of influenza countermeasures for the Strategic National Stockpile, including, but not limited to, antiviral medications and vaccines. These funds are most welcome, but TFAH believes that Congress should provide additional funds during the FY 2006 appropriations cycle to continue to build the nation’s antiviral stockpiles from the current level of two percent of the U.S. population to cover a higher percentage of the population.
Does the United States have enough medical supplies to handle a large surge in patients?
Does the National Strategic Stockpile Include ALL Necessary Medical Supplies That Will Be Necessary to Respond to a Pandemic? In addition to stockpiling antivirals and vaccines, when they are available, the U.S. must also stockpile critical medical supplies such as masks, gloves, gowns, bed linens, and all other equipment needed to assure that hospitals and other health care providers are properly protected when the usual supply chain is disrupted either abroad or in the U.S.
Let me answer that question: Of course not! This is all the more reason to avoid getting sick in the first place. If you could go live in a cabin in the mountains for a couple of years and see no one other than those who initially travel there with you then you could avoid getting sick and therefore avoid dying.
We also need an enormous amount of face masks and other paraphernalia that the general population will use to avoid transmission of the pandemic influenza strain in public places.
You might need to wait as long 18 months from the time the pandemic begins before you can be vaccinated against the virus.
Is There a Rapid Response Plan to Develop, Test, and Produce a Vaccine? It will take an estimated six to nine months after a pandemic emerges to develop a vaccine. Questions of how to rapidly review and test the vaccine once it is created remain, including concerns about speeding the approval process by the Food and Drug Administration (FDA), liability protection for vaccine manufacturers, and what type of preservative will be used in the vaccine. In addition, industry representatives have suggested that current production capacity is insufficient to meet the demand for a pandemic influenza vaccine, and that it could take 12-18 months to meet appropriate production levels.26
We need to get beyond the old fashioned fertilized chicken egg technology for growing influenza viruses for vaccines. Newer and faster technologies for making vaccines would go far to reduce the size of the disruption and the number of deaths from a flu pandemic.
We also need better ways to reorganize just about every job and economic function in society so that fewer people have to come in contact with each other while they are working, going to school, going shopping, or receiving services.
If a half million or more Americans were at risk from some type of terrorist attack billions of dollars would be thrown at the problem. We should do the same with the avian flu threat. Avian flu is far more likely to kill you in the next 5 years than anything terrorists might accomplish. Our preparations for it should be commensurate with the scale of the threat it poses.
Foreign Affairs has a series of articles coming out in their July/August 2005 edition on the threat posted by the Avian Influenza H5N1 strain. Michael Osterholm makes the argument that governments have not sufficiently prepared for the possibility of a bird flu pandemic in human populations.
What should the industrialized world be doing to prepare for the next pandemic? The simple answer: far more. So far, the World Health Organization and several countries have finalized or drafted useful but overly general plans. The U.S. Department of Health and Human Services has increased research on influenza-vaccine production and availability. These efforts are commendable, but what is needed is a detailed operational blueprint for how to get a population through one to three years of a pandemic. Such a plan must involve all the key components of society. In the private sector, the plan must coordinate the responses of the medical community, medical suppliers, food providers, and the transportation system. In the government sector, the plan should take into account officials from public health, law enforcement, and emergency management at the international, federal, state, and local levels.
The full articles are not yet available online. But you can read longer excerpts if you click through.
In the same Foreign Affairs issue Laurie Garrett is interviewed on how the avian flu could kill hundreds of millions of people and cause trillions of dollars in economic losses.
Q: If an outbreak does occur, what is the state of preparedness planning between nations, across regions, among departments and ministries of individual governments and throughout the non profit sectors?
Planning is abysmally inadequate, given the likely severity of a pandemic caused by a human-to-human transfer of a virus as virulent as the current H5N1 strain.
Q: Without adequate preparations, what would be the likely toll of such a pandemic globally and in the United States?
The answer depends on the virulence level of the pandemic virus. The 1918 strain, which killed 50 to 100 million people, only killed about two to three percent of the people it infected. The H5N1 strain now in circulation kills 100 percent of the birds it infects and has killed more than 50 percent of the people known to be infected so far. If it manages to mutate into a human-to-human form, and retains even half its current virulence, the death toll would be in the hundreds of millions. The WHO issued a report a few months ago putting the estimate at eight million and has since retracted that estimate, preferring far higher reckonings.
