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PANDEMIC ALERT LEVEL
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Tracking the next pandemic: Avian Flu Talk

HK: No Cases Positive for BF - Event Date: June 27 2006
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    Posted: June 27 2006 at 4:37am
Hospital Authority's Enhanced Surveillance Programme
****************************************************

    In view of a human case of avian influenza H5N1 in Shenzhen, the Hospital Authority started the three-week Enhanced Surveillance Programme on June 15.

     Public hospitals should report to the Authority's e-Flu system all patients fulfilling the case definition of having pneumonia (all types) of unidentified etiology and who had travelled in the seven days before the onset of symptoms, to affected areas/countries with confirmed human cases of avian influenza infection in the past six months.

     The Hospital Authority today (June 27) received the report of nine cases (five male and four female, aged 1 to 83 years). So far a total of 127 cases (72 male and 55 female, aged two months to 89 years) have been received. These patients have visited Guangdong, Hunan, Hubei, Fujian, Zhejiang and Thailand before the onset of symptoms. The Hospital Authority has reported the cases to the Centre for Health Protection. Public hospitals have been providing rapid tests for these patients.

     At 5pm today, none of the cases had tested positive to Influenza A (H5) virus.

Ends/Tuesday, June 27, 2006
Issued at HKT 18:21

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Guests Quote  Post ReplyReply Direct Link To This Post Posted: June 27 2006 at 6:24am

"At 5pm today, none of the cases had tested positive to Influenza A (H5) virus."

Hmm.. they actually tested and then released (although not much) info. on the results...? Rather surprised at that.
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Originally posted by PonyGirl PonyGirl wrote:

Hospital Authority's Enhanced Surveillance Programme
****************************************************

       The Hospital Authority today (June 27) received the report of nine cases (five male and four female, aged 1 to 83 years). So far a total of 127 cases (72 male and 55 female, aged two months to 89 years) have been received. 
     At 5pm today, none of the cases had tested positive to Influenza A (H5) virus.

 
So they have verified that nine of the 127 are not H5.....
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Originally posted by jofg jofg wrote:

[QUOTE=PonyGirl]Hospital Authority's Enhanced Surveillance Programme
****************************************************

       The Hospital Authority today (June 27) received the report of nine cases (five male and four female, aged 1 to 83 years). So far a total of 127 cases (72 male and 55 female, aged two months to 89 years) have been received. 
     At 5pm today, none of the cases had tested positive to Influenza A (H5) virus.

So they have verified that nine of the 127 are not H5.....
 
Hmmmm... maybe you have worked for some of the agency's I have
 
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Guests Quote  Post ReplyReply Direct Link To This Post Posted: June 27 2006 at 7:39am
Good catch, jofg.
I am so tired of all these articles being so unclear and ambiguous. Is that on purpose, and you know there is something more to it, or are they just bad writers?









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Post Options Post Options   Thanks (0) Thanks(0)   Quote Guests Quote  Post ReplyReply Direct Link To This Post Posted: June 27 2006 at 8:02am
Most Interesting!

I had speculated that it could be SARS that they are pointing to, but it could just as well be a new improved H3, H2 or H1 variety of influenza.  Something is causing those people to get pneumonia like symptoms.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Guests Quote  Post ReplyReply Direct Link To This Post Posted: June 27 2006 at 8:05am
Originally posted by grace grace wrote:

Good catch, jofg.
I am so tired of all these articles being so unclear and ambiguous. Is that on purpose, and you know there is something more to it, or are they just bad writers?


The writers can only put down in print what they have been told.  The actual issue is, "How much can the Hong Kong doctors tell us?"

The "tested negative for H5" comment may be an official lie, too.  We won't know, but perhaps we need to look on Boxun to see what they are saying.
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Is the increase a result of better surveillance or increased disease?
 
