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July 23rd, 2008, 07:50 AM
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
Thank you Kent.
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July 23rd, 2008, 08:14 AM
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
Quote:
Originally Posted by tropical
#148, Kent.N.
"ProMED: ...
Laboratory tests on 6 samples of the H5N1 strain of avian influenza collected from poultry in Indonesia in 2005 showed they were between 15 and 30 times less sensitive to Tamiflu than a family of the viruses collected in Southeast Asia a year earlier."
Does the above means results from poultry lab. experiments provenience,
or inc. folks treated infected farming poultry with Tamiflu antivirals and those poultry exibited than the above lab results of resistance?
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The antiviral resiatnce was reported at the Options VI meeting over a year ago (which means they had the data almost 2 years ago). These results would be for testing of H5N1 from samples. There was no specific change (like H274Y) in the isolates.
The only human H5N1 sequence I know of is from the Karo patient who stopped taking his Tamiflu. He died and H274Y was in his H5N1 sequence.
Tamiflu is dispersed like candy in Indonesia, and the last public human sequence was from January, 2007.
It is likely that there is unreported H274Y in H5N1 and H1N1 in Indonesia.
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July 23rd, 2008, 08:18 AM
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
Quote:
Originally Posted by miso
Dr Niman,
Thank you for spending time on my questions. Obviously I have a lot to learn with regards to sequencing and interpreting NCBI data. The data you are relying on seems to be contributed by two groups. One that does not mention zanamivir in their submissions (as I noted in an above post) and the other group who seem to be submitting a mix of influenza data with no mention of zanamivir and a title for an as yet unpublished paper. The sooner they are published, the sooner we'll (I'll) know degrees of resistance, viability of the resistant strain etc.
I would have thought this would have been a priority for the medical community, an opportunity to say Relenza is as big a dud as Tamiflu (as happened with the behaviour warning from Japan).
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LOCUS CY030873 1396 bp cRNA linear VRL 17-MAR-2008
DEFINITION Influenza A virus (A/Thailand/39/2008(H1N1)) segment 6 sequence.
ACCESSION CY030873
VERSION CY030873.1 GI:170026929
KEYWORDS .
SOURCE Influenza A virus (A/Thailand/39/2008(H1N1))
ORGANISM Influenza A virus (A/Thailand/39/2008(H1N1))
Viruses; ssRNA negative-strand viruses; Orthomyxoviridae;
Influenzavirus A.
REFERENCE 1 (bases 1 to 1396)
AUTHORS Hurt,A.C., Kelso,A. and Barr,I.G.
TITLE Community cases of zanamivir-resistant human influenza viruses with
a novel mutation in the neuraminidase gene
JOURNAL Unpublished
REFERENCE 2 (bases 1 to 1396)
AUTHORS Hurt,A.C., Deng,Y.-M. and Komadina,N.
TITLE Direct Submission
JOURNAL Submitted (14-MAR-2008) WHO Collaborating Centre for Reference and
Research on Influenza, 45 Poplar Rd, Parkville, Victoria 3052,
Australia
FEATURES Location/Qualifiers
source 1..1396
/organism="Influenza A virus (A/Thailand/39/2008(H1N1))"
/mol_type="viral cRNA"
/strain="A/Thailand/39/2008(H1N1)"
/serotype="H1N1"
/isolation_source="gender:M; age:23"
/specific_host="Human"
/db_xref="taxon: 511421"
/segment="6"
/lab_host="MDCKX passage(s)"
/country="Thailand"
/collection_date="02-Jan-2008"
gene 1..>1396
/gene="NA"
CDS 1..>1396
/gene="NA"
/codon_start=1
/product="neuraminidase"
/protein_id=" ACB05991.1"
/db_xref="GI:170026930"
/translation="MNPNQKIITIGSISIAIGIISLMLQIGNIISIWASHSIQTGSQN
NTGICNQRIITYENSTWVNHTYVNINNTNVVAGEDKTSVTLAGNSSLCSI SGWAIYTK
DNSIRIGSKGDVFVIREPFISCSHLECRTFFLTKGALLNDKHSNGTVKDR SPYRALMS
CPLGEAPSPYNSKFESVAWSASACHDGMGWLTIGISGPDNGAVAVLKYNG IITGTIKS
WKKQILRTQESECVCMNGSCFTIMTDGPSNKAASYKIFKIEKGKVTKSIE LNAPNFHY
EECSCYPDTGIVMCVCRDNWHGSNRPWVSFNQNLDYQIGYICSGVFGDNP RPEDGEGS
CNPVTVDGANGVKGFSYKYDNGVWIGRTKSNRLRKGFEMIWDPNGWTNTD SDFSVKQD
VVAITDWSGYSGSFVQHPELTGLDCIRPCFWVELVRGLPRENTTIWTSGS SISFCGVN
SDTANWSWPDGAELP"
ORIGIN
1 atgaatccaa atcaaaaaat aataaccatt ggatcaatca gtatagcaat cggaataatt
61 agtctaatgt tgcaaatagg aaatattatt tcaatatggg ctagtcactc aatccaaact
121 ggaagtcaaa acaacactgg aatatgcaac caaagaatca tcacatatga aaacagcacc
181 tgggtgaatc acacatatgt taatattaac aacactaatg ttgttgcagg agaggacaaa
241 acttcagtga cattggccgg caattcgtct ctttgttcta tcagtggatg ggctatatac
301 acaaaagaca acagcataag aattggctcc aaaggagatg tttttgtcat aagagaacct
361 ttcatatcat gttctcactt ggaatgcaga accttttttc tgaccaaagg 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 agtgactgtt
1021 gatggagcaa acggagtaaa agggttttca tacaaatatg ataatggtgt ttggatagga
1081 aggaccaaaa gtaacagact tagaaagggg tttgagatga tctgggatcc taatggatgg
1141 acaaataccg acagtgattt ctcagtgaaa caggatgttg tagcaataac tgattggtca
1201 gggtacagcg gaagtttcgt ccaacatcct gagttaacag gattggactg tataagacct
1261 tgcttctggg ttgagttagt cagagggctg cctagagaaa atacaacaat ttggactagt
1321 gggagcagca tttctttttg tggcgttaat agtgatactg caaactggtc ttggccagac
1381 ggtgctgagt tgccat
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July 23rd, 2008, 08:23 AM
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Retired
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
Quote:
Originally Posted by miso
Dr Niman,
Thank you for spending time on my questions. Obviously I have a lot to learn with regards to sequencing and interpreting NCBI data. The data you are relying on seems to be contributed by two groups. One that does not mention zanamivir in their submissions (as I noted in an above post) and the other group who seem to be submitting a mix of influenza data with no mention of zanamivir and a title for an as yet unpublished paper. The sooner they are published, the sooner we'll (I'll) know degrees of resistance, viability of the resistant strain etc.
I would have thought this would have been a priority for the medical community, an opportunity to say Relenza is as big a dud as Tamiflu (as happened with the behaviour warning from Japan).
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Abstract of CDC presentation at Options VI
Abstract O66
Monitoring of Influenza Virus
Susceptibility to Neuraminidase
Inhibitors (NAIs) LV Gubareva, VM Deyde, X Xu, RA Bright *, TG Sheu, AI Klimov
Influenza Division, National Center for Immunization and Respiratory Diseases,
Centers for Disease Control and Prevention, Atlanta Georgia, USA *Present address:
Novavax, One Taft Court, Suite 200 Rockville, Maryland 20850 USA
Oseltamivir and zanamivir are currently approved NAIs for
the control of influenza infections; a third drug, peramivir, is
undergoing clinical evaluation. NAI-susceptibility is commonly
assessed through an enzyme activity inhibition assay with either
chemiluminogenic or fluorogenic substrate. Standardization
of assay conditions is essential for reliable drug resistance
monitoring. As a part of continued influenza strain surveillance,
we utilized a recently developed NAStar kit for the detection
of NAI-resistant mutants by means of chemiluminescence.
Zanamivir and oseltamivir were used to determine IC 50 values
for 133 A(H1N1), 186 A(H3N2), and 118 B viruses collected in
2005-2007. All viruses appeared sensitive to both drugs with
one exception. An influenza B virus, with a R371K substitution
at the enzyme active site, exhibited elevated IC50 values when
tested with both zanamivir (~150nM) and oseltamivir (~1,000
nM), which indicates drug resistance. Another influenza B
virus, although sensitive to both drugs, contained substitution
H274Y in the NA active site, which was previously shown to
confer in-vitro resistance to peramivir. The two newly identified
variants and a panel of well-characterized oseltamivir- or
zanamivir-selected mutants and their respective wild types
(WT) were then tested with four NAIs (oseltamivir, zanamivir,
peramivir, and A-315675). When tested with oseltamivir, the
oseltamivir-selected mutants [e.g., H274Y(N1)] exhibited 10-
fold or greater IC50 values than their WT. In contrast, a majority
of the zanamivir-resistant viruses [e.g., E119G(N2)] had <10-
fold increase in IC50 values compared to their WT, when tested
with zanamivir. Nevertheless, when tested with oseltamivir,
two of those mutants [R152K(B) and R292K(N2)] exhibited >10-
fold increase in their IC50 values compared to their WT viruses.
The H274Y(B) variant exhibited a 4-fold increase in IC50 value
for peramivir compared to that of the control virus. When the
same variant was tested in fluorescent assay, increase in IC50
values was greater for both peramivir (~10-fold) and oseltamivir
(~5-fold). The R371K variant exhibited cross-resistance to all
four NAIs in both assays (≥10 fold). A majority of NAI-resistant
mutants were detected with NAStar kit; thus, it could be
useful for drug resistance surveillance. To ensure dependable
detection of every zanamivir- and peramivir-resistant mutant, improvements to the kit should be considered.
