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.
Vigilance engendered by the possible family cluster of H5N1 avian influenza cases in Pakistan has led to many more reports of potential cases there, a World Health Organization (WHO) official said today.
Gregory Hartl, a WHO spokesman in Geneva, told CIDRAP News there have been reports of "many more potential cases due to heightened sensitivity and enhanced surveillance," though no more preliminary positive H5N1 tests have been reported.
...US Navy Medical Research Unit 3 in Cairo has a portable laboratory that will arrive in Pakistan tomorrow to begin confirmatory tests of samples from the suspected cases.
More than 30 contacts of the suspected patients have been tested for H5N1 so far, with no positive results, Hartl said. Regarding testing of people with suspicious symptoms, he said, "Last one tested that I know of was on Saturday, and he tested negative."
Meanwhile, Indonesian officials said today they are investigating several recent human H5N1 cases in which patients had no known contact with infected birds...
The vast majority of human H5N1 cases have been attributed to contact with infected birds, but probable human-to-human transmission has occurred in a few cases. Increased human-to-human transmission would be regarded as the possible prelude to a pandemic.
According to AFP, Bayu Krisnamurthi, head of Indonesia's National Avian Influenza Committee, told reporters, "In the last three or four months, we have had four cases where the poultry in the victims' neighborhoods (tested) negative for the virus. The number is significant enough for us to intensify our investigations so that we could have a more accurate explanation."
Krisnamurthi said the proportion of cases involving no known contact with poultry has increased from 20% in 2006 to 30% this year, AFP reported.
Krisnamurthi said the agriculture ministry vaccinated 70% of Indonesia's farmed poultry against H5N1 this year, but the quality of the vaccine needs improvement, AFP reported.
h5n1 human to human tranmission in pakistan specifics?
recombinomics commentary
december 19, 2007
the eight individuals in pakistan who are suspected to have bird flu probably have a combination of infections from poultry and limited person-to-person transmission from close contact, a top world health organization expert said on tuesday. keiji fukuda, coordinator of who's global influenza program, said while unconfirmed, any human-to-human spread seemed similar to previous outbreaks in thailand and indonesia -- affecting close family members caring for sick loved ones.
the above comments confirm the data represented by the consensus media reports. however, these reports lack hard dates, including disease onset dates,which suggest the cluster may be the longest in term of links in the chain, as well as persistance of the chain. the metrics could raise concerns that the h5n1 in circulation will generate similar chains in pakistan, as well as downstream locations in europe, the middle east and africa, which could generate unprecedented numbers of confirmed h5n1 cases.
although pakistan has not released any h5n1 sequence data from their poultry outbreaks in 2006 and 2007 (see satellite map), public 2006 sequences from adjacent afghanistan and india have been published. these sequences have some similarities, and it is likely that earlier sequences from pakistan are similar to those from neighboring countries. however, neither india nor afghanistan have released sequences from reported outbreaks this year.
sequences have been released by krasnodar and germany, and these sequences are related to 2006 sequences from uva lake. these uva lake sequences are also related to the earlier sequences from india and afghanistan, so it is likely that the current sequences in pakistan are also related to these uva lake sequences.
these sequences are widespread. they first appeared in kuwait at the beginning of this year. then they appear in multiple countries in europe of the summer (czech republic, germany, france). similar sequences were the published from krasnodar, and subsequent infections in england and germany are also said to be similar, suggesting that recent outbreaks in romania, poland, rostov, and saudi arabia are also similar.
therefore the ability of these sequences to transmit human-to-human (h2h) is of broad interest, so prompt reporting of the specifics of the h2h transmission is important. the larger cluster includes the index case, four brothers, a cousin, and one or two health care workers. media reports indicate this cluster began with exposure(s) during a cull on october 21-23. the index case developed symptoms on october 25, and two brothers died november 19 and 25. moreover, a health care worker may still be hospitalized, suggesting the cluster may be h2h2h2h or longer and may have persisted for almost 2 months. in addition, media reports suggest there are three additional confirmed patients representing another familial cluster.
