A systematic review of mechanistic models used to study avian influenza virus transmission and control.

The global spread of avian influenza A viruses in domestic birds is causing increasing socioeconomic devastation. Various mechanistic models have been developed to better understand avian influenza transmission and evaluate the effectiveness of control measures in mitigating the socioeconomic losses caused by these viruses. However, the results of models of avian influenza transmission and control have not yet been subject to a comprehensive review. Such a review could help inform policy makers and guide future modeling work. To help fill this gap, we conducted a systematic review of the mechanistic models that have been applied to field outbreaks. Our three objectives were to: (1) describe the type of models and their epidemiological context, (2) list estimates of commonly used parameters of low pathogenicity and highly pathogenic avian influenza transmission, and (3) review the characteristics of avian influenza transmission and the efficacy of control strategies according to the mechanistic models. We reviewed a total of 46 articles. Of these, 26 articles estimated parameters by fitting the model to data, one evaluated the effectiveness of control strategies, and 19 did both. Values of the between-individual reproduction number ranged widely: from 2.18 to 86 for highly pathogenic avian influenza viruses, and from 4.7 to 45.9 for low pathogenicity avian influenza viruses, depending on epidemiological settings, virus subtypes and host species. Other parameters, such as the durations of the latent and infectious periods, were often taken from the literature, limiting the models' potential insights. Concerning control strategies, many models evaluated culling (n = 15), while vaccination received less attention (n = 6). According to the articles reviewed, optimal control strategies varied between virus subtypes and local conditions, and depended on the overall objective of the intervention. For instance, vaccination was optimal when the objective was to limit the overall number of culled flocks. In contrast, pre-emptive culling was preferred for reducing the size and duration of an epidemic. Early implementation consistently improved the overall efficacy of interventions, highlighting the need for effective surveillance and epidemic preparedness.

Impact of palmiped farm density on the resilience of the poultry sector to highly pathogenic avian influenza H5N8 in France.

We analysed the interplay between palmiped farm density and the vulnerability of the poultry production system to highly pathogenic avian influenza (HPAI) H5N8. To do so, we used a spatially-explicit transmission model, which was calibrated to reproduce the observed spatio-temporal distribution of outbreaks in France during the 2016-2017 epidemic of HPAI. Six scenarios were investigated, in which the density of palmiped farms was decreased in the municipalities with the highest palmiped farm density. For each of the six scenarios, we first calculated the spatial distribution of the basic reproduction number (R0), i.e. the expected number of farms a particular farm would be likely to infect, should all other farms be susceptible. We also ran in silico simulations of the adjusted model for each scenario to estimate epidemic sizes and time-varying effective reproduction numbers. We showed that reducing palmiped farm density in the densest municipalities decreased substantially the size of the areas with high R0 values (> 1.5). In silico simulations suggested that reducing palmiped farm density, even slightly, in the densest municipalities was expected to decrease substantially the number of affected poultry farms and therefore provide benefits to the poultry sector as a whole. However, they also suggest that it would not have been sufficient, even in combination with the intervention measures implemented during the 2016-2017 epidemic, to completely prevent the virus from spreading. Therefore, the effectiveness of alternative structural preventive approaches now needs to be assessed, including flock size reduction and targeted vaccination.

Highly Pathogenic Avian Influenza A(H5N8) Clade 2.3.4.4b Virus in Dust Samples from Poultry Farms, France, 2021.

Avian influenza A(H5N8) virus has caused major epizootics in Europe since 2016. We conducted virologic analysis of aerosol and dust collected on poultry farms in France during 2020-2021. Our results suggest dust contributes to viral dispersal, even early in an outbreak, and could be a valuable surveillance tool.

Pathobiology of highly pathogenic H5 avian influenza viruses in naturally infected Galliformes and Anseriformes in France during 2015-2016.