Hong Kong - Death Rates for Leading Causes, 2001 - 2005
http://www.chp.gov.hk/data.asp?lang=en&cat=4&dns_sumID=117&id=27&pid=10&ppid=

(Number of Registered Deaths per 100 000 Population)

Classification of diseases and causes of death is based on the International Statistical Classification of Diseases and Related Health Problems (ICD) 10th Revision from 2001 onwards. The disease groups for the purpose of ranking causes of death have also been redefined based on the ICD 10th Revision, and new disease groups have been added. Figures from 2001 onwards may not be comparable with figures for previous years which were compiled based on the ICD 9th Revision. Therefore, figures before 2001 have been put down in a separate table.

Death rates for leading causes of death (based on ICD 10th Revision) : 2001 - 2005
List of ranking is based on 2004's number of deaths.

Cause of Death 2001* 2002* 2003* 2004* 2005*
1. Malignant neoplasms (ICD10: C00-C97) 169.6 171.8 169.2# 171.3 175.0#
2. Diseases of heart (ICD10: I00-I09, I11, I13, I20-I51) 69.9 73.2 78.0# 85.2 87.0#
3. Pneumonia (ICD10: J12-J18) 45.0 47.1 56.8# 53.4 59.2#
4. Cerebrovascular diseases (ICD10: I60-I69) 46.5 47.4 50.9# 49.6 49.4#
5. External causes of morbidity and mortality+ (ICD10: V01-Y89) 27.4 30.5 30.0# 32.6 29.0#
All other causes 136.7 135.7 150.4# 150.1 158.1#
All causes 495.2 505.6 535.4 542.3 557.7


Notes:
* The figures in the tables from 1998 onwards are compiled based on the population estimates under the "resident population" approach instead of the "extended de facto" approach.
+ According to the ICD 10th Revision, when the morbid condition is classifiable under Chapter XIX as "injury, poisoning and certain other consequences of external causes", the codes under Chapter XX for "external causes of morbidity and mortality" should be used as the primary cause of death.
# Provisional figure.
The mortality figures in this table are based on number of "registered" deaths.
The disease codes according to the classification are shown in brackets.
Figures may not add up to total due to rounding.

Number of Deaths by Leading Causes of Death by Sex by Age in 2004

http://www.chp.gov.hk/data.asp?lang=en&cat=4&dns_sumID=206&id=27&pid=10&ppid=
Cause of Death* Age Group
All Ages   0   1 - 4 5 - 14 15 - 44 45 - 64 65 & above Unknown
1 Malignant neoplasms (ICD10: C00-C97) Male 7183 2 1 12 315 2051 4801 1
Female 4608 1 2 8 318 1030 3249 0
Total 11791 3 3 20 633 3081 8050 1
2 Diseases of heart (ICD10: I00-I09, I11, I13, I20-I51) Male 3015 1 3 1 93 492 2421 4
Female 2851 1 0 4 36 151 2659 0
Total 5866 2 3 5 129 643 5080 4
3 Pneumonia (ICD10: J12-J18) Male 1905 1 2 2 27 135 1734 4
Female 1771 1 0 3 18 43 1706 0
Total 3676 2 2 5 45 178 3440 4
4 Cerebrovascular diseases (ICD10: I60-I69) Male 1730 0 1 0 33 264 1431 1
Female 1686 1 1 1 27 113 1543 0
Total 3416 1 2 1 60 377 2974 1
5 External causes of morbidity and mortality† (ICD10: V01-Y89) Male 1508 0 1 8 613 449 424 13
Female 735 1 0 8 267 145 313 1
Total 2243 1 1 16 880 594 737 14
6 Chronic lower respiratory diseases‡(ICD10: J40-J47) Male 1516 0 0 1 11 106 1398 0
Female 607 0 0 1 3 21 582 0
Total 2123 0 0 2 14 127 1980 0
7 Nephritis, nephrotic syndrome and nephrosis (ICD10: N00-N07, N17-N19, N25-N27) Male 542 0 0 0 9 73 460 0
Female 640 0 0 0 3 38 599 0
Total 1182 0 0 0 12 111 1059 0
8 Diabetes mellitus (ICD10: E10-E14) Male 311 0 0 0 9 34 268 0
Female 417 0 0 0 5 25 387 0
Total 728 0 0 0 14 59 655 0
9 Septicaemia (ICD10: A40-A41) Male 294 3 1 3 3 44 240 0
Female 321 2 0 0 2 24 293 0
Total 615 5 1 3 5 68 533 0
10 Aortic aneurysm and dissection (ICD10: I71) Male 241 0 0 0 6 42 193 0
Female 144 0 0 0 2 12 130 0
Total 385 0 0 0 8 54 323 0
  Other causes Male 2778 50 5 11 189 519 1987 17
Female 2513 57 4 8 101 192 2147 4
Unknown 5 0 0 0 0 0 0 5
Total 5296 107 9 19 290 711 4134 26
  All causes Male 21023 57 14 38 1308 4209 15357 40
Female 16293 64 7 33 782 1794 13608 5
Unknown 5 0 0 0 0 0 0 5
Total 37321 121 21 71 2090 6003 28965 50

