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Funding and financing for One Health initiatives at country level remain challenging as investments commonly require demonstrated evidence of economic value or returns. The objectives of this review were to i) identify, critically analyse and summarise quantitative evidence of the net economic value of One Health initiatives; ii) document methodologies commonly used in the scientific literature; and iii) describe common challenges and any evidence gaps. Scientific databases were searched for published literature following the PRISMA guidelines and an online survey and workshop with subject matter experts were used to identify relevant grey literature. Studies were included if they reported on quantitative costs and benefits (monetary and non-monetary) and were measured across at least two sectors. Relevant publications were analysed and plotted against the six action tracks of the Quadripartite One Health Joint Plan of Action to help classify the initiatives. Ninety-seven studies were included. Eighty studies involved only two sectors and 78 reported a positive economic value or return. Of those studies that reported a positive return, 49 did not compare with a sectoral counterfactual, 28 studies demonstrated an added value of using a cross-sectoral approach, and 6 studies demonstrated an added value of One Health communication, collaboration, coordination, and capacity building. Included studies most frequently related to endemic zoonotic, neglected tropical and vector-borne diseases, followed by health of the environment and food safety. However, diversity in economic analysis methodology between studies included resulted in difficulty to compare or combine findings. While there is a growing body of evidence of the value of One Health initiatives, a substantial part of the evidence still focuses on "traditional" One Health topics, particularly zoonoses. Developing a standardised and practical approach for One Health economic evaluation will facilitate assessment of the added value and gather evidence for One Health to be invested in and endorsed by multiple sectors., Competing Interests: A grant from the Foundation funded AA's, BH's and ER's time. The grant also funded a partnership contract with CIRAD. Project grant code: MTF /GLO/1040/BMG. BH is a member of the One Health Lancet Commission. MP is an expert member of the technical advisory panel of the Pandemic Fund and member of PREZODE initiative secretariat. The authors declare no other competing interests., (© 2024 The Authors. Published by Elsevier B.V.)

Background: Strengthening the surveillance of zoonotic diseases emergence in the wild meat value chains is a critical component of the prevention of future health crises. Community hunters could act as first-line observers in zoonotic pathogens surveillance systems in wildlife, by reporting early signs of the possible presence of a disease in the game animals they observe and manipulate on a regular basis., Methods: An experimental game was developed and implemented in a forested area of Gabon, in central Africa. Our objective was to improve our understanding of community hunters' decision-making when finding signs of zoonotic diseases in game animals: would they report or dissimulate these findings to a health agency? 88 hunters, divided into 9 groups of 5 to 13 participants, participated in the game, which was run over 21 rounds. In each round the players participated in a simulated hunting trip during which they had a chance of capturing a wild animal displaying clinical signs of a zoonotic disease. When signs were visible, players had to decide whether to sell/consume the animal or to report it. The last option implied a lowered revenue from the hunt but an increased probability of early detection of zoonotic diseases with benefits for the entire group of hunters., Results: The results showed that false alerts-i.e. a suspect case not caused by a zoonotic disease-led to a decrease in the number of reports in the next round (Odds Ratio [OR]: 0.46, 95% Confidence Interval [CI]: 0.36-0.8, p < 0.01). Hunters who had an agricultural activity in addition to hunting reported suspect cases more often than others (OR: 2.05, 95% CI: 1.09-3.88, p < 0.03). The number of suspect case reports increased with the rank of the game round (Incremental OR: 1.11, CI: 1.06-1.17, p < 0.01) suggesting an increase in participants' inclination to report throughout the game., Conclusion: Using experimental games presents an added value for improving the understanding of people's decisions to participate in health surveillance systems., (© 2024. The Author(s).)

Human pressure on the environment is increasing the frequency, diversity, and spatial extent of disease outbreaks. Despite international recognition, the interconnection between the health of the environment, animals, and humans has been historically overlooked. Past and current initiatives have often neglected prevention under the One Health preparedness cycle, largely focusing on post-spillover stages. We argue that pandemic prevention initiatives have yet to produce actionable targets and indicators, connected to overarching goals, like it has been done for biodiversity loss and climate change. We show how the Driver-Pressure-State-Impact-Response framework, already employed by the Convention on Biological Diversity, can be repurposed to operationalize pandemic prevention. Global responses for pandemic prevention should strive for complementarity and synergies among initiatives, better articulating prevention under One Health. Without agreed-upon goals underpinning specific targets and interventions, current global efforts are unlikely to function at the speed and scale necessary to decrease the risk of disease outbreaks that might lead to pandemics. Threats to the environment are not always abatable, but decreasing the likelihood that environmental pressure leads to pandemics, and developing strategies to mitigate these impacts, are both attainable goals., (© 2023. The Author(s).)

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., (© 2023 The Authors.)