In late 2015, an epizootic of Highly Pathogenic Avian Influenza (H5Nx) was registered in Southwestern France, including more than 70 outbreaks in commercial poultry flocks. Phylogenetic analyses suggested local emergence of H5 viruses which differed from A/goose/Guangdong/1/1996 clade 2.3.4.4b lineage and shared a unique polybasic cleavage site in their hemagglutinin protein. The present work provides an overview of the pathobiological picture associated with this epizootic in naturally infected chickens, guinea fowls and ducks. Upon necropsy examination, selected tissues were sampled for histopathology, immunohistochemistry and quantitative Real Time Polymerase Chain Reaction. In Galliformes, HPAIVs infection manifested as severe acute systemic vasculitis and parenchymal necrosis and was associated with endothelial expression of viral antigen. In ducks, lesions were mild and infrequent, with sparse antigenic detection in respiratory and digestive mucosae and leukocytes. Tissue quantifications of viral antigen and RNA were higher in chickens and guinea fowls compared to duck. Subsequently, recombinant HA (rHA) was generated from a H5 HPAIV isolated from an infected duck to investigate its glycan-binding affinity for avian mucosae. Glycan-binding analysis revealed strong affinity of rHA for 3'Sialyl-LacNAc and low affinity for Sialyl-LewisX, consistent with a duck-adapted virus similar to A/Duck/Mongolia/54/2001 (H5N2). K222R and S227R mutations on rHA sequence shifted affinity towards Sialyl-LewisX and led to an increased affinity for chicken mucosa, confirming the involvement of these two mutations in the glycan-binding specificity of the HA. Interestingly, the rHA glycan binding pattern of guinea fowl appeared intermediate between duck and chicken. The present study presents a unique pathobiological description of the H5 HPAIVs outbreaks that occurred in 2015-2016 in Southwestern France.

Undetected Circulation of African Swine Fever in Wild Boar, Asia.

African swine fever is a growing threat to the livestock industry. We examined data indicating that in most countries in Asia, most notified events were related to farm outbreaks; meanwhile, only a few wild boar cases were reported. We hypothesize the virus circulates unnoticed in wild boar populations in Asia.

Role of Live-Duck Movement Networks in Transmission of Avian Influenza, France, 2016-2017.

The relative roles that movement and proximity networks play in the spread of highly pathogenic avian influenza (HPAI) viruses are often unknown during an epidemic, preventing effective control. We used network analysis to explore the devastating epidemic of HPAI A(H5N8) among poultry, in particular ducks, in France during 2016-2017 and to estimate the likely contribution of live-duck movements. Approximately 0.2% of live-duck movements could have been responsible for between-farm transmission events, mostly early during the epidemic. Results also suggest a transmission risk of 35.5% when an infected holding moves flocks to another holding within 14 days before detection. Finally, we found that densely connected groups of holdings with sparse connections between groups overlapped farmer organizations, which represents important knowledge for surveillance design. This study highlights the importance of movement bans in zones affected by HPAI and of understanding transmission routes to develop appropriate HPAI control strategies.

Spatio-temporal patterns of highly pathogenic avian influenza virus subtype H5N8 spread, France, 2016 to 2017.

IntroductionFrance is one of Europe's foremost poultry producers and the world's fifth largest producer of poultry meat. In November 2016, highly pathogenic avian influenza (HPAI) virus subtype H5N8 emerged in poultry in the country. As of 23 March 2017, a total of 484 confirmed outbreaks were reported, with consequences on animal health and socio-economic impacts for producers. Methods: We examined the spatio-temporal distribution of outbreaks that occurred in France between November 2016 and March 2017, using the space-time K-function and space-time permutation model of the scan statistic test. Results: Most outbreaks affected duck flocks in south-west France. A significant space-time interaction of outbreaks was present at the beginning of the epidemic within a window of 8 km and 13 days. This interaction disappeared towards the epidemic end. Five spatio-temporal outbreak clusters were identified in the main poultry producing areas, moving sequentially from east to west. The average spread rate of the epidemic front wave was estimated to be 5.5 km/week. It increased from February 2017 and was negatively associated with the duck holding density. Conclusion: HPAI-H5N8 infections varied over time and space in France. Intense transmission events occurred at the early stages of the epidemic, followed by long-range jumps in the disease spread towards its end. Findings support strict control strategies in poultry production as well as the maintenance of high biosecurity standards for poultry holdings. Factors and mechanisms driving HPAI spread need to be further investigated.

Transmission tree of the highly pathogenic avian influenza (H5N1) epidemic in Israel, 2015.