Notes:
The mortality figures in this table are based on number of "registered" deaths.

* Classification of diseases and causes of death is based on the International Statistical Classification of Diseases and Related Health Problems (ICD) 10th Revision from 2001 onwards. The disease groups for the purpose of ranking causes of death have also been redefined based on the ICD 10th Revision, and new disease groups have been added. Figures presented above may not be comparable with figures for years before 2001 which were compiled based on the ICD 9th Revision. The disease codes according to the classification are shown in brackets.

According to the ICD 10th Revision, when the morbid condition is classifiable under Chapter XIX as "injury, poisoning and certain other consequences of external causes", the codes under Chapter XX for "external causes of morbidity and mortality" should be used as the primary cause of death.

Chronic lower respiratory diseases has been included as a disease group for the purpose of ranking the causes of death since 2001.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Guests Quote  Post ReplyReply Direct Link To This Post Posted: June 27 2006 at 8:28am

The phrase...

“The Hospital Authority today (June 27) received the report of nine cases (five male and four female, aged 1 to 83 years)”

refers to the number of new flu patients hospitals reported to the Hospital Authority on June 27.    “Public hospitals should report to the Authority's e-Flu system all patients fulfilling the case definition of having pneumonia.”

Each of these updates has the number of new patients reported on that day as well as the running total of flu patients.

It would be clearer if they’d say received the report of nine additional cases…
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That is a 30 percent increase in pneumonia cases from 2001!
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So either ALL 127 or the 9 cases today are negative.

Have my eye on this situation as am getting the feeling something is not right here.
 
Also their Center for Health Protection is INUNDATED with NEW information including lists of Dr's who are STOCKPILING ANTIVIRALS:
 
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I agree with you.  Could be that the pandemic has started and China is lying like hades, AGAIN, to keep the people placated.

I note in a news release today that China is now claiming that they believe they had the first H5N1 fatality in the world in December 2003.  They ignore the fatal cases in Hong Kong in 1997.  Obfuscation and gobbledygook to keep the people confused and ignorant.
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     Virtually all of the increased mortality stastistics for HK are related to smoking and to a lesser degree population ageing. The increase mortality stastics across the board are typical of smoking induced disease. The Chinese now smoke about a third of all cigarettes smoked in the world and HK is the leader of the Chinese pack.     ER Doc
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Originally posted by Frisky Frisky wrote:

     Virtually all of the increased mortality stastistics for HK are related to smoking and to a lesser degree population ageing. The increase mortality stastics across the board are typical of smoking induced disease. The Chinese now smoke about a third of all cigarettes smoked in the world and HK is the leader of the Chinese pack.     ER Doc
 
That would make sense as well.  With more money people would have increased access to cigaretts and the advertisers would be after them. 
 
Detailed lab results on all of this would help!  # tested ~ # negative
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Hospital Authority's Enhanced Surveillance Programme
****************************************************

    In view of a human case of avian influenza H5N1 in Shenzhen, the Hospital Authority (HA) started the three-week Enhanced Surveillance Programme from June 15.

