Case summary: A 4.5-year-old male castrated, predominantly indoor-housed domestic shorthair cat presented with lethargy, anorexia and fever, progressing rapidly to severe respiratory distress and neurologic dysfunction. Clinical evaluation and advanced diagnostics revealed widespread systemic disease involving the lower respiratory tract, nervous and hepatic systems. Despite aggressive supportive care, including intravenous fluids, antiemetics and non-steroidal anti-inflammatory drugs, the cat´s condition deteriorated, necessitating humane euthanasia. Post-mortem gross findings included consolidated lungs with peribronchiolar pallor, multifocal to coalescing hepatic hemorrhage and multifocal gastrointestinal ulcerations. Histopathologic examination revealed necrotizing and neutrophilic meningoencephalitis and fibrinonecrotizing bronchointerstitial pneumonia alongside necrotizing lesions in the vascular, hepatic, lymphoid, pancreatic and gastrointestinal tissues. Influenza A/H5 subtype (highly pathogenic avian influenza) was confirmed in the brain and pulmonary tissues using real-time RT-PCR. Rabies was excluded via negative indirect fluorescent antibody test performed on brain tissue. Feline calicivirus and feline herpesvirus-1 were not detected in the lung tissues via RT-PCR. No other organisms were observed in tissues by microscopy after histochemical staining.

Relevance and novel information: This case documents highly pathogenic avian influenza infection in a domestic shorthair cat with minimal known outdoor access, confirmed by real-time RT-PCR in both lung and brain tissues. Low cycle threshold values indicated exceptionally high viral loads and pronounced neurotropism. The rapid onset of necrotizing meningoencephalitis and severe bronchointerstitial pneumonia, concurrent with low cycle threshold values, highlights the relationship between high tissue viral burden and fulminant multisystemic pathology. This case expands the current understanding of feline exposure risk by supporting the possibility of indirect environmental contamination or involvement of unrecognized transport hosts.