The transmission tree of the Israeli 2015 epidemic of highly pathogenic avian influenza (H5N1) was modelled by combining the spatio-temporal distribution of the outbreaks and the genetic distance between virus isolates. The most likely successions of transmission events were determined and transmission parameters were estimated. It was found that the median infectious pressure exerted at 1 km was 1.59 times (95% CI 1.04, 6.01) and 3.54 times (95% CI 1.09, 131.75) higher than that exerted at 2 and 5 km, respectively, and that three farms were responsible for all seven transmission events.

Epidemiological analysis of African swine fever in the European Union during 2023.

In 2023, 14 Member States were affected by African swine fever (ASF), including Croatia and Sweden where ASF emerged (wild boar outbreaks only) and Greece where ASF re-emerged after being free since 2021. The number of ASF outbreaks among domestic pigs in the EU was five times higher than in 2022, reaching a similar magnitude to that in 2019. This was predominantly driven by the introduction and subsequent spread of ASF in Croatia and its resurgence in Romania, representing 96% of the EU outbreaks. ASF outbreaks in domestic pigs were clearly seasonal in all countries, with 88% of outbreaks reported between July and October. Most of the ASF outbreaks among domestic pigs were detected through clinical suspicion (94%), followed by tracing from affected establishments (3%), and the weekly testing of at least two dead pigs in establishments (3%). In wild boar, a 10% increase in the number of notified outbreaks was observed in the EU in comparison with 2022, with considerable variations between countries. A winter peak was observed only in Poland, Slovakia and Hungary. The epidemiological situation in wild boar improved in Germany and Hungary, as suggested by the decrease in the number of outbreaks and in the proportions of PCR-positive samples from dead wild boar. Overall, 31% of wild boar carcasses found during passive surveillance tested positive by PCR, representing 69% of the ASF outbreaks in wild boar in the EU. In contrast, 0.4% of hunted wild boar tested positive, representing 31% of the outbreaks. Despite the introduction of ASF into new countries and the increase in the number of outbreaks, the size of restricted zones in the EU remained stable, due to the highly clustered outbreaks in Croatia, and the reduction of restricted zones in Poland, Slovakia and Bulgaria (in domestic pigs), and Hungary (in wild boar).

Mathematical modeling at the livestock-wildlife interface: scoping review of drivers of disease transmission between species.

Modeling of infectious diseases at the livestock-wildlife interface is a unique subset of mathematical modeling with many innate challenges. To ascertain the characteristics of the models used in these scenarios, a scoping review of the scientific literature was conducted. Fifty-six studies qualified for inclusion. Only 14 diseases at this interface have benefited from the utility of mathematical modeling, despite a far greater number of shared diseases. The most represented species combinations were cattle and badgers (for bovine tuberculosis, 14), and pigs and wild boar [for African (8) and classical (3) swine fever, and foot-and-mouth and disease (1)]. Assessing control strategies was the overwhelming primary research objective (27), with most studies examining control strategies applied to wildlife hosts and the effect on domestic hosts (10) or both wild and domestic hosts (5). In spatially-explicit models, while livestock species can often be represented through explicit and identifiable location data (such as farm, herd, or pasture locations), wildlife locations are often inferred using habitat suitability as a proxy. Though there are innate assumptions that may not be fully accurate when using habitat suitability to represent wildlife presence, especially for wildlife the parsimony principle plays a large role in modeling diseases at this interface, where parameters are difficult to document or require a high level of data for inference. Explaining observed transmission dynamics was another common model objective, though the relative contribution of involved species to epizootic propagation was only ascertained in a few models. More direct evidence of disease spill-over, as can be obtained through genomic approaches based on pathogen sequences, could be a useful complement to further inform such modeling. As computational and programmatic capabilities advance, the resolution of the models and data used in these models will likely be able to increase as well, with a potential goal being the linking of modern complex ecological models with the depth of dynamics responsible for pathogen transmission. Controlling diseases at this interface is a critical step toward improving both livestock and wildlife health, and mechanistic models are becoming increasingly used to explore the strategies needed to confront these diseases.

Epidemiological analysis of African swine fever in the European Union during 2022.

