Concerns arise over symptomless Egypt bird flu cases

[sharon sanders]

Re: Concerns arise over symptomless Egypt bird flu cases

I think IOH means that our contribution as a forum is to make clearer the various data and other information that we see from other media and sources.

All of flublogia makes clearer the fog of the data that is in the media. We have seen many rumours, false information, and actual denials that an influenza pandemic may re-occur.

We analyze, debate, and present our responses and data, and in the end, make a valuable contribution to the body of information that exists in the general media regarding bird flu and other issues.

 

[HenryN]

Re: Concerns arise over symptomless Egypt bird flu cases

WHO/FAO/OIE may start a wide sero-surveys activities but I wonder they could have some preliminary virological data suggesting changes in Hemagglutinin receptor binding domains and or in internal sub-units (ie: polymerase complex, nucleoprotein, non-structural ...)

The 3 BP deletion removes S129, which is involved in receptor binding. There is a MAJOR problem in Egypt and those doing the planning have seen the sequences.

 

[HenryN]

Re: Concerns arise over symptomless Egypt bird flu cases

WHO/FAO/OIE may start a wide sero-surveys activities but I wonder they could have some preliminary virological data suggesting changes in Hemagglutinin receptor binding domains and or in internal sub-units (ie: polymerase complex, nucleoprotein, non-structural ...)

Here's the problem

http://www.recombinomics.com/News/04150901/H5N1_Egypt_S129del.html

 

[AlaskaDenise]

Re: Concerns arise over symptomless Egypt bird flu cases

Here's the problem

http://www.recombinomics.com/News/04150901/H5N1_Egypt_S129del.html

Commentary

H5N1 Receptor Binding Domain Changes In Egypt

Recombinomics Commentary 04:27
April 15, 2009

Similarly the results of H5N1 strains from Egypt (Figure 2) may be indicative of a possible viral evolution towards receptor usage similar to that of H1N1 viruses, which efficiently replicate in the upper respiratory tract. The protein domain, which seems to be involved in this subtle change, corresponds to amino acid domain 99-132.

The above comments, from ?Characterization of conserved properties of hemagglutinin of H5N1 and human influenza viruses: possible consequences for therapy and infection control? describe a subset of H5N1 sequences from Egypt that have chacteristics that match H1N1 seasonal flu. These matches include sequences from the Ghabiya cluster, as well as two Qena siblings with mild H5N1 in the spring of 2007. The sequences from the siblings had a 3 BP deletion that produce S129del, which is within the region listed above, Although the disease onset date of the index case was withheld from the WHO update, the hospital admission dates were four days apart, signaling the infection of the brother (4M) by his sister (6F). The sequences from the Qena siblings were identical, further supporting H2H transmission. Moreover, additional family members had symptoms, but tested negative.

This year there has been another cycle of mild cases in Egypt, but instead of affecting children between the ages of 3 and 10, like the siblings above, 10/12 cases are toddlers. However, like the cases in the spring of the 2007, the case fatality rate is low (in 2007 only 1/17 died, and this year 0/12 have died) and most patients did not develop pneumonia. These mild cases, coupled with the younger age group, raise concerns that H5N1 spread in the past two year was far more extensive than indicated by the confirmed cases, and were missed by current testing, which requires a poultry contact for H5N1 PCR testing.

Although NAMRU-3 has not released any human or poultry sequences this year, the first two human isolates were represented in a recent HA tree of vaccine targets. Although public sequences are not on the branch with the 2009 isolates, the location of the branch suggests these isolates also have the 3 BP deletion and are closely related to the sequences in the siblings from 2007.

The four day gap in admission dates for the Qena siblings, matches the four day gap in the disease onset dates for two cousins (both 2M) from Beheira. The cousins are next door neighbors, and the four day gap also indicated human to human transmission, further supporting the spread of mild H5N1.

The 3 BP deletion produces S129del and position 129 is in the receptor binding domain. This deletion maps to the region in H5N1 with similarities with H1N1, suggesting more efficient transmission, consistent with the clusters in Qena and Beheira.

Release of the sequences from the H5N1 cases this year would be useful. If these sequences have the same deletion as seen in the Qena cluster, an extensive screening of toddlers without a poultry connect is critical.

