Concerns arise over symptomless Egypt bird flu cases

[ironorehopper]

I continue to highlight the persistent lack of details about clinical course of pediatric H5N1 infections.

There aren't anamnestic details, vaccination status (ie: pneumococcal vaccine, Hemophilus Influenzae b vax etc.), treatment course, environmental and domestic hygiene descriptions.

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 ...)

If not, I think it is strange this upsurge in both Egyptian and foreign interest in less then a dozen of cases occurring during the last three months.

I suspect that the impending turmoil in Egyptian political scenario is playing a role in this incident.

A decades-long Egyptian regime is rumbling under internal and international pressure. The things don't happen almost alone...

We have:

1) a dozen of confirmed pediatric cases;
2) a time frame of several months;
3) different locations;
4) uncertain clinical courses, except for media sources and Egyptian official reports;
5) lack of clinical course and anamnestic description by the WHO;
6) no virological update by the WHO;
7) no clear epidemiologic changes described by the WHO;
8) no data about treatment courses and effectiveness of interventions;
9) widespread poultry epizootics;
10) poultry vaccinations effectiveness data is lacking;
11) environmental contamination of patient's houses unknown;
12) follow-up reports about pediatric cases by WHO continue to be absent.
13) increasing political turmoil;
14) civil unrests;
15) re-aligning international alliances and perspectives;
16) discrepancy in media interviews and statement and official public press releases by WHO;
17) unclear role of foreign laboratory and research facilities in Egypt.

I am surprised by the lack of travel warning for tourists directed to Egyptian resorts if there is a strong suspect of increased human-to-human transmissibility of H5N1 virus and likely existence of milder or abortive illness.

Migrants from Alexandria toward Italian Mediterranean Sea continue to arrive en masse.

No atypical or undiagnosed illness among them and among destination islands.

This post expresses only the opinions of the author (Inororehopper) and doesn't imply any endorsement by this website directors/members/owners.

(PS: Is it also possible that H5N1 virus involved in recent pediatric cases could have changed its human epithelial cells affinity or is it replication defective? Could be the virus resulted attenuated by exposure to environmental factors / solar radiation / dew / temperature?)

[HenryN]

Originally Posted by Laidback Al

Table 5, passive surveillance of HPAI in the household poultry sector (page 11), reports 17 positive samples from 46 tests from 8 governorates, about 1 positive result for every three samples tested. However, 16 of the the tested samples were from Beheira (Behaira) where the two cousins were infected. Ten of the 16 samples, more than 60%, were positive, the highest percentage for any of the governorates that were subjected to testing.

This still leaves open the possibility that the infection of the the two children was B2H rather than H2H.

Beheira is a large governorate and the map of the outbreaks there clearly show ZERO confirmed cases near the cousins for the ENTIRE season (all of the poultry outbreaks, including those in March/April are in the north).

The H2H is WELL into the obvious category. The 4 day gap in disease onset dates is NOT a coincidence.

[HenryN]

Originally Posted by ironorehopper

I continue to highlight the persistent lack of details about clinical course of pediatric H5N1 infections.

There aren't anamnestic details, vaccination status (ie: pneumococcal vaccine, Hemophilus Influenzae b vax etc.), treatment course, environmental and domestic hygiene descriptions.

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 ...)

If not, I think it is strange this upsurge in both Egyptian and foreign interest in less then a dozen of cases occurring during the last three months.

I suspect that the impending turmoil in Egyptian political scenario is playing a role in this incident.

A decades-long Egyptian regime is rumbling under internal and international pressure. The things don't happen almost alone...

We have:

1) a dozen of confirmed pediatric cases;
2) a time frame of several months;
3) different locations;
4) uncertain clinical courses, except for media sources and Egyptian official reports;
5) lack of clinical course and anamnestic description by the WHO;
6) no virological update by the WHO;
7) no clear epidemiologic changes described by the WHO;
8) no data about treatment courses and effectiveness of interventions;
9) widespread poultry epizootics;
10) poultry vaccinations effectiveness data is lacking;
11) environmental contamination of patient's houses unknown;
12) follow-up reports about pediatric cases by WHO continue to be absent.
13) increasing political turmoil;
14) civil unrests;
15) re-aligning international alliances and perspectives;
16) discrepancy in media interviews and statement and official public press releases by WHO;
17) unclear role of foreign laboratory and research facilities in Egypt.

I am surprised by the lack of travel warning for tourists directed to Egyptian resorts if there is a strong suspect of increased human-to-human transmissibility of H5N1 virus and likely existence of milder or abortive illness.

Migrants from Alexandria toward Italian Mediterranean Sea continue to arrive en masse.

No atypical or undiagnosed illness among them and among destination islands.