This report presents the epidemiological analysis of African swine fever (ASF) during 2022 based on the surveillance and pig population data submitted by the European Union (EU) affected countries and one neighbouring country. Coinciding with regulatory changes and an important decrease in ASF outbreaks in 2022 in the EU, the number of domestic pig samples tested as part of active surveillance decreased by 80%, while the number of samples from passive surveillance almost doubled compared with 2021. Most outbreaks among domestic pigs in the EU were detected by testing clinical suspicions (93% of outbreaks), followed by tracing activities (5%) and weekly testing of the first two dead pigs per establishment (2%). Although most of the wild boar samples came from hunted animals, the probability of detecting PCR-positive animals was much higher in wild boar found dead. The ASF outbreaks among domestic pigs in the EU decreased by 79% while a decrease of 40% in the wild boar cases was observed in comparison with 2021. This was strongly marked in Romania, Poland and Bulgaria, with a reduction of 50-80% compared with 2021. In many countries, an important decrease in the number of pig establishments was observed, especially of small establishments with fewer than 100 pigs. The regional between farm incidence and proportion of pigs lost due to ASF in the EU was in general very low (average of 1%) apart from some regions in Romania. The impact of ASF on wild boar populations was variable, with a decline in wild boar abundance observed in certain countries versus a stable or even increased population after ASF introduction. This supports the negative relationship observed in this report between the proportion of the country with restricted zones due to ASF in wild boar and wild boar hunting bags.

Validation of an RNAscope assay for the detection of avian influenza A virus.

Highly pathogenic avian influenza (HPAI) is an acute viral disease associated with high mortality and great economic losses. Immunohistochemistry (IHC) is a common diagnostic and research tool for the demonstration of avian influenza A virus (AIAV) antigens within affected tissues, supporting etiologic diagnosis and assessing viral distribution in both naturally and experimentally infected birds. RNAscope in situ hybridization (ISH) has been used successfully for the identification of a variety of viral nucleic acids within histologic samples. We validated RNAscope ISH for the detection of AIAV in formalin-fixed, paraffin-embedded (FFPE) tissues. RNAscope ISH targeting the AIAV matrix gene and anti-IAV nucleoprotein IHC were performed on 61 FFPE tissue sections obtained from 3 AIAV-negative, 16 H5 HPAIAV, and 1 low pathogenicity AIAV naturally infected birds, including 7 species sampled between 2009 and 2022. All AIAV-negative birds were confirmed negative by both techniques. All AIAVs were detected successfully by both techniques in all selected tissues and species. Subsequently, H-score comparison was assessed through computer-assisted quantitative analysis on a tissue microarray comprised of 132 tissue cores from 9 HPAIAV-infected domestic ducks. Pearson correlation of r = 0.95 (0.94-0.97), Lin concordance coefficient of ρc = 0.91 (0.88-0.93), and Bland-Altman analysis indicated high correlation and moderate concordance between the 2 techniques. H-score values were significantly higher with RNAscope ISH compared to IHC for brain, lung, and pancreatic tissues (p ≤ 0.05). Overall, our results indicate that RNAscope ISH is a suitable and sensitive tool for in situ detection of AIAV in FFPE tissues.

Improving the communication between farmers and veterinarians to enhance the acceptability of bovine tuberculosis eradication programmes.

France and Spain have been fighting against bovine tuberculosis (bTB) for years, even though new outbreaks continue to appear on both sides of the border, generating misconceptions about the disease and social distrust in the eradication programme and competent authorities. The perceived disease risk and the commitment of all interested parties are key factors for the successful implementation of control programmes, as they might influence the acceptability of recommended measures. Effective communication can contribute to increasing knowledge, trust and stakeholders' engagement, thus ensuring the acceptability of the eradication programme. This study was conducted in Catalonia (Spain) and Pyrenees-Atlantiques (France) in the frame of the INNOTUB project (https://innotub.eu/) to characterise the communication on bTB in the trans-Pyrenees region and provide recommendations to improve it. The communication on bTB was characterised by analysing 153 (Spain) and 66 (France) online freely available texts, published between 2018 and 2020, through Content Analysis and Critical Metaphor Analysis. Moreover, six farmers and four veterinarians were in-depth interviewed in each area to gather information about the communication on bTB. Interviews were made in original languages and analysed using a qualitative thematic approach. A pilot participatory intervention inspired by the Systematic Tool for Behavioural Assumption Validation and Exploration (STAVE) method was used to develop a list of proposals to improve communication and to promote the creation of territorial networks/committees on bTB prevention and control. It included three focus groups with farmers and veterinarians, a meeting with representatives of the regional veterinary services, and a final deliberative workshop. Results highlight the existence of a controversial debate on bTB and a heterogeneous understanding between stakeholders. Institutional and scientific communication mainly focus on bTB detection and control while other aspects are left in the background. On the contrary, farmers extend their communication to a greater variety of topics. The metaphorical framing strongly differed among actors, while veterinary services and researchers "fight" against bTB and "progress" toward the eradication, farmers place themselves in a framework of "sacrifice" and, particularly in Spain, they play a passive role. The proposals developed by the participants to improve the current communication on bTB included: (i) create participatory meeting spaces to share opinions and information; (ii) improve data accessibility (on epidemiological situations); (iii) develop clearer and written protocols and informative visual material; (iv) redesign the training courses (v) increase the stakeholders' participation in the design of protocols.

