First detected in chickens in Scotland in 1959, H5N1–avian influenza, or bird flu – is a type of avian influenza A virus that causes a highly infectious and severe respiratory disease in birds (Mahase, 2023a). According to the US Centers for Disease Control and Prevention (CDC, 2022), influenza A viruses are divided into subtypes based on two glycoproteins on the surface of the virus: hemagglutinin (H) and neuraminidase (N). There are 18 different hemagglutinin subtypes and 11 different neuraminidase subtypes, which can be further broken down into different genetic ‘clades’ based on the similarity of their gene sequences.
Avian influenza and poultry
Highly pathogenic avian influenza (HPAI) type A (H5N1) infections during the 2021–2022 epidemiological year have been the largest in European history, involving 37 countries; 2520 HPAI outbreaks in poultry resulting in 50 million dead or culled birds in affected establishments; 227 detections in captive birds; and 3867 detections in wild birds (Adlhock et al, 2023). Further, the high infection pressure due to the continuous circulation of H5N1 ‘in the wild reservoir has led to frequent introductions of the virus into poultry populations across Europe’ (Adlhock et al, 2023).
And as Sun et al (2023) explain, whereas the COVID-19 pandemic has been associated with a notable decrease in seasonal human influenza infections worldwide compared to previous flu seasons, ‘in contrast, the risk of avian influenza infections has increased during the COVID-19 pandemic.’ In addition, ‘the spread and outbreaks of [avian influenza] have increased due to global trade, poultry production, climate change, bird migration, human movement, and an increasing global population’ (Sun et al, 2023).
Avian influenza and humans
The first report of human infection with lethal avian influenza H5N1 was in 1997 in Hong Kong, causing the deaths of 6 of 18 infected people (Shi et al, 2023). And according to the World Health Organization (WHO, 2023), ‘whenever avian influenza viruses are circulating in poultry, there is a risk for sporadic infection or small clusters of human cases due to exposure to infected poultry or contaminated environments.’ Thus, between 2003 and 25 February 2023, 873 human cases of infection with avian influenza H5N1 and 458 deaths have been reported from 21 countries worldwide (WHO, 2023).
Following the recent death of an 11-year-old girl in southern Cambodia, who died after infection with avian influenza A, genome sequencing revealed that she had died from an H5N1 subtype with a clade designated 2.3.2.1c, different to the clade 2.3.4.4b causing mass deaths in wild and domestic birds globally (Mallapaty, 2023). The H5N1 subtype clade 2.3.2.1c is an endemic strain in the southern Cambodia region and has been detected intermittently in poultry in Cambodia since 2013, including in chickens found at live bird markets (Mallapaty, 2023).
Has human-to-human transmission of H5N1 occurred?
That is one of the questions asked by Mahase (2023b), who states that following the death of the 11-year-old in southern Cambodia from H5N1 (Mallapaty, 2023), ‘of the girl's 12 close contacts who were identified (four with symptoms, eight without), only one, the girl's father, tested positive for H5N1.’
Can we infer, therefore, that human-to-human transmission has occurred? It appears not, with Mahase (2023b) citing a WHO update explaining that ‘while further characterisation of the virus from these human cases is pending, available epidemiological and virological evidence suggests that current A(H5) viruses have not acquired the ability of sustained transmission among humans, thus the likelihood of sustained human-to-human spread is low.’
But if avian influenza H5N1 has been circulating among bird and poultry populations over many years, why is there such concern at this time? It seems, according to Mahase (2023b), that the current circulating clade, 2.3.4.4b, appears to be not only better adapted to infecting wild birds, but is also able to spread in parts of the world and during times of the year not seen before. For example, ten South American countries have recorded their first ever cases, with Argentina and Uruguay declaring national health emergencies; some 55 000 wild birds in Peru have died in coastal nature reserves; and in October 2022 H5N1 was detected in a Spanish mink farm (Mahase, 2023b). However, ‘workers of [sic] the mink farm have been tested and no detection of avian influenza virus in humans related to this outbreak in mink has been identified’ (Adlhock et al, 2023).
Avian influenza risk to humans, treatments, and vaccine prospects
According to Adhlock et al (2023) ‘the risk of human transmission due to avian influenza viruses of the currently circulating clade 2.3.4.4b in Europe is assessed as low for the general population and low to moderate for people occupationally or otherwise HPAI virus exposed.’
‘As far as a human vaccine against H5N1 is concerned, although one is not yet available, WHO have a list of potential candidate vaccines against a range of influenza viruses considered to pose a risk to public health.’
As for treatment, Mahase (2023a) cites the chief medical officer in the CDC's influenza division, who advises ‘that people infected with avian influenza A virus should be treated as soon as possible with antiviral drugs that have been approved for treating seasonal flu. These include antiviral drugs such as oseltamivir, zanamivir, peramivir, and baloxavir.’
As far as a human vaccine against H5N1 is concerned, although one is not yet available, WHO have a list of potential candidate vaccines against a range of influenza viruses considered to pose a risk to public health, with Mahase (2023b) noting that ‘WHO has recently recommended that the candidate vaccine viruses for H5 be updated’, and she cites the head of virology at the UK's Animal and Plant Health Agency, who observed in February this year ‘that it would be “foolhardy to make a vaccine to H5 now” because it's not clear which strain, if any, would make the jump to humans.’
Finally
As Sun et al (2023) make clear, globally around 75% of zoonotic diseases and 60% of emerging infectious diseases are of animal origins, and ‘a range of emerging and re-emerging zoonotic infections significantly impact the lives of humans and animals, placing substantial economic burdens on social development.’ One of the lessons of the COVID-19 pandemic is that the microbial landscape is constantly changing, and in focussing our aim as the avian influenza threat evolves and changes, we similarly must be prepared to evolve and refine strategies … a perpetual challenge.