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.
Up to now, scientists believed it was a genetic switch in the virus that allowed it to bind to human rather than bird receptors, thus making the much-feared "species jump" possible.
But the study, led by Massachusetts Institute of Technology (MIT) professor Ram Sasisekharan, says that the big factor is the shape of the sugar receptors in human lung cells.
The human alpha 2-6 receptors come in two shapes, one broadly resembling an umbrella, and the other a cone. To infect humans, flu viruses must bind to the umbrella-shaped receptors, the researchers found.
Ilaria Capua, veterinary expert at an OIE laboratory and eminent member of the OFFLU network, wins the “ Scientific American 50” award
Dr Ilaria Capua, veterinary expert at the OIE Reference Laboratory for avian influenza, based in Padova, Italy, has won the “ Scientific American 50” award, a prize awarded annually by this prestigious scientific magazine to researchers and firms around the world that have made a significant contribution to advances in the field of science, technology or economics.
Dr Capua receives the award for her commitment to the exchange of avian influenza virus strains, samples and genetic sequences, a crucial component of the worldwide surveillance and control strategy for the disease.
The OIE/FAO Network of Expertise on Avian Influenza (OFFLU), of which Dr Capua is Secretary General, was set up specifically to develop research on avian influenza, monitor H5N1 strains worldwide, exchange isolates between animal health laboratories, human health laboratories and the relevant reference laboratories, and then publish the genetic sequences in publicly accessible databases. This is a vital step in enabling human vaccines to be developed as early as possible in the event of a pandemic.
The man...is part of a large family of brothers involved in a cluster of confirmed, probable and suspect cases. The other surviving brothers live in Pakistan's North-West Frontier Province.
...the World Health Organization believes there was limited person-to-person spread of the virus among the relatives.
One member of the family, a veterinary worker, fell ill in late October after helping to cull H5N1-infected poultry...at least two of his brothers nursed him
The veterinary worker survived but the two brothers died, one in mid-November and the other on Nov. 28. The first man to die was never tested for H5N1. But a specimen taken from the second showed he was infected with the virus. Another brother was also ill and was hospitalized. Still another showed no signs of illness.
The brother from Long Island experienced mild cold-like symptoms after returning from Pakistan. And his young son, who did not make the trip with him, also had a cold; it appeared to get worse after his father's return.
The U.S. Centers for Disease Control even sent a plane to New York to collect specimens from the man and his son for testing in the CDC's Atlanta labs.
They were both negative. But, a negative test isn't proof positive there was no infection. A test taken too late in the course of an infection could come back negative.
To close the book on the incident, authorities collected blood samples from the man and the son to look for the antibodies that would be present if they had been infected with the virus. Both the father and the son were negative in antibody testing.
Whenever confirmed human cases of bird flu appear in an area there usually follows heightened sensitivity to new cases of severe pneumonia. Are they bird flu too? Severe pneumonia is pretty common, so you can't automatically assume that "if it quacks like a duck and walks like a duck it must be a duck." It turns out there are a lot of birds that look like ducks that aren't ducks, at least when it comes to influenza-like illnesses. On the other hand, "testing negative" with PCR, which on its own is a pretty sensitive and specific test is also not foolproof. "On its own" means under the best conditions. But the conditions in the field aren't usually the best. Specimens can be taken too late, taken improperly, masked by antiviral treatment, stored improperly, analyzed improperly, etc. So false negative tests do happen. Let's pause to think about testing more generally.
There are two measures of the accuracy of a test: its sensitivity and its specificity.
Sensitivity is the probability that a test will actually pick up that a person is infected (how "sensitive" is it to detecting a signal that's really there).
Specificity is the same thing but for the absence of infection: what is the probability that an uninfected person will be correctly classified as uninfected.
A false positive results from a test that is not 100% specific.
A false negative from one that is not 100% sensitive.
For any test it is always possible to make them either 100% sensitive or 100% specific.
In fact it's trivial: either call all tests negative or all tests positive, respectively.