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July 23rd, 2008, 08:25 AM
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
Q136R abstract
Abstract O67
Novel Mutations in the ‘150-Cavity’
of N1 Neuraminidase Confer Reduced
Sensitivity to the Neuraminidase Inhibitors Aeron C Hurt 1,2, Ian G Barr1,2
1 World Health Organisation Collaborating Centre for Reference and Research on
Influenza, Parkville, Victoria 3052, Australia; 2Monash University, School of Applied
Sciences, Churchill, Victoria 3842, Australia
The neuraminidase (NA) inhibitors are a specifically designed
class of antiviral drugs that bind to the active site of the NA
surface glycoprotein of newly formed influenza virus particles
and prevent their efficient release from the host cell. Although
resistance to these inhibitors is relatively rare, investigation
of circulating strains for changes in susceptibility remains
important. Analysis of recent influenza isolates received at
the WHO Collaborating Centre for Influenza in Melbourne has
revealed four A(H1N1) strains with increased IC 50 (50% inhibitory
concentration) values to either zanamivir or oseltamivir
carboxylate. These isolates were received from locations
where little or no NA inhibitors were in use and are therefore
assumed to be derived from patients not being treated with
the NA inhibitors. Two of the strains, which demonstrated a
250-fold increase in zanamivir IC50 but no change in oseltamivir
carboxylate IC50, were found to have a Q136K mutation in the
NA gene, while a third strain which had a 30-fold increase in
zanamivir IC50 and no change in oseltamivir carboxylate IC50
was found to have a K150T mutation in the NA gene. The fourth
A(H1N1) virus identified to confer reduced sensitivity to the NA
inhibitors, had a 30-fold increase in zanamivir IC 50 and a 10-fold
change in oseltamivir carboxylate IC50 and was found to have a
K143R NA gene mutation. Interestingly, all of the four mutants
contained substitutions at residues located in and around
the recently identified ‘150-cavity’ (Russell et al, 2006), which
following x-ray crystallography was shown to be adjacent to
the NA active site of group-1 neuraminidases (N1, N4, N5, N8),
but is not present in group-2 neuraminidases (N2,N3,N6,N7,N9).
None of these sites has previously been identified as conferring
NA inhibitor resistance either in vitro or in clinical studies. Given
that residues in this cavity appear to impact on zanamivir
sensitivity, and to a lesser extent oseltamivir sensitivity, it will
therefore be important to determine the extent to which both
H1N1 and highly pathogenic H5N1 viruses with mutations in
this region may be circulating.
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July 23rd, 2008, 08:27 AM
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
Abstract O69
Indonesian H5N1 Isolates Demonstrate
Decreased Sensitivity to Oseltamivir JL McKimm-Breschkin 1, P Selleck2, T Usman3, M Johnson2
1 CSIRO Molecular and Health Technologies, Parkville, Australia; 2CSIRO Livestock
Industries, Geelong, Australia; 3Disease Investigation Centre, Yogjakarta, Indonesia
Two different strains of highly pathogenic H5N1 avian influenza
have been circulating since 2003. Clade 1 has been found in
Vietnam, Thailand, Cambodia, Laos and Malaysia. Clade 2
subsequently emerged and spread from China to Indonesia,
Europe and Africa in 2004-2005. Due to its systemic availability
oseltamivir is the drug of choice for treating infected humans.
We tested the drug sensitivity of NAs from eight H5N1 viruses
from 2004 from Vietnam, two from 2004 from Malaysia, six
from Cambodia from 2004, four from 2005 and six clade 2 2005
viruses from Indonesia. Viruses were isolated from chickens,
ducks, geese and quail. In the absence of a validated cell culture
assay the IC 50 measured in the MUNANA based NA enzyme
inhibition assay was used for measuring drug sensitivity. All
clade 1 and clade 2 viruses had a similar sensitivity to zanamivir
as the reference human H1N1 NA. Sensitivities of the NAs to
oseltamivir fell into three groups compared to the human H1N1
strain. The clade 1 isolates from 2004 were all more sensitive
to oseltamivir than the human H1N1 control. However the NAs
of the 2005 Cambodian viruses showed a 6-7 fold decrease
specifically in oseltamivir sensitivity compared to the 2004
Cambodian isolates. These 2005 isolates came from the same
area as one of the more sensitive 2004 isolates, suggesting
regional evolution had occurred. Of more concern was the
third group. The NAs from all the clade 2 2005 Indonesian
viruses demonstrated a 25-30-fold decrease in sensitivity
specifically to oseltamivir compared to the clade 1 viruses. This
decrease in sensitivity is even greater than that conferred by
the N294S recently detected in Egypt, known to be selected
for by oseltamivir treatment. There was no altered sensitivity
to a third inhibitor, 4-AminoNeu5Ac2en, which shares the
4-amino substitution with oseltamivir, but has the original
glycerol side chain at the 6’ position. This indicates that the
altered binding of oseltamivir was due to altered interaction
with its hydrophobic pentyl ether group, thus explaining why
no altered binding to zanamivir was seen.
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July 23rd, 2008, 08:37 AM
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
#152,....
Thank you Dr. Niman.
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July 23rd, 2008, 05:24 PM
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Registered User
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Posts: 37
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
Yes, thank you.
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July 27th, 2008, 01:40 AM
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
A/Paris/963/2008 matches Hawaii
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July 27th, 2008, 09:18 PM
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
Quote:
Originally Posted by niman
A/Paris/963/2008 matches Hawaii
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Below is the travel log linking the movement of H274Y from New Caledonia (red bold) to Brisbane (blue bold)
gb|EU551821.1| Influenza A virus (A/Paris/963/2008(H1N1)) neu... 36.2 0.62
gb|EU716580.1| Influenza A virus (A/Florida/02/2008(H1N1)) se... 36.2 0.62
gb|EU516125.1| Influenza A virus (A/Hawaii/28/2007(H1N1)) seg... 36.2 0.62
gb|EU516123.1| Influenza A virus (A/Hawaii/28/2007(H1N1)) seg... 36.2 0.62
gb|EU516112.1| Influenza A virus (A/Hawaii/21/2007(H1N1)) seg... 36.2 0.62
gb|EU516141.1| Influenza A virus (A/Minnesota/23/2007(H1N1)) ... 36.2 0.62
gb|EU516028.1| Influenza A virus (A/Massachusetts/05/2007(H1N... 36.2 0.62
gb|EU516027.1| Influenza A virus (A/Texas/31/2007(H1N1)) segm... 36.2 0.62
gb|CY027037.1| Influenza A virus (A/Kansas/UR06-0104/2007(H1N... 36.2 0.62
gb|EU516199.1| Influenza A virus (A/Georgia/20/2006(H1N1)) se... 36.2 0.62
gb|EU516198.1| Influenza A virus (A/Georgia/20/2006(H1N1)) se... 36.2 0.62
gb|EU516197.1| Influenza A virus (A/Georgia/20/2006(H1N1)) se... 36.2 0.62
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November 17th, 2008, 09:13 AM
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
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November 17th, 2008, 10:51 AM
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
Preliminary> influenza (A/H1N1) oseltamivir-resistant strain (H275Y *) occur in the domestic situation [second report]
はじめに First
2007年11月頃から、ノイラミニダーゼ（NA）蛋白質の275番目のアミノ酸がヒスチジンからチロシン （H275Y * ）に置換し、オセルタミビルに対して強い耐性となるA/H1N1亜型インフルエンザウイルスが、ノルウェーの67％を筆頭に、EU諸国全体では20％以上の高頻度 で検出されるようになった1)。 11 around 2007, neuraminidase (NA) 275 proteins from the second histidine tylosin amino acids (H275Y *) to replace the strong resistance to oseltamivir for influenza A/H1N1 virus subtype, and 67 percent in Norway Led, EU countries, more than 20 percent of the overall high-frequency has to be found in 1). このため、WHOグローバルインフルエンザサーベイランスネットワークでは、全世界的なNA阻害剤（NAI ）耐性株サーベイランスを強化し、各国における耐性株出現状況を報告するように要請した。 For this reason, WHO GUROBARUINFURUENZASABEIRANSUNETTOWAKU the global NA inhibitor (NAI) to strengthen surveillance-resistant strain, resistant strain emerged in the country to report the situation said. これを受けて世界各国から週単位または月単位で情報が寄せられ、それらの集計結果は定期的にWHOのホーム ページ（HP）に掲載されるようになった2）。 This was the week or month from around the world have information in their units, their results of the WHO website on a regular basis (HP) came to be published in the 2). 2008年4月～10月現在での世界全体の出現頻度は39％であり、2007年後半～今年3月までの16％ を大きく上回り、南半球諸国を含めて世界的に耐性株が広がり始めている。 April-October 2008 of the current frequency in the entire world is 39 percent, from late 2007 until March of this year's 16 percent larger than the Southern Hemisphere countries in the world, including the resistant strain is starting to spread . 特に、セネガル、南アフリカではA/H1N1分離株の100％が耐性であり、アフリカ地域全体でも88％が耐性株となっている2）。 In particular, Senegal, South Africa A/H1N1 isolate the resistance of 100 percent and 88 percent in Africa but the entire region is a two-resistant strain). これら耐性株はオセルタミビルを服用していない患者から分離されており、通常の病原性をもった市中流行株と して人々の間に広がっており3)、インフルエンザ対策上大きな問題となっている。 These shares oseltamivir resistance is not taking patients have been isolated from the normal trend of the market share with virulence as the spread between people, and 3), the flu is a big problem.
一方、わが国は世界のオセルタミビル生産量の70％以上を臨床現場で使用していることから、市中流行の耐性 株に加えて、薬剤の選択圧による耐性株の高頻度出現が危惧され、世界中がわが国における耐性株の発生動向を 注目している。 Meanwhile, the country of the world's production of oseltamivir for more than 70 percent have clinical use in the field, because in addition to the market trend-resistant strain of the selective pressure of drug-resistant strain of the emergence of high-frequency危惧SA of the world Shares in the incidence of resistance in the country are watching developments. このような背景から、国立感染症研究所（感染研）では地方衛生研究所（地研）の協力を得て、2 007/08シーズンに国内で分離されたA/H1N1株に対する耐性株緊急サーベイランスを実施することとした。 Against this background, the National Institute of Infectious Diseases (lab infection), the local Public Health Research Institute (research areas) with the cooperation of the 2007/08 season, A/H1N1 strain isolated in the country for emergency surveillance-resistant strain To be implemented.
わが国における緊急サーベイランスの経過報告は、第1報としてIASR 6月号に掲載されているが4）、今回は、それ以降に追加された分離株の解析結果を含む2007/08シーズン分離株の総まとめとして第2報で報告する。 The progress report in Japan that an emergency surveillance, as the first report on the issue IASR 6 is 4), this time, was later added to isolate the analysis results of the 2007/08 season, including the separation of the total shares As reported in the second report together.
