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Influenza A(H1N1) virus resistance to oseltamivir - 2008 influenza season, southern hemisphere [WHO - NEW]

Giuseppe

Giuseppe

Emeritus
Influenza A(H1N1) virus resistance to oseltamivir - 2008 influenza season, southern hemisphere

Influenza A(H1N1) virus resistance to oseltamivir - 2008 influenza season, southern hemisphere

22 September 2008

During the weeks 33?36 (10 August ? 6 September), overall influenza activity in the southern hemisphere declined, except for New Zealand where influenza activity remained widespread with
predominating influenza B virus and co-circulating A(H3) virus.

In Australia, local activity was reported during weeks 35-36 with co-circulation of A and B viruses.

Between weeks 33 to 36, in the southern hemisphere, sporadic influenza activity was detected in Argentina (A,B), Brazil (A), Chile (B, A) and New Caledonia (H1). Activity was low in the rest of the world ? declining influenza activity (H1, H3) was reported from Hong Kong SAR, China and only sporadic influenza activity was reported from Canada (H1, B) and Japan (H3).

WHO has received several reports from National Influenza Centres (NIC) in the southern hemisphere regarding influenza A(H1N1) virus resistance to oseltamivir.

In South Africa, a total of 283 A(H1N1) viruses have been isolated during the 2008 influenza season as of 9 September.

Of those, 129 isolates have been tested for oseltamivir resistance by the National Institute of Communicable Diseases (NICD) and 100% were found to be resistant to oseltamivir by genotypic
analysis.

Only one of these 129 patients was receiving oseltamivir at the time of sampling, and no unusual clinical features or underlying conditions were found.

In Australia, 25 of 26, Argentina, 11 of 25, Chile, 6 of 44 A(H1N1) viruses analysed showed the specific neuraminidase mutation (H274Y) associated with oseltamivir resistance, respectively.

WHO has also received reports from NICs in other parts of the world; In the Russian Federation, 9 of 20, and Philippines, 10 of 11 A(H1N1) viruses tested were found to be resistant, respectively.

WHO is collecting global data about this phenomenon from multiple laboratories participating in Global Influenza Surveillance Network. Data from European countries participating in EISS were
provided by the EISS and VirGil project. This summary table will be updated regularly (every four weeks).

Oseltamivir resistance results were based on phenotypic and/or genotypic analyses.

For background and summary until week 24, 2008, see Influenza A(H1N1) virus resistance to oseltamivir, Last quarter 2007 to first quarter 2008, Preliminary summary and future plans
http://www.who.int/csr/disease/influenza/oseltamivir_summary/en/index.html
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http://www.who.int/csr/disease/influenza/H1N1webupdate20080922.pdf
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Re: Influenza A(H1N1) virus resistance to oseltamivir - 2008 influenza season, southern hemisphere [WHO - NEW]

niman said:
Commentary

http://www.recombinomics.com/News/09290802/H274Y_Fix_Philippines.html
Click to expand...
Commentary

Fixing H1N1 Tamiflu Resistance In the Philippines
Recombinomics Commentary 19:07
September 29, 2008

In South Africa, a total of 283 A(H1N1) viruses have been isolated during the 2008 influenza season as of 9 September.

Of those, 129 isolates have been tested for oseltamivir resistance by the National Institute of Communicable Diseases (NICD) and 100% were found to be resistant to oseltamivir by genotypic analysis.

In Australia, 25 of 26, Argentina, 11 of 25, Chile, 6 of 44 A(H1N1) viruses analysed showed the specific neuraminidase mutation (H274Y) associated with oseltamivir resistance, respectively.

WHO has also received reports from NICs in other parts of the world; In the Russian Federation, 9 of 20, and Philippines, 10 of 11 A(H1N1) viruses tested were found to be resistant, respectively.

The above comments provide additional updates on Tamiflu resistance in the southern hemisphere and indicate that resistance is at or near 100% in South Africa (129/129), Australia (25/26), and the Philippines (10/11).

The levels suggest the Tamiflu resistance is becoming fixed in the above countries, and will likely become fixed in new versions of clade 2B that emerge in the upcoming season, in spite of targeting Brisbane/59 in the current vaccine for the northern hemisphere and the upcoming vaccine for the southern hemisphere.


.
 
