The H5N1 strain of influenza - often referred to as bird flu - is first known to have jumped from chickens to humans in 1997. Since 2004 it has ripped through poultry and wild bird populations across Eurasia, and had a 53% mortality rate in the first 147 people it is known to have infected. Health authorities fear this strain, or its descendent, could cause a lethal new flu pandemic in people with the potential to kill billions.
Flu has been a regular scourge of humanity for thousands of years. Flu viruses each possess a mere 10 genes encoded in RNA. All of the 16 known genetic subgroups originate in water birds, and especially in ducks.The virus is well adapted to their immune systems, and does not usually make them sick. This leaves the animals free to move around and spread the virus - just what it needs to persist.
But sometimes a bird flu virus jumps to an animal whose immune system it is not adapted to.
Via the Globe and Mail: Need cleanup funds, say owners of farm closed
by bird flu.
The owners of the Saskatchewan chicken farm where avian flu was discovered last week are shocked at the lack of support for their plight and are pleading for public money to handle the cleanup.
Thomas Glen, whose family owns the Pedigree Poultry farm north of Regina, said they feel terrible to be the centre of international attention, and he can't understand why the federal government and poultry industry haven't come forward to offer financial assistance.
Frankly, I can't understand it either. Just because they are a small enterprise, like it does not affect anybody else in that country?
Not good for public health, and not good for the poultry industry...
UPDATE
Well, U.S. Customs in this country was concerned also:
U.S. Customs officials in Minnesota and North Dakota seized more than 4,100 birds from hunters re-entering the United States from Canada following an outbreak of avian flu at a commercial chicken farm near Regina, Saskatchewan.
Mike Milne of U.S. Customs and Border Protection says the birds were confiscated at entry points in Warroad, Minn., and Portal and Pembina, N.D.
Birds also were confiscated at border crossings in Montana and at Canadian airports
Within five months, a family from Rawa Buaya subdistrict in West Jakarta lost two children to what was diagnosed as typhoid fever by doctors at the Sumber Waras Hospital.
AR, 22, died last Friday after suffering from high fever, headaches and respiratory problems. His 19-year-old sister died after suffering similar symptoms in April. However, on Monday the Health Ministry confirmed that the cause of both deaths was avian influenza.
...the head of the neighborhood unit, Mamat, 50, said the two siblings helped sell their uncle's chickens at Kemiri market before their deaths.
"The two of them helped clean up and slaughter chickens," said Mamat.
I want to know how at this late date the sister's "typhoid" death can now be identified as H5N1. If it's official, then her brother's recent death was (at least) the 87th in Indonesia.
Swedish scientists say that Tamiflu -- the frontline weapon in any bird-flu pandemic -- cannot be broken down by sewage systems and this could help the virus mutate dangerously into a drug-resistant strain.
Countries around the world are stockpiling Tamiflu in the belief it will help curb any future outbreak of H5N1 avian flu among humans.
Scientists led by Jerker Fick, a chemist at Umea University, tested the survivability of the Tamiflu molecule in water drawn from three phases in a typical sewage system.
Tamiflu's active ingredient survived all three processes, which means that it is released in the waste water leaving the plant.
The finding is important because of the risk that Tamiflu, if overprescribed, could end up in the wild in concentrations high enough to let H5N1 adapt to this key drug, the authors say.
Flu viruses are common among waterfowl, especially dabbling ducks such as mallards which often forage for food near sewage outlets.
These avian viruses could then recombinate with ordinary human flu viruses, creating new strains that are resistant to Tamiflu, he said.
"Antiviral medicines such as Tamiflu must be used with care and only when the medical situation justifies it," Olsen warned. "Otherwise, there is a risk that they will be ineffective when most needed, such as during the next influenza pandemic."
Chinese doctors may have found a new approach for treating bird flu: Give bird flu patients plasma from bird flu survivors.
Antibodies in the bird flu survivors' plasma might help bird flu patients recover, the doctors report.
At least, that's what happened when they tried that technique on a Chinese bird flu patient.
The doctors -- who included Boping Zhou, MD, PhD, of the Shenzhen Donghu Hospital in Shenzhen, China -- describe that case in The New England Journal of Medicine.
Indonesian Bird Flu Vaccine Is Ready for Use
This vaccine was developed thru a deal with Baxter Labs
from a strain of avian flu present in their country. But, there are,
The WHO is urging that Indonesia stockpile their new vaccine, and wait until a pandemic erupts to use it. The Indonesians are intent on using it now, to forestall a possible pandemic.
