speculation about the unknown Indonesia H5N1-reservoir for the human sequences in Java:
from the other thread “severe pandemic likely” :
De jure – at 08:16 Monotreme, for some time now I’ve been mulling over your theory that the virus is being carried in some unknown mammal reservoir(s), and I have a couple of questions for you. If the virus is being transmitted from mammals to humans and not birds to humans, then why does it seem that Vietnam’s aggressive bird culling operation seems so successful? Afterall, they have plenty of other mammals there but haven’t seen the virus resurface. 2nd question: Has it ever been proven that the virus can spread from asymptomatic pigs to humans? Even if the virus has been found in pigs, how good are pigs at efficiently transmitting it to humans? Why haven’t we found human cluster evidence around pig farms, in other words, if pigs were a significant vector? Lastly, it seems to me that perhaps there is a partially adapted H5N1 circulating in the human populations where there have been outbreaks, which would explain the sequence diffences between avian and human. It seems that the current tests are having trouble positively identifying the virus. Recent findings suggest it is more effective to make a positive determination from autopsies (lung tissue presentations), in my opinion due to the rapid mutation that this virus is undergoing. It seems harder to get these autopsy findings due to cultural and religious reasons in the countries that have been hit the hardest. Perhaps when seroprevalence studies are done to look for specific antibodies, the antibodies don’t show up because they are so different than the viral strain being tested? I don’t know. My professional training is not in such matters. It would seem to me to be a good idea to encourage all countries that have been hit by this virus to collect and test more autopsy samples (on both the victims and those who’ve died from “natural” causes). I suspect that if a very few people may be able to carry the virus asymptomatically (and shed the virus while doing so), then it would be very, very hard to detect with current seroprevalence studies. Monotreme – at 08:28 anonymous – at 23:16 I think there are multiple things happening, some of which are relevant to pandemic onset, some of which aren’t. I’m sure some people have been directly infected by birds, but I think this is very rare. I think more people have been infected either by another mammal or by another person. Which sequences a particular human isolate matches gives a clue as to how they were infected. This is why it is so critical to tie sequences to specific patients, to sample every person and animal near that patient and to make it clear exactly where every infected animal is found and to describe the relationship between the sequences, regardless of source, to very specific geographical regions. This should have been done from the very beginning of the H5N1 outbreaks. I continue to be stunned that it is not being done today. I don’t know what they people who should be doing this are thinking. Monotreme – at 08:35 anonymous – at 23:19 …are you assuming the humans in Indonesia give the virus along to some other animals where it continues to evolve in a host’s-cycle ?? I’m not assuming it, but I consider it a possibility. I don’t think so. Too few human infections. Animal infections are more likely to stay undetected. Human to pig transmission has been suggested for other flu viruses, so it’s a possiibility. The probability would depend on the what the real number of human infections are and how efficient human to mammal transmission is. I think this is much more efficient that bird to human or bird to other mammals. The high prevalence and clusters suggests that human to human during close contact is very high. Monotreme – at 08:36 NS1 – at 23:26 So, I think we agree on the facts but not the interpretation. That’s OK. I have always had the highest respect for how you conduct yourself on Flu Wiki. Monotreme – at 08:39 Dude – at 01:24 My point is we need to look at this problem with the data we know and see if we can then make any patterns that make sense. What we can know is date, place, some sequences, weather and the kind of animals. It is one level to the puzzel. Yes, I agree this is important and I’d like to work on it, but there is never enough time. anonymous – at 08:39 de jure, we are only speaking of Java here. In Vietnam and elsewhere they probably did get it directly from the chickens. Monotreme – at 08:41 a’Akova – at 01:54 Are you thinking only of the first two of a triplet which determines an amino acid ? I suspect that even the third may be under selection in certain viruses, specifically if the third nucleotide has some effect on how the RNA folds and is encased by virus coat protiens. We think of a successful virus as one which is capable of infecting a cell, but a successful virus is also one that assembles itself correctly. There are a number of sequences under selection that don’t directly relate to coding of amino acids. I don’t think there is anything we really disagree about. Monotreme – at 08:57 De jure – at 08:16 If the virus is being transmitted from mammals to humans and not birds to humans, then why does it seem that Vietnam’s aggressive bird culling operation seems so successful? Afterall, they have plenty of other mammals there but haven’t seen the virus resurface. I don’t know the answer to your question, but here are some possibilities. 