Confirmation of Avian Influenza H7N2 Infection in Wales

[scottmcpherson]

Re: Confirmation of Avian Influenza H7N2 Infection

Excellent AP story. Well-written. And of course, not carried hardly at all by the American media.

Maybe if Paris Hilton contracted bird flu, we could accomplish both media focus and a potential reduction in the gene pool.

[Vibrant62]

Re: Confirmation of Avian Influenza H7N2 Infection

That is incorrect. Both H5 and H7 can convert by adding or changing amino acids at the cleavage site.

There is no evidence that an H5/H7 reassortant would be bad.

Comments on H5 vs H7 mechanism of transformation to HPAI are supported by the following paper. I wholly agree that there is no guarantee that an H7 virus would be bad, merely that it has the potential (like H5 viruses) to convert to HPAI variants, relatively readily. Therefore an H7 pandemic could be quite a serious matter, even if at present it only causes mild human disease; as human experience of H7 infections of a high path variant are (fortunately) very limited, no one can state with any certainty what the disease profile might be in humans. However, a high path human variant must be viewed as likely to be quite severe. This was a primary concern of WHO planners I worked with some years ago, when working on selection of annual vaccine strains. An H7 or an H5 human virus was often quoted as the 'nightmare scenario', and one we should hope would never happen as the world would be in deep trouble if it were to occur. It is the reason I have followed the H5N1 virus so closely for the last few years.

Lee CW, Lee YJ, Senne DA, Suarez DL. Pathogenic potential of North American H7N2 avian influenza virus: A mutagenesis study using reverse genetics. Virology. 2006 Jul 7; [Epub ahead of print]
submited by wanglh at Jul, 14, 2006 8:30 AM from Virology. 2006 Jul 7; [Epub ahead of print]

An H7N2 subtype avian influenza virus (AIV) first appeared in the live bird marketing system (LBMS) in the Northeastern United States in 1994. Since then this lineage of virus has become the predominant subtype of AIV isolated from the LBMS and has been linked to several costly commercial poultry outbreaks. Concern for this low pathogenicity isolate mutating to the highly pathogenic form has remained high because of the increasing number of basic amino acids at the hemagglutinin (HA) cleavage site, which is known to be associated with increased pathogenicity of AIV. To address the risk of low pathogenic LBMS-lineage H7N2 virus mutating to the highly pathogenic form of the virus, we generated a series of mutant viruses that have changes in the sequence at the HA cleavage site by using plasmid-based reverse genetics. We confirmed that a conserved proline at -5 position from the HA cleavage site could be changed to a basic amino acid, producing a virus with five basic amino acids in a row at the cleavage site, but with no increase in virulence. Increased virulence was only observed when additional basic amino acids were inserted. We also observed that the virus preferred the arginine instead of lysine at the -4 position from the cleavage site to manifest increased virulence both in vitro and in vivo. Using helper virus-based reverse genetics, where only one transcription plasmid expressing a mutated HA vRNA is used, we identified specific HA cleavage site sequences that were preferentially incorporated into the low pathogenic wild-type virus. The resultant reassortant viruses were highly pathogenic in chickens. This study provides additional evidence that H7 avian influenza viruses require an insertional event to become highly pathogenic, as compared to H5 viruses that can become highly pathogenic strictly by mutation or by insertions.

See Also:

http://www.ncbi.nlm.nih.gov/entrez/...ubmed_docsum***

The concerns for an H5/H7 reassortant are based on the supposition that the virulence genes are spread across three seperate RNA strands, and therefore the odds of a reassortant virus acquiring increased virulence are reasonably high but by no means certain. Much depends how accurate the findings of the following paper are with regard to virulence distribution; additionally, I had not meant to imply that an H7 pandemic virus would certainly be bad, merely possible and with a high degree of risk that an HP variant would emerge if such a virus became widespread. If that was not the way in which my comment was read, please do accept my apologies.

