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H5N6 risk assessment
There are at least 2 different lineages of highly pathogenic avian influenza (HPAI) A(H5N6) circulating in poultry. The Asian lineage strains of HPAI H5N6 have been responsible for outbreaks in poultry in China and South East Asia since 2014 and are associated with severe human disease.
During 2017, a second lineage of HPAI H5N6, a reassortant of H5N8 was identified in birds in Korea, Japan and across Europe. The reassortant strain is considered unrelated to the Asian lineage and has not been associated with human cases. The World Organisation for Animal Health (OIE)/Food and Agriculture Organisation for Avian Influenza at the Animal and Plant Health Agency has conducted a detailed genetic analysis of a small number of H5N6 HPAI viruses detected in both Europe and Asia. The reassortant strains can be differentiated from those strains associated with zoonotic infection in Asia. Previous follow-up of humans exposed to this reassortant lineage has not identified any symptomatic individuals; therefore, the rest of this risk assessment focuses on the Asian lineage which has been associated with human infections.
Epidemiology in birds and humans
Asian lineage H5N6
Since 2014, HPAI A(H5N6) has been responsible for widespread outbreaks in birds across China, Japan and South East Asia and in 2018 significant outbreaks have been reported from Mainland China, Japan, South Korea, Taiwan, Hong Kong and Vietnam. The Philippines has also reported H5N6 in poultry. The virus is highly pathogenic in birds and has been isolated from both poultry and wild birds.
In April 2014, the World Health Organization (WHO) first reported a case of human infection with avian influenza A(H5N6) from China. As of 3 November 2021, a total of 50 human cases of infection with avian influenza A(H5N6) have been reported internationally and at least 25 cases were fatal. Apart from one case in Laos, all cases have occurred in mainland China. Seven of these cases were in children and the remaining 43 were adult cases.
The majority of human cases of HPAI A(H5N6) in mainland China are known to have had contact with birds or their environments or exposure to suspected contaminated meat prior to becoming ill, and there is currently no evidence of human-to-human transmission. WHO considers that the H5 avian influenza viruses have not acquired the ability to transmit easily among humans and therefore the risk of sustained human-to-human transmission is low at present.
Asian lineage H5N6
The potential risk to human health from Asian lineage HPAI A(H5N6) relates to:
- lack of population immunity to H5 haemagglutinin (HA). The emergence of this virus involved the evolution of the H5 HA of highly pathogenic avian influenza (HPAI) A(H5N1) viruses, for which it is known that there is little population immunity to the HA
- neuraminidase immunity may contribute to protection but there is likely to be little population immunity to the N6 neuraminidase subtype
- the internal genes of this virus are derived from the progenitor of the A(H5N1) virus and include sequence correlates of mammalian adaptation and virulence
Furthermore, the internal genes of A(H5N1) viruses have frequently become re-assorted with other subtypes of avian influenza viruses since the emergence of A(H5N1) and the internal gene cassette of influenza A(H5N6) has the potential to support recombination events to produce viruses which are even more suited to adaptation and transmission in humans.
Asian lineage H5N6
Areas of the world affected by the Asian lineage of avian influenza A(H5N6) include China and anywhere with outbreaks within the last 12 months:
- the risk of influenza A(H5N6) infection to UK residents within the UK is very low
- the risk of influenza A(H5N6) infection to UK residents who are travelling to China or affected areas with confirmed outbreaks and incidents in avian species is low
- the level of risk of influenza A(H5N6) infection in those who arrive in the UK from China or affected areas and meet the case definition for novel avian influenza infection is low but warrants testing
- the probability that a cluster of cases of severe respiratory illness in the UK is due to influenza A(H5N6) is very low, but warrants testing – a history of travel to China or other affected areas and close contact with either avian species or a confirmed human case, or a history of direct exposure to a confirmed H5N6 incident in avian species in the UK, would increase the likelihood of influenza A(H5N6)
- if there is good compliance with guidance on infection control measures, the risk to healthcare workers caring for cases of influenza A(H5N6) in the UK is very low; however, new febrile or respiratory illness in healthcare workers caring for cases of influenza A(H5N6) requires testing
- the risk to contacts of laboratory confirmed human or avian cases of influenza A(H5N6) infection is low but warrants follow-up in the 10 days following exposure and urgent investigation of any new febrile or respiratory illness
No specific restrictions are advised for most people. However, people who are undergoing public health follow-up following a confirmed exposure to H5N6 are advised not to travel for the purposes of ensuring rapid access to care and investigations.
To help reduce the risk of infection, the National Travel Health Network and Centre (NaTHNaC) advised travellers visiting China or other areas affected by the Asian lineage of H5N6 to:
- avoid close or direct contact with live poultry
- avoid visiting live bird and animal markets (including ‘wet’ markets) and poultry farms
- avoid contact with surfaces contaminated with animal faeces
- avoid untreated bird feathers and other animal and bird waste
- do not eat or handle undercooked or raw poultry, egg or duck dishes
- do not pick up or touch dead or dying birds
- do not attempt to bring any poultry products back to the UK
- maintain good personal hygiene with regular hand washing with soap
- use alcohol-based hand rubs
Travellers to China or other affected areas should be alert to the development of signs and symptoms of influenza for 10 days following their return. It is most likely that anyone developing a mild respiratory tract illness during this time is suffering from seasonal influenza or some other commonly circulating respiratory infection. However, if they become concerned about the severity of their symptoms, they should seek appropriate medical advice and inform the treating clinician of their travel history.
Advice for clinicians and health professionals
Clinicians should retain a high level of suspicion of influenza A(H5N6) when managing patients with:
- suspected influenza or confirmed Influenza A (unsubtyped) or
- confirmed influenza A (unsubtypable as seasonal H3 or H1N1 pdm09)
And one of the following:
- a history of travel to China or one of the affected areas and contact with avian species in the 10 days before symptom onset
- a history of travel to China or one of the affected areas and contact with a confirmed human case of influenza A(H5N6) or a human case of severe unexplained respiratory illness resulting in death, in the last 10 days before symptom onset
- any history of exposure to a laboratory confirmed H5N6 incident in avian species
Clinicians should also remember to consider testing for influenza A(H5N1) and influenza A(H7N9) in patients with an appropriate similar travel history. Clinicians should also remember to consider testing for other avian influenza viruses in patients with an appropriate similar travel history.
Guidance on the public health management of possible human cases of novel avian influenza and their contacts is available online.
The local UK Health Security Agency (UKHSA) Public Health Laboratory can provide advice on arranging testing for possible cases of influenza A due to H5/H7.