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Indonesian H5N1 Bird and Human Sequences Do Not Ma |
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Jhetta
Valued Member Joined: March 28 2006 Status: Offline Points: 1272 |
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Posted: July 03 2006 at 4:55pm |
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Commentary
Indonesian H5N1 Bird and Human Sequences Do Not Match Recombinomics Commentary July 3, 2006 The recent meeting in Jakarta on human H5N1 in Indonesia raised additional question on the origin of the human H5N1. The meeting included a phylogenetic tree of HA sequences from human, cat, and bird isolates. The human and cat sequences formed a separate branch which did not include avian sequences. The names of those isolates are listed below and are on lower branch of the phylogenetic tree. The report in Jakarta also listed those bird flu isolates with their novel cleavage site RESRRRKKA. All such isolates are on the lower branch of the tree which has all human isolates in Indonesia other than the Kao cluster and the second reported case. Included in the lower branch is a cat sequence, feline/IDN/CDC1/06. The slide that listed the amantadine resistant isolates included the age, gender, date, and location of the human case. These cases extend from the first reported case in July of 2005, IND/05/05, through cases in May 2006, IDN/554H/06 and IDN/557H/06. The cases include isolates in and around Jakarta as well as a case in East Java. Thus; although the human cases have been isolated for almost a year and throughout the island of Java, none of the human isolates match a bird isolate. A recent phylogenetic tree has 19 bird and two swine H5N1 isolates from isolates across Indonesia. Thus, the number of non-human isolates in Indonesia now exceeds fifty and only the cat isolate falls on the human branch which has 20 H5N1's isolated in Hong Kong (in addition to corresponding isolates by the CDC). The failure of the twenty human isolates to match the 50 avian isolates suggests birds are not the source of H5N1 in most of the human cases in Indonesia. In spite of this failure to match, WHO updates continue to cite bird deaths in some sort of association with the human cases. However, H5N1 is widespread in birds in Indonesia, and the sequences indicate that the correlation between human and avian H5N1 does not exist, based on the sequences described in the Jakarta meeting and released in the form of phylogenetic trees.
The failure to match human and avian sequences raise serious credibility issues regarding WHO updates. The two cased listed above were described in the Who update of May 29 One newly confirmed case is an 18-year-old man from East Java Province. He developed symptoms on 6 May and was hospitalized on 17 May. He is now recovering. The investigation found a history of exposure to dead chickens in his home within the week prior to symptom onset. No further cases of influenza-like illness have been identified during the investigation and monitoring of his close contacts. An additional case occurred in a 39-year-old man from West Jakarta. He developed symptoms on 9 May, was hospitalized on 16 May, and died on 19 May. The investigation determined that the man cleaned pigeon faeces from blocked roof gutters at his home shortly before symptom onset. No further potential source of exposure was identified. The isolate from the 18M, IDN/554H/06, and 39M, IDN/557H/06.were both similar to the first human Indonesian isolate IDN/05/05 and have the same RESRRKKR cleavage site. No reported avian isolates from 2003 to 2005 have this cleavage site or sufficient similarity to be placed on the same branch of the phylogenetic tree, yet the updates continue to use dead or wild birds as a likely cause of the human infections. WHO is well aware of the failure to find match bird isolates, yet bird contacts are used in updates and Indonesia uses history of contact with dead or dying birds as a criteria for H5N1 testing. These approaches fail to address the true origins of H5N1 infections in Indonesia and create a climate of deception. The WHO and Indonesian approaches for surveillance and containment of H5N1 in humans in Indonesia are increasing causes for concern. Indonesian human isolates on lower branch of HA phylogenetic tree IDN/175H/05 IDN/07/05 IDN/160H/05 IDN/557H/06 IDN/177H/06 IDN/554H/06 IDN/05/05 IDN/195H/05 IDN/298H/06 IDN/542H/06 IDN/567H/06 IDN/321H/06 IDN/341H/06 IDN/245H/06 IDN/304H/06 IDN/239H/05 IDN/292H/06 IDN/286H/06 IDN/283H/06 IDN/282H/06 Media Sources Phylogenetic Trees |
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Jhetta
Valued Member Joined: March 28 2006 Status: Offline Points: 1272 |
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He is basically saying based on the H5N1 sequences that he has been able to examine... it looks like the humans who contracted H5N1 did not get it from birds!
My bet would be pigs!
