Posted on 05/09/2005 10:18:08 AM PDT by Dog Gone
Some folks suggested that we begin a thread similar to the Marsburg Surveillance Project for monitoring developments regarding Avian Flu.
The purpose is to have an extended thread where those interested can post articles and comments as this story unfolds.
If we're lucky, the story and this thread will fade away.
WASHINGTON (Reuters) - The feared avian influenza virus is showing signs it can evade the drug considered the first line of defense against bird flu, researchers said on Friday. They found so-called resistant strains in a Vietnamese girl who recovered from a bird flu infection after being treated with Tamiflu. They also found evidence she was directly infected by her brother and not by chickens, a rare case of human-to-human transmission of the virus.
When bacteria and viruses develop resistance to a drug, it means higher doses of the drug are needed to eradicate or control an infection. Ultimately it means the drug will stop working. This has happened with many antibiotics, starting with penicillin, and is common among AIDS drugs. The finding illustrates the need to find and use other drugs to treat influenza and to work quickly to develop a vaccine, the researchers said.
"I don't think we need to panic based on this finding," Yoshihiro Kawaoka of the University of Wisconsin-Madison, who led the study, said in a telephone interview. But the report, to be published in the journal Nature next week, is bad news for doctors around the world who already have precious little in the arsenal against bird flu should it become a human disease. "This is the first line of defense," Kawaoka said. "It is the drug many countries are stockpiling, and the plan is to rely heavily on it."
The H5N1 strain of avian influenza is considered by health experts to be the biggest single disease threat to the world. Since surfacing in Hong Kong in 1997, it has spread in flocks of poultry across Asia and is now in Turkey. It does not yet move easily from birds to humans but it has infected 117 people in four Asian countries and has killed 60 of them, according to the World Health Organization.
WHO believes it will eventually acquire the ability to move easily from human to human and that when it does, it will cause a pandemic that will sweep the world in weeks or months and kill millions if not tens of millions of people.
STOCKPILING SUPPLIES
Countries are stockpiling supplies of Tamiflu, an antiviral drug known generically as oseltamivir invented by Gilead Sciences and made and marketed by Swiss drug giant Roche Holdings.
They are to a lesser degree buying up supplies of Relenza, developed by Australia's Biota Holdings and marketed by GlaxoSmithKline. Known generically as zanamivir, this drug is also effective against avian flu but is given via the nose and considered less desirable than a pill like Tamiflu.
An older flu drug called amantadine is already considered to be of little use against H5N1 avian influenza. Work is proceeding on a vaccine but flu vaccines take months to make and cannot be formulated until after an epidemic has begun because they must use the precise strain of virus circulating.
Kawaoka, who is also at the University of Tokyo, worked with colleagues in Japan and Vietnam to analyze samples of virus taken from a 14-year-old Vietnamese girl, called "patient 1," who recovered from an H5N1 infection last March. "Patient 1 had not had any known direct contact with poultry, but had cared for her 21-year-old brother (patient 2) while he had a documented H5N1 virus infection," Kawaoka and colleagues wrote in their report, She had been given Tamiflu three days before she became ill, and then was treated with the drug when it failed to prevent her infection.
Kawaoka's team found several types of H5N1 virus in the girl's sample, some of which had developed genetic mutations to make Tamiflu virtually worthless against it. "It is a mixture," he said. "Within the mixture we found virus that is highly, highly resistant. When you look at the virus as a whole, it is partially resistant," Kawaoka said. "I think what is important here is that the vast majority of H5N1 viruses are still very sensitive to oseltamivir," Kawaoka said.
"Although our findings are based on a virus from only a single patient, they raise the possibility that it might be useful to stockpile zanamivir as well as oseltamivir in the event of an H5N1 influenza pandemic," the researchers wrote. And it will be important to test the virus regularly to see if it is changing and becoming resistant to drugs, they said.
Dead chicken mystery in Kosovo:
http://www.freerepublic.com/focus/f-news/1502547/posts
Thanks for the ping.
Wish I could think of some clever or humorous response to this story, but I can't. This H5N1 has me scared. I really wish I could curtail my husband's and son's travel overseas. I'm seriously thinking of quarantining them both upon their return.