Optimizing environmental viral surveillance: bovine serum albumin increases RT-qPCR sensitivity for high pathogenicity avian influenza H5Nx virus detection from dust samples.

IMPORTANCE: With the circulation of high pathogenicity avian influenza viruses having intensified considerably in recent years, the European Union is considering the vaccination of farmed birds. A prerequisite for this vaccination is the implementation of drastic surveillance protocols. Environmental sampling is a relevant alternative to animal sampling. However, environmental samples often contain inhibitory compounds in large enough quantities to inhibit RT-qPCR reactions. As bovine serum albumin is a molecule used in many fields to overcome this inhibitory effect, we tested its use on dust samples from poultry farms in areas heavily affected by HPAIV epizootics. Our results show that its use significantly increases the sensitivity of the method.

"It's a habit. They've been doing it for decades and they feel good and safe.": A qualitative study of barriers and opportunities to changing antimicrobial use in the Indonesian poultry sector.

Interventions to change antimicrobial use (AMU) practices can help mitigate the risk of antimicrobial resistance (AMR) development. However, changing AMU practices can be challenging due to the complex nature of the factors influencing AMU-related behaviours. This study used a qualitative approach to explore the factors that influenced decision-making on AMU by farmers and other actors in the Indonesian poultry sector. Thirty-five semi-structured interviews were conducted with farmers, technical services staff from the private sector, and representatives of associations, universities, and international organisations in Central Java, West Java, and East Java. Thematic analysis identified three patterns of influence on AMU: how farmers used information to make AMU-related decisions, the importance of farmers' social and advisory networks, and the motivations driving changes in AMU behaviours. Key barriers identified included a lack of shared understanding around when to use antibiotics, financial pressures in the poultry sector, and a lack of engagement with government veterinary services. Potential opportunities identified included high farmer awareness of AMU, identification of private sector actors and peer networks as the stakeholders with established relationships of trust with farmers, and the importance of farmers' conceptions of good farming practices, which could be engaged with to improve AMU practices.

Avian influenza vaccination of poultry and passive case reporting, Egypt.

We investigated the influence of a mass poultry vaccination campaign on passive surveillance of highly pathogenic avian influenza subtype (H5N1) outbreaks among poultry in Egypt. Passive reporting dropped during the campaign, although probability of infection remained unchanged. Future poultry vaccination campaigns should consider this negative impact on reporting for adapting surveillance strategies.

The African swine fever modelling challenge: Objectives, model description and synthetic data generation.

African swine fever (ASF) is an emerging disease currently spreading at the interface between wild boar and pig farms in Europe and Asia. Current disease control regulations, which involve massive culling with significant economic and animal welfare costs, need to be improved. Modelling enables relevant control measures to be explored, but conducting the exercise during an epidemic is extremely difficult. Modelling challenges enhance modellers' ability to timely advice policy makers, improve their readiness when facing emerging threats, and promote international collaborations. The ASF-Challenge, which ran between August 2020 and January 2021, was the first modelling challenge in animal health. In this paper, we describe the objectives and rules of the challenge. We then demonstrate the mechanistic multi-host model that was used to mimic as accurately as possible an ASF-like epidemic, provide a detailed explanation of the surveillance and intervention strategies that generated the synthetic data, and describe the different management strategies that were assessed by the competing modelling teams. We then outline the different technical steps of the challenge as well as its environment. Finally, we synthesize the lessons we learnt along the way to guide future modelling challenges in animal health.

