The venerable and slightly right-of-center (but excellent, nonetheless!) British publication, The Economist, has taken note of the Indonesian decision to release the bird flu sequences. [NB: also see Addendum, after the continuation below the fold. The Peiris and Guan labs in Hong Kong are now fully open on sequences. Kudos to them. Additional note: Excellent article by Helen Branswell here on the same subject.]
"For the sake of basic human interests, the Indonesian government declares that genomic data on bird-flu viruses can be accessed by anyone." With those words, spoken on August 3rd, Siti Fadilah Supari started a revolution that could yet save the world from the ravages of a pandemic disease. That is because Indonesia's health minister has chosen a weapon that may prove more useful than today's best vaccines in tackling such emerging threats as avian flu: transparency.At the moment, the world's pandemic-alert system is distressingly secretive. Some countries, such as Vietnam, have been fairly open about new outbreaks of the sorts of infectious disease that might lead to pandemics, and have even invited foreigners in to help diagnose the problem. Most, however, have not been so forthright. Public-health experts point to China and Thailand, both of which suffered outbreaks of potential pandemic illnesses in the past few years (SARS in China and avian influenza in Thailand) as examples of places that do not fully disclose the relevant details. (The Economist)
Now the pressure is on others. China and Thailand have been mentioned as other countries who have failed to provide isolates and sequences. The Economist notes one reason for their reticence: desire to protect export and tourist revenues. These countries should be considered infected unless they make a satisfactory showing, with provisions for international inspection and verification, that they are not. The incentives should be toward openness, and one way to do this is to assume guilt unless there is satisfactory transparency to assure innocence.
It will also mean, however, that those demanding transparency also be transparent. This includes scientists. We think The Economist has it right:
The least defensible motive is vanity. Individual researchers, academic institutes and even national governments want the glory and research funding that come with solving the puzzle of a new pandemic and being first to publish. In this, developing countries are not alone. America's Centres for Disease Control (CDC) also restricts access to some of the genetic data that it has analysed from various parts of the world.
A sizable number of scientists recognize this. In 2005, organized by the UN's Food and Agriculture Organization (FAO) and World Organization for Animal Health (OIE) into a group called OFFLU , they pledged to make their expertise and genetic sequence data available to the world scientific community. Headquartered in Italy and including avian flu luminaries like Ilaria Capua, whose public plea to her fellow scientists to make sequences available was a notably forthright statement, OFFLU is a model for how scientists should behave.
We're getting there, but not fast enough. It is time for the flu virology community to make a statement on the matter of transparency.
Addendum: Henry Niman notes that Peiris and Guan in Hong Kong are now depositing sequences immediately. We are in a remote location with limited access so we appreciate this update from Henry. This is dramatic progress.
First, kudos to Peiris and Guan. Now let's get all your colleagues on board, at CDC, St. Judes, Mt. Sinai and elsewhere.
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Niman said today in his post, these sequences show the source for human H5N1 infections in Indonesia is not poultry; and that the source in unknown, but may reside in one or more mammals. The only blood match is a cat.
And in a recent report today on a girl in Indonesia infected with H5N1, it says the source was probably her pet pigeons; and they are examining poultry in the area to see if it is infected.
In the 1918 Spanish Flu Pandemic, some people carried a rabbit's foot or a lucky charm to protect them from the deadly virus.
And now, leaders in Indonesia do the equilivant of carrying a lucky charm, by looking for sick chickens.
The H5N1 virus that is infecting humans in Indonesia is
probably not to be located in sick chickens, since the avian strains of H5N1 do not match the human strains. It may reside in some mammal strain, and animals in the areas impacted should be immediately tested.
The medical community should be admired for their stupidity and ignorance, by ignoring the scientific evidence that the source of H5N1 in humans in not chickens. This is equilavent to those insisting the world is flat in past centuries, even though the scientific evidence indicated it was not flat.