Q: How serious might be the economic, social and political impacts?
One Oxford University computer model, assuming a virus with low virulence, put global losses at two to three trillion dollars. The Oxford team concluded that it is impossible to guess the catastrophic economic toll of a high virulence strain.
Trillions of dollars add up to a serious amount of money. Major killer pandemic have occurred within the lifespan of some people still living. The most famous pandemic in modern times occurred in 1918 with 20 to 50 million killed from a much smaller world population. The avian flu cases recorded in humans to date killed at least half of those infected. A world pandemic of such a lethal strain would make the 1918 outbreak seem mild in comparison.
In a separate article Garrett underscores the unpredictability of avian flu's future path.
According to the March 2005 National Academy of Science's Institute of Medicine flu report, the "current ongoing epidemic of H5N1 avian influenza in Asia is unprecedented in its scale, in its spread, and in the economic losses it has caused."
In short, doom may loom. But note the "may." If the relentlessly evolving virus becomes capable of human-to-human transmission, develops a power of contagion typical of human influenzas, and maintains its extraordinary virulence, humanity could well face a pandemic unlike any ever witnessed. Or nothing at all could happen. Scientists cannot predict with certainty what this H5N1 influenza will do. Evolution does not function on a knowable timetable, and influenza is one of the sloppiest, most mutation-prone pathogens in nature's storehouse.
We do not know the probability for an avian flu crossover into the human population that would develop the abiltiy to cause a massive pandemic. We do not know what the fatality rate would be from such a pandemic. Political leaders have reacted to this uncertainty by doing very little. The public has done the same.
Osterholm points out that food distribution networks do not have large reserves of stored food.
He saved his most flatly worded warning, however, for a news conference organized by the Council on Foreign Relations, which publishes the respected journal. In an interview from Washington following the briefing, he repeated his blunt message of how dire things would be if a pandemic starts in the short term.
"We're pretty much screwed right now if it happens tonight," said Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.
Osterholm said the "just-in-time" delivery model by which modern corporations operate means food distribution networks don't have warehouses brimming with months worth of inventory.
Most grocery store chains have only several days worth of their most popular commodities in warehouses, he explained, with perhaps 30 days worth of stock for less popular items.
Anthony Fauci says the emergence of a deadly pandemic is just a matter of time.
Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said the threat of a deadly pandemic is growing.
"This is not going to go away," Fauci said during a forum on the issue Thursday at the Council on Foreign Relations. "Get rid of the 'if.' This is going to occur."
Some fairly cheap things could be stockpiled in advance. High quality face masks seem the most obvious. Given that governments look set to fail to make adequate preparations you might want to buy your own stockpile of high quality particulate filtering face masks. On Google Froogle check out 3M N95 models which can go for less than $1 USD per mask when buying boxes of 20 or more. Note that those masks last for only several hours (forget the exact amount of time). A possibly more cost effective choice is the 3M N100 models which cost more but last for 150 hours. The 3M P100 models also last 150 hours.
One drug might help. Seriously consider getting a Tamiflu prescription and store the package unopened.
How and when should I take TAMIFLU?
TAMIFLU should be taken twice daily (once in the morning and once in the evening) for five days. TAMIFLU can be taken with or without food. As with many medicines, if taken with a light snack, milk, or a meal, the potential for stomach upset may be reduced. You should complete the entire treatment of ten capsules, even if you are feeling better. Never share TAMIFLU with anyone, even if they have the same symptoms. It is important that you begin your treatment with TAMIFLU as soon as possible from the first appearance of your flu symptoms.
Tamiflu comes in 10 and 30 tablet amounts. The 10 tablet amount is enough for 1 person. If you are not living alone or have other people you'd want to help in event of an outbreak then keep in mind that the 30 tablet size costs much less per tablet. In the United States you are looking at perhaps $70 to $80 USD for the 10 tablet amount for a single person and perhaps $190 for 30 tablets (and don't skimp by buying from the more questionable online vendors - go brand name). Canadians living in price controlled socialism get to pay less (and get to live off of the labors of market price paying Americans). But once the big crunch comes don't expect to be able to pay even current American prices if you can find Tamiflu at all.
