#18,783
Overnight the WHO published an updated DON (Disease Outbreak News) report on the uptick in human H5N1 cases in Cambodia over the first half of 2025.
This update only includes 11 of the 12 cases we've seen reported this year (#12, is reportedly a toddler from Takeo Province), but they note the unusual rise in cases during the month of June.
While the same subtype, the H5N1 virus in Cambodia is an older, and more virulent, strain (clade 2.3.2.1.e) that the HPAI H5 virus currently circulating in much of the rest of the world (clade 2.3.4.4b).
Influenza viruses evolve primarily through abrupt reassortment and much slower antigenic drift. A little over a year ago we learned that this older clade had reassorted with the newer clade 2.3.4.4b virus in late 2023.
This reassortment was recently reclassified as clade 2.3.2.1e (see WHO: Influenza at the Human-Animal Interface Report - Identifies New H5 Clade 2.3.2.1e Infections in Cambodia & Vietnam).
Although much of what is included in today's report is information we've seen previously, it provides an excellent overview of the outbreak in Cambodia over the past 6 months.
Due to its length, I've only reproduced part of this report, including the risk assessment. Follow the link to read it in its entirety. I'll have more after the break.
Disease Outbreak News
Avian Influenza A(H5N1) - Cambodia
5 July 2025
Situation at a glance
Between 1 January and 1 July 2025, the World Health Organization (WHO) was notified by Cambodia’s International Health Regulations (IHR) National Focal Point (NFP) of 11 laboratory-confirmed cases of human infection with avian influenza A(H5N1) virus. Seven of the 11 cases were reported in June, an unusual monthly increase. Avian influenza A(H5N1) was first detected in Cambodia, in December 2003, initially affecting wild birds. Since then, 83 cases of human infection with influenza A(H5N1), including 49 deaths (case fatality ratio [CFR] of 59%), have been reported in the country.
While the virus continued to circulate in avian species, no human cases were reported between 2014 and 2022, after which, the virus re-emerged in humans in February 2023. Since the re-emergence of human A(H5N1) infections in Cambodia in 2023, a total of 27 cases have been reported (six in 2023, 10 in 2024, and 11 to date in 2025), of which 12 were fatal (CFR 44%).
Seventeen of the cases occurred in children under 18 years old. Avian influenza A(H5N1) is circulating in wild birds, poultry and some mammals around the world, and occasional human infections following exposure to infected animals or contaminated environments are expected to occur. In cases detected in Cambodia, exposure to sick poultry, often poultry kept in backyards, has been reported.
According to the IHR, a human infection caused by a novel influenza A virus subtype is an event that has the potential for high public health impact and must be notified to the WHO. Based on currently available information, WHO assesses the current risk to the general population posed by this virus as low. For those occupationally exposed to the virus, such as farm workers, the risk is low to moderate, depending on the measures in place. WHO routinely reassesses this risk to factor in new information.
Description of the situation
Between 1 January and 1 July 2025, the National IHR Focal Point (NFP) of the Kingdom of Cambodia notified WHO of 11 laboratory-confirmed case of human infection with avian influenza A(H5N1) virus (clade 2.3.2.1e- formerly classified as 2.3.2.1c; from cases where virus sequences are available to date) including six deaths [CFR: 54%]. These cases are reported from the provinces of Siem Reap (4), Takeo (2), Kampong Cham (1), Kampong Speu (1), Kratie (1), Prey Veng (1), Svay Rieng (1). Of the total cases reported in 2025, seven cases were reported in June 2025.
Males account for 63% of the cases. Of the 11 cases, three cases were reported in less than five-year-olds, two cases were between the age of 5 and 18 years and six cases were reported in the age group 18-65 years. All cases had exposure – handling or culling - of sick poultry, often kept in backyards.
Avian influenza A(H5N1) was detected for the first time in Cambodia in December 2003, initially affecting wild birds. Between 2014 and 2022, there were no reports of human infection with A(H5N1) viruses. However, the re-emergence of human infections with A(H5N1) viruses in Cambodia was reported in February 2023.