Hi Revere,
I'm moved from a months-long silence by your description of the Economist as "slightly right of center." When i actually have a coherent opinion about anything beyond my desk, it is informed by the Economist. I don't personally know anyone who reads the Economist. I'm in a sort of exile here in (apparently ultra-conservative and anti-intellectual) Dallas/Fort Worth, and have found my thoughts about nearly everything to be objectionable if not disturbing to the humans I do encounter. Including, most especially, those most surely gleaned from the Economist. When i make the mistake of worrying about "asset bubbles" and "the current account deficit" aloud, I might as well be taking bird flu seriously--aloud. I, myself cannot tell that the Economist is slightly conservative under these circumstances. Indeed, I suspected it was otherwise. Especially since I have never found myself going "hey, wait a minute here!" while reading it.
So I write with two questions for you: 1) Is your assessment of the Economist's slight bias personal or conventional wisdom? 2) Do you know of an good source of news that is known to provide a "slightly left of center" balance to the Economist?
Thanks!
Suzanne
Transparency is one good thing. But an example of punishment is how the publication of an outbreak of a low pathogene H7 strain in the Netherlands is received in other countries. Although it was tested and contained as quickly as possible and poses no threat anymore, Russia, Phillipines, Singapore, Taiwan and Hongkong now have put a ban on Dutch chicken products. It takes a lot of diplomacy to get back to business with these countries.
On the other hand the Dutch Institute for Animal illness control is now looking for a link between the outbreak recently and that in 2003. I think that is sensible too.
I knew a lot of people in the first half of 2003 who had some kind of terrible flu and developed a pneumonia at the end of it. My suspicion is that many people in 2003 who were infected with H7N7 were not detected.
I won't forget to thank Indonesia, and those labs of Peiris and Guan for releasing their sequences!
Thank you for that and I wish you all will cooperate when new information is coming forth in the future about Avian Influenza.
As evidence I'll note that they endorsed Bush for president in 2000, and endorsed Kerry in 2004 with a heavy heart (it was more of a "he's not as bad as Bush" endorsement).
revere, I think you have an unclosed bold tag in the addendum to your post.
Davis,
'nuff said! My excuse: I've only been a subscriber since '04.
The Economist should obviously be praised for the publication of the report on the release of the sequences.
And the Jakarta Post should be praised for the publication of the following statement in an editorial today:
In refering to the struggle in Indonesia to eliminate the virus, "And if the fight means killing the virus hosts-our beloved pet birds, chickens, ducks, and other carriers-then there should be no hesitation."
The above statement in profound in its meaning in a culture where pet birds, and other fowl are loved as we in the West love our dogs and cats. It represents a terrible sacrifice for the Indonesian people.
And the above statement refers to other hosts. What other hosts? Of course the culling of fowl is a good thing, in that it may stop the virus from mutating into a form that is transmissible to humans.
But what do we in the West do, especially if the virus arrives in the US; if it is scientifically proven, beyond a doubt; as Niman may now be saying; that the source of human infection is not in poultry. What if it is determined that dogs and cats are the source of human infection, or some other mammal? And if dogs and cats are proven to be the source, you may see an editorial in the New York Times that reads:
"And if the fight means killing the virus hosts-our beloved dogs,cats, and possibly our pigs, the latter being an important food source-then there should be no hesitation."
In my previous post today I implied that the culling of chickens is a bad thing because it may not be removing the source of human infections with H5N1. But of course culling
birds may stop the virus from mutating into an H2H form.
A note of caution re Indonesian human and poultry conclusions. The human sequences have been released first and shown a fairly clear split into two groups most readily defined by thier cleavage sites. The 'traditional' RERRRKKR and the novel RESRRKKR found in the Karo cluster. Thier are not many '05/06 poultry sequences out yet and they provide a good match for the RER human cases but the only non-human RES type released so far was for a cat. There has been a large sample release to Australia but until all of these are sequenced and released it may be hasty to conclude RES is not common in poultry. If Dr Niman, Revere or others disagree with my conclusions I hope they will post and explain where I am in error.
I may be wrong here also but my understanding was that Karo, interesting enough, since it had possibly the best example of h2h2h (although we haven't actually seen the sequence from the uncle that apparently had multiple polymorphisms)still had the RER cleavage site and a more close relation to poultry.
The lower branch mostly from West Java, Jakarta area, I think has the novel RES and is not yet showing the clear relation to poultry. I think this branch also has the cat sequence and is the potential vaccine candidate.
We shouldn't be talking about bird flu. We should be talking about pet flu.