（*）各種論文ではH274Yの表記をしているが、これは、H3N2亜型ウイルスのNA蛋白質のアミノ酸番 号をもとにした表記法(N2表記法)であり、H1N1のNA蛋白質の場合は、耐性マーカーのアミノ酸番号は メチオニンから数えて275番目となる。 (*)'s H274Y in the various papers have representation, which, H3N2 subtype of the virus NA proteins, amino acids were based on the number notation (N2 notation) and, H1N1 cases in the NA protein , A marker of resistance from the amino acid methionine number at 275 and counting. よって、本文では耐性マーカーのアミノ酸番号をH275Yで統一する。 Thus, the amino acids in the body and a number of resistance markers in a unified H275Y.
1. 日本国内の耐性株発生状況
今回の耐性株緊急サーベイランスに協力が得られた地研から寄せられた耐性株検出状況を都道府県 別に 表1 (pdf)に示した（耐性ウイルスの検出法はIASR 6月号第1報の方法の項を参照）4)。 1. Occur the domestic situation
-resistant strain of the emergency-resistant strain of surveillance research obtained in the cooperation received from the State-resistant strain detected by the situation in Table 1 (pdf) to the (virus-resistant The detection method IASR 6 issue the first report of the methods section) 4). 総解析数1,734株中45株の耐性株が同定され、国内の耐性株の発生頻度は2.6％であった （ 表1 ）。 Analysis of 1734 total number of shares of stock during the 45-resistant strain is identified, the frequency of domestic-resistant strain was 2.6 percent (Table 1). 発生頻度を年別に見ると、2007年は331株中1株（0.3%）、2008年は1,403株中44株（3 .1%）で、2008年に入ってからの発生頻度が高かった。 Past look at the frequency incidence, and in 2007 the 331 shares per share (0.3 percent), while 44 stocks in 2008, 1403 shares (3.1 percent), since 2008 the incidence of high frequency. しかしながら、わが国は世界一のオセルタミビル使用国にもかかわらず、諸外国に比べるとその発生頻度は著し く低かった。 However, our use of oseltamivir in the country in the world, despite Compared to other countries and their extremely low frequency.
耐性株が分離されたのは本州の10県であったが（ 図1 pdf）、鳥取県を除いた9県それぞれでの発生頻度は、1.2～7.3%であった。 -Resistant strain was isolated in the 10 prefectures of Honshu (Figure 1 pdf), Tottori Prefecture, which excludes often occur in nine prefectures, respectively, from 1.2 to 7.3 percent.
一方、鳥取県では68株中22株が耐性株で、発生頻度は32.4％と突出していた（ 図1 ）。 Meanwhile, shares in Tottori Prefecture during the 22 stocks in the 68-resistant strain, the frequency has been outstanding and 32.4 percent (Figure 1). これら耐性株の発生状況を市町村別に見ると（ 図2 pdf）、鳥取市を中心とした県東部から１月下旬に多く分離された株は、NA遺伝子系統樹上ハワイ系統(系 統樹解析の項参照)に属していたが、２～３月の分離株は北欧系統に入るものもあり、両系統が混 在していた。 These state-resistant strain occurred in the city and another (Figure 2 pdf), with a focus on the city of Tottori Prefecture in late January from the eastern most isolated stocks, NA Hawaii strain on the genetic family tree (the term analysis of the evolutionary tree ) Belongs to, but separate shares in February and March into the Nordic some strains, the two strains were mixed. 一方、倉吉市を中心とした県中部からは、２～３月に耐性株が多く分離され、それらは北欧系統に 属していた。 On the other hand, with a focus on Kurayoshi from the central prefecture, February and March are resistant to the separation of stocks, they belong to the Nordic system. このことから鳥取県では県東部、県中部で遺伝的に異なる２つの系統の耐性株が広く流行していたことが示唆さ れた。 From the eastern part of Tottori Prefecture, the prefectural government, in the central prefecture of two different genetic strains resistant strain of the epidemic have been widely suggested.
鳥取県内でこれほど耐性株が流行していたにもかかわらず、近隣県の発生頻度が高くないのは、当該県での耐性 株感染者は低年齢層が多かったため、県を越えた移動が少なかったことが原因のひとつと考えられ る。 In Tottori Prefecture, the so-resistant strain was prevalent, despite the high frequency of the neighboring prefecture of the resistant strain of the infected people in the province are low due to age, moving beyond the County One of the few considered to be the cause.
2. 系統樹解析 2. Phylogenetic tree analysis
2007/08シーズンに流行したA/H1N1インフルエンザウイルスは、NA遺伝子の系統樹上でサブクレード２Ｂ（アミノ酸マーカー：H45N 、G249K、T287I、K329E、G354D）およびサブクレード２Ｃ（アミノ酸マーカー：S82P 、M188I、I267M、L367I、V393I、T453I）に分かれる[ 図３ :左上 (pdf)]。 Prevalent in the 2007/08 season, influenza A/H1N1 virus, NA SABUKUREDO on the evolutionary tree of a gene 2B (amino acid marker: H45N, G249K, T287I, K329E, G354D) and SABUKUREDO 2C (amino acid marker: S82P, M188I, I267M, L367I, V393I, T453I) into the Figure 3: upper left corner (pdf)]. 国内外の耐性株のほとんどすべては今期ワクチン株のA/ブリスベン/59/2007を含むサブクレード２Ｂに属していた。 Most of the foreign-resistant strain of the vaccine strain of the season for all A / Brisbane / 59/2007, including SABUKUREDO belongs to 2B. サブクレード２Ｂ内ではさらに２つの系統に別れ、D354Gのマーカーを持ち世界中で広く分離されている北 欧系統の耐性株と、このマーカーを持たないワクチン株A/ブリスベン/59/2007を含むハワイ系統の耐性株に分けられた。 2B SABUKUREDO two more within goodbye to the strains, D354G marker in the world and are widely separated Scandinavian-resistant strains of the shares, the markers do not have a vaccine strain A / Brisbane / 59/2007, including strains of Hawaii Resistance was divided into shares. ハワイ系統の耐性株は分離株数から見ると世界的には少数派である。 Shares of Hawaiian-resistant strains isolated from the number of shares and the world is in the minority.
わが国で分離された耐性株は、ハワイ系統に属するものが多く認められたが、横浜市、鳥取県および岡山県から の耐性株は北欧系統に属するものも検出されている。 -Resistant strain isolated in Japan, Hawaii, a lot of strain was recognized as belonging to the city of Yokohama, Tottori and Okayama prefectures from belonging to resistant strains of the Nordic stock is also detected. 一方、2007年11月に横浜市で分離された一株（A/横浜/91/2007株）は、サブクレード２Ｃに属していた。 Meanwhile, in November 2007 and separated in the city of Yokohama shares (A / Yokohama / 91/2007), belongs to 2C SABUKUREDO.
3. 抗原解析 3. Antigenic analysis
15株の国内耐性株について、新旧ワクチン株およびその類似株に対するフェレット参照抗血清を用いた赤血球 凝集抑制（ＨＩ）試験で抗原解析を実施した結果、国内で分離されたハワイ系統および北欧系統いずれの耐性株 も、今期のワクチン株A/ブリスベン/59/2007類似株であった (IASR 6月号、第1報参照) 4)。 15 shares for shares in the resistance, and its share of old and new vaccine for ferrets to see a similar line with anti-serum hemagglutination inhibition (HI) test was conducted to analyze the results of antigen in the country and Nordic strains isolated strains either Hawaii -Resistant strain, the current term of the vaccine strain A / Brisbane / 59/2007 shares were similar (IASR 6 issue, the first report) 4). このことから、これら耐性株に対して、今冬のワクチンは有効であることが示唆された。 For this reason, these stocks resistant to the vaccine this winter suggested that to be effective.
4. 薬剤感受性 4. Chemosensitivity
2007/08シーズンに分離された薬剤感受性株240株（ 表１ ：青字）に対するNAI薬剤感受性試験の結果、薬剤感受性株のオセルタミビルに対する50％NA活性阻害濃 度（IC50）の平均値は0.09nMであった。 The separation of the 2007/08 season, 240 shares drug-sensitive stocks (Table 1: blue) drug susceptibility testing for the NAI as a result of the drug oseltamivir-sensitive shares, 50% NA activity inhibition concentration (IC50) in the average value of the 0.09nM . 一方、国内耐性株のオセルタミビルに対するIC50値は、おおむね30.0nM以上を示し、薬剤感受性株に 比べて300倍以上もオセルタミビルに対して感受性が低下していた。 On the other hand, domestic resistance to oseltamivir IC50 value of the shares, or more generally indicates 30.0nM, drug-sensitive shares compared to 300 times more sensitive to oseltamivir also has been slow. これらの耐性株のほとんどすべてはザナミビルに対しては感受性であったが、鳥取県で分離された １株（A/鳥取/44/2008）はオセルタミビル、ザナミビル両方に耐性であった。 These Zanamivir-resistant strain to the most sensitive of all, but isolated in Tottori Prefecture per share (A / Tottori / 44/2008), oseltamivir, was resistant to both Zanamivir. また、別の1株（A/鳥取/16/2008）は、ザナミビルに耐性であった（ 表２ ）。 Another per share (A / Tottori / 16/2008), was resistant to Zanamivir (Table 2). 一方、クレード２Cに属する横浜市の分離株（A/横浜/91/2007）は、NAIとは別の作用機序を持つ抗インフルエンザウイルス薬のアマンタジンに対する耐性マーカ ー（M2タンパク質のS31N）をもち、オセルタミビルとアマンタジンの2剤耐性と考えられた 。 On the other hand, belong to the clade Yokohama 2C isolate (A / Yokohama / 91/2007), NAI is a different mechanism of action of anti-flu drug amantadine resistance to the virus marker (M2 protein S31N) and Life Oseltamivir and amantadine-resistant and 2.
