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Influenza viruses resistant to oseltamivir, news and updates

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Wanna bet that 'sudden' influenza B adaptation might be due to the same factor of vaccine production and strain selection?
 
Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Oracle said:
Only point in that posting was the mention of inappropriate choice of vaccine strains driving evolutionary pressure that results in (perhaps) new-to-human strains, causing epidemics.

..........The thrust of this thread is this: we have plenty of evidence that inappropriate choice of vaccine strains and their widespread use for one or more seasons can potentially harm more than help.

..............
Where vaccination is vigorously employed to contain outbreaks, and the viral genome is plastically adept at immune evasion, the 'wrong' choice of vaccine strain to combat human and animal disease may carry heavy consequences in subsequent years........
Click to expand...

It's interesting to remember that the original H1N1 was fairly stable until we started vaccinations - then there was the 1947 mini-pandemic. See earlier discussion at http://www.flutrackers.com/forum/showthread.php?t=56695&highlight=1947+H1N1+pandemic

.
 
Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

AlaskaDenise said:
It's interesting to remember that the original H1N1 was fairly stable until we started vaccinations - then there was the 1947 mini-pandemic. See earlier discussion at http://www.flutrackers.com/forum/showthread.php?t=56695&highlight=1947+H1N1+pandemic

.
Click to expand...
It should be noted that by the time the Solomon Island H1N1 vaccine was used (this season for the northern hemisphere), the Solomon Island clade 2A had been replaced by Brisbane clade 2B and Hong Kong clade 2C.

This past season there is NO evidence for the presence of clade 2A in the US (or anywhere else) in the 2007/2008 season, MMWR/CDC reports notwithstanding.

This appears to be a MAJOR snow job (commentary soon).
 
Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

If such antiviral resistance strain mess came out because of seasonal vaccines, what would happen if (like suggested in one thread) the pre-pandemic bf vaccines will be injected (to prime, or else) in endemic areas before any pandemic?

Wouldn't than the outcome result be much worse - inducing an more resistant human bf new strain enabled that way to go pandemic, instead using existing pre-pand. vacc. only when the pandemic realy starts?
 
Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

tropical said:
If such antiviral resistance strain mess came out because of seasonal vaccines, what would happen if (like suggested in one thread) the pre-pandemic bf vaccines will be injected (to prime, or else) in endemic areas before any pandemic?

Wouldn't than the outcome result be much worse - inducing an more resistant human bf new strain enabled that way to go pandemic, instead using existing pre-pand. vacc. only when the pandemic realy starts?
Click to expand...
Seasonal flu is established in human populations, while pandemic H5N1 is not. Attacking an established strain with a mismatched vaccine simply pushes the evolution (like treating Brisbane/Hong Kong with Solomon Island or use of H5N2 to vaccinate poultry).

A pre-pandemic vaccine, especially when used as a bootser (and followed up a year later with another boost), PREVENTS the estrablishment of the pandemic strain in the human population.
 
Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Thank you Dr. Niman for your clarification.

Than the suggested WHO/countries/local preparations are wrong when suggesting not enaugh pre-pandemics vacc. quantity production, and it's applying only after the start, based on triages, instead of pre-pand. vacc. for all citizens stocked now and distributed as a prevention measure.

But the main trail guidelines/production aren't changed ...
 
Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

I sent email to CDC, asking to confirm this season's H1N1-numbers
 
Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

niman said:
Seasonal flu is established in human populations, while pandemic H5N1 is not. Attacking an established strain with a mismatched vaccine simply pushes the evolution (like treating Brisbane/Hong Kong with Solomon Island or use of H5N2 to vaccinate poultry).

A pre-pandemic vaccine, especially when used as a bootser (and followed up a year later with another boost), PREVENTS the estrablishment of the pandemic strain in the human population.
Click to expand...

I wonder:

What has decades of influenza vaccine use, human virus cultured in eggs, done to blur viral recognition between species? Especially when it's intended for use in the our most susceptible subpopulations?

(I shudder to consider the effect of a growing cohort of HIV-infected individuals, on promoting viral escape, as they are proficient silent carriers).