If you think that come a crisis Tamiflu production will rapidly scale up think again. While research a previous post on avian flu I found an expert who claims it would take 18 months to scale up Tamiflu production. Higher demand from governments to stockpile Tamiflu would help make more available. But don't count on governments. If you can afford to then protect yourself and your loved ones.
If you can afford to stockpile food and have the room to store it then buy a lot of dried and canned food. Keep in mind that if you think you are going to eat the food eventually then the money won't be wasted.
If money is no object here is my deluxe version of what to do:
Isn't survivalism fun? Though if your country hideaway doesn't have DSL don't expect me to visit.
If you aren't rich but have some money to spend then at least consider some cheaper measures you can take now such as purchase of high quality face masks and Tamiflu. If you live in an apartment with central air you might want to get HEPA air filters for your apartment. If you live in a city but can afford a cheap small piece of country land you could park a cheap travel trailer on it. Don't expect to be able to buy most of these things when the pandemic starts.
If your work lends itself to use of a home office then set one up in advance. Even if your employer does not currently allow working from home make sure you have the basic supplies of a computer, broadband internet connection, and other materials. When a pandemic starts employers will become much more flexible about working conditions than they are now. Any person who can avoid entering the office during a deadly flu outbreak is one less person who might infect the boss.
My guess is that in Western industrialized countries the first year of an avian flu outbreak will bring millions of deaths. But by the second year the mechanisms for how to operate societies while minimizing human-to-human contact will be well worked out. Also, by the second season an increasing number of people will have been vaccinated or will have survived infection. So more people will be able to safely move around and carry out the tasks that involve more human-to-human contact.
The economic and human losses from a highly lethal flu pandemic could be greatly reduced with aggressive advanced preparation by governments and industry. But until the public at large becomes concerned I don't expect governments to do much about it. If biological scientists and medical doctors think this threat deserves greater preparation efforts then a lot more scientists and doctors ought to write op/eds and letters to the editor. Too few people are sounding the alarm. Until that changes you are on your own.
Back during the early Cold War era many people took steps such as building fall out shelters to protect themselves against nuclear war. Today we face a danger whose probability of coming true might well be higher than the chance of nuclear war during the Cold War. Yet few people are taking any steps to protect themselves from a highly lethal pandemic because pandemics do not evoke dramatic images. Infections do not create huge visible blasts. Our buildings and other physical structures are left unharmed by a virus. So governments and individuals do far too little to prevent or defend against a massive killer outbreak that could kill many more people than all the wars of the 20th century.
The other odd thing about the lack of preparation for the avian flu is the larger effort being made to protect against bioterrorism. At this point in time in the year 2005 I think we are at far greater risk from a new natural killer influenza strain produced by Darwinian natural selection than we are from a man made strain produced in a laboratory. Yet in the West we have become so accustomed to controlling and defeating the will of nature that we fear more what other humans can do than what nature can throw up at us. I see this as a premature shift in emphasis. Perhaps 20 years or 30 years from now we will face greater threats from bioterrorism than from natural pathogens. But I think right now we are still living in the twilight of the era when natural selection is more likely than terrorists to produce a new deadly pathogen strain.
Also see the special avian flu articles from Nature.
Nature's editorial on avian flu makes clear they think too little is being done.
If the next pandemic were to arise five years from now, there would have been breathing space to stimulate our drug and vaccine industries to limit the damage it would cause. But that requires urgent action now. As matters stand, a vaccine against a pandemic flu would not be ready until at least six months after a pandemic starts. Too late: by then the worst of the pandemic would already have happened.
A vaccine that can be produced more quickly demands a research effort akin to that for a strategic military weapon, not business as usual. We also need to be able to produce enough of such a vaccine to cope with the surge in demand during a pandemic. At present, the entire world production capacity can produce only enough doses for 450 million people. To stimulate an increase in capacity, we need health policies that boost demand for existing flu vaccines in ordinary years. The same goes for antiviral drugs.
But the worst-case scenario is that a pandemic starts within two years. We would have no vaccine and few drugs, and we would be dependent on governments and the WHO to try to extinguish the first outbreaks at source. That's why the first priority must be to prevent a pandemic emerging in the first place, by extinguishing the disease in animals.