Re: Influenza A(H1N1) virus resistance to oseltamivir - 2008 influenza season, southern hemisphere [WHO - NEW]

http://www.recombinomics.com/News/09290801/H274Y_Fix.html
"... isolates from Africa and South America, which are largely evolving versions of the dominant Brisbane/59 (clade 2B) sub-clade with H274Y. ...
... evidence of additional independent introductions, indicating Tamiflu resistance is evolving through two mechanisms. One involves evolution of the dominant sub-clade, while he other involves movement of H274Y from the dominant sub-clade, to other clade 2B sub-clades, raising concerns that H274Y will soon be fixed in H1N1. ...
The recent HA sequences from Seychelles have the same non-synonymous changes seen in isolates from South Africa, raising concerns that the effectiveness of the Brisbane/59 vaccine that is being introduced this season will have limited utility. ...
... dramatic increase in the H1N1 genetic reservoir with H274Y, which creates concern that the frequency of H274Y will continue to increase as H1N1 continues to evolve."

So, in exception with maybe NewRelenza (in exper. quantities), we loosed any antiviral medication onto this kind of H1N1.
Additionaly, the WHO 08/09 vaccine would not probably be enaugh effective.

Acknowledging that the strains evolves, and we can't be sure if the northern flu strains would change much from the actual,
exists at the moment some scientific reason why this one resistant, not well matched in a vaccine, seasonal H1N1 strain would not became shortly an serious pandemic virus instead of the dreaded H5N1?
Low virulence, bland infection course, ...?
 
Re: Influenza A(H1N1) virus resistance to oseltamivir - 2008 influenza season, southern hemisphere [WHO - NEW]

resistance against Tamifly is no big indicator for a virus going pandemic.

It's still H1N1 and thus no new serotype, which would be typical for panemics
 
Re: Influenza A(H1N1) virus resistance to oseltamivir - 2008 influenza season, southern hemisphere [WHO - NEW]

gsgs said:
resistance against Tamifly is no big indicator for a virus going pandemic.

It's still H1N1 and thus no new serotype, which would be typical for panemics
Click to expand...
So the actual H1N1 can't spread enaugh good to infect vast parts of populations, but if it change raising virulence further, it would?
The S.African epidemic cases seems enaugh serious, or not?
 
Re: Influenza A(H1N1) virus resistance to oseltamivir - 2008 influenza season, southern hemisphere [WHO - NEW]

tropical said:
So the actual H1N1 can't spread enaugh good to infect vast parts of populations, but if it change raising virulence further, it would?
The S.African epidemic cases seems enaugh serious, or not?
Click to expand...
This version of H1N1 can efficiently transmit human to human (but is in competition with H3N2 and influenza B). Many regions have a significant level of H1N1 (it was widespread in the US and Europe last season) and this upcoming season should be dominated by H1N1 with H274Y, which can be transfered to H5N1 if H5N1 becomes efficiently transmitted to humans.
 
Re: Influenza A(H1N1) virus resistance to oseltamivir - 2008 influenza season, southern hemisphere [WHO - NEW]

So not pandemic from that H1N1 for now on the horizon, but we start to loose oseltamivir eficacy wider.

Thank You Dr. Niman, and gsgs.
 
Re: Influenza A(H1N1) virus resistance to oseltamivir - 2008 influenza season, southern hemisphere [WHO - NEW]