５. A/H3N2およびB型インフルエンザウイルスに対するNAI耐性株サーベイランス
感染研ではNAI耐性株サーベイランスとして、A/H3N2およびB型インフルエンザウイルスについても、全長のNA遺伝子解析およびNAI薬剤感受性試験を 平行して実施している。 5. A/H3N2 and B-NAI-resistant strain of influenza virus infection surveillance
surveillance research for the NAI-resistant strain, A/H3N2 and B-type influenza viruses, the total length of the NA gene analysis and drug susceptibility testing parallel NAI Are carried out. 表２は、A/H1N1株に加えて2007/08シーズンに国内で分離されたA/H3N2とB型株における耐性株検出状況をまとめたものである。 Table 2, A/H1N1 in addition to the shares in the separation of the 2007/08 season, A/H3N2 and B-type strain was resistant strain found in the summarize the situation. A/H3N2（89株）およびB型（78株）についてはオセルタミビルおよびザナミビルに対して明確な耐性を示 す株は見つからなかった。 A/H3N2 (89 shares) and type B (78 shares) and Zanamivir for oseltamivir resistance is indicating clearly that found no shares.
おわりに Conclusion
2007/08シーズンA/H1N1分離株に対する今回の薬剤耐性株緊急サーベイランスにより、わが国での耐性株の発生頻度は海外諸国 に比べて低く、今のところEU諸国、アフリカ諸国、豪州のような深刻な状態になっていない。 For the 2007/08 season, A/H1N1 isolate emergency surveillance of the drug-resistant strain, resistant strain of the outbreak in Japan is often lower than in foreign countries, EU countries so far, African countries, like Australia, serious Is not ready. また、A/H3N2およびB型インフルエンザウイルスに対する耐性株は確認されておらず、今のところ国内におけるオセ ルタミビルによるインフルエンザの治療方針に大きな影響はないと思われる。 In addition, A/H3N2 and B-resistant strain of the flu virus had not been confirmed so far in the domestic policies oseltamivir in the treatment of influenza will not be a big influence. また、今回分離された国内耐性株は今季のワクチン株A/ブリスベン/59/2007に遺伝的にも抗原的にも類似しているため、ワクチンは有効であると考えられる。 In addition, the separation of the domestic season-resistant strain of the vaccine strain A / Brisbane / 59/2007 on the genetic and antigenic are similar, the vaccine is believed to be valid. これに加えて、2株の例外はあるが、耐性株のほとんどすべてはザナミビルに対しては感受性であることから、 ザナミビルによる治療も有効である。 In addition, the two share some exceptions, almost all of the Zanamivir-resistant strain that is sensitive, and effective treatment with Zanamivir.
これまでも、NA阻害剤耐性株はA/H1N1、A/H3N2およびB型インフルエンザウイルスで低頻度（0.11～0.68％）ながら見つかってきたが（IA SR 6月号、第1報、表１ ）4）、これらは市中流行株としてヒトからヒトへ伝播拡大することはなく、自然消滅していた。 So far, NA stock inhibitor-resistant A/H1N1, A/H3N2 and B-type influenza virus in the low-frequency (0.11 to 0.68%) have been found and (IASR 6 issue, the First Report, Table 1) 4 ), Which shares the market as a fashion spread from human to human, not to expand natural been extinguished. しかし、今回諸外国で見つかっているオセルタミビル耐性株は市中流行株と変わらぬ伝播能力を持ち、国によっ ては流行の主流になっている。 However, other countries of the oseltamivir-resistant strain has been found in the continued transmission capacity and market share trends, and in some countries is becoming a major epidemic. わが国でも、理由は不明であるが、鳥取県で突出して高い発生頻度が観察され、今冬の全国的な流行拡大が心配 される。 Japan also is not clear why the projection in Tottori Prefecture, and high frequency been observed, this winter to expand the nation feared an epidemic. オセルタミビル耐性株は通常の感受性株と比べて臨床症状に違いは認められないが、オセルタミビルを多用して いるわが国にとって、耐性株がアマンタジン耐性株のように流行株の主流になった場合は、本薬剤による治療方 針に大きな影響をもたらすことになる。 Shares of oseltamivir resistance than normal-sensitive stocks and can not accept the differences in clinical symptoms, but then Oseltamivir is a lot for our country, shares of resistance to amantadine-resistant strain of If the epidemic is in the mainstream of shares, Treatment with a drug policy will be a big impact. 臨床現場では、迅速診断キットによってA型またはB型の識別は可能であるが、A/H1とA/H3亜型の識別は不可能であることから、耐性株を排出している患者にもオセルタミビルを処方することにもな りかねない。 In the clinical field, and rapid diagnostic kit of the type A or B type is possible to identify, A/H1 and A/H3 subtype is impossible to identify the emission shares are resistant to the patient To prescribe oseltamivir could. このことから、今冬の流行においても、A/H1N1株だけでなくA/H3N2およびB型インフルエンザウイルスを含めた全国レベルでの継続した監視が必要である。 Thus, even in winter fashions, A/H1N1 and B-shares as well as influenza A/H3N2 virus at the national level, including the need for continued monitoring.
1) http://ecdc.europa.eu/en/Health_topi...als_graph.aspx (EU, EEA countries, the frequency-resistant strain)
2) http://www.who.int/csr/disease/influ.../en/index.html (frequency-resistant strain of international news)
3) http://www.who.int/csr/disease/influ.../en/index.html (H275Y-resistant strain on the FAQ)
4) IASR 29: 155-159, 2008 (oseltamivir-resistant strain A/H1N1 influenza H275Y (*) caused domestic First Report)
国立感染症研究所ウイルス第三部第一室インフルエンザ薬剤耐性株サーベイランスチーム製品評価技術基盤機構 バイオテクノロジー本部ゲノム解析部門・インフルエンザウイルス遺伝子解析チーム全国地方衛生 研究所 The Third National Institute of Infectious Diseases Department viral drug-resistant strain of influenza surveillance room team Biotechnology Institute of Technology and Evaluation Division headquarters influenza virus genome analysis of the local National Institutes of Health genetic analysis team
http://translate.google.com/translat...n%26as_qdr%3Dd
http://idsc.nih.go.jp/iasr/rapid/pr3462.html
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November 18th, 2008, 09:05 AM
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
| Country | Subgroup | Period | Year | Value | Source | | Communicable Diseases -> Influenza -> Influenza viruses detected | | (Periodicity: Week, Applied Time Period: from 41/2008 to 46/2008) | | 1. | Belarus | A (H1) | 44 | 2008 | 0 | view | | 2. | Belarus | A (H1) | 45 | 2008 | 0 | view | | 3. | Belgium | A (H1) | 41 | 2008 | 0 | view | | 4. | Belgium | A (H1) | 42 | 2008 | 0 | view | | 5. | Belgium | A (H1) | 43 | 2008 | 0 | view | | 6. | Belgium | A (H1) | 44 | 2008 | 0 | view | | 7. | Brazil | A (H1) | 41 | 2008 | 0 | view | | 8. | Brazil | A (H1) | 42 | 2008 | 0 | view | | 9. | Brazil | A (H1) | 43 | 2008 | 0 | view | | 10. | Brazil | A (H1) | 44 | 2008 | 0 | view | | 11. | Brazil | A (H1) | 45 | 2008 | 0 | view | | 12. | Brazil | A (H1) | 46 | 2008 | 0 | view | | 13. | Bulgaria | A (H1) | 41 | 2008 | 0 | view | | 14. | Bulgaria | A (H1) | 42 | 2008 | 0 | view | | 15. | Bulgaria | A (H1) | 43 | 2008 | 0 | view | | 16. | Bulgaria | A (H1) | 44 | 2008 | 0 | view | | 17. | Bulgaria | A (H1) | 45 | 2008 | 0 | view | | 18. | Cameroon | A (H1) | 41 | 2008 | 0 | view | | 19. | Cameroon | A (H1) | 42 | 2008 | 1 | view | | 20. | Cameroon | A (H1) | 43 | 2008 | 0 | view | | 21. | Cameroon | A (H1) | 44 | 2008 | 0 | view | | 22. | Cameroon | A (H1) | 45 | 2008 | 2 | view | | 23. | Cameroon | A (H1) | 46 | 2008 | 0 | view | | 24. | Canada | A (H1) | 41 | 2008 | 0 | view | | 25. | Canada | A (H1) | 42 | 2008 | 0 | view | | 26. | Canada | A (H1) | 43 | 2008 | 0 | view | | 27. | Canada | A (H1) | 44 | 2008 | 0 | view | | 28. | Canada | A (H1) | 45 | 2008 | 0 | view | | 29. | Chile | A (H1) | 41 | 2008 | 0 | view | | 30. | Chile | A (H1) | 43 | 2008 | 0 | view | | 31. | Chile | A (H1) | 44 | 2008 | 0 | view | | 32. | China | A (H1) | 41 | 2008 | 25 | view | | 33. | China | A (H1) | 42 | 2008 | 16 | view | | 34. | China | A (H1) | 43 | 2008 | 7 | view | | 35. | China | A (H1) | 44 | 2008 | 7 | view | | 36. | China | A (H1) | 45 | 2008 | 5 | view | | 37. | China | A (H1) | 46 | 2008 | 6 | view | | 38. | Colombia | A (H1) | 41 | 2008 | 0 | view | | 39. | Colombia | A (H1) | 42 | 2008 | 0 | view | | 40. | Denmark | A (H1) | 41 | 2008 | 0 | view | | 41. | Denmark | A (H1) | 42 | 2008 | 0 | view | | 42. | Denmark | A (H1) | 43 | 2008 | 0 | view | | 43. | Denmark | A (H1) | 44 | 2008 | 0 | view | | 44. | Denmark | A (H1) | 45 | 2008 | 0 | view | | 45. | Egypt | A (H1) | 43 | 2008 | 0 | view | | 46. | Egypt | A (H1) | 44 | 2008 | 0 | view | | 47. | Egypt | A (H1) | 45 | 2008 | 0 | view | | 48. | Finland | A (H1) | 41 | 2008 | 0 | view | | 49. | Finland | A (H1) | 42 | 2008 | 0 | view | | 50. | Finland | A (H1) | 43 | 2008 | 0 | view | | 51. | Finland | A (H1) | 44 | 2008 | 0 | view | | 52. | Finland | A (H1) | 45 | 2008 | 0 | view | | 53. | France | A (H1) | 41 | 2008 | 0 | view | | 54. | France | A (H1) | 42 | 2008 | 0 | view | | 55. | France | A (H1) | 43 | 2008 | 0 | view | | 56. | France | A (H1) | 44 | 2008 | 0 | view | | 57. | France | A (H1) | 45 | 2008 | 0 | view | | 58. | Germany | A (H1) | 41 | 2008 | 0 | view | | 59. | Germany | A (H1) | 42 | 2008 | 0 | view | | 60. | Greece | A (H1) | 41 | 2008 | 0 | view | | 61. | Greece | A (H1) | 42 | 2008 | 0 | view | | 62. | Greece | A (H1) | 43 | 2008 | 0 | view | | 63. | Greece | A (H1) | 44 | 2008 | 0 | view | | 64. | Greece | A (H1) | 45 | 2008 | 0 | view | | 65. | Honduras | A (H1) | 41 | 2008 | 0 | view | | 66. | Iran (Islamic Republic of) | A (H1) | 41 | 2008 | 0 | view | | 67. | Iran (Islamic Republic of) | A (H1) | 42 | 2008 | 0 | view | | 68. | Iran (Islamic Republic of) | A (H1) | 43 | 2008 | 0 | view | | 69. | Iran (Islamic Republic of) | A (H1) | 44 | 2008 | 0 | view | | 70. | Iran (Islamic Republic of) | A (H1) | 45 | 2008 | 1 | view | | 71. | Iran (Islamic Republic of) | A (H1) | 46 | 2008 | 0 | view | | 72. | Japan | A (H1) | 41 | 2008 | 0 | view | | 73. | Japan | A (H1) | 42 | 2008 | 0 | view | | 74. | Japan | A (H1) | 43 | 2008 | 4 | view | | 75. | Japan | A (H1) | 44 | 2008 | 0 | view | | 76. | Japan | A (H1) | 45 | 2008 | 0 | view | | 77. | Kenya | A (H1) | 41 | 2008 | 0 | view | | 78. | Kenya | A (H1) | 42 | 2008 | 0 | view | | 79. | Kenya | A (H1) | 43 | 2008 | 0 | view | | 80. | Kenya | A (H1) | 44 | 2008 | 0 | view | | 81. | Kenya | A (H1) | 45 | 2008 | 0 | view | | 82. | Latvia | A (H1) | 41 | 2008 | 0 | view | | 83. | Latvia | A (H1) | 42 | 2008 | 0 | view | | 84. | Latvia | A (H1) | 44 | 2008 | 0 | view | | 85. | Latvia | A (H1) | 45 | 2008 | 0 | view | | 86. | Mexico | A (H1) | 41 | 2008 | 0 | view | | 87. | Mexico | A (H1) | 42 | 2008 | 0 | view | | 88. | Mexico | A (H1) | 43 | 2008 | 0 | view | | 89. | Mongolia | A (H1) | 41 | 2008 | 0 | view | | 90. | Mongolia | A (H1) | 42 | 2008 | 0 | view | | 91. | Mongolia | A (H1) | 43 | 2008 | 0 | view | | 92. | Mongolia | A (H1) | 44 | 2008 | 0 | view | | 93. | Netherlands | A (H1) | 42 | 2008 | 0 | view | | 94. | Norway | A (H1) | 41 | 2008 | 0 | view | | 95. | Norway | A (H1) | 42 | 2008 | 0 | view | | 96. | Norway | A (H1) | 43 | 2008 | 0 | view | | 97. | Norway | A (H1) | 44 | 2008 | 1 | view | | 98. | Norway | A (H1) | 45 | 2008 | 0 | view | | 99. | Oman | A (H1) | 41 | 2008 | 0 | view | | 100. | Oman | A (H1) | 42 | 2008 | 0 | view | | 101. | Oman | A (H1) | 43 | 2008 | 0 | view | | 102. | Oman | A (H1) | 44 | 2008 | 0 | view | | 103. | Oman | A (H1) | 45 | 2008 | 0 | view | | 104. | Poland | A (H1) | 41 | 2008 | 0 | view | | 105. | Poland | A (H1) | 42 | 2008 | 0 | view | | 106. | Poland | A (H1) | 43 | 2008 | 0 | view | | 107. | Poland | A (H1) | 44 | 2008 | 0 | view | | 108. | Poland | A (H1) | 45 | 2008 | 0 | view | | 109. | Portugal | A (H1) | 41 | 2008 | 0 | view | | 110. | Portugal | A (H1) | 42 | 2008 | 0 | view | | 111. | Portugal | A (H1) | 43 | 2008 | 0 | view | | 112. | Portugal | A (H1) | 44 | 2008 | 0 | view | | 113. | Portugal | A (H1) | 45 | 2008 | 0 | view | | 114. | Romania | A (H1) | 41 | 2008 | 0 | view | | 115. | Romania | A (H1) | 42 | 2008 | 0 | view | | 116. | Romania | A (H1) | 43 | 2008 | 0 | view | | 117. | Romania | A (H1) | 44 | 2008 | 0 | view | | 118. | Romania | A (H1) | 45 | 2008 | 0 | view | | 119. | Russian Federation | A (H1) | 41 | 2008 | 2 | view | | 120. | Russian Federation | A (H1) | 42 | 2008 | 4 | view | | 121. | Russian Federation | A (H1) | 43 | 2008 | 5 | view | | 122. | Russian Federation | A (H1) | 44 | 2008 | 4 | view | | 123. | Russian Federation | A (H1) | 45 | 2008 | 0 | view | | 124. | Slovenia | A (H1) | 41 | 2008 | 0 | view | | 125. | Slovenia | A (H1) | 42 | 2008 | 0 | view | | 126. | Slovenia | A (H1) | 43 | 2008 | 0 | view | | 127. | Slovenia | A (H1) | 44 | 2008 | 0 | view | | 128. | Slovenia | A (H1) | 45 | 2008 | 0 | view | | 129. | South Africa | A (H1) | 41 | 2008 | 0 | view | | 130. | Spain | A (H1) | 41 | 2008 | 0 | view | | 131. | Spain | A (H1) | 42 | 2008 | 0 | view | | 132. | Spain | A (H1) | 43 | 2008 | 0 | view | | 133. | Spain | A (H1) | 44 | 2008 | 0 | view | | 134. | Sri Lanka | A (H1) | 41 | 2008 | 0 | view | | 135. | Sri Lanka | A (H1) | 42 | 2008 | 0 | view | | 136. | Sri Lanka | A (H1) | 43 | 2008 | 0 | view | | 137. | Sri Lanka | A (H1) | 44 | 2008 | 0 | view | | 138. | Sweden | A (H1) | 41 | 2008 | 0 | view | | 139. | Sweden | A (H1) | 42 | 2008 | 0 | view | | 140. | Switzerland | A (H1) | 41 | 2008 | 0 | view | | 141. | Switzerland | A (H1) | 42 | 2008 | 0 | view | | 142. | Switzerland | A (H1) | 43 | 2008 | 0 | view | | 143. | Switzerland | A (H1) | 44 | 2008 | 0 | view | | 144. | Switzerland | A (H1) | 45 | 2008 | 0 | view | | 145. | Tunisia | A (H1) | 44 | 2008 | 0 | view | | 146. | Tunisia | A (H1) | 45 | 2008 | 1 | view | | 147. | Tunisia | A (H1) | 46 | 2008 | 1 | view | | 148. | Ukraine | A (H1) | 44 | 2008 | 0 | view | | 149. | United Kingdom of Great Britain and Northern Ireland | A (H1) | 41 | 2008 | 2 | view | | 150. | United Kingdom of Great Britain and Northern Ireland | A (H1) | 42 | 2008 | 0 | view | | 151. | United Kingdom of Great Britain and Northern Ireland | A (H1) | 43 | 2008 | 3 | view | | 152. | United Kingdom of Great Britain and Northern Ireland | A (H1) | 44 | 2008 | 1 | view | | 153. | United Kingdom of Great Britain and Northern Ireland | A (H1) | 45 | 2008 | 4 | view | | 154. | United States of America | A (H1) | 41 | 2008 | 4 | view | | 155. | United States of America | A (H1) | 42 | 2008 | 12 | view | | 156. | United States of America | A (H1) | 43 | 2008 | 14 | view | | 157. | United States of America | A (H1) | 44 | 2008 | 2 | view | | 158. | Uruguay | A (H1) | 41 | 2008 | 0 | view |
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November 18th, 2008, 09:07 AM
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
H1N1 is dominant serotype in US, but typing is lagging and H274Y data is lagging even more than serotyping:
| 154. | United States of America | A (H1) | 41 | 2008 | 4 | view | | 155. | United States of America | A (H1) | 42 | 2008 | 12 | view | | 156. | United States of America | A (H1) | 43 | 2008 | 14 | view | | 157. | United States of America | A (H1) | 44 | 2008 | 2 | view |
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November 18th, 2008, 01:35 PM
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
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November 18th, 2008, 07:12 PM
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
Quote:
Originally Posted by niman
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Commentary
Evolution of H1N1 Tamiflu Resistance in Japan
Recombinomics Commentary 18:37
November 18, 2008
in Tottori Prefecture during the 22 stocks in the 68-resistant strain, the frequency has been outstanding and 32.4 percent.
The above comments are from an updated Japan NIH report on Tamiflu resistance in Japan in the 2007/2008 season. As noted above, the most concentrated Prefecture for H274Y was Tottori, where the rate was above 32% in H1N1 isolates. The new report has an updated phylogenetic tree that demonstrates that H1N1 in Tottori included the dominant Brisbane sub-clade that accounted for the majority of H274Y cases in Europe and the United States, but also included isolates on branches that had isolate that did and did not have H274Y, indicating the H274Y positive isolates had independently acquired H274Y (see list below), supporting acquisition via homologous recombination.
As seen in the updated tree, the majority of cases reported in Japan were in isolates that were not on the dominant branch (shaded in pink), but were on multiple separate branches.
Similar data was seen in recent sequences released from England, where several of the H274Y isolates (England/654/2007 and England/684/2007) did not map on the branch with the dominant sub-clade, providing evidence for more independent acquisitions which are most easily explained by homologous recombination. These multiple branches ion England and Japan offer additional clades which could become dominant this season.
Recent data from the southern hemisphere over the summer, and early isolates in the northern hemisphere this season, raise concerns that the resistance levels will approach 100% of H1N1 isolates in many countries. Sequence data on isolates, including the US where H1N1 is the dominant serotype this season, would be useful.
