Is seems to me there are several medical tests that could show whether it was h2h by blood test. Wouldnt it show that the virus had mutaed after being passed from one person .

What I mean is should there be medical test that would be decisive in this matter/
Im not sure I buy the WHO being not sure or vague

This is the first I've heard of defeathering swans in connection with this cluster.  (It was mentioned widely in the Azerbijain cluster.)

Did I miss something, or is this new?

It would be interesting to know how the WHO classifies H2H - respiratory only, handling body fluids, sharing towels, drinking from the same cup?  I hope they are focusing on the actuals results (that is, H2H has occured) rather than the means.  They explained 3 cases by saying they all slept in the same room together.  That seems to me to be pretty reliable H2H, and what about the others?  The fact that they are holding out hope to find another source tells me they just don't want to come out and say it has occured.  If they weren't so afraid of the truth, perhaps the media would cover it more.  All this wishy-washy stuff means people aren't preparing.

xx
    
    

But of course we did hear about swan feathers before - so if you're not really paying attention it makes sense.....

joining the conspiracy theorists 

From Survivors post:

"Sequencing ... found no evidence of genetic reassortment ... and no evidence of significant mutations," the agency said in a statement.

No one can check up on this because they won't release the sequences.   Until they do, I don't believe we can really know what's happening.

Commentary
 
Human H5N1 Sequences from North Sumatra Indonesia

Recombinomics Commentary
May 23, 2006

Full genetic sequencing of two viruses isolated from cases in this cluster has been completed by WHO H5 reference laboratories in Hong Kong and the USA. Sequencing of all eight gene segments found no evidence of genetic reassortment with human or pig influenza viruses and no evidence of significant mutations. The viruses showed no mutations associated with resistance to the neuraminidase inhibitors, including oseltamivir (Tamiflu).

The human viruses from this cluster are genetically similar to viruses isolated from poultry in North Sumatra during a previous outbreak.

Although the above WHO description has more detail than earlier description of the first confirmed human case in Indonesia

Genotyping of the PCR-amplified isolate from the confirmed case shows high homogeneity with other H5N1 isolates from poultry in Java, and no evidence of reassortment.

Or the second confirmed case

The sequence showed that the virus was essentially the same A(H5N1) avian influenza virus that had already been circulating in poultry in Indonesia, he said.

The sequence from the first case has been made public and it had a number of features that distinguishing it from poultry in Java.  There was high homology with the poultry isolates, but the sequence had a novel HA cleavage site as well as an extra glycosylation site on HA.  Subsequent reports indicated almost all isolates from West Java / Lampung had the novel cleavage site raising question of the origin of the H5N1 infecting people in the area.

In contrast, as noted above, the second sequence was "essentially the same" as avian influenza. But not considered essentially the same as the first isolate, suggest the second isolate from Indonesia was the sequence without the novel cleavage site. 

For the index isolate, only the HA and NA sequence of the CDC has been released.  It is likely that the described Hong Kong version of the sequences are virtually identical.

The two North Sumatra sequences sound like they are closely related to each, which would have been expected  for isolates from relatives infected around the same time in the same location. The comments on reassortment are not surprising.  H5N1 has never been shown to reassort with human or swine sequences although H5N1 isolates have acquire mammalian polymorphism via recombination.  Similarly, the H1N1 pandemic strain of 1918 had no evidence of reassortment, but had polymorphisms from human and swine H1N1 isolates from the early 1930's indicating the pandemic strain was also a recombinant between two H1N1 serotypes.  Swine H5N1 is closely related to avian H5N1 and neither are efficiently transmitted to humans.

However, the North Sumatra cluster was generated by extended human to human transmission (H2H), covering at least three generations (H2H2H2H), raising questions about acquired plymorphisms which may not be considered "significant" by the sequencers.  Interestingly they only spoke of wild type NA sequences, resulting in Tamiflu sensitivity.  This would be expected, since yesterday the United States announced deployment of its Tamflu reserves to Asia.

However, yesterday WHO announced use of amantadines in combination with Tamiflu, but the above description fails to indicate that the isolates are amantadine sensitive.  Since prior poultry isolates in Indonesia have been shown to be amantadine resistant, but none have been shown to be Tamiflu resistant, the exclusion of comments on amantadine suggests the human isolates, like some of the poultry isolates, are amantadine resistant.

Similarly, there is no mention of the presence of the PB2 polymorphism, E627K, which when combined with a wild type H5N1 cleavage site is almost always fatal in mammals.  This change has been found in human H5N1 isolates from the 1997 outbreak in Hong Kong as well as outbreaks in more recent outbreaks in Vietnam and Thailand.  The change has also been found in fatal infections of wild and domestic cats and well as a domestic dog.

