#18,937
Not quite 3 years ago (Feb 2023), a long-dormant strain of HPAI H5 (clade 2.3.2.1c) began to spillover again into humans in Cambodia after a 9 year absence. Since then, 33 cases have been confirmed, with nearly half of those proving fatal.
In contrast to the newer clade 2.3.4.4b viruses - which currently circulate across most of the globe - these older clades appear to produce more severe illness in humans.
In April of 2024, the FAO released a statement on the Reassortment Between H5N1 Clade 2.3.4.4b & Clade 2.3.2.1c Viruses In Mekong Delta Region, which was later redesignated by the WHO as New H5 Clade 2.3.2.1e Infections in Cambodia & Vietnam.
So far, clade 2.3.2.1e has only been detected in Cambodia and Vietnam, but today we learn of a similar reassortment - between a clade 2.3.2.1a and clade 2.3.4.4b in Nepal - which has produced another hybrid virus.
While these two hybrids are different, they came via the same process; whereby an older, nearly extinct clade reassorts with the newer, 2.3.4.4b clade.
While we've not seen the same surge in human cases in Nepal, this new reassortant reportedly has `. . . a high identity with 2.3.2.1a clade viruses identified in humans and cats in India in 2024–2025'.This reports notes several secondary mammalian-adaptation markers of interest in the reassortant virus (e.g., PB2 L89V, M1 N30D/T215A, NS1 P42S/D92E, HA V226I), but none fall into the `red flag' category (e.g. PB2 E627K/D701N, HA Q226L/G228S, etc.).
I've posted the abstract, and some excerpts below, but you'll want to follow the link to read it in its entirety. I'll have a brief postscript after the break.
Zoonotic Implications of the Co-Circulation of Clade 2.3.4.4b and 2.3.2.1a H5N1 Avian Influenza Viruses in Nepal in 2023
Pragya Koirala 1, Manju Maharjan 2, Sharmila Chapagain 3, Barun K. Sharma 1,
Tirumala B. K. Settypalli 4, Charles E. Lamien 4 and William G. Dundon 4,*
Viruses 2025, 17(11), 1481; https://doi.org/10.3390/v17111481
Abstract
Samples collected from two avian influenza outbreaks in Bagmati Province in central Nepal between January and March 2023 were positive for H5N1. Full genomes were generated for both viruses, which revealed that one of the viruses was very similar to clade 2.3.4.4b H5N1 identified in Bangladesh in 2021/2022.
The second virus was a reassortant H5N1 virus consisting of four genes (HA, NA, NP, and M) originating from a clade 2.3.2.1a H5N1 and the remaining four genes (NS, PB1, PB2, and PA) originating from a 2.3.4.4b H5N1. Notably, this second virus had a high identity with 2.3.2.1a clade viruses identified in humans and cats in India in 2024–2025.
These are the first full genome sequences of H5N1 avian influenza viruses from Nepal and given the recent human infections by 2.3.2.1a H5N1 viruses in the region, these data will be of interest to both public health and veterinary authorities.
Results and Discussion
Epidemiological investigations identified two primary transmission routes of the viruses into the farms. The predominant route most likely involved indirect transmission via fomites, such as contaminated vehicles, feed, equipment, and human activity, which facilitated the spread of the virus into and between farms. A second potential transmission pathway was through contact with wild birds, which are known natural reservoirs of HPAI viruses. Nepal is a part of the Central Asian Flyway, which overlaps with the East Asian–Australasian Flyway that covers much of eastern Asia.
(SNIP)
Since its arrival in North and South America in 2022, clade 2.3.4.4b H5N1 viruses have now become the dominant subtype globally [15]. Recently, clade 2.3.4.4b viruses have been identified in Bangladesh and India [16,17]. The first clade 2.3.4.4b identified by Barman et al. (2023) in Bangladesh in 2021, and now referred to as genotype BD-1, was similar to H5N1 clade 2.3.4.4b viruses from Europe [16,18].
The authors conducted further surveillance and characterization in Bangladesh between January 2022 and November 2023 and identified three additional genotypes of clade 2.3.4.4b viruses (BD-2, BD-3, and BD-4), highlighting the diverse and dynamic nature of viruses in the region [18]. From the BLAST and phylogenetic analysis of A/chicken/Nepal/A146_079_80/2023, it was revealed that this virus belonged to the original genotype BD-1 identified in Bangladesh in 2021 (Supplementary file Figure S1).
In conclusion, the current study has identified both a clade 2.3.4.4b and a clade 2.3.2.1a/2.3.4.4b reassortant virus (Figure 3) in Nepal for the first time.
The clade 2.3.2.1a/2.3.4.4b reassortant virus was highly similar to viruses that have caused recent human fatalities in India, and so, these findings should encourage Nepalese authorities to increase surveillance and molecular characterization of AIVs present in their country. The study should also encourage further studies in order to better understand the impact of circulating avian influenza viruses and their zoonotic potential.
There are some limitations in this report, including:
- This study analyzed only two poultry isolates - taken from two different farms roughly 10 km apart in early 2023 - which tells us very little about prevalence or spread of variants the region.
- No phenotypic or antigenic testing was performed, so any mutation effects are inferred from past findings, not demonstrated with this reassort ant.