Antimicrobial resistance (AMR) is a global public health threat responsible for 700,000 deaths per year worldwide. There is scientific evidence of the causal relationship between antimicrobial use (AMU) along the food chain and AMR. Improving AMU in livestock is therefore a key component in the fight against AMR. To improve AMU in livestock, there is no one-size-fits-all solution and strategies must be context-adapted and socially acceptable for actors in order to increase AMU sustainability. AMU decision-making is based on an interdependent set of economic, behavioral, ethical, and cultural factors that need to be assessed to advise on the potential impacts of measures. We hypothesized that a participatory strategic planning approach may increase the plausibility and the efficacy of the strategies formulated by facilitating the dialogue between actors of diverse backgrounds, stimulating innovative thinking and constant considerations of contextual factors, actors and impacts. We adapted and applied the ImpresS ex ante approach (IMPact in reSearch in the South, https://impress-impact-recherche.cirad.fr/) within a Living Lab engaging actors from the French pig and poultry sectors in co-creation of innovative strategies towards improved AMU. We conducted semi-structured interviews and participatory workshops between April 2021 and March 2022. The results describe 1) an initial diagnosis of the current AMU situation in the pig and poultry sectors in France; 2) a common vision of the future to which participants would like to contribute through the intervention; 3) an identification of the current problems opposed to this vision of the future; 4) a defined scope of the intervention; 5) a typology of actors protagonist or impacted by those issues and 6) outcome maps to solve a priority problem related to indicators and monitoring. This study provides recommendations for decision-makers on plausible and innovative strategies to sustainably improve AMU in pig and poultry sectors in France and evidence of the benefits of participatory strategic planning approaches., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Guenin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The epidemic of COVID-19 has shown different developments in Africa compared to the other continents. Three different approaches were used in this study to analyze this situation. In the first part, basic statistics were performed to estimate the contribution of the elderly people to the total numbers of cases and deaths in comparison to the other continents; Similarly, the health systems capacities were analysed to assess the level of underreporting. In the second part, differential equations were reconstructed from the epidemiological time series of cases and deaths (from the John Hopkins University) to analyse the dynamics of COVID-19 in seventeen countries. In the third part, the time evolution of the contact number was reconstructed since the beginning of the outbreak to investigate the effectiveness of the mitigation strategies. Results were compared to the Oxford stringency index and to the mobility indices of the Google Community Mobility Reports. Compared to Europe, the analyses show that the lower proportion of elderly people in Africa enables to explain the lower total numbers of cases and deaths by a factor of 5.1 on average (from 1.9 to 7.8). It corresponds to a genuine effect. Nevertheless, COVID-19 numbers are effectively largely underestimated in Africa by a factor of 8.5 on average (from 1.7 to 20. and more) due to the weakness of the health systems at country level. Geographically, the models obtained for the dynamics of cases and deaths reveal very diversified dynamics. The dynamics is chaotic in many contexts, including a situation of bistability rarely observed in dynamical systems. Finally, the contact number directly deduced from the epidemiological observations reveals an effective role of the mitigation strategies on the short term. On the long term, control measures have contributed to maintain the epidemic at a low level although the progressive release of the stringency did not produce a clear increase of the contact number. The arrival of the omicron variant is clearly detected and characterised by a quick increase of interpeople contact, for most of the African countries considered in the analysis., Competing Interests: The authors have declared that no competing interests exist.

The Ebola virus disease epidemic that threatened West Africa between 2013 and 2016 was of unprecedented health magnitude. After this health crisis, studies highlighted the need to introduce community-based surveillance systems and to adopt a One Health approach. This study aimed to provide preparatory insights for the definition of a community-based surveillance system for emerging zoonoses such as viral hemorrhagic fevers in Guinea. The objective was to explore the disease detection capacity and the surveillance network opportunities at the community level in two pilot areas in the forest region of Guinea, where the epidemic emerged. Based on a participatory epidemiological and One Health approach, we conducted Focus Group Discussions with human, animal and ecosystem health actors. We used a range of participatory tools, included semi-structured interviews, ranking, scoring and flow diagram, to estimate the local knowledge and perception of diseases and clinical signs and to investigate the existing health information exchange network and its related strengths and weaknesses. The results showed that there is heterogeneity in knowledge of diseases and perception of the clinical signs among actors and that there are preferred and more effective health communication channels opportunities. This preparatory study suggests that it is necessary to adapt the case definitions and the health communication channels to the different actors who can play a role in a future community-based surveillance system and provides recommendations for future surveillance activities to be carried out in West Africa., Competing Interests: The authors have declared that no competing interests exist.

Public-private partnerships (PPPs) in the veterinary domain are joint approaches in which public veterinary services and private actors such as private veterinarians, producers' associations, or private companies work together to address complex animal health challenges. They are implemented worldwide and can help to strengthen the capacities of veterinary services, but few have been evaluated. None of the evaluations developed in the veterinary domain explicitly addressed PPPs, their complex program design, their evolving governance, and coordination system, and their impacts. This work represents the first application of the participatory impact pathway methodology for the evaluation of a PPP in the veterinary domain. The PPP evaluated aimed at developing the poultry sector in Ethiopia and improving poultry health service coverage, particularly in remote areas. The combination of semi-structured interviews ( n = 64) and collective reflection during three workshops ( n participants = 26, 48, 18), captured the viewpoints of public and private partners, actors who influenced the partnership, and actors impacted by it. The context of the PPP was analyzed, and the causal relationships between the PPP and its impacts were investigated. This work showed that collaboration between the public and private sector occurred at several administrative levels. The actors considered a variety of impacts, on the economy, business, trust, and health, which were then measured through different indicators. The actors also identified the added value of the PPP to enrich those impacts. The participatory impact pathway methodology helped to strengthen the engagement of actors in the PPP and to formulate recommendations at the policy level to favor positive results. This case study represents a milestone in building a participatory evaluation framework of PPP in the veterinary domain., Competing Interests: FT and UD were employed by Ethiochicken at the time of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 N'Guessan, Poupaud, Dieuzy-Labaye, Asfaw, Wieland, Tesfu, Daniel, Tulayakul and Peyre.)

