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Commentary
 
Qinghai H5N1 Bird Flu Sequences Spread in Indonesia

Recombinomics Commentary

August 8, 2006

Recently the H5N1 bird flu sequences from human cases in Indonesia were released from the WHO private database.  These sequences supported earlier observations that the human isolates from the Jakarta area did not match the public avian sequences and had a number of unique polymorphisms in HA.  Similarly, the sequences from the Karo cluster were also distinct from the avian sequences but were more closely related to a subset of the avian sequences.

Analysis of the newly released sequences, however, indicates that the Karo sequences have a number of polymorphism found in Qinghai isolates. The Qinghai sequences are genetically distinct from the Indonesian sequences.  However, the Karo sequences have the Qinghai sequences overlaid on the Indonesia background.  The examples of the HA polymorphisms included one that was present in some of the more recent Indonesian avian sequences as well as the second confirmed case from Jakarta.  That case is the only Jakarta isolate that does not have the novel cleavage site.

Additional Qinghai sequences are in the NS gene of the Karo cluster.  However, one of the polymorphisms is also several of the more recent cases from the Jakarta area.  These more recent cases have the novel HA cleavage site and are readily distinguished from the sequences from the Karo cluster.  The polymorphism is not detected in any of the avian sequences.  Thus, in Indonesia it is only in the human sequences and punctuates two distinct sets of human sequences, those found on Java between late 2005 and 2006, as well as the Karo cluster from 2006.

Thus, H5N1 in Indonesia is evolving, but representative sequences have not been reported in the avian isolates. These data highlight the need for a more robust surveillance.

Recently two additional fatalities were reported in the Jakarta area and connections with sick or dying birds were cited.  However, these is no indication that the birds are H5N1 positive and there is no sequence data from recent isolates.

WHO should now have data on the recent samples sent to Australia.  Thus far there has been no announcement of the detection of the novel cleavage site or matches between the recent avian and human  isolates.

The evolution of the H5N1 in Indonesia, which includes the aquisition of Qinghai sequences that are genetically and geographically distinct is cause for concern, as are the increased reports of fatal cases In Thailand.

Qinghai NS polymorphisms are listed below.  Qinghai isolates are in black bold.  Karo cluster isolates are in red bold.  Java isolates are in blue bold.