That CACO2 intestinal cell line study, now that was a interesting study. It suggested that human influenza viruses were easily 'chickenized' by nearly-universal vaccine production methods.

I think that just might have 'trickle down' effects in later decades, don't you, where human viruses meet avian - in say, viral mixmastering swine populations?

.
 
Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

gsgs said:
I sent email to CDC, asking to confirm this season's H1N1-numbers
Click to expand...
The CDC has published well over 100 sequences from this season and there are ZERO clade 2A, which is also true for the sequences published by the Air Force as well as teh various phylogenetic trees which have ZERO clade 2A isolates from the 2007/2008.

The story is in the sequence and the story on Clade 2A (Solomon Islands) in 2007/2008 is VERY clear.

On a related the Relenza resistance (Q137K) is also on a Brisbane backgound and has now appeared in the US (Pennsylvania this year).

LOCUS EU516286 1413 bp cRNA linear VRL 11-JUN-2008
DEFINITION Influenza A virus (A/Pennsylvania/01/2008(H1N1)) segment 6
neuraminidase (NA) gene, complete cds.
ACCESSION EU516286
VERSION EU516286.1 GI:168828050
KEYWORDS .
SOURCE Influenza A virus (A/Pennsylvania/01/2008(H1N1))
ORGANISM Influenza A virus (A/Pennsylvania/01/2008(H1N1))
Viruses; ssRNA negative-strand viruses; Orthomyxoviridae;
Influenzavirus A.
REFERENCE 1 (bases 1 to 1413)
AUTHORS Garten,R., Barnes,J., Myrick,A., Xu,X. and Klimov,A.
TITLE Direct Submission
JOURNAL Submitted (25-FEB-2008) Centers for Disease Control and Prevention,
Mailstop G-161600, Clifton Road NE, Atlanta, GA 30333, USA
COMMENT Sequence entered on behalf of submitter by database staff.
FEATURES Location/Qualifiers
source 1..1413
/organism="Influenza A virus
(A/Pennsylvania/01/2008(H1N1))"
/mol_type="viral cRNA"
/strain="A/Pennsylvania/01/2008"
/serotype="H1N1"
/isolate="2008705103"
/specific_host="Homo sapiens"
/db_xref="taxon:505568"
/segment="6"
/country="USA"
/collection_date="02-Jan-2008"
/note="passage details: X/C1
A/SOLOMON ISLANDS/03/2006-like (H1N1) low;
adamantane-sensitive; oseltamivir-sensitive"
gene 1..1413
/gene="NA"
CDS 1..1413
/gene="NA"
/codon_start=1
/product="neuraminidase"
/protein_id="ACA33667.1"
/db_xref="GI:168828051"
/translation="MNPNQKIITIGSISIAIGIISLMLQIGNIISIWASHSIQTGSQN
NTGICNQRIITYENSTWVNHTYVNINNTNVVAGEDKTSVTLAGNSSLCSISGWAIYTK
DNSIRIGSKGDVFVIREPFISCSHLECRTFFLTXGALLNDKHSNGTVKDRSPYRALMS
CPLGEAPSPYNSKFESVAWSASACHDGMGWLTIGISGPDNGAVAVLKYNGIITGTIKS
WKKQILRTQESECVCMNGSCFTIMTDGPSNKAASYKIFKIEKGKVTKSIELNAPNFHY
EECSCYPDTGIVMCVCRDNWHGSNRPWVSFNQNLDYQIGYICSGVFGDNPRPEDGEGS
CNPMTVDGANGVKGFSYKYDNGVWIGRTKSNRLRKGFEMIWDPNGWTNTDSDFSVKQD
VVAITDWSGYSGSFVQHPELTGLDCIRPCFWVELVRGLPRENTTIWTSGSSISFCGVN
SDTASWSWPDGAELPFTIDK"
misc_feature 1..1413
/note="ISDN285829"
ORIGIN
1 atgaacccaa atcaaaagat aataaccatt ggatcaatca gtatagcaat cggaataatt
61 agtctaatgt tgcaaatagg aaatattatt tcaatatggg ctagtcactc aatccaaact
121 ggaagtcaaa acaacactgg aatatgcaac caaagaatca tcacatatga aaacagcacc
181 tgggtgaatc acacatatgt taatattaac aacactaatg ttgttgctgg agaggacaaa
241 acttcagtga cattggccgg caattcatct ctttgttcta tcagtggatg ggctatatac
301 acaaaagaca acagcataag aattggctcc aaaggagatg tttttgtcat aagagaacct
361 ttcatatcat gttctcactt ggaatgcaga accttttttc tgaccmaagg cgctctatta
421 aatgacaaac attcaaatgg gaccgtaaag gacagaagtc cttatagggc cttaatgagc
481 tgtcctctag gtgaagctcc gtccccatac aattcaaagt tcgaatcagt tgcatggtca
541 gcaagcgcat gccatgatgg catgggctgg ttaacaatcg gaatttctgg tccagacaat
601 ggagctgtgg ctgtactaaa atacaacgga ataataactg gaaccataaa aagttggaaa
661 aagcaaatat taagaacaca agagtctgaa tgtgtctgta tgaacgggtc atgtttcacc
721 ataatgaccg atggcccgag taataaggcc gcctcgtaca aaattttcaa gatcgaaaag
781 gggaaggtta ctaaatcaat agagttgaat gcacccaatt ttcattatga ggaatgttcc
841 tgttacccag acactggcat agtgatgtgt gtatgcaggg acaactggca tggttcaaat
901 cgaccttggg tgtcttttaa tcaaaacttg gattatcaaa taggatacat ctgcagtgga
961 gtgttcggtg acaatccgcg tcccgaagat ggagagggca gctgcaatcc aatgactgtt
1021 gatggagcaa acggagtaaa agggttttca tacaaatatg ataatggtgt ttggatagga
1081 aggaccaaaa gtaacagact tagaaagggg tttgagatga tttgggatcc taatggatgg
1141 acaaataccg acagtgattt ctcagtgaaa caggatgttg tagcaataac tgattggtca
1201 gggtacagcg gaagtttcgt ccaacatcct gagttaacag gattggactg tataagacct
1261 tgcttctggg ttgagttagt cagagggctg cctagagaaa atacaacaat ctggactagt
1321 gggagcagca tttctttttg tggcgttaat agtgatactg caagctggtc ttggccagac
1381 ggtgctgagt tgccgttcac cattgacaag tag
 
