Does the H5N1 avian influenza pose a substantial epidemic threat to humans? Or has the H5N1 fear benefited us by spurring us to prepare for much more likely causes of killer pandemic influenza?
Dr. Paul Offit, a vaccine specialist at Children's Hospital in Philadelphia, was one of those who, he jokes, "dared to be stupid" by bucking the alarmist trend in 2005.
"H5 viruses have been around for 100 years and never caused a pandemic and probably never will," he said.
But Offit said he backed all preparedness efforts because he expected another pandemic from an H1, H2 or H3, the subtypes responsible for six previous epidemics, including the catastrophic one in 1918.
"What I worry is that this has been a 'boy who cried wolf' phenomenon," he said. "When the next pandemic comes, people will say, 'Yeah, yeah, we heard that last time.' "
The efforts to develop faster ways to produce vaccines will eventually pay off in a big way when another dangerous flu strain pops up. Regardless of what strain turns out to cause the next pandemic the preparations made for an H5N1 pandemic will serve us well. But we still do not have the ability to rapidly scale up vaccine production.
Right now, said Dr. Klaus Stöhr, who was chief of flu vaccines for the WHO and now does the same for Novartis, it would take manufacturers about one year to produce a billion doses of any vaccine based on a new pandemic strain. But the pandemic would have circled the globe within three months.
"The peak would be over, and, principally, you'd be vaccinating survivors," Stöhr said.
We need vaccine production technologies that lend themselves to very fast and easy scaling. The ability to grow vaccines in microorganisms would let us scale up production most rapidly.
Vaccines and drugs will not be enough to slow or prevent a pandemic of influenza, according to a U.S. government report released on Tuesday.
The report from the U.S. Government Accountability Office confirms what most experts have been stressing for years -- that the pharmaceutical industry cannot be relied on alone to protect the world from bird flu.
If you want to survive a pandemic the key is to be able to isolate yourself. You can do this by yourself or with family or friends or a work group. The most essential quality in such a group is trustworthiness. Can you trust them not to sneak off somewhere and unnecessarily expose themselves to people outside the group? That is what you need to eliminate the risk of death from a deadly influenza pandemic.
One of the problems with use of vaccines to stop a flu pandemic is that it takes many months to develop and manufacture vaccines against a new flu strain. Even worse, the manufacturing capacity for making vaccines is woefully inadequate for the case of a global pandemic. In a pandemic the need for vaccine would go up over an order of magnitude and the current process for making flu vaccine is hard to scale up. One way to partially solve this problem would be to manufacture vaccines in advance using flu strains that are not exact matches for an eventual pandemic strain. Support for pre-pandemic vaccine production is building.
"People are taking pre-pandemic vaccination seriously," says Derek Smith at the University of Cambridge. In May, a meeting of scientists and manufacturers at the World Health Organization in Geneva, Switzerland, recommended the development of vaccines that could be used to inoculate people before a pandemic takes hold. These, they said, must have long-lasting effects, and be "broad-spectrum" enough to work against whatever pandemic virus emerges. Several novel vaccines that do both are now close to testing in humans. They include the addition of immunity-stimulating chemicals called adjuvants, vaccines made of DNA instead of the virus itself, and perhaps the ultimate - a vaccine that protects against every kind of flu.
While there is no way of knowing before a pandemic starts exactly how well the vaccine will work, the risks of doing nothing could be far greater. "Stockpiling pre-pandemic vaccines is more valuable than people realise," Robert Webster of St Jude Children's Research Hospital in Memphis, Tennessee, told a flu conference in Singapore last month. "It may not necessarily protect you from infection, but it will probably stop you dying."
I've been in favor of this idea for years and continue to think that movement in the direction of developing pre-pandemic vaccines is too slow. The problem with pre-pandemic vaccines is that they won't be an exact match for whatever strain of influenza eventually becomes pandemic. But if an H5N1 avian flu strain mutates into a human pandemic strain then even a vaccine made from a different H5N1 strain will provide partial immunity to the pandemic strain. That partial immunity might some day save millions of lives.
The article reports on promising advances in DNA-based vaccines and in adjuvants (which amplify immune system response to vaccines). Production of DNA vaccines could be scaled up much more rapidly than the current chicken egg-based vaccine manufacturing process.