1. Vietnam was affected early in H5N1 outbreaks. H5N1 has evolved since 2003. Some of the new strains have different properties. Clusters may be growing more common than they were. 2. Maybe certain species of birds are necessary to be part of the mammal to mammal evolution. Quail have been suggested. Has it ever been proven that the virus can spread from asymptomatic pigs to humans? I’m not sure about this, maybe someone else knows. Even if the virus has been found in pigs, how good are pigs at efficiently transmitting it to humans? No-one knows. Every strain of virus is different. Why haven’t we found human cluster evidence around pig farms, in other words, if pigs were a significant vector? Some have suggested that this has happened in China, but was attributed to another disease, S. suis. Also,pigs and chickens are often on the same farm, at least in China. The fact that a farmer kept chickens is always emphasized in reports. The fact that he also kept pigs is usually not mentioned. Lots of pigs have been dying in China. Promed has requested that they be tested for a variety of pathogens including H5N1. To my knoledge this has not been done. Lastly, it seems to me that perhaps there is a partially adapted H5N1 circulating in the human populations where there have been outbreaks, which would explain the sequence diffences between avian and human. I don’t buy this. There is no evidence for it. This would not explain why the sequences from a human cluster more closely resemble a sequence from a cat than they do sequences from other humans. See my post on this on the previous thread. Also, if subclinical spread were occuring, it would be all around the world by now. anonymous – at 09:00 well, the synonymous mutations don’t seem entirely random when you look at it statistically. But I never saw an explanation why and how they change the properties of the virus ? De jure – at 11:51 Monotreme at 8:57: “2. Maybe certain species of birds are necessary to be part of the mammal to mammal evolution. Quail have been suggested.” Hmmm…you’ve got me thinking. Let’s hypothesize that the Vietnamese strain required avian help while the new Indonesian strains don’t need this assistance. It would seem that you would be able to look at the differences between the strains and tell which polymorphisms were making the virus more adaptable to people. Just a thought. By the way, thanks for your response. Intriguing as always. anon_22 – at 14:02 I’m thinking cats. Not pigs. anonymous – at 14:13 Why not rats or mice ? AVanarts – at 14:49 “anonymous – at 14:13 Why not rats or mice ? “ Why not? That’s one reason that I am an advocate of stocking lots of d-Con among the preps. Call of the Wild – at 21:27 Surely the spread has to be something that can travel long distances relatively quickly and achieve contact with some fairly remote areas. This means wild birds have a role rather than insects and mammals, or even the villager types who have been doing all the dying so far. disgruntled – at 22:10 Call of the Wild – at 21:27 If the spread was by wild birds, then why don’t the wild bird sequences match the human sequences? I rather suspect the long-distance vector is two-legged, two-wheeled and two-stroke. Swann – at 23:12 Monotreme: I may be totally off-base, but in trying to follow your theories, I have been reading about the mammals of Indonesia. Black macaques are found there (in particular, Sulawesi), they are endangered because of over-hunting for food as they are considered delicacies and are served at feasts or special occasions such as weddings, and they are mostly vegetarian but are known to eat nesting birds. Macaques are also found in China. I’m sorry, I cannot make my link to Durrell Wildlife work tonight. anonymous – at 23:22 the special human sequences are only in Java, and different from most bird sequences, so they shouldn’t get it by hunting birds but rather spread it from member to member within that reservoir. And occasionally spread it to humans, but rarely to (other) birds. We have a duck in Indramaju and two chickens in Sumatra with that virus, but all other birds have a different strain. Some humans also got that different strain, e.g. Karo. Karo could also be viewed as such a special, isolated strain ,…, if they hadn’t happened to test the Dairi-chicken and some others. There can always develope some branches, which you can’t easily link, but with the humans in Java it’s more obvious and separated as usual. Monotreme – at 23:25 De jure – at 11:51 It