     Public hospitals should report to the Authority's e-Flu system all patients fulfilling the case definition of having pneumonia (all types) of unidentified etiology and who had travelled in the seven days before the onset of symptoms, to affected areas/countries with confirmed human cases of avian influenza infection in the past six months.

     HA today (June 28) received the report of a total of 3 cases (3 male, aged 38 to 83).  So far a total of 130 cases (75 male, 55 female, aged 2-month to 89) have been received.  These patients have visited Guangdong, Hunan, Hubei, Fujian, Zhejiang and Thailand before the onset of symptoms.  HA has reported the cases to the Centre for Health Protection.  Public hospitals have been providing rapid tests for these patients.

     As at 5pm today, none of the test results is positive to Influenza A (H5) virus.

Ends/Wednesday, June 28, 2006
Issued at HKT 18:39

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"As at 5pm today, none of the test results is positive to Influenza A (H5) virus."
 
Ok, so now all of a sudden they are putting that on each daily report? Why weren't they putting it on there before the 27th?
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I'm still concerned about the young girl that recently passed, but tested negative with the throat swab. After she passed her lung tissue tested positive, but throat swabs were still showing a false negative. Wonder how thorough the testing being done actually is??
     
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Guests Quote  Post ReplyReply Direct Link To This Post Posted: June 28 2006 at 6:13am

"I'm still concerned about the young girl that recently passed, but tested negative with the throat swab. After she passed her lung tissue tested positive, but throat swabs were still showing a false negative. Wonder how thorough the testing being done actually is?? "

Which girl was this?
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  The really revealing pneumonia stastic above is 50 deaths age 5 to 44 and 3440 deaths age 65 and above. About 90% of all H5N1 deaths are age 5 to 44 and the number of documented H5N1 deaths in the elderly is only a few.  ER Doc
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Originally posted by Hope4Us Hope4Us wrote:

"I'm still concerned about the young girl that recently passed, but tested negative with the throat swab. After she passed her lung tissue tested positive, but throat swabs were still showing a false negative. Wonder how thorough the testing being done actually is?? "


Which girl was this?





Hope,
It's (false negatives) have been going on for awhile. Here is a section of the article and the link. It was in the NY Times mid-month. I posted it, but something else was going on at the time, so it slid off the page. No telling what the real count is. They aren't even counting the brother as an AI death even though it seems pretty obvious?

By DONALD G. McNEIL Jr.
Published: June 16, 2006
Yesterday the Indonesian Health Ministry said the death of a 7-year-old girl in Banten Province on June 1 was the country's 38th from avian flu. The girl's 10-year-old brother died May 29, but he was buried before specimens were taken, so he was not included in the count. Chickens in the family's household had died earlier.

According to news agency reports quoting health officials, the 7-year-old had tested negative for avian flu in nose and throat swabs taken when she was alive, but then tested positive when lung tissue was taken after her death.

Nose and throat swabs — the routine way of diagnosing regular flu — may give false negatives because the bird flu virus attaches to cells deep in the lungs, not to the upper respiratory tract. In January, according to the World Health Organization, the same error caused the first human cases in Turkey's outbreak to be misdiagnosed.

http://www.nytimes.com/2006/06/16/world/asia/16flu.html?ex=1151640000&en=e23f14bb1b68f113&ei=5070


    
    
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Ah, yes. I've got that one on my list
 

06/01/06 7 F

The girl developed symptoms on May 26, was hospitalized on May 30, and died on June 1. Her 10-year-old brother died of respiratory disease on May 29, but no specimens were taken for testing and the cause of his death cannot be determined. An investigation found a history of chicken deaths in the household and neighborhood prior to symptom onset. Laboratory testing of surviving family members and close contacts has been conducted and no further cases were found. Indonesia Tangerang

Thanks!
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Originally posted by bellabecky bellabecky wrote:

[QUOTE=Hope4Us]

Hope,
It's (false negatives) have been going on for awhile. Here is a section of the article and the link. It was in the NY Times mid-month. I posted it, but something else was going on at the time, so it slid off the page. No telling what the real count is. They aren't even counting the brother as an AI death even though it seems pretty obvious?