local confirmation of the initial lab positives was projected to be completed yesterday, and disease onset dates for the cluster members should have been known for some time.this information is usually released in who situation updates, which give the age and gender of confirmed cases, as well as disease onset dates, hospitalization dates, and dates of death as well as relationships between cluster members.
virtually all of the data has not been released even though the outbreak began almost 2 months ago, and who has been aware of this cluster for at least a week.
yesterday, media reports described a new suspect case in kuwait, which when coupled with the massive outbreaks in poultry in saudi arabia and the high concentration of pilgrims at the hajj, create cause for concern.
with permission from recombinomics, here is more commentary
on the likelihood of human to human transmission of h5n1.
the case for its common occurrence has been well presented by
dr. henry niman, imo.
human to human transmission is frequently referred to as h2h.
sustained human to human h5n1 transmission in pakistan?
recombinomics commentary
december 19, 2007
"right now it doesn't look like pure human to human transmission. it looks like the veterinarian, who was the index case, and a number of other suspect cases had poultry exposure," fukuda told reuters in an interview.
"it is definitely possible that we have a mixed scenario where we have poultry to human infection and possible human to human transmission within a family, which is not yet verified." but human to human transmission "would not be particularly surprising or unprecedented," he added.
in thailand, a mother was killed by the virus in 2004 after cradling her dying infected daughter all night. the largest known cluster of human bird flu cases worldwide occurred in may 2006 in indonesia's north sumatra province, where as many as seven people in an extended family died.
the above comments on the human to human (h2h) transmission in pakistan, and two examples of such infections in the past are accurate, but the extensive h2h transmission in pakistan is likely to cause confusion, because media reports and the public believe that h2h of h5n1 is rare, when it is very common. the more extended transmission chains, as noted above, are rarer, and the transmission in pakistan may be the most sustained h2h reported to date, but h2h among family members is quite common, and most first reports of h5n1 in patients are h2h clusters.
the h5n1 h2h usually involves only two people, which are the index case and a family member caring for the index case. these small clusters have the diagnostic time gap between onset dates, but the linkage of the index case to a poultry source extends to a family member, so the proof of h2h is not absolute.
when there are two time gaps, suggesting h2h2h, then the likelihood of h2h increases markedly, especially when there is epidemiological data linking the cases.
however, the number of cited h2h examples is also reduced because samples are frequently not collected from the index case, and testing of contacts may use samples collected after the start of prophylactic oseltamivir (tamiflu) treatment.
in the first example above. the lack of a poultry connection added to the likelihood that h2h was involved, and the number in the cluster was three and there were two time gaps. therefore, it has been cited as the first example of h2h. the index case was a child staying with her aunt in rural thailand. her mother was an office worker in bangkok. the index case was likely infected by a pet chicken, which died and was buried by the child. however, she was mis-diagnosed as having dengue fever. consequently, there was no protective equipment given to her visiting mother, who was probably infected while holding her daughter in the hospital. the daughter died and was never tested for h5n1, but the mother developed symptoms after returning to bangkok, and the aunt of the index case also developed symptoms several days after the mother left. initially the mother was not tested either, but after she died, a nurse notified investigators of the bird flu symptoms, and samples were collected just prior to cremation. the mother was h5n1 positive and the aunt was also h5n1 positive, although initial tests on the aunt were inconclusive. thus, if there wasn't a cluster, it is likely that none of the cases would have been official confirmed cases. however, because of the lab confirmation in the mother and aunt, the cluster is a strong example of h2h or h2h2h.
the cluster in indonesia is also considered to be a cluster because there were two time gaps, and there was epidemiological evidence for h2h2h. however, the index case died prior to collection of a sample. seven family members tested positive for h5n1 and the onset of symptoms was several days after the index case, most of whom slept in the same room as the index case while she was very sick and coughing extensively. the son of one of the infected brothers also developed symptoms several days after his father, so the indonesia clusters was h2h2h, although the index case was not lab confirmed.