Although currently available data indicate that Africa has the lowest usage of antimicrobials in animals in the world (adjusted by animal biomass), data show a high prevalence of antimicrobial resistance in foodborne pathogens isolated from animals and animal products. Apart from the lack of solid data on antimicrobial use in many countries in Africa, different hypotheses could explain this situation. Qualitative interviews of farmers show a lack of knowledge and uninformed use of antimicrobials. Considering the development of animal farming to meet an increasing demand for proteins, this deficiency represents a serious public health issue. We advocate for policies that consider the specific challenges faced by family farmers in Africa, to simultaneously improve access to veterinary drugs while strengthening the regulation of their use. We propose a global approach targeting the agri-food system, offering innovative social and technical interventions on antimicrobial usage, adapted to family farmers.

Public-private partnerships (PPPs) in the veterinary domain are widely implemented worldwide and can help to strengthen the capacities of Veterinary Services. Few analyses have been made of these initiatives. This study is aimed at developing an evaluation tool based on participatory approaches and focusing on the quality of PPP processes in the veterinary domain. The tool was divided into ten sections relevant to PPP process organisation and activities. The 44 evaluation criteria and six quality attributes (operationality, relevance, acceptability, inclusiveness, adaptability, and stability) were identified based on literature review and case-study application. The tool was adjusted during four regional PPP training workshops bringing together stakeholders from both public and private sectors. Finally, the tool was validated through an experts' elicitation process and applied in the field in Paraguay. The tool was developed in a non-normative perspective to help the partners adapt the PPP to their specific context, to maximize the opportunities and minimize the risks of such collaborations, and to formulate adapted recommendations to strengthen and improve the PPP collaborative process and thus the outcomes. In an ex-ante perspective, this tool would also help public and private actors to engage and develop a PPP process following the best possible practices. The aim of this tool is to help decision making in terms of PPP development and implementation in the veterinary domain to ensure the added value and relevance of such a collaborative approach in different countries worldwide., Competing Interests: The authors have declared that no competing interests exist.

France recently faced two epizootic waves of highly pathogenic avian influenza (HPAI) in poultry (H5N6 in 2015-2016 and H5N8 in 2016-2017), mainly in the fattening duck production sector. Vaccination against avian influenza (AI) is currently not authorised in France even though its potential benefits were discussed during these epizootic events. The objective of this work was to evaluate the potential efficiency of different vaccination strategies that could be applied against AI in France. The EVACS tool, which is a decision support tool developed to evaluate vaccination strategies, was applied in several French poultry production sectors: broiler, layer, turkey, duck and guinea fowl. EVACS was used to simulate the performance of vaccination strategies in terms of vaccination coverage, immunity levels and spatial distribution of the immunity level. A cost-benefit analysis was then applied based on EVACS results to identify the most efficient strategy. For each sector, vaccination protocols were tested according to the production type (breeders/production, indoor/outdoor), the integration level (integrated/independent) and the type of vaccine (hatchery vaccination using a recombinant vaccine/farm vaccination using an inactivated vaccine). The most efficient protocols for each sector were then combined to test different overall vaccination strategies at the national level. Even if it was not possible to compare vaccination protocols with the two vaccines types in "foie gras" duck, meat duck and guinea fowl production sectors as no hatchery vaccine currently exist for these species, these production sectors were also described and included in this simulation. Both types of vaccination (at hatchery and farm level) enabled protective immunity levels for the control of AI, but higher poultry population immunity level was reached (including independent farms) using hatchery vaccination. We also showed that hatchery vaccination was more efficient (higher benefit-cost ratio) than farm vaccination. Sufficient and homogeneously spatially distributed protective levels were reached in the overall poultry population with vaccination strategies targeting breeders, chicken layers and broilers and turkeys, without the need to include ducks and guinea fowls. However, vaccination strategies involving the highest number of species and production types were the most efficient in terms of cost-benefit. This study provides critical information on the efficiency of different vaccination strategies to support future decision making in case vaccination was applied to prevent and control HPAI in France., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

From May 2013 to April 2014, 15 swine family-run farms (17 pig litters) in two districts in Hung Yen province, near Hanoi, were virologically and epizootiologically monitored for swine influenza viruses (SIV) monthly. No SIV was isolated from nasal swabs. Maternal antibodies were detected in 10 litters, and seroconversion against SIV was detected in six litters. There was a marked difference in patterns of SIV transmission in the two districts. Van Lam district which has low density of swine with mainly smallholder farms had low intensity of SIV, with much of the infection caused by H1N1 2009 pandemic-like viruses A(H1N1)pdm09, likely originated from humans. In contrast, Van Giang district, which has high swine density and larger farms, had high levels of typical SIV (triple reassortants H3N2 and H3N2 Binh Duong lineage viruses) circulating within swine. With one exception, the SIV lineages detected were those we concurrently isolated from studies in a large central abattoir in Hanoi. Influenza-like illness symptoms reported by farmers were poorly correlated with serological evidence of SIV infection., (© 2019 Blackwell Verlag GmbH.)