Update on public sequences with H274Y

gb|FJ227689.1| Influenza A virus (A/HongKong/1313/2008(H1N1))... 32.2 10
gb|FJ227688.1| Influenza A virus (A/HongKong/1052/2008(H1N1))... 32.2 10
gb|FJ227687.1| Influenza A virus (A/HongKong/942/2008(H1N1)) ... 32.2 10
gb|FJ179363.1| Influenza A virus (A/Illinois/15/2007(H1N1)) s... 32.2 10
gb|FJ179362.1| Influenza A virus (A/Illinois/16/2007(H1N1)) s... 32.2 10
gb|FJ179361.1| Influenza A virus (A/Pennsylvania/13/2007(H1N1... 32.2 10
gb|EU914908.1| Influenza A virus (A/Johannesburg/45/2008(H1N1... 32.2 10
gb|EU914907.1| Influenza A virus (A/Johannesburg/36/2008(H1N1... 32.2 10
gb|EU914906.1| Influenza A virus (A/Johannesburg/35/2008(H1N1... 32.2 10
gb|EU914905.1| Influenza A virus (A/Johannesburg/33/2008(H1N1... 32.2 10
gb|EU914904.1| Influenza A virus (A/Johannesburg/14/2008(H1N1... 32.2 10
gb|EU914903.1| Influenza A virus (A/Johannesburg/21/2008(H1N1... 32.2 10
gb|EU914902.1| Influenza A virus (A/CapeTown/26/2008(H1N1)) n... 32.2 10
gb|EU914901.1| Influenza A virus (A/Johannesburg/12/2008(H1N1... 32.2 10
gb|EU685788.1| Influenza A virus (A/Paris/1170/2008(H1N1)) ne... 32.2 10
gb|EU551826.1| Influenza A virus (A/Paris/749/2007(H1N1)) neu... 32.2 10
gb|EU551824.1| Influenza A virus (A/Paris/847/2007(H1N1)) neu... 32.2 10
gb|EU551821.1| Influenza A virus (A/Paris/963/2008(H1N1)) neu... 32.2 10
gb|EU551815.1| Influenza A virus (A/Paris/577/2007(H1N1)) neu... 32.2 10
gb|EU551814.1| Influenza A virus (A/Paris/1157/2008(H1N1)) ne... 32.2 10
gb|EU551813.1| Influenza A virus (A/Paris/1208/2008(H1N1)) ne... 32.2 10
gb|EU551812.1| Influenza A virus (A/Paris/1154/2008(H1N1)) ne... 32.2 10
gb|EU551811.1| Influenza A virus (A/Paris/341/2007(H1N1)) neu... 32.2 10
gb|EU551810.1| Influenza A virus (A/Paris/910/2007(H1N1)) neu... 32.2 10
gb|EU551809.1| Influenza A virus (A/Paris/644/2007(H1N1)) neu... 32.2 10
gb|EU887035.1| Influenza A virus (A/South Carolina/01/2008(H1... 32.2 10
gb|EU879082.1| Influenza A virus (A/Zhejiang/Xiangshan522/200... 32.2 10
gb|EU879064.1| Influenza A virus (A/Gansu/Chenguan/1129/2007(... 32.2 10
gb|EU851986.1| Influenza A virus (A/Minnesota/01/2008(H1N1)) ... 32.2 10
gb|EU851982.1| Influenza A virus (A/Hawaii/02/2008(H1N1)) seg... 32.2 10
gb|EU851980.1| Influenza A virus (A/Hawaii/01/2008(H1N1)) seg... 32.2 10
gb|EU779650.1| Influenza A virus (A/North Carolina/02/2008(H1... 32.2 10
gb|EU779643.1| Influenza A virus (A/New Jersey/10/2008(H1N1))... 32.2 10
gb|EU779641.1| Influenza A virus (A/Memphis/03/2008(H1N1)) ne... 32.2 10
gb|EU681266.1| Influenza A virus (A/Bursa-TR/1231/2007(H1N1))... 32.2 10
gb|EU681265.1| Influenza A virus (A/Istanbul-TR/1219/2007(H1N... 32.2 10
gb|EU681264.1| Influenza A virus (A/Istanbul-TR/1198/2007(H1N... 32.2 10
gb|EU681263.1| Influenza A virus (A/Ankara-TR/170/2008(H1N1))... 32.2 10
gb|EU681262.1| Influenza A virus (A/Istanbul-TR/111/2008(H1N1... 32.2 10
gb|EU702755.1| Influenza A virus (A/Hong Kong/17/2008(H1N1)) ... 32.2 10
gb|EU716587.1| Influenza A virus (A/Washington/01/2008(H1N1))... 32.2 10
gb|EU716580.1| Influenza A virus (A/Florida/02/2008(H1N1)) se... 32.2 10
gb|EU624316.1| Influenza A virus (A/England/557/2007(H1N1)) s... 32.2 10
gb|EU570806.1| Influenza A virus (A/Bursa-TR/28/2008(H1N1)) n... 32.2 10
gb|EU567014.1| Influenza A virus (A/New Jersey/06/2008(H1N1))... 32.2 10
gb|EU567011.1| Influenza A virus (A/Indiana/01/2008(H1N1)) se... 32.2 10
gb|EU567009.1| Influenza A virus (A/Arizona/13/2007(H1N1)) se... 32.2 10
gb|EU567006.1| Influenza A virus (A/Arizona/14/2007(H1N1)) se... 32.2 10
gb|EU566999.1| Influenza A virus (A/Wisconsin/01/2008(H1N1)) ... 32.2 10
gb|EU566998.1| Influenza A virus (A/Maryland/04/2007(H1N1)) s... 32.2 10
gb|EU566987.1| Influenza A virus (A/New Jersey/20/2007(H1N1))... 32.2 10
gb|EU566983.1| Influenza A virus (A/New Jersey/05/2008(H1N1))... 32.2 10
gb|EU566977.1| Influenza A virus (A/Pennsylvania/02/2008(H1N1... 32.2 10
gb|EU566968.1| Influenza A virus (A/Arizona/15/2007(H1N1)) se... 32.2 10
gb|EU516201.1| Influenza A virus (A/New Jersey/16/2007(H1N1))... 32.2 10
gb|EU516200.1| Influenza A virus (A/Illinois/10/2007(H1N1)) s... 32.2 10
gb|EU516199.1| Influenza A virus (A/Georgia/20/2006(H1N1)) se... 32.2 10
gb|EU516198.1| Influenza A virus (A/Georgia/20/2006(H1N1)) se... 32.2 10
gb|EU516197.1| Influenza A virus (A/Georgia/20/2006(H1N1)) se... 32.2 10
gb|EU516196.1| Influenza A virus (A/Arizona/03/2007(H1N1)) se... 32.2 10
gb|EU516148.1| Influenza A virus (A/New Jersey/15/2007(H1N1))... 32.2 10
gb|EU516141.1| Influenza A virus (A/Minnesota/23/2007(H1N1)) ... 32.2 10
gb|EU516125.1| Influenza A virus (A/Hawaii/28/2007(H1N1)) seg... 32.2 10
gb|EU516123.1| Influenza A virus (A/Hawaii/28/2007(H1N1)) seg... 32.2 10
gb|EU516112.1| Influenza A virus (A/Hawaii/21/2007(H1N1)) seg... 32.2 10
gb|EU516028.1| Influenza A virus (A/Massachusetts/05/2007(H1N... 32.2 10
gb|EU516027.1| Influenza A virus (A/Texas/31/2007(H1N1)) segm... 32.2 10
gb|CY027037.1| Influenza A virus (A/Kansas/UR06-0104/2007(H1N... 32.2 10
 
