Bird Flu Watch

Too early to call re Pakistani human to human transmission

Link: Effect Measure : Now I'm the one complaining about WHO (again).

The World Health Organisation on Friday ruled out any mutation of the potentially fatal H5N1 strain of the bird flu virus after a case of inter-human transmission of bird flu may have been detected in Pakistan.     "There is no suggestion that the virus has changed into a form that poses a broader risk," WHO spokesman John Rainford told AFP. "If that had been the case, we would have witnessed more cases of human transmission."     Rainford said that the genetic sequencing of the virus involved in the latest case was being continued. (Agence France Presse)

What's wrong with this? Suppose (for the sake of argument) it takes two changes to turn a virus into one that "poses a broader risk" and only one has occurred in this case. We wouldn't know this by seeing if there were more cases. We would only know this if we looked at the sequence and further, we knew what to look for (which two changes to track). It isn't clear that the viral sequence in this case has been examined completely (and we hope that when it is examined, the sequence will be deposited immediately into a publicly accessible database like GenBank). It is also quite clear we don't know what to look for, so a categorical statement that "a mutation" has been "ruled out" isn't true and cannot be true at this point.

New Swine Flu Has Avian Flu Genes

Link: New Swine Flu Has Avian Flu Genes | Lancaster Farming.

The group studied an unknown pathogen — first identified by University of Minnesota veterinary diagnostician Marie Gramer — that infected two groups of pigs at separate production facilities in 2006. Both facilities used pond water frequented by migrating waterfowl. Molecular studies indicated the unknown pathogen was an H2N3 influenza virus that is closely related to an H2N3 strain found in mallard ducks. But this was the first time it had been observed in mammals. Influenza viruses have eight gene segments, all of which can be swapped between different virus strains. Two of these gene segments code for virus surface proteins that help determine whether an influenza virus is able to infect a specific host and start replicating — the first step in the onset of influenza infection. 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.

Vietnames detect genetic drift

Link: Promed.

Avian H5N1 influenza in the country has mutated into a more dangerous version, according to the local newspaper Youth. The daily reported on Sat 12 Nov 2005 that results of the Institute's research on 24 virus samples from infected poultry and people in the southern region between December 2003 and March 2005 show there are some changes in gene segments coding for the surface antigens HA and NA and some other gene segments of the H5N1 virus in Viet Nam in early 2005. The changes indicate that the virus has been mutating to reproduce effectively in cells of mammals and increase its attacking capability. All the viruses researched by the institute in southern Ho Chi Minh City are resistant to the 2 antiviral medicine agents Amantadine and Rimantadine. The Institute has decoded completely or partly genes of 24 virus samples. 5 samples from humans and 16 from fowl have been decoded completely. However, the institute has been unable to define which kinds of mutations allow human-to-human transmission, and which conditions lead to the mutations.

Human to human - a growing trend?

Link: Fourth Human H5N1 Bird Flu Fatality in Jakarta Indonesia.

More provocative thoughts from Recombinomics

The fourth fatality in Indonesia is again in Jakarta, where there have also been reports of H5N1 in swine.  The swine sequences were similar to H5N1 in Yunnan China.  The three earlier cases formed a familiar cluster with a bimodal distribution of onset dates, provide solid evidence for human-to-human transmission.  This transmission profile matches earlier familial clusters in Thailand, Cambodia, and Vietnam.

Sequence data from the earlier cluster would be useful.  Earlier H5N1 isolates from Indonesia were the Z genotype, but there are regional differences and early sequences from Indonesia are distinct from those for fatal cases in Vietnam, Thailand, and Cambodia.

Effect Measure: Thai newspaper: pandemic phase 4?

Link: Effect Measure: Thai newspaper: pandemic phase 4?.

While many dismiss claims of a coming epidemic as far fetched the evidence grows.

Dr. Kamnuan is indeed a "flu insider," having reported the first widely accepted case of human to human transmission in the medical literature. The Nation records him as deploring his government's continued insistence that human to human transmission has not been demonstrated, characterizing it as "false information."