By DONALD G. McNEIL Jr.
Published: June 16, 2006
Yesterday the Indonesian Health Ministry said the death of a 7-year-old girl in Banten Province on June 1 was the country's 38th from avian flu. The girl's 10-year-old brother died May 29, but he was buried before specimens were taken, so he was not included in the count. Chickens in the family's household had died earlier.

According to news agency reports quoting health officials, the 7-year-old had tested negative for avian flu in nose and throat swabs taken when she was alive, but then tested positive when lung tissue was taken after her death.

Nose and throat swabs — the routine way of diagnosing regular flu — may give false negatives because the bird flu virus attaches to cells deep in the lungs, not to the upper respiratory tract. In January, according to the World Health Organization, the same error caused the first human cases in Turkey's outbreak to be misdiagnosed.

http://www.nytimes.com/2006/06/16/world/asia/16flu.html?ex=1151640000&en=e23f14bb1b68f113&ei=5070


    
    


It has been shown that some forms of H5N1 have developed the ability to survive at lower temperatures and are testing postive in throat swabs. Not all strains will do so. Therefore you could have a type which is more classic in the deep lung and less systemic as other forms have become.
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Originally posted by Hope4Us Hope4Us wrote:

Ah, yes. I've got that one on my list
 

06/01/06 7 F


The girl developed symptoms on May 26, was hospitalized on May 30, and died on June 1. Her 10-year-old brother died of respiratory disease on May 29, but no specimens were taken for testing and the cause of his death cannot be determined. An investigation found a history of chicken deaths in the household and neighborhood prior to symptom onset. Laboratory testing of surviving family members and close contacts has been conducted and no further cases were found. Indonesia Tangerang



Thanks!




Hope,
Do you have any news about more thorough testing in the works? I was telling my husband about it and wondering if there was a test that could check for AI in the lungs. He said, "would you want someone taking a sample from your lungs?". YES! I would rather have that done, than realize too late that I am actually positive and die! It seems reasonable to think that they could come up with a more effective test. Especially if they believe the current nose/throat swab could likely be unreliable. We can go to the moon, but we can't make a feasible test to check for AI reliably?




    
    
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Guests Quote  Post ReplyReply Direct Link To This Post Posted: June 28 2006 at 8:54am

Where is the latest update to the WHO website...? Are we to believe there are no NEW CASES of flu..?
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Bellabecky, sorry, no I don't. Wish I knew...

Ponygirl, I have been wondering that myself! The last records I have are the 13 yr. old male in Indonesia on 6-14 (of which his grandfather helped him slaughter diseased chickens, but as of that date he was still healthy..) and the 31 Male from Shenzhen on 6-15. What... It just stops there?? Curious.............
 
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Originally posted by Frisky Frisky wrote:

  The really revealing pneumonia stastic above is 50 deaths age 5 to 44 and 3440 deaths age 65 and above. About 90% of all H5N1 deaths are age 5 to 44 and the number of documented H5N1 deaths in the elderly is only a few.  ER Doc
 
That is why I highlighted Age 65 and above in Bold Red.
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Originally posted by Hope4Us Hope4Us wrote:

Ah, yes. I've got that one on my list
 
06/01/06 7 F

The girl developed symptoms on May 26, was hospitalized on May 30, and died on June 1. Her 10-year-old brother died of respiratory disease on May 29, but no specimens were taken for testing and the cause of his death cannot be determined. An investigation found a history of chicken deaths in the household and neighborhood prior to symptom onset. Laboratory testing of surviving family members and close contacts has been conducted and no further cases were found. Indonesia Tangerang

Thanks!

 
 
Are these the kid's in question?  Not sure, but happened on this article and sounded familiar?
 