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Have there been reports of pigs or other animals in Indonesia dying? If not then asymptomatic animals passing deadly H5N1 to humans? So, there is some unidentified source of the virus that killed all those people? Oh boy! |
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hmm........................ |
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If it is in fact pigs that have been the transfer point to humans....it might be short term "good news" -- but in the medium / long term it is very bad news.
The "good" news is that pigs don't fly. H5N1 cannot migrate via pigs. Thus--short term, this limitation would logically limit H5N1's spread in a form that infects humans.
The bad news is...swine happen to be (apparently) the only mammalian "mixing pot" for H5N1 -- they are susceptiable to both human flu AND H5N1. When both viruses have infected a swine host, the virii can reassort--recombine DNA material between them at a very rapid pace....making for very rapid mutations in H5N1.
One of the logically possible mutations, given this scenario, is H5N1 could easily gain the easy transmissibility of the common flu into humans, while retaining its lethality.
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Jhetta
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Here is some background info... H5N1 was detected long ago in indonesia's pigs; they can be asymptomatic and they have repeately failed to cull pigs or poultry!
An internal audit at Indonesia's agriculture ministry has found suspected corruption in the provision of vaccines to fight a bird flu outbreak.
http://www.abc.net.au/ra/news/stories/s1477919.htm THE WASHINGTON POST
Indonesia's great bird flu conspiracy
http://www.thestandard.com.hk/news_detail.asp?we_cat=9&art_id=3857&sid=5091911&con_type=1&d_str=20051021 Failed Indonesian bird flu response concerns experts http://www.abc.net.au/am/content/2006/s1578301.htm Nature report on H5N1 virus in pigs in Indonesia
http://www.nature.com/nature/journal/v435/n7041/full/435390a.html
Indonesian pigs have avian flu virus http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/may2705avflu.html HIGHLY PATHOGENIC AVIAN INFLUENZA IN INDONESIA
Follow-up report No. 8 (H5N1 infection detected in pigs) HIGHLY PATHOGENIC AVIAN INFLUENZA IN INDONESIA (2006 Avian) Follow-up report No. 12
http://www.oie.int/eng/info/hebdo/AIS_21.HTM#Sec2 |
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jhetta, have you seen the report from channel 4 news? its on www.microbes
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Jhetta
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No... not yet.. I do not watch much TV... is it good?
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Jhetta
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jhetta go to microbes.info and click on flu then on channel 4 news it was from today i thought it was a little alarming. i still dont know how to post stuff so thats why i asked you cause your smart. thanks sherrie
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A recent phylogenetic tree has 19 bird and two swine H5N1 isolates from isolates across Indonesia. Thus, the number of non-human isolates in Indonesia now exceeds fifty and only the cat isolate falls on the human branch which has 20 H5N1's isolated in Hong Kong (in addition to corresponding isolates by the CDC).
I think the cats are the spreaders, I read a study not to long ago (sorry I can't remember where) about the possibility of cats being a 'mixing pot' for avian influenza. Conventional thought is that the pig is the mixer and they are, but new thinking is that the cat is too. Since the human sequences more closely match the cat than the pig or the bird sequences, I hope someone is rounding up some cats.
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Jhetta
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Is this it? Sounds accurate to me... still watching the video... thanks... best news feed I have seen so far! Great find Sherrie... I suspect they are trying to keep the news under raps as much as they can. This is probably even a little conservative... Indonesian crisis?
Published: 3 Jul 2006 By: Ian Williams Dead chickens litter the streets, but has Bird Flu begun to spread between humans too? >>Watch the report It's registered more deaths from bird flu than any other country this year - just today tests confirmed a five year old boy became Indonesia's fortieth victim of the disease. Scientists already believe there could have been limited human to human transmission of the virus when six members of the same family died in North Sumatra. However they still don't know much about how the disease spreads among chickens. Our Asia correspondent Ian Williams has travelled to West Java - where a team of veterinary experts from around the world are racing to set up a surveillance system to understand how bird flu has spread. Their early findings aren't encouraging. |
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yes thats it, see i knew you were smart. i find things but thats all im good for. i thought it was under control in indo. since no recent reports until today.
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Jhetta
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Would not be surprised by that either.... however pigs are suseptible to both avian and human virus... and they have both 2.3 and 2.6 receptors.
Will have to look into cat receptors... there are documented cases of wide spread infections of tigers at a zoo and cats infected in germany etc... will post that info later... I have to get ready for a dinner date!