Revere,
I just read you post, where among other things you said:
"...there are many avenues that urgently need exploration,
cats being one of them. There are currently not enough hands to do all of this. So we better hope we get lucky in the avenues we go down. Your concern with cats is just one."
And I thought my campaign to do cat research was a great idea. But my supposed brillance faded into deep humility when you said "we better hope we get lucky."
And of course, if I were to ask you what happens if we are not lucky, and go down the wrong avenues? I think you might say you do not know.
And if you say you do not know, then let me answer the question.
There are indications the virus may be mutating into a form that is infecting mammals exclusively, and this mammalian vector may now be infecting humans, which could eventually lead to H2H. Of course, all this requires more researh and time to verify. And we may very soon run out of time.
Thinlina,
"We should'nt be talking about bird flu. We should be talking about pet flu."
Your statement is the best summary of the problem I have read in a long time. But I would recommend one slight change.
We should be talking about mammal flu, based on recent evidence regarding the sequences submitted from Indonesia.
And the mammal may not be a pet. For example, the vector could be the rat. And I think this is one of the avenues that should be explored. If it is the rat, it would be called rat flu.
And then any report regarding the death of an H5N1 infected patient would state: "He or she was killed by rat flu. And he kept pet rats, so that may be the source of infection. And public health officials have gone down into the sewers of Jakarta, looking for H5N1 infected rats, in order to cull them. And if you happen to wander down into a sewer in Jakarta, and you find any rat that appears to be sick, you should capture it and take it in to your local hospital for analysis. And if the rat bites you, then of course, you will have to be hospitalized. But it is you duty to capture those sick rats. And if you refuse, you will be incarcerated."
william :D "But it is you duty to capture those sick rats. And if you refuse, you will be incarcerated."
I thought about the name "mammal flu" too, but I think it's not as informative about the psychosocial threats and consequences as "pet flu" would be. "Pet flu" isn't quite as accurate as "mammal flu", but it would suit media better and give people a near enough viewpoint.
thinlina,
Yes, I agree. Pet flu is the best way to describe a monster H5N1 on the loose.
JJackson, Although there are no 2006 avian sequences available at this time, I do not expect a match with the human sequences with the novel cleavage site. The novel sequence was present in the first human isolate, which was circulating in July, 2005. That isolate had a number of additional polymorphisms in HA as well as the other seven gene segments that were not in any Indonesian poultry isolates. There have already been a good number of 2005 sequences published. Most do not have the isolation date available (other than sometime in 2005). The CDC just released two sequences with Oct isoaltion dates, and the first 6 Indoensian bird isolates from Australia have been released. Like the earlier 2005 isolates, these newer sequences do not have the the polymorphsisms that were human specific in mid-2005 (many of these polymorphisms are found in other isoaltes, including mamamlian, but are not in Indonesian poultry).
The more recent human sequences have additional polymorphsism not found in the Indonesian poultry. Some of these may show up in 2006 poultry isolates.
However, finding the human specific sequences in human cases on Java was not difficult. The majority of the human specific polymorphisms were found in ALL human H5N1's but none were foiund in ANY avian H5N1 (i believe the number of human speciic polymorphsims is in the range of 25-30 - there were 11 in HA alone.
The segregation is quite dramatic and therefor indicates the source of the H5N1 in humans is not domestic poultry. There are no Indonesian wild bird sequences that are public, and the only mammalian sequence is from the cat, and it is a "match" and contains the "human specific" sequences.
Thus, I do NOT expect to see the human sequences at high frequency in poultry. Some sequences may appear, but those are likely to infect poultry FROM the alternative reservoir, which is also the source for human infections. The human specific sequences include a number of polymorphisms also found in wild birds (and interactions between these birds and various species are like to be diverse).
Dr Niman, You mean like those wild birds flying around pigs on the farms (sorry my language)?
BTW, how many polymorphic mutations are supposed to happen during one H2H? If one per one, would 30 human specific polymorphisms meand the virus had passed from person to person about 29 times?
THEORY
As I've said for many, many months on this site, the source of virus in an increasing number of cases especially Indonesia, is not chickens. What I find interesting is that the new sequences have not so much been released because of public pressure, but because most likely they are scared that the new cleavage site and sequences from human isolates bear a lot of divergence from avian sequences. I wonder how long it will finally take to sink in that chickens are not the only source of infection.