With just 2 million doses, for a country of 235 million people, the amount on hand may be inadequate for either use.
Up until now, Indonesia has been using Tamiflu, often dispensed liberally, in order to contain outbreaks of the H5N1 virus. Dispensaries in villages have handed out tens of thousands of courses of the drug to anyone complaining of `pilek', cold or flu symptoms.
...in a new study a team of researchers from the University of Wisconsin-Madison report the identification of a key step the virus must take to facilitate the easy transmission of the virus from person to person.
Writing today (Oct. 4, 2007) in the journal Public Library of Science Pathogens, a team of researchers led by virologist Yoshihiro Kawaoka of the UW-Madison School of Veterinary Medicine has identified a single change in a viral protein that facilitates the virus' ability to infect the cells of the upper respiratory system in mammals. By adapting to the upper respiratory system, the virus is capable of infecting a wider range of cell types and is more easily spread, potentially setting the stage for a flu pandemic.
"The viruses that are in circulation now are much more mammalian-like than the ones circulating in 1997," says Kawaoka, an internationally recognized authority on influenza. "The viruses that are circulating in Africa and Europe are the ones closest to becoming a human virus."
Roche Holding AG's Tamiflu persists in waste water, which may make the drug a less effective weapon in an influenza pandemic, Swedish researchers said.
The medicine's active ingredient, oseltamivir carboxylate, is excreted in the urine and feces of those taking it. Scientists at Sweden's Umea University found the drug isn't removed or degraded in normal sewage treatment, and its presence in waterways may allow flu-carrying birds to ingest it and incubate resistant viruses.
The findings add to concern about the availability of effective medicines in the event of a pandemic sparked by bird flu. Strains either resistant or less sensitive to Tamiflu have been linked to the deaths of at least five people in Vietnam and Egypt. A separate study found Tamiflu may be becoming a weaker weapon against the H5N1 avian flu strain in Indonesia, where the virus has killed the most people.
Scientists say waterfowl, including ducks, are the natural hosts of avian flu. These birds often forage for food in water near sewage outlets. It's possible they might encounter oseltamivir in concentrations high enough to develop resistance in the viruses they carry
The biggest threat is that resistance will become common among low pathogenic influenza viruses carried by wild ducks,'' Olsen said. These viruses could then recombine with others that make humans sick to create new ones resistant to the drugs currently available, he said.
As much as 80 percent of the Tamiflu taken in each dose is excreted in its active form in urine and feces and the drug could potentially be ``maintained in rivers receiving treated wastewater,The potential for resistant strains to emerge this way is greatest in Southeast Asia, ``where humans and waterfowl frequently come into close direct or indirect contact, and where significant Tamiflu deployment is envisaged,'' the study's authors said.
They recommended developing methods to minimize the release of the active Tamiflu ingredient into the waste stream, ``such as biological and chemical pre-treatment in toilets, which could eliminate much of the `downstream' risk.''
Scientists led by Jerker Fick, a chemist at Umea University, tested the survivability of the Tamiflu molecule in water drawn from three phases in a typical sewage system.
The first was raw sewage water; the second was water that had been filtered and treated with chemicals; the third was water from "activated sludge," in which microbes are used to digest waste material.
Okay, add Tamiflu to the list of medications you should never dump down the toilet. As we know, environmentalists have been pleading with consumers for years not to dump expired medicine down the crapper, because many of these compounds simply do not break down in the treatment process.
What this study also did, by proxy, is help confirm a suspicion that we can adapt an old World War II medical trick for use in a pandemic. This is old news, but it bears repeating. During WWII, medics and corpsmen learned that penicillin use could be extended with the addition of a simple drug -- probenecid. Probenecid slows down the kidneys' natural desire to flush substances quickly. The effect is to double the ability of a drug to perform its desired function. The bottom line effect in wartime was to effectively double the available supply of penicillin. What a clever innovation!
Roche found that probenicid doubled the time that Tamiflu spent circulating in the human bloodstream, effectively halving the dose necessary to treat someone with the flu.
"Giving the flu drug together with probenecid doubles the time that Tamiflu's active ingredient stays in the blood, doubles its maximum blood concentration, and multiplies 2.5-fold the patient's total exposure to the drug (see graph, and G. Hill et al. Drug Metab. Dispos. 30, 13-19; 2002)"
The noted infectious disease rock star Dr. Yoshihiro Kawaoka of the University of Wisconsin-Madison ...and his team of researchers have confirmed that the H5N1 "Qinghai" substrain (Clade 2.2)has mutated into a form that is much easier for humans to catch.
