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Starting in February of 2023, Cambodia began reporting human infections from an older clade (2.3.2.1c) of the H5N1 virus, one which had not spilled over into humans there since 2014.
The map above shows that at least 16 cases have been identified since - mostly among children and adolescents - with nearly a 40% fatality rate.
While the exact reasons behind this uptick in cases isn't known, last April in - FAO Statement On Reassortment Between H5N1 Clade 2.3.4.4b & Clade 2.3.2.1c Viruses In Mekong Delta Region - we learned that a new genotype - made up of this older clade and the current 2.3.4.4b clade of H5N1 - had emerged in Southeast Asia.
In Asia, several clades continue to circulate, including A(H5N1) 2.3.4.4b, 2.3.2.1c and others, which can lead to reassortment and the appearance of viruses with new characteristics. A novel reassortant influenza A(H5N1) virus has been detected across the Greater Mekong Subregion (GMS), causing infections in both humans and poultry since mid- 2022.
This virus has recently caused human outbreaks in Cambodia early this year. This virus contains the surface proteins from clade 2.3.2.1c that has circulated locally, but internal genes from a more recent clade 2.3.4.4b virus.
The introduction and widespread circulation of this reassortant influenza A(H5N1) virus into the GMS poses a significant risk to both animal and human health, given the historical impact of HPAI outbreaks in the region. Further, this reassortment event indicates not only the adaptive capacity of the virus but also the ever-present risk of the emergence of new, potentially more virulent strains.
While most texts continue to refer to the Cambodian cases simply as clade 2.3.2.1c, the acquisition of the internal genes from clade 2.3.4.4b adds a new layer of uncertainty. How this affects this virus - both in humans and in other hosts - is largely unknown.
Yesterday the WHO published their first major update on Cambodia since last winter, detailing the latest case, and discussing this new reassortment. Due to its length, I've only posted some excerpts, including their Risk Assessment.
I'll return with more after the break.
Avian Influenza A(H5N1) - Cambodia
2 September 2024
Situation at a glance
On 20 August 2024, the World Health Organization (WHO) was notified by the country’s International Health Regulations (IHR) National Focal Point (NFP) of a laboratory-confirmed case of human infection with avian influenza A(H5N1) virus (clade 2.3.2.1c) in a 15-year-old child in the Kingdom of Cambodia. This case is one of 10 human cases of influenza A(H5N1) infection reported in Cambodia in 2024. From 2003 to the present, 72 cases of human infection with influenza A(H5N1), including 43 deaths (case fatality ratio [CFR] of 59.7%), have been reported in the country. According to the IHR (2005), 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.
Description of the situation
On 20 August 2024, the IHR NFP of the Kingdom of Cambodia notified WHO of one case of human infection with influenza A(H5N1) in a 15-year-old with no underlying medical conditions, from Prey Veng Province. The child had an onset of fever on 11 August 2024. On 17 August, the patient was hospitalized in Phnom Penh at a severe acute respiratory infection (SARI) sentinel site. On admission, the patient presented with a fever, cough, sore throat, and difficulty breathing, and on the same day, treatment with oseltamivir was initiated. Nasopharyngeal and oropharyngeal swab specimens were collected on 17 August, and the patient died on 20 August.
Swab specimens collected on 17 August arrived at the National Institute of Public Health of Cambodia on 19 August and tested positive for influenza A(H5N1) by quantitative reverse transcription polymerase chain reaction (RT-qPCR) on 20 August. The results were confirmed by the Institut Pasteur du Cambodge (IPC) the same day. The sample was successfully sequenced, and phylogenetic analysis of the haemagglutinin (HA) gene showed the virus to be H5 clade 2.3.2.1c, similar to the viruses circulating in Cambodia and Southeast Asia since 2013-2014. However, its internal genes belong to H5 clade 2.3.4.4b viruses. This novel reassortant influenza A(H5N1) virus has been detected in human cases reported in Cambodia since late 2023.
According to early investigations, there were reports of dead poultry in the village about five days before the patient’s onset of illness. The patient's family was given some of these chickens for consumption and the girl was exposed to the chicken while preparing food.
