LATEBREAKER
Infectious Disease
A rapid review contrasting the evidence on avian influenza A(H5Nx) clades 2.3.4.4b and 2.3.2.1c in humans Tricia Corrin* Tricia Corrin Kaitlin Young Mavra Qamar Kusala Pussegoda Austyn Baumeister Nicole Atchessi Erin Leonard Lisa
Background: Avian influenza viruses (AIV) circulate in wild and domestic bird populations posing an on-going risk for zoonotic transmission and virus adaptation to mammals and humans. The A(H5Nx) clades 2.3.2.1c and 2.3.4.4b currently circulating caused sporadic infections in humans including six cases of A(H5N1) 2.3.2.1c in Cambodia, 13 cases of A(H5N1) 2.3.4.4b across eight countries, and 31 cases of A(H5N6), assumed to be clade 2.3.4.4b, in China, since January 2022-December 2023. A rapid review (RR) was conducted to contrast the evidence on A(H5Nx) clade 2.3.2.1c and 2.3.4.4b infection in humans.
Methods: Adhering to PRISMA guidelines a protocol a was developed a priori. The search was conducted in December 2023 for English or French primary research articles pertaining to AIV clades 2.3.4.4.b or 2.3.2.1c in Scopus, PubMed and EuropePMC to capture both published and preprint articles. Search verification and a grey literature search was also conducted in January 2024. Full-text relevance screening was conducted independently by two reviewers. Data extraction and risk of bias (ROB) assessment was conducted by one reviewer and verified by a senior reviewer. ROB was assessed using Joanna Briggs Institute critical appraisal checklists and the Newcastle Ottawa Scale depending on the study design. Results were reported narratively.
Results: Forty articles were included in this RR and were published between 2014 and 2023. Studies found no discernible difference in the likely mode of exposure, transmission, or the potential of AIV infection in humans between A(H5Nx) clades 2.3.4.4b and 2.3.2.1c. Seropositivity, seroconversion, and hospitalization rates were also similar for the two clades, while intensive care unit admission and fatalities were higher for A(H5Nx) clade 2.3.2.1c. Several markers of mammalian adaptation and mutations associated with increased viral replication, polymerase activity, and virulence in mammals and/or mice were found in both clades. Most studies were considered to be at high ROB due to their study design and poor reporting, some well-designed cohort studies were at moderate ROB.
Conclusion: This summary can be used to inform what is known about A(H5Nx) in humans for the two clades and suggests that there is on-going adaptation pressure from circulating AIVs that should be closely monitored. Due to the scarcity of studies for each outcome and the low level of evidence based on the study designs, the conclusions from this RR could change with future research. It is important to continue surveillance in birds, mammals, and humans, conduct large epidemiological studies, and develop mitigation strategies from a one health perspective.