EPINEST, an agent-based model to simulate epidemic dynamics in large-scale poultry production and distribution networks.

The rapid intensification of poultry production raises important concerns about the associated risks of zoonotic infections. Here, we introduce EPINEST (EPIdemic NEtwork Simulation in poultry Transportation systems): an agent-based modelling framework designed to simulate pathogen transmission within realistic poultry production and distribution networks. We provide example applications to broiler production in Bangladesh, but the modular structure of the model allows for easy parameterization to suit specific countries and system configurations. Moreover, the framework enables the replication of a wide range of eco-epidemiological scenarios by incorporating diverse pathogen life-history traits, modes of transmission and interactions between multiple strains and/or pathogens. EPINEST was developed in the context of an interdisciplinary multi-centre study conducted in Bangladesh, India, Vietnam and Sri Lanka, and will facilitate the investigation of the spreading patterns of various health hazards such as avian influenza, Campylobacter, Salmonella and antimicrobial resistance in these countries. Furthermore, this modelling framework holds potential for broader application in veterinary epidemiology and One Health research, extending its relevance beyond poultry to encompass other livestock species and disease systems.

Bidirectional Movement of Emerging H5N8 Avian Influenza Viruses Between Europe and Asia via Migratory Birds Since Early 2020.

Migratory birds play a critical role in the rapid spread of highly pathogenic avian influenza (HPAI) H5N8 virus clade 2.3.4.4 across Eurasia. Elucidating the timing and pattern of virus transmission is essential therefore for understanding the spatial dissemination of these viruses. In this study, we surveyed >27,000 wild birds in China, tracked the year-round migration patterns of 20 bird species across China since 2006, and generated new HPAI H5N8 virus genomic data. Using this new data set, we investigated the seasonal transmission dynamics of HPAI H5N8 viruses across Eurasia. We found that introductions of HPAI H5N8 viruses to different Eurasian regions were associated with the seasonal migration of wild birds. Moreover, we report a backflow of HPAI H5N8 virus lineages from Europe to Asia, suggesting that Europe acts as both a source and a sink in the global HPAI virus transmission network.

Genetic diversity, recombination and cross-species transmission of a waterbird gammacoronavirus in the wild.

Viruses emerging from wildlife can cause outbreaks in humans and domesticated animals. Predicting the emergence of future pathogens and mitigating their impacts requires an understanding of what shapes virus diversity and dynamics in wildlife reservoirs. In order to better understand coronavirus ecology in wild species, we sampled birds within a coastal freshwater lagoon habitat across 5 years, focussing on a large population of mute swans (Cygnus olor) and the diverse species that they interact with. We discovered and characterised the full genome of a divergent gammacoronavirus belonging to the Goose coronavirus CB17 species. We investigated the genetic diversity and dynamics of this gammacoronavirus using untargeted metagenomic sequencing of 223 faecal samples from swans of known age and sex, and RT-PCR screening of 1632 additional bird samples. The virus circulated persistently within the bird community; virus prevalence in mute swans exhibited seasonal variations, but did not change with swan age-class or epidemiological year. One whole genome was fully characterised, and revealed that the virus originated from a recombination event involving an undescribed gammacoronavirus species. Multiple lineages of this gammacoronavirus co-circulated within our study population. Viruses from this species have recently been detected in aquatic birds from both the Anatidae and Rallidae families, implying that host species habitat sharing may be important in shaping virus host range. As the host range of the Goose coronavirus CB17 species is not limited to geese, we propose that this species name should be updated to 'Waterbird gammacoronavirus 1'. Non-invasive sampling of bird coronaviruses may provide a tractable model system for understanding the evolutionary and cross-species dynamics of coronaviruses.

Estimation of Rift Valley fever virus spillover to humans during the Mayotte 2018-2019 epidemic.

Rift Valley fever (RVF) is an emerging, zoonotic, arboviral hemorrhagic fever threatening livestock and humans mainly in Africa. RVF is of global concern, having expanded its geographical range over the last decades. The impact of control measures on epidemic dynamics using empirical data has not been assessed. Here, we fitted a mathematical model to seroprevalence livestock and human RVF case data from the 2018-2019 epidemic in Mayotte to estimate viral transmission among livestock, and spillover from livestock to humans through both direct contact and vector-mediated routes. Model simulations were used to assess the impact of vaccination on reducing the epidemic size. The rate of spillover by direct contact was about twice as high as vector transmission. Assuming 30% of the population were farmers, each transmission route contributed to 45% and 55% of the number of human infections, respectively. Reactive vaccination immunizing 20% of the livestock population reduced the number of human cases by 30%. Vaccinating 1 mo later required using 50% more vaccine doses for a similar reduction. Vaccinating only farmers required 10 times as more vaccine doses for a similar reduction in human cases. Finally, with 52.0% (95% credible interval [CrI] [42.9-59.4]) of livestock immune at the end of the epidemic wave, viral reemergence in the next rainy season (2019-2020) is unlikely. Coordinated human and animal health surveillance, and timely livestock vaccination appear to be key to controlling RVF in this setting. We furthermore demonstrate the value of a One Health quantitative approach to surveillance and control of zoonotic infectious diseases.