The failure to recognize the significance of the mild cases in 2007 is cause for concern. The failure to aggressively act at this time is beyond scandalous, and is hazardous to the world?s health.

.

 

[AlaskaDenise]

Re: Concerns arise over symptomless Egypt bird flu cases

...maps to the region in H5N1 with similarities with H1N1 suggesting more efficient transmission...

Does this mean this strain has a binding more similar to H1N1, or that the entire region is more similar? If it's the region, does that imply that this region may contain some of the "unknown" factors that potentially contribute to a pandemic influenza?

.

 

[HenryN]

Re: Concerns arise over symptomless Egypt bird flu cases

Does this mean this strain has a binding more similar to H1N1, or that the entire region is more similar? If it's the region, does that imply that this region may contain some of the "unknown" factors that potentially contribute to a pandemic influenza?

.

The region has the deletion (at position 129) in the Qena cluster (and it is likely that the same deletion is in the first two isolates from 2009, but NAMRU-3 hasn't released the sequences yet).

The Gharbiya cluster has a nearby change, A127T.

One report indicates S129L is in 95% of human H5N1 isolates (I have not confirmed this yet).

 

[Readymom]

Re: Concerns arise over symptomless Egypt bird flu cases

Sorry -can we please have this translated to 'laymens' language. Situation you are documenting seems to be serious, but I could be misunderstanding.

I've been away for the past week, and trying to catch up. If I'm reading and digesting all this news, this is all indicating a very real possibility of an easily transmittable virus close to developing, (closer than we've been in the past) bringing us much closer to a panflu scenario.

My apologies for such a 'simple' question. -k

 

[HenryN]

Re: Concerns arise over symptomless Egypt bird flu cases

Commentary

http://www.recombinomics.com/News/04150903/H5N1_Egypt_H2H_Denial.html

 

[AlaskaDenise]

Re: Concerns arise over symptomless Egypt bird flu cases

Commentary

http://www.recombinomics.com/News/04150903/H5N1_Egypt_H2H_Denial.html

Commentary


H5N1 Transmission Denials Raise Pandemic Concerns in Egypt

Recombinomics Commentary 15:39
April 15, 2009

Two cases of infection of two brothers in the West, said the four cases were subjected to thorough studies in the central laboratory and the Center for example is 3 and audit by the international reference laboratory of the United Kingdom did not report the results of any mutations in the virus and the infection was caused by infected birds and no cases of infection.

The above translation uses comments from WHO, and sequence data from Mill Hill or Weybridge, to deny human transmission between the toddler cousins (both 2M) in Beheira (see updated map). Although no sequences from confirmed 2009 cases in Egypt have been released, the sequence data analysis was likely directed at reassortment, which is a pet pandemic theory of WHO consultants. They have been trying to identify H5N1 with human flu genes for over a decade, and have no examples. Although reassortment with human flu genes was involved in the emergence of mild pandemics in 1957 and 1968, the sequences from all eight genes from the 1918 pandemic have no evidence of reassortment. Moreover, there have been several acknowledged H5N1 clusters involving human to human to human transmission, and these sequences have no human flu genes, which is also true of dozens of shorter clusters which have the diagnostic gap in disease onset dates.

Instead, those sequences support recombination, which involves exchanges of pieces of genes. Almost all polymorphisms in all eight gene segments from multiple 1918 H1N1 isolates can be found in human H1N1 (A/WSN/33) and swine (A/swine/Iowa/1976/31 or A.swine/Iowa/15/30) H1N1 sequences. Moreover, attempts to create H5N1 reassortant with human flu genes and enhanced transmission have failed. Most reassortants don’t grow or fail to grow in mice, in contrast to H5N1 with 8 avian gene segments, which can grow and kill mice.

The ability of H5N1 to grow and kill mammals, including humans, is linked to the polybasic cleavage site, which was not present in prior pandemic sequences. The components that are lacking are changes in the receptor binding domain which increases transmission efficiency. Such increases are typically characterized by clusters of cases, such as the recent Beheira cluster, or the Qena cluster in 2007. Sequences from the siblings in the Qena cluster have been released, and they contain a deletion of position 129, which interacts with the receptor binding domain. Moreover, analysis of this region matches the profile of H1N1 seasonal flu, which is efficiently transmitted.