The key is the ability of the virus to infect the upper respiratory tract. H5N1 normally has a tremendous affinity for the lower respiratory tract -- deep in the bottom of the lungs. This makes it extremely difficult for humans to catch the virus. But it also dooms most of the flu's human victims to death. The mutation noted by Kawaoka and his team adapts the virus to the comparatively colder regions of the human throat and nose.
The detection of E627K in dead wild birds at Qinghai Lake in May, 2005 signaled a major change in the global spread of H5N1. At the time “Asian” H5N1 had not been reported in any country west of China. The massive die-off at Qinghai Lake signaled the movement of H5N1 in long range migratory birds and the strain of a major geographical expansion.
The data on the temperature dependence of E627K also explains why many surveillance programs fail to detect Qinghai H5N1 in live wild birds, including locations where H5N1 is readily detected in dead or dying wild birds. The body temperature of live wild birds keeps the levels of the virus low, below the detection levels of these assays. Dead and dying birds have a lower body temperature, allowing levels of the virus to rise.
Although the effect of E627K on viral replication has been known (sic) since 2001, this fact has been ignored in the surveillance programs that focus on live birds. Instead of measuring H5N1 antibody levels, which are more stable and reliable, these groups test thousands of birds and then use the false negatives to issue assurances and denials of the transport and transmission of H5N1 by wild birds.
The Editors of Effect Measure are senior public health scientists and practitioners. Paul Revere was a member of the first local Board of Health in the United States (Boston, 1799). The Editors sign their posts "Revere" to recognize the public service of a professional forerunner better known for other things.
Paper on mutation that enhances infection of upper airways
Category: Bird flu * biology
Posted on: October 6, 2007 7:26 AM, by revere
The headline was worrisome: "Bird flu becoming riskier for humans." The story was about a new paper in PLoS Pathogens from Kawaoka's lab that was said to identify "a specific change that could make bird flu grow in the upper respiratory tract of humans," according to the lab leader.
Birds usually have a body temperature of 41 degrees Celsius, and humans are 37 degrees Celsius. The human nose and throat, where flu viruses usually enter, is usually around 33 degrees Celsius.
"So usually the bird flu doesn't grow well in the nose or throat of humans," Kawaoka said. This particular mutation allows H5N1 to live well in the cooler temperatures of the human upper respiratory tract.
H5N1 caused its first mass die-off among wild waterfowl in 2005 at Qinghai Lake in central China, where hundreds of thousands of migratory birds congregate.
That strain of the virus was carried across Asia to Africa and Europe by migrating birds. Its descendants carry the mutation, Kawaoka said.
"So the viruses circulating in Europe and Africa, they all have this mutation. So they are the ones that are closer to human-like flu," Kawaoka said. (Australia Associated Press)
This is pretty scary sounding but it isn't new scary sounding. Kawaoka confirmed and filled in the picture about a mutation we already knew about, which is why he looked at it more closely in this paper. As far as we know the suspicion that a mutation in the PB2 gene at position 627 that substitutes lysine for glutamic acid (the mutation is written E627K in shorthand) goes as far back as 1992 when Subbarao, London and Murphy showed it was needed for a bird virus to infect mammalian cells. The idea that temperature is important was reported by Massin and colleagues in 2001. The viral RNA genome is packaged inside ribonucleoprotein (RNP) particles comprised of nucleoprotein and three RNA-dependent RNA polymerase subunits, PA, PB1 and PB2. This package takes the virus's RNA genetic material and uses it to make new viral protein and new viral genetic material. PB2 is part of this protein-making and gene replicating machine. It all gets packed up inside a viral outcoat that includes both the hemagglutinin and neuriaminidase proteins (the Hs and Ns of the various subtypes like H5N1) as well as some other proteins.This paper confirms that a switch from glutamine to lysine in PB2 makes a difference.