Sequestration and Destruction of Rinderpest Virus-Containing Material 10 Years after Eradication.

In 2021, the world marked 10 years free from rinderpest. The United Nations Food and Agriculture Organization and World Organisation for Animal Health have since made great strides in consolidating, sequencing, and destroying stocks of rinderpest virus-containing material, currently kept by only 14 known institutions. This progress must continue.

Genomic Epidemiology of Early SARS-CoV-2 Transmission Dynamics, Gujarat, India.

Limited genomic sampling in many high-incidence countries has impeded studies of severe respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic epidemiology. Consequently, critical questions remain about the generation and global distribution of virus genetic diversity. We investigated SARS-CoV-2 transmission dynamics in Gujarat, India, during the state's first epidemic wave to shed light on spread of the virus in one of the regions hardest hit by the pandemic. By integrating case data and 434 whole-genome sequences sampled across 20 districts, we reconstructed the epidemic dynamics and spatial spread of SARS-CoV-2 in Gujarat. Our findings indicate global and regional connectivity and population density were major drivers of the Gujarat outbreak. We detected >100 virus lineage introductions, most of which appear to be associated with international travel. Within Gujarat, virus dissemination occurred predominantly from densely populated regions to geographically proximate locations that had low population density, suggesting that urban centers contributed disproportionately to virus spread.

Transmission Dynamics of African Swine Fever Virus, South Korea, 2019.

African swine fever (ASF) is a substantial concern for global food production and security. However, lack of epidemiologic data in affected areas has limited the knowledge of the main drivers of ASF virus (ASFV) transmission. To assess the role of vehicle movements and wild boar populations in spreading ASFV to pig farms in South Korea, we combined data generated by ASF surveillance on pig farms and of wild boars with nationwide global positioning system-based tracking data for vehicles involved in farming activities. Vehicle movements from infected premises were associated with a higher probability of ASFV incursion into a farm than was geographic proximity to ASFV-infected wild boar populations. Although ASFV can spill over from infected wild boars into domestic pigs, vehicles played a substantial role in spreading infection between farms, despite rapid on-farm detection and culling. This finding highlights the need for interventions targeting farm-to-farm and wildlife-to-farm interfaces.

A dynamic model of transmission and elimination of peste des petits ruminants in Ethiopia.

Peste des petits ruminants (PPR), a devastating viral disease of sheep and goats, has been targeted by the global community for eradication within the next 15 years. Although an efficacious attenuated live vaccine is available, the lack of knowledge about the transmission potential of PPR virus (PPRV) may compromise eradication efforts. By fitting a metapopulation model simulating PPRV spread to the results of a nationwide serological survey in Ethiopia, we estimated the level of viral transmission in an endemic setting and the vaccination coverage required for elimination. Results suggest that the pastoral production system as a whole acts as a viral reservoir, from which PPRV spills over into the sedentary production system, where viral persistence is uncertain. Estimated levels of PPRV transmission indicate that viral spread could be prevented if the proportion of immune small ruminants is kept permanently above 37% in at least 71% of pastoral village populations. However, due to the high turnover of these populations, maintaining the fraction of immune animals above this threshold would require high vaccine coverage within villages, and vaccination campaigns to be conducted annually. Adapting vaccination strategies to the specific characteristics of the local epidemiological context and small ruminant population dynamics would result in optimized allocation of limited resources and increase the likelihood of PPR eradication.

Prevalence of Avian Influenza A(H5) and A(H9) Viruses in Live Bird Markets, Bangladesh.

We conducted a cross-sectional study in live bird markets (LBMs) in Dhaka and Chittagong, Bangladesh, to estimate the prevalence of avian influenza A(H5) and A(H9) viruses in different types of poultry and environmental areas by using Bayesian hierarchical logistic regression models. We detected these viruses in nearly all LBMs. Prevalence of A(H5) virus was higher in waterfowl than in chickens, whereas prevalence of A(H9) virus was higher in chickens than in waterfowl and, among chicken types, in industrial broilers than in cross-breeds and indigenous breeds. LBMs with >1 wholesaler were more frequently contaminated by A(H5) virus than retail-only LBMs. Prevalence of A(H9) virus in poultry and level of environmental contamination were also higher in LBMs with >1 wholesaler. We found a high level of circulation of both avian influenza viruses in surveyed LBMs. Prevalence was influenced by type of poultry, environmental site, and trading.