Sequences from two of the mild cases in Egypt this season were used in the HA phylogenetic tree in the WHO report on vaccine targets. The position of the 2009 isolates on the tree suggests these sequences are closely related to the sequences from the Qena cluster, that contain the deletion. This deletion is also acquired via recombination. The same deletion is in clade 7 sequences from Shanxi and Hunan provinces in China. Moreover, WHO consultants are largely in denial over recombination. The deletion in Qena cluster was presented in Toronto at the Options VI conference in 2007, and WHO consultants maintained that the deletion was a "lab error". However, there are now 13 public sequences from Egypt that have the deletion, and the sequences were generated by multiple independent labs in 2007 and 2008 and involved human and poultry isolates. These examples are in addition to clade 7 sequences from China which have the same deletion, supporting recombination.

Moreover, the WHO updates of these clusters have significant omissions. The disease onset date of the index case in Qena was withheld, and the symptomatic relatives were not mentioned. Similarly, the Beheira cousins were said to be infected by dead or dying poultry, but no confirmed H5N1 cases have been reported in the area. Moreover, the fact that the two confirmed toddlers were cousins and next door neighbors were also omitted. This relationship, and the four day gap in disease onset dates strongly suggests that these cases involved human to human transmission. In addition, WHO has failed to confirm H5N1 in poultry in the area.

However, the relationship between the two H5N1 confirmed toddlers raises enhanced transmission concerns, even if both cousins were independently infected over a four day period. These concerns of increased transmission efficiencies are increased by the concentration of mild cases in toddlers this year, in contrast to the concentration in children in the spring of 2007.

This change in target population raises concerns that the spread of H5N1 in the human population was much greater than the small number of confirmed cases. Less than 1% of hospitalized suspect cases are PCR confirmed and the cases in the Spring of 2007 and 2009 were mild and could reflect a large population that either tests negative or is not tested at all because of resolution without treatment, or treatment as seasonal flu.

The above data raises concerns over reliance of lack of human flu genes as evidence for a lack of human transmission, and the failure to understand how influenza evolves and expands its host range.

.

 

[HenryN]

Re: Concerns arise over symptomless Egypt bird flu cases

Published: Apr 15, 2009
Bird Flu Attacks Children In Egypt - Bird Flu Epidemic On The Rise?
by Mitch Marconi

There is an epidemic going on in Egypt again over the bird flu
. According to reports, the infection is only attacking children and not adults. An investigation is ongoing by US and African officials.

According to Independent.co.uk, "The World Health Organisation is to back an investigation into a change in the pattern of the disease in Egypt, the most seriously affected country outside Asia. Although infections have been on the rise this year, with three more reported last week, they have almost all been in children under the age of three, while 12 months ago it was mainly adults and older children who were affected. And the infections have been much milder than usual; the disease normally kills more than half of those affected; all of the 11 Egyptians so far infected this year are still alive."

Some good news though is that the bird flu as of recently has gotten less deadly. Bad news is that some scientists apparently feel that this could cause a pandemic more likely to hit the world causing millions of people to die. Although they are only speculations and we just hope this stays under control.

http://www.postchronicle.com/news/original/article_212223215.shtml

 

[Giuseppe]

Re: Concerns arise over symptomless Egypt bird flu cases

ECDC Health Content: Egypt, Observed low case fatality ratio in 2008-9.

Observed low case fatality ratio in 2008-9

Information made available to WHO indicates that, on 8 April 2009 the Ministry of Health of Egypt reported 3 new confirmed human cases of infection with avian influenza A(H5N1).


The latest report can be accessed here

The first case is a 2 year-old boy from Kom Hamada District, El Behira Governorate who developed symptoms on 27 March and was admitted to hospital on the 30 March where he was started on oseltamivir the same day. He is reported to remain in a stable condition.

The second case is also a 2 year old male from the same district and was detected through the investigation around the first case. He developed symptoms on 31 March and was admitted to hospital on 1 April where he was also started on oseltamivir the same day. He is also reported to remain in a stable condition.

Both boys are reported to have had contact with sick/dead poultry prior to the illness onset. Close contacts of both boys have been identified and none has as yet shown symptoms of the infection.