Last week, Joe Howton, medical director at the Adventist Medical Center in Portland, Oregon, suggested a way to double supplies, after browsing basic safety data from Roche for a talk on avian flu.
The technique was invented during the Second World War to extend precious penicillin supplies. Scientists found that a simple benzoic acid derivative called probenecid stops many drugs, including antibiotics, being removed from the blood by the kidneys. Probenecid is readily available and is still widely used alongside antibiotics to treat gonorrhoea and syphilis, and in emergency rooms, where doctors need their patients to have high, sustained levels of antibiotics in their blood.
Howton believes that Tamiflu doses could be cut in half when taken with Probenecid. This would effectively double the amount of Tamiflu available should a pandemic occur. To make this work Probenecid would need to be made in sufficient quantity. But quite possibly other existing drugs could be found that also interfere with Tamiflu excretion.
Drugs that may adversely interact with Tamiflu are the drugs containing Probenecid. Combining Tamiflu and drugs containing Probenecid may result in higher blood levels for patients.
Coadministration of probenecid results in an approximate 2-fold increase in exposure to the active metabolite due to a decrease in active anionic tubular secretion in the kidney. Other drugs excreted via anionic tubular secretion have not been evaluated.
If you haven't already stockpiled your own Tamiflu supply your odds of getting Tamiflu during a pandemic are rather slim even if Probenecid works to stretch Tamiflu supplies. The key to surviving a highly lethal influenza pandemic would be to greatly reduce your exposure to other people who might be influenza carriers. My favorite proposal for reducing the risk of getting a pandemic virus while simultaneously reducing the economic disruption of a pandemic is "workplace cocooning".
I also think we should have large crash programs for the development of cellular methods for growing flu vaccine and for the development of DNA vaccines as well. Plus, I'd gladly take a shot of a vaccine against existing H5N1 avian flu strains as a way to get partial immunity against an eventual possible human pandemic strain of H5N1.
Update: Do not casusally go taking probenecid to avoid the flu. First off, it does no good unless taken in combination with Tamiflu. Second, probenecid has potentially dangerous side effects and should not be taken casually. Do not take extra doses. You could kill yourself if you do.
Roche's Tamiflu (a.k.a. oseltamivir phosphate) is the most effective known drug against influenza infections. Should an H5N1 avian influenza strain mutate into a form capable of causing a large deadly human pandemic then for those infected Tamiflu might be the only drug that will reduce the odds of dying. With that in mind I've decided to start looking for information on national Tamiflu stockpiles around the world. If anyone comes across information about countries buying large amounts of Tamiflu let me know what you find.
United States Health and Human Services Secretary Mike Leavitt says the US government plans to build up a 20 million dose stockpile of Tamiflu.
Leavitt said the federal government was looking to stockpile 20 million doses of a bird flu vaccine and another 20 million doses of Tamiflu, an antiviral medication to treat the illness.
While those talks with Roche are still underway currently the United States has just 2.3 million Tamiflu doses available.
The United States has a stock pile of 2.3 million doses of Tamiflu, enough for just one percent of its population.
The United States currently has a population of 295.734 million. So the current 2.3 million dose stockpile provides only 0.778% coverage, not even a whole percentage point. Once the stockpile reaches 20 million doses (and that probably will take years the coverage level will still be just 6.7% and probably lower than that due to population growth. Plus, in event of an outbreak I expect a lot of Mexicans to cross into the United States illegally seeking treatment. This'll accelerate the spread of the virus as well as placing a still heavier burden on completely overwhelmed hospitals.
The ministry has also ordered 835,000 courses of Tamiflu, the last of which should arrive by the end of the year.
New Zealand has 4.035 million people. So New Zealand will soon have a 20.7% coverage rate. Plus, New Zealand can much more easily cut itself off from the rest of the world in order to prevent the spread of the virus.
Best stockpile for Tamiflu I've come across so far is in France with 14 million doses expected to be in stock by the end of 2005. With about 60.656 million people France will soon have an impressive 23.8% coverage rate.
The UK government said on Tuesday it had ordered 14.6 million doses, enough for one in four of the population.
The UK order is worth around $384.4 million and the doses will be delivered over two years. Analysts at Morgan Stanley estimate that potential U.S. and European sales could total $3.9 billion.