However, such interpretations of carefully parsed updates should not be necessary.  All eight gene segments of all of the H5N1 in Indonesia should be released.  The sequences in West Java raise serious question about the origin of the infections and the determine of the what is and is not significant in the current isolates should be determined by the scientific community and not a small group of sequencers overly focused on reassortment, which was also not demonstrated in earlier lab experiments mixing 1997 avian H5N1 with human H3N2 genes and will probably not be demonstrated when 2004 H5N1 is mixed with human H3N2 genes.

The current cluster has extended H2H transmission chains.  Careful analysis of the full sequences could provide genetic clues on possible reason why the transmission was efficient and deadly.  Seven of the eight cluster members have died, making this cluster the deadliest reported to date.  This deadly combination may be due to a wild type cleavage site of RERRRKKR coupled with a PB2 E627K polymorphism, which in the past has been fatal in almost all human infections coupled with the RERRRKKR cleavage site.

However, there is no reason to be speculating on the sequestered sequences. 

They should be released immediately.

Media Link

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INFLUENZA >>  AVIAN INFLUENZA >>  NEWS >> 

Case for human spread of avian flu in Indonesia grows

May 23, 2006 (CIDRAP News) – All seven confirmed cases of H5N1 avian influenza in the family cluster in Indonesia involved "close and prolonged exposure" to another infected person, suggesting person-to-person transmission, the World Health Organization (WHO) said today.

However, the WHO statement stopped short of a definite conclusion that the virus spread from person to person. In addition, the agency said it has found no evidence of genetic reassortment or mutation in two H5N1 viruses collected from cases in the cluster and no evidence of continuing or efficient human-to-human transmission.

"All confirmed cases in the cluster can be directly linked to close and prolonged exposure to a patient during a phase of severe illness," the WHO said. "Although human-to-human transmission cannot be ruled out, the search for a possible alternative source of exposure is continuing."

The WHO also confirmed today that the 32-year-old man in the family cluster who died yesterday is officially Indonesia's 42nd case and 33rd fatality. He was the father of the 10-year-old boy who died May 13 and the brother of the initial case-patient. "The father was closely involved in caring for his son, and this contact is considered a possible source of infection," the agency said.

Although the WHO stressed that investigation of the outbreak is ongoing, preliminary findings indicate that three of the infected family members had spent the night of April 29 in a small room with the 38-year-old woman who is considered the index case. She had developed symptoms April 27 and was coughing frequently on April 29, according to the WHO.

She died May 4 and was not tested for H5N1 because samples were not obtained before her burial, but her signs and symptoms pointed to avian flu infection.

Those who shared the room with her that night in Kubu Sembelang village were her two sons, both of whom died of avian flu, and her 25-year-old brother, the only surviving member of the cluster. Other infected relatives, according to the WHO, lived in adjacent homes.

As yet, the investigation by officials from the WHO, the US Centers for Disease Control and Prevention, and the Indonesian Ministry of Health has found no evidence of avian flu spreading in the community, the WHO said. Investigators are focusing their search on any additional cases among family members, other close contacts, or area residents, as well as on an alternative source such as infected animals or feces.

Human-to-human transmission of H5N1 probably occurred at least once before, when the mother and an aunt of an infected girl in Thailand fell ill after caring for her in 2004. But no instances of sustained transmission have been documented.

The WHO also reported today that complete genetic sequencing of two H5N1 isolates from the North Sumatra cluster has been completed by WHO reference laboratories in Hong Kong and the United States. The sequencing of all eight gene segments revealed no evidence of genetic reassortment with human or pig influenza virus.

It also showed no evidence of significant mutation. Specifically, the WHO noted, viruses tested showed no mutations associated with resistance to the neuraminidase inhibitors, including oseltamivir.

In addition, viruses in this outbreak are genetically similar to those isolated from poultry in the province during a previous outbreak, the WHO said.

This latest confirmed H5N1 case brings the worldwide total in humans to 218, including 124 deaths. Indonesia's numbers since 2003 are second only to Vietnam, which has reported no new cases since November 2005, according to WHO data. In 2006, Indonesia's WHO-confirmed cases total 25, including 22 deaths, well exceeding other countries.

See also:

WHO's May 23 Indonesia update
http://www.who.int/csr/don/2006_05_23/en/index.html

WHO cumulative case count
http://www.who.int/csr/disease/avian_influenza/country/cases_table_2006_05_23/en/index.html

Center for Infectious Disease Research & Policy Academic Health Center -- University of Minnesota Copyright © 2006 Regents of the University of Minnesota