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Amantadine Resistance in Karo Cluster in Sumatra Indonesia
June 25, 2006
The recent meeting on human H5N1 in Indonesia revealed additional detail on the sequences from the Karo cluster and presented several phylogenetic trees representing various genes of the humans isolates.
The H5N1 isolates from the Karo cluster had been described in a prior WHO update. The update had some information on the bird flu sequences of the H5N1 genes from the family members. In the WHO update, the Tamiflu sensitivity of the isolates was noted.
Full genetic sequencing of two viruses isolated from cases in this cluster has been completed by WHO H5 reference laboratories in Hong Kong and the USA. Sequencing of all eight gene segments found no evidence of genetic reassortment with human or pig influenza viruses and no evidence of significant mutations. The viruses showed no mutations associated with resistance to the neuraminidase inhibitors, including oseltamivir (Tamiflu).
The human viruses from this cluster are genetically similar to viruses isolated from poultry in North Sumatra during a previous outbreak.
However, the report failed to mention that all isolates were amantadine resistant. Data at the conference indicated that most of the human isolates in Indonesia were resistant. Prior media reports had indicated that human isolates were sensitive.
In addition, information was presented on the father of the 10 year old nephew of the index case. Media reports had indicated a minor mutation had linked the isolates from the father and son. However, in addition to the minor mutation shared by father and son, the father had 8 additional changes in HA, 3 in NA and 2 in M. These changes suggest that the father had been infected with another flu virus, leading to acquisition of a number of polymorphisms by recombination.
The rapid accumulation of polymorphisms, coupled with amantadine resistance, is cause for concern.
Amantadine resistant isolates:
A/Indonesia/160H/2005 16F East Jakarta
A/Indonesia/534H/06 18M Karo-North Sumatra
A/Indonesia/535H/06 1.5F Karo-North Sumatra
A/Indonesia/536H/06 29M Karo-North Sumatra
A/Indonesia/538H/06 19M Karo-North Sumatra
A/Indonesia/546H/06 10M Karo-North Sumatra
A/Indonesia/560H/06 35M Karo-North Sumatra
A/Indonesia/245H/2005 7M East Jakarta
A/Indonesia/286H/2006 4M Indramayu
A/Indonesia/283H/2006 13F Indramayu
A/Indonesia/304H/2006 15M Indramayu
A/Indonesia/292H/06 9F Indramayu
A/Indonesia/239H/2005 39M South Jakarta
A/Indonesia/6H/2005 37F West Jakarta
A/Indonesia/542H/2005 12M Bekasi-West Java
A/Indonesia/7H/2005 23M Bogor-West Java
A/Indonesia/341H/06 27F Cibinong-West Java
A/Indonesia/321H/06 23M East Jakarta
A/Indonesia/554H/06 18M Kediri-East Java
A/Indonesia/175H/2005 20F North Jakarta
A/Indonesia/298H/2006 22M South Jakarta
A/Indonesia/5/2005 38M Tangerang-Bantan
A/Indonesia/195H/2005 20F Tangerang-Bantan
A/Indonesia/557H/06 39M West Jakarta