Poultry production has significantly increased worldwide, along with the number of avian influenza (AI) outbreaks and the potential threat for human pandemic emergence. The role of wild bird movements in this global spread has been extensively studied while the role of animal, human and fomite movement within commercial poultry production and trade networks remains poorly understood. The aim of this work is to better understand these roles in relation to the different routes of AI spread. A scoping literature review was conducted according to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) using a search algorithm combining twelve domains linked to AI spread and animal/human movements within poultry production and trade networks. Only 28 out of 3,978 articles retrieved dealt especially with the role of animal, human and fomite movements in AI spread within the international trade network (4 articles), the national trade network (8 articles) and the production network (16 articles). While the role of animal movements in AI spread within national trade networks has been largely identified, human and fomite movements have been considered more at risk for AI spread within national production networks. However, the role of these movements has never been demonstrated with field data, and production networks have only been partially studied and never at international level. The complexity of poultry production networks and the limited access to production and trade data are important barriers to this knowledge. There is a need to study the role of animal and human movements within poultry production and trade networks in the global spread of AI in partnership with both public and private actors to fill this gap., Competing Interests: This study was funded by Ceva Santé Animale (https://www.ceva.com/en/). Claire Hautefeuille and Gwenaëlle Dauphin are employees of Ceva Santé Animale. CIRAD has a collaborative research agreement with Ceva as part of the private-public funded PhD scholarship of Claire Hautefeuille. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Information about infectious diseases at the global level relies on effective, efficient and sustainable national and international surveillance systems. Surveillance systems need to be regularly evaluated to ensure their performance, the quality of the data and information provided, as well as to allocate resources efficiently. Currently available frameworks for evaluation of surveillance systems in animal or human health often treat technical, process and socio-economic aspects separately instead of integrating them. The surveillance evaluation (EVA) tool, a support tool for the evaluation of animal health surveillance systems, was developed to provide guidance for integrated evaluation of animal health surveillance including economic evaluation. The tool was developed by international experts in surveillance and evaluation in an iterative process of development, testing and revision taking into account existing frameworks and guidance, scientific literature and expert opinion. The EVA tool encompasses a web interface for users to develop an evaluation plan, a Wiki classroom to provide theoretical information on all required concepts and a generic evaluation work plan to facilitate implementation and reporting of outputs to decision makers. The tool was tested by planning and conducting epidemiological and economic evaluations of surveillance for classical and African swine fever, bovine virus diarrhoea, avian influenza, and Salmonella Dublin in five European countries. These practical applications highlighted the importance of a comprehensive evaluation approach to improve the quality of the evaluation outputs (economic evaluation; multiple attributes assessment) and demonstrated the usefulness of the guidance provided by the EVA tool. At the same time they showed that comprehensive evaluations might be constrained by practical issues (e.g. confidentiality concerns, data availability) and resource scarcity. In the long term, the EVA tool is expected to increase professional evaluation capacity and help optimising animal health surveillance system efficiency and resource allocation for both public and private actors of the surveillance systems., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Animal health surveillance is an important tool for disease mitigation and helps to promote animal health and welfare, protect human health, support efficient animal production, and enable trade. This study aimed to assess adoption of recommended standards and best practice for surveillance (including risk-based approaches) in Europe. It included scoping interviews with surveillance experts in Denmark, the Netherlands, Norway, and Switzerland to gather information on knowledge acquisition, decisions and implementation of surveillance, and perceptions. This was followed by an online survey among animal health and food safety surveillance users in EU, EEA, and Schengen countries. A total of 166 responses were collected from 27 countries; 111 were eligible for analysis. A strong preference for legislation and established standards was observed, with peer-reviewed publications, conferences, symposia, and workshops to be major sources of information. The majority of respondents indicated a need for international evaluation for surveillance and implied that considerations of cost-effectiveness were essential when making a decision to adopt new surveillance standards. However, most of the respondents did not use a formal evaluation to inform the adoption of new standards or only conducted a descriptive assessment before their implementation or adaptation. Only a few respondents reported a quantitative economic evaluation despite economic efficiency being considered as a highly relevant criterion for surveillance implementation. Constraints mentioned in the adoption of new surveillance standards included insufficient time, financial and human resources, and lack of competency. Researchers aiming to achieve impact by their surveillance work are advised to consider ways of influencing binding standards and to disseminate their work pro-actively using varied channels of engagement tailored to relevant target audiences and their needs. Generally, a more formal linkage between surveillance information and disease mitigation decisions-for example, by using systematic evaluation-could help increase the economic value of surveillance efforts. Finally, a collaborative, international platform for exchange and learning on surveillance as well as co-design and dissemination of surveillance standards is recommended., (Copyright © 2019 Häsler, Garza, Bisdorff, Léger, Tavornpanich, Peyre, Lindberg, van Schaik, Alban and Stärk.)

Public-Private Partnerships (PPPs) are defined as a collaborative approach in which the public and private sector share resources, responsibilities and risks to achieve common objectives and mutual benefits in a sustainable manner. PPPs are identified as a key solution to reinforce Veterinary Services. However only limited information is available on the scope, added value and enabling factors of PPPs in this sector. The aims of this study were to develop a typology of PPPs in the veterinary field and to identify key success factors and obstacles to their implementation. A structured questionnaire was sent to all 181 World Organisation for Animal Health (OIE) Member Countries and to 47 private contacts. 36 different variables characterizing PPP initiatives were collected. 97 examples of PPPs were retrieved from 76 countries. Dimensionality reduction techniques were combined with clustering and discrimination methods to establish a typology of PPPs and to derive a set of simple rules to classify new instances of PPPs. Three clusters were identified, separated according to two main variables: the type of private partners and the type of interaction. Cluster 1, transactional PPPs, represented the traditional understanding of PPPs by Veterinary Services, initiated and funded by the public sector, giving service delivery accreditation to mostly private veterinarians; cluster 2, collaborative PPPs, included partnerships between producer associations and public Veterinary Services, driven by trade interests; cluster 3, transformational PPPs, represented joint programs initiated and funded by private companies and initially driven by business development objectives. Specific success factors and key obstacles affecting the performances and sustainability of these initiatives were identified for each cluster. This study represents the first practical attempt to develop a meaningful typology of PPPs in the field of animal health and to identify fundamental obstacles currently inhibiting the development of PPPs, and suggests ways to support national Veterinary Services in overcoming these obstacles., Competing Interests: The authors have declared that no competing interests exist.