Oh yeah we are safe. The vaccine program could have begun this new mutation infecting humans.
I give credit to Bush for starting the process. He is on the ball on this one. Maybe they are waking up in the WH.
don't raise your hands, folks (see above)
Not out of the woods yet:
Indonesia's health minister called on people to be vigilant against bird flu in the upcoming rainy season, saying they could be especially susceptible to the disease during that time.
"We are asking people to be careful," Health Minister Siti Fadila Supari told reporters Friday, saying the number of bird flu cases could rise in November and December.
The H5N1 strain of bird flu has swept through poultry populations in many parts of Asia since 2003, jumping to humans and killing more than 60 people regionwide -- including three in Indonesia.
Dr. Steven Bjorge, a World Health Organization technical officer in Jakarta, said health experts know very little about the H5N1 virus in humans. But since the number of people who have human influenza peaks during the rainy season, it "seems prudent" to upgrade awareness of bird flu during those months as well, he said.
The U.N. health agency recommends adopting good hygiene practices and thoroughly cooking poultry products, including eggs.
Meanwhile, Agriculture Minister Anton Apriyantono said Friday Indonesia will evaluate stocks of bird flu vaccines used on poultry after discovering some made or distributed by local firms were below standard requirements. Apriyantono said legal action could be taken against three local companies. The ministry's spokesman said the matter had already been referred to the Attorney General's office. Local newspapers have reported the vaccines had low protection rates.
"The government has found vaccines made by local producers that were not in line with the world's animal health body," Apriyantono told reporters, referring to the Paris-based World Organization for Animal Health (OIE). "I've handed this over to law enforcement (agencies)."
He named the three firms as PT Medion Farma Nusantara, PT Bio Farma, and Pusvetma, a firm affiliated with the Agriculture Ministry.
A spokesman for state firm PT Bio Farma, Elvin Fajrul, said the company was unaware of the allegations. He added that Bio Farma did not make the vaccines, but distributed them.
Peter Yan, deputy director at vaccine producer PT Medion Farma Nusantara, said: "We guarantee the quality is in accordance with standards."
Pusvetma officials could not be reached for comment.
http://www.chinapost.com.tw/asiapacific/detail.asp?ID=70242&GRP=C
It gets worse in that area of the world:
The archipelago of Indonesia is being battered from several different fronts. The country had barely recovered from the devastating tsunami that struck last year. Then two weeks ago, the heart of the critical tourism industry in Bali was hit by yet another bombing. The casualty count may not have been as high as the 2002 attacks, which killed more than 200 people, but the fall out of this second assault could wreak havoc on the economy.
At the same time, the nation is reeling from the after effects of a fuel price hike. Rising global oil prices in the aftermath of Hurricane Katrina and Rita, forced Jakarta to cut back government subsides for petrol and kerosene. The move has fueled inflation fears. Finally, there is the mounting threat of avian influenza in Indonesia. The virus has already claimed five lives and infected dozens more. With worldwide fears of bird flu at an all-time high, epicentres of the virus, like Indonesia, could be permanently scarred.
The October 1 Bali bombings may be the most heart-breaking of all these events. However, they may turn out to be the least of all evils. Experts are divided on the eventual impact of the attack. These blasts, though unexpected, are nowhere near the scale of the 2002 tragedy that caught Indonesia and indeed the region off guard. Some feel tourists are getting increasingly inured to terrorist attacks and remain unfazed about such incidents.
However, even though the immediate effect of such blasts on tourism may be less dramatic, long-term data does reflect a reticence among tourists to patronise destinations targeted by insurgents. Even three years after the first Bali attack, tourism has not bounced back. Last year saw 1.5 million people visit Bali. This August the island welcomed its millionth visitor for 2005. Earlier, close to 2.5 million tourists used to routinely flock to Bali every year. And these tourists are a critical driver of not only Bali’s but Indonesia’s economy.
Tourism accounts for 5% of the country’s $258 billion economy and employs eight million people. Diminishing revenues from tourism is not the only factor impacting the country’s ballooning budget deficit.