The third case is a 6 year-old boy from Shubra El Khema District, Qaliobia Governorate. He developed symptoms on 22 March and was admitted to hospital on the 28 March where he was again started on oseltamivir (on 3rd April). He was also reported to have been exposed to sick/dead poultry prior to the onset of his illness. He was reported to be in a critical condition.

For all of the three cases reported above, infection with H5N1 avian influenza virus was following testing by the Egyptian Central Public Health Laboratory and subsequently confirmed by the United States Naval Medical Research Unit No. 3 (NAMRU-3).

Of the 63 cases confirmed to date in Egypt, 23 have been fatal. The last fatal case, had an onset date of December 8th 2008 and died on December 15th see here. Details of all the Egyptian cases can be seen through the general country page on the WHO web-site. It means than since December 2008 there have been 12 new confirmed A(H5N1) infections in humans all in children under age 3 apart from one woman in her 30s and none of the 12 are known to have died as of April 16th .


ECDC Comment (09-04-15):

The low Case Fatality Ratio (CFR) for human infections with Highly Pathogenic Avian Influenza (HPAI) H5N1 virus in Egypt is most welcome. However it was noted at a WHO global review two years ago.(2)

Therefore, what is being described now is not entirely new, except that there have been a series of 12 cases in 2009 with no deaths.

Clinically, mild illness with HPAI H5N1 virus infection has been reported in children in several countries apart from Egypt i.e. Turkey, Indonesia and Bangladesh and it should be noted that Egypt seems to be testing more children with milder illness soon after onset than any other countries.

This could be because children are brought to medical care for H5N1 testing early in their illness.

Moreover, testing and care (including early commencement of the antivial oseltamivir as recommended by WHO and ECDC (3,4)) seems to be relatively available in Egypt. It is noticeable in the recent reports how soon after onset dates treatment with oseltamivir seems to have started.

The occurrence of so many cases late in 2008 and early in 2009 is not in itself unusual.

It was also the pattern in the 2007-8 period.(Figure) (5)

Despite the above speculation, it is not yet known how to explain the commendable low CFR being achieved in Egypt with a virus that overall has been observed to have a CFR of around 60-70%.(5)

Various hypotheses have to be tested.

It could reflect a further adaptation of the virus to humans and a lessening of its virulence but equally it could be the result of good local surveillance, or that the clade 2.2 virus infections in Egypt has a lower CFR, or that its because early oseltamivir and other treatment has a better outcome.

There are no reports as yet of a change in the virological sequences and it is commendable that the Egyptian authorities have been sharing viruses with the global community as evidence from the WHO A(H5N1) Tracking Mechanism.(6)

The clade hypothesis theory seems unlikely since in nearby Turkey the same clade of H5N1 cases in 2005/6 resulted in a CFR for Turkey of 4 out of 12 in circumstances where it was difficult to achieve early treatment (a rural areas in then middle of a severe winter).(5)

Hence the good surveillance / early treatment theory seems the strongest hypothesis.

However uncertainty remains and it will be important to investigate further. It is very welcome that the Egyptian authorities have invited WHO to send senior staff to Egypt next week to assess the current epidemiological situation.

It is especially reassuring that despite the low CFR and apart from two of the cases in the most recent report there have been no clusters in the cases suggesting more easy human to human transmission.

However it would be hoped that this would be investigated in Egypt with serological surveys to look for milder and asymptomatic cases and any suggestion of clustering since even though the seeming lack of significant change in the sequence of the virus is reassuring the changes can be subtle and its how the viruses behave that is most important.(7)

A good example of such investigations were recently published in the Weekly Epidemiological Report of joint National / WHO work done in Pakistan in 2007.(8)

<table style="width: auto;"><tbody><tr><td></td></tr><tr><td style="font-family: arial,sans-serif; font-size: 11px; text-align: right;">From TABLES</td></tr></tbody></table>
graph - reference 5


References:

1. Media Report New bird flu cases suggest the danger of pandemic is risingIndependent UK April 12th 2008
2. Writing Committee of the second WHO consultation on clinical aspects of human infection with avian influenza A (H5N1) virus. NEJM 2008; 358: 261-73 .
3. WHO Clinical management of human infection with avian influenza A (H5N1) virus August 2007
4. ECDC Oseltamivir prophylaxis following suspected exposure of humans to Highly Pathogenic Avian Influenza (HPAI) with particular reference to HPAI type A/H5N1, Version 30th April 2006
5. WHO Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO April 8th 2009 (see figure below)
6. WHO Influenza Virus Tracking System (interim)
7. Nicoll A (Yet) another human A/H5N1 influenza case and cluster ? when should Europe be concerned? Eurosurveillance 2008; Volume 13, Issue 15, 10 April 2008
8. WHO Human cases of avian influenza A(H5N1) in North- West Frontier Province, Pakistan, October?November 2007 WER 2008 3 October 2008, vol. 83, 40 (pp 357?364)
-
​

<cite cite="http://ecdc.europa.eu/en/health_content/episu/090416_av_hh.aspx">ECDC Health Content</cite>

 

[HenryN]

Re: Concerns arise over symptomless Egypt bird flu cases

ECDC Health Content: Egypt, Observed low case fatality ratio in 2008-9.

There are no reports as yet of a change in the virological sequences and it is commendable that the Egyptian authorities have been sharing viruses with the global community as evidence from the WHO A(H5N1) Tracking Mechanism.(6)


​

<cite cite="http://ecdc.europa.eu/en/health_content/episu/090416_av_hh.aspx">ECDC Health Content</cite>

There has been NO sharing of the information for the 2009 isolates as shown below from the WHO H5N1 Tracking Mechanism

<table class="searchResults"><thead><tr><th><table><tbody><tr><td style="border: 0px none ;">UID </td><td style="border: 0px none ;"> </td></tr></tbody></table> </th> <th> <table border="0"><tbody><tr><td style="border: 0px none ;"> Specimen original ID </td><td style="border: 0px none ;"> </td></tr></tbody></table> </th> <th> <table border="0"><tbody><tr><td style="border: 0px none ;"> Country of origin </td><td style="border: 0px none ;"> </td></tr></tbody></table> </th> <th> <table border="0"><tbody><tr><td style="border: 0px none ;"> Type of material </td><td style="border: 0px none ;"> </td></tr></tbody></table> </th> <th> <table border="0"><tbody><tr><td style="border: 0px none ;"> Original collection date </td><td style="border: 0px none ;"> </td></tr></tbody></table> </th> <th> <table border="0"><tbody><tr><td style="border: 0px none ;"> PCR H5 + </td><td style="border: 0px none ;"> </td></tr></tbody></table> </th> <th> <table border="0"><tbody><tr><td style="border: 0px none ;"> Egg or cell isolate </td><td style="border: 0px none ;"> </td></tr></tbody></table> </th> <th> <table border="0"><tbody><tr><td style="border: 0px none ;"> Risk to human assessment </td><td style="border: 0px none ;"> </td></tr></tbody></table> </th> <th> <table border="0"><tbody><tr><td style="border: 0px none ;"> Distributed to external laboratories </td><td style="border: 0px none ;"> </td></tr></tbody></table> </th> <th> <table border="0"><tbody><tr><td style="border: 0px none ;"> Distributed among Collaborative Centres and Reference Laboratories </td><td style="border: 0px none ;"> </td></tr></tbody></table> </th> <th> <table border="0"><tbody><tr><td style="border: 0px none ;"> Updated at </td><td style="border: 0px none ;"> </td></tr></tbody></table> </th> <th> <table border="0"><tbody><tr><td style="border: 0px none ;"> Virus selected for vaccine development </td><td style="border: 0px none ;"> </td></tr></tbody></table> </th> <th> <table border="0"><tbody><tr><td style="border: 0px none ;"> Vaccine virus available for distribution </td><td style="border: 0px none ;"> </td></tr></tbody></table> </th> <th> <table border="0"><tbody><tr><td style="border: 0px none ;"> Sequenced </td><td style="border: 0px none ;"> </td></tr></tbody></table> </th> <th> <table border="0"><tbody><tr><td style="border: 0px none ;"> Sequence publicly available </td><td style="border: 0px none ;"> </td></tr></tbody></table> </th> </tr> </thead> <tbody> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">293</td> <td>2009900604</td> <td>Egypt</td> <td>swab</td> <td>2009-02-03</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-02-08</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">294</td> <td>2009900605</td> <td>Egypt</td> <td>swab</td> <td>2009-02-03</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-02-08</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">295</td> <td>2009900606</td> <td>Egypt</td> <td>swab</td> <td>2009-02-07</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-02-09</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">296</td> <td>2009901310</td> <td>Egypt</td> <td>swab</td> <td>2009-02-28</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-03-03</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">297</td> <td>2009902039</td> <td>Egypt</td> <td>swab</td> <td>2009-03-03</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-03-10</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">298</td> <td>2009902407</td> <td>Egypt</td> <td>swab</td> <td>2009-03-09</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-03-10</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">299</td> <td>2009902563</td> <td>Egypt</td> <td>swab</td> <td>2009-03-14</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-03-17</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">300</td> <td>2009902564</td> <td>Egypt</td> <td>swab</td> <td>2009-03-15</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-03-17</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td></tr></tbody></table>

