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H5N1 Human to Human Transmission in Thailand?

Recombinomics Commentary
May 19, 2005
>>  Phylogenetic analysis of all H5N1 human isolates along with a subset of avian viruses from clade 1 isolated during 2004 and 2005 in Cambodia, Thailand and Viet Nam indicates that the viruses from northern Viet Nam and Thailand have begun to form a somewhat separate cluster from viruses isolated from southern Viet Nam and Cambodia.  <<

The formation of a separate cluster of virus from northern Viet Nam and Thailand raises serious questions regarding Thailand's claim to have no human H5N1 infections in 2005.  The number of 2004 H5N1 isolates at Genbank is large.  There are 610 gene sequences from 156 isolates and additional 2003 sequences.  Most of these sequences are from Vietnam and Thailand.  Analysis of these sequences reveals regional polymorphisms, as well as polympohisms found in isolates from Vietnam and Thailand, but not in other H5N1 isolates.  These plymorphisms however, are found in mammalian isolates and are associated with human H5N1 infections.

In 2005, isolates in northern Vietnam appear to have recombined with less lethal isolates from China and Japan, resulting in a virus that is more transmissible to humans, but more difficult to detect because of primer mismatches.  The Institute for Hygiene and Epidemiology in Hanoi collected 1000 samples for analysis, and many or all were shipped to the CDC in Atlanta for analysis last month.  Although the results of this analysis have not been formally announced, an urgent meeting in Manila was held several weeks later.  Media comments strongly suggested that many or most of the samples would be positive, and support efficient transmission of H5N1 to humans.

Although there have been widespread outbreaks of H5N1 in Thailand in domestic and wild birds this season, as well as humans and tigers last season, it is hard to imagine why there would be no human cases this season.  There have been media reports of symptoms in children from H5N1 infected regions who developed symptoms and tested positive for influenza A.  PCR tests for H5N1 may generate false negatives, as has been reported for both north and south Vietnam.

The development of Tamiflu resistance in a H5N1 patient in northern Vietnam casts serious doubt of the success of a Tamiflu containment strategy for H5N1.  Resistance is likely to develop quickly if large numbers of patients are infected with H5N1 and treated.  Evidence for large scale H5N1 infections may already exist in the samples from northern Vietnam.  However, it would seem likely that similar infections exist for patients in Thailand.

Many of the cases in northern Vietnam are milder.  The Haiphong family of five provided one of the clearest public signals that there was efficient H5N1 transmission.  All five family members were H5N1 positives and neighbors also developed symptoms and were hospitalized.  However, the family of five recovered in a short time and were discharged.  It seems likely that other families with similar or slightly milder infections would not be hospitalized or see a doctor.  Without an H5N1 test, the avian flu would produce symptoms similar to a human flu.

Attempts to manage or control an emerging bird flu pandemic require some knowledge of the location and genetic composition of the viruses involved.  Press releases on false negatives do little to stop additional infections and spread. 

A comprehensive H5N1 screening of patients throughout southeast Asia is long overdue.

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