In a bid to control this spiraling deficit in the wake of Hurricane Katrina, the government recently cut subsidies on domestic fuel, thereby sharply pushing up prices. The price of kerosene, widely used by the poor for cooking, has almost tripled while that of petrol has doubled. Inflationary pressure has now begun mounting. Inflation for September 2005, which is prior to the price increase, stood at 9%, the highest it has been in almost three years. Analysts expect it to climb up to 12% in the coming weeks.
The prices of foodstuff and transportation fares are also feeling the ripple effects. In some areas labourers are shelling out as much as 40% of their salary just to get to work and back.
If the Indonesian economy is sounding like it may be headed for a recession soon, then an outbreak of bird flu, widely predicted as being around the corner by global health experts, may indeed be the final nail in the coffin.
Research by scientists in the US has revealed that the Spanish flu that killed millions between 1918 and 1919 was actually a strain of Avian flu identified as H1N1 (the current strain sweeping across Asia is H5N1). The finding is significant in that it indicates that a virus from birds that has the ability to leap to humans can eventually mutate to allow for human-to-human transmission.
If this happens with the H5N1 virus, it will most likely lead to a global pandemic. Indonesia has already confirmed five deaths from avian influenza and has as many as 50 suspected cases. Things took a turn for the worse when a corruption scandal involving the production of sub-standard doses of a bird flu vaccine was revealed.
Indonesia could well be facing a triple whammy in coming months. We all remember how the outbreak of Severe Acute Respiratory Syndrome (SARS) in 2003 single-handedly sent several economies in the region into recession. Add to that, Indonesia’s domestic troubles and it may not bode too well for the country’s economy
http://www.financialexpress.com/fe_full_story.php?content_id=105643
Yeah, this is going to just kill me. We have a rooster who has been gentle with my kids, and a wonderful guardian for the last ten years. Sport is his name. Plus a great broody hen that I really wanted to see hatch some chicks next spring.
I used to be on the ping list but I think I might need to be reinstated. I have had to search for the threads. Could you please put me on the list? Thanks a lot.
Several companies are working on an H5N1 vaccine, and the furthest along in development is France's Sanofi-Aventis. U.S.-based Chiron Corp. aims to test its H5N1 vaccine later this year and Britain's GlaxoSmithKline Plc plans large-scale clinical trials in 2006. The ordinary flu vaccine does not protect against avian flu.
http://www.pulse24.com/News/Top_Story/20051008-004/page.asp
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Dr. William Winkenwerder Jr., assistant secretary of Defense for Health Affairs, said the virus is not easily transferred between birds and humans. But, if the virus genetically mutates, it may more easily pass from birds and humans and more easily pass from human to human, Winkenwerder said. "We have to prepare for the possibility of an outbreak," he said.
The doctor said the National Institutes of Health has developed a vaccine for the H5N1 avian flu strain. The Defense Department currently has about 200,000 doses.
"As we speak, that vaccine is being mass produced. By the end of this year, we will have a few million doses of that vaccine," he said. "By the end of 2006 we will have tens of millions of doses of that vaccine.
http://www.dcmilitary.com/navy/journal/10_41/national_news/37608-1.html
Unseen makes the following points on Avian Influenza in his posting of 10/12/2005 (#1,753 in this threat):
1. there is no cure, no vaccine and the drugs are becoming resistant
2. The virus is able to jump from bird to human.
3. The virus appears able to spread from human to human with close contact (seen by family clusters with different onset dates)
4. the 1918 flu caused massive death, economic hardships, and changed society for several years and we would be fools to think it can not happen again.
5. The governments in the region are not gathering information in a timely reliable manner.
6. The 1918 flu had a 3% fatality rate. 2005 bird flu in the present form of known outcomes has a 50% fatality rate.
Regrettably, Unseen also drifts into non-science by stating: “However, it is the person that plans for the worse that is pleasantly surprised when the worse does not happen.” While this is certainly true, it is true for a thousand worries or more, and we can’t plan for them all. My understanding of this thread’s purpose is to help prioritize or determine the actual threat from avian flu, not to monger additional worry in a world full of them.
Also, Unseen states (among other incorrect critiques, but I won’t respond to them all in the interest of brevity): “Second you make a lot of assumptions that are not correct. The trillion interaction is just wrong. That's like saying if I shake hands with 100 people but and get sick then the virus is only 1% effective at transmission. It says nothing on the rate of infection nor the ease with which that infection was transferred or if 99 of the patients were not sick”.