NS polymorphism

first polymorphism

DQ676837    A/chicken/Krasnodar/01/2006  2006 H5N1
DQ676833    A/chicken/Mahachkala/05/2006 2006 H5N1
DQ529294    A/chicken/Nigeria/641/2006  2006 H5N1
DQ533583    A/Cygnus olor/Italy/742/2006  2006 H5N1
DQ852605    A/grebe/Tyva/Tyv06-2/06  2006 H5N1
ISDN140814 A/Indonesia/534H/2006 2006 H5N1
ISDN140906 A/Indonesia/535H/2006  2006 H5N1
ISDN140907 A/Indonesia/536H/2006  2006 H5N1
ISDN140822 A/Indonesia/538H/2006  2006 H5N1
ISDN140908 A/Indonesia/546H/2006  2006 H5N1
ISDN185501 A/Indonesia/560H/2006  2006 H5N1
ISDN140839 A/Indonesia/CDC594/06  2006 H5N1
ISDN140847 A/Indonesia/CDC595/06  2006 H5N1
ISDN140855 A/Indonesia/CDC596/06  2006 H5N1
ISDN140863 A/Indonesia/CDC597/06  2006 H5N1
ISDN140870 A/Indonesia/CDC599/06  2006 H5N1
ISDN183778 A/Indonesia/CDC599N/2006  2006 H5N1
ISDN183745 A/Indonesia/CDC625/2006   2006 H5N1
ISDN183777 A/Indonesia/CDC625L/2006  2006 H5N1
ISDN133100 A/Turkey/12/2006   2006 H5N1
ISDN133374 A/Turkey/15/06     2006 H5N1
ISDN133360 A/Turkey/651242/06 2006 H5N1
ISDN133368 A/Turkey/65596/06  2006 H5N1
DQ683027    A/turkey/Israel/345/2006  2006 H5N1
DQ683030    A/turkey/Israel/446/2006  2006 H9N2
AB265204    A/whooper swan/Mongolia/2/06  2006 H5N1
AB239306     A/bar-headed goose/Mongolia/1/05  2005 H5N1
DQ237953    A/bar-headed goose/Qinghai/0510/05  2005 H5N1
DQ095701    A/Bar-headed Goose/Qinghai/12/05  2005 H5N1
DQ095697    A/Bar-headed Goose/Qinghai/5/05  2005 H5N1
DQ095692    A/Bar-headed Goose/Qinghai/59/05  2005 H5N1
DQ095695    A/Bar-headed Goose/Qinghai/60/05  2005 H5N1
DQ095698    A/Bar-headed Goose/Qinghai/61/05  2005 H5N1
DQ095700    A/Bar-headed Goose/Qinghai/62/05  2005 H5N1
DQ095702    A/Bar-headed Goose/Qinghai/65/05  2005 H5N1
DQ095703    A/Bar-headed Goose/Qinghai/67/05  2005 H5N1
DQ095693    A/Bar-headed Goose/Qinghai/68/05  2005 H5N1
DQ095699    A/Bar-headed Goose/Qinghai/75/05  2005 H5N1
DQ100570    A/black-headed goose/Qinghai/1/2005  2005 H5N1
DQ100571    A/black-headed goose/Qinghai/2/2005  2005 H5N1
DQ100572    A/black-headed gull/Qinghai/1/2005   2005 H5N1
DQ095696    A/Brown-headed Gull/Qinghai/3/05     2005 H5N1
DQ650662    A/chicken/Crimea/04/2005         2005 H5N1
DQ650667    A/chicken/Crimea/08/2005         2005 H5N1
DQ321139    A/chicken/Fujian/1042/2005         2005 H5N1
DQ321161    A/chicken/Guangxi/604/2005 2005 H5N1
DQ449636    A/chicken/Kurgan/05/2005  2005 H5N1
DQ323679    A/chicken/Kurgan/3/2005  2005 H5N1
DQ095706    A/Chicken/Shantou/810/05 2005 H5N1
DQ840527    A/chicken/Tula/Russia/Oct-5/2005 2005 H5N1
DQ389160    A/Cygnus olor/Astrakhan/Ast05-2-1/2005  2005 H5N1
DQ434887    A/Cygnus olor/Astrakhan/Ast05-2-10/2005 2005 H5N1
DQ359693    A/Cygnus olor/Astrakhan/Ast05-2-2/2005  2005 H5N1
DQ358752    A/Cygnus olor/Astrakhan/Ast05-2-3/2005  2005 H5N1
DQ363926    A/Cygnus olor/Astrakhan/Ast05-2-4/2005  2005 H5N1
DQ365010    A/Cygnus olor/Astrakhan/Ast05-2-5/2005  2005 H5N1
DQ365003    A/Cygnus olor/Astrakhan/Ast05-2-6/2005  2005 H5N1
DQ363927    A/Cygnus olor/Astrakhan/Ast05-2-7/2005 2005 H5N1
DQ399538    A/Cygnus olor/Astrakhan/Ast05-2-8/2005 2005 H5N1
DQ399544    A/Cygnus olor/Astrakhan/Ast05-2-9/2005  2005 H5N1
DQ321138    A/duck/Fujian/897/2005  2005 H5N1
DQ497232    A/duck/Guangdong/DG-01/2005  2005 H5N1
DQ321162    A/duck/Guangxi/793/2005  2005 H5N1
DQ321164    A/duck/Guangzhou/20/2005 2005 H5N1
DQ449644    A/duck/Kurgan/08/2005  2005 H5N1
DQ234074    A/duck/Novosibirsk/56/2005  2005 H5N1
DQ321185    A/Environment/Qinghai/31/2005  2005 H5N1
DQ676842    A/goose/Krasnoozerka/627/2005  2005 H5N1
DQ095708    A/Goose/Shantou/1621/05          2005 H5N1
DQ321178    A/goose/Shantou/2216/2005  2005 H5N1
DQ100573    A/great black-headed gull/Qinghai/1/2005  2005 H5N1
DQ095694    A/Great Black-headed Gull/Qinghai/2/05   2005 H5N1
DQ234073    A/grebe/Novosibirsk/29/2005   2005 H5N1
DQ321179    A/migratory duck/Jiangxi/1653/2005 2005 H5N1
DQ321180    A/migratory duck/Jiangxi/1657/2005 2005 H5N1
DQ321181    A/migratory duck/Jiangxi/1701/2005 2005 H5N1
DQ095707    A/Quail/Shantou/911/05 2005 H5N1
DQ840526    A/swan/Astrakhan/Russia/Nov-2/2005 2005 H5N1
ISDN129517 A/turkey/Turkey/1/05        2005 H5N1
AB239313    A/whooper swan/Mongolia/3/05  2005 H5N1
AB239320    A/whooper swan/Mongolia/4/05  2005 H5N1
AB239327    A/whooper swan/Mongolia/6/05  2005 H5N1
AY651582    A/peregrine falcon/Hong Kong/D0028/2004  2004 H5N1
AY651552     A/Viet Nam/1194/2004  2004 H5N1
AY526747     A/Viet Nam/1196/04   2004 H5N1

second polymorphism

ISDN140814 A/Indonesia/534H/2006  2006 H5N1
ISDN140906 A/Indonesia/535H/2006  2006 H5N1
ISDN140907 A/Indonesia/536H/2006  2006 H5N1
ISDN140822 A/Indonesia/538H/2006  2006 H5N1
ISDN140908 A/Indonesia/546H/2006  2006 H5N1
ISDN185501 A/Indonesia/560H/2006  2006 H5N1
ISDN181369 A/Indonesia/CDC523/2006 2006 H5N1
ISDN183301 A/Indonesia/CDC523E/2006 2006 H5N1
ISDN183309 A/Indonesia/CDC523T/2006 2006 H5N1
ISDN183317 A/Indonesia/CDC582/2006  2006 H5N1
ISDN140839 A/Indonesia/CDC594/06  2006 H5N1
ISDN140847 A/Indonesia/CDC595/06  2006 H5N1
ISDN140855 A/Indonesia/CDC596/06  2006 H5N1
ISDN140863 A/Indonesia/CDC597/06  2006 H5N1
ISDN140870 A/Indonesia/CDC599/06  2006 H5N1
ISDN183778 A/Indonesia/CDC599N/2006 2006 H5N1
ISDN183745 A/Indonesia/CDC625/2006  2006 H5N1
ISDN183777 A/Indonesia/CDC625L/2006 2006 H5N1
ISDN183753 A/Indonesia/CDC634/2006  2006 H5N1
ISDN183761 A/Indonesia/CDC634P/2006 2006 H5N1
ISDN183769 A/Indonesia/CDC634T/2006 2006 H5N1
DQ100573    A/great black-headed gull/Qinghai/1/2005  2005 H5N1
DQ095694    A/Great Black-headed Gull/Qinghai/2/05    2005 H5N1
ISDN132410 A/Indonesia/239H/2005  2005 H5N1
ISDN137840 A/Indonesia/CDC287e/05 2005 H5N1

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