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New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/jan1807tamiflu.html

Tamiflu-resistant H5N1 strain surfaces in Egypt

Lisa Schnirring
purple-speck.gif
Contributing Writer


Jan 18, 2007 (CIDRAP News) ? Two patients who recently died of H5N1 avian influenza in Egypt had a strain of the virus that was moderately resistant to oseltamivir (Tamiflu), the World Health Organization (WHO) announced today, but the finding has not prompted new health advisories.

News of the drug-resistant strain came as Egypt's health ministry announced a new human H5N1 case, involving a 27-year-old woman from the town of Beni Suef, about 62 miles south of Cairo. The report was carried today by IRIN, a United Nations news and information service.

Oseltamivir is recommended by the WHO as the first-line drug for H5N1 patients. The patients who had resistant infections were a 16-year-old girl and her 26-year-old uncle, who lived in the same house in Egypt's Gharbiyah province, in the Nile delta 50 miles northwest of Cairo. They got sick in December; the man was hospitalized on the 17th, followed by his niece 2 days later, the WHO said. Both received 2 tablets of oseltamivir on Dec 21 and were transferred to a referral hospital on Dec 23, the same day samples were taken.

The girl died Dec 25 and her uncle died Dec 28. They were part of a possible family cluster; H5N1 avian influenza was also confirmed in a 30-year-old woman in the household, said to be the man's sister, who died, though few details are available about her. The WHO said the patients reportedly had contact with sick ducks. The two cases boosted Egypt's avian flu total to 18 cases and 10 fatalities, all of which occurred in 2006.

Genetic sequencing was done at US Naval Medical Research Unit 3 in Cairo and at WHO collaborating centers in Atlanta and London, the WHO said.

Tests suggested that the virus had "moderately reduced susceptibility" to osteltamivir. The same type of mutation was previously identified in a Vietnamese case in 2005, the WHO said.

But in contrast to the Egyptian cases, the virus in the Vietnamese case appeared to be highly resistant to oseltamivir. The case, reported in December 2005 in the New England Journal of Medicine (NEJM), involved a 13-year-old girl who was started on oseltamivir the day she was hospitalized, receiving the recommended dose of 75 mg twice a day for 5 days.

The girl was one of 8 patients whose cases were analyzed after they were treated for H5N1 infection in Ho Chi Minh City in 2004 and 2005.

Researchers sequenced the H5N1 virus's neuraminidase gene to look for resistance, signaled by the substitution of tyrosine for histidine at amino acid position 274. The mutation was found in the 13-year-old girl, who died of severe pneumonia on her seventh day in the hospital.

The viral load in her throat was higher by the time of her death than it was earlier, which, with other laboratory evidence, suggested that drug resistance contributed to treatment failure and ultimately death, the NEJM report noted.

The mutation was also found in an 18-year-old girl, but the researchers said the relationship between the viral resistance and her death was less clear.

Fred Hayden, a WHO avian flu and antiviral expert, told the Associated Press (AP) today the drug-resistant strains in the Egyptian patients likely developed after they were treated with oseltamivir. He said a more worrying scenario would be if oseltamivir-resistant strains were circulating in birds.

The mutations in Egypt are different from the ones in Vietnam, Hayden told the AP. The Vietnamese strains were definitely resistant to oseltamivir, but the Egyptian ones were only shown to be less susceptible to the drug.

There is no evidence that oseltamivir-resistant strains are spreading in Egypt or elsewhere, the WHO said. The agency said it is not changing its antiviral treatment recommendations, because the clinical level of resistance of the mutations is not yet well established.

Public health implications of the findings are limited because the mutation is not associated with any known changes in transmissibility of the virus between humans, the WHO said, adding that it would not be raising the pandemic alert level.

Because of concerns about drug-resistant strains, avian flu experts have suggested that a higher dosage, longer treatment course, or combination therapy with other antiviral drugs may be needed to ensure the effectiveness of oseltamivir.

Terence Hurley, a US spokesperson for Roche, the maker of Tamiflu, told CIDRAP News by e-mail that studies are being conducted to gauge the optimal oseltamivir regimens for use in H5N1 flu cases. "These activities are based upon laboratory data and from information from patients infected with H5N1 who have been treated with Tamiflu," he said.