My comment on this is that Unseen confuses absolute probability with conditional probability. My argument (not his) is that GIVEN that there are infected flocks and further GIVEN that the collective respiratory and fecal secretions of these flocks (though not necessarily ALL individual birds) are infected, and finally GIVEN that there are BILLIONS of people who have made THOUSANDS of trips to either markets (most common) or chicken houses (much less common but much higher dose risk-exposure), that the virus obviously does not transmit well from birds and/or their contaminated surfaces to humans (and we know that H5N1 remains viable for at least many hours after it is shed from the respiratory of gastrointestinal trancts of birds). So, my conclusion stands, and is correct. Unseen confuses it with transmission from ANY SINGLE bird, not flocks (which is a far more accurate description of the exposure environment).
Now I will take each of Unseens conclusions in turn (and on some we are not as far apart as he/she seems to believe).
1. “there is no cure, no vaccine and the drugs are becoming resistant”
Comment: No disagreement with their being no cure (I never said there wasn’t) nor that the organism is already becoming resistant to Tamiflu (as I predicted, any hypermutable virus exposed to a drug that binds at a SINGLE point in the target protein –neuraminidase – is almost certain to become resistant. This is why I have opposed the stockpiling of Tamiflu at the cost of billions of dollars as either a cornerstone of our preparation or as a significant percentage of our investment. It is bound to be a poor one). However, there IS a vaccine that I believe will work out reasonably well: a DNA vaccine now being tested by a company in Britain (with the odd name “Powder-MED”). You can read more about it – and my agreements and disagreements with the investors in PowderMED who, after all want to sell vaccine – in the upcoming issue of “For the Record” (http://www.fortherecordmag.com/) a healthcare industry news and semi-academic publication.
The nice thing about DNA vaccines (as I’ve pointed out in my book “Microbe: Are we ready for the next plague” which specifically addresses response to novel avian flu viruses – of multiple subtypes – is that unlike the protein based vaccines grown in eggs, DNA can be produced in huge quantities in weeks, literally enough to cover everyone. The problems with DNA vaccines are mostly theoretical: worries about integration of the DNA into mammalian genome (which has never occurred after millions of vaccinations in animals) and, an apparent lack of immunogenicity in humans (as opposed to mice or non-primates) that now appears to have been solved (see: “Effect of plasmid backbone modification by different human CpG motifs on the immunogenicity of DNA vaccine vectors
JOURNAL OF LEUKOCYTE BIOLOGY; SEP 2005; v.78, no.3, p.647-655”).
2. The virus is able to jump from bird to human.
Comment: Already addressed above mostly, but yes on rare occasion it does. Probable reasons in these very, very rare cases are:
- absencee of N1 antibodies in a few people which are probably protective (see more below)
- unknown immunosuppression in rare individuals
- huge doses of virus (e.g. in or near chicken farms
There is now data from the WHO’s OIE on H5N1 in Russia. Not a single case of seroconversion in humans (let alone disease) has been reported despite the handling of countless birds with known H5N1 (see: http://www.oie.int/downld/Missions/2005/ReportRussia2005Final2.pdf
Of course, absence of evidence isn’t evidence of absence and all anyone can do in trying to “rule-out” a hypothesis is make it ever less credible. COULD avian flu become easily able to jump from birds to humans? Sure. It hasn’t in 6 six years and despite numerous mutations (strain subtypes or clones of H5N1) it just hasn’t happened. But, I’d keep the DNA vaccine around in case it does.
“3. The virus appears able to spread from human to human with close contact (seen by family clusters with different onset dates)”
Comment: I’ve already agreed with this AND have explained that IF spread occurs it occurs ONLY with intimate contact (or as Unseen would say “family clusters”). Just like in 1918.
“4. the 1918 flu caused massive death, economic hardships, and changed society for several years and we would be fools to think it can not happen again.”