For some years we have been fixated on apparent differences between the cellular receptors preferred by bird flu viruses and human viruses. We have written quite a bit about it here.... But it was becoming ever clearer that the receptor story wasn't the whole story or even the main story. Other things were involved. Early on, E627K came under suspicion. What Kawaoka and his colleagues have done is show that two H5N1 isolates taken from the same patient in Vietnam in 2004, one from the lower respiratory tract and the other from the upper respiratory tract, differed genetically in a few places, one being at position 627 of PB2. They then showed that this single change made a difference in the ability of the virus to infect cells from the upper and lower respiratory tract in the test tube and in inoculated mice. To show it wasn't other genetic variations, they mutated that single position in each of the two isolates and showed that the biological properties of the virus switched with it: what before easily infected the lungs but not the upper tract now did the reverse, etc. It is quite elegant.
The relationship between transmissibility and infection of the upper tract is both on the giving and the receiving end. Infected cells in the upper tract are likely to shed more virus when the patient coughs and sneezes and an exposed person is more likely to expose susceptible cells. While we've known about this mutation for some time, this paper provides more direct evidence that the Glu-to-Lys mutation at PB2-627 affects growth in mammalian cells and the ability to infect cells in the upper respiratory tract. The effects are not completely clearcut. The avian version was also able to infect upper tract cells in some instances. The paper also shows it is not the only change involved. Other changes, as yet unknown, seem also to be important.
This work makes us more confident we are pursuing a reasonable line of inquiry, no small matter in a confusing question. But we haven't as yet unlocked the key to what would make easy transmissibility in humans.
Linda Tismery was a resident of PT Chevron Pacific Indonesia (CPI) housing complex at Rumbai, Pekanbaru with her husband and children. Right, it is Chevron as in the oil company. Her husband works for Chevron.
As we have learned over the weekend, the suspected bird flu death of 44-year old Linda Tismery of Pekanbaru, Riau Province, Indonesia, has been confirmed as H5N1. This is the second H5N1 death in a week for the nation of Indonesia...
Now the Indonesian press is reporting that two of the nurses who attended to Ms. Tismery have also begun exhibiting bird flu symptoms...
The nurses had duties over some 63 patients. All 63 are appearing to be OK, but the two nurses are quite ill. This is always a cause for concern, because human-to-human transmission is becoming less and less rare in Indonesia, and any preliminary report of health care staff becoming ill causes ashen faces and worried looks both in Jakarta and in Geneva.
UPDATE
The nurses and all of the contacts have tested negative, we were told, but there have since been reports that
two nurses have died. These reports have odd and conflicting information, and it is not clear if they are
true or not. We have also been told that even though these nurses died, their deaths were unrelated
because they did not take care of this patient with bird flu. Very strange when they are mentioned in the
same articles. The Indonesian Health Minister, Supari keeps insisting that no human to human contact
has occurred but meanwhile the Indonesian translations of an official on the ground is saying something
It's taken longer than many of us wanted, but some new data on host susceptibility is now coming in. The influenza research group at St. Jude's has just published a paper in CDC's journal, Emerging Infectious Diseases, verifying that common land based birds can be infected with highly pathogenic avian influenza virus H5N1. The St. Jude's group inoculated house sparrows, European starlings and pigeons with four strains of H5N1 that were isolated in 2004 - 2006.
Hi path H5N1 was first found in poultry in southern China in 1996. It is lethal to chickens and other poultry. Ducks are usually unaffected, although some strains are lethal to ducks as well. The combination of poultry movements and movement of infected aquatic wildfowl have spread hi path H5N1 widely to poultry and birds from Asia to Europe to the Middle East to Africa. Most affected birds are poultry species like chickens, turkey, ducks and quail, but on occasion other birds have been found infected, including budgerigars, finches, mapgpies, tree sparrows, pigeons and a crow. The St. Jude study looked at three small landbased birds to get a better handle on the biology of the virus in these common species.
Sparrows, starlings and pigeons were inoculated with one or more of four H5N1 isolates to test their susceptibility to infection and see how much and how long they shed virus if infected. They also co-housed uninfected birds of the same species with infected ones to see if there was transmissibility. Two of the viruses were isolated from a duck and a quail in Thailand in 2005. The other two were obtained from dead wild birds, a Common Magpie and a Japanese White Eye, whose corpses were collected in early 2006 when Hong Kong intensified surveillance.
The sparrows fared poorly. All or most died within a week, with high viral loads in brain and lung. None of the starlings or pigeons died, but all of the starlings were infected and some of the pigeons, depending upon the virus. The virus isolated from the Common Magpie had the broadest host range, infecting all the sparrows, starlings and pigeons, but the duck virus, so lethal to the sparrows, could not be recovered from inoculated pigeons. There was no evidence of any transmission between birds of the same species, the place were transmission would be most likely. One instance of transmission was seen in starlings but couldn't be repeated with additional trials.