Yes, in the first case you got no false positives and in the second no false negatives, but this strategy usually isn't very helpful. Of course if the test is perfect (100% sensitivity and at the same time 100% specificity) then you are home free.
Usually tests aren't that good, either on their own or because of the other ancillary conditions (like imperfect specimens or storage or whatever). Then you adjust your test conditions so that you get the best result you can in terms of the mix of false negatives and false positives. In doing this you may take into account the relative "costs" of the two kinds of mistakes, false positives and false negatives.
For any particular test and its conditions of application you will almost certainly have less than 100% accuracy (on both measures). So there is a cost.
You can either decide to ignore the consequences of your mistakes or decide that the cost of a false negative, for example, is too severe in terms of the risk of missing an infected person that you want to invest more effort into confirming it wasn't a mistake.
If the cost is high in terms of money or use of resources you won't confirm every negative test, especially if there are a lot of them as there are for influenza-like illnesses.
But for those where the index of suspicion is high (for example a symptomatic contact of a confirmed case) you may go ahead and do some follow-up testing. For H5N1 the most common way to do this is to examine paired acute and convalescent sera to see if there is the development of antibodies to H5N1 which would indicate recent infection. This requires getting a blood sample at the time of the initial negative test and another one several weeks later.
Here's an example of its use in the recent Pakistani cases:
Blood testing has confirmed that a U.S. resident whose brother was Pakistan's first confirmed case of H5N1 infection never contracted the disease.
The New York State health department revealed that the man's blood showed no antibodies to H5N1, indicating he had not caught the virus while attending his brother's funeral in Pakistan late last year.
"His final test came back. He showed no avian flu and no antibodies to avian flu, which means he never got it," Claudia Hutton, the department's director of public affairs, said in an interview from Albany.
[snip]
The brother from Long Island experienced mild cold-like symptoms after returning from Pakistan. And his young son, who did not make the trip with him, also had a cold; it appeared to get worse after his father's return.
The man went to his doctor, the doctor notified local public health authorities and they in turn alerted the state. The U.S. Centers for Disease Control even sent a plane to New York to collect specimens from the man and his son for testing in the CDC's Atlanta labs.
They were both negative. But, a negative test isn't proof positive there was no infection. A test taken too late in the course of an infection could come back negative.
To close the book on the incident, authorities collected blood samples from the man and the son to look for the antibodies that would be present if they had been infected with the virus. Both the father and the son were negative in antibody testing.(Helen Branswell, Canadian Press)
There is also no guarantee the confirmatory tests are accurate either. What if it is possible to be infected but not show the particular antibody that is used for follow-up testing or the confirmatory test is itself insensitive or poorly done or . . . ?
While there is no guarantee it would mean that both tests (the first one and the follow-up) would have to be wrong. The probability of this is presumably less than just the probability of the first test being wrong so you are still ahead. But it is still a possibility and depends on the second test having a reasonable specificity.
The problem of test accuracy is common to many disease outbreak investigations. False negatives and false positives are particular to tests and test settings. As the tests get better and easier the accuracy improves, so we are not stuck with the same level of false positives and negatives forever and all time. Still, we need to interpret test results in the light of what is known about the test's accuracy and that requires information that is not always ready to hand.
Decision-making under conditions of uncertainty is a fact of life. Since this requires judgment and not just the application of some mechanical algorithm, questions of transparency, trust and credibility now enter the mix.
Need I say more?
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.
In previous cases, human errors such as contaminated transport or feed were found to have caused outbreaks of the disease in birds.
The mute swans had not migrated into Britain - when they do fly, they normally travel very short distances. It appears likely they caught the virus from other wild birds or ducks that came into the swannery for the winter months.
Tests being carried out at government laboratories will reveal whether the birds had a highly dangerous form of the virus, categorised as "low pathogen" or "high pathogen".
