EFSA: The Role of Mammals in Avian Influenza: A Review

 #17,941

Today the ESFA (European Food Safety Authority) has published an extensive systematic review of the literature on mammalian infection with a wide array of avian influenza viruses, with an emphasis on the recent and worrying rise of HPAI H5 clade 2.3.4.4b.

The objective of this review was to answer four questions:

1. Do wild mammals play a role in the maintenance of the Avian Influenza virus (HPAI and other subtypes different from H5 and H7) favouring current or future spill back to wild birds and spill over to humans or other taxa?
2. Can wild mammals acquire immunity and become a reservoir for the AI virus subtypes that are the object of this review?
3. According  to  epidemiological  and  experimental  evidence,  how  likely  is  mammal-to-mammal transmission of AI virus?
4. Considering the answers to the above questions, what could be the role of mammals in a potential pandemic caused by AI viruses? Could this taxon represent a risk due to the recent increase in cases? And which could be the drivers for a potential pandemic?

While this this 54-page PDF focuses primarily on HPAI viruses (H5, H7, & H10 (corr. should have been LPAI H10 - mpc), they also single out two LPAI viruses - H3N8 & H9N2 - as being of heightened interest. 

Due to its length I've only posted the Abstract and some excerpts from the conclusions. You'll want to follow the link to review the full report. Supporting Publications

External scientific report

Open Access

The role of mammals in Avian Influenza: a review

ENETWILD Consortium, Occhibove Flavia, Knauf Sascha, Sauter-Louis Carola, Staubach Christoph, Allendorf Valerie, Anton Alina, Barron Sophia, Bergmann Hannes, Bröjer Caroline … See all authors 

First published: 07 March 2024

 

https://doi.org/10.2903/sp.efsa.2024.EN-8692

Question number: EFSA-Q-2024-00030

PDF

Abstract

Avian influenza (AI) is an infectious viral disease of birds, including domestic poultry, which has been causing outbreaks worldwide, leading to several millions of dead wild birds and culled poultry. AI is mainly found in birds, but recently, there was an increase in reported infections in mammals, ranging from no symptoms to mass mortality events and some human cases. Epidemiologically of great concern, evidence of mammalian adaptations have been found, but the transmission routes and pathogenesis in mammals are still to be defined. 

Hence, it is paramount to address all facets of AI viruses epidemiology, including investigating taxa not customarily thought to be involved in the transmission and/or trafficking of AI, such as wild mammals. The scope of this report was to assess the role of mammals in AI epidemiology, virology and pathology, i.e. AI maintenance, reservoir role, immunity, role of mammals in a potential pandemic. 

To do so, we performed an all-encompassing review of the literature on the topic with a two-fold approach: a systematic review of the published AI cases in wild mammals and a narrative approach to provide an expert opinion on the role of mammals in AI spread. The final number of peer-reviewed papers included in the systematic literature review was 76, resulting in 120 unique infection records with AI in wild mammal species. 

The most represented taxa were included in the order Carnivora. The risk of infection was identified mainly as predation (or feeding) upon infected birds or contact with avian species. Evidence of mammal-to-mammal transmission in the wild is only circumstantial and yet to be confirmed. Cases of AI from the systematic review of experimental findings were discussed concerning epidemiology, pathology and virology. Knowledge gaps and potential pandemic drivers were identified.

In summary, although a greater number of infections in wild mammals have been reported, there is no hard evidence for sustained mammal-to-mammal transmission in the wild. The factors contributing to the increased number of infections found in wild carnivores are not clear yet, but the unprecedented global spread of highly pathogenic avian influenza (HPAI) viruses creates ample opportunities for intense, mostly alimentary, contact between infected wild birds and carnivores. Close surveillance of circulating strains and continued assessment of new epidemiological situations are crucial to quickly identify strains with enhanced mammalian fitness.

          (SNIP)

Conclusion and recommendations for surveillance

• Mammal-to-mammal transmission was not detected in wild mammals, although some experimental evidence suggested that this might be possible, although not very effective, for some combinations of viral genotypes-hosts.

• In wild mammals, sustained mortality events due to H5N1 have thus far only been reported in seals (Puryear et al., 2023). No seal-to-seal transmission was identified as a primary route of infection. Yet, the high likelihood of continuous contact of this species with potentially infected birds requires ongoing vigilance, as this increases potential opportunities for further reassortment or adaptation of these viruses to mammalian hosts.

• In experimental settings, the transmission route was mostly similar to that occurring in birds, i.e. sharing environmental resources, not airborne. Nonetheless, mammal species may play a role in the circulation of the Avian Influenza virus (HPAI and other subtypes).

• It might be possible that wild mammals, especially synanthropic and periurban species, might serve as bridge hosts, favouring the potential reassortment of various AIVs. 