Time for action
Unfortunately, the current situation does not bode well for the abilities of governments and international agencies to cope with this challenge. We should be monitoring in almost real time the genetic changes in the avian and human viruses that could herald the emergence of a pandemic strain, for example. But there is no international funding to help affected countries build decent and sustained surveillance programmes. And while outside researchers want data from affected countries, they aren't engaging enough in the meaningful collaboration needed to build trust and open sharing. The international community is not offering incentives, such as drugs for the Asian countries that would be in the front line of a pandemic. Combine this with the fact that countries are reluctant to share the few data they have because their analysis could affect their trade and economies, and the current mess in surveillance is hardly surprising.
If I was King I'd allocate $20 billion per year in the United States for preparations against avian flu. But I'm not King and neither is anyone else. So instead I'll just give you my warning: We ought to do orders of magnitude more than we are currently doing to get ready for the next highly lethal influenza outbreak, whenever it might come.
A dangerous strain of the flu virus that caused a worldwide pandemic in 1957 was sent to thousands of laboratories in the United States and around the world, triggering a frantic effort to destroy the samples to prevent an outbreak, health officials revealed Tuesday.
Because the virus is easily transmitted from person to person and many have no immunity to it, the discovery has raised alarm that it could cause another deadly pandemic if a laboratory worker became infected, officials said.
...
The virus, known as an H2N2 strain, killed one million to four million people worldwide in 1957 and 1958, including about 70,000 in the United States.
The world population is a lot bigger today. So the potential death toll from outbreak of the same strain could be much higher.
In this case, the kits and samples were designed for groups that assist labs with proficiency testing. Dr. Jared Schwartz, an official with the College of American Pathologists, said Meridian was told to pick an influenza sample and chose from its stockpile the deadly H2N2 strain, which it had received from a "germ library" in 2000.
The College of American Pathologists has said it sent 3,747 kits to various U.S. labs.
At the moment I'm writing this the Meridian Bioscience web site is suspended. My guess: A rarely visited web site was suddenly swamped by a huge number of visitors coming to see what Meridian has to say about their potentially deadly error.
If an outbreak does not happen as a result of this error we might benefit in the long run from the publicity surrounding the error. There is an obvious question that ought to be asked at this point: Which other companies, academic, and government labs already have the 1957 strain or other past killer influenza strains? If you would have asked me before this story broke to guess at how many organizations had the 1957 H2N2 strain I would have guessed a few government labs and maybe a couple of academic labs. Now I'm guessing at least hundreds of labs already had it even before Meridian's latest distribution. The same applies to other past killer strains.
Meridian and the World Health Organization think the risk of outbreak is low.
"While a few H2N2 laboratory acquired infections have been documented in the past, the likelihood of laboratory-acquired influenza infection is considered low when proper biosafety precautions are followed," Meridian said in a statement. "The risk for the general population is also considered low." The WHO also has said the risk of an outbreak is slight.
Klaus Stohr of the World Health Organization says that the CDC doesn't classify this pathogen as so dangerous that its distribution should be restricted.
Stohr said the company which sent out the virus samples - Meridian Bioscience Inc. of Newtown, Ohio - abided by current U.S. regulations.
"At the moment, H2N2 is classified as a BSL2, or biosafety level 2, pathogen," he said. "They are allowed to (send it out as part of a test kit).
"They sent it properly packaged, they informed the recipient, they only became aware after the whole matter was better understood that (the U.S. Center for Disease Control and Prevention) is working on a change in the biosafety level for H2N2."
This error was not discovered quickly or reacted to quickly.
The virus samples were distributed by the CAP in October 2004, but the problem was discovered only by a Canadian laboratory only last month.
So the virus was sitting in labs for 5 months, was discovered last month by a Canadian lab (good for them!), and only now is the word going out to destroy the samples. One can argue that labs which get these sorts of samples follow all sorts of safety procedures. But don't you think those lab workers would be more diligent (if not to say scared) if they were made aware that they were receiving a influenza virus that has more lethality than the average strain?
Coincidentally, a great vaccine developer and the man who led the development of the original vaccine for the 1957 Hong Kong flu strain has just died.
Maurice Ralph Hilleman, 85, whose vaccines probably saved more lives than any scientist in the past century, and whose research helps the medical establishment predict and prepare for upcoming flu seasons, died April 11 of cancer at Chestnut Hill Hospital in Philadelphia.