would seem that you would be able to look at the differences between the strains and tell which polymorphisms were making the virus more adaptable to people. Yes, I think so, although the WHO doesn’t. And thanks. Monotreme – at 23:39 I’m going to add the following to the next iteration of this thread, but just to assure people that the title of this thread is not a fringe opinion: The likelihood of an H5N1 influenza pandemic seems high, and the consequences could be catastrophic. Recent findings suggest that the 1918 “Spanish flu” pandemic may have resulted from a similar interspecies transmission event in which a purely avian virus adapted directly to human-to-human transmission without prior reassortment From: Establishment of multiple sublineages of H5N1 influenza virus in Asia: Implications for pandemic control Authors: H. Chen, G. J. D. Smith, K. S. Li, J. Wang, X. H. Fan, J. M. Rayner, D. Vijaykrishna, J. X. Zhang, L. J. Zhang, C. T. Guo, C. L. Cheung, K. M. Xu, L. Duan, K. Huang, K. Qin, Y. H. C. Leung, W. L. Wu,H. R. Lu, Y. Chen, N. S. Xia, T. S. P. Naipospos, K. Y. Yuen, S. S. Hassan, S. Bahri, T. D. Nguyen, R. G. Webster, J. S. M. Peiris, and Y. Guan Published in the Proceedings of the National Academy of Sciences. Monotreme – at 23:49 Call of the Wild – at 21:27 One of the interesting things about the H5N1 found in Indonesia is that it came directly from China. Not Viet Nam, not Thailand, not Malayasia. It came direct from China. Here’s a map of Southeast Asia. Now what was the species of bird that brought it there? Anyone know? Reference Evolution and adaptation of H5N1 influenza virus in avian and human hosts in Indonesia and Vietnam Monotreme – at 23:52 Swann – at 23:12 A perfectly reasonable hypothesis. The only question is how much contact to people in Jakarta have with monkeys? I’m guessing not a lot, but I don’t really know. OTOH, it’s certainly reasonable to suggest that they could be part of a complex mammal to mammal chain of infection. anonymous – at 23:57 likelyhood is “high” ? high = 10% ? 50% ? 90% ? and in which timeframe ? “could be” became famous after Webster’s ABC-statement. Too imprecise. 06 October 2006 Monotreme – at 00:04 anonymous – at 23:57 For a scientist, the language used was very strong. I would interpret “high” as over 50%. I think they are also implying that there is good reason to believe that an H5N1 pandemic would be as bad as 1918. JMO, of course. anonymous – at 00:06 some rare species of monkeys ? They should have noticed the connection if several human cases had monkey-contacts in common. Leo7 – at 00:06 So, if the bird and human sequences don’t match well and cats are a possibility—why hasn’t the virus jumped to a major city? That elusive mammal would have to not be in the big, overcrowded cities wouldn’t it? How else can you explain the fact it isn’t in the big cities yet? I’m thinking cities with international airlines or seaports? I vote for a mammal, not avian, that a cat mingles with, but what? Pixie – at 00:10 Leo7 – at 00:06 - Cats like mice. anonymous – at 00:14 mono 00:04, I don’t read that from the statement. “could be” when Webster said it, hardly meant more than 10% (?) , why should “could be” in a similar context be more than 50% now ? no one knows. Also Webster said 50% for efficient h2h with H5N1, which seems to be necessary for a pandemic. So less than 50% for a H5N1 pandemic for one of the Coauthors. gharris – at 00:27 Ontario Health is now saying that 35% of population may become infected with AI - http://tinyurl.com/oy7q5 or visit Canadian Preppers thread for other technicolour dreams!! disgruntled – at 00:34 Monotreme— Where the chinese sequences came from: ISDN184026 A/chicken/Hong Kong/947/2006 HA (4) 1706 2006 H5N1 ISDN207246 A/Chicken/Karo/BBPVII/2006 HA (4) 1703 2006 H5N1 ISDN138756 A/chicken/Malaysia/935/2006 HA (4) 1721 2006 H5N1 ISDN207245 A/Chicken/Padang/BBPVII/2006 HA (4) 1708 2006 H5N1 ISDN207244 A/Chicken/Pulau Rampang/BBPVII/2006 HA (4) 1738 2006 H5N1 ISDN184030 A/Common Magpie/Hong Kong/645/2006 HA (4) 1662 2006 H5N1 ISDN138780 A/duck/Laos/3295/2006 HA (4) 1719 2006 H5N1 ISDN140810 A/Indonesia/534H/2006 HA (4) 1679 2006 H5N1 ISDN140894 A/Indonesia/535H/2006 HA (4) 1703 2006 H5N1 Mainly it’s the ducks that are the long-range carriers, with songbirds as local carriers to chickens. Hurricane Alley RN – at 00:35 Leo7 - Cats like a varied menu---birds of any feather, mice, rats and even the occasional squirrel. Does anybody see a possible link? gina disgruntled – at 00:39 from the news thread: The traffic in chickens and poultry cannot be controlled because the demand is so high, which traders will do anything to meet. Traders in Bogor confessed that they would bring chickens in from anywhere, such as Bandung and Sukabumi, and that sometimes their stocks would be bought by traders from Tangerang or Jakarta. Government officials are not empowered to interfere with this traffic, but at the same time they must campaign about how dangerous bird flu virus is.