 

[HenryN]

Re: Concerns arise over symptomless Egypt bird flu cases

More NO's for 2009 (sequences from 2008 have been released)

<table class="searchResults"><tbody><tr><td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">277</td> <td>2008913352</td> <td>Egypt</td> <td>swab</td> <td>2008-12-14</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-01-20</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">278</td> <td>2008900001</td> <td>Egypt</td> <td>swab</td> <td>2007-12-31</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-01-20</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">279</td> <td>2008901898</td> <td>Egypt</td> <td>swab</td> <td>2008-02-19</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-01-20</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">280</td> <td>2008901980</td> <td>Egypt</td> <td>swab</td> <td>2008-02-24</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-01-20</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">281</td> <td>2008902289</td> <td>Egypt</td> <td>swab</td> <td>2008-02-28</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-01-20</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">282</td> <td>2008902514</td> <td>Egypt</td> <td>swab</td> <td>2008-03-02</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-01-20</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">283</td> <td>2008902546</td> <td>Egypt</td> <td>swab</td> <td>2008-03-06</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-01-20</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">284</td> <td>2008902547</td> <td>Egypt</td> <td>swab</td> <td>2008-03-06</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-01-20</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">285</td> <td>2008902548</td> <td>Egypt</td> <td>swab</td> <td>2008-03-08</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-01-20</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">286</td> <td>2008903158</td> <td>Egypt</td> <td>swab</td> <td>2008-04-03</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-01-20</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">287</td> <td>2008903300</td> <td>Egypt</td> <td>swab</td> <td>2008-04-09</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-01-20</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">288</td> <td>2008903401</td> <td>Egypt</td> <td>swab</td> <td>2008-04-14</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-01-20</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">289</td> <td>2008904481</td> <td>Egypt</td> <td>swab</td> <td>2008-05-01</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-01-20</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">290</td> <td>2008904482</td> <td>Egypt</td> <td>swab</td> <td>2008-05-01</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-01-20</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">291</td> <td>2009900001</td> <td>Egypt</td> <td>swab</td> <td>2009-01-11</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-01-20</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td> </tr> <tr> <td style="background: rgb(204, 204, 204) none repeat scroll 0% 0%; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">292</td> <td>2009900585</td> <td>Egypt</td> <td>swab</td> <td>2009-01-23</td> <td>no</td> <td>no</td> <td>no</td> <td>0</td> <td>1</td> <td>2009-01-26</td> <td>no</td> <td>no</td> <td>no</td> <td>no</td></tr></tbody></table>

 

[HenryN]

Re: Concerns arise over symptomless Egypt bird flu cases

The WHO tracking data confirms that A/Egypt/0001-NAMRU3/2009 was from a sample collected on 1/11/2009 and A/Egypt/0585-NAMRU3/2009 was collected on 1/23/2009 confirming that these two isolates were from the first 2 confirmed cases in Egypt in 2009, which were from toddlers with mild H5N1.