Roche is collaborating with the US National Institutes of Health on clinical studies to determine the efficacy of oseltamivir in the treatment of severe influenza, including H5N1, Hurley reported. "The NIH study is comparing standard doses of Tamiflu versus double doses for the treatment of people infected with avian influenza and other severe influenza infections in the Far East," he wrote. "Results of the study will be reported as soon as they are available."

The Egyptian woman reported today as a new H5N1 patient was admitted to a hospital Jan 11 after having given birth on Jan 2, IRIN reported. She initially denied contact with poultry, but WHO spokesman Hassan el-Bushra told IRIN that ducks and pigeons were found in her home and chickens had died nearby.

If her case is confirmed by the WHO, it will be Egypt's 19th.

See also:

Jan 18 WHO report

Dec 27 WHO report

Dec 22, 2005 CIDRAP News article "Tamiflu resistance in avian flu victims sparks concern"

De Jong MD, Thanh TT, Khanh TH, et al. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med 2005 Dec 22;353(25):2667-72 [Full text]
 
Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

niman said:
It would seem that the sequence from the patient in Vietnam in 2005 is "hidden" in the WHO private database, if the WHO update is accurate.

Try DQ250165 A/Vietnam/CL2009/2005
 
Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

Mamabird said:
Try DQ250165 A/Vietnam/CL2009/2005
The sequence is wild type at postion 294 (has an N), but does have H274Y.
 
Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

niman said:
The sequence is wild type at postion 294 (has an N), but does have H274Y.

Sensitive: LNAPNYHYEE

Resistant: LNAPNYYYEE
 
Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

Mamabird said:
Sensitive: LNAPNYHYEE

Resistant: LNAPNYYYEE
Correct. That is H274Y. However, that is in Vietnam in patients that developed Tamiflu resistance during treatment.

However, the change in Egypt is N294S, which is not in any public human sequence, which were was listed in the earlier post. All public sequences have N (and not S) at position 294.

Today's WHO update indocated that the change in Egypt (N294S) was in ONE patient in Vietnam. H274Y has been reported in several patients in Vietnam that developed resistance during Tamiflu treatment.
 
Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

Mamabird said:
Sensitive: LNAPNYHYEE

Resistant: LNAPNYYYEE

N294S has been seen in H5N1 in ducks (but not public human H5N1)

<TABLE class=resultstable cellSpacing=0 cellPadding=4 width="100%" border=0><TBODY><TR bgColor=#a7c4ef><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=212477 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>DQ997411 </TD><TD>A/duck/Zhejiang/bj/2002 </TD><TD>NA (6) </TD><TD>1458 </TD><TD>2002 </TD><TD>H5N1 </TD><TD></TD></TR><TR bgColor=white><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=14560 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>AY075034 </TD><TD>A/Duck/Hong Kong/380.5/2001 </TD><TD>NA (6) </TD><TD>1427 </TD><TD>2001 </TD><TD>H5N1 </TD></TR></TBODY></TABLE>
 
Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

niman said:
Correct.Today's WHO update indocated that the change in Egypt (N294S) was in ONE patient in Vietnam. H274Y has been reported in several patients in Vietnam that developed resistance during Tamiflu treatment.

I apoligize, but I can find no statement by any WHO official that stated that a Vietnam patient had N294S. All I can locate is a statement by a reporter that the so called "294S" mutation was also in Vietnam. As everyone knows, that has never been the case, nor has WHO ever represented that to be the case as far as anyone knows.

The point is, and always has been, that when Tamiflu is given to infected patients, H5N1 quickly attempts to overt the roadblock that binds the new virons to the host cell. It has four different mutations that it uses to accomplish that, only one of which is N294S.
 
Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

<hr style="border: 1px none ; height: 1px; background-color: rgb(0, 0, 0); width: 100%;" align="left">
Avian influenza - situation in Egypt - update


18 January 2007
Viruses with a genetic mutation, linked in laboratory testing to moderately reduced susceptibility to oseltamivir, have been discovered in two persons previously reported with H5N1 infections in Egypt. Both patients had been on treatment with oseltamivir for two days before the clinical samples that yielded the viruses were taken.
The two patients from whom samples were taken were a 16 year-old female and a 26 year-old male from Gharbiyah Province, Egypt.<sup>1</sup> They were a niece and uncle, respectively, who lived in the same house. The girl was admitted to a hospital on 19 December 2006, while the man was admitted on 17 December. On 21 December they began receiving 2 tablets per day of oseltamivir. On 23 December they were moved to a referral hospital. The samples which have so far been tested were taken from the two patients on 23 December. The girl died on 25 December and the man died on 28 December 2006.
In this and all other H5N1 investigations there is close, ongoing coordination between Egypt's Ministry of Health and Population (MOH&P) and WHO. It was Egypt's monitoring and rapid virological analysis conducted at the Central Public Health Laboratory in Cairo that initially allowed the diagnoses of H5N1 to be made. Confirmatory testing and genetic sequencing was done at NAMRU-3 and at two WHO Collaborating Centres located in Atlanta, USA and London, UK.
At this time there is no indication that oseltamivir resistance is widespread in Egypt or elsewhere. WHO is not making any changes in antiviral treatment recommendations for H5N1-infected persons published in June 2006 because the clinical level of resistance of these mutations is not yet well established. Current laboratory testing suggests that the level of reduced susceptibility is moderate. This mutation has previously been identified in Viet Nam in one case in 2005. Moreover, these mutations are not associated with any known change in the transmissibility of the virus between humans. Based on these considerations, the public health implications at this time are limited. Finally, these findings do not indicate a need for a change in phase level. The WHO pandemic preparedness level remains at three.
The Egyptian authorities, WHO and its Collaborating Centres will continue to share with the public all relevant information from the on-going investigations and analyses as soon as it becomes available.

rule.gif

<sup>1</sup>The ages and dates in this update related to the two patients, may differ slightly from earlier reports, but reflect the most recent information provided to WHO.



http://www.who.int/csr/don/2007_01_18/en/print.html
<!-- include footer--> <!-- include ftr-->
 
Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

Mamabird said:
I apoligize, but I can find no statement by any WHO official that stated that a Vietnam patient had N294S. All I can locate is a statement by a reporter that the so called "294S" mutation was also in Vietnam. As everyone knows, that has never been the case, nor has WHO ever represented that to be the case as far as anyone knows.

The point is, and always has been, that when Tamiflu is given to infected patients, H5N1 quickly attempts to overt the roadblock that binds the new virons to the host cell. It has four different mutations that it uses to accomplish that, only one of which is N294S.
Either 2 reporters got it wrong or there is a piece missing from the public domain.

http://www.cidrap.umn.edu/cidrap/con...07tamiflu.html

Tamiflu-resistant H5N1 strain surfaces in Egypt

Lisa Schnirring
purple-speck.gif
Contributing Writer

**snipped**
Tests suggested that the virus had "moderately reduced susceptibility" to osteltamivir. The same type of mutation was previously identified in a Vietnamese case in 2005, the WHO said.
AND this one:
Moderately Tamiflu-resistant bird flu in Egypt--WHO
18 Jan 2007 14:49:57 GMT

By Stephanie Nebehay


GENEVA, Jan 18 (Reuters) - Two people who died of bird flu in Egypt last month had a strain of the H5N1 virus which has shown "moderate" resistance to the frontline antiviral Tamiflu, the World Health Organisation (WHO) said on Thursday.

Known as "294S", the mutated strain was first detected in 2005 in a teenage girl in Vietnam who survived, but this is the first evidence of it spreading beyond Asia, it said.
 
Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

Mamabird said:
I apoligize, but I can find no statement by any WHO official that stated that a Vietnam patient had N294S. All I can locate is a statement by a reporter that the so called "294S" mutation was also in Vietnam. As everyone knows, that has never been the case, nor has WHO ever represented that to be the case as far as anyone knows.

The point is, and always has been, that when Tamiflu is given to infected patients, H5N1 quickly attempts to overt the roadblock that binds the new virons to the host cell. It has four different mutations that it uses to accomplish that, only one of which is N294S.

From the WHO update:

This mutation has previously been identified in Viet Nam in one case in 2005
 
Last edited:
Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

Niko said:
Either 2 reporters got it wrong or there is a piece missing from the public domain.

