Avian influenza is a zoonosis that over the years has caused serious problems for animal health and the poultry industry involved. Its spread and the ‘species jump’, recorded in some dairy cattle and in rare cases also in humans, has led to the adoption of safety measures including, in the European Union, the purchase of vaccines for human use. In-depth study.
Avian Influenza, Background
Avian influenza (Avian Influenza, AI) is described by the European Centre for Disease Prevention and Control (ECDC) of the European Union as an infectious disease, caused by RNA viruses, which manifests itself mainly with respiratory signs and symptoms.
The infection mainly affects and spreads via wild waterfowl. Strains are distinguished into high pathogenicity (HPAI, i.e. A/H5, A/H7) and low pathogenicity (LPAI). Some of them have caused sporadic transmission events in humans. (1)
Spread in Europe
The avian influenza A(H5N1) virus, first identified in Southern China and Hong Kong, emerged in 1996 and proved capable of killing a high percentage of infected poultry.
Its spread in Europe, only sporadic in poultry and wild birds until 2021, has since caused the largest epidemics ever observed in these species (over 50 million birds, by 2022):
– 2014/2015. Identification of the A(H5N8) subtype in Europe. Following this, this and other subtypes spread in the various Member States to the point of triggering full-blown epidemics;
– 2016/2017. First identification of A(H5N8) in a wild bird in Hungary, then also in farms in 19 Member States. A(H5N6), in 2017, in poultry in Italy and Hungary;
– 2018. Low levels of A(H5N6) in Finland, Sweden, the Netherlands, Germany, Ireland, Slovakia, the UK and Denmark. H5N8 outbreaks in poultry in Bulgaria;
– 2019. Confirmation of A(H5N6) in wild birds, strongly related to viruses from previous years. Few outbreaks in poultry, concentrated in Bulgaria;
– 2020. Several outbreaks of A(H5N8) in flocks in Poland, Czech Republic, Germany, Slovakia, Romania and Hungary. Followed by widespread outbreaks of H5N5, H5N1 and H5N3 subtypes in wild birds, starting in the Netherlands;
– 2021. Significant improvement in the situation, with some outbreaks concentrated in the summer period among wild birds;
– 2022. H5N1 outbreaks in 25 EU Member States in wild birds, poultry and other captive birds. Wild seabirds were among the most affected, and it was difficult to take measures to contain the virus in poultry. Especially in France, Italy and Hungary where outbreaks were most numerous;
– 2023. Spread to 26 Member States, more outbreaks but less severity. The number of mammalian species identified with the virus, especially H5N1, increased with wild carnivores, fur-bearing animals, marine mammals and pets (albeit in very rare cases);
– 2023/2024. From Q2 2023 the situation improved, but a new epidemic season started in October 2023 with new introductions of the HPAI virus by migratory wild birds (common cranes were the most affected species). (2)
Cases of human infection
ECDC reports that transmission of the A(H5N1) strain from birds to humans is rare, although it can cause serious illness, and no human-to-human transmission has been observed. In contrast, the A(H7N9) strain, identified in China in 2013, was found to be very virulent and lethal on humans, although it is classified as LPAI. Mass vaccination on poultry has helped contain the risk of human infection.
Concerns for human health have increased due to the genetic variations that the A (H5N1) strain has undergone over time, repeated outbreaks in wild and domestic birds, and species hopping on some mammals (e.g. sea lions, mink).
Knowledge of the transmission routes, reservoirs, genetic sequence (also as a result of mutations), pathogenesis and other aspects related to the virus are crucial for the development of prevention (e.g. vaccines) and diagnostic tools, in order to limit potential epidemics or pandemics in humans. (3)
Recent human cases of infection
WHO (World Health Organisation) recorded 891 cases of human infection with avian influenza A (H5N1), including 463 deaths, from 24 countries between 2003 and 22 May 2024. Almost all cases are linked to close contact with infected live or dead birds, or contaminated environments. Despite this, WHO rates the risk to the general population from A(H5) viruses as ‘low’, as the transmission capacity and probability of human-to-human spread are low.
Australia
On 22 May 2024, a laboratory-confirmed case of human A(H5N1) infection was reported to WHO in Melbourne, Victoria. (4) The infection from an unconfirmed source involved a 2-year-old girl, now in good health, returning from a trip to India. Reported symptoms included loss of appetite, irritability, fever and vomiting.
The case caused quite a stir due to the fact that it was the first recorded report in Australia, but also due to the absence (declared by the parents) of the child’s contact with sick animals or people while in India. Therefore, it is assumed that transmission occurred in a contaminated environment.
Mexico
The latest ECDC zoonoses report reported the first laboratory-confirmed case of human infection with the A(H5N2) virus in Mexico, whose risk of transmission in the EU is considered low (5.6). The man was hospitalised in Mexico City, and died on the same day. Again, the man did not appear to have been exposed to poultry or other animals and the source of the infection is unknown, except that several outbreaks of A(H5N2) in poultry have been reported in Mexico.