Since this re-emergence, Cambodia has reported 27 cases of laboratory confirmed human infection with avian influenza A(H5N1) including 12 fatalities (CFR 44%). The cases have been reported from eight provinces: Kampong Cham (1), Kampong Speu (1), Kampot (3), Kratie (3), Prey Veng (6), Svay Rieng (4), Siem Reap (5), Takeo (4).
Figure 1: Epicurve of Avian Influenza A (H5N1) cases reported in Cambodia by year from 2003- 1 July 2025
(SNIP)
WHO risk assessment
From 2003 to 1 July 2025, a total of 986 human cases of infection of influenza A(H5N1) have been reported globally to WHO from 25 countries, including this case. Almost all of these have been linked to close contact with A(H5N1) infected live or dead birds or mammals, or contaminated environments. Human infection can cause severe disease with a high mortality rate: of the 986 infections reported globally, there have been 473 deaths (CFR 48%).
In this event, cases have been reported from seven provinces in 2025. All cases have reported direct exposure to sick/dead poultry.
While human-to-human transmission cannot be ruled out, the more likely source of exposure of these cases is infected poultry of contaminated environment.
Based on information available at this time, the overall public health risk from currently known influenza viruses circulating at the human-animal interface has not changed and remains low. For those occupationally exposed to the virus, such as farm workers, the risk is low to moderate, depending on the measures in place. Additional cases in persons with exposure to sick/dead poultry is to be expected. The occurrence of sustained human-to-human transmission in this event based on currently available information is currently considered unlikely. This can, however, change and the risk assessment will be reviewed as needed if additional information becomes available.
Close analysis of the epidemiological situation, further characterization of the most recent influenza A(H5N1) viruses in both human and animal populations, and serological investigations are critical to update associated risk assessments for public health and promptly adjust risk management measures.
Current seasonal influenza vaccines are unlikely to protect humans against infections with influenza A(H5N1) viruses. Vaccines against influenza A(H5) infection in humans have been developed and licensed in some countries. WHO continues to update the list of zoonotic influenza candidate vaccine viruses (CVVs), which are selected twice a year at the WHO consultation on influenza virus vaccine composition, and on an ad hoc basis as needed. The list of such CVVs is available on the WHO website, see reference below. In addition, the genetic and antigenic characterization of contemporary animal and zoonotic influenza viruses are published here. This risk assessment will be reviewed as needed if additional information becomes available.
If there is one constant with influenza viruses, it is their ability to continually change and evolve. An essential trait for a virus that leaves behind a degree post-infection immunity, otherwise it would quickly run out of susceptible hosts.
Sometimes change comes gradually, through a process called antigenic drift. Drift is the standard evolutionary process of influenza viruses, and comes about due to replication errors that are common with single-strand RNA viruses (see NIAID Video: Antigenic Drift).
These evolutionary changes can either increase or decrease the fitness, transmissibility, host range, or virulence of a virus. Evolution is not a linear process, and thankfully most reassortments end up as evolutionary dead ends.
But we find ourselves - nearly 30 years after the first detection of an H5 A/Goose/Guangdong/1/1996 (gs/GD) lineage in China - in a world where H5's descendants have not only flourished, they have diversified into dozens of clades and subclades (many now extinct), and hundreds of genotypes, across multiple subtypes.
Early, Rapid Diversification of H5Nx
A virus that was once confined to small patch of Southeast China has spread successfully to nearly every continent, and now threatens humans, wildlife, and livestock around the globe (see Nature Reviews: The Threat of Avian Influenza H5N1 Looms Over Global Biodiversity).
Granted, we've looked into the H5Nx abyss before, only to see the virus suddenly lose momentum. And that could certainly happen again - but as its viral diversity increases - the impact of any single negative reassortment likely diminishes.
While we could easily be blindsided by something else percolating in the wild outside of our view - if pedigree, longevity, and past performance are worthwhile indicators - the threat posed by H5Nx is one that we simply can't afford to ignore.