Dominant Brisbane sub-clade
Okayama/11/08
Tottori/41/08
Tottori/42/08
Tottori/43/08
Tottori/44/08
Tottori/46/08
Tottori/50/08
Tottori/52/08
Tottori/53/08
Tottori/55/08
Tottori/56/08
Tottori/57/08
Tottori/59/08
Tottori/60/08
Tottori/67/08
Yokohama/77/08
Yokohama/78/08
Yokohama/79/08
Other branches
Branch 1
Yamagata/68/08
Branch 2
Shimane/59/08
Branch 3
Tochigi/34/08
Tochigi/39/08
Branch 4
Tottori/28/08
Tottori/29/08
Tottori/34/08
Tottori/35/08
Tottori/37/08
Tottori/63/08
Branch 5
Gifu-C/17/08
Gifu-C/38/08
Tottori/21/08
Tottori/23/08
Branch 6
Aichi/76/08
Kobe/27/08
Kobe/31/08
Kobe/32/08
Branch 7
Yokohama/22/08
Yokohama/30/08
Yokohama/31/08
Yokohama/34/08
Yokohama/35/08
Branch 8
Tochigi/8/08
Branch 9
Nagano/1100/08
Nagano/1107/08
.
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November 19th, 2008, 09:07 AM
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
The "early" movers of H274Y into Bisbane/59
gb|FJ445025.1| Influenza A virus (A/England/654/2007(H1N1)) s... 48.1 4e-04
gb|FJ445066.1| Influenza A virus (A/England/594/2006(H1N1)) s... 48.1 4e-04
gb|FJ445080.1| Influenza A virus (A/England/494/2006(H1N1)) s... 48.1 4e-04
gb|FJ403587.1| Influenza A virus (A/Scotland/5/2007(H1N1)) se... 48.1 4e-04
gb|FJ403586.1| Influenza A virus (A/England/684/2007(H1N1)) s... 48.1 4e-04
gb|FJ179361.1| Influenza A virus (A/Pennsylvania/13/2007(H1N1... 48.1 4e-04
gb|EU551821.1| Influenza A virus (A/Paris/963/2008(H1N1)) neu... 48.1 4e-04
gb|EU716580.1| Influenza A virus (A/Florida/02/2008(H1N1)) se... 48.1 4e-04
gb|EU516199.1| Influenza A virus (A/Georgia/20/2006(H1N1)) se... 48.1 4e-04
gb|EU516198.1| Influenza A virus (A/Georgia/20/2006(H1N1)) se... 48.1 4e-04
gb|EU516197.1| Influenza A virus (A/Georgia/20/2006(H1N1)) se... 48.1 4e-04
gb|EU516141.1| Influenza A virus (A/Minnesota/23/2007(H1N1)) ... 48.1 4e-04
gb|EU516125.1| Influenza A virus (A/Hawaii/28/2007(H1N1)) seg... 48.1 4e-04
gb|EU516123.1| Influenza A virus (A/Hawaii/28/2007(H1N1)) seg... 48.1 4e-04
gb|EU516112.1| Influenza A virus (A/Hawaii/21/2007(H1N1)) seg... 48.1 4e-04
gb|EU516028.1| Influenza A virus (A/Massachusetts/05/2007(H1N... 48.1 4e-04
gb|EU516027.1| Influenza A virus (A/Texas/31/2007(H1N1)) segm... 48.1 4e-04
gb|CY027037.1| Influenza A virus (A/Kansas/UR06-0104/2007(H1N... 48.1 4e-04
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November 21st, 2008, 09:52 AM
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
21 November 2008
Oseltamivir resistant influenza A(H1N1) virus in the UK, 2008/09
The below article was published in the Health Protection Agency publication Health Protection Report 21 November 2008 , Volume 2, No 47.
Following the recently reported, first UK oseltamivir resistant influenza A case (H1N1) in the 2008/09 season [1], several further cases have been detected. From week 36/08 up to 19 November 2008, twelve of the 13 influenza A(H1N1) isolates detected in England have been found to be resistant to oseltamivir. All these cases are from the south west of England. Two oseltamivir resistant influenza A(H1N1) cases have also been detected in Scotland. All the H1N1 cases from England remain sensitive to zanamivir and amantadine and are antigenically similar to the H1N1 reference strain A/Brisbane/59/2007, which is included in this season's influenza vaccine.
Since the start of the current 2008/09 flu season, between weeks 40/08 and 46/08, sporadic laboratory-confirmed influenza infections have been detected across the UK including 58 influenza A(H3), 13 influenza A(H1), 57 influenza A (not subtyped) and three influenza B viruses [2]. Although clinical indicators of influenza activity remain below base-line levels throughout the UK, a recent trend of increasing levels in these indicators is apparent.
The oseltamivir resistant cases are focused in one geographical area of England. Most cases, where age is known, have occurred in the 20-29 year age group. Investigation of the cases by the Avon, Gloucestershire and Wiltshire Health Protection Unit, in collaboration with HPA South West and HPA Centre for Infections, is continuing. There is no evidence of any increased morbidity in these cases to date.
It remains too early to predict which strain(s) of influenza virus will predominate this season. The Agency will continue to monitor closely the characteristics of circulating isolates including drug susceptibility. It remains important that respiratory samples are taken from suspected influenza cases, and that outbreaks of acute respiratory illness are investigated. Respiratory samples confirmed as influenza virus positive should be forwarded to the HPA Centre for Infections Respiratory Virus Unit for culture and anti-viral testing.
Efforts should continue to encourage people in the CMO-defined influenza risk groups to take up the recommendation of seasonal influenza vaccination [3].
Influenza virus detections across Europe remain low so far in this season. Oseltamivir-resistant influenza A(H1N1) isolates have also been reported in a small number of other countries. Oseltamivir-resistant influenza A(H1N1) viruses emerged last season in association with the H274Y mutation, which confers resistance to oseltamivir, but not to zanamivir. By the end of the 2007/08 season, 26 of 34 reporting European countries had reported H1N1 oseltamivir resistance and, in the UK, 38 out of 347 (11%) were found to be oseltamivir resistant [4, 5]. The epidemiological evidence from the 2007/08 season suggested no reported increase in morbidity associated with these confirmed oseltamivir-resistant cases.
References
1. HPA. Identification in the UK of the first oseltamivir resistant-influenza virus (H1N1). Health Protection Report [serial online] 2008, 2(43): news, 24 October 2008. Available at:
http://www.hpa.org.uk/hpr/archives/2008/news4308.htm#ah1n1.
2. Weekly HPA influenza report, week 46. http://www.hpa.org.uk/web/HPAwebFile/HPAweb_C/1226478484902.
3. DH. PL CMO (2008)3, PL CNO (2008)2, PL CPHO (2008)1: The influenza immunisation programme 2008/09. http://www.dh.gov.uk/en/Publicationsandstatistics/Lettersandcirculars/Professionalletters/
Chiefmedicalofficerletters/DH_083812.
4. European Centre for Disease Prevention and Control. Antivirals and antiviral-resistant influenza – resistance to oseltamivir (Tamiflu) in some influenza A(H1N1) virus samples. ECDC website [online] September 2008 [cited 24 October 2008]. http://ecdc.europa.eu/Health_topics/influenza/antivirals.html.
5. WHO. Influenza A(H1N1) virus resistance to oseltamivir. 13 October 2008. http://www.who.int/csr/disease/influenza/h1n1_table/en/index.html.
http://www.hps.scot.nhs.uk/news/spdetail.aspx?id=175
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November 21st, 2008, 10:50 AM
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November 21st, 2008, 04:34 PM
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
The first influenza A in Canada was H1N1 and Tamiflu resistance and reported a mont ago
http://www.recombinomics.com/News/10...4Y_Canada.html
They are now in a don't ask / don't tell mode. The latest report on Tamiflu resistance (which includes the positive of a month ago):
http://www.phac-aspc.gc.ca/fluwatch/.../index-eng.php
The NML has also tested 5 influenza isolates (1 A/H1N1, 1 A/H3N2 & 3 B) for oseltamivir (Tamiflu) resistance and found that the H1N1 isolate tested was resistant to oseltamivir due to the H274Y mutation whereas the H3N2 and B isolates were susceptible; resulting in 20% (1/5) resistance among all influenza isolates tested.
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November 27th, 2008, 04:54 AM
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Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
Neuraminidase inhibitor susceptibility testing on 30 A (H3) isolates since week 36/08 showed that all are sensitive to
oseltamivir and zanamivir but resistant to amantadine. All of the four influenza B isolates received since week 36/08
are sensitive to oseltamivir and zanamivir . Fourteen of fifteen A (H1) specimens tested in the same time frame are
resistant to oseltamivir but sensitive to zanamivir and amantadine. The majority of these resistant viruses come from
the south west of England with the remaining from Wales and northern England. Two influenza A (H1) isolates have
been found to be resistant to oseltamivir in Scotland this season.
http://www.hpa.org.uk/web/HPAwebFile.../1227688116018
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December 18th, 2008, 11:02 AM
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Re: Influenza viruses resistant to oseltamivir, news and updates
ECDC Health Content: Possible scientific basis for neuraminidase inhibitor activity of resistant influenza viruses
SCIENTIFIC ADVANCES – Antiviral Resistance
Possible scientific basis for neuraminidase inhibitor activity of resistant influenza viruses
Lakenby A, Thompson C, Democratis J. The potential impact of neuraminidase inhibitor resistant influenza. Curr Opin Inf Dis 2008; 216: 626-638. For Abstract click here
Description:
In this review the authors describe our as yet limited understanding of the scientific basis for lack of susceptibility in influenza viruses to neuraminidase inhibitors. The authors focus on two influenza sub-types particularly A(H1N1) but also A(H5N1).
ECDC Comment:
When influenza A(H1N1) viruses resistant to oseltamivir (type H274Y) emerged early this year a degree of surprise was expressed as though some such viruses had seen seen before, even with the H(274)Y mutation, notably in Japan, they were not at all fit, that is those viruses were unable to transmit readily. However the new A(H1N1) viruses proved top be fit for example resulting in outbreaks without pressure of antiviral treatment. This article suggests a number of reasons why this might be the case. ECDC Health Content
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December 23rd, 2008, 03:37 PM
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Re: Influenza viruses resistant to oseltamivir, news and updates
Change in U.S. guidance on use of antivirals by clinicians for seasonal influenza – less likely to be applicable in Europe because of epidemiological differences - ECDC Health Content
Change in U.S. guidance on use of antivirals by clinicians for seasonal influenza – less likely to be applicable in Europe because of epidemiological differences
Description:
In a recent report of a Public Health Development (issued December 18th) ECDC highlighted apparent differences between the United States and Europe during the early stages of their 2008-2009 season influenza epidemics.