Re: Influenza A(H1N1) virus resistance to oseltamivir - 2008 influenza season, southern hemisphere [WHO - NEW]

One of the three Hong Kong partial (575 BP) sequences, A/HongKong/942/2008, is an exact match of the sequences below

gb|FJ227687.1| Influenza A virus (A/HongKong/942/2008(H1N1)) ... 1038 0.0
gb|EU914903.1| Influenza A virus (A/Johannesburg/21/2008(H1N1... 1038 0.0
gb|EU914902.1| Influenza A virus (A/CapeTown/26/2008(H1N1)) n... 1038 0.0
gb|EU685788.1| Influenza A virus (A/Paris/1170/2008(H1N1)) ne... 1038 0.0
gb|EU551826.1| Influenza A virus (A/Paris/749/2007(H1N1)) neu... 1038 0.0
gb|EU551824.1| Influenza A virus (A/Paris/847/2007(H1N1)) neu... 1038 0.0
gb|EU551813.1| Influenza A virus (A/Paris/1208/2008(H1N1)) ne... 1038 0.0
gb|EU551812.1| Influenza A virus (A/Paris/1154/2008(H1N1)) ne... 1038 0.0
gb|EU551811.1| Influenza A virus (A/Paris/341/2007(H1N1)) neu... 1038 0.0
gb|EU551810.1| Influenza A virus (A/Paris/910/2007(H1N1)) neu... 1038 0.0
gb|EU551809.1| Influenza A virus (A/Paris/644/2007(H1N1)) neu... 1038 0.0
gb|EU887035.1| Influenza A virus (A/South Carolina/01/2008(H1... 1038 0.0
gb|EU851980.1| Influenza A virus (A/Hawaii/01/2008(H1N1)) seg... 1038 0.0
gb|EU779643.1| Influenza A virus (A/New Jersey/10/2008(H1N1))... 1038 0.0
gb|EU702755.1| Influenza A virus (A/Hong Kong/17/2008(H1N1)) ... 1038 0.0
gb|EU716587.1| Influenza A virus (A/Washington/01/2008(H1N1))... 1038 0.0
gb|EU624316.1| Influenza A virus (A/England/557/2007(H1N1)) s... 1038 0.0
gb|EU566999.1| Influenza A virus (A/Wisconsin/01/2008(H1N1)) ... 1038 0.0
gb|EU566987.1| Influenza A virus (A/New Jersey/20/2007(H1N1))... 1038 0.0
gb|EU566983.1| Influenza A virus (A/New Jersey/05/2008(H1N1))... 1038 0.0
gb|EU516148.1| Influenza A virus (A/New Jersey/15/2007(H1N1))... 1038 0.0
 
