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Neurological Problems Associated with Bird Flu in Thailand

Recombinomics Commentary
February 3, 2005

>> More than 1,000 chickens have been found with bird flu-like symptoms in Suphan Buri and Phitsanulok following the launch a few days ago of a nationwide inspection programme.

Dr Nirundorn Aungtragoolsuk, director of the Livestock Development Department's Bureau of Disease Control and Veterinary Services, said the sick fowls were both layer and home-raised chickens. They were found in three locations in Suphan Buri and in eight Phitsanulok tambons.

Provincial officials had culled the birds before sending tissues to the lab to be tested for the virus, Dr Nirundorn said, adding the lab results are expected in four to eight days.

``They had nerve problems and some died. So the officials culled them as instructed,'' he said.

Dr Nirundorn said officials had also detected sick birds in four other provinces _ Phichit, Nakhon Sawan, Phetchabun, and Udon Thani _ but their symptoms were unlike avian infuenza. <<

The "nerve problems" mentioned above are cause for concern.  Although the association of neurological problems with influenza goes back to the 1918 pandemic, there are no reports indicating that the unusual neurological cases reported in Asia recently have been tested for bird flu.

Neurological problems were noted in the 1918 pandemic.  To study neurological problems associated with influenza, researchers infected mice in 1940 with the first human influenza isolate WS/33.  Variants isolated from the mouse brain were named WSN/33 and NWS/33.  WSN/33 was highly virulent in mice and became a popular lab strain.  Unfortunately, the human lab virus from 1933 has now somehow made its way into swine in Korea. Although the sequences from these isolates have been publicly available for over 2 months, there still has not been an official acknowledgment of the problem in Korea, even though at least two of the isolates were H1N1.

Neurotropism of H5N1 isolates also has a long history.  Isolates from Hong Kong in 2001 were able to grow in mice without adaptation and virus was also isolated from mouse brains.  These isolates were virulent and cause hind leg paralysis in mice.

More recently, the isolate from Vietnam, A/Vietnam/1203/04, that is being used to create a pandemic vaccine, also causes hind leg paralysis in ferrets.

Therefore, finding birds in Phitsanulok with "nerve problems" is not surprising, although prior recent  H5N1 reports have been lacking.  There have been several outbreaks of laboratory confirmed H5N1 in various regions of Phitsanulok in the past several weeks, so it is likely that these new infections will also be H5N1 positive. 

It would probably also be wise to test the other birds for H5N1 also, even though their symptoms were "unlike avian influenza".  Recently 3000 ducks in Vietnam died with leg paralysis. H5N1 infections were not considered because the paralysis was not considered a symptom of bird flu.  The ducks were thought to have died from cholera.

In the 1918 pandemic, flu cases had a variety of presentations and were mistakenly diagnosed as cholera, dengue fever, and typhoid.  The lack of H5N1 testing raises concerns that history will repeat itself in 2005.

Indeed the index case of the human to human transmission cluster in Thailand that was published in the New England Journal of Medicine last week was misdiagnosed as dengue fever.  Moreover the unusual cases of meningococcemia-like illness in the Philippines have had high case fatality ratios associated with infections of adults, which were easily transmitted.  Although meningococcemia is a secondary infection of influenza and some cases developed meningitis, there are no reports of these patients being tested for H5N1 avian influenza.

Likewise, there are no reports of H5N1 testing in the cases of hemorrhagic dengue fever in Timor-Lesta or meningitis in many locations in China. 

The failure to H5N1 test the patients associated with the unusual outbreaks remains scandalous.

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