Okay then, what is? Cats? We're looking for a source now that has been an independent source for quite some time. Thats means that the H5N1 population in this source has been evolving independently for some time. I don't think it's cats. Cats might be getting their infections from the source, in which case, they're collateral damage. Because of the case in which the sequences from a cat and human in Indonesia are the same, it's tempting to think the human got it from the cat. Possibly, but cats are still probably not the source. This brings us to another major question. Is the H5N1 causing major pathological consequences in the source species, or is the source species merely a carrier--a repository?
I did some research on chicken mites and lice, and ruled them out on the basis that they don't have the ability to survive/interface much with humans or other mammalian species.
Let's go back to SARS. Sometime after the outbreak, civets were thought of as the SARS repository. This was true, but they were not the ultimate repository; it was probably Chinese horseshoe bats Lau et al., 2005. (see also Woo et al., 2006).
In addition, John Stavrinides & Guttman's work suggested a recombinomic event between an avian and mammalian source in the S gene: "Irrespective of its taxonomic grouping, it is clear that the SARS coronavirus is a mosaic, with at least two distinct evolutionary histories. Our analyses indicate that the SARS coronavirus is mammalian-like through the replicase protein, and avian-like through the M and N
proteins and that there is a mammalian-avian mosaic in the S protein. The gene encoding the S protein lies between the
replicase gene and the M and N genes. We propose that a
recombination event likely occurred within the S gene, as demonstrated by our bootscan analysis. Since the S protein is responsible for host specificity, this event may have been the critical step in the switch to a human host and the subsequent emergence of this new pathogen."
Could this event have happened in bats? Were they the mixing vessel in this case? Possibly.
Back to H5N1. First we have to rule out that other flu strains (H1, etc) might be contributing to these new polymorphisms in Indonesia. I haven't done that. I don't think this is the case, but it needs to be checked. Now that we have some H5N1 sequences, we can do that. There has been a "seasonal" flu outbreak going on for quite some time in Indonesia, so strains causing the "seasonal" flu might have had an opportunity to mix in humans. Let's suppose we don't find any matches. What next?
We need to be thinking about a source, possibly mammalian, that can come into contact with humans, cats, or our other furry friends, or even domestic cattle, pigs, periodically. This source probably does not interface with birds or chickens. My guess is that it is probably a bat, but not necessarily.
I would argue that "pet flu" is the WRONG name to use in America. We love our dogs & cats here, and we have a strong anti-authoritarian streak in our social history. Remember the people who wouldn't leave New Orleans after Hurricane Katrina because they wouldn't abandon their pets? Start talking about "pet flu" in America, and you're going to polarize the debate along an already dangerous fracture line. Some portion of the general public will be stalking around threatening to shoot the neighbor's seeing-eye dog and granma's two apartment-bound kittens, and a (probably much larger) portion will be stockpiling kibble and shutting down any further discussion of means & methods.
One reason the "bird flu" discussion has advanced as far as it has here is that most Americans DON'T have a strong emotional reaction concerning birds... we eat some of them, we like to see them at our feeders, we may know someone who keeps a parrot, but we don't have strong emotional ties where we say birds "are just like part of the family". If you think non-compliance with local chicken slaughter laws is a problem in far-away places like Indonesia, try thinking realistically about how well laws banning pit bulls work in America cities right now. Or the no-pets bans in the local housing project or your old college dormitory. And then call your local animal rescue and ask how many feral cats they're tracking, or how many "stray" animals get picked up by the neighborhood animal control department.
If you can't stand the phrase "mammal flu", I'd vote for "rat flu". Yeah, I know plenty of people keep pet rats, too, but rat lovers know enough about other people's prejudices that most of them won't automatically assume the worst about government policy.
THEORY
As I've said for many, many months on this site, the source of virus in an increasing number of cases especially Indonesia, is not chickens. What I find interesting is that the new sequences have not so much been released because of public pressure, but because most likely they are scared that the new cleavage site and sequences from human isolates bear a lot of divergence from avian sequences. I wonder how long it will finally take to sink in that chickens are not the only source of infection.