Re: Influenza A(H1N1) virus resistance to oseltamivir - 2008 influenza season, southern hemisphere [WHO - NEW]

Two of the isolates from Hong Kong with H274Y are clade 2C:

gb|FJ227689.1| Influenza A virus (A/HongKong/1313/2008(H1N1))... 34.2 2.5
gb|FJ227688.1| Influenza A virus (A/HongKong/1052/2008(H1N1))... 34.2 2.5
gb|EU551807.1| Influenza A virus (A/Paris/6/2007(H1N1)) neura... 34.2 2.5
gb|CY034126.1| Influenza A virus (A/NYMC X-163(NYMC X-157-St.... 34.2 2.5
gb|EU879082.1| Influenza A virus (A/Zhejiang/Xiangshan522/200... 34.2 2.5
gb|EU879078.1| Influenza A virus (A/Hubei/Jiangan/1251/2006(H... 34.2 2.5
gb|EU879064.1| Influenza A virus (A/Gansu/Chenguan/1129/2007(... 34.2 2.5
gb|EU791308.1| Influenza A virus (A/Ulaanbaatar/1809/2007(H1N... 34.2 2.5
gb|EU791304.1| Influenza A virus (A/Orkhon/1901/2007(H1N1)) s... 34.2 2.5
gb|EU791302.1| Influenza A virus (A/Ulaanbaatar/1830/2007(H1N... 34.2 2.5
gb|EU791300.1| Influenza A virus (A/Sainshand/1142/2007(H1N1)... 34.2 2.5
gb|EU791298.1| Influenza A virus (A/Ulaanbaatar/1094/2007(H1N... 34.2 2.5
gb|EU779656.1| Influenza A virus (A/Hawaii/46/2007(H1N1)) neu... 34.2 2.5
gb|EU779644.1| Influenza A virus (A/Hawaii/05/2008(H1N1)) neu... 34.2 2.5
gb|EU716602.1| Influenza A virus (A/Hawaii/42/2007(H1N1)) seg... 34.2 2.5
gb|EU716592.1| Influenza A virus (A/Hawaii/43/2007(H1N1)) seg... 34.2 2.5
gb|EU716582.1| Influenza A virus (A/Hawaii/44/2007(H1N1)) seg... 34.2 2.5
gb|EU716529.1| Influenza A virus (A/Hawaii/45/2007(H1N1)) seg... 34.2 2.5
gb|EU097734.1| Influenza A virus (A/Denmark/110/2005(H1N1)) n... 34.2 2.5
gb|EU097730.1| Influenza A virus (A/Denmark/79/2005(H1N1)) ne... 34.2 2.5
gb|EU097729.1| Influenza A virus (A/Denmark/22/2005(H1N1)) ne... 34.2 2.5
gb|EU097725.1| Influenza A virus (A/Denmark/54/2005(H1N1)) ne... 34.2 2.5
gb|EU097721.1| Influenza A virus (A/Denmark/226/2005(H1N1)) n... 34.2 2.5
gb|EU097719.1| Influenza A virus (A/Denmark/116/2005(H1N1)) n... 34.2 2.5
gb|EU097718.1| Influenza A virus (A/Denmark/184/2005(H1N1)) n... 34.2 2.5
gb|EU566972.1| Influenza A virus (A/Massachusetts/01/2008(H1N... 34.2 2.5
gb|EU516282.1| Influenza A virus (A/Oregon/06/2007(H1N1)) seg... 34.2 2.5
gb|EU516276.1| Influenza A virus (A/Hawaii/38/2007(H1N1)) seg... 34.2 2.5
gb|EU516270.1| Influenza A virus (A/Hawaii/38/2007(H1N1)) seg... 34.2 2.5
gb|EU516149.1| Influenza A virus (A/Minnesota/25/2007(H1N1)) ... 34.2 2.5
gb|EU516146.1| Influenza A virus (A/Hawaii/19/2007(H1N1)) seg... 34.2 2.5
gb|EU516140.1| Influenza A virus (A/Hawaii/17/2007(H1N1)) seg... 34.2 2.5
gb|EU516137.1| Influenza A virus (A/Hawaii/16/2007(H1N1)) seg... 34.2 2.5
gb|EU516120.1| Influenza A virus (A/Hawaii/19/2007(H1N1)) seg... 34.2 2.5
gb|EU516118.1| Influenza A virus (A/Hawaii/15/2007(H1N1)) seg... 34.2 2.5
gb|EU304359.1| Influenza A virus (A/Busan/08/2007(H1N1)) neur... 34.2 2.5
gb|EU304358.1| Influenza A virus (A/Busan/03/2007(H1N1)) neur... 34.2 2.5
gb|CY027709.1| Influenza A virus (A/Virginia/UR06-0549/2007(H... 34.2 2.5
gb|CY026565.1| Influenza A virus (A/Texas/UR06-0397/2007(H1N1... 34.2 2.5
gb|CY026525.1| Influenza A virus (A/Colorado/UR06-0053/2007(H... 34.2 2.5
gb|EU199384.1| Influenza A virus (A/New York/08/2007(H1N1)) s... 34.2 2.5
gb|EU100488.1| Influenza A virus (A/Virginia/1e/2006(N1)) seg... 34.2 2.5
gb|CY022535.1| Influenza A virus (A/Auckland/605/2001(H1N1)) ... 34.2 2.5
dbj|AB286013.1| Influenza A virus (A/Hanoi/TX09/2006(H1N1)) g... 34.2 2.5
gb|CY009334.1| Influenza A virus (A/Fort Worth/50(H1N1)) segm... 34.2 2.5
gb|CY008990.1| Influenza A virus (A/Denver/57(H1N1)) segment ... 34.2 2.5
 