I still think the vector is two-legged, and two-wheeled. Pixie – at 00:39 disgruntled - at 00:34: “Mainly it’s the ducks that are the long-range carriers” Are we talking domestic ducks or wild ducks in these sequences? disgruntled – at 00:42 Wild ducks, I think, but the sequence labels aren’t too specific. Leo7 – at 00:52 Disgruntled: If human then why isn’t it in the big cities? anonymous – at 00:54 wild ducks do meet in Indramaju, where the human sequence was found in ducks. I assume they travel to/from Sumatra. But there are also farms with domwestic ducks in that area. How about parasites ? I was speculating about Freyana Anserina with these swans in Europe. Leo7 – at 00:55 Hurricane Alley RN- Like them all, but which one hasn’t been sampled? Maybe, have been and they are in the sequences the CDC are holding back, as disgruntled commented on earlier. anonymous – at 00:58 we are getting off-topic. I start a new thred : Indonesian reservoir
you expect people to be able to read this? :-)
I forgot to format it :-( . Fluwiki requires these double backslashes to indicate line-end. It’s double posted anyway. See the “severe pandemic” thread, which went off topic.
Unknown mammalian H5N1 resevoir? Asymptomatic shrews, fecal contamination of both humans and cats. Their high metabolism and body temperature would make the very efficient bioreactors for the production and shedding of H5N1.
Since monotreme first talked about a hidden mamalian resevoir, my intuition tells me that cats play a key role. this would be worse than pigs or other animals that we could cull or isolate. Cats come into contact with many species in the “wild” than come into our houses and have contact with us and our children. Cats have been known carriers of h5n1 for years in several countries including Indonesia.
anon_22 – at 01:25 ‘you expect people to be able to read this? :-)’
He could write it upside and backwards and I would still read it. :)
that would mean that the virus goes cat2cat2…2cat2… over years. Considering how close we humans are to cats and how well even ferrits infections are assumed to model human infections this is a bit frightening. OTOH, it doesn’t seem to harm the cat-population very much.
OK on the subject of Cats being the unknown resevoir…What if we looked at it from a slightly different perspective. Instead of the Cats speading H5N1 to humans directly through contact. WHAT IF humans were catching the Flu via Consuming the Cat Meat? Then passing it H2H? Would we see a difference in the sequences then? Or would they read exactly as they are now, with the cat sequences being the same/closest to the human ones. Would there still be a need for an additional vector?
A former Lurker – at 13:04
Instead of the Cats speading H5N1 to humans directly through contact. WHAT IF humans were catching the Flu via Consuming the Cat Meat?
I don’t think we need such a drastic explanation. Just regular inadequate hand hygiene would do it. There was one study from Thailand last year about risk of contracting bird flu from poultry, and one of top 3 risks was ‘not having indoor tap’.
While cats have been proven to be able to carry H5N1, so far we only have one cat sequence from Indonesia that matches the human sequences. My understanding is that Indonesians do not favor cats for eating, nor do they typically keep them as pets.
The cat that was swabbed that had the sequences that matched humans nearby who were infected was a kitten. The fact that it was a kitten means that we have to account for the “adorable factor” here. If the cat were just another feral cat, I would expect that the locals would probably ignore it. But a kitten, even a feral one, is pretty hard to ignore. The “adorable factor” means that the kitten was more likely to have been in direct contact with one of the infected humans, who might have picked it up and played with it, than a feral cat. So, transmission from human to cat, or from cat to human, might have been aided in this particular case by very close proximity. The question is: did the cat give it to the human, or the human to the cat?