Dr. Hilleman created eight of the 14 most commonly used vaccines, including those for mumps, measles, chicken pox, pneumonia, meningitis, rubella and many other infectious diseases. He developed more than three dozen vaccines, more than any other scientist. His measles vaccine alone is estimated to prevent 1 million deaths worldwide every year.
This article on Hilleman makes him sound like an unusually independent, creative, and driven mind:
He discovered Darwin in eighth grade and was caught reading "The Origin of the Species" in church.
He reminds me of similar unknown, Norman Borlaug, whose work developing crop strains has saved more people from hunger than any other person in history.
Staphylococcus aureus or staph is a bacteria that occasionally causes deadly infections. Methicillin-Resistant Staphylococcus Aureus or MRSA is a strain (or probably a group of strains) of staph that are resistant to many antibiotics. For a long time MRSA and other resistant strains were rarely found outside of hospital settings. Now a new article published by CDC researchers in the New England Journal of Medicine reports that drug resistant staph is increasingly being found in people who have no obvious connection to hospitals or other risk factors.
Overall, they found 17 percent of drug-resistant staph infections were caught in the community and did not have any apparent links to health-care settings.
"Close to one-fifth of what used to be a hospital-specific problem is now a community problem. And that's a large number," said the CDC's Dr. Scott K. Fridkin. "We didn't think it would be anywhere near that high when we started the study."
The drug resistant strains have become more robust.
The CDC researchers checked up to two years of lab reports for drug-resistant staph. More than 80 percent of the 12,553 cases were excluded because the patients had been hospitalized, had a history of surgery or dialysis or had another risk factor.
About 17 percent overall, or 2,107 cases, were determined to be community-acquired staph. The rate was 20 percent in Atlanta, 12 percent in Minnesota and 8 percent in Baltimore.
"When they got out in the community, it was felt these strains weren't strong enough to make it on their own. That no longer appears to be the case," said Dr. Henry F. Chambers of the University of California at San Francisco, who wrote an accompanying editorial.
Those cases are from a small number of cities for 2001 and 2002. The national figure is much higher. MRSA causes 130,000 people to be hospitalized per year.
Previously, MRSA was seen only in the hospital in patients with underlying diseases or compromised immune systems. Now the organism appears to be common among people everywhere, including those in communal settings such as the military, prisons, daycare facilities, and on athletic teams. The CDC estimates that roughly 130,000 people are hospitalized with MRSA each year.
This state of affairs is the result of decades of overuse of antibiotics. Natural selection has produced mutations to allow bacteria to resist many different antibiotics. Bacterial infections are starting to get scary again. Worse yet, the MRSA strains of staph could be stopped with Vancomycin. But Vancomycin resistant staph (VRSA) is believed to be spreading rapidly.
For years, the best treatment for MRSA was the powerful antibiotic vancomycin. But even this weapon has failed against new strains of staph that have emerged. Some infectious-disease experts predict that by 2010, 40% of staph infections will be vancomycin-resistant. And for the moment, there are few alternatives. Cubist Pharmaceuticals Inc. (CBST ) in Lexington, Mass., won approval in September for a new type of antibiotic, Cubicin, that works as well as vancomycin against staph. But experts figure it’s only a matter of time before the bug learns to evade Cubicin, too.
Worse yet, previously the "flesh eating" (really flesh killing) disease necrotizing fasciitis was caused mainly by strep. But now staph is developing the ability to spread rapidly in skin even as it develops the ability to resist a larger set of antibiotics.
In a separate article in the journal, researchers reported that they had linked drug-resistant staph infections to a rare, often-deadly disease known as necrotizing fasciitis, or more commonly, "flesh eating" syndrome.
"Necrotizing fasciitis is a terrible disease, but before now, Staph aureus was never the cause," said Dr. Robert Daum, a pediatrics professor at the University of Chicago and one of the first physicians to notice wider circulation of drug-resistant staph.
Surgeons cut large chunks of skin off of people suffering from drug-resistant necrotizing fasciitis. Even amputations of extremities are necessary in some cases. Sometimes the people survive badly scarred. Other times they die anyway.