most clusters however only involve two family members. the first cases in cambodia were a cluster. the index case collected dead chickens. he developed bird flu symptoms and died prior to sample collection. when his sister developed symptoms, she went to vietnam for treatment and was h5n1 confirmed after she died, so although the brother likely infected his sister, the cluster was not considered h2h because no sample was collected from the brother. the first cases in hunan china were also a cluster with a time gap, but were not considered a cluster until a rising antibody titer was detected in the index case after he died. the first cases in indonesia were also a cluster, but there were no early samples from the index case, no sample was collected from her sister, and h5n1 was confirmed in the father after his two daughters had died. this cluster had two time gaps, but one sister was not an official case because she was not tested.
there are dozens of similar examples. some of the earlier clusters from vietnam and thailand were published, but there have been many examples since the earlier clusters were reported, and these clusters include the first case from turkey, iraq, azerbaijan, and nigeria. all of these cases involve the qinghai strain of h5n1, which is almost certainly the case for the cluster from pakistan.
however, this cluster is likely to the most sustained to date. the index case was a veterinarian who developed symptoms on october 25. two brothers developed symptoms after visiting the index case in the hospital, and the dates of death on november 19 and 29 suggest this transmission chain was h2h2h. however, at least two more brothers were infected, and one or two health care workers had symptoms or were h5n1 confirmed, so they represent h2h2h2h, if confirmed, and since one is still hospitalized, the transmission has been sustained for two months. moreover, samples of contacts are being collected after the start of tamiflu treatment, so additional transmissions may not be lab confirmed.
the detail of this cluster will be clearer when disease onset dates are released, but the current cluster appears to be the most sustained h5n1 cluster reported to date, and also representing the largest number of links on the chain.
Hey, don't want to derail your thread but I was wondering if you'd seen this:
Researchers have identified a new strain of swine influenza--H2N3--which belongs to the group of H2 influenza viruses that last infected humans during the 1957 pandemic. This new strain has a molecular twist: It is composed of avian and swine influenza genes.
In the newly isolated swine H2N3, the avian H2 and N3 gene segments mixed with gene segments from common swine influenza viruses. This exchange--and additional mutations--gave the H2N3 viruses the ability to infect swine. Lab tests confirmed that this strain of H2N3 could also infect mice and ferrets.
These findings provide further evidence that swine have the potential to serve as a "mixing vessel" for influenza viruses carried by birds, pigs and humans.
WHO's new spin on human to human bird flu transmission
Category: Bird flu * China * Infectious disease * Pandemic preparedness * Public health preparedness * Surveillance * WHO
WHO [World Health Organization] is now saying that human to human (H2H) transmission has not been ruled out in China or Pakistan:
China:
The World Health Organization said Friday it was impossible to say whether a case of bird flu in China involving a 52- year-old man was due to human-to-human transmission - but, even if it was, it was down to very close contact between the victims.
The Assistant Director-General for Health Security at WHO, Dr David Heymann, said the only proven transmission of this nature so far, in Indonesia and Thailand, had been as a result of very 'close contact' in a 'very circumscribed area.' (via Monsters and Critics)
Pakistan:
The World Health Organisation (WHO) suspects there has been only limited human-to-human transmission of the H5N1 virus in Pakistan, but international test results are pending, an official said on Friday.
David Heymann, WHO assistant director-general for health security and environment, said no new suspect human bird flu cases had emerged in Pakistan since Dec. 6, signalling there had been no further spread.