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.

Interventions for avian influenza A (H5N1) risk management in live bird market networks.

Highly pathogenic avian influenza virus subtype H5N1 is endemic in Asia, with live bird trade as a major disease transmission pathway. A cross-sectional survey was undertaken in northern Vietnam to investigate the structure of the live bird market (LBM) contact network and the implications for virus spread. Based on the movements of traders between LBMs, weighted and directed networks were constructed and used for social network analysis and individual-based modeling. Most LBMs were connected to one another, suggesting that the LBM network may support large-scale disease spread. Because of cross-border trade, it also may promote transboundary virus circulation. However, opportunities for disease control do exist. The implementation of thorough, daily disinfection of the market environment as well as of traders' vehicles and equipment in only a small number of hubs can disconnect the network dramatically, preventing disease spread. These targeted interventions would be an effective alternative to the current policy of a complete ban of LBMs in some areas. Some LBMs that have been banned still are very active, and they likely have a substantial impact on disease dynamics, exhibiting the highest levels of susceptibility and infectiousness. The number of trader visits to markets, information that can be collected quickly and easily, may be used to identify LBMs suitable for implementing interventions. This would not require prior knowledge of the force of infection, for which laboratory-confirmed surveillance would be necessary. These findings are of particular relevance for policy development in resource-scarce settings.

Spatiotemporal trends in the discovery of new swine infectious agents.

A literature review was conducted to assess the spatiotemporal trend and diversity of infectious agents that were newly found in pigs between 1985 and 2010. We identified 173 new variants from 91 species, of which 73 species had not been previously described in pigs. These new species, of which one third was zoonotic, were taxonomically diverse. They were identified throughout the study period, predominantly in the main pork producing countries, with the rate of discovery of new virus variants doubling within the last 10 years of the study period. Whilst infectious agent species newly detected in high-income countries were more likely to be associated with higher virulence, zoonotic agents prevailed in low- and middle-income countries. Although this trend is influenced by factors conditioning infectious agent detection - diagnostic methods, surveillance efforts, research interests -, it may suggest that different scales and types of production systems promote emergence of certain types of infectious agents. Considering the rapid transformation of the swine industry, concerted efforts are needed for improving our understanding of the factors influencing the emergence of infectious agents. This information then needs to inform the design of risk-based surveillance systems and strategies directly mitigating the risk associated with these factors.

Modelling the transmission dynamics of H9N2 avian influenza viruses in a live bird market.

H9N2 avian influenza viruses (AIVs) are a major concern for the poultry sector and human health in countries where this subtype is endemic. By fitting a model simulating H9N2 AIV transmission to data from a field experiment, we characterise the epidemiology of the virus in a live bird market in Bangladesh. Many supplied birds arrive already exposed to H9N2 AIVs, resulting in many broiler chickens entering the market as infected, and many indigenous backyard chickens entering with pre-existing immunity. Most susceptible chickens become infected within one day spent at the market, owing to high levels of viral transmission within market and short latent periods, as brief as 5.3 hours. Although H9N2 AIV transmission can be substantially reduced under moderate levels of cleaning and disinfection, effective risk mitigation also requires a range of additional interventions targeting markets and other nodes along the poultry production and distribution network.

Rinderpest virus sequestration and use in posteradication era.

After the 2011 declaration of rinderpest disease eradication, we surveyed 150 countries about rinderpest virus stocks. Forty-four laboratories in 35 countries held laboratory-attenuated strains, field strains, or diagnostic samples. Vaccine and reagent production and laboratory experiments continued. Rigorous standards are necessary to ensure that stocks are kept under safe conditions.

Simulating contact networks for livestock disease epidemiology: a systematic review.

