Pandemic Influenza Then and Now
Recombinomics Commentary
January 14, 2005
Since there are many diseases that resemble pandemic influenza, it is worth reviewing the H5N1 virus as well as a few comments on the 1918 pandemic.
At the molecular level a subset of the 2004 H5N1 isolates collected throughout most of Asia had much in common including a poly-basic region at the HA cleavage site, a 20 aa deletion in NA and a 5 aa deletion in NS. However, there were regional specific polymorphisms. Some were specific for Vietnam, some for Thailand, and some found almost exclusively in Vietnam of Thailand. These polymorphisms were not found in other H5N1 isolates, but were found in mammalian isolates and represented various recombinations that acquired the polymorphisms, which were associated with an expanded host range. Moreover, Vietnam and Thailand were the only two countries with reported fatalities.
This type of molecular change is common for influenza and is not limited to H5N1. The same types of changes are seen in WSN/33 isolated from swine in Korea. These isolates have human genes from 1933. The virus was isolated from mouse brain to study some of the neurological aspects of the 1918 pandemic. The 1933 virus has picked up "modern" polymorphism, again via recombination with more recent viruses infecting swine. In addition the virus has recombined and reassorted with very recent Korean H9N2 isolates.
Thus, it is quite clear that bird flu is a moving target and reliance on last years data for this years diagnosis is dangerous. The meningococcemia-like illness in the Philippines is not the same as the disease influenza in Vietnam and Thailand. It is more easily transmitted human to human and Neisseria Meningitidis A has been isolated from a small subset of patients. The number of cases described in the most recent announcement by WHO was 33 with 8 confirmed meningo cases. The 25 meningo-like cases had a case fatality rate of 68%. Media reports indicated the number of cases in Baguio City is closer to 60 and the number throughout the country at more than 80, including the southern most regions. The most common clinical features of the patients are fever and skin petechia.
A recent monograph on preparedness for pandemic influenza includes the following:
"Symptoms in 1918 were so unusual that initially influenza was misdiagnosed as dengue, as cholera, as typhoid. Wrote one observer, "One of the most striking of the complications was hemorrhage from mucous membranes, especially from the nose, stomach, and intestine. Bleeding from the ears and petechial hemorrhages in the skin also occurred."
In view of the ability of avian influenza to rapidly change genetically as well as unusual symptoms associated with pandemic flu, diagnostic testing for influenza in fatal illnesses would be warranted.