Okay then, what is? Cats? We're looking for a source now that has been an independent source for quite some time. Thats means that the H5N1 population in this source has been evolving independently for some time. I don't think it's cats. Cats might be getting their infections from the source, in which case, they're collateral damage. Because of the case in which the sequences from a cat and human in Indonesia are the same, it's tempting to think the human got it from the cat. Possibly, but cats are still probably not the source. This brings us to another major question. Is the H5N1 causing major pathological consequences in the source species, or is the source species merely a carrier--a repository?
I did some research on chicken mites and lice, and ruled them out on the basis that they don't have the ability to survive/interface much with humans or other mammalian species.
Let's go back to SARS. Sometime after the outbreak, civets were thought of as the SARS repository. This was true, but they were not the ultimate repository; it was probably Chinese horseshoe bats Lau et al., 2005. (see also Woo et al., 2006).
In addition, John Stavrinides & Guttman's work suggested a recombinomic event between an avian and mammalian source in the S gene: "Irrespective of its taxonomic grouping, it is clear that the SARS coronavirus is a mosaic, with at least two distinct evolutionary histories. Our analyses indicate that the SARS coronavirus is mammalian-like through the replicase protein, and avian-like through the M and N
proteins and that there is a mammalian-avian mosaic in the S protein. The gene encoding the S protein lies between the
replicase gene and the M and N genes. We propose that a
recombination event likely occurred within the S gene, as demonstrated by our bootscan analysis. Since the S protein is responsible for host specificity, this event may have been the critical step in the switch to a human host and the subsequent emergence of this new pathogen."
Could this event have happened in bats? Were they the mixing vessel in this case? Possibly.
Back to H5N1. First we have to rule out that other flu strains (H1, etc) might be contributing to these new polymorphisms in Indonesia. I haven't done that. I don't think this is the case, but it needs to be checked. Now that we have some H5N1 sequences, we can do that. There has been a "seasonal" flu outbreak going on for quite some time in Indonesia, so strains causing the "seasonal" flu might have had an opportunity to mix in humans. Let's suppose we don't find any matches. What next?
We need to be thinking about a source, possibly mammalian, that can come into contact with humans, cats, or our other furry friends, or even domestic cattle, pigs, periodically. This source probably does not interface with birds or chickens. My guess is that it is probably a bat, but not necessarily.
Anne Laurie, I agree partly with you. But I think that as long as the name of the flu is too distant from everyday emotional vicinity, we won't be able as a global community to prepare with an adequate efficiency. Hope that we will, but I think if the name of the flu (what ever it will be) doesn't touch home brewing and affectionate emotions, the world won't be moved as easily.
Just a thought.
Anne Laurie,
As you explained in a very concise and understanble way, there is no chance Americans are going to kill their cats and dogs.
And if it becomes clear dogs and cats are vectors; the only realistic solution is allow the virus to kill as many Americans as it can, and leave the animals alone. If this sounds cold blooded, it is because it is.
I too still like the term rat flu. It has a nice sound to it.
But in contrast to the Americans, it may be possible the Indonesians will realize what needs to be done, and proceed to kill the animals propagating the cat, rat, or dog flu to humans.
Marissa,
As to the source, I want it to be noted for all to see that I vote for the rat.
This is a little off-topic, but somehow this seems to be a good place to ask the question. The flu virus primer on the Flu Wiki is OK (I'm referring mainly to the item "Influenza Primer II"), but somehow I'm thinking there's maybe something even better?
Any suggestions?
ssal: LOL. Since I wrote it, I'm probably not the one to ask, but in my defence it was well over a year ago and I haven't looked at it since. What more would you like to see? Until Labor Day I'm not at a place where I can do much on it, but I'm willing to upgrade it.
And remember, it's a wiki, so anyone else can, too. That's what we envisaged when we started the wiki.
Hadn't I seen, last year, people were translating that some Chinese were calling H5N1 "the birds and beasts flu"?
Although, I think telling people to prepare 'Because
federal, state, and (perhaps) local authorities are not going to be able to help them if a "Killer Flu" pandemic happens'
would get attention "the bird flu" doesn't
(perhaps even promote public preparedness action?).