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Jhetta
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It would be nice if Niman could look at current data from cats, pigs, humans in all areas where people have died in recent weeks/months.
Leaning towards cats... at this point
Commentary
Indonesian H5N1 Swine and Bird Sequences Are Similar Recombinomics Commentary July 4, 2006 The recent meeting on human H5N1 bird flu in Indonesia included phylogenetic trees of HA and M genes. The HA tree identified two separate groupings of the human isolated, color coded in green. The Karo cluster was related to avian isolates. This group is shaded in pink. Another human isolate, IDN/06/05 is the second confirmed Indonesian human case and it is located on a nearby branch. However, the remaining human cases formed a separate branch, located at the bottom of the tree. The only non-human isolate on this branch is an H5N1 isolate from a cat, feline/IDN.CDC1/06. Like the other isolates on the branch, it had a novel cleavage site, RESRRKKR. The presence of the novel cleavage site in human and cat isolates raised the possibility that the source of the human infections was mammalian rater than human. This first human isolate in Indonesia was in Banten in July 2005. At the time H5N1 was found in swine in Banten and a recent presentation included two H5N1 swine isolates from Banten, as well as 19 chicken isolates from locations throughout Indonesia. These are listed in a phologenetic tree and show that the swine sequences are similar to bird sequences in Indonesia. Moreover, the swine sequences have the common HA cleavage site RERRRKKR, which is in all but two 2003 isolates on the phylogenetic tree. Similarly, most of the Indonesian bird isolates in Indonesia are RERRKKR. These data indicate the H5N1 in the swine in Banten are not the source of the H5N1 in humans in and around the Jakarta area. In the past year, the human isolates continue to point away from an avian source. There are now over 50 avian isolates collected between 2003 and 2005 in Indonesia. There are a few isolates with novel cleavage sites of RERRRIKR, RERRRIKK, RERRRK_R, and GERRRKKR. However, the vast majority of the bird sequences are RERRRKKR. In contrast, other than the Karo cluster and the second human isolate in Indonesia, all other human isolates form a separate branch on the tree and virtually all have an RESRRKKR cleavage site. The failure to find a matching source for these sequences, other than one cat isolate, is cause for concern. This failure raises serious surveillance issues in Indonesia and raises doubts concerning transparency in WHO updates, which continue to point toward bird interactions, but fail to identify H5N1 in contact poultry and fail to find matching sequences in a growing number of bird isolates. The human sequences continue to evolve, yet the sequences of the isolates remain sequestered in a WHO private database. The only HA sequence made public is the sequence from the first human case confirmed in Indonesia. That sequence was placed in the WHO database on August 1, 2005. The phylogenetic tree lists human sequences from over 25 individuals. The time for release of these data has past. Media Sources Phylogenetic Trees |
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Jhetta
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Here is the info I promised regarding expanding host range... i.e. cats
I emailed key parts of this info to the labs that will be screening both human and animals for H5N1 infections in San Diego so they will be aware that it does not just infect birds.
Bird flu: Don’t put the cat among the chickens, warn Dutch team
http://www.khaleejtimes.com/DisplayArticle.asp?xfile=data/theworld/2006/April/theworld_April157.xml§ion=theworld&col=
(AFP) 5 April 2006 PARIS - A leading team of European virologists has appealed for health authorities to step up vigilance about household pets, saying cats and possibly dogs too are at risk from bird flu.