Comment: This isn’t really a scientific statement, so is hard to critique from a scientific perspective. There is no question in my mind that there WILL be new pandemics (of flu and other, perhaps-as-yet-identified) viruses from time to time (that’s what the whole field of “emerging disease” is about), but the question here is whether or not this particular virus (H5N1 in its multiple subtypes) is that long-awaited pandemic. I believe I’ve shown that it is unlikely (though not impossible). The real problem with Unseen’s conclusion is that this is what people THOUGHT was the case with SARS (the “overdue flu pandemic”) which caused us to (a) restrict travel; (b) restrict trade; and thus cost billions of dollars unnecessarily whereas a simple plot showed that the SARS epidemic was growing at a linear rate – not an exponential one – thereby ruling-out a pandemic virus type very early in the course of the outbreak (before we even knew what the organism was). For more see: 25 APRIL 2003 VOL 300 SCIENCE, pages 558-9 where my modeling predicted – correctlyas it turned out—that SARS was no pandemic threat). Anybody could havce drawn the graph, and why no one at the WHO or CDC did is something that I still don’t understand to this day. But the point is that a silly OVER-response could have been avoided (and what effect, if any, cring “the sky is falling” then or now has on public confidence in disease surveillance predictions might make for a good political discussion).
“5. The governments in the region are not gathering information in a timely reliable manner.”
Comment: Can’t argue with this. But, there is at least SOME progress with serosurveillance (or better PCR surveillance) of birds. See the OIE site for some surprisingly current data: http://www.oie.int/eng/en_index.htm. What remains missing (and again, I don’t understand why we don’t have this data) is a seroprevalence study of a statistically significant sample of humans in SE Asia. My guess – and it is just a guess – is that more than 1% of humans in the region have antibodies against H5N1 meaning that they have (a) been exposed; (b) become infected – meaning the organism has multiplied and engendered an immune response; and (c) didn’t have any illness. This is what happens most of the time when we humans encounter a new bug. But, only the data will answer the question and I’ve never argued anything else other than the single biggest piece of data missing is this seroprevalence information which would go a long, long way to resolving the issue over how dangerous avian influenza is to humans and if we ought not turn our attention to other places (like, for example, garden-variety influenza and the failure of most people – and more than 70% of health care workers – to get immunized routinely).
6. The 1918 flu had a 3% fatality rate. 2005 bird flu in the present form of known outcomes has a 50% fatality rate.
Comment: Hard to know what Unseen’s point is here. Pedestrian motor-vehicle collisions have a near 100% fatality and are far more frequent than H5N1 influenza in humans. If the point is to say that “WHEN avian influenza becomes human-to-human transmissible it will kill 50% of its victims” that is specious for all of the viral adaptation facts I gave in my last posting. It will only have high fatality in very VERY crowded conditions – like the densities of unfortunate domestic fowl or the horrific living and wartime conditions of 1918.
One final point: Unseen may or may not have had time to read the references I posted showing that “H” immunity is no more important for protection than is “N” immunity (and most of us already have N1 immunity as earlier explained). In case any readers remain unconvinced (Unseen appears to be), I’ve listed below a few even more compelling recent references that make the point again.
Hope this helps.
Respectfully,
APZ
A protective immune response in mice to viral components other than hemagglutinin in a live influenza A virus vaccine model
Source: VACCINE; JUN 2 2004; v.22, no.17-18, p.2244-2247
Antibody responses and protection against influenza virus infection in different congenic strains of mice immunized intranasally with adjuvant-combined A/Beijing/262/95 (H1N1) virus hemagglutinin or neuraminidase
Protection against influenza virus infection in BALB/c mice immunized with a single dose of neuraminidase-expres sing DNAs by electroporation
Source: VACCINE; JUL 29 2005; v.23, no.34, p.4322-4328
Cross-protection against a lethal influenza virus infection by DNA vaccine
Source: VACCINE; AUG 1 2000; v.18, no.28, p.3214-3222
Publisher: ELSEVIER SCI LTD
Protection and antibody responses in different strains of mouse immunized with plasmid DNAs encoding influenza virus haemagglutinin, neuraminidase and nucleoprotein
Source: JOURNAL OF GENERAL VIROLOGY; OCT 1999; v.80, pt.10, p.2559-2564
Title: Recombinant neuraminidase vaccine protects against lethal influenza
Source: VACCINE; APR 1996; v.14, no.6, p.561-569
Protection of mice against a lethal influenza challenge by immunization with yeast-derived recombinant influenza neuraminidase
Source: EUROPEAN JOURNAL OF BIOCHEMISTRY; JUL 1 1997; v.247, no.1, p.332-338
Role of antineuraminidase antibody for the protection against Influenza
Author: Aymard, M; Gerentes, L; Kessler, N
Source: BULLETIN DE L ACADEMIE NATIONALE DE MEDECINE; 1998; v.182, no.8, p.1723-1737
Protection against a European H1N2 swine influenza virus in pigs previously infected with H1N1 and/or H3N2 subtypes
Source: VACCINE; MAR 28 2003; v.21, no.13-14, p.1375-1381
Since wild bird flu is front and center now, it is worth briefly reviewing why they are central.