(That "bird flu" term seems to roll off some minds like water off a duck's back...)
marissa, It will only take about another month before it is crystal clear that the human cases are not from poultry. It is already pretty obvious, but some are grasping for the last straw by citing collection dates. However, 91 recent samples were sent to Australis, and the first six have already been published (atleast HA and NA have). I suspect another 1-2 dozen will come out in a week or two and when they don't match it will be pretty obvious. Another 1-2 dozen 1-2 weeks after that will seal the deal.
The existing data leaves little doubt. The first sequence with RES was last July. The second case followed two months later and it was RER. Proving that the RER was tightly linked to poultry was easy. Similarly, the Karo cluster was in mud 2006 and it too was easy to show a closer link to poultry than the RES sequences. Thus, failure to have 2006 or a karge number of late 2005 samples were no problem for the RER samples. Similarly, several of the first six samples from Australia link the Karo cluster to poultry.
Thus, poulty linkage was easy for two sets with RER, but not even close for all of the other human cases, which are RES. Similarly, the vast sequnece in early 2006 was easily identified as a match.
The human RES sequence is quite consistant and widespread. There are a large number of human specific markers that have been present for over a year. There are more showing up in the more resent samples. The human H5N1 is evolving independent of avian H5N1. It is slow but steady and the slow evolution mimics swine evoltion.
The surveillance in Indonesia is a joke. The Australian samples are "catch up" for the lack of poultry sequences in the past 12 months. There are no wild bird, or any mammalian samples except the one cat and there has been little testing of "seasonal flu" or dengue, or "thyphoid" patients.
There is quite a bit going omne in Indonesia, but it doesn't involve human or swine reassortants. Recombination remains the name of the game.
Dr. Niman The question Marissa raised was what is the teriary mammal host for H5N1 that is the bridge between birds and cats and humans?
One thing is sure, it is a common vector to birds and humans. Cats someone said might be a dead end carrier of it. But a dead end carrier can be for that species only and a massive vector for everything else. I agree though, they need to test EVERYTHING with more than one leg. Its a common but unrecognized thread. They might still be able to stop it. We are coming up on the beginning of the peak season and that typhoon ran everyone into close quarters this week. China could break with the superbug anyday. If we have the right information, it can still be stopped. Airborne bug bombers as we did with the Medfly population could slow it for sure. Blowflies? Might as well have said it was ants because we wouldnt be able to stop that on a good day.
Tom DVM, Since nothing is being tested, the reservoir could be anything, but pigs and humans are at the top of my list.
Dr. Niman Thanks.
Thinlina, there is a local tv commercial mocking the cluelessness of someone who doesn't listen to the right news station. Clueless is asked "Do you worry about bird flu?" and responds "Nah - just lift their lil wings & give 'em a shot!" If this is the consensus on "cute" names, maybe we want something scarier than "pet flu", which could suggest a cuddly companion virus?
William, I would never choose to keep pets (even my pets) alive at the cost of letting people die. However, creating a perception that "The Guvmint" wants to kill everyone's dogs & cats is not, in my opinion, a good way to focus Americans' attention on any useful course of action. Realistically, by the time any H5 pandemic reaches America, it's not going to be birds or pets or even rats we'll have to worry about -- it'll be OTHER PEOPLE. And, despite worst-case wargamming suggested by certain posters, I don't think Americans will even consider slaughtering any significant number of humans in an attempt to create a viral firebreak (if only because we aren't liable to have a window where such slaughter would work).
One possible advantage to "rat flu" is that most people have a vague memory of being told that the Black Death was caused by rats. This is one reason rats don't get good press; perhaps we can use the stereotype of disease-carrying vermin swarming out of the sewers as a way to focus public attention in a more productive fashion?
Tom, Since you are from Canada, you might want to check out one of the travel logs of one of the polymorphisms in the most recent isolates in Indonesia (where another case was announced this morning)
http://www.flutrackers.com/forum/showthread.php?p=24941#post24941
The latest case in Indonesia is a 17F confirmed at NAMRU and a second local facility. The case is fro, West Java, so it is unclear if this is one of the two cases reported several days ago and is in the news because the H5N1 has now been confirmed.
However, the more ominous statement quotes the WHO new policy of using two independent confiming local labs as sufficient confirmation. Thus, the samples may not be sent to the CDC or Hong Kong, and therefore the H5N1 won't be isolated or sequenced, and the flow of human sequence data from Indonesia may have ended.