Albert Osterhaus and colleagues at the Erasmus maskmanal Centre in Rotterdam, the Netherlands, say that the World Health Organisation (WHO) and other agencies have under-estimated the risk from cats in their campaign against avian influenza. They point to several documented cases in Thailand, Indonesia and Germany in which domestic cats, farmyard cats and zoo felines have fallen sick or died after eating H5N1-infected chickens or wild birds, including the death of 147 tigers at a Thai zoo in 2004. And they say that lab tests they have conducted prove that cats can catch the virus in several ways -- either from eating infected chicks, through contact with infected birds or through virus administered directly into the respiratory tract. “The available evidence, albeit incomplete, suggests that cats are more than collateral damage in avian flu’s deadly global spread and may play a greater role in the epidemiology of the virus than previously thought,” the Dutch experts say in a commentary published on Thursday in Nature. The Osterhaus team acknowledge that no-one knows if an infected cat can pass on H5N1 to humans. Just as unknown is whether the animal, by harbouring the virus, can help it to mutate into a pandemic form -- a pathogen that is not only lethal for humans but contagious, too. But, they say, this risk cannot be ruled out, and precautions should thus be incorporated into the guidelines of the WHO, the Food and Agricultural Organisation (FAO) and the World Organisation for Animal Health (OIE). They recommend that steps be taken to prevent contact between cats and infected birds or their droppings; cats suspected of such contacts should be quarantined; and in temperate climates where there has been an outbreak of bird flu, cats should be kept indoors. Surveillance should also be boosted for any sign of the bird flu virus among dogs, foxes, weasels, stoats and seals, as “we now know that H5N1 virus has the ability to infect an unprecedented range of hosts, including carnivores,” the commentary adds Special Reports H5N1 In Cats and Dogs Timeline of (H5N1) avian influenza in cats and other felidae (and civets) 1970s & 1980s Research revealed that infection of domestic cats with influenza A subtypes H3N2 from humans, H7N3 from a turkey, and H7N7 from a harbor seal (Phoc vitulina) produces transient virus excretion and a temporary increase in body temperature but did not induce any other clinical signs of disease. December 2003 Two leopards and two tigers died at a zoo in Thailand after feeding on chicken carcasses. Investigation confirmed H5N1 in tissue samples from all 4 animals. This was the first report of influenza causing disease and death in big cats. September 2004 Research shows that domestic cats experimentally infected with H5N1 develop severe disease and can spread infection to other cats. October 2004 A H5N1 outbreak in zoo tigers in Thailand reportedly fed on chicken carcasses. Eventually, 147 out of the population of 441 tigers died or had to euthanized for animal welfare reasons. June 2005 Tests on three civets that died late June 2005 in Viet Nam revealed H5N1, marking the first infection of this species with the virus. These endangered Owston’s palm civets were raised in captivity; source of infection is still unknown. October 05 February 06 FAO field veterinarians report unusual high cat mortality in Iraq and Indonesia in the vicinity of H5N1 outbreaks in poultry. 28 February 2006 H5N1 confirmed in a cat on the Baltic Sea island of Ruegen (Germany). Over 100 wild birds had been found dead on the island during previous weeks. Report to the local veterinary authority any evidence of significant bird mortality both wild and domestic Advice to pet owners (see above) The hr phenotype is associated with restriction of viral replication in the respiratory tract of squirrel monkeys and humans. To identify the genetic basis of the hr phenotype, we isolated four phenotypic hr mutant viruses that acquired the ability to replicate efficiently in mammalian tissue. Segregational analysis indicated that the loss of the hr phenotype was due to a mutation in the PB2 gene itself. Avian influenza (H5N1) viruses isolated from humans in Asia in 2004 exhibit increased virulence in mammals. The origins of new pandemic viruses: the acquisition of new host ranges by canine parvovirus and influenza A viruses. Evolution In Action: Why Some Viruses Jump Species H5N1 in Dogs and Cats ~"The expanded geographical reach and host range of H5N1 is cause for concern. The spread of H5N1 allows for more dual infections, recombinations, and new sequences causing new problems. Moreover, these new sequences can increase the affinity for human receptors, such as S227N, and can be generated in avian hosts infected with H5N1 and H9N2 as predicted previously." H5N1 Canine Deaths in Thailand "However, if it is passed from dog to dog, it is another cause for concern because the H5N1 circulating in Thailand generates a very high case fatality rate in humans and there is little difference between H5N1 isolated from birds and cats and H5N1 isolated from fatal human cases." H5N1 Bird Flu Infection in Mink Expands Host Range ~ "E627K is found in all human H1, H2, H3 serotypes and is associated with the ability of the polymerase to efficiently function at lower temperatures (33 C) compared to E627 (41 C). Prior to last year, E627K had not been found in any bird H5N1 isolates. However, at Qinghai Lake, all 16 bird isolates has E627K and all Qinghai H5N1 strain isolates reported since last year have had E627K. The presence of E627K in all Qinghai isolates may increase the likelihood of mammalian infections from eating H5N1 infected birds. Therefore, the number of mammalian species infected with H5N1 may be significantly higher than those reported above. Transmission of H5N1 to other mammalian species increases the likelihood of recombination and acquisition of mammalian polymorphisms, which can lead to an expanded host range. The fixing of E627K in H5N1 in long range migratory birds may have significant impact" H5N1 Bird Flu Detected in Live Cats in Austria |
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