Wild birds have always been key in influenza evolution.
Flu evolves via dual infections, which happens when one organism is infected by two viruses. The two viruses can exchange genetic information. In the case of flu, its 8 genes are a separate pieces of genetic information. The genetic exchange can be with whole genes (a new viruses take some genes from one parent and some from another) or pieces of genes (the new gene is a chimera with some input from each parent).
Swapping whole genes is pretty easy to see, and that is one thing that influenza analysts look for. Some think that H5N1 needs to get a whole human/pig gene to go pandemic. They have been watching and waiting, and helping WHO write its press releases announcing the latest H5N1 has no human genes, but that is not how H5N1 will go pandemic. It has never been reported to have gone that route, and there is no logical reason to think that reassortment is a requirement.
Swapping pieces of genes is harder to see. This happens via recombination, and although such a process is not new, its widespread role in evolution, especially from rapidly evolving viruses like avian flu, is not understood, and in fact is denied by those advising WHO and controlling information flow.
Thus, WHO doesn't talk about recombination because its advisors don't know how to recognize it, and if they do see it, the try to explain it by random mutation. However, the changes are far from random, and in fact can be traced back to genes of parental viruses.
Flu doesn't have time for random changes. To survive, it needs to change its genetic composition each year, and it does so via recombination, which requires dual infections.
Nature reserves offer an ideal environment for such an exchange and Qinghai Lake in China is a good example. Many species arrive at the same time from several geographically distinct region carrying distinct viruses. At the reserves, there are dual infections and the virus evolves. The birds then fly the virus back to areas where other indigenous viruses are and the virus evolves some more.
Most of these exchanges in the past where not easily seen, because there was not a good database of wild bird sequences, and much of the exchange involved wild bird sequences from serotypes like H9N2 mixing with H5N1, which were read as random mutations.
In May that changed because the H5N1 ar Qinghai Lake left a trail of dead bodies because it was killing wild waterfowl. The H5N1 was a clear recombinant, with parts of its genes from Europe, and parts from Asia. The HA cleavage site, which makes it pathogenic, was the characteristic KKKRRK, which was only found in H5N1 in Asia since 1996.
This signaled the beginning of a geographical expansion of H5N1. It was now in long range migratory birds, and can travel 1000 miles in a day. The H5N1 moved from Qinghai Lake to Chany Lake in Russia and also spread to neighboring Kazakhstan and Mongolia. Prior to July, Asian H5N1 had never been reported in any of the three countries.
Now H5N1 is entering Europe as the birds from Siberia migrate in. They have the same Asian H5N1 and signal the start of a global expansion outside of Asia. This will spread worldwide in the next 12 months.
This geographical expansion will allow the H5N1 to dually infect new organisms with new viruses, including mammalian ones in swine and humans. H5N1 will become more human like and achieve efficient transmission.
That is the problem. It is driven by recombination and will accelerate in the upcoming months. That's why the pandemic is a when, not an if, and why the when is measured in months, not years.
The pandemic is not dependent on random mutations or reassortment. It is driven by recombination, and H5N1 is collecting a lot of new toys to play with as it goes global.
...end of Dr. Niman's first posting....
Maybe you or someone else also knowledgeable can explain Mother Abigail's post and comment above. After reading Dr. Niman's article, my simpleminded brain says "how can they make a vaccine when it's not done recombining yet, but the article above it says that a vaccine is being made?"
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