The subject developed fever, shortness of breath, diarrhoea, nausea and general malaise, conditions already manifested in the previous three-week period of bed rest. No cases of human-to-human transmission were found, which was also confirmed in a suspected case that tested negative for influenza A by polymerase chain reaction (PCR).
United States of America
A worker in contact with allegedly infected dairy cattle became infected with the A(H5N1) virus in the US. This is the second case of avian influenza contracted in the US by workers exposed to contact with infected mammals. WHO registered the notification on 1 April 2024. (7) Diagnosis of conjunctivitis without development of other diseases. The infection was not transmitted to relatives or other persons with whom the worker came into contact.
Numerous wild birds have been infected since 2022, with sporadic cases in farm animals (poultry) and mammals, including cats near dairy farms, reported in 50 states or territories. The Centers for Disease Control and Prevention (CDC) in the U.S. has published the sequences of the identified virus and the genome of the virus in patients, which shows minor changes compared to animal viruses, to help identify new cases of A(H5N1).
Virus transmission to other mammals, EFSA report
EFSA (European Food Safety Authority), following an increase in reports of avian influenza cases on mammals, prepared with experts from Enetwild a report on the epidemic potential of the virus, based on a systematic peer review of 76 scientific articles, using different mammalian species as reservoirs and sources of infection. (8)
The most represented taxa are in the carnivore order, with the risk of infection mainly attributed to predation (or feeding) on infected birds or contact with avian species. Evidence of mammal-to-mammal transmission in nature is only circumstantial and has yet to be confirmed. However, trophic modes of transmission must be carefully considered to assess the risk of food-borne transmission of the virus, especially of modified strains.
Among the subtypes to be monitored, H3N8 and H9N2 were considered the most important due to their greater ease of replication in the cells of mammalian respiratory tracts (including humans), potentially favouring spread to humans. Active monitoring and effective surveillance systems in the wild and in captive settings are recommended to identify mutations and/or modes that favour the spread of the virus to these species.
Monitoring and Management of Avian Influenza in the EU
Avian Influenza is among the diseases covered by EU surveillance programmes to be managed according to the general rules of Animal Health Law. These provide specific rules for prevention and control, together with surveillance and eradication programmes, the adoption of emergency measures in case of outbreaks, and the implementation of emergency prophylactic vaccinations. (9)
IZS – Istituto Zooprofilattico delle Venezie is the Union Reference Laboratory (EURL), the national reference centre for avian influenza, and the reference laboratory of the World Organisation for Animal Health (WOAH). (10) IZS has developed a reporting system of total avian influenza cases notified by WHO Member States, in relation to commercial poultry flocks, backyard flocks, other captive birds and wild birds. (11) ECDC, on the other hand, publishes weekly reports on zoonoses.
EFSA, in turn, has developed a tool to facilitate both the prediction of avian influenza outbreaks and the adoption of early warnings to enable appropriate risk management by the various Member States. The ‘Migration Mapping Tool’ allows the assessment of data on the abundance, distribution and movement of wild birds, while the ‘Bird Flu Radar’ lays the groundwork for the adoption of various measures, also extended to farms. (12)
WOAH, monitoring and management
WOAH – World Organisation for Animal Health – has included avian influenza in the list of diseases subject to monitoring and management.
Monitoring
The 183 member states of WOAH must report the following cases of infection:
– highly pathogenic avian influenza viruses, regardless of their subtypes, detected in birds (domestic and wild);
– birds other than poultry, including wild birds, with highly pathogenic influenza A virus;
– domestic and captive wild birds with low pathogenic avian influenza viruses that have been shown to be naturally transmitted to humans with serious consequences. (13)
On a voluntary basis, WOAH Member States may report cases of low pathogenic avian influenza (LPAI) in wild birds, as well as declare the absence of avian influenza in their territory or area.
Management
The management of avian influenza by WOAH is provided for in its Terrestrial Code and Terrestrial Manual, which stipulate, in addition to the specific measures to be taken for the management of this disease, the compartmentalisation measures to be adopted (in place of or in complement to regionalisation) as a biosecurity measure.
Compartmentalisation, as seen in the case of African swine fever, is certainly more effective in ensuring quicker solutions that do not compromise production and trade.
WOAH and FAO jointly launched the OFFLU network in order to:
- facilitate the exchange and research of data and biological material (including virus strains) to foster the dissemination of knowledge by researchers and veterinary authorities, and
- adopt prevention, diagnosis, surveillance and control plans. Through the network, for example, an FAO alert on avian influenza, which can occur during poultry trade before and during the Lunar New Year holidays in Asia, was disseminated. (14) WHO, in turn, offers a weekly update on human cases of avian influenza. (15)
European Union, procurement of human vaccines
The European Commission, through its Health Emergency Preparedness and Response Authority (HERA), signed on behalf of the Member States a joint procurement framework contract for the supply of 665,000 doses, up to 40 million doses over 4 years, of the ‘pandemic’ Zoonotic Influenza Vaccine Seqirus vaccine, to be targeted at those most exposed to potential bird or animal flu transfers, such as poultry farmers and veterinarians. (16)
CSL Seqirus UK is the manufacturer of the vaccine’s biological active ingredient, and is part of the Australian-based CSL Group.