See: Why is the world so poorly prepared for a pandemic of hypervirulent avian influenza?

http://www.informaworld.com/smpp/content~content=a768149644~db=all~order=page

Authors: Olav Albert Christophersen; Anna Haug a

a Norwegian University of Life Sciences. Ås. Norway

DOI: 10.1080/08910600600866544

Publication Frequency: 3 issues per year

Published in: Microbial Ecology in Health and Disease, Volume 18, Issue 3 & 4 December 2006 , pages 113 - 132

Keywords: avian influenza; virulence factors; virulence evolution; risk estimates; emergency preparedness

[vinny]

Re: Confirmation of Avian Influenza H7N2 Infection

Mild bird flu in Britain has pandemic potential, experts say
The Associated PressPublished: May 29, 2007



The four presumed human H7N2 bird flu cases identified in Britain last week are a reminder that the next flu pandemic could be sparked by a virus other than the feared H5N1 strain, experts say.

While the global health community's attention in recent years has targeted the H5N1 virus, which has killed at least 186 people worldwide since 2003, some experts worry that attention is being diverted from seemingly less dangerous bird flu subtypes like H7.

"There may be a bit of complacency when it comes to recognizing the pandemic potential of H7 viruses," World Health Organization bird flu expert Dr. Michael Perdue said Monday.

Last week, British authorities confirmed that four people apparently tested positive for H7N2, a mild strain of bird flu, after 15 chickens at a small farm in Wales died. Health officials are currently investigating 36 people who may also be infected, of whom 11 have symptoms of flu or conjunctivitis.

Having so many human cases at once is a potential concern. In Asia, where H5N1 has circulated most widely, millions of people have been exposed to millions of infected birds, resulting in about one new infection per week.



"Here, we're talking about a small number of birds and yet we still have four cases," Perdue said. "Unless there's something unusual about the contact with birds, that suggests the virus is finding new ways of getting into humans."

The H7 subtype has previously sparked human outbreaks. In a large outbreak in the Netherlands in 2003, 89 human cases were reported, mostly of conjunctivitis, as well as one death. There were also at least three likely instances of human-to-human transmission involving family members of poultry workers. In the case of the single fatality, officials noticed that particular virus had about 10 mutations.

British officials have been quick to reassure the public that the "low pathogenic" H7N2 virus ? in comparison to the "highly pathogenic" H5N1 virus ? poses little risk to the population. Indeed, H7N2 appears to cause only mild symptoms such as eye infections.

But low pathogenic viruses can quickly morph into highly pathogenic ones, sometimes within weeks. Too little is known about flu viruses to predict with any certainty which ones are most lethal for humans.

"The pandemic risk from low pathogenic avian viruses is almost as bad as that from highly pathogenic avian viruses," said Dr. Angus Nicoll, an influenza expert at the European Centre of Disease Prevention and Control.

"When people say low pathogenic or highly pathogenic, that only refers to how unpleasant the disease is for birds," Nicoll explained. "That's almost irrelevant for humans."

Like all flu viruses, low pathogenic viruses mutate rapidly, and could theoretically transform into a pandemic strain without the warning signals of a more virulent strain, which would leave many dead chickens ? and perhaps humans ? in its wake. Experts also worry about the possibility of a bird flu virus mixing with a human flu virus to create a new pandemic strain.

"If you have an H7 virus causing mild symptoms, that might give the virus the chance to reassort into a more dangerous virus before anybody notices," Perdue said. And for health officials hoping to quash a pandemic in its emerging stages, it might be too late to contain a global outbreak without an early warning.

Most experts believe that the preoccupation with H5N1 as the most likely pandemic candidate is justified.

"The situation with H5N1 is very intense," said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in the United States. "We know that H7 can cause outbreaks in chickens and that it can occasionally jump the species barrier, but it has not done it nearly to the extent of the H5N1 virus."

Unlike many other bird flu subtypes, which disappear off the radar after a short period, H5N1 has remained entrenched in the environment, and continues to spread to new areas.

Still, while no bird flu virus can be ruled out when it comes to igniting the next pandemic, some clues may exist. Though H5N1 has several worrying characteristics, other flu subtypes are also in the running for the pandemic title.

