Histopathological Analysis of Surviving Mallards Infected with H5 Subtype Clade 2.3.4.4b High Pathogenicity Avian Influenza Viruses

High pathogenicity avian influenza (HPAI) viruses of clade 2.3.4.4b have caused outbreaks worldwide, affecting both wild and domestic birds, as well as occasionally mammals. Mallards (Anas platyrhynchos), the natural hosts of influenza A viruses, are major migratory birds in Japan and strong contributors to the transmission and maintenance of the viruses. To further understand the pathological consequences and potential for viral persistence, histopathological examinations were conducted on mallards that survived 14 days post-inoculation with H5N1 and H5N8 clade 2.3.4.4b HPAI isolates. Five of the ten mallards that underwent autopsy exhibited multifocal encephalitis of variable severity. Two showed severe encephalomalacia and calcifications, one of which also had persistent viral antigens within the necrotic foci. Furthermore, marked atrophy of the lymphoid tissues, particularly the thymus, was observed and appeared to correlate with the severity of encephalitis. These findings indicate that residual encephalitis and lymphoid depletion can persist despite resolution of the infection, suggesting potentially lasting health effects in mallards following HPAI viral infection. Notably, some mallards showed no histological lesions, indicating their potential as viral carriers.