My only is interest is to properly represent the statements by WHO officials, and attempt to avoid the oft used easy way out: "If my theories are not supported by the data, then obviously someone is hiding the data."

It's hard enough to fight this ugly virus, and I would just as soon stick to the facts as we all work through the puzzel. I hope I have not misrepresented them in any of my posts.
 
Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

Mamabird - you have not misrepresented them. It is a briar patch sorting through all of the facts and issues.

WHO is working hard to ascertain the facts and disseminate information.

They are bashed on other forums and blogs as if they hold the keys to all mysteries H5N1.

We support all international agencies in their efforts to solve the AI problems. Are they perfect? No.

No one is.
 
Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

Mamabird said:
I apoligize, but I can find no statement by any WHO official that stated that a Vietnam patient had N294S. All I can locate is a statement by a reporter that the so called "294S" mutation was also in Vietnam. As everyone knows, that has never been the case, nor has WHO ever represented that to be the case as far as anyone knows.

The point is, and always has been, that when Tamiflu is given to infected patients, H5N1 quickly attempts to overt the roadblock that binds the new virons to the host cell. It has four different mutations that it uses to accomplish that, only one of which is N294S.
Just to clarify, I have seen the sequences from the Gharbiya cluster. Both patients have N294S. 274 is H (wild type).

That is the point. The tamiflu resistance in Egypt is NOT the same as the resistance in the public sequences in Vietnam. The WHO update says ONE patient had it in Vietnem. For H274Y SEVERAL patients have had it.

N294S has never been reported (although WHO says they have seen it).
 
Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

Mamabird said:
My only is interest is to properly represent the statements by WHO officials, and attempt to avoid the oft used easy way out: "If my theories are not supported by the data, then obviously someone is hiding the data."

It's hard enough to fight this ugly virus, and I would just as soon stick to the facts as we all work through the puzzel. I hope I have not misrepresented them in any of my posts.

The WHO update isuued today is quite clear. See bold below:

<TABLE cellSpacing=0 cellPadding=0 width=741 border=0><TBODY><TR><TD vAlign=top width=599><TABLE cellSpacing=0 cellPadding=0 width=599 border=0><TBODY><TR><TD>Avian influenza - situation in Egypt - update
18 January 2007
Viruses with a genetic mutation, linked in laboratory testing to moderately reduced susceptibility to oseltamivir, have been discovered in two persons previously reported with H5N1 infections in Egypt. Both patients had been on treatment with oseltamivir for two days before the clinical samples that yielded the viruses were taken.
The two patients from whom samples were taken were a 16 year-old female and a 26 year-old male from Gharbiyah Province, Egypt.<SUP>1</SUP> They were a niece and uncle, respectively, who lived in the same house. The girl was admitted to a hospital on 19 December 2006, while the man was admitted on 17 December. On 21 December they began receiving 2 tablets per day of oseltamivir. On 23 December they were moved to a referral hospital. The samples which have so far been tested were taken from the two patients on 23 December. The girl died on 25 December and the man died on 28 December 2006.
In this and all other H5N1 investigations there is close, ongoing coordination between Egypt's Ministry of Health and Population (MOH&P) and WHO. It was Egypt's monitoring and rapid virological analysis conducted at the Central Public Health Laboratory in Cairo that initially allowed the diagnoses of H5N1 to be made. Confirmatory testing and genetic sequencing was done at NAMRU-3 and at two WHO Collaborating Centres located in Atlanta, USA and London, UK.
At this time there is no indication that oseltamivir resistance is widespread in Egypt or elsewhere. WHO is not making any changes in antiviral treatment recommendations for H5N1-infected persons published in June 2006 because the clinical level of resistance of these mutations is not yet well established. Current laboratory testing suggests that the level of reduced susceptibility is moderate. This mutation has previously been identified in Viet Nam in one case in 2005. Moreover, these mutations are not associated with any known change in the transmissibility of the virus between humans. Based on these considerations, the public health implications at this time are limited. Finally, these findings do not indicate a need for a change in phase level. The WHO pandemic preparedness level remains at three.
The Egyptian authorities, WHO and its Collaborating Centres will continue to share with the public all relevant information from the on-going investigations and analyses as soon as it becomes available.
rule.gif

<SUP>1</SUP>The ages and dates in this update related to the two patients, may differ slightly from earlier reports, but reflect the most recent information provided to WHO.