"The last two flu pandemics were the result of a human flu virus recombining with low pathogenic avian viruses," said Perdue. The H7N2 recently detected in Britain would fall into that category. "Given that historical context, perhaps we should concentrate our efforts a little more in that direction."

http://www.iht.com/articles/ap/2007/05/29/europe/EU-MED-Britain-Bird-flu.php

[HenryN]

Re: Confirmation of Avian Influenza H7N2 Infection

So why aren't the Egyptian cases spreading as quickly as the UK cases, since they both have M230I?

.

Egyptian cases are H5. Gharbiya is the largest cluster reported to date from Egypt.

[HenryN]

Re: Confirmation of Avian Influenza H7N2 Infection

Here is more text, clearly stating that the four patients were positive for avian influenza (bold added)

The Health Protection Agency is providing expert support and advice to the National Public Health Service for Wales after an H7N2 avian influenza infection was found in birds on a small farm in north Wales. The Agency has carried out tests on specimens from nine people associated with the incident; seven are from Wales and two were from north west England.
Four of the test results were positive - two of these were from Wales and two were from north west England.The remaining five test results came back as negative. However because these five cases were associated with the birds and had a compatible illness, they are being treated as a precaution.
H7N2 is a low pathogenic strain of avian flu. It is different to the highly pathogenic H5N1 strain currently circulating in South East Asia, and in Europe last year. In almost all human cases to date, H7N2 infection has generally been associated with a mild disease. The risk to the general public is considered to be very low.
Pat Troop, Chief Executive of the Health Protection Agency said:-
?As a routine precaution, we have tested those who were associated with the infected or dead birds and reported flu-like symptoms. We tested samples from nine people in our laboratories and confirmed infection in four.
?These test results confirm that human infection with the avian flu virus has occurred. The cases so far have been associated with the infected birds. ?It is important to remember that H7N2 avian flu remains largely a disease of birds.

[AlaskaDenise]

Re: Confirmation of Avian Influenza H7N2 Infection

M230I is on H7 in Engkand and on H5 in Egypt.

So why aren't the Egyptian cases spreading as quickly as the UK cases, since they both have M230I?

.

[HenryN]

Re: Confirmation of Avian Influenza H7N2 Infection

Would someone mind please posting the URL to the government statement that gives the details of the 2 positives from N-W England? Thanks

Here's the text on the four positives

"Four of the test results were positive - two of these were from Wales and two were from north west England.The remaining five test results came back as negative. However because these five cases were associated with the birds and had a compatible illness, they are being treated as a precaution"

[HenryN]

Re: Confirmation of Avian Influenza H7N2 Infection

Would someone mind please posting the URL to the government statement that gives the details of the 2 positives from N-W England? Thanks

The link was p[osted on your H5N1 ebs and flow thread. The direct link is to the official statements is

http://www.hpa.org.uk/hpa/news/articles/press_releases/2007/070525_avian_flu_H7N2.htm

[HenryN]

Re: Confirmation of Avian Influenza H7N2 Infection

Avian flu contacts 'identified'
Health officials say they have identified all the people who came into close contact with an outbreak of avian flu at a smallholding in north Wales.

The number of people who may have had contact with the disease rose over the weekend to 142.
The disease, which is the H7N2 strain of bird flu, not the more virulent H5N1, was first found last week among chickens at a farm near Corwen, Conwy.
Children at a Denbighshire school are being offered anti-viral medication.
A year five pupil at Ysgol Henllan suspected of contracting the virus has been linked to the smallholding.
A dozen children aged nine and 10 and two teachers at the school are being given tamiflu treatments as a precaution.
School meeting
The National Public Health Service of Wales has said a total of 142 people have had either direct or indirect contact with the smallholding.
Four people have tested positive for bird flu and 12 have flu-like symptoms, but no-one is seriously ill.
Of the 142 to come into contact with the virus, 47 came into contact "in the household setting," 14 in the school and 81 in "the workplace setting".
Health officials held a meeting for concerned parents at the school on Monday evening, in which it was stressed the risk of anyone contracting the virus is very small.