At week 49/50 there are still few data but what are available confirms that the United States is presently observing a predominance of influenza A(H1N1) and a minority of A(H3N2) while in Europe the relative amounts are the other way around.
In both situations the majority of typed A(H1N1) viruses have been shown to be resistant to oseltamivir but susceptible to zanamivir and most of the A(H3N2) viruses tested to date were resistant to amantadine and rimantidine (see Table below with links to US and European surveillance reports).
Antivirals are used to a greater extent in the United States than in Europe for treating people testing positive for influenza or with presumed influenza and the US Centers for Disease Control promulgate recommendations on their use from an advisory group through the 2008 ACIP Guidance on Prevention and Control of (seasonal) Influenza.
In the light of these recent findings and specifically the fact that at this stage the majority of sub-typed influenza A viruses in the USA are A(H1N1) and are resistant to oseltamivir CDC has now revised its guidance to clinicians and public health authorities.
ECDC Comment (December 23rd 2008):
ECDC does not issue recommendations on the clinical management of patients as that is outside its mandate.
However it is worthwhile noting that given the different epidemiological circumstances at this early stage of the winter epidemics, namely that in Europe A(H1N1) viruses are far less common than A(H3N2) such changes in recommendations on drug use in the USA will be less applicable in Europe.
The US findings are based on results from only a few centres and it may be that in time greater heterogeneity in the level of oseltamivir resistance of A(H1N1) viruses may be observed, as experienced in the 2007-8 season in Europe.
Since then while over all the picture remains heterogeneous the global summary issued and updated by WHO indicates there have been reports of more uniformly high proportions of A(H1N1) viruses being oseltamivir resistant in the later 2008 Southern Hemisphere epidemics (e.g. in South Africa, Argentina and Australia).
Some country level reports have to be viewed cautiously as they are based on low numbers and little is known about how the samples are taken.
Finally it should be remembered that what is true at one point in an influenza season can change over time.
At the start of the European 2007-8 epidemics influenza A(H1N1) viruses were in the majority but by the end it was influenza B viruses that predominated.
United States (CDC) / Weeks 40 to 49 (cumulative) / Europe (EISS-ECDC) / Weeks 40 to 50 (cumulative)
* Influenza A(H1) / 157 (Of 46 tested, 45 were resistant to oseltamivir, while all were susceptible to zanamivir. None of 25 were resistant to amantadine or rimantadine) / 34(Of 20 tested for resistance to neuraminidase inhibitors, 19 were resistant to oseltamivir but none to zanamivir. Only 1 of 11 tested was resistant to amantadine and rimantadine)
* Influenza A(H3) / 18 (All viruses tested were sensitive to oseltamivir and zanamivir. All five viruses tested were resistant to amantadine and rimantadine) / 516 (No resistance to neuraminidase inhibitors was detected among 27 tested. All 26 tested were resistant to amantadine and rimantadine)
* All influenza A (including not subtyped) / 408 (233 unsubtyped) / 1022 (472 unsubtyped)
* Influenza B / 99 / 65
Comment to: influenza@ecdc.europa.eu
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ECDC Health Content
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December 29th, 2008, 09:59 AM
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Re: Influenza viruses resistant to oseltamivir, news and updates
With resistant viruses, doctors face dilemma treating flu this season
Provided by: Canadian Press
Written by: Helen Branswell, Medical Reporter, THE CANADIAN PRESS
Dec. 19, 2008
TORONTO - Early signs from this flu season suggest doctors face a vexing dilemma in treating the illness.
Testing to date in Canada, the United States and Europe shows that nearly all H1N1 viruses are resistant to oseltamivir (sold as Tamiflu) and susceptible to the adamantane drugs, amantadine and rimantadine. The inverse is true for H3N2 viruses, which are universally resistant to the adamantanes and susceptible to oseltamivir.
Given that in reality little point-of-care testing is done to determine whether a patient actually has influenza, let alone which variety of the bug is behind the illness, the resistance situation could see doctors making choices that lead to treatment failure this season.
"This is a very challenging situation," Dr. Tim Uyeki, deputy chief of influenza surveillance and prevention for the U.S. Centers for Disease Control admitted about the bizarre resistance picture coming into focus in the early days of the flu season.
"It definitely adds to the complexity of trying to manage influenza," Dr. Maria Zambon, head of the respiratory viruses unit of Britain's Health Protection Agency, agreed in an interview.
In the face of these early results, the CDC issued a health alert Friday to bring the U.S. medical community up to speed and recommend changes in the usage of flu drugs for the time being.
The upshot? When in doubt - and when the patient's age and health permits - use the only other option, the drug zanamivir, which is sold under the brand name Relenza. So far, all influenza A viruses (H1N1 and H3N2 are subtypes of influenza A) as well as influenza B viruses seem to be susceptible to zanamivir.
Oseltamivir could be used in combination with one of the adamantane drugs, but should only be used alone when local surveillance shows the viruses circulating are likely to be H3N2 or influenza B, the CDC guidance says.
As U.S. surveillance suggests most disease there so far this season is being caused by the H1N1 viruses, zanamivir appears to be a better bet than oseltamivir - or at least it is for patients who can use it. Zanamivir isn't licensed for use in children under seven years of age, and can't be used by people with chronic underlying airways disease or who can't manage the drug's inhalation device.
While they struggle to craft guidance for doctors, both the CDC and the Public Health Agency of Canada have a straightforward piece of advice for the public: Get a flu shot. This year's vaccine is well matched to the H1N1 viruses and the majority of H3N2 viruses currently making the rounds.
On the issue of antivirals, Canadian authorities aren't yet offering new treatment advice to the medical community in this country, though they are closely monitoring the situation, said Dr. Arlene King, director general for the Public Health Agency of Canada's centre for immunization and respiratory infectious diseases.
The National Microbiology Laboratory in Winnipeg has only tested 16 influenza viruses so far this season, finding all the H1N1s (three) resistant to oseltamivir and all the H3N2s (five) resistant to the adamantane drugs. The British Columbia Centre for Disease Control has tested another 19 H1N1 viruses, with 14 showing resistance and the results from the other five deemed inconclusive.
King said for now the recommendation is that doctors treating patients in long-term care facility outbreaks, for instance, should use oseltamivir. But they should be aware of the situation and be ready to shift gears.
"If physicians feel that treatment is merited, then they need to be obviously aware of this issue and should there be issues related to treatment failures, then they would have to consider other alternate drugs - zanamivir being, of course, a good choice," she said.
In Europe, the resistance pattern looks identical to what's being seen in North America, said Zambon. But H3N2 viruses currently appear to be responsible for about 90 per cent of confirmed flu cases, leading European authorities to conclude oseltamivir will probably be effective in most situations.
In the first few years after oseltamivir's introduction to the market, it was thought drug resistance wasn't likely to pose too much of a problem for the drug. Laboratory testing suggested resistant viruses, if they developed, would be too weak to spread.
That theory proved far off the mark when earlier this year reports emerged from Europe of a new resistant strain of H1N1 viruses. The strain has disseminated widely and rapidly; 100 per cent of H1N1 viruses tested in South Africa during that country's recent winter carried the mutation that makes the viruses resistant.
In the face of this development, doctors who have already expressed skepticism over the merits of the available flu drugs may be even more reluctant to prescribe them in an out-patient setting or use them in hospitalized patients.
Experts, who feel the drugs are already underutilized, hope that isn't the case.
"I think that these recommendations are really meant to provide physicians with guidance on how they should use or could use antivirals," said Dr. Joe Bresee, the CDC's chief of influenza surveillance and prevention.
"So I really do hope these new recommendations won't scare anybody away from the use of antivirals but will in fact remind them about the value of use of antivirals and encourage them to use them appropriately."
http://chealth.canoe.ca/channel_heal...&news_id=27016
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December 29th, 2008, 10:07 AM
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Re: Influenza viruses resistant to oseltamivir, news and updates
BRITISH COLUMBIA (BC)
INFLUENZA SURVEILLANCE
2008-2009 UPDATE
- 1 -
Travis Hottes, Naveed Janjua, & Danuta Skowronski Number 4: Weeks 49 and 50
BCCDC Influenza & Emerging Respiratory Pathogens Team Nov 30 – Dec 13, 2008 Influenza Activity Continues to be Sporadic in BC Highlights Influenza activity in BC remains limited with a
small increase in laboratory detections. During
weeks 49 and 50 (Nov 30 – Dec 13, 2008), BC
laboratories reported 12 positive respiratory
specimens for influenza A and no positive
specimens for influenza B. To date this
season (Dec 18), 83% (19 / 23) of the
influenza isolates in BC have been sub-typed
as A/H1. Nineteen A/H1 viruses have been
assessed genotypically for oseltamivir
resistance; 14 showed this resistance
mutation, and the other 5 were indeterminate.
One school ILI outbreak (pathogen unknown)
was reported in week 50, and no facility
influenza outbreaks were reported. The rate of
ILI visits to physicians remains lower than
average for this time of year. Please remember to notify BCCDC if an
outbreak of ILI occurs in your region, by
emailing ilioutbreak@bccdc.ca and
attaching the outbreak report form (a copy
is found at the end of this report).
Sentinel Physicians
Based on the historic range for this time of
year, the rate of ILI visits to sentinel physicians
was lower than expected in both weeks. In
week 49, the percentage of all patient visits
due to ILI was 0.28%, and in week 50, the
percentage was 0.12%. (See graph and table
on page 4.) ILI Outbreaks One ILI outbreak (pathogen unknown) in a
school was reported in BC during week 50.
Since the start of the season (Sept 28),
specimens have been submitted to BCCDC
Laboratory Services in relation to 19 ILI
outbreak investigations. Rhino/enterovirus was
identified in 9 (47%) of the investigations, RSV
was identified in 1 (5%) investigation, and no
pathogen was identified in the other 9
investigations. (See graph on page 5.) Laboratory Reports During weeks 49 and 50 (Nov 30 – Dec 13,
2008), BCCDC Laboratory Services tested 96
respiratory specimens. Influenza A was
identified in 12 specimens. Of these, 11 were
sub-typed as H1, and 1 was sub-typed as H3.
