Avian influenza spillover into mammals

Since late 2020, a strain of highly pathogenic avian influenza virus A(H5N1) clade 2.3.4.4b has been circulating globally, leading to more than 50 million dead wild birds and culled poultry. Concerningly, the virus has also started to be detected in mammals. Cases of H5N1 infection have been previously noted in species such as minks in Spain and dolphins in South America. More recently (June 2022), an outbreak of A(H5N1) virus infections was reported among harbour and grey seals in New England, USA, that was concurrent with a large number of avian infections in the region. The outbreak in the seal population, thought to have resulted from environmental transmission of shed virus, caused an unusual mortality event in a seal population. There was also evidence of mammalian adaptation of the virus in a few seals, indicating the potential for zoonotic spillover into other species and possibly including humans. With the world still grappling with the COVID-19 pandemic caused by the zoonotic spillover of a virus from animals to humans, concerns over the potential for another virus to take hold are understandable, and global health organisations are closely monitoring the current outbreak of avian influenza. However, although a substantially greater number of birds have died in the current wave than in previous outbreaks, there have so far been only a sporadic number of cases of avian influenza infection in people—ie, two cases of A(H5N1) were reported in 2023 in Cambodia, one of whom died; three cases of A(H3N8) infection in 2022 and 2023 in China, one of whom died; and a case of A(H5N1) clade 2.3.4.4b in Chile who is in intensive care receiving mechanical ventilation as of April 21, 2023. Overall, 874 human cases of avian influenza A(H5N1) have been reported in 23 countries since 2004 and 458 people have died—a case fatality rate of 52·4%. However, most human cases have been noted in individuals in close contact with infected birds, and the current risk of A(H5N1) virus transmission to humans is low. Timothy M Uyeki (Centers for Disease Control and Prevention, Atlanta, GA, USA) commented “To date, no genetic changes have been found in A(H5N1) viruses that have infected wild birds, poultry, or mammals to indicate that they can bind efficiently to receptors predominately found in the upper respiratory tract of humans, which would increase the risk of transmission to people.” He also noted that “No cases of human-to-human transmission of clade 2.3.4.4b A(H5N1) virus have been identified.” However, due to reports of nearly 900 sporadic cases of A(H5N1) infections in people over the past 20 years with a high case fatality rate and the continued evolution of A(H5N1) viruses as they circulate, vaccines are under development as part of pandemic influenza preparedness activities. Candidate vaccine viruses are developed and updated based on antigenic changes noted in A(H5N1) viruses that are circulating among birds and that have spilled over into mammals and caused sporadic human infections. Although a few A(H5N1) vaccines were licensed by the US Food and Drug Administration, these vaccines were developed against previously circulating clades and do not antigenically match the currently circulating clade 2.3.4.4b viruses. Uyeki said “A(H5N1) vaccines are poorly immunogenic, and clinical trials of A(H5N1) candidate vaccine viruses have shown that two doses with an adjuvant are needed to induce a sufficient immune response. [If] there were indications that a pandemic was imminent or had started (eg, sustained human-to-human transmission), efforts would be initiated immediately to develop candidate vaccine viruses against the specific pandemic influenza virus.” The continued genetic evolution of A(H5N1) viruses, including substitutions noted in PB2 from a bronchoalveolar lavage specimen from the Chilean patient that are likely to enhance replication in mammals, highlight the need for vigilance, ongoing surveillance, and preparedness regarding candidate vaccines. Uyeki commented “A(H5N1) viruses are not the only viruses of concern. Any human infection with a novel influenza A virus of animal origin that is antigenically distinct from seasonal influenza A viruses poses pandemic potential. Surveillance of influenza A viruses in animals and people worldwide is essential to inform pandemic preparedness and response.” As a general precaution during the current avian influenza outbreak, direct contact with birds and prolonged exposure to sources of the virus, including saliva, mucous, and faeces, should be avoided.