It would be very helpful if other cats were tested, particlularly those near the human clusters. I’d bet it would be fairly easy to bait and catch a hungry feral cat. So far that H5N1-positive kitten found near the human cluster is a one-off, both in the fact that it happened to have been tested and its sequences matched. If we are to hang the wide spread of H5N1 in Indonesia on cats as a potential unseen reservoir, it would seem to be a quick enough project to test at least a few more felines to see what their sequences tell us. Unfortunately, feral cats probably do not come under the purview of FAO, OIE,or the other customary livestock agencies so there’s probably quite some debate over who should do this kind of testing.
I’ve been unable to get on for two days (server issues) but I posted a Q? the other day and perhaps someone can help. The fact that this virus is spreading to so many mammals is a scary prospect. But, are those animals asympotomatic? I remember the tigers in Thailand died, but what about other mammals? If cats even just carry the virus, even if there isn’t Cat-to-human transmission, people in the West who keep cats as pets will freak. It’s one thing to cull birds, but pets? The shelters will instantly fill with abandoned pets.
How many new cases?
pixie, the cat was swabbed two weeks after the human cases. I assume they were both infected from a third source.
LauraB, people did “freak” after past episodes at media reports in UK and Europe, because they weren’t told ahead of time what was probably safe and what wasn’t (and, some will refuse to follow advice to not let cats outdoors, ect, when they hear it)
-people wanted to get rid of their indoor pet parrots after hearing a parrot locked up in international import quarantine (it was really other species mixed together) had deadly H5N1, for example. Abandoning or killing animals creates new sets of problems, (but reducing feral populations now might not be a totally bad thing, as well as making sure all pets are sterilized so they don’t make unwanted offspring).
Here are the FAO recommendations (should have been titled Mammals and H5N1, but) for the public and animal vets (read the whole thing - always read the “for professionals” stuff even if you aren’t a professional - can see what else is in the message, and usually the info is not “over our heads”).
The Flu Wiki species list has some details as to the animals dying Mammals shown to be infected with H5N1
(Hunters or farmers, say in North America, also may not be used to taking precautions involving not touching their faces - I’ve seen recommnedations they not smoke, ect, without disinfecting their hands first, if working with possibly infected animals/carcases.)
Thanks anonomousR - at 9:35.
So then a third source sounds right. Thanks - it is always a good thing to remove one theory from consideration. Could the kitten’s mom have been an asymptomatic carrier? Have we seen any cats carrying the virus asympomatically either in vitro or in vivo? Then there’s those mice.
(I looked at cat photos from Indonesia on flickr, and they do have cats in the streets, looking for food scraps; even saw a photo of one carrying away a live rat - and -saw macaques grooming a stray kitten! also saw photo of a wild cat species, Prionailurus planiceps. Then there are the photos from Indonesia that have pigs in them… including “Adu Bagong, a kind of animal fight In Indonesia, where Pig (forrest/guinea pig) and dog (pitbull/etc.) are matched. as an old tradition, this fight involves one pig and lots of dogs (up to 30 dogs). The referee usually takes a 3-minute timing for one dog to bite the pig. Once it bites, the match is over and another match begins (with a new dog). Just like that, till the last turn.” Also, pigs being butchered for some special occaisions -outside on the ground, by hand, group activity. )
So many species to test, so much cross-contact, and so little testing, or money/staff/test facilities, right?
i bet the mice and rats are carriers…
Let’s talk about the practical side of having an animal host for H5N1 from which humans, spread throughout a 2,000 mile wide archipelago, are becoming infected. How has the virus managed to change so consistently? There are only a few ways the widespread infection of humans can be happening if the poultry sequences do not match the human sequences:
Which one of these ideas is consistent with what we know about viral hosts and evolution?
Which one of these ideas best accounts for the spread of human infections with the virus throught the islands, from Medan to Sulawesi?
Or what are the other theories out there to explain how the animal reservoir and the humans (with the non-bird sequences) are being infected in practicality?
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