[snip]
"The team feels that this could be an instance of close contact human-to-human transmission in a very circumscribed area and non-sustained, just like happened in Indonesia and Thailand," Heymann told a news briefing in Geneva. (Reuters)
This is the new line. Yes, sometimes there is human to human transmission. But it requires very close contact. Casual contact isn't enough. Sounds reasonable. But here's my problem. In a lot of cases there is no history at all of contact with sick poultry. Maybe theses cases came in contact with a virus shedding bird somewhere but was it similarly close contact? Or is casual contact with birds capable of transmitting infection but not from another person? Even more to the point, lots of people have close contact with sick poultry and they don't get infected. Only some people get infected. We don't know why that is, but it would seem more sensible to ask the same question about the rare human to human transmission. Why these people and not others? Instead of asking that question, they are falling back on the "close and heavy exposure" explanation.
I guess they don't want to alarm us. Or something.
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.
Partridges contaminated with virus of avian influenza
Four one thousand birds slaughtered in Mafra
The authorities expect that the transaction is completed by the end of the day today. After slaughtered, the partridges are buried within the small bags landfill created for that purpose, under the guidance of the services of the Ministry of Environment.
In zone was established a perimeter of safety to prohibit the movement of people, which could undermine the work of the brigades of the DGV. The security measures were also imposed to prevent the spread of the virus to neighbouring farms.
"The presence of the H5N1 virus has been confirmed by the State Veterinary Institute in (dead) chickens found on an egg-producing farm in the district of Zuromin," PAP cited a statement from Poland's Chief Veterinary Office as saying.
This is the eighth case of the H5N1 bird flu virus in Poland since the start of December, when an outbreak was reported at a turkey farm in the Plock area, 80 km (50 miles) north-west of Warsaw.
the recent report of a novel influenza virus in pigs, the h2n3 subtype, has been raised some alarm in certain quarters. i just read the paper itself (doi: 10.1073/pnas.0710286104) and then the account in cidrap news, which is both accurate and complete. i recommend it highly as a summary of this work. i have a bit to add, but first their concise summary of events leading to the investigation:
the discovery of the new virus began with an illness outbreak in pigs at a missouri swine nursery in september 2006, according to the report. the pigs' lungs showed obvious signs of pneumonia, and tests showed the presence of an influenza gene, but the subtype could not be determined. samples were submitted to the ars [agricultural research service] in ames, where genetic sequencing and a search of a flu sequence database showed the virus subtype to be h2n3.
after the virus was subtyped, a record search revealed that another unidentified virus had been submitted in april 2006, from a 12-week-old pig at another missouri swine farm, according to the report. analysis by the ars showed that this isolate too was an h2n3, and the two viruses were nearly identical.
the two outbreak sites are about 8 miles apart, according to marie gramer of the university of minnesota college of veterinary medicine in st. paul, a coauthor of the report. she said there was no connection between the two operations.
phylogenetic analysis showed that the virus's hemagglutinin (ha) gene most closely matched the genes of h2 viruses isolated from north american mallard ducks, while the neuraminidase (na) gene was closely related to that of an h4n3 virus found in blue-winged teal. five of the other six genes were derived from swine flu viruses currently circulating in the united states, the scientists determined.
the source of the virus is unknown, but the likeliest possibility is pond water, which was used to clean barns and water the animals on both farms, according to the report. that transmission pathway has been described before. (robert roos, cidrap news)
this virus has not been described in pigs previously, but the 1957 pandemic was an h2 influenza subtype, h2n2. h3n2 succeeded h2n2 as a circulating flu virus after the 1968 pandemic. since that time only h1 and h3 subtypes have circulated, so if you are younger than 40 you've not had any exposure to an h2 flu virus. but this virus is in pigs, not humans. so what's the concern?
as most people know by now, flu viruses keep changing. they have more than one way to change and at least two of these, maybe three, have been involved in the changes that enabled the influenza virus to become a pandemic scourge in the last century. in the infamous 1918 spanish flu, the virus appears to have jumped directly from birds to humans after some subtle and possibly minor genetic changes, but mark and adrian gibbs have championed the idea the 1918 event was caused by homologous recombination between a human and swine virus, however, so some controversy remains. there is general agreement, however, that the 1957 and 1968 pandemics were the result of reassortment, that is, the swapping of entire segments of eight segments of the avian and human viruses. this virus seems to be a reassortant virus involving bird and pig viruses mixing and matching. the story, though, is a bit more complicated than this.
