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Human H5N1 Infection in Indonesia Confirmed

Recombinomics Commentary
June 15, 2005

>> The worker from southern Sulawesi island is healthy and currently shows no symptoms of the illness but two tests at a Hong Kong laboratory confirmed that he had been infected by avian influenza, health officials said.

The laboratory results make Indonesia the fourth country to register a human case of bird flu, which international health experts warn could easily undergo genetic change, sparking a global pandemic.  <<

The confirmation of a human H5N1bird flu case in Indonesia raises a number of red flags. Although the worker is healthy, H5N1 infections of poultry in Indonesia are widespread are closely related to the H5N1 found throughout Asia. 

The H5N1 that was widely detected in poultry in Asia in 2004 was designated as the Z genotype base on the constellation of the eight influenza genes.  Each of these constellations had a number of regional specific polymorphisms.  Although H5N1 in Vietnam and Thailand had polymorphisms unique to each country, they also had a considerable number of markers that were exclusives to the countries.  These markers correlated with human infections, because only Vietnam and Thailand reported human infections and fatalities in 2004.

However, the Z genotype in Vietnam and Thailand were more closely related to H5N1 in other countries such as China, Indonesia, South Korea, and Japan, than and H5N1 isolated from a Hong Kong family in 2003.  That constellation was designated Z+ because the NA gene did not have the 20 amino acid deletion found in the Z genotype isolates.

Moreover, the H5N1 human infections in Hong Kong in 1997 involved a constellation of genes that included internal genes found in H6N1 and H9N2 isolates, and was therefore quite different than either Z or Z+ genotypes.  Thus, it was clear that a wide range of H5N1 genotypes could infect and kill humans and these was little a priori reason to assume Z genotype H5N1 could not infect humans.

The H5N1 diversity was increased again this season, when a new version appeared in northern Vietnam.  Although no 2005 H5N1 sequences are publicly available at GenBank, reports from the Manila meeting last month indicated the isolates from northern Vietnam contained an HA gene that was missing three codons for an arginine reside in the HA cleavage site.  This cleavage site would then match H5N1 isolates from 2003 and 2004 in Hong Kong, China, and Japan.  Although cases in northern Vietnam are less lethal this season than last, there are still significant numbers of fatal cases and the virus appears to be transmitted from human to human more efficiently.  In addition, asymptomatic cases have been reported.

The confirmed case in Indonesia also appears to have been mild and relatively rare.  However, the case does show that H5N1 in Indonesia can infect humans and raises the possibility that H5N1 human infections are much more widespread than is being reported.  Recently three poultry workers in India also tested positive for H5N1 antibodies in serum collected in 2002.  Since these workers had not been out of the country, they were probably infected in India although India has denied any H5N1 infections in poultry.

Recently bar headed geese at Qinghai Lake were found dead from H5N1 infections.  Reports indicate that the H5N1 in western China is similar to H5N1 in southeastern China, which is again the Z genotype and includes isolates missing the aginine.  Since the bar head geese winter in India and Bangladesh, it seems likely that they were infected prior to the start of their 24 hour migration in early May, suggesting H5N1 is present in India and Bangladesh also.

These latest observations of human H5N1 in Indonesia and India, as well as outbreaks in Qinghai and Xinjiang provinces in China, raise serious concerns about H5N1 monitoring in human and animal populations in Asia.

Failure to monitor the presence of H5N1 in Asia will limit intervention plans to stop or slow the spread of H5N1 worldwide.

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