Thailand has been more diligent of late in surveillance and prompt reporting of poultry infections to the OIE (the international agency that keeps track of animal disease outbreaks). But they need to face the facts they report. Whether this is obfuscation to avoid alarming their citizenry or just plain denial is unclear, but Dr. Kamnuan is right on the mark here.

This virus is Hurricane Katrina a thousand times over.

H5N1 virulence differ within species from same area

Link: The Journal of Virology.

The current alarm is based in empirical evidence of increased virulence as the increasing number of academic papers testify.

We recently analyzed a series of H5N1 viruses isolated from healthy ducks in southern China since 1999 and found that these viruses had progressively acquired the ability to replicate and cause disease in mice. In the present study, we explored the genetic basis of this change in host range by comparing two of the viruses that are genetically similar but differ in their ability to infect mice and have different pathogenicity in mice. A/duck/Guangxi/22/2001 (DKGX/22) is nonpathogenic in mice, whereas A/duck/Guangxi/35/2001 (DKGX/35) is highly pathogenic. We used reverse genetics to create a series of single-gene recombinants that contained one gene from DKGX/22 and the remaining seven gene segments from DKGX/35. We find that the PA, NA, and NS genes of DKGX/22 could attenuate DKGX/35 virus to some extent, but PB2 of DKGX/22 virus attenuated the DKGX/35 virus dramatically, and an Asn-to-Asp substitution at position 701 of PB2 plays a key role in this function.

2004 human cases more virulent than 1997 isolates

Link: The Journal of Virology.

Click the link above for more from this academic abstract

Rapid disease progression and high lethality rates in ferrets distinguished the highly virulent 2004 H5N1 viruses from the 1997 H5N1 viruses. A pair of viruses isolated from the same patient differed by eight amino acids, including a Lys/Glu disparity at 627 of PB2, previously identified as an H5N1 virulence factor in mice. The virus possessing Glu at 627 of PB2 exhibited only a modest decrease in virulence in mice and was highly virulent in ferrets, indicating that for this virus pair, the K627E PB2 difference did not have a prevailing effect on virulence in mice or ferrets. Our results demonstrate the general equivalence of mouse and ferret models for assessment of the virulence of 2003 and 2004 H5N1 viruses. However, the apparent enhancement of virulence of these viruses in humans in 2004 was better reflected in the ferret.

Mallards could host Fatal Bird Flu Variant

Link: Co-circulation of H5N1 and H7N7 Bird Flu in Europe?.

  The H5N1 from Qinghai Lake has acquired sequences from European swine via recombination, and its presence in Europe this year will lead to more dual infections and more recombination.

Co-circulation of H5N1 and H7N7 is particularly dangerous, because H7N7 is efficiently passed from human to human.  Thus, H5N1 could acquire sequences allowing efficient human-to-human transmission, and this acquisition could happen in mallard ducks, which are known to be infected with H5 from Chany Lake, A/Anas platyrhynchos/Chany Lake/9/03(H5N3), or Primorie, A/duck/Primorie/2633/01(H5N3).  Birds infected with H7N7 have also led to isolates from the Netherlands, A/avian/Netherlands/065/03(H7N7).

Rapid Evolution in Qinghai Lake Migratory Bird Flu H5N1

Link: Rapid Evolution in Qinghai Lake Migratory Bird Flu H5N1.

The need for additional specimens from Qinghai Lake is clear.  China only collected samples from 12 dead birds, 10 bar-headed geese, a great black headed gull, and a brown headed gull.  The sequences from all 12 isolates were very similar.  They all have acquired the human PB2 polymorphism E627K, which had not been seen previously in a H5N1 isolate from a bird.  All prior H5N1 with that change had common form mammals, including humans.  Virtually all humans infected with a virus containing E627K had died, suggesting the Qinghai isolates have the potential for being lethal in people also.

Flu mutates more quickly than thought

Link: Flu mutates more quickly than thought.

U.S. National Institute of Health researchers say they have found flu viruses can swap many genes more rapidly than thought to make new resistant strains. Scientists previously believed gene swapping progressed gradually from season to season, the BBC reported. But the NIH team found, instead, influenza A exchanged several genes at once, thereby causing sudden and major changes to the virus.