Another meeting for those who could not attend is planned for Tuesday evening.
Hugh Pennington, a microbiologist and bird flu expert from Aberdeen University, said there was no risk of the virus being spread from person to person.
Professor Pennington said: "You have to be in quite close contact with infected birds to get infected.
"It doesn't spread from one infected person to another.
"It's still a bird virus - someone infected isn't going to cause any more human cases."
Professor Pennington added that distribution of tamiflu was a sensible precaution.
Birds slaughtered
The first confirmed case involved a smallholding at Llanfihangel Glyn Myfyr, Conwy.
Owners Tony Williams and Barbara Cowling, who have tested negative for the virus, called in a vet after their Rhode Island Red chickens began to die.
They bought the chickens at Chelford Market at Macclesfield, Cheshire, some 70 miles (112 km) away, on 7 May.
A total of 30 chickens from the smallholding have now been slaughtered after 15 birds died.
Officials have stressed that the disease found at the Conwy farm was the H7N2 strain of bird flu, not the more virulent H5N1.
The second possible case emerged on Saturday about 35 miles (56 km) away, at a farm on the outskirts of Efailnewydd, near Pwllheli. It has also been linked to the market.

Story from BBC NEWS:

http://news.bbc.co.uk/go/pr/fr/-/1/hi/wales/6699595.stm

[HenryN]

Re: Confirmation of Avian Influenza H7N2 Infection

Why is the M230I in the UK cases spreading more quickly than the M230I in Al Gharbaya? Are there other genes in the RBD that are different in these two cases?

.

M230I is on H7 in Engkand and on H5 in Egypt.

[AlaskaDenise]

Re: Confirmation of Avian Influenza H7N2 Infection

A reassortant with an increased H2H efficiency would be H7, so it is not clear that such a virus would be virulent, because an H7 may not fit in with H5 internal genes, and therefore the cases may be even milder and less infectious than H7N2. This was seen in reassortant tests with H5N1 done by the CDC with human flu genes.

Why is the M230I in the UK cases spreading more quickly than the M230I in Al Gharbaya? Are there other genes in the RBD that are different in these two cases?

.

[KBD]

Re: Confirmation of Avian Influenza H7N2 Infection

Would someone mind please posting the URL to the government statement that gives the details of the 2 positives from N-W England? Thanks

[gsgs]

Re: Confirmation of Avian Influenza H7N2 Infection

they couldn't get any reassortants at all. Not viable.

But they could only test some possible combinations and few possible strains ,
of course.

[HenryN]

Re: Confirmation of Avian Influenza H7N2 Infection

Can you qualify "bad"? For instance, I would consider any novel virus that spreads easily H2H as "bad" regardless of mortality rate.

A reassortant with an increased H2H efficiency would be H7, so it is not clear that such a virus would be virulent, because an H7 may not fit in with H5 internal genes, and therefore the cases may be even milder and less infectious than H7N2. This was seen in reassortant tests with H5N1 done by the CDC with human flu genes.

[HenryN]

Re: Confirmation of Avian Influenza H7N2 Infection

The first news release refers to H7N2 and specifies 4 persons. It could be badly written?

"...The Health Protection Agency is providing expert support and advice to the National Public Health Service for Wales after an H7N2 avian influenza infection was found in birds on a small farm in north Wales. The Agency has carried out tests on specimens from nine people associated with the incident; seven are from Wales and two were from north west England.
Four of the test results were positive - two of these were from Wales and two were from north west England.The remaining five test results came back as negative. However because these five cases were associated with the birds and had a compatible illness, they are being treated as a precaution.
H7N2 is a low pathogenic strain of avian flu...."

It's not the press release that was badly written. It was quite clear that two were from the north west and two were from Wales.

I suspect the two from Wales were the vet and a family member (as in child), while the two from the north west were investigators called in by the local vet.

I am sure that the child's classmate know the student's identity and relationship to the farm. Since media reports also indicate that the farm owners initially had symptoms, they may have infected the child. Since the owners were tested late, they had probably already cleared the virus, so they were negative, but will almost certainly be positive in a convalescent antibody test.