Re: _|ANTIVIRALS RESISTANCE BAFFLED SCIENTISTS|_

Re: _|ANTIVIRALS RESISTANCE BAFFLED SCIENTISTS|_

Oracle said:
I was only able to find reports of Relenza resistance to one influenza virus: type B, which I believe hadn't shown antiviral resistance before this year. I hadn't heard about Relenza resistance.

I've wondered if substandard dosing is the culprit behind sudden rise of geographically distinct, but not distant (as in Paris and Southern France) resistance of H1N1 to tamiflu.

(the following is purely speculative babble)...

Maybe there is something in the food or regional favorite drink that either inhibits the esterase cleavage of precursor form of Tamiflu or enhances its drug metabolism, clearing it from the system before it has a chance to work properly. Provence and Parisian/Bordeaux cuisine are quite different.

Tamiflu is, after all, derived from natural product (unlike Relenza, which is purely synthetic and I believe active in its administered form, although it has poor uptake when administered orally).

The spice it is most like is burned as incense in Japan, and consumed elsewhere in Arabic and European cooking/appertifs.
Click to expand...
Relenza resistance is showing up on Brisbane H1H1 in Asia, and has now appeared in the US.

Asia isolates

gb|CY030877.1| Influenza A virus (A/Christchurch/62/2007(H1N1... 40.1 0.040
gb|CY030875.1| Influenza A virus (A/Brisbane/308/2007(H1N1)) ... 40.1 0.040
gb|CY030873.1| Influenza A virus (A/Thailand/39/2008(H1N1)) s... 40.1 0.040
gb|CY030871.1| Influenza A virus (A/Brisbane/334/2007(H1N1)) ... 40.1 0.040
gb|CY030868.1| Influenza A virus (A/Philippines/905/2006(H1N1... 40.1 0.040
gb|CY030866.1| Influenza A virus (A/Philippines/604/2006(H1N1... 40.1 0.040
gb|CY030864.1| Influenza A virus (A/Philippines/1279/2006(H1N... 40.1 0.040
gb|EU124179.1| Influenza A virus (A/Brisbane/297/2006(H1N1)) ... 40.1 0.040
 
Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

niman said:
A pre-pandemic vaccine, especially when used as a bootser (and followed up a year later with another boost), PREVENTS the estrablishment of the pandemic strain in the human population.
Click to expand...
.........but not the establishment of a milder mini-pandemic strain? Can pre-pan vax with boosters prevent the establishment of H5N1 in the human population?
 
Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Dr Niman,

As this discussion has gone beyond the capabilities of my usual search methods, could you please direct me to information concerning the H1N1 mutation Q137K and it's interaction with zanamivir?



Cheers,

John
 
Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

miso said:
Dr Niman,

As this discussion has gone beyond the capabilities of my usual search methods, could you please direct me to information concerning the H1N1 mutation Q137K and it's interaction with zanamivir?



Cheers,

John
Click to expand...
I think the only references so far are the characterization sheets, like the one posted.
 
Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

referring to the meeting (post #113) where they determine
the vaccine for the next season :

wouldn't it be better to discuss such things in an internet forum ?

no problems with people being absent, you post when you have time,
several people can talk at the same time, votes can be changed, links to documents can be given,
others may contribute (after moderation)
 
Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

gsgs said:
referring to the meeting (post #113) where they determine
the vaccine for the next season :

wouldn't it be better to discuss such things in an internet forum ?

no problems with people being absent, you post when you have time,
several people can talk at the same time, votes can be changed, links to documents can be given,
others may contribute (after moderation)
Click to expand...
The meetings are on deadline. No one is going to wait for someone to post when they have the time. These meetings last a few hours (no internet required).
 
Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

yes, that's the disadvantage of the meetings vs. internet-forum
 
Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

miso said:
Dr Niman,

As this discussion has gone beyond the capabilities of my usual search methods, could you please direct me to information concerning the H1N1 mutation Q137K and it's interaction with zanamivir?



Cheers,

John
Click to expand...
Actually, the above should read Q136K. There is also Q136R as a mixture in a recent NJ isolate suggesting it will also be zanamivir (Relenza) resistant.
 
Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

LOCUS EU716607 1427 bp cRNA linear VRL 05-JUN-2008
DEFINITION Influenza A virus (A/New Jersey/08/2008(H1N1)) segment 6
neuraminidase (NA) gene, complete cds.
ACCESSION EU716607
VERSION EU716607.1 GI:188076366
KEYWORDS .
SOURCE Influenza A virus (A/New Jersey/08/2008(H1N1))
ORGANISM Influenza A virus (A/New Jersey/08/2008(H1N1))
Viruses; ssRNA negative-strand viruses; Orthomyxoviridae;
Influenzavirus A.
REFERENCE 1 (bases 1 to 1427)
AUTHORS Garten,R., Barnes,J., Myrick,A., Smith,C., Xu,X. and Klimov,A.
TITLE Direct Submission
JOURNAL Submitted (14-MAY-2008) Centers for Disease Control and Prevention,
Mailstop G-161600 Clifton Road NE, Atlanta, GA 30333, USA
COMMENT Sequence entered by GenBank staff on behalf of submitter.
FEATURES Location/Qualifiers
source 1..1427
/organism="Influenza A virus (A/New Jersey/08/2008(H1N1))"
/mol_type="viral cRNA"
/strain="A/New Jersey/08/2008"
/serotype="H1N1"
/isolate="2008705634"
/specific_host="Homo sapiens"
/db_xref="taxon:529046"
/segment="6"
/country="USA"
/collection_date="21-Jan-2008"
/note="passage details: MX/C2
A/SOLOMON ISLANDS/03/2006-like (H1N1);
adamantane-sensitive; oseltamivir-sensitive"
misc_feature 1..1427
/note="ISDN289956"
gene 1..1413
/gene="NA"
CDS 1..1413
/gene="NA"
/codon_start=1
/product="neuraminidase"
/protein_id="ACD47210.1"
/db_xref="GI:188076367"
/translation="MNPNQKIITIGSISIAIGIISLMLQIGNIISIWASHSIQTGSQN
NTGICNQRIITYENSTWVNHTYVNINNTNVVAGEDKTSVTLAGNSSLCSISGWAIYTK
DNSIRIGSKGDVFVIREPFISCSHLECRTFFLTXGALLNDKHSNGTVKDRSPYRALMS
CPLGEAPSPYNSKFESVAWSASACHDGMGWLTIGISGPDNGAVAVLKYNGIITGTIKS
WKKQILRTQESECVCMNGSCFTIMTDGPSNKAASYKIFKIEKGKVTKSIELNAPNFHY
EECSCYPDTGIVMCVCRDNWHGSNRPWVSFNQNLDYQIGYICSGVFGDNPRPEDGEGS
CNPMTVDGANGVKGFSYKYDNGVWIGRTKSNRLRKGFEMIWDPNGWTNTDSDFSVKQD
VVAITDWSGYSGSFVQHPELTGLDCIRPCFWVELVRGLPRENTTIWTSGSSISFCGVN
SDTASWSWPDGAELPFTIDK"
ORIGIN
1 atgaacccaa atcaaaagat aataaccatt ggatcaatca gtatagcaat cggaataatt
61 agtctaatgt tgcaaatagg aaatattatt tcaatatggg ctagtcactc aatccaaact
121 ggaagtcaaa acaacactgg aatatgcaac caaagaatca tcacatatga aaacagcacc
181 tgggtgaatc acacatatgt taatattaac aacactaatg ttgttgctgg agaggacaaa
241 acttcagtga cattggccgg caattcatct ctttgttcta tcagtggatg ggctatatac
301 acaaaagaca acagcataag aattggctcc aaaggagatg tttttgtcat aagagaacct
361 ttcatatcat gttctcactt ggaatgcaga accttttttc tgacccragg cgctctatta
421 aatgacaaac attcaaatgg gaccgtaaag gacagaagtc cttatagggc cttaatgagc
481 tgtcctctag gtgaagctcc gtccccatac aattcaaagt tcgaatcagt tgcatggtca
541 gcaagcgcat gccatgatgg catgggctgg ttaacaatcg gaatttctgg tccagacaat
601 ggagctgtgg ctgtactaaa atacaacgga ataataactg gaaccataaa aagttggaaa
661 aagcaaatat taagaacaca agagtctgaa tgtgtctgta tgaacgggtc atgtttcacc
721 ataatgaccg atggcccgag taataaggcc gcctcgtaca aaattttcaa gatcgaaaag
781 gggaaggtta ctaaatcaat agagttgaat gcacccaatt ttcattatga ggaatgttcc
841 tgttacccag acactggcat agtgatgtgt gtatgcaggg acaactggca tggttcaaat
901 cgaccttggg tgtcttttaa tcaaaacttg gattatcaaa taggatacat ctgcagtgga
961 gtgttcggtg acaatccgcg tcccgaagat ggagagggca gctgcaatcc aatgacagtt
1021 gatggagcaa acggagtaaa agggttttca tacaaatatg ataatggtgt ttggatagga
1081 agaaccaaaa gtaacagact tagaaagggg tttgagatga tttgggatcc taatggatgg
1141 acaaataccg acagtgattt ctcagtgaaa caggatgttg tagcaataac tgattggtca
1201 gggtacagcg gaagtttcgt ccaacatcct gagttaacag gattggactg tataagacct
1261 tgcttctggg ttgagttagt cagagggcta cctagagaaa atacaacaat ctggactagt
1321 gggagcagca tttctttttg tggcgttaat agtgatactg caagctggtc ttggccagac
1381 ggtgctgagt tgccgttcac cattgacaag tagttcgttg aaaaaaa
 
Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Dr Niman,

I'm sure there are degrees of Relenza resistance. It could be said that the conga line of suckholes that unconditionally supported Tamiflu (CDC WHO etc.) are also resistant to Relenza.
It seems the albatross has to start stinking before they'll change their recommendations and acknowledge the state of unpreparedness they are responsible for. Shouldn't be long now........
 
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