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H5N1 Tiger to Tiger Transmission with Neurological Involvement

Recombinomics Commentary

April 18, 2005

>>  All animals that died had serosanguinous nasal discharge, and some had neurologic signs of infection. Necropsy was performed on 3 tigers on October 18. The lungs were severely congested and had been hemorrhaging. Serosanguinous exudate was seen throughout the tracheal and bronchiolar lumen, and pleural effusion was also seen. Microscopic findings showed moderate congestion of the brain with mild nonsuppurative meningoencephalitis (Figure 1A), severe diffuse lung hemorrhage and edema, and moderate multifocal necrotizing hepatitis. Immunohistochemical procedures were performed on all tissue by using mouse monoclonal antibody to the nucleoprotein of influenza A H5N1 (B.V. European Veterinary Laboratory, Woerden, the Netherlands). Strongly positive, brown staining was prominently displayed in the nuclei of the hepatocytes and in the cerebral neurons. Positive staining of both nuclei and cytoplasm was also apparent in the neurons (Figure 1B) and bronchiolar epithelium. <<

The details of the necropsy on three of the tigers that died at the Sri Racha tiger zoo in Thailand last fall provide evidence for infection in multiple organs.  This includes neurological signs of infection and hemorrhaging similar to infections of patients during the flu pandemic of 1918. 

The details of the infections and treatments were consistent with media reports last fall that indicated the number of tigers initially infected was small, but the virus spread in spite of prophylactic treatment using a double dose of Tamiflu, and frequent euthanasia of infected animals.  Eventually 147 tigers died or were euthanized, decimating the group of tigers that were exposed to the virus.  The details clearly show that the later spread was tiger-to-tiger, and intense efforts to limit the spread failed.

The sequence of the genes from these tigers indicated that they were virtually identical to isolates from leapards and tigers that died in an adjacent zoo at the beginning of 2004.  Moreover, the genes were closely related to sequences from the mother of the index case in the human-to-human bird flu cluster described previously in the New England Journal of Medicine.  Sequences from all eight genes of the earlier tiger and leopard have been published, and 6 of the 8 genes of the more recent isolates have been placed on deposit at Genbank.  All are closely related to each other and contain no reassorted human genes.

These genes are also closely related to genes from isolates from patients and birds in Vietnam, indicating that under certain circumstances the virus can be readily transmitted from mammal to mammal (tiger-to-tiger in the zoo and similar efficiencies for feline-to-feline in a lab setting), while maintaining a very high case fatality rate.

These data provide yet another signal that H5N1 in Asia is a significant pandemic threat, and can infect multiple organs that may alter the clinical presentation in infected patients.

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