The economic evaluation of health surveillance systems and of health information is a methodological challenge, as for information systems in general. Main present threads are considering cost-effectiveness solutions, minimizing costs for a given technically required output, or cost-benefit analysis, balancing costs with economic benefits of duly informed public interventions. The latter option, following a linear command-and-control perspective, implies considering a main causal link between information, decision, action, and health benefits. Yet, valuing information, taking into account its nature and multiple sources, the modalities of its processing cycle, from production to diffusion, decentralized use and gradual building of a shared information capital, constitutes a promising challenge. This work proposes an interdisciplinary insight on the value of health surveillance to get a renewed theoretical framework integrating information and informatics theory and information economics. The reflection is based on a typological approach of value, basically distinguishing between use and non-use values. Through this structured discussion, the main idea is to expand the boundaries of surveillance evaluation, to focus on changes and trends, on the dynamic and networked structure of information systems, on the contribution of diverse data, and on the added value of combining qualitative and quantitative information. Distancing itself from the command-and-control model, this reflection considers the behavioral fundaments of many health risks, as well as the decentralized, progressive and deliberative dimension of decision-making in risk management. The framework also draws on lessons learnt from recent applications within and outside of health sector, as in surveillance of antimicrobial resistance, inter-laboratory networks, the use of big data or web sources, the diffusion of technological products and large-scale financial risks. Finally, the paper poses the bases to think the challenge of a workable approach to economic evaluation of health surveillance through a better understanding of health information value. It aims to avoid over-simplifying the range of health information benefits across society while keeping evaluation within the boundaries of what may be ascribed to the assessed information system.

Swine are an important intermediate host for emergence of pandemic influenza. Vietnam is the largest swine producer in South East Asia. Systematic virological and serological surveillance of swine influenza viruses was carried out in Northern Vietnam from May 2013 to June 2014 with monthly sampling of pigs in local and large collective slaughterhouses and in a live pig market. Influenza A seroprevalence in the local slaughterhouses and in the large collective slaughterhouse was 48.7% and 29.1%, respectively. Seventy-seven influenza A viruses were isolated, all from the large collective slaughterhouse. Genetic analysis revealed six virus genotypes including H1N1 2009 pandemic (H1N1pdm09) viruses, H1N2 with H1 of human origin, H3N2 and H1N1pdm09 reassortants, and triple-reassortant H3N2 viruses. Phylogenetic analysis of swine and human H1N1pdm09 viruses showed evidence of repeated spill-over from humans to swine rather than the establishment of H1N1pdm09 as long-term distinct lineage in swine. Surveillance at the large collective slaughterhouse proved to be the most efficient, cost-effective, and sustainable method of surveillance for swine influenza viruses in Vietnam.

This study aimed to analyze the financial impact of foot-and-mouth disease (FMD) outbreaks in cattle at the farm-level and the benefit-cost ratio (BCR) of biannual vaccination strategy to prevent and eradicate FMD for cattle in South Vietnam. Production data were collected from 49 small-scale dairy farms, 15 large-scale dairy farms, and 249 beef farms of Long An and Tay Ninh province using a questionaire. Financial data of FMD impacts were collected using participatory tools in 37 villages of Long An province. The net present value, i.e., the difference between the benefits (additional revenue and saved costs) and costs (additional costs and revenue foregone), of FMD vaccination in large-scale dairy farms was 2.8 times higher than in small-scale dairy farms and 20 times higher than in beef farms. The BCR of FMD vaccination over 1 year in large-scale dairy farms, small-scale dairy farms, and beef farms were 11.6 [95% confidence interval (95% CI) 6.42-16.45], 9.93 (95% CI 3.45-16.47), and 3.02 (95% CI 0.76-7.19), respectively. The sensitivity analysis showed that varying the vaccination cost had more effect on the BCR of cattle vaccination than varying the market price. This benefit-cost analysis of biannual vaccination strategy showed that investment in FMD prevention can be financially profitable, and therefore sustainable, for dairy farmers. For beef cattle, it is less certain that vaccination is profitable. Additional benefit-cost analysis study of vaccination strategies at the national-level would be required to evaluate and adapt the national strategy to achieve eradication of this disease in Vietnam.

The value chain (VC) is a major operational concept for socioeconomic analysis at meso level. Widely mobilized in development practice, it is still undergoing conceptual and practical refining, e.g., to take account of environmental and social sustainability. Briefly, VC refers to a system of value creation through the full set of actors, links, technical and commercial activities and flows involved in the provision of a good or service on a market. In the past decade, this concept has been promoted in the management of animal health. In particular, the emergence of highly pathogenic avian influenza (HPAI) has triggered an interdisciplinary dynamic including VC analysis as a central tool. These efforts promoted participatory investigation methods in the analysis of health systems. Using qualitative and quantitative data, these methods acknowledge the usefulness of actors' involvement and knowledge, hence facilitating the transdisciplinarity needed for effective action. They fit into adaptive and action-oriented strategies, fostering stakeholders' participation. Recent research on HPAI surveillance in South-East Asia merged VC and participatory approaches to develop innovative tools for analyzing constraints to information flow. On-going interventions for HPAI prevention and control as well as the prevention of other emerging zoonotic risks in Africa are presently building on this VC framework to develop strategies for its application at national and regional scales. Based on the latter experiences, this article proposes a field-based perspective on VC applications to animal and public health systems, within a One Health approach responding to the overall challenge of complexity.