From the Reuters report
"The teenager's swab samples will only be sent to a World Health Organisation-accredited laboratory if the health ministry thinks the specimens need further testing"
It might be useful to explain to Indonesia why it is important to keeep sequencing H5N1 positive samples from Indonesia (which are NOT from poultry).
I said the latest case was a 17F, but the report just says "youth" so it could be a male or female. However, the two recent cases from Jakarta suburbs were described as both 17 and 16 and involved both a male and female teenager.
kent nickell:
I think you are right the released Karo Sequences are RER apologies to all. I have not found a good way to relate sequences to people/places/case history/month etc. as this is not on the sequence data sheets I would be most graetful if any one knew of a database that tied the two together.
Henry Niman:
Thanks, as always, for the time you take to in responding to my posts.
ssal:
I had a crack at writing an introduction for my family which can be browsed at www.JCSonline.co.uk or - if useful- downloaded from Gujo's excellent collection of BF related docs. at http://www.mipodcast.com/H5N1/JJackson_Pandemic_Manual.pdf
To all:
Re transmission vectors - I had my doubts about mosquitos as an H5N1 vector but am now not so sure......
Mechanical transmission of porcine reproductive and respiratory syndrome virus by mosquitoes, Aedes vexans
Abstract
The objective of this study was to determine whether porcine reproductive and respiratory syndrome virus (PRRSV) could be transmitted to naïve pigs by mosquitoes following feeding on infected pigs. During each of 4 replicates, mosquito-to-pig contact took place on days 5, 6, and 7 after PRRSV infection of the donor pig. A total of 300 mosquitoes [Aedes vexans (Meigen)] were allowed to feed on each viremic donor pig, housed in an isolation room. After 30 to 60 s, feeding was interrupted, and the mosquitoes were manually transferred in small plastic vials and allowed to feed to repletion on a naïve recipient pig housed in another isolation room. Prior to contact with the recipient pig, the mosquitoes were transferred to clean vials. Swabs were collected from the exterior surface of all vials, pooled, and tested for PRRSV. Separate personnel handled the donor pig, the recipient pig, and the vial-transfer procedure. Transmission of PRRSV from the donor to the recipient pig occurred in 2 out of 4 replicates. The PRRSV isolated from the infected recipient pigs was nucleic-acid-sequenced and found to be 100% homologous with the virus used to infect the donor pigs. Homogenates of mosquito tissues collected in all replicates were positive by either polymerase chain reaction or swine bioassay. All control pigs remained PRRSV negative, and PRRSV was not detected on the surface of the vials. This study indicates that mosquitoes (A. vexans) can serve as mechanical vectors of PRRSV.
Also see the paper on blowflies - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&do…
Local Indonesian languare reports suggest that today's Rueters story is simply a confirmation of the earlier case(s). Moreover, the translation appears to indicate that neither sample will be sent out, and human H5N1 sequencing from samples in Indonesia may have ended:
"From results of this test of the Department of the Health of not sending results of the sample of blood both of them to the laboratory of the World of reconciliation of the Health Body (WHO) in Hong Kong."
The latest AP story gives more detail, indicating the latest case (17M) is from Garut in West Java and still alive, so this is the third lab confirmed case in western Java this month (the two earlier H5N1 deaths this week were from Bekasi and a Jakarta suburb).
However, the concern over the sequencing halt remains.
Dr. Niman. As I have said before, I have little knowledge of what you speak...but offhand, it would seem to me that there is a possibility that influenza viri have such a high mutation rate that the same mutation can occur over extended time periods in different sub-types in different places.
However, I hold to no particular theory and if you are right about recombination and if you can use it to predict the most likely pandemic virus genetics and you can use this information to produce a vaccine that actually works, which has not and will not happen with current technoloties, then I say lets get going...and we'll nominate you for the Nobel later!!
Marissa, you say "Because of the case in which the sequences from a cat and human in Indonesia are the same, it's tempting to think the human got it from the cat."
I wonder, could the cat have gotten it from the human?
You also say: "I did some research on chicken mites and lice, and ruled them out on the basis that they don't have the ability to survive/interface much with humans or other mammalian species."