The authors observe that these experiments show pigeons, starlings and sparrows more susceptible to these recent H5N1 isolates than they were previously reported to be to an earlier 1997 isolate. They suggest this is consistent with the wider host range of the recent viruses, including mice, ferrets and cats. The evidence that host range has increased is still scant, however. They conclude:
A critical question concerning these small avian species is whether they can serve as intermediate hosts or reservoirs for influenza (H5N1) viruses and transmit them to poultry and mammals. Sparrows were highly susceptible to influenza (H5N1) infection; however, they did not transmit to sentinel contact birds, despite a relatively low infectious dose . . . and the fact that virus was common in drinking water and fecal samples. Although it is possible that the high pathogenicity of these viruses prevented bird-to-bird transmission, the data suggest that this species can act as an intermediate host and potentially transmit to both poultry and mammals but not serve as a reservoir for prolonged shedding of highly pathogenic influenza (H5N1) viruses. In contrast, the characteristics of influenza (H5N1) infection in starlings, i.e., nonfatal with longer-term shedding, suggest that starlings could act as an intermediate host and a reservoir for influenza (H5N1) virus. However, evidence of transmission to contact starlings was limited, which implies that these strains are unsustainable in a starling population. Because pigeons shed only low amounts of virus upon infection and they did not transmit to contact birds, their role in the ecology of influenza (H5N1) virus may be minor.
Our results indicate that there are considerable differences in susceptibility to influenza (H5N1) virus among various small terrestrial wild bird species. The high virulence of several recent isolates in sparrows suggests that this and other populations of small terrestrial birds may have substantial losses during current and future outbreaks. Further mutation of circulating influenza (H5N1) viruses might enhance their adaptation to hosts such as starlings and sparrows, further increasing virulence or allowing these species to become efficient intermediate hosts in the ecology of influenza (H5N1) viruses. (Boon et al., Emerging Infectious Diseases, [Epub ahead of print])
We agree that whether these birds or other animal species can serve (or do serve?) as a reservoir for this virus is a critical question. Given the variability in response seen here and the small number of animals, experiments and isolates, we think it premature to dismiss the possibility of small land birds as a reservoir. All that can be said is that these experiments do not show evidence this is currently or potentially the case. But the authors acknowledge the experiments are extremely limited.
Still, this is the kind of work that urgently needs to be done, not just in birds but in other possible reservoirs and intermediate hosts (usually a transitory or secondary host as a vehicle for an agent moving between one host and another). What about other small mammals, reptiles, even arthropods?
So many questions. So little time.
The Editors of Effect Measure are senior public health scientists and practitioners. Paul Revere was a member of the first local Board of Health in the United States (Boston, 1799). The Editors sign their posts "Revere" to recognize the public service of a professional forerunner better known for other things.
The boy from the Jakarta suburb of Tangerang started to developed bird flu symptoms last week, and reportedly had contacts with infected chickens, the ministry said in a statement.
His case brings total bird flu cases in human in Indonesia to 109, with 87 deaths or the highest among other affected countries.
HANOI, Oct 11 (Reuters) - Bird flu returned to southern Vietnam this week after an absence of two months...
Tests performed at a laboratory for the Mekong delta region confirmed the H5N1 virus in the samples taken from ducks at the farm in Tra Cu district in Tra Vinh province, Tien Phong (Vanguard) newspaper said.
At least five ducks were dead among 300 at the farm, officials said.
Agriculture Minister Cao Duc Phat on Tuesday urged animal health authorities to step up vaccinating poultry because bird flu would soon return among unvaccinated birds, especially as the weather cooled in autumn and winter in northern provinces.
We don't actually know how long a pandemic can last, but we do know the Spanish Flu of 1918 lasted at least 18 months. I say `at least' because there is at least some evidence it may have lasted longer.
indigo girl
5,173 Posts
Canada
What is wrong with this picture. If I lived in Canada, I would be very, very
concerned.
http://crofsblogs.typepad.com/h5n1/2007/10/canada-need-cle.html
Via the Globe and Mail: Need cleanup funds, say owners of farm closed
by bird flu.
Frankly, I can't understand it either. Just because they are a small enterprise, like it does not affect anybody else in that country?
Not good for public health, and not good for the poultry industry...
UPDATE
Well, U.S. Customs in this country was concerned also:
http://www.startribune.com/462/story/1459331.html