 
False alarm on bird flu

A boy and a girl were admitted into separate hospitals in Sukhothai on suspicion that they could possibly have contacted bird flu as their families raised chickens which recently died mysteriously.

However, the public health office in Sukhothai announced on Wednesday that a blood test on the boy and girl showed that they were free of bird flu.

The threeyearold girl from Sawankalok district had just caught a cold while the tenyearold boy had influenza, doctors said.

Meanwhile Sukhothai's livestock office has already dispatched a team of veterinarians to villages of the boy and girl to collect information and discover the cause of the death of the chickens.

As precautionary measures, about 5,000 chickens were culled.

The Nation

 
 
 
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Sand,

No, the kids in your article are from Bangkok, if I'm not mistaken. The ones I referred to are from Indonesia. But, thanks anyhow! Smile
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Ponygirl, I have been wondering that myself!
 
The silence is deafening...FROM WHO.
 
Also the reports from Alaska seem to have dropped off the radar.
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Also what about the last family member in the cluster who had fallen ill with a serious infection around the brain. Is he alive, deceased or has he fallen into the bureaucratic  
black hole at WHO ?
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Guests Quote  Post ReplyReply Direct Link To This Post Posted: June 28 2006 at 4:50pm
Every single important report you hear of either ends up disappearing or was a "mistake", mistaken case of bird flu.
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Points: 396 		Post Options Post Options   Thanks (0) Thanks(0)   Quote bellabecky Quote  Post ReplyReply Direct Link To This Post Posted: June 28 2006 at 5:11pm
Originally posted by PonyGirl PonyGirl wrote:

Ponygirl, I have been wondering that myself!

<FONT style=": #222222"> 

<FONT style=": #222222">The silence is deafening...FROM WHO.

<FONT style=": #222222"> 

<FONT style=": #222222">Also the reports from Alaska seem to have dropped off the radar.



What was/is going on in Alaska? Did I miss that one?



    
"IN THE BEGINNING OF A CHANGE THE PATRIOT IS A SCARCE MAN, and brave, and hated and scorned. When his cause succeeds, the timid join him, For then it costs nothing to be a patriot. Mark Twain, 1904
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Testing birds for avian flu.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Guests Quote  Post ReplyReply Direct Link To This Post Posted: June 28 2006 at 6:21pm

China strenghens surveillence of flu-like outbreaks

China's Ministry of Health on Wednesday issued guidelines for reporting and investigating flu-like cases to strengthen surveillance of possible outbreaks.

The timely discovery and response to the outbreaks will help control the spread of the disease, the ministry statement said.

China has seen a number of influenza-like outbreaks in recent years and the outbreaks usually occur at places where a lot of people are clustered together such as schools.

The flu-like symptoms include fever, coughing or a sore throat, according to the guidelines.

The guidelines require that places with more than 30 flu-like cases in a week, or five cases of hospitalization, or one fatality caused by these diseases should report to the county's center for disease control and prevention (CDC) within two hours after the discovery.

Once lab tests confirm the cases as influenza, information of every individual case should be reported directly to the ministry through the network, the statement said.

China's first human bird flu case, a nine-year old boy in central China's Hunan province, was sick with the flu-like symptoms and his parents thought it was just flu at first.

China reported the 19th human case of bird flu early this month.

Scientists fear the H5N1 virus will mutate into a highly contagious form, possibly sparking a global pandemic. So far, most human cases have been linked to infected birds.

Source: Xinhua



People's Daily Online --- http://english.people.com.cn/
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Guests Quote  Post ReplyReply Direct Link To This Post Posted: June 28 2006 at 6:52pm

Minor mutations in avian flu virus increase chances of human infection

March 20, 2006 -  Few adaptations are needed to transform it into a potential pandemic virus

The H5N1 avian influenza virus, commonly known as "bird flu," is a highly contagious and deadly disease in poultry. So far, its spread to humans has been limited, with 177 documented severe infections, and nearly 100 deaths in Indonesia, Vietnam, Thailand, Cambodia, China, Iraq, and Turkey as of March 14, 2006, according to the World Health Organization (www.who.int).