Nine specimens tested positive for RSV, 8 for
rhino/enterovirus, 4 for parainfluenza, and 3
for adenovirus.
During week 49 (Nov 30 – Dec 6, 2008),
Children’s and Women’s Health Centre
Laboratory tested 55 respiratory specimens.
Twenty specimens tested positive for RSV and
1 tested positive for parainfluenza. (See
graphs on page 6.) Contents: Overview Page 1
Sentinel Physicians Page 1
ILI Outbreaks Page 1
Laboratory Reports Page 1
Oseltamivir Resistance Page 1
Canadian Data Page 2
International Data Page 2
Avian Influenza Page 2
Vaccine Composition Page 3
Activity Level Definitions Page 3
List of Acronyms Page 3
Web Sites Page 3
Weekly ILI Graph Page 4
ILI by Health Authority Page 4
ILI Outbreaks Graph Page 5
Lab Summary Graphs Page 6
ILI Outbreak Form Page 7
BRITISH COLUMBIA (BC)
INFLUENZA SURVEILLANCE
2008-2009 UPDATE
- 2 - Oseltamivir Resistance During the 2007-08 season, oseltamivir
resistance was identified among circulating
A/H1N1 viruses worldwide. Testing in Canada
indicated that 26% of last season’s A/H1N1
isolates were resistant to oseltamivir. Influenza
activity remains low, and only a small sample
of viruses is yet available for assessment. To
date (Dec 18), BCCDC has assessed 19
A/H1N1 isolates for oseltamivir resistance; 14
show genotypic evidence of oseltamivir
resistance, and the other 5 are indeterminate.
These specimens were from communitybased
cases of ILI; none was associated with
an outbreak. Health care providers considering use of
antivirals are advised to regularly consult
public health and surveillance updates and
to stay informed about influenza activity
and resistance patterns throughout the
season. This may be relevant to the
appropriate choice among antiviral
options.
CANADA
Flu Watch During week 49, sporadic activity was reported
in BC, Ontario, and Quebec, and localized
activity was reported in Alberta. ILI outbreaks
in schools have been reported in Alberta and
BC during weeks 49 and 50. Since August 24,
2008 provincial/territorial laboratories have
detected 89 cases of influenza, 54 influenza A
and 35 influenza B. The national rate of ILI
visits to sentinel physicians (12 cases per
1,000 visits during week 49) is below the
expected range for this time of the season. National Microbiology Laboratory Since Sept 1, 16 influenza isolates from
provincial and hospital labs have been
characterized at the National Microbiology
Laboratory (NML):
1 A/Brisbane/59/07(H1N1)-like* from Nova
Scotia,
2 A/Brisbane/10/07(H3N2)-like* from BC
(week 43: Oct 19 – 25) and Ontario,
3 B/Florida/04/06(Yamagata)-like* from
Alberta and Ontario,
and 10 B/Malaysia/2506/04(Victoria)-like from
Alberta and Ontario. * indicates a strain match to the vaccine component. Antiviral Resistance Drug susceptibility testing at the NML showed
that the H1N1 isolate from Nova Scotia was
sensitive to amantadine and zanamivir but
resistant to oseltamivir and that both H3N2
isolates were resistant to amantadine but
sensitive to oseltamivir and zanamivir. Eleven
influenza B viruses have been tested for
oseltamivir resistance, and all were found to
be sensitive. Nine influenza B viruses have
been tested for zanamivir resistance, and all
were found to be sensitive. INTERNATIONAL A low level of Influenza activity was reported
during week 49 (Nov 30 – Dec 6) in the United
States. Localized activity was reported in
Hawaii, Texas, and Massachusetts, and
sporadic activity was reported elsewhere. The
rate of ILI visits to sentinel physicians
remained below national baseline levels. To
date this season, US laboratories have typed
507 influenza-positive specimens: 408 (81%)
influenza A and 99 (20%) influenza B. Of the
influenza A isolates, 175 have been subtyped,
of which 90% were A/H1. Forty-five of
46 A/H1 viruses tested were found to be
resistant to oseltamivir. For information about
influenza surveillance indicators in the United
States, please visit: .
Most countries in Europe continued to report
lower than average activity during week 49. Of
the 668 influenza virus detections in Europe
since the start of the season (week 40), 621
(93%) were influenza A, and of those
subtyped, 92% were A/H3. For more
information, please visit: http://www.eiss.org.
BRITISH COLUMBIA (BC)
INFLUENZA SURVEILLANCE
2008-2009 UPDATE
- 3 - Avian Influenza Four additional cases of human H5N1 AI have
been reported by the WHO since Sept 10,
2008 (2 in Indonesia, 1 in Cambodia, and 1 in
Egypt). Since 2003, the WHO has confirmed
391 human AI cases and 247 deaths. For
more information on human avian influenza
cases please visit: For further information on confirmed avian
influenza outbreaks in poultry, please visit: .
Vaccine Composition This year’s (2008-09) influenza vaccine contains
the following virus antigens: A/Brisbane/59/2007(H1N1)-like
A/Brisbane/10/2007(H3N2)-like
Note: A/Uruguay/716/2007(H3N2) is
antigenically equivalent to
A/Brisbane/10/2007(H3N2) and may be
included by vaccine producers.
B/Florida/04/2006(Yamagata lineage)-like
Activity Level Definitions Sporadic influenza activity: sporadically occurring
ILI and laboratory-confirmed influenza during
previous 4 weeks, with no outbreaks.
Localized influenza activity: as for sporadic activity,
but with ILI outbreaks in schools and worksites, or
laboratory-confirmed influenza outbreaks in
residential institutions occurring in less than 50% of
the influenza surveillance regions during the week
of reporting.
Widespread influenza activity: as for localized
activity, but with outbreaks occurring in greater
than or equal to 50% of the influenza surveillance
regions during the week of reporting.
Contact Us: List of Acronyms
AI: Avian Influenza
FHA: Fraser Health Authority
HPAI: Highly Pathogenic Avian Influenza
HSDA: Health Service Delivery Area
IHA: Interior Health Authority
ILI: Influenza-Like Illness
LTCF: Long Term Care Facility
NHA: Northern Health Authority
NML: National Microbiological Laboratory
OIE: World Organization for Animal Health
RSV: Respiratory syncytial virus
VCHA: Vancouver Coastal Health Authority
VIHA: Vancouver Island Health Authority
WHO: World Health Organization
Web Sites
1. Influenza Web Sites Canada – Flu Watch: NACI Statement on Influenza Vaccination for the
2008-09 Season: http://www.phacaspc.
gc.ca/publicat/ccdr-rmtc/08vol34/acs-3/indexeng.
php
Washington State Flu Updates: USA Weekly Surveillance reports: European Influenza Surveillance Scheme: WHO – Global Influenza Programme: WHO – Weekly Epidemiological Record: Influenza Centre (Australia): 2. Avian Influenza Web Sites World Health Organization – Avian Influenza: World Organization for Animal Health: 3. This Report On-line Epidemiology Services BC Centre for Disease Control (BCCDC)
655 W. 12 th Ave, Vancouver BC V5Z 4R4
Tel: (604) 660-6061 / Fax: (604) 660-0197
InfluenzaFieldEpi@bccdc.ca - 4 - W EEKLY ILI
Percentage of Patient Visits due to Influenza Like Illness (ILI) per Week
Compared to Average Percentage of ILI Visits for the Past 19 Seasons
Sentinel Physicians, British Columbia, 2008-2009 0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
40 42 44 46 48 50 52 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 Week Number of the Year % of patient visits due to ILI 0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
2008/2009 season 1989/90 to 2007/08 seasons (Average +/- (2 standard units)) I NFLUENZA-LIKE ILLNESS BY HEALTH AUTHORITY
Week 49 Nov 30 – Dec 6 Week 50
HEALTH Dec 7 – 13
AUTHORITY ILI
Visits
Total
Visits
% ILI ILI
Visits
Total
Visits
% ILI Fraser 5 2,448 0.20% 8 9,475 0.08%
Interior 1 570 0.18% 2 721 0.28%
Northern 1 370 0.27% 1 332 0.30%
Vancouver Coastal 7 1,680 0.42% 0 1,263 0.00%
Vancouver Island 5 1,809 0.28% 5 1,809 0.28% BC Total 19 6,877 0.12% 16 13,600 0.12% - 5 - ILI O UTBREAKS
Number of Influenza-Like Illness (ILI) Outbreaks Investigated or Reported,
Compared to Current ILI Rate and Average ILI Rate for past 19 years, per Week
British Columbia, 2008-2009 0
10
20
30
40
40
42
44
46
48
50
52
2
4
6
8
10
12
14
16
18
20
22
24
26
28
30
32
34
36
38 Week #
# ILI Outbreaks
Investigated/Reported -0.1
0.1
0.3
0.5
0.7
0.9
1.1
1.3
1.5 % of sentinel patient visits due to ILI # Influ LTCF*
# Other LTCF*
# ILI (No Pathogen) LTCF*
# ILI Acute Hospitals
# ILI Schools
Avg ILI Rate
Current ILI Rate
* Influ LTCF = Long-term care facility, influenza identified
* Other LTCF = Long-term care facility, other pathogen identified (including RSV, parainfluenza, adenovirus, and rhino/enterovirus)
* ILI (No Pathogen) LTCF = Long-term care facility, no pathogen identified - 6 -
http://www.bccdc.org/downloads/pdf/e...49-50_0809.pdf
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December 29th, 2008, 10:09 AM
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Retired
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Join Date: Feb 2006
Posts: 20,294
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Re: Influenza viruses resistant to oseltamivir, news and updates
To date this
season (Dec 18), 83% (19 / 23) of the
influenza isolates in BC have been sub-typed
as A/H1. Nineteen A/H1 viruses have been
assessed genotypically for oseltamivir
resistance; 14 showed this resistance
mutation, and the other 5 were indeterminate.
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December 29th, 2008, 11:37 AM
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Retired
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Posts: 20,294
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Re: Influenza viruses resistant to oseltamivir, news and updates
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