While climate is often presented as a key factor influencing the seasonality of diseases, the importance of anthropogenic factors is less commonly evaluated. Using a combination of methods - wavelet analysis, economic analysis, statistical and disease transmission modelling - we aimed to explore the influence of climatic and economic factors on the seasonality of H5N1 Highly Pathogenic Avian Influenza in the domestic poultry population of Vietnam. We found that while climatic variables are associated with seasonal variation in the incidence of avian influenza outbreaks in the North of the country, this is not the case in the Centre and the South. In contrast, temporal patterns of H5N1 incidence are similar across these 3 regions: periods of high H5N1 incidence coincide with Lunar New Year festival, occurring in January-February, in the 3 climatic regions for 5 out of the 8 study years. Yet, daily poultry meat consumption drastically increases during Lunar New Year festival throughout the country. To meet this rise in demand, poultry production and trade are expected to peak around the festival period, promoting viral spread, which we demonstrated using a stochastic disease transmission model. This study illustrates the way in which economic factors may influence the dynamics of livestock pathogens.

This study aims to explore the farmers' perceptions of foot-and-mouth disease (FMD) vaccination using a reflexive research method called Q methodology. A structured sample was composed of 46 farmers selected according to gender, farming experience, level of education, and production type. Statements relevant to the farmers' perceptions of and attitudes toward FMD vaccination, related to confidence, logistics, costs, and impacts of vaccination were developed. Results were analyzed by principal component analysis and factor analysis. The influence of demographics and characterized variables on the respondent's contribution to each factor was also tested. Regarding the different beliefs and behavior toward FMD vaccination, the common perceptions held by Vietnamese cattle and pig farmers were divided into three discourses named Confidence (24 subjects), Belief (12 subjects), and Challenge (6 subjects). The identified discourses represented 57.3% of the variances. Consensus points were found, such as the feeling of being more secure after FMD vaccination campaigns; the fact that farmers take vaccination decisions themselves without being influenced by other stakeholders; the opinion that FMD vaccination is cheaper than the costs of treating a sick animal; and that vaccines provided by governmental authorities are of high quality. Part of the studied population did not consider vaccination to be the first choice strategy in prevention. This raises the question of how to improve the active participation of farmers in the FMD vaccine strategy. Taking into consideration farmers' perceptions can help to implement feasible vaccination strategies at the local level.

Background: The emergence of the 2009 influenza pandemic virus with a swine origin stressed the importance of improving influenza surveillance in swine populations. The objectives of this systematic review and meta-analysis were to describe epidemiological features of swine influenza (SI) across the world and identify factors impacting swine influenza virus surveillance., Methods: The systematic review followed the PRISMA guidelines. Articles published after 1990 containing data on SI on pig and herd-level seroprevalence, isolation and detection rates, and risk factors were included. Meta-regression analyses using seroprevalence and virological rates were performed., Results: A total of 217 articles were included. Low avian influenza (AI) seroprevalence (means pig = 4.1%; herd = 15%) was found, showing that AIV do not readily establish themselves in swine while SIV seroprevalence was usually high across continents (influenza A means pig = 32.6-87.8%; herd = 29.3-100%). Higher pig density and number of pigs per farm were shown by the meta-regression analyses and/or the risk factor articles to be associated with higher SI seroprevalence. Lower seroprevalence levels were observed for countries with low-to-medium GDP. These results suggest that larger industrial farms could be more at risk of SIV circulation. Sampling swine with influenza-like illness (ILI) was positively associated with higher isolation rates; most studies in Europe, Latin and North America were targeting swine with ILI., Conclusions: To improve understanding of SI epidemiology, standardization of the design and reporting of SI epidemiological studies is desirable. Performance of SI surveillance systems in low-to-medium GDP countries should be evaluated to rule out technical issues linked to lower observed SIV prevalence. Targeting certain swine age groups, farming systems and swine with ILI may improve the surveillance cost-effectiveness. However, focusing on pigs with ILI may bias virus detection against strains less virulent for swine but which may be important as pandemic threats.

Global economic impacts of epidemics suggest high return on investment in prevention and One Health capacity. However, such investments remain limited, contributing to persistent endemic diseases and vulnerability to emerging ones. An interdisciplinary workshop explored methods for country-level analysis of added value of One Health approaches to disease control. Key recommendations include: 1. systems thinking to identify risks and mitigation options for decision-making under uncertainty; 2. multisectoral economic impact assessment to identify wider relevance and possible resource-sharing, and 3. consistent integration of environmental considerations. Economic analysis offers a congruent measure of value complementing diverse impact metrics among sectors and contexts., (© The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Surveillance of Classical Swine Fever (CSF) should not only focus on livestock, but must also include wild boar. To prevent disease transmission into commercial pig herds, it is therefore vital to have knowledge about the disease status in wild boar. In the present study, we performed a comprehensive evaluation of alternative surveillance strategies for Classical Swine Fever (CSF) in wild boar and compared them with the currently implemented conventional approach. The evaluation protocol was designed using the EVA tool, a decision support tool to help in the development of an economic and epidemiological evaluation protocol for surveillance. To evaluate the effectiveness of the surveillance strategies, we investigated their sensitivity and timeliness. Acceptability was analysed and finally, the cost-effectiveness of the surveillance strategies was determined. We developed 69 surveillance strategies for comparative evaluation between the existing approach and the novel proposed strategies. Sampling only within sub-adults resulted in a better acceptability and timeliness than the currently implemented strategy. Strategies that were completely based on passive surveillance performance did not achieve the desired detection probability of 95%. In conclusion, the results of the study suggest that risk-based approaches can be an option to design more effective CSF surveillance strategies in wild boar.