</TD></TR></TBODY></TABLE></TD></TR><TR><TD colSpan=5><!-- include ftr--><TABLE cellSpacing=10 cellPadding=0 width=741 border=0><TBODY><TR><TD align=middle>
</TD></TR></TBODY></TABLE></TD></TR></TBODY></TABLE>
 
Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

Florida1 said:
Mamabird - you have not misrepresented them. It is a briar patch sorting through all of the facts and issues.

WHO is working hard to ascertain the facts and disseminate information.

They are bashed on other forums and blogs as if they hold the keys to all mysteries H5N1.

We support all international agencies in their efforts to solve the AI problems. Are they perfect? No.

No one is.
The issue is what was stated in today's WHO update, which indicates N294S was seen in ONE patient in Vietnam in 2005. There is no public H5N1 sequence with N294S from a patient in Vietnam in 2005.
 
Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

Mamabird said:
My only is interest is to properly represent the statements by WHO officials, and attempt to avoid the oft used easy way out: "If my theories are not supported by the data, then obviously someone is hiding the data."

It's hard enough to fight this ugly virus, and I would just as soon stick to the facts as we all work through the puzzel. I hope I have not misrepresented them in any of my posts.
Here is a 1, 2 3.

1. A new tamiflu resistant polymorphism is in both patients from the Gharbiya cluster.

2. Both patients have N274S.

3. Who issued a Situation update today on Egypt.

4. The situation update was devoted to N274S.

5. WHO indicates that the change has been seen in ONE patient in Vietnam in 2005.

6. The H5N1 from that ONE patient is not in the public domain.

7. The likely explation is that the private data base maintained by WHO for its network.

8. The hoarding continues (NAMRU-3 sends samples to CDC and Weybridge for sequencing - CDC has released ZERO sequneces from Egypt, Weybridge has released 2, NAMRU-3 has released 12).
 
Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

Mamabird said:
My only is interest is to properly represent the statements by WHO officials, and attempt to avoid the oft used easy way out: "If my theories are not supported by the data, then obviously someone is hiding the data."

It's hard enough to fight this ugly virus, and I would just as soon stick to the facts as we all work through the puzzel. I hope I have not misrepresented them in any of my posts.

I would not want any statements to be misrepresented either. I simply seek the truth and know you do as well. I appreciate and welcome your comments.
 
Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

niman said:
The issue is what was stated in today's WHO update, which indicates N294S was seen in ONE patient in Vietnam in 2005. There is no public H5N1 sequence with N294S from a patient in Vietnam in 2005.

I understand this. There is some inconsistent data. There is a sequence mystery. There are missing sequences. Yes, we want them.

There are many dedicated individuals that work at the International agencies and Federal departments.

I am not going to argue about this. Publicly berating these groups does not result in release.
 
Last edited:
Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

><input name="getSeqGi" value="79081898" onclick="synchronizeCheck(this.value, 'getSeqAlignment1', 'getSeqGi', this.checked)" type="checkbox">gi|79081898|gb|ABB51960.1| neuraminidase [Influenza A virus (A/Taiwan/30017/2002(H1N1))]
Length=470

Score = 41.8 bits (91), Expect = 0.004
Identities = 11/11 (100%), Positives = 11/11 (100%), Gaps = 0/11 (0%)

..Query 1 CVCRDSWHGSN 11
Sbjct 290 CVCRDSWHGSN 300

is one of them? N294S
 
Re: New Strain of Bird Flu Found in Egypt Is Resistant to Antiviral Drug

Sonny said:
><INPUT onclick="synchronizeCheck(this.value, 'getSeqAlignment1', 'getSeqGi', this.checked)" type=checkbox value=79081898 name=getSeqGi>gi|79081898|gb|ABB51960.1| neuraminidase [Influenza A virus (A/Taiwan/30017/2002(H1N1))]
Length=470

Score = 41.8 bits (91), Expect = 0.004
Identities = 11/11 (100%), Positives = 11/11 (100%), Gaps = 0/11 (0%)

..Query 1 CVCRDSWHGSN 11
Sbjct 290 CVCRDSWHGSN 300

is one of them? N294S
That is the human case (H1N1).
 
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