The Abbotsbury swannery is a highly popular visitor attraction in the summer, and was originally set up during the 1040s by monks in Dorset who regarded swan meat as a great delicacy. Close to the south Dorset shore, it consists of different pools in which swans can feed and breed. From mid-May to late June, hundreds of fluffy cygnets hatch from eggs in nests on or near the pathways.
three dead swans found on a nature reserve in dorset were today found to have been carrying the lethal strain of bird flu, sparking fears that the virus had again landed on britain's shores.
urgent tests were under way to check the other birds and ducks at the swannery in abbotsbury, where the dead mute swans were found in the past 48 hours. the department for the environment, food and rural affairs (defra) was expected to issue a statement later this today to confirm that the h5n1 strain had been found in the birds.
the above comments strongly suggest that the uva lake strain of h5n1 in wild birds in england will be announced shortly. 48 hours is enough time to confirm h5n1, and wild waterfowl are generally resistant to avian influenza. however, dead mute swans are frequently killed by h5n1.
the earlier outbreak of h5n1 in free range turkeys indicated h5n1 was flying around undetected in england. the turkeys were infected with the uva lake strain, which had been found in wild birds in germany, the czech republic, and france over the summer. it was then found in a whooper swan in krasnodar in september. more recently the outbreaks in northern germany and romania have involved the uva lake strain, strongly suggesting that outbreaks in poland and rostov will also be the uva lake strain.
thus, it is increasingly clear that h5n1 has spread throughout europe, and those countries that have not reported h5n1 in recent weeks have a poor surveillance system.
this will be the first time defra has found h5n1 in a wild bird that did not wash up on its shores, as happened in scotland two years ago (those sequences were just released, almost two years after collection). defra, like most surveillance systems in europe have yet to find h5n1 in live wild birds, further confirming major limitations in the surveillance system. in addition to failing to detect h5n1, these agencies hoard the sequence data. defra has not released the sequences from the earlier outbreak in suffolk, and weybridge is still holding sequences from october, 2005 from the outbreak in romania. similarly, weybridge, acting as a who regional center, is mailed samples for europe, the middle east, south asia, and africa, and continues to hoard the sequences.
the time for release of the data has long since passed.
positive confirmation of highly pathogenic h5n1 in uk swans
LONDON (Reuters) - Governments around the world need to do more to prepare for the dramatic economic impact of the next flu pandemic, the United Nations influenza coordinator said on Thursday.
The bird flu center's Suyono said that two months before she fell ill, several chickens in her neighborhood had died suddenly.
"She also ate three eggs half-cooked two weeks before getting sick... The eggs might not have been washed properly before being cooked," he said, referring to the fact that chicken faeces, which can carry the virus, may have been on the shells.
But Suyono said that the health ministry had not yet confirmed whether the chickens in her neighborhood had tested positive for the virus.
In news reports yesterday, Dr. Bernard Vallat, director-general of the Paris-based OIE, was quoted as saying that the H5N1 virus is "extremely stable," implying that it is unlikely to evolve into a human pandemic strain.
In interviews today, experts such as Dr. Kathy Neuzil, MD, chair of the Infectious Diseases Society of America's (IDSA's) Pandemic Influenza Task Force, countered that the virus has been known to mutate many times already and that both science and history suggest it still represents a very real threat.
Accounts from the Associated Press (AP), Agence France-Presse (AFP), and Reuters offered somewhat different versions of Vallat's comments, with the AP making him sound the most reassuring—or complacent.
According to the AP, Vallat said, "The risk [of a pandemic] was overestimated." Concern a few years ago about a possibly imminent pandemic represented "just nonscientific supposition," he said.
An AFP account focused on Vallat's statements about the stability of the H5N1 virus. "We have never seen a virus which has been so stable for so long," Vallat was quoted as saying. "Compared to other viruses, it is extremely stable, which minimizes the risk of mutation" into a pandemic strain.
He also said the virus is endemic in Indonesia, Egypt, and to a lesser extent Nigeria, according to AFP. "If we could eradicate the virus in those countries, the problem of a pandemic from Asian H5N1 would be resolved," he asserted.
