Why Cambodia’s H5N1 reassortant virus needs close monitoring

• Cambodia experienced a sudden surge in H5N1 cases in humans, with 16 cases reported between February 2023 and August 2024.
• 14 cases were caused by a novel mixing or reassortment of A/H5N1 virus, resulting from the mixing of gene segments from clade 2.3.2.1c known to circulate in Southeast Asia with the newer 2.3.4.4b clade that has spread globally.
• Three human cases were in contact with sick poultry or bird droppings, and three deaths have been reported.
• A detailed genetic analysis of the novel H5N1 reassortant was published by the Pasteur Institute in Cambodia, providing new details on the spillover timeline and emphasizing the need for stepped-up surveillance.
• The reassortment likely facilitated by high-density poultry farming, wild bird migration, and cross-border poultry trade in Southeast Asia.
• After the emergence of the novel reassortant genotype, the clade 2.3.2.1c is no longer in circulation in Cambodian poultry.
• Hemagglutinin (HA) sequences from both humans and poultry in Cambodia displayed significant divergence from earlier Cambodia strains since October 2023.
• The presence of certain amino acid mutations in both human and poultry viruses in the gene segment of 2.3.4.4b suggests enhanced capacity for mammalian infection.
• Further risk assessment in silico, ex vivo, in vivo, and in vitro is critical to better understand the zoonotic risk that these viruses pose.