Re: Influenza A(H1N1) virus resistance to oseltamivir - 2008 influenza season, southern hemisphere [WHO - NEW]

niman said:
Commentary

http://www.recombinomics.com/News/10190802/H274Y_Fixing_Additional.html
Click to expand...
Commentary

Additional Worldwide Fixing of H1N1 Tamiflu Resistance
Recombinomics Commentary 21:36
October 19, 2008

In South Africa, a total of 306 A(H1N1) viruses have been isolated during the 2008 influenza season as of 6 October.

Of those, 225 isolates have been tested for oseltamivir resistance by the National Institute of Communicable Diseases (NICD) and 100% were found to be resistant to oseltamivir by genotypic analysis

In Australia, 47 of 59, Argentina, 15 of 33, Chile, 10 of 79, Kenya, 1 of 4, New Caledonia, 7 of 7, New Zealand, 2 of 2, and Uruguay 13 of 16 A(H1N1) viruses analysed showed the specific neuraminidase mutation (H274Y) associated with oseltamivir resistance, respectively.

WHO has also received reports from NICs in other parts of the world; in Algeria, 4 of 13, Canada, 1of 2, Ghana 5 of 13, Guatemala, 4 of 5, Honduras, 5 of 8, Ivory Coast, 2 of 5, the Netherlands, 1 of 2, Nigeria, 1 of 1, Senegal 10 of 10 and the United States of America, 3 of 7 A(H1N1) viruses tested were found to be resistant, respectively.

The above comments describe a global expansion of H274Y in H1N1. In South Africa, where the dominant HA sequence has acquired five changes in proximity to position 190 (H3 numbering), 225/225 sequenced isolates have H274Y in NA. Other countries at 100% oseltamivir resistance include New Caledonia (7/7), New Zealand (2/2), Nigeria (1/1), Senegal (10/10). Countries with resistance at 50% or higher include Australia (47/59), Uraguay (13/26), and Canada (1/2), indicating the resistance is spreading worldwide.

Recent HA sequences from Kenya have two tandem changes, G604A and G605A, which are present in the South African and Seychelles isolates, signaling additional recombination. Two adjacent tandem changes (C610T and G617A) match H1N1 from the 1940?s, while the fifth change (A599G) is in a recent clade 2C isolate from Hong Kong. Four of the five changes produce non-synonymous changes flanking the receptor binding domain position at 190 (N187S, G189N, A193T).

The sequences with the cluster of changes evolved from the Brisbane/59 sub-clade that was dominant in northern Europe in 2007/2008. The result from South Africa suggests this sub-clade continues to evolve and expand. Some countries still have other H1N1 sub-clade in circulation, but the countries reporting H274Y levels at or near 100% of H1N1 isolates suggests this change will soon be fixed in H1N1 worldwide.


.
 
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