But the Reuters report depicted Vallat as more cautious. "We notice that the virus is now extremely stable but there is no base to say that the H5N1 will not mutate," he said. "Bird flu will always remain a risk, be it H5N1 or another."
Despite the somewhat conflicting accounts, the other experts asserted that Vallat was sending the wrong signal.
"The main message that should be out there is that the threat is real," said Neuzil, senior clinical advisor with the nonprofit organization PATH in Seattle.
She and others pointed to the recent history of pandemics.
Anyone who has been following the information on these panflu threads
would probably remember reading many times about the different
changes that H5N1 has made. One human case in Egypt had a strain
of virus that had acquired M2301,a piece of viral information that is
found in all human influenzas.The finding of this single nucleotide
polymorphism (SNP) was a very unpleasant surprise.
Look at what Dr. Robert Webster, the pre-eminent influenza research
scientist at St. Jude has said about H5N1 back in 2005:
"How pathogenic is it, how bad a virus is this one?" The prototype of these viruses is called Vietnam H5N1. If we inoculate this virus into chickens this afternoon, they're all dead tomorrow morning. It's a real killer. It kills ducks in one to two days, high risk of death in humans, with diarrhea, respiratory signs, and neurological symptoms. Diarrhea and neurological symptoms are not standard flu.
If we put these viruses into ferrets, the animal that we classically use for working with influenza, [in which] influenza usually causes a mild infection, respiratory [signs], and a high fever. This [virus causes] respiratory signs, diarrhea, hind leg paralysis, and they die. This is the first one of these influenza viruses that kills the ferrets--spreads throughout the body to the brain, and they die with paralysis.
These are extraordinarily bad viruses. I've worked with influenza all my life, and these are the worst influenza viruses I've ever seen.
What about pigs? We mentioned earlier on that the pig probably plays an important role in getting these viruses across from the avian reservoir to humans, and I should point out, at this time, the only characteristic this virus doesn't have is its ability to transmit human-to-human. It transmits from the chicken population to humans and kills a high percentage.
What this virus hasn't learned to do yet is to transmit from you to me, me to you. If it learns that trait, then we're in terrible trouble, and we ask this question: Would these viruses replicate and transmit in the pig? Because that would an indicator of what's happening.
We put a human, a chicken, a duck, a goose virus into pigs in our isolated facilities. We put two pigs in a cage, and the virus infected every one of the pigs, but it didn't transmit. The virus hasn't got the characteristics of transmissibility, and there is a tendency, at the moment, to think what's been done since 1997. It hasn't learned to transmit yet. Well, we can forget about it--it's not going to do it.
Don't believe it. This virus is going to learn to do it. Historically we can go back to Helen of Troy. We've seen influenza all centuries, and we've had the privilege, if you like, of watching this one evolve very slowly from 1997-acquired new characteristics, and it's probably going to do it . . .
[sick chickens were fed to tigers and leopards in Thailand, they all died . . . [a] group in the Netherlands fed the infected chickens to domestic cats, they died. [They] not only died, they transmitted . . . cat-to-cat. Many people in this room have cats as pets. If this virus gets away, that's going to be another animal for transmitting.
A Indonesian woman from an area just west of the capital Jakarta has died of bird flu, taking the country's confirmed human death toll from the virus to 95, a health ministry official said on Monday.
The 32-year-old woman from Tangerang died at her home last Thursday after her family had taken her out of a hospital where she had been receiving treatment a day before, said Suharda Ningrum of the health ministry's bird flu centre.
indigo girl
5,173 Posts
How Humans Get Bird Flu
To understand how influenza viruses attack humans, you have to have some
knowledge of the Receptor Binding Domain (RBD). The first essay from
Avian Flu Diary is here, in case you missed it:
http://afludiary.blogspot.com/2007/12/rbd-looking-for-sweet-spot.html
Now there is some new research just released about the RBD, and how
viruses make that jump from one species to another:
Receptor Binding Domains: Take Two
http://afludiary.blogspot.com/2008/01/receptor-binding-domain-take-two.html
http://web.mit.edu/newsoffice/2008/bird-flu-0106.html