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Efficient Feline to Feline Transmission of Bird Flu

Recombinomics Commentary
March 12, 2005

>> Probable Tiger-to-tiger Transmission of Avian Influenza H5N1, R. Thanawongnuweche et al <<

The article titled above will be published in the May issue of Emerging and Infectious Diseases.  Its conclusion is reflected in the title.  The article describes the bird flu epidemic among tigers at the Sri Racha Tiger Zoo in Thailand last summer.  The zoo held 441 Bengal tigers at the start of the epidemic and eventually 147 died, 45 from H5N1 infections and 102 from euthanization because of the advanced state of their H5N1 infection.  The epidemic had a bimodal distribution of onset dates.  Small numbers of tigers died daily initially, followed by a large surge, consistent with tiger-to-tiger transmission. 

The epidemic began with a small number of H5N1 infected chickens fed to the tigers.  The details will be in the publication on how many tigers ate the chickens, when they were quarantined, and when Tamiflu treatment was initiated.  However, it is clear that one third of the tigers died, and the case fatality rate in those that were infected may be much closer to 100% than the 33% for the entire population.  The epidemic provides a sobering picture of how well H5N1 transmits and how ineffective the control measures are.  The details will clearly highlight inadequate pandemic preparedness planning.  These plans take an optimistic view of case fatality rates and effectiveness of antiviral medicines in halting an H5N1 pandemic.

Although the details have not been published, the sequences of isolates from tigers have been published.  The sequences of the HA, NA, NS, PB2 genes of the tigers (A/tiger/Chonburi/Thailand/CU-T3/04(H5N1) and A/tiger/Chonburi/Thailand/CU-T7/04(H5N1) are very similar to the sequences of isolates from a tiger and leopard, (A/tiger/Suphanburi/Thailand/Ti-1/04(H5N1) and A/leopard/Suphanburi/Thailand/Leo-1/04(H5N1)), that were infected in a nearby zoo in the early part of 2004.  These sequences do not contain human reassorted genes, yet the H5N1 was very efficiently transmitted to a large number of tigers quarantined in the zoo.

However, the sequences are also closely related to other avian isolates in Thailand as well as the sequences from the mother of the index case frequently cited as the best example of human-to-human transmission of H5N1.  The sequences are also closely related to other human isolates from Thailand and Vietnam.  The isolates can be used to experimentally infecte domestic cats under controlled laboratory settings, and these infections are also transmitted cat to cat.

Thus, feline isolates closely related to human isolates are efficiently transmitted cat to cat, domestic and wild, and do not require additional genetic changes or human reassorted genes.

Reassurances that human isolates do not contain human influenza genes do not address efficient mammal-to-mammal transmission seen at the zoo and lab. 

The recent clustering of human bird flu cases in Thai Binh is cause for concern.  The familial clusters are bimodal, a strong indicator of human-to-human transmission.  Moreover, the extended transmission chain involving both family members and health care workers are indications that human-to-human transmission is becoming more efficient.  There is no evidence that human reassortants are required for improved efficiencies. 

H5N1 has evolved over the years to broaden both host ranges and tissue tropism in the absence of any reported human reassortment.  Thus, repeated assurances on the lack of human reassortment or failure to acquire a human receptor binding domain means little.

H5N1 has evolved into a virus associated with a high case fatality rate and extended human-to-human transmission in the absence of these genetic changes.

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