• Beyond HPAIV, subtypes H3N8, and H9N2 should be monitored as more easily replicating in mammalian (including humans) respiratory tract cells, favouring potential spillover to humans.

• Information on species-specific susceptibility, and morbidity and mortality of viral genotype-host combinations are scarce; further studies on the susceptibility of mammalian species to infection with the currently circulating strains of the HPAI H5N1 may be warranted, especially in light of the unprecedented reassortment of the Newfoundland-like virus with North American wild bird origin influenza viruses.

• Subclinical infections are of great importance, while current investigations mostly focus on mass mortality events of marine mammals and other species of conservation interest. Yet, these have been documented experimentally and in the wild, making it very challenging to implement an active surveillance strategy in wild animals. 

• From this review it can be observed that viral mutations are happening, especially with regards to the polymerase activity and the ability to escape mammalian restriction factors, which might favour infections in humans, but no reassortant with human viruses were isolated. 

• Evaluations of North American HPAI H5N2 and H5N8 isolates in human airway cells demonstrated that these were capable of replication, but at reduced titers compared with H5N1 and H1N1 viruses.Currently, there is not enough evidence to determine whether wild mammal species might represent a reservoir for AIVs.

• Understanding the complex interplay of intrinsic and extrinsic drivers is imperative for pandemic preparedness. Intrinsic drivers might be summarised in host susceptibility and genetic adaptations within mammalian species. Host features that seemed to favour infection were certainly scavenging feeding habits (e.g. generalist mesopredators such as red foxes and mustelids), and, in general, carnivores were more exposed to infection and displayed more viral mammalian adaptations. Broadly, extrinsic risk factors include human-driven influences such as intensive farming practices that create environments conducive to cross-species transmission. Deforestation, urbanisation, and changes in habitats contribute to increased interactions between domestic and wild species, influencing the transmission dynamics of avian influenza. Global trade and travel facilitate the spread of AIVs, with infected avian and mammalian hosts potentially introducing novel strains to different regions.

Considering the above conclusive points, active monitoring is recommended for early detection of AIVs mutations and/or adaptations favouring the spread in mammals, including humans.Vigilant surveillance, research on transmission mechanisms, and proactive measures to mitigate human-wildlife interactions are critical components in averting potential pandemics.

Surveillance actions might include testing synanthropic and peridomestic birds as well as syndromic surveillance of “at risk” individuals/workers, e.g. people at poultry farms or dealing with infected deceased animals (Leguia et al., 2023; Burns et al., 2012). Coupling PCR-based diagnostics  and/or  serology  of  suspected  cases  is also  highly  recommended  for early detection of clinical infections and transmission (Leguia et al. 2023). Active surveillance should  focus  on  the  wildlife-livestock-domestic  animal  interface,  particularly  investigating periurban/peridomestic   mammals   (multiple   samples   from   different   apparatus   are recommended  if  possible). 

Nonetheless,  these  species  are  usually  difficult  to  monitor,  e.g. synanthropic  wildlife  such  as  rodents  are  very  abundant  and  it  is  challenging  to  test  an adequate proportion of the population. Additionally, diagnostic tests with high sensitivity and specificity  are  not  necessarily  available  for  every  single  species  (e.g.  serologic  tests  might have different sensitivity/specificity in different species). Mice have been commonly observed in rearing poultry facilities and at farms in general and might represent bridgehosts, so rodent control  programs  might  be  an  addition  to  current  biosecurity  programs  in  poultry  farms, specifically  for  AIVs  control  (Shriner  et  al.,  2016).  In  general,  rodents  are  considered reservoirs for zoonotic diseases and thrive in anthropogenically modified habitats (Mendoza et  al.,  2020;  Plourde  et  al.,  2017). 

Other  management  actions  to  reduce  the  risk  of transmission between synanthropic wildlife and poultry, at a farm level might be: removing and/or  reducing  wildlife  attractants  such  as  ponds,  standing  water,  food  sources,  and waste/carcasses; preventing wildlife access to poultry facilities; increasing wildlife deterrents (Shriner et al., 2016).Finally, capacity building in disease prevention, outbreak investigations, and controlling the spread  of  disease  in  wildlife  (e.g., through  carcass  removal)  should  be  priorities.

Our data support the outcomes of other risk assessments on this topic, e.g.t he CDC Influenza Risk Assessment Tool determination that states that HPAI H5N1 viruses do not pose a substantial (although  highly  potential)  risk  to  public  health  at  this  time  (CDC,  2022).  However,  close surveillance  of  circulating  strains  and  continued  assessment  of  new  viruses  are  crucial  to ensure strains with enhanced mammalian fitness are quickly identified.