A discrete choice experiment (DCE) is carried out to value socio-economic factors influencing the farmer's decision to report swine diseases and to assess the willingness of farmers to report swine diseases. Data were collected between March and July 2015 in two provinces in the Red River Delta, Northern Vietnam, from 196 pig producers by face-to face interview. A conditional logit model is used to measure the relative importance of the socio-economic factors and calculate the expected probability of disease reporting under changes of levels of these factors. Results of the study indicated that the likelihood of compensation and the type of culling implemented (all or only unrecovered pigs) are the two most important factors influencing farmer reporting. Compensation level, movement restriction and delay in compensation payment also have significant impacts on farmer's decision to report animal disease but they are not as important as the above factors. Three different scenarios including changes in six different factors (attributes) are tested to predict probability of animal disease reporting. Under the current situation (uncertainty of being compensated), only 4% of the farmers would report swine disease outbreak to the official surveillance system if the culling policy involves all pigs in affected farms. This number is increased to 26% if culling in affected farms is restricted to unrecovered pigs only. Ensuring certainty of compensation increases reporting probability by up to 50% and 90% if all or only unrecovered pigs are destroyed, respectively. The results of this study are important for improving the performance and sustainability of swine disease surveillance system in Vietnam., (Copyright © 2017 Elsevier B.V. All rights reserved.)

One Health (OH) positions health professionals as agents for change and provides a platform to manage determinants of health that are often not comprehensively captured in medicine or public health alone. However, due to the organization of societies and disciplines, and the sectoral allocation of resources, the development of transdisciplinary approaches requires effort and perseverance. Therefore, there is a need to provide evidence on the added value of OH for governments, researchers, funding bodies, and stakeholders. This paper outlines a conceptual framework of what OH approaches can encompass and the added values they can provide. The framework was developed during a workshop conducted by the "Network for Evaluation of One Health," an Action funded by the European Cooperation in Science and Technology. By systematically describing the various aspects of OH, we provide the basis for measuring and monitoring the integration of disciplines, sectors, and stakeholders in health initiatives. The framework identifies the social, economic, and environmental drivers leading to integrated approaches to health and illustrates how these evoke characteristic OH operations, i.e., thinking, planning, and working, and require supporting infrastructures to allow learning, sharing, and systemic organization. It also describes the OH outcomes (i.e., sustainability, health and welfare, interspecies equity and stewardship, effectiveness, and efficiency), which are not possible to obtain through sectoral approaches alone, and their alignment with aspects of sustainable development based on society, environment, and economy.

An epidemic of Ebola Virus Disease (EVD) broke out in Guinea in December 2013. It was only identified in March 2014 while it had already spread out in Liberia and Sierra Leone. The spill over of the disease became uncontrollable and the epidemic could not be stopped before 2016. The time evolution of this epidemic is revisited here with the global modeling technique which was designed to obtain the deterministic models from single time series. A generalized formulation of this technique for multivariate time series is introduced. It is applied to the epidemic of EVD in West Africa focusing on the period between March 2014 and January 2015, that is, before any detected signs of weakening. Data gathered by the World Health Organization, based on the official publications of the Ministries of Health of the three main countries involved in this epidemic, are considered in our analysis. Two observed time series are used: the daily numbers of infections and deaths. A four-dimensional model producing a very complex dynamical behavior is obtained. The model is tested in order to investigate its skills and drawbacks. Our global analysis clearly helps to distinguish three main stages during the epidemic. A characterization of the obtained attractor is also performed. In particular, the topology of the chaotic attractor is analyzed and a skeleton is obtained for its structure.

Background: Surveillance measures can only be effective if key players in the system accept them. Acceptability, which describes the willingness of persons to contribute, is often analyzed using participatory methods. Participatory epidemiology enables the active involvement of key players in the assessment of epidemiological issues. In the present study, we used a participatory method recently developed by CIRAD (Centre de Coopération Internationale en Recherche Agronomique pour le Développement) to evaluate the functionality and acceptability of Classical Swine Fever (CSF) surveillance in wild boar in Germany, which is highly dependent on the participation of hunters. The acceptability of alternative surveillance strategies was also analyzed. By conducting focus group discussions, potential vulnerabilities in the system were detected and feasible alternative surveillance strategies identified., Results: Trust in the current surveillance system is high, whereas the acceptability of the operation of the system is medium. Analysis of the acceptability of alternative surveillance strategies showed how risk-based surveillance approaches can be combined to develop strategies that have sufficient support and functionality. Furthermore, some surveillance strategies were clearly rejected by the hunters. Thus, the implementation of such strategies may be difficult., Conclusions: Participatory methods can be used to evaluate the functionality and acceptability of existing surveillance plans for CSF among hunters and to optimize plans regarding their chances of successful implementation.

The immunity profile against H5N1 highly pathogenic avian influenza (HPAI) in the commercial poultry value chain network in Egypt was modeled with the use of different vaccination scenarios. The model estimated the vaccination coverage, the protective seroconversion level, and the duration of immunity for each node of the network and vaccination scenario. Partial budget analysis was used to compare the benefit-cost of the different vaccination scenarios. The model predicted that targeting day-old chick avian influenza (AI) vaccination in industrial and large hatcheries would increase immunity levels in the overall poultry population in Egypt and especially in small commercial poultry farms (from <30% to >60%). This strategy was shown to be more efficient than the current strategy of using inactivated vaccines. Improving HPAI control in the commercial poultry sector in Egypt would have a positive impact to improve disease control.