This post expresses only the opinions of the author (Inororehopper) and doesn't imply any endorsement by this website directors/members/owners.

(PS: Is it also possible that H5N1 virus involved in recent pediatric cases could have changed its human epithelial cells affinity or is it replication defective? Could be the virus resulted attenuated by exposure to environmental factors / solar radiation / dew / temperature?)

The mild cases in Egypt this year are a REPEAT of the mild cases in the spring of 2007, except the population target has changed. In 2007 the cases involved children, age 3-10. In 2009 the target population is toddlers, confirming that the 2007 cases were just the tip of a VERY large iceberg, which created protective immunity to H5N1 in a large segment of the population.

The mild cases were bracketed by severe cases. The CFR in the the 10 cases preceding the mild cases in 2007 was 100%. The cases between the two mild outbreaks involved cases that were in CRITICAL condition, and most died.

The low CFR in the two clusters of mild cases (1/17 in the spring of 2007 and 0/12 in 2009) is in addition to the fact that the patients not only didn't die, but most were never very sick and never developed pneumonia.

The low number of cases create concern, because the manipulation of the WHO case definition is OBVIOUS and has been OBVIOUS since 2005, which it was used to hide the mild cases in northern Vietnam (and has been used ever since to hide mild cases, as is done in India, where suspect cases that don't develop pneumonia are simply not tested).

[HenryN]

AVIAN INFLUENZA, HUMAN (73): EGYPT, VIRULENCE
***********************************************
A ProMED-mail post
<http://www.promedmail.org>
ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>

Date: Mon 13 Apr 2009
Source: Bloomberg News online [edited]
<http://www.bloomberg.com/apps/news?p...3DakmwbqDeHpvE>


Egypt asked the World Health Organization [WHO] to help investigate
an outbreak of bird flu after a dozen non-fatal cases of the disease
this year [2009] prompted speculation the virus may be becoming less
virulent. Two WHO doctors and a scientist will travel to Cairo later
this week at the request of Egypt's Ministry of Health, said Gregory
Hartl, a spokesman for the United Nations agency in Geneva, in an
interview today [13 Apr 2009]. The UN team will assist local
authorities to identify how the patients were infected with the H5N1
strain of avian influenza and whether there have been any significant
changes in disease patterns in the virus itself.

Scientists have been following H5N1 for more than a decade because of
concern it could spark a pandemic if it becomes as infectious for
humans as it is for poultry. A less lethal strain could be more
contagious because people would have longer to transmit it through
coughing and sneezing. None of the 12 Egyptian cases reported to the
WHO this year [2009] has been fatal.

These data do indeed suggest that there may have been a reduction in
the virulence of the outbreak strain, and there is a perceived risk
of progression of the virus to a less virulent but more transmissible
form, the International Society for Infectious Diseases said today
[13 Apr 2009] in an e-mail via its ProMED-mail program [see, "Avian
influenza, human (72): Egypt, virulence 20090412.1403"]. The survival
of H5N1 patients in Egypt also may reflect early treatment with
antiviral medicines, ProMED said.

At least 417 people in 15 countries have contracted the virus since
2003. Three of every 5 cases worldwide were fatal. Most cases were
caused by contact with infected poultry, such as children playing
with them or adults butchering them or plucking feathers, according
to WHO.

H5N1 is continuing to circulate in poultry in Egypt, though there is
no evidence so far of any significant changes in the virus, said
Joseph Domenech, chief veterinary officer with the Food and
Agriculture Organization [FAO]. The Rome-based UN agency has also
agreed to a request by Egypt's government to provide technical
assistance, Domenech said in an interview today [13 Apr 2009].

Egypt has the highest number of avian-flu cases outside Asia, with 63
cases reported to WHO since 2006, of which 23 were fatal. In
comparison, more than 80 percent of the 141 people reported to have
been infected in Indonesia died.

Roche Holding AG says its Tamiflu antiviral medicine can reduce the
severity and duration of flu symptoms if taken within 48 hours of the
onset of disease. Early treatment for H5N1 may improve survival, some
uncontrolled studies have shown.

[Byline: Jason Gale]

--
Communicated by:
ProMED-mail Rapporteur Mary Marshall

[The participation of the FAO in the WHO-led investigation of the
current H5N1 epidemic situation in Egypt is a logical development. As
of today (13 Apr 2009), the 11 cases of avian H5N1 influenza virus
confirmed in 2009 (all children) remain alive. This is in marked
contrast to the period from 2006 to 2008 when 23 of 51 H5N1-confirmed
patients did not survive infection. This suggests that there may have
been a change in the virulence of the H5N1 virus circulating in Egypt
at the present time. While diminished virulence is clearly
advantageous for the Egyptian population, it is feared that reduction
in virulence may favor increased transmissibility of the virus, which
might have adverse consequences for the global population.