"With continued outbreaks of the H5N1 virus in poultry and wild birds, further human cases are likely," said Ian Wilson, a Scripps Research professor of molecular biology and head of the laboratory that conducted the recent study. "The potential for the emergence of a human-adapted H5 virus, either by re-assortment or mutation, is a clear threat to public health worldwide."

Of the H5N1 strains isolated to date, the researchers looked at A/Vietnam/1203/2004 (Viet04), one of the most pathogenic H5N1 viruses studied so far. The virus was originally isolated from a 10-year-old Vietnamese boy who died from the infection in 2004. The hemagglutinin (HA) structure from the Viet04 virus was found to be closely related to the 1918 virus HA, which caused some 50 million deaths worldwide.

Using a recently developed microarray technology-hundreds of microscopic assay sites on a single small surface-the study showed that relatively small mutations can result in switching the binding site preference of the avian virus from receptors in the intestinal tract of birds to the respiratory tract of humans. These mutations, the study noted, were already "known in [some human influenza] viruses to increase binding for these receptors."

The study was published on March 16, 2006 by ScienceXpress, the advance online version of the journal Science.

Receptor specificity for the influenza virus is controlled by the glycoprotein hemagglutinin (HA) on the virus surface. These viral HAs bind to host cell receptors containing complex glycans-carbohydrates-that in turn contain terminal sialic acids. Avian viruses prefer binding to ?2-3-linked sialic acids on receptors of intestinal epithelial cells, while human viruses are usually specific for the ?2-6 linkage on epithelial cells of the lungs and upper respiratory tract. Such interactions allow the virus membrane to fuse with the membrane of the host cell so that viral genetic material can be transferred to the cell.

The switch from ?2-3 to ?2-6 receptor specificity is a critical step in the adaptation of avian viruses to a human host and appears to be one of the reasons why most avian influenza viruses, including current avian H5 strains, are not easily transmitted from human-to-human following avian-to-human infection. However, the report did suggest that "once a foothold in a new host species is made, the virus HA can optimize its specificity to the new host."

"Our recombinant approach to the structural analysis of the Viet04 virus showed that when we inserted HA mutations that had already been shown to shift receptor preference in H3 HAs to the human respiratory tract, the mutations increased receptor preference of the Viet04 HA towards specific human glycans that could serve as receptors on lung epithelial cells," Wilson said. "The effect of these mutations on the Viet04 HA increases the likelihood of binding to and infection of susceptible epithelial cells."

The study was careful to note that these results reveal only one possible route for virus adaptation. The study concluded that other, as yet "unidentified mutations" could emerge, allowing the avian virus to switch receptor specificity and make the jump to human-to-human transmission.

The glycan microarray technology, which was used to identify the mutations which could enable adaptation of H5N1 into the human population in the laboratory, could also be used to help identify new active virus strains in the field by monitoring changes in the receptor binding preference profile where infection is active, according to according to Jeremy M. Berg, the director of the National Institute of General Medical Sciences (NIGMS), part of the National Institutes of Health (NIH). The glycan microarray was developed by The Consortium for Functional Glycomics, an international group led by Scripps Research scientists and supported by the NIGMS.

"This technology allows researchers to assay hundreds of carbohydrate varieties in a single experiment," Berg said. "The glycan microarray offers a detailed picture of viral receptor specificity that can be used to map the evolution of new human pathogenic strains, such as the H5N1 avian influenza, and could prove invaluable in the early identification of emerging viruses that could cause new epidemics."

Other authors of the study include James Stevens of Scripps Research; Ola Blixt of Scripps Research and Glycan Array Synthesis Core-D, Consortium for Functional Glycomics; Terrence M. Tumpey, Influenza Branch, Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention; Jeffery K. Taubenberger, Department of Molecular Pathology, Armed Forces Institute of Pathology, and; James C. Paulson, Scripps Research and Glycan Array Synthesis Core-D, Consortium for Functional Glycomics.