Modelling African swine fever virus spread in pigs using time-respective network data: Scientific support for decision makers.

African swine fever (ASF) represents the main threat to swine production, with heavy economic consequences for both farmers and the food industry. The spread of the virus that causes ASF through Europe raises the issues of identifying transmission routes and assessing their relative contributions in order to provide insights to stakeholders for adapted surveillance and control measures. A simulation model was developed to assess ASF spread over the commercial swine network in France. The model was designed from raw movement data and actual farm characteristics. A metapopulation approach was used, with transmission processes at the herd level potentially leading to external spread to epidemiologically connected herds. Three transmission routes were considered: local transmission (e.g. fomites, material exchange), movement of animals from infected to susceptible sites, and transit of trucks without physical animal exchange. Surveillance was represented by prevalence and mortality detection thresholds at herd level, which triggered control measures through movement ban for detected herds and epidemiologically related herds. The time from infection to detection varied between 8 and 21 days, depending on the detection criteria, but was also dependent on the types of herds in which the infection was introduced. Movement restrictions effectively reduced the transmission between herds, but local transmission was nevertheless observed in higher proportions highlighting the need of global awareness of all actors of the swine industry to mitigate the risk of local spread. Raw movement data were directly used to build a dynamic network on a realistic timescale. This approach allows for a rapid update of input data without any pre-treatment, which could be important in terms of responsiveness, should an introduction occur.

Exposure assessment for avian influenza and Newcastle disease viruses from peridomestic wild birds in a conservation breeding site in the United Arab Emirates.

Worldwide, wild birds are frequently suspected to be involved in the occurrence of outbreaks of different diseases in captive-bred birds although proofs are lacking and most of the dedicated studies are insufficiently conclusive to confirm or characterize the roles of wild birds in such outbreaks. The aim of this study was to assess and compare, for the most abundant peridomestic wild birds, the different exposure routes for avian influenza and Newcastle disease viruses in conservation breeding sites of Houbara bustards in the United Arab Emirates. To do so, we considered all of the potential pathways by which captive bustards could be exposed to avian influenza and Newcastle disease viruses by wild birds, and ran a comparative study of the likelihood of exposure via each of the pathways considered. We merged data from an ecological study dedicated to local wild bird communities with an analysis of the contacts between wild birds and captive bustards and with a prevalence survey of avian influenza and Newcastle disease viruses in wild bird populations. We also extracted data from an extensive review of the scientific literature and by the elicitation of expert opinion. Overall, this analysis highlighted those captive bustards had a high risk of being exposed to pathogens by wild birds. This risk was higher for Newcastle disease virus than avian influenza virus, and House sparrows represented the riskiest species for the transmission of both viruses through direct exposure from direct contact with an infectious bird that got inside the aviary and indirect exposure from consumption of water contaminated from the faeces of an infected bird that got inside the aviary for Newcastle disease virus and avian influenza virus, respectively. These results also reaffirm the need to implement biosecurity measures to limit contacts between wild and captive birds and highlight priority targets for a thoughtful and efficient sanitary management strategy.

SARS-CoV-2 Infection in Companion Animals: Prospective Serological Survey and Risk Factor Analysis in France.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for COVID-19 in people, has been detected in companion animals on rare occasions. A limited number of large-scale studies have investigated the exposure of companion animals to SARS-CoV-2. The objective of this prospective study was to estimate seroprevalence in privately owned dogs and cats presented in veterinary clinics in different French regions and to test the hypothesis that the occurrence of an episode of COVID-19 in the household and close contact with the owner would increase the chances of the animals being seropositive. One hundred and sixty-five dogs and 143 cats were blood-sampled between March 2020 and December 2021. Neutralizing SARS-CoV-2 antibodies were detected in 8.4% of cats (12/143) and 5.4% of dogs (9/165). Seven animals (three dogs and four cats) were seropositive in the absence of an episode of COVID-19 in the household. Despite not being statistically significant (chi-square test, p-value = 0.55), our data may suggest that the occurrence of an episode of COVID-19 in the household could increase the risk of animal seropositivity (odds ratio = 1.38; 95% confidence interval = 0.55-3.77). This survey indirectly shows that SARS-CoV-2 circulates in canine and feline populations, but its circulation appears to be too low for pets to act as a significant viral reservoir.