Contact structure among livestock populations influences the transmission of infectious agents among them. Models simulating realistic contact networks therefore have important applications for generating insights relevant to livestock diseases. This systematic review identifies and compares such models, their applications, data sources and how their validity was assessed. From 52 publications, 37 models were identified comprising seven model frameworks. These included mathematical models (n = 8; including generalized random graphs, scale-free, Watts-Strogatz and spatial models), agent-based models (n = 8), radiation models (n = 1) (collectively, considered 'mechanistic'), gravity models (n = 4), exponential random graph models (n = 9), other forms of statistical model (n = 6) (statistical) and random forests (n = 1) (machine learning). Overall, nearly half of the models were used as inputs for network-based epidemiological models. In all models, edges represented livestock movements, sometimes alongside other forms of contact. Statistical models were often applied to infer factors associated with network formation (n = 12). Mechanistic models were commonly applied to assess the interaction between network structure and disease dissemination (n = 6). Mechanistic, statistical and machine learning models were all applied to generate networks given limited data (n = 13). There was considerable variation in the approaches used for model validation. Finally, we discuss the relative strengths and weaknesses of model frameworks in different use cases.

Elasticity and substitutability of food demand and emerging disease risk on livestock farms.

Disease emergence in livestock is a product of environment, epidemiology and economic forces. The environmental factors contributing to novel pathogen emergence in humans have been studied extensively, but the two-way relationship between farm microeconomics and outbreak risk has received comparably little attention. We introduce a game-theoretic model where farmers produce and sell two goods, one of which (e.g. pigs, poultry) is susceptible to infection by a pathogen. We model market and epidemiological effects at both the individual farm level and the community level. We find that in the case of low demand elasticity for livestock meat, the presence of an animal pathogen causing production losses can lead to a bistable system where two outcomes are possible: (i) successful disease control or (ii) maintained disease circulation, where farmers slaughter their animals at a low rate, face substantial production losses, but maintain large herds because of the appeal of high meat prices. Our observations point to the potentially critical effect of price elasticity of demand for livestock products on the success or failure of livestock disease control policies. We show the potential epidemiological benefits of (i) policies aimed at stabilizing livestock product prices, (ii) subsidies for alternative agricultural activities during epidemics, and (iii) diversifying agricultural production and sources of proteins available to consumers.

Modelling flock heterogeneity in the transmission of peste des petits ruminants virus and its impact on the effectiveness of vaccination for eradication.

Peste des petits ruminants (PPR) is an acute infectious disease of small ruminants targeted for global eradication by 2030. The Global Strategy for Control and Eradication (GSCE) recommends mass vaccination targeting 70% coverage of small ruminant populations in PPR-endemic regions. These small ruminant populations are diverse with heterogeneous mixing patterns that may influence PPR virus (PPRV) transmission dynamics. This paper evaluates the impact of heterogeneous mixing on (i) PPRV transmission and (ii) the likelihood of different vaccination strategies achieving PPRV elimination, including the GSCE recommended strategy. We develop models simulating heterogeneous transmission between hosts, including a metapopulation model of PPRV transmission between villages in lowland Ethiopia fitted to serological data. Our results demonstrate that although heterogeneous mixing of small ruminant populations increases the instability of PPRV transmission-increasing the chance of fadeout in the absence of intervention-a vaccination coverage of 70% may be insufficient to achieve elimination if high-risk populations are not targeted. Transmission may persist despite very high vaccination coverage (>90% small ruminants) if vaccination is biased towards more accessible but lower-risk populations such as sedentary small ruminant flocks. These results highlight the importance of characterizing small ruminant mobility patterns and identifying high-risk populations for vaccination and support a move towards targeted, risk-based vaccination programmes in the next phase of the PPRV eradication programme. Our modelling approach also illustrates a general framework for incorporating heterogeneous mixing patterns into models of directly transmitted infectious diseases where detailed contact data are limited. This study improves understanding of PPRV transmission and elimination in heterogeneous small ruminant populations and should be used to inform and optimize the design of PPRV vaccination programmes.

Revealing the Relational Mechanisms of Research for Development Through Social Network Analysis.

Achieving impact through research for development programmes (R4D) requires engagement with diverse stakeholders across the research, development and policy divides. Understanding how such programmes support the emergence of outcomes, therefore, requires a focus on the relational aspects of engagement and collaboration. Increasingly, evaluation of large research collaborations is employing social network analysis (SNA), making use of its relational view of causation. In this paper, we use three applications of SNA within similar large R4D programmes, through our work within evaluation of three Interidsiplinary Hubs of the Global Challenges Research Fund, to explore its potential as an evaluation method. Our comparative analysis shows that SNA can uncover the structural dimensions of interactions within R4D programmes and enable learning about how networks evolve through time. We reflect on common challenges across the cases including navigating different forms of bias that result from incomplete network data, multiple interpretations across scales, and the challenges of making causal inference and related ethical dilemmas. We conclude with lessons on the methodological and operational dimensions of using SNA within monitoring, evaluation and learning (MEL) systems that aim to support both learning and accountability. Supplementary Information: The online version contains supplementary material available at 10.1057/s41287-023-00576-y.