Scripps Research Institute
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Preventing a pandemic: Study suggests strategies for containing a flu outbreak

August 04, 2005 -  Containment in a medium-sized Southeast Asian community may be possible, though challenging, if implemented early, researchers say

Though quick to caution about the many things that could go wrong, researchers say that it may be possible to contain a Southeast Asian outbreak of avian influenza in humans, buying precious time for the production of a vaccine.

Using a computer model to simulate an outbreak in a rural Southeast Asian population, the scientists have shown how a combination of strategies, including targeted administration of antivirals, quarantine and prevaccination - even with a poorly effective vaccine - could potentially contain an outbreak in Southeast Asia under many circumstances.

The study, by Ira Longini of Emory University and colleagues, will be published online by the journal Science, at the Science Express website, on Thursday, 4 August.

"Our findings indicate that we have reason to be somewhat hopeful. If - or, more likely, when - an outbreak occurs in humans, there is a chance of containing it and preventing a pandemic. However, it will require a serious effort, with major planning and coordination, and there is no guarantee of success," said coauthor Elizabeth Halloran of Emory University.

"Early intervention could at least slow the pandemic, helping to reduce morbidity until a well-matched vaccine could be produced," she said.

The danger of avian flu is that the virus could develop into a new strain that could be transmitted among humans. The virus might mutate, or it might jump over to a human already infected with the flu and then mix, or "reassort," with the human flu virus. Because humans would have little or no immune protection against this strain, it could potentially cause a massive pandemic.

"There were three influenza pandemics in the 20th century alone. The threat of another pandemic, related to avian influenza, is real and very serious. Fortunately, as the new study shows, for the first time in human history, we have a chance of stopping the spread of a new influenza strain at the source through good surveillance and aggressive use of public health measures," said Katrina Kelner, Deputy Editor, Life Sciences, at Science.

A rural Southeast Asian population is a likely place for the new strain to emerge, so Longini and his colleagues based their model on the Thai 2000 census and a previous study of the social networks in the Nang Rong District in rural Thailand.

With this information, they simulated a population of 500,000 in which individuals mixed in a variety of settings, including households, household clusters, preschool groups, schools, workplaces, and a hospital. Social settings for casual contacts, such as might take place in markets, shops, and temples, were also included.

Using the model, the researchers analyzed how the disease, starting with a single case, would spread through the population in a variety of different scenarios.

They found that targeted use of antiviral drugs could be effective for containment as long as the intervention occurred within 21 days and the virus' reproductive number (which represents the average number of people within a population someone with the disease is able to infect) had a relatively moderate value of roughly 1.6.

A process of administering antiviral drugs to the people in the same mixing groups as the infected person, called TAP for "targeted antiviral prophylaxis," could contain the outbreak as long as it reached 80 percent of the people targeted. A related strategy, GTAP, for "geographically targeted antiviral prophylaxis," which targets people within a certain geographic range of the initial case, produced similar results as long as it achieved coverage of 90 percent.

Vaccination before the outbreak, even with a vaccine that is poorly matched to the actual virus strain, increased the effectiveness of TAP and GTAP.

For even higher viral reproductive numbers, household quarantines would also be necessary to contain the virus. A combination of TAP, prevaccination and quarantine could contain strains with a reproductive number around 2.4. A value of 2.4 is relatively contagious, though some other viruses such as measles are substantially higher. In all cases, early intervention would be essential.

The authors note in their study that the current World Health Organization stockpile of antivirals for avian flu could probably be sufficient to help contain a pandemic in a population like the one in the model, if the stockpile were deployed within two to three weeks of detection.

As part of their study, the researchers consulted with Thai ministry of health officials and concluded that public health workers may decide that TAP, rather than GTAP, is the more realistic strategy, given their resources.

This research effort is part of a network called MIDAS (Models for Infectious Disease Agents Study), supported by the National Institute of General Medical Sciences. A related paper from another group of MIDAS researchers is being published simultaneously in the journal Nature.

American Association for the Advancement of Scienc
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