For example, with a hospital infection rate of 5%, of which 10% are bloodstream infections, and an attributable mortality rate of 15%, 26,250 deaths can be directly linked to nosocomial bloodstream infections. However, if a 20% attributable mortality rate is assumed, the number of deaths is from 17,500 (with a 2.5% nosocomial infection rate) to 70,000 (with a 10% total nosocomial infection rate).
Drug-resistant bacteria might be killing more people per year than are killed by car accidents. If that is not the case now it might be the case 5 years from now - barring either big advances in techniques to avoid infection or the development of better antibiotics to use on infected patients.
Another obstacle to drug development is the increased regulatory requirements for antibiotics. In the early 1990s, the FDA introduced guidelines that resulted in new and costly demands for the development of antibiotics.7 In an era when hospital- and community-acquired infections are increasingly drug resistant, the efficacy of new drugs are benchmarked against susceptible strains, such as methicillin-susceptible Staphylococcus aureus.
An FDA advisory board has stated that novel antibacterial agents, to be considered for approval, should demonstrate frank superiority to existing antibiotics.6 However, innovative products that fight drug-resistant strains are unlikely to be better than existing drugs that can effectively treat susceptible strains. New antimicrobials would be more likely to make it to market if the FDA introduced new references, such as drug-resistant strains of bacteria, and used new pathogenic targets to evaluate efficacy, such as the inhibition of toxins or prevention of biofilms.
Why should the FDA measure efficacy of new antibiotics against strains that are not antibiotic-resistant? Isn't the biggest need for new antibiotic drugs due to the development of resistant strains of bacteria?
Also, why should the FDA require that new antibiotics be better than existing antibiotics? What is wrong with allowing new competitors that are no better than existing choices? Keep in mind that some people are allergic to or otherwise react adversely to multiple antibiotics. They need more choices.
Think help is on the way in the form of new antibiotics? Don't count on it. Many drug companies have decreased or ended their efforts to develop new antibiotics.
Part of our problem is due to the overuse of antibiotics for humans and also in agriculture. Antibiotics derived from natural sources such as the penicillin family found in a mold have been used so much that resistant strains are now quite common. It is harder to develop an antibiotic totally from scratch. But another obstacle is the FDA. This problem is unlikely to be fixed until the yearly body counts from bacterial infections in the United States get much larger. The public fears dangerous drugs and generally wants more regulation, not less.
By contrast, Tyler Cowen points to a recent post by Bryan Caplan (and these four guys I'm mentioning are all economists) who reports on work by Dan Klein and Alex Tabarrok on how economists see the FDA.
What happens, however, if we listen to economists who specialize in the FDA, rather than random economists at the AEA? Klein reports that opposition becomes very one-sided indeed:
Alexander Tabarrok and I review much of the literature in our website “Is the FDA Safe and Effective?” (FDAReview.org). We include a compendium of 22 quotations by economists calling for significant liberalization of FDA control, and we explain that we have been unable to find quotations favorable to current levels of control by economists who work on the FDA. I believe economics reaches a clear conclusion in favor of significant liberalization of FDA control of pharmaceuticals. Thus, given the range of response options provided by the question, the first two options [strongly support/mildly support] are simply wrongheaded.
Bottom line: The public thinks the FDA is great. Regular economists think it's pretty good. And economists who specialize in the FDA think it's pretty bad. I think I see a familiar pattern.
To address the problem of drug resistant antibiotics We need:
Stay well rested, well nourished, healthy, and away from hospitals. Wash your hands and body after exposure to others - especially after contact sports. Also, don't go visiting someone in the hospital if you have even so much as a cold.
BALTIMORE, MD -- March 21, 2005 -- Using a strategy involving a genetically modified baculovirus and caterpillar cells scientists from Protein Sciences Corporation have been able to speed up a key step in the development of an experimental cell-based influenza vaccine. They report their findings today at the 2005 American Society for Microbiology Biodefense Research Meeting.
"The bird flu may become the next flu pandemic strain. It could happen at any time," says Keyang Wang, a scientist at Protein Sciences Corp. and a researcher on the study. "The most effective method to control such an outbreak is the widespread use of a vaccine. The traditional egg-based method requires 3 to 6 months to develop the vaccine. With our cell-based method, the time from receipt of the virus strain to the final vaccine product would be shortened to approximately 1 to 2 months."