 

[HenryN]

Re: Concerns arise over symptomless Egypt bird flu cases

<a rel="nofollow" href="http://www.recombinomics.com/News/04210901/H5N1_Egypt_WHO_Europe.html">Commentary</a>

 

[AlaskaDenise]

Re: Concerns arise over symptomless Egypt bird flu cases

<a rel="nofollow" href="http://www.recombinomics.com/News/04210901/H5N1_Egypt_WHO_Europe.html">Commentary</a>

Commentary

Europe Supports WHO Investigation of Egyptian H5N1 Clusters

Recombinomics Commentary 01:18
April 21, 2009

There are no reports as yet of a change in the virological sequences and it is commendable that the Egyptian authorities have been sharing viruses with the global community as evidence from the WHO A(H5N1) Tracking Mechanism.(6)

However uncertainty remains and it will be important to investigate further. It is very welcome that the Egyptian authorities have invited WHO to send senior staff to Egypt next week to assess the current epidemiological situation.

It is especially reassuring that despite the low CFR and apart from two of the cases in the most recent report there have been no clusters in the cases suggesting more easy human to human transmission.

However it would be hoped that this would be investigated in Egypt with serological surveys to look for milder and asymptomatic cases and any suggestion of clustering since even though the seeming lack of significant change in the sequence of the virus is reassuring the changes can be subtle and its how the viruses behave that is most important.(7)

A good example of such investigations were recently published in the Weekly Epidemiological Report of joint National / WHO work done in Pakistan in 2007.(8)

The above comments from the European Centre for Disease Prevention and Control report on the low case fatality rate in Egypt were published last week when there was only one cluster, the Beheira cousins in the Kom Hamada district. However, there were 3 subsequent cases in the past three days, which created <a rel="nofollow" href="http://www.recombinomics.com/News/04200901/H5N1_Egypt_CC.html">two more clusters</a>. One is in the Kellin district of Kafr el Shiekh where case #64 (33F) and #66 (1.5F) were <a rel="nofollow" href="http://www.recombinomics.com/News/04190901/H5N1_Kellin_Cluster.html">confirmed over the weekend</a>. The other is in northern Cairo, where case #65 (25F) and #63 (6M) are located. Both were admitted to the same hospital, where <a rel="nofollow" href="http://www.recombinomics.com/News/04190902/H5N1_Cairo_Delays.html">treatment was delayed</a> in both cases, presumably because the patients denied a poultry contact. Thus, the above comment on hints of one cluster have already grown to three clusters.

Similarly, the WHO phylogenetic tree suggests that many of the new 2009 cases willl have the same genetic markers, S129del and the associated I152T, which was identified in escape mutants in the Webster lab. Both of these markers are in all thirteen public H5N1 sequences in this sub-clade, which included the<a rel="nofollow" href="http://www.recombinomics.com/News/04150902/H5N1_Qena_Pandemic.html">Qena cluster</a> (6F and 4M) from <a rel="nofollow" href="http://www.recombinomics.com/News/04010701/H5N1_Egypt_Qena_Cluster.html">2007</a> and likely in the first two human H5N1 isolates from 2009.

Although Egypt has provided samples of the cases to NAMRU-3, none have been released. The finding of S129del and I152T in the 2009 would provide a genetic signature for these cases and the similarities of the sequences with H1N1 is cause for concern.

This season the cases have not just been focused in children, but have been in toddlers (11 of the 12 confirmed cases in children). This concentration in this narrow age group (1 ½ to 2 ½) raises additional concerns that the PCR testing of suspect cases in Egypt lacks sensitivity.

Such a lack of sensitivity was seen in the Pakistan cluster mentioned above. Although four brothers were symptomatic and had x-ray confirmed pneumonia, only one was PCR positive. One was not tested, but the other two were negative in spite of high H5 antibody levels (titers of 2560 and 320). Moreover, another brother who was asymptomatic and PCR negative also had an H5 titer of 320.

Thus, the Pakistan study demonstrated the limitations in PCR testing and raises concerns that many of the PCR negatives among the 99% of suspect hospitalized patients in Egypt are false negatives.

Therefore, antibody testing of these suspect cases, as well as toddlers that have symptoms but lack a poultry contact, are welcome and necessary and should be addressed by the <a rel="nofollow" href="http://www.recombinomics.com/News/04200902/H5N1_Egypt_WHO.html">WHO investigation</a>.

.

 

[AlaskaDenise]

Re: Concerns arise over symptomless Egypt bird flu cases

bump this

...so newcomers can read why FT members are concerned about the impeding arrive of swine A/H1N1/2009 into Egypt in light of the above described issues.

.