The Cambodian Communicable Disease and Control Department (CDC), Ministry of Health, and local Rapid Response Team conducted further investigations. Six close contacts were identified, and oseltamivir was provided to them. All close contacts are being monitored and are asymptomatic. Further investigations and response measures are ongoing for public and animal health and the environment. Test results for samples collected from chickens and ducks from the village are pending.
Avian influenza A(H5N1) was detected for the first time in Cambodia in December 2003, initially affecting wild birds. From then until 2014, sporadic human cases were reported due to transmission from poultry to humans, either directly or indirectly through contaminated environments. 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; six cases were reported that year. This case is one of 10 human cases of influenza A(H5N1) infection reported in Cambodia in 2024. Two of the 10 cases were fatal, and nine involved persons under 18 years of age. From 2003 to the present, 72 cases of human infection with influenza A(H5N1), including 43 deaths (CFR 59.7%), have been reported in the country.
WHO risk assessment
From 2003 to 20 August 2024, a total of 903 human cases of infection of influenza A(H5N1) have been reported globally to WHO from 24 countries, including this case. Almost all cases of human infection with avian influenza A(H5N1) have been linked to close contact with A(H5N1)-infected live or dead birds or mammals, or contaminated environments.
Available epidemiological and virological evidence suggests that A(H5N1) viruses have not acquired the capacity for sustained transmission among humans. Therefore, the likelihood of sustained human-to-human spread is low at present. Since the virus continues to circulate in poultry, particularly in rural areas in Cambodia, further sporadic human cases can be expected.
Currently, based on available information, WHO assesses the overall public health risk posed by this virus to be low. 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 poultry populations, and serological investigations are critical to assess associated risks to public health and promptly adjust risk management measures.
Vaccines against seasonal influenza viruses will not protect humans against infections with influenza A(H5N1) viruses. Candidate vaccines to prevent influenza A(H5) infection in humans have been developed for pandemic preparedness in some countries. WHO continues to update the list of zoonotic influenza candidate vaccine viruses (CVV), which are selected twice a year at the WHO consultation on influenza virus vaccine composition. The list of such CVVs is available on the WHO website, at the reference below. In addition, the genetic and antigenic characterization of contemporary zoonotic influenza viruses is published here.
Today's report is another reminder that the H5N1 virus continues to evolve in unpredictable ways, and that anything we say about its capabilities, or threat level today, is subject to change over time.
While it isn't at all clear how much of a threat this new reassorted virus poses, each new evolutionary change serves as a bridge to the next. A process that over time, could eventually lead to a more dangerous virus (or if we get lucky, its attenuation).
While details were not provided, the WHO state this latest (fatal) case in Cambodia `. . . was exposed to the chicken while preparing food'. A scenario which we've seen a number of times before.
As we've discussed previously (see Mixed Messaging On HPAI Food Safety), there does appears to be some risk entailed in the preparation of raw poultry. PAHO (the Pan-American Health Organization) mentions this on their Avian Influenza landing page:While we see assurances from the USDA and other agencies that `Avian influenza is not transmissible by eating properly prepared poultry, so properly prepared and cooked poultry and eggs are safe to eat.' - there is a catch.
Transmission
The most common way for the virus to enter a territory is through migratory wild birds. The main risk factor for transmission from birds to humans is direct or indirect contact with infected animals or with environments and surfaces contaminated by feces. Plucking, handling infected poultry carcasses, and preparing poultry for consumption, especially in domestic settings, may also be risk factors.
And just week the WHO published Interim Guidance to Reduce the Risk of Infection in People Exposed to Avian Influenza Viruses, which lists a number of `risk factors', including:
- keep live poultry in their backyards or homes, or who purchase live birds at markets;
- slaughter, de-feather and/or butcher poultry or other animals at home;
Although it gets mentioned, far more attention needs to be paid to safe food handling practices in this time of HPAI. Unfortunately, very little is published specifically about H5N1 safety during food preparation, with links usually to generic `safe poultry handling' advice.
- handle and prepare raw poultry for further cooking and consumption;