With 60.441 million people the UK coverage level will eventually reach 24.2 %. But that will not happen for two years. Whereas the French will achieve their 23.8% coverage rate by the end of 2005. The French are clearly most ready and will continue to be most ready for quite some time.
What is an adequate coverage rate? It depends on what percentage of the population gets a pandemic flu strain. If the total infected can be kept to 20% or less (and that seems achievable in industrialized countries) then 20% coverage is adequate.
Your best bet during a highly lethal pandemic is to isolate yourself. Home school your kids. Try to get work you can do from home. Shop rarely, buy lots of stuff when you do shop, and shop at off hours when few are in stores. Better yet, get delivery. Also, stockpile your own Tamiflu and get face masks, preferably longer last face masks such as the 3M N100.
If anyone comes across reports on national Tamiflu stockpiles and order levels let me know.
Update: Australia has 3.5 million doses of Tamiflu stockpiled. (and that link has an excellent discussion of what a severe pandemic would be like including an image of a deserted NYC Grand Central Station).
Officials in Australia, however, have 3.5 million courses of treatment, and in Great Britain, officials say they have ordered enough to cover a quarter of their population.
Australia has 20.09 million people. So Australia's coverage comes it at a very respectable 17.42%. Australia already has 3 times better Tamiflu coverage than the US government hopes to achieve in a couple of years.
The WHO was also working with the government to source new stocks of the anti-viral drug Tamiflu from India to bolster local stocks, he said.
"It's not very much, it's rather puny. They definitely need some more," Petersen said, adding that stocks being rushed from India were less than 1,000 doses.
Tamiflu is an anti-viral tablet that can help against infection. Several companies are working on a vaccine, but tests are not expected to begin until later this year.
Supari said Indonesia had 10,000 Tamiflu tablets.
I suspect Supari meant "doses" and not "tablets". Indonesia has 242 million people. Indonesia typifies the vast bulk of the countries in the world: Should the pandemic come I expect most countries will fail totally in attempts to control the pandemic. Order will break down in many countries as soldiers and police abandon their posts in order to avoid exposure to the virus.
According to public health officials, Southeast Asia needs to stockpile antiviral drugs to treat at least 3 million people if the deadly H5N1 virus mutates to one that could explode into a pandemic.
But meeting this demand is already proving to be a problem due to limited stocks for the developing world. The World Health Organization (WHO) is due to receive 1 million doses from Swiss pharmaceutical giant Roche, the producer of Tamiflu, by the end of this year and another 2 million by mid-2006.
WHO currently maintains a stockpile of about 80,000 treatment courses of oseltamivir, known commercially as Tamiflu, Omi told reporters outside a WHO conference in New Caledonia.
Last month, Swiss-based Roche Holding AG announced it would donate 3 million treatment courses of Tamiflu to a WHO-managed stockpile, but the first million courses will not be ready until early next year and the remaining 2 million will not be ready until mid-2006.
Also see the comments where one commenter claims a double dose of Tamiflu is more effective than a single dose. If this is true then you folks who are stockpiling for your families ought to double your orders.
Until this week, Indonesian doctors had only a few hundred courses of the anti-viral drug oseltamivir. Sold by pharmaceutical giant Roche as Tamiflu, the drug is widely seen as one of the few effective options to treat the H5N1 virus in humans and, potentially, contain an outbreak.
Even after 10,000 courses ordered through the World Health Organisation are added this week, supplies for the country of 220m will be dwarfed by the far wealthier nearby island-state of Singapore, which is assembling a stockpile of 350,000 courses for 4.2m citizens - or the 700,000 Thailand has now and the 3m it wants by 2007.
Singapore is trying to achieve 8.3% coverage. But it is not clear when they will do so. Thailand has 65.444 million people and so their 700,000 doses count up to 1.07 coverage. They might achieve 4.6% coverage some time in 2007 which would still be very inadequate.
The federal Centers for Disease Control and Prevention have stockpiled enough to treat 2.3 million people. Hoffmann-La Roche, the Swiss pharmaceutical giant that is the world's sole supplier of the drug, has pledged to build a U.S. plant to produce Tamiflu before the year's end, but the drug supplies from that plant would not be ready until late 2006.
The later a pandemic comes the better the shape we'll be in to handle it.