Wang is absolutely correct to state that the current chicked egg-based method for manufacturing vaccine takes a long time. Plus, it can not easily be scaled up quickly. Should a big killer influenza strain break out into human populations existing vaccine manufacturers would be hard pressed to produce billions of doses of influenza vaccine. My guess is they would be able to satisfy only a small fraction of the demand for vaccine.
The existing approach for making vaccines in eggs might not work with a killer avian influenza strain. The egg embryos might be killed by the virus before much vaccine could be produced.
Today's flu vaccines are prepared in fertilized chicken eggs. The eggshell is punctured, and the influenza virus is injected into the fluid surrounding the embryo. The egg is then resealed, the embryo becomes infected, and the resulting virus is then harvested, purified and used to produce the vaccine. In addition to the long development time, another drawback to this method is the possibility that an avian influenza virus would be lethal to embryos in the eggs.
The vaccine strategy pursued by Protein Sciences, known commercially as FluBlok, does not rely on whole vaccine virus. It uses a purified concentration of a key molecule on the surface of the virus, called hemagglutinin, to elicit an immune response against that specific strain of the virus.
Wang and his colleagues have developed a methodology for rapidly producing and purifying hemagglutinin from an influenza virus. They extract the genes responsible for the production of hemagglutinin from the virus and insert them into a baculovirus. Caterpillar cells are then infected with the virus and begin to produce the hemagglutinin.
The FluBlok vaccine has recently finished phase II clinical trials, where it has established safety and the ability to elicit a strong antibody response in humans.
"Since all the media used here are chemically stable and commercially available, the process can be easily scaled up for commercial manufacture," says Wang. "New FluBlok vaccines can be developed quickly and safely to address late appearing influenza viruses and to reduce the impact of a potential flu pandemic."
It is interesting to note that this vaccine is being developed by a commercial company. The US government and other governments have been slow to respond to the need for vaccines that can be manufactured more rapidly and for which manufacturing can more easily be scaled up. Both capabilities are needed in order to produce large numbers of vaccine doses should a major killer influenza strain become established in human populations. With that thought in mind it is worth looking at more of what Protein Sciences has to say for itself.
The FluBlØk™ vaccine may even provide more protection than current commercially available vaccines.
FluBlØk™, derived from Recombinant hemagglutinin (rHA) is a patented replacement vaccine for the current licensed vaccines that are produced in eggs using 40-year old technology. FluBlØk™ consists of three rHA proteins corresponding to the flu strains selected by the World Health Organization and the Center for Disease Control for each year's vaccine. These proteins are produced in serum free insect cells and formulated in PBS without preservatives or adjuvants. Clinical trials have shown safety and efficacy in healthy adults and the elderly population:
- Several Phase I and II trials conducted by the National Institute of Allergy and Infectious Diseases (NIAID) involving over 600 subjects demonstrated safety and efficacy as reported in four published studies in the Journal of Infectious Diseases. A significantly higher percentage of elderly subjects receiving a higher dose of our vaccine develop protective antibody titers compared to the licensed vaccine.
If this vaccine lives up to its claims it will both work better and be faster and easier to manufacture.
This vaccine is made using a virus to infect caterpillar cells grown in culture.
There are many advantages of using the baculovirus expression system, including: high expression levels, limitless size of the expressed protein, efficient cleavage of signal peptides and processing of the protein, post-translational modifications and simultaneous expression of multiple genes. In addition to these advantages, expressed proteins are correctly folded and biologically active. Human clinical studies have demonstrated that proteins produced in the baculovirus expression system can be safely administered to humans. Because the cells die during the manufacturing process, the BEVS system is uniquely able to produce proteins from genes of unknown function.
If you page down to the bottom of that list link you'll see a graphical chart comparing how this vaccine production method compares to several other vaccine production methods in terms of speed, cost, glycosylation (coating of virus antigen proteins with sugars that would be found on them naturally), folding (vaccine proteins have folded 3 dimensional shapes that need to be duplicated), and ease of FDA approval.
I wish these folks luck in their attempts to bring their vaccine to market. We'd all be better off with an influenza vaccine that can be made more rapidly and cheaply and which even elicit a stronger immune response. This vaccine may even save many of our lives some day.