first the h2 part of the story. h2 influenza viruses continue to circulate in birds but there appear to be two lineages in birds, a eurasian lineage and a north american one. the eurasian h2 is more like the human h2 from the 1957 pandemic, but the new pig h2n3's h2 segment is more like the north american one seen in the h2n2 of mallard ducks.but it isn't identical. in particular, it differed at six places from the bird h2 and one of those places was position 226, known to be involved in the receptor binding determinant of the virus
positions 226 and 228 are both important in differentiating "avian" from "human" receptors (but see the posts just linked for important qualifications regarding this too easy distinction) but only position 226 is changed to a more mammalian form in the new virus. the paper notes that in the 1957 pandemic, 226 changed first and then 228, so this pig version is like the early h2 virus in the 1957 pandemic but not yet like the full blown version with changes at both 226 and 228. even if the virus had a full human type receptor, that isn't sufficient to make the virus into a transmissible human virus, since there is quite a bit of swine h1n1 with human receptors that doesn't circulate in humans.
the n3 was most like an n3 that currently circulates in blue-winged teals (an h4n3). an internal gene (pa) was similar to one found in mallards, but an h6n5, different than the h2n2 from mallards that contributed the h2. that leaves five more segments and they are characteristic of an influenza virus currently circulating in pigs, but the twist is that this virus is itself a triple reassortant of a bird, human and pig virus: pb1 is originally human, pb2 originally avian, and np, m and ns swine. so the segments come from at least three different bird viruses, a human virus and a pig virus (possibly more).
this virus is also competent in more mammals than pigs. it was able to infect mice and ferrets and there was transmission to co-housed same species pigs or ferrets. it is thus mammalian adapted and there was serologic (blood antibody) evidence it continues to circulate in the pig stocks where it was isolated. [/b]no human illnesses have been reported among employees of these pig operations but antibody studies are only now underway so we don't yet know if there was any infection (albeit asymptomatic) in humans.
how big a deal is this? no one knows. here are two views:
when asked whether the newfound virus currently represents a threat to humans, gramer replied, "no more than any other influenza virus in the world. transmission of flu from pigs to humans is likely rare. this flu itself is rare and we don't know if it is currently circulating in this farm or any other farm in the usa. we haven't found it again."
[snip]
another expert, michael t. osterholm, phd, mph, generally concurred with gray. "i think it's a potentially serious threat," said osterholm, director of the university of minnesota center for infectious disease research and policy, publisher of cidrap news. "i think one of the problems we have is that we tend to think of influenza today, because of h5n1, as an asian disease, with the roots of any future pandemic planted deep in asia. but we have to be very careful because we don't know that."
take your pick. i know which one i prefer. but wishing won't make it so.
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.
A 24-year-old Indonesian woman from West Jakarta has died from avian influenza, putting the total fatalities in the country to 94, the Indonesian Health Ministry said Tuesday.
The woman died on Tuesday morning at Cengkareng Hospital in the capital and both of her laboratory tests showed that she was positively infected by H5N1 virus, said Nyoman Kandun, director of the ministry.
The large number of outbreaks in Egypt ... allow for extensive recombination between closely related clade 2.2 sequences. This lead to more genetic complexity last season, including the Tamiflu resistance marker, N294S, which was in H5N1 from the Gharbiya cluster collected prior to treatment.
The reports of H5N1 circulating in Europe and the Middle East, as well as a large human cluster in Pakistan, increases the likelihood of new human sequences in the region, with novel combinations of polymorphisms, including receptor binding domain changes, leading to larger clusters.
indigo girl
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CIDRAP Update Pakistan and Indonesia
http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/dec1807flu.html