However, other factors such as the role of the age of the victims,
the absence of evidence of person-to-person transmission, and the
effectiveness of treatment protocols have still to be evaluated. An
update on the current situation is awaited. - Mod.CP]

[see also:
Avian influenza, human (72): Egypt, virulence 20090412.1403
Avian influenza, human (71): Egypt, Viet Nam, WHO 20090408.1359
Avian influenza, human (70): Egypt (QL), 63rd case 20090406.1336
Avian influenza, human (69): Egypt (BH) 62nd case 20090404.1299
Avian influenza, human (66): Egypt (BH) 20090402.1271
Avian influenza, human (59): Viet Nam (ST) NOT 20090325.1162
Avian influenza, human (56): Viet Nam (DT) NOT, (ST) susp. 20090321.1128
Avian influenza, human (55): Egypt (AT), Viet Nam (DT) 20090320.1118
2006
----
Avian influenza (208): NS1 virulence determinant 20061106.3183]
.................................................. ........cp/msp/lm

[HenryN]

Originally Posted by niman

AVIAN INFLUENZA, HUMAN (73): EGYPT, VIRULENCE
***********************************************


[The participation of the FAO in the WHO-led investigation of the
current H5N1 epidemic situation in Egypt is a logical development. As
of today (13 Apr 2009), the 11 cases of avian H5N1 influenza virus
confirmed in 2009 (all children) remain alive. This is in marked
contrast to the period from 2006 to 2008 when 23 of 51 H5N1-confirmed
patients did not survive infection. This suggests that there may have
been a change in the virulence of the H5N1 virus circulating in Egypt
at the present time. While diminished virulence is clearly
advantageous for the Egyptian population, it is feared that reduction
in virulence may favor increased transmissibility of the virus, which
might have adverse consequences for the global population.

However, other factors such as the role of the age of the victims,
the absence of evidence of person-to-person transmission, and the
effectiveness of treatment protocols have still to be evaluated. An
update on the current situation is awaited. - Mod.CP]

The point is that the mild cases in 2009 are a REPEAT of the mild cases in 2007 except the target population has changed from children, age 3-10, to toddlers, age 1 1/2 to 2 1/2. The mild cases of 2007 are combined with the 100% CFR in the 10 patients prior to the mild cases, as well as the high CFR in the patients between to the two mild clusters to produce the rather normal (but low) CFR for the entire population prior to 2009.

This analysis hides the VERY glaring cluster in the spring of 2007, when only 1 of the 17 confirmed cases died, and extends the media myth that the mild cases in 2009 in Egypt are NEW, instead of a REPEAT (which signals H5N1 cases that are orders of magnitude higher than the confirmed cases).

[ironorehopper]

Originally Posted by niman

The mild cases in Egypt this year are a REPEAT of the mild cases in the spring of 2007, except the population target has changed. In 2007 the cases involved children, age 3-10. In 2009 the target population is toddlers, confirming that the 2007 cases were just the tip of a VERY large iceberg, which created protective immunity to H5N1 in a large segment of the population.

The mild cases were bracketed by severe cases. The CFR in the the 10 cases preceding the mild cases in 2007 was 100%. The cases between the two mild outbreaks involved cases that were in CRITICAL condition, and most died.

The low CFR in the two clusters of mild cases (1/17 in the spring of 2007 and 0/12 in 2009) is in addition to the fact that the patients not only didn't die, but most were never very sick and never developed pneumonia.

The low number of cases create concern, because the manipulation of the WHO case definition is OBVIOUS and has been OBVIOUS since 2005, which it was used to hide the mild cases in northern Vietnam (and has been used ever since to hide mild cases, as is done in India, where suspect cases that don't develop pneumonia are simply not tested).

I know well as nonfatal cases aren't a news, as the history of H5N1 panzootics is now longer and longer.

Despite that, none of my questions have found a reply.

It this story is so obvious, why does nobody seem able to explain to large public almost a couple of the above questions?

It could be the case that the questions per se would be stupid or irrelevant but the aim of a public forum with a number of non-professional readers and contributors should be to make clear facts amidst the instense fog of media.

[sharon sanders]

"..but the aim of a public forum with a number of non-professional readers and contributors should be to make clear facts amidst the instense fog of media."

I agree.

Your points in post # 91 are very pertinent.

[vinny]

Does anyone think a pandemic could be close then,with whats happening in egypt.the reason i ask is because we no longer have a preps and i would need to restock,thanks.

[ironorehopper]

Originally Posted by vinny

Does anyone think a pandemic could be close then,with whats happening in egypt.the reason i ask is because we no longer have a preps and i would need to restock,thanks.