Pour que les programmes de recherche pour le développement (R4D ou Research for Developmement en anglais) aient un impact, il faut un engagement entre diverses parties prenantes dans les domaines de la recherche, du développement et des politiques. Il est nécessaire de se concentrer sur les aspects relationnels de l'engagement et de la collaboration si l'on souhaite comprendre la façon dont ce type de programme permet l'émergence de résultats. L'évaluation des grands consortia de recherche utilise de plus en plus fréquemment l'analyse des réseaux sociaux (SNA ou social network analysis en anglais) en appliquant sa vision relationnelle de la causalité. Dans cet article, en vue d'explorer son potentiel en tant que méthode d'évaluation, nous utilisons trois applications d'analyse des réseaux sociaux au sein de grands programmes R4D similaires dans le cadre de notre travail d'évaluation de trois pôles interdisciplinaires du Fonds de recherche sur les défis mondiaux. Notre analyse comparative montre que l'analyse des réseaux sociaux peut révéler les dimensions structurelles des interactions au sein de ces programmes et permettre d'apprendre comment les réseaux évoluent dans le temps. Nous menons une réflexion quant aux défis communs qui émanent de ces cas, y compris la gestion de différentes formes de biais qui résultent de données de réseau incomplètes, de multiples interprétations sur des échelles différentes et les défis liés au fait d'établir une inférence causale et les dilemmes éthiques connexes. Nous concluons par des leçons sur les dimensions méthodologiques et opérationnelles de l'utilisation de l'analyse des réseaux sociaux dans les systèmes de suivi, d'évaluation et d'apprentissage (SEA) qui visent à soutenir à la fois l'apprentissage et la redevabilité.

Quantitative and qualitative analysis of antimicrobial usage and biosecurity on broiler and Sonali farms in Bangladesh.

Antimicrobial use (AMU) is a major contributing factor to the rising threat of antimicrobial resistance (AMR) in human and animals. To control AMR, indiscriminate antibiotic use needs to be restricted, preventive measures such as biosecurity must be prioritized and proper action plans must be implemented. This study aimed to quantify and associate AMU and biosecurity status of broiler and Sonali farms in Bangladesh. Data on all antimicrobial treatments administered during a batch production cycle and antimicrobials purchased over a year were collected from 94 conventional broiler and 51 Sonali (cross-breed) farms from the northern and southeast regions of Bangladesh. Flock-level AMU was quantified using Treatment Incidence (TI) per 100 days based on the Defined Daily Dose (TIDDDvet) expressing the number of days per 100 animal-days at risk that the flock receives a standard dose of antimicrobials. The biosecurity status (external and internal) of these farms was assessed by means of the Biocheck.UGent scoring system and the correlation between biosecurity and TIDDDvet were assessed by Pearson's correlation coefficients. Median flock TIDDDvet was 60 and 58 for broilers and Sonali flocks, indicating that the birds were treated around 60% and 58% of their lifetime with an antimicrobial dose, respectively. Minimum and maximum values of TIDDDvet ranged from 18 -188 and 31-212 in broilers and Sonali, respectively. Fluoroquinolones, sulfonamides, tetracyclines and aminopenicillins were the most frequently used antimicrobial classes. The mean external and internal biosecurity scores were 39% and 61% for broilers and 44% and 61% for Sonali, respectively. There was a statistically significant difference in the external biosecurity score in broiler farms in the two regions (p ≤ 0.001), whereas, the internal biosecurity score was borderline not statistically significantly different (p = 0.065). The biosecurity score was negatively correlated with AMU in broiler and sonali farms both for external (R2 =-0.38; -0.36) and internal biosecurity (R2 =-0.33; -0.32), respectively. As most of the farmers treated their birds with antimicrobials for a very large part of the production, it could be concluded that there is a high overuse of antimicrobials both in broiler and Sonali poultry production in Bangladesh. This study also highlighted a low level of farm biosecurity practices. Overuse of antimicrobials and low level of biosecurity practice may be due to a lack of knowledge, ignorance, avoid loss and/or lack of monitoring by governmental agencies. Therefore, urgent action is required to increase awareness and biosecurity levels and to reduce AMU in these production systems.

Contrasting seasonality of African swine fever outbreaks and its drivers.

The seasonality of African swine fever (ASF) outbreaks in domestic pigs differs between temperate and subtropical/tropical regions. We hypothesise that variations in the importance of wild boar-to-farm and farm-to-farm transmission routes shape these contrasting patterns, and we emphasise the implications for effective ASF control.