Information on the vaccine, whose authorisation (recently amended) is held by the Italian office, is available on the Union Register of Medicinal Products, from which all product information can be verified. (17)
WOAH regards vaccination as a fundamental tool for the prevention of a possible avian influenza pandemic. In cooperation with WHO, it has also developed recommendations for the pharmacological management of A(H5N1)-infected persons and the exchange of epidemiological information to develop effective vaccines (18,19,20).
Provisional conclusions
The development of highly pathogenic avian influenza poses a serious risk to the livestock sector and to the health of wild birds.
Preventive measures, including vaccination of farm animals, are identified by WOAH as a necessary and indispensable strategy to ensure animal health and continued production and trade in poultry and poultry products. (21)
Concerns remain about the European Commission’s decision to purchase millions of doses of vaccines for human use after the ‘health dictatorship’ of uncertain outcome imposed under Covid.
Dario Dongo and Andrea Adelmo Della Penna
Note
(1) V. https://www.ecdc.europa.eu/en/avian-influenza
(2) V. https://food.ec.europa.eu/animals/animal-diseases/diseases-and-control-measures/avian-influenza_en
(3) Charostad J. et al. (2023) A comprehensive review of highly pathogenic avian influenza (HPAI) H5N1: An imminent threat at doorstep. Travel Medicine and Infectious Disease 55:102638, https://doi.org/10.1016/j.tmaid.2023.102638
(4) Disease Outbreak News. Avian Influenza A (H5N1) – Australia. 7.6.24 https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON519
(6) Disease Outbreak News – Avian Influenza A (H5N2) –Mexico. 5.6.24. https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON520
(7) Disease Outbreak News – Avian Influenza A (H5N1) – United States of America. 9.4.24. https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON512
(8) Enetwild Consortium et al. (2024) The role of mammals in Avian Influenza: a review. EFSA Supporting Publications 21(3):8692E, https://doi.org/10.2903/sp.efsa.2024.EN-8692
(9) The reference regulations are Reg. (EU) 2016/429; Delegated Reg. (EU) 2020/687; Delegated Reg. (EU) 2020/689; Implementing Reg. (EU) 2020/690, Delegated Reg. (EU) 2023/361, and Implementing Decision (EU) 2023/2447.
(10) V. https://www.izsvenezie.it/istituto/centri-di-referenza/influenza-aviaria-e-malattia-di-newcastle/
(11) V. https://eurlaidata.izsvenezie.it/epidemio.php
(12) V. https://app.bto.org/mmt/avian_influenza_map/avian_influenza_map.jsp. Selezionare il cursore ‘Migration Map’ per passare alla Migration Mapping Tool.
(13) V. https://www.woah.org/en/disease/avian-influenza
(14) FAO. FAO alert on avian influenza – risk of upsurge and regional spread through increased poultry trade prior to and during Lunar New Year festivities in Asia. https://openknowledge.fao.org/handle/20.500.14283/cc9524en
(15) WHO. Avian Influenza Weekly Update 2024. https://iris.who.int/handle/10665/375483
(16) European Commission. Commission secures access for Member States to 665,000 doses of zoonotic influenza vaccines to prevent avian flu. 11.6.24. https://ec.europa.eu/commission/presscorner/detail/en/ip_24_3168
(17) V. https://ec.europa.eu/health/documents/community-register/html/h1761.htm
(18) WHO (2006) WHO rapid advice guidelines on pharmacological management of humans infected with avian influenza A (H5N1) virus. https://iris.who.int/handle/10665/69373
(19) Schünemann H.J. et al. (2007) WHO Rapid Advice Guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus. Lancet Infect Dis. 7(1):21-31, https://doi.org/10.1016/S1473-3099(06)70684-3
(20) WOAH. Influenzas with zoonotic potential: the contribution of the animal health sector for pandemic preparedness. 15.5.22. https://www.woah.org/en/influenzas-with-zoonotic-potential-the-contribution-of-the-animal-health-sector-for-pandemic-preparedness/
(21) WOAH. Avian influenza vaccination: why it should not be a barrier to safe trade. https://www.woah.org/en/document/avian-influenza-vaccination-why-it-should-not-be-a-barrier-to-safe-trade/
Dario Dongo, lawyer and journalist, PhD in international food law, founder of WIISE (FARE - GIFT - Food Times) and Égalité.
Graduated in Food Technologies and Biotechnologies, qualified food technologist, he follows the research and development area. With particular regard to European research projects (in Horizon 2020, PRIMA) where the FARE division of WIISE Srl, a benefit company, participates.