Disaster preparedness is a valuable activity, and should be done even for other natural or man-made disaster such as eartquakes, floods, hurricanes, civil unrests etc.

So, if you want to restock your personal stockpile, you can done this without problems.

It is enough you save money to daily life, ...

[Commonground]

"..but the aim of a public forum with a number of non-professional readers and contributors should be to make clear facts amidst the instense fog of media."

the aim should be to make clear facts. Clear facts from whom?

[sharon sanders]

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]

Originally Posted by ironorehopper

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]

Originally Posted by ironorehopper

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/04...t_S129del.html

[AlaskaDenise]

Originally Posted by niman

Here's the problem

http://www.recombinomics.com/News/04...t_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]

...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]

Originally Posted by AlaskaDenise

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]

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]

Commentary

http://www.recombinomics.com/News/04...2H_Denial.html

[AlaskaDenise]

Originally Posted by niman

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]

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/or...12223215.shtml

[ironorehopper]

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)

From TABLES

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)
-

ECDC Health Content

[HenryN]

Originally Posted by ironorehopper

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)

ECDC Health Content

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

UID	Specimen original ID	Country of origin	Type of material	Original collection date	PCR H5 +	Egg or cell isolate	Risk to human assessment	Distributed to external laboratories	Distributed among Collaborative Centres and Reference Laboratories	Updated at	Virus selected for vaccine development	Vaccine virus available for distribution	Sequenced	Sequence publicly available
293	2009900604	Egypt	swab	2009-02-03	no	no	no	0	1	2009-02-08	no	no	no	no
294	2009900605	Egypt	swab	2009-02-03	no	no	no	0	1	2009-02-08	no	no	no	no
295	2009900606	Egypt	swab	2009-02-07	no	no	no	0	1	2009-02-09	no	no	no	no
296	2009901310	Egypt	swab	2009-02-28	no	no	no	0	1	2009-03-03	no	no	no	no
297	2009902039	Egypt	swab	2009-03-03	no	no	no	0	1	2009-03-10	no	no	no	no
298	2009902407	Egypt	swab	2009-03-09	no	no	no	0	1	2009-03-10	no	no	no	no
299	2009902563	Egypt	swab	2009-03-14	no	no	no	0	1	2009-03-17	no	no	no	no
300	2009902564	Egypt	swab	2009-03-15	no	no	no	0	1	2009-03-17	no	no	no	no

[HenryN]

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

277	2008913352	Egypt	swab	2008-12-14	no	no	no	0	1	2009-01-20	no	no	no	no
278	2008900001	Egypt	swab	2007-12-31	no	no	no	0	1	2009-01-20	no	no	no	no
279	2008901898	Egypt	swab	2008-02-19	no	no	no	0	1	2009-01-20	no	no	no	no
280	2008901980	Egypt	swab	2008-02-24	no	no	no	0	1	2009-01-20	no	no	no	no
281	2008902289	Egypt	swab	2008-02-28	no	no	no	0	1	2009-01-20	no	no	no	no
282	2008902514	Egypt	swab	2008-03-02	no	no	no	0	1	2009-01-20	no	no	no	no
283	2008902546	Egypt	swab	2008-03-06	no	no	no	0	1	2009-01-20	no	no	no	no
284	2008902547	Egypt	swab	2008-03-06	no	no	no	0	1	2009-01-20	no	no	no	no
285	2008902548	Egypt	swab	2008-03-08	no	no	no	0	1	2009-01-20	no	no	no	no
286	2008903158	Egypt	swab	2008-04-03	no	no	no	0	1	2009-01-20	no	no	no	no
287	2008903300	Egypt	swab	2008-04-09	no	no	no	0	1	2009-01-20	no	no	no	no
288	2008903401	Egypt	swab	2008-04-14	no	no	no	0	1	2009-01-20	no	no	no	no
289	2008904481	Egypt	swab	2008-05-01	no	no	no	0	1	2009-01-20	no	no	no	no
290	2008904482	Egypt	swab	2008-05-01	no	no	no	0	1	2009-01-20	no	no	no	no
291	2009900001	Egypt	swab	2009-01-11	no	no	no	0	1	2009-01-20	no	no	no	no
292	2009900585	Egypt	swab	2009-01-23	no	no	no	0	1	2009-01-26	no	no	no	no

[HenryN]

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]

Commentary

[AlaskaDenise]

Originally Posted by niman

Commentary

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 two more clusters. One is in the Kellin district of Kafr el Shiekh where case #64 (33F) and #66 (1.5F) were confirmed over the weekend. The other is in northern Cairo, where case #65 (25F) and #63 (6M) are located. Both were admitted to the same hospital, where treatment was delayed 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 theQena cluster (6F and 4M) from 2007 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 WHO investigation.

.

[AlaskaDenise]

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.

.