I wish you or others might revisit some of that research and not rule things out based on one line of thinking. There have to be some alternative hypotheses that might be explored concerning these vectors. Maybe chicken mites and lice can't survive well on humans, but might they for a short time "jump ship" and try, just long enough to perhaps bite the human handling the dead or dying chicken. (I found a kitten once that was so infested with fleas that it died in my hands, and at the instant of death all the fleas started jumping off the kitten and on to me, in search of a new host.) Has anyone looked for the presence of H5N1 in chicken mites or lice? One thing interesting about mites is that they can be so tiny (not sure about the ones specific to poultry, I just mean in general ) they could actually be aspirated and carried to the lungs. This potentially could answer how working with dead infected chickens might cause a respiratory illness in humans.
Has any post mortem work on H5N1 victims been done to look for signs of such vectors in the lungs?
Anyway, all this concern about what name to call this flu based on names of potential vectors is pretty silly, IMO. As is the amount of concern being generated about whether or not to "cull cats" should they prove to be the vectors. By the time the flu reaches any of us it's a H2H pandemic, and you might as well talk about culling ones neighbors.
Silly, perhaps. But at least a growing number of people are opening their minds to the possibility that poultry are not the only potential source of H5N1 infections. A lot of attention seems to be focused on rats, but from personal experience here at my little farm, mice are much more prevalent, actually living in the coop where they come into close contact with my chickens as well as the cat and dog who hunt them. Not to mention me, cleaner of said coop. My vote, then, would be for RODENT FLU instead of Rat Flu - to include mice as possible carriers.
rat->cat->dad->lad->sad->...
And what's the difference anyhow? Indonesians and chinese are not willing to release non-avian sequences anyway...:/
Suzanne: You ask whether the Economist is generally considered slightly right of center. In British terms it would be considered quite right wing, but considering that Ned Lamont seems to be considered an extreme leftist by some in the US, I think there might be a difference in perceptions here. A good news source with "a slightly left of center bias" in European terms would be the Guardian - http://www.guardian.co.uk/. But that would probably be considered by US Republicans as something akin to the Communist Manifesto.
A detailed analysis of the HA sequences in Indonesia adds additional evidence against a poultry source for the human sequneces. The analysis include the 6 sequences from Australia released on Thursday, as well as the two sequences from the CDC released last week. The CDC sequences were from Oct 2005 collections. The Australian sequences were also from 2005, by not dated or broken down by location. Although these isoaltes have a few polymorphisms in the human sequences, there are still many polymorphsims that are only found in the human sequneces with the novel cleavage site. Similarly, the Karo cluster is clearly closer to poultry isolates from north Sumatra, but those isolates also have a number of polymrohsims not found in the Indonesian sequences.
There is clearly a need for more avian sequences from 2005 and 2006, and new sequences are expected to be steadily streaming out of the WHO affiliated lab in Austrailia. However, the first 6 were not very close to the human sequences, and matches appear unlikely, especially for the large number of cases from tje island of Java, which includes the Jakarta area and west java, the location of the three more confirmed cases this week.
These cases, as well as the cat sequence, all have the novel cleavage site and are evolving away from the existing poultry sequences. Many of these new polymorphsims are flying in via migratory birds, and there are no H5N1 sequences from wild birds in Indonesia.
The release of the sequences is a step in the right direction, but the data points toward a need for much more robust surveillance (which also applies to the outbreaks in Thailand, Vietnam, Laos, and Cambodia as well as neighbors not reporting outbreaks).
Just a test
Mary, Yes it's possible two-way transmission can occue between cat and man--we haven't ruled that out. When I indicated that the role of chicken mites, etc was an unlikely possibility, I was basing that on the research done to date interactionwise between humans and these little beasties. no one's done any testing on them for H5N1 that I know of or PM work. To have a vector that participates in the infection of disease it must have easy contact with humans. Flies and mosquitoes worry me a little bit on that basis.
Suzanne, while the economist is generally slightly right of center, I
respect them very much. They always give their reasoning, and appear willing to change their opinions if new data suggests the old conclusion was wrong. If only more of the public would be as open to reasoned policy choices!
In any case I can sympathize with being out of sync with your co-workers. As a person who tries very hard to have a non partisan thinking approach to issues, I'm considered right wing extremist by the leftish crowd, and left wing extremist by the right. The middle ground seems to be no place for people looking for frienship.