The implementation of regular and relevant evaluations of surveillance systems is critical in improving their effectiveness and their relevance whilst limiting their cost. The complex nature of these systems and the variable contexts in which they are implemented call for the development of flexible evaluation tools. Within this scope, participatory tools have been developed and implemented for the African swine fever (ASF) surveillance system in Corsica (France). The objectives of this pilot study were, firstly, to assess the applicability of participatory approaches within a developed environment involving various stakeholders and, secondly, to define and test methods developed to assess evaluation attributes. Two evaluation attributes were targeted: the acceptability of the surveillance system and its the non-monetary benefits. Individual semi-structured interviews and focus groups were implemented with representatives from every level of the system. Diagramming and scoring tools were used to assess the different elements that compose the definition of acceptability. A contingent valuation method, associated with proportional piling, was used to assess the non-monetary benefits, i.e., the value of sanitary information. Sixteen stakeholders were involved in the process, through 3 focus groups and 8 individual semi-structured interviews. Stakeholders were selected according to their role in the system and to their availability. Results highlighted a moderate acceptability of the system for farmers and hunters and a high acceptability for other representatives (e.g., private veterinarians, local laboratories). Out of the 5 farmers involved in assessing the non-monetary benefits, 3 were interested in sanitary information on ASF. The data collected via participatory approaches enable relevant recommendations to be made, based on the Corsican context, to improve the current surveillance system., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Surveillance systems produce data which, once analysed and interpreted, support decisions regarding disease management. While several performance measures for surveillance are in use, no theoretical framework has been proposed yet with a rationale for defining and estimating effectiveness measures of surveillance systems in a generic way. An effective surveillance system is a system whose data collection, analysis and interpretation processes lead to decisions that are appropriate given the true disease status of the target population. Accordingly, we developed a framework accounting for sampling, testing and data interpretation processes, to depict in a probabilistic way the direction and magnitude of the discrepancy between "decisions that would be made if the true state of a population was known" and the "decisions that are actually made upon the analysis and interpretation of surveillance data". The proposed framework provides a theoretical basis for standardised quantitative evaluation of the effectiveness of surveillance systems. We illustrate such approaches using hypothetical surveillance systems aimed at monitoring the prevalence of an endemic disease and at detecting an emerging disease as early as possible and with an empirical case study on a passive surveillance system aiming at detecting cases of Highly Pathogenic Avian Influenza cases in Vietnamese poultry., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Regular and relevant evaluations of surveillance systems are essential to improve their performance and cost-effectiveness. With this in mind several organizations have developed evaluation approaches to facilitate the design and implementation of these evaluations., Methods: In order to identify and to compare the advantages and limitations of these approaches, we implemented a systematic review using the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)., Results: After applying exclusion criteria and identifying other additional documents via citations, 15 documents were retained. These were analysed to assess the field (public or animal health) and the type of surveillance systems targeted; the development process; the objectives; the evaluation process and its outputs; and the attributes covered. Most of the approaches identified were general and provided broad recommendations for evaluation. Several common steps in the evaluation process were identified: (i) defining the surveillance system under evaluation, (ii) designing the evaluation process, (iii) implementing the evaluation, and (iv) drawing conclusions and recommendations., Conclusions: A lack of information regarding the identification and selection of methods and tools to assess the evaluation attributes was highlighted; as well as a lack of consideration of economic attributes and sociological aspects.

Outbreaks of highly pathogenic avian influenza have occurred and have been studied in a variety of ecological systems. However, differences in the spatial resolution, geographical extent, units of analysis and risk factors examined in these studies prevent their quantitative comparison. This study aimed to develop a high-resolution, comparative study of a common set of agro-environmental determinants of avian influenza viruses (AIV) in domestic poultry in four different environments: (1) lower-Northern Thailand, where H5N1 circulated in 2004-2005, (2) the Red River Delta in Vietnam, where H5N1 is circulating widely, (3) the Vietnam highlands, where sporadic H5N1 outbreaks have occurred, and (4) the Lake Alaotra region in Madagascar, which features remarkable similarities with Asian agro-ecosystems and where low pathogenic avian influenza viruses have been found. We analyzed H5N1 outbreak data in Thailand in parallel with serological data collected on the H5 subtype in Vietnam and on low pathogenic AIV in Madagascar. Several agro-environmental covariates were examined: poultry densities, landscape dominated by rice cultivation, proximity to a water body or major road, and human population density. Relationships between covariates and AIV circulation were explored using spatial generalized linear models. We found that AIV prevalence was negatively associated with distance to the closest water body in the Red River Delta, Vietnam highlands and Madagascar. We also found a positive association between AIV and duck density in the Vietnam highlands and Thailand, and with rice landscapes in Thailand and Madagascar. Our findings confirm the important role of wetlands-rice-ducks ecosystems in the epidemiology of AI in diverse settings. Variables influencing circulation of the H5 subtype in Southeast Asia played a similar role for low pathogenic AIV in Madagascar, indicating that this area may be at risk if a highly virulent strain is introduced.

Highly pathogenic avian influenza (AI) due to H5N1 virus was first reported in Egypt in February 2006; since then, the government has allowed avian influenza vaccination in poultry. The present study evaluated the impact of AI vaccination in terms of cumulative annual flock immunity (CAFI): the percentage of bird × weeks protected by immunity. This evaluation took account of the combined effects of vaccination coverage, vaccine efficacy (VE), and different characteristics of household poultry production on the effectiveness of the adopted vaccination strategy (VS), and provided alternative options for improvement. The evaluation used a population and vaccination model that calculates the CAFI. Participatory approaches were employed in 21 villages to develop the vaccination and flock parameters required for the model. The adopted VS were compared in the model with three alternative VS scenarios in terms of the CAFI. Vaccination coverage varied among villages but was generally low (between 1 and 48 %; median 14 %). Under the adopted VS, the CAFI predicted for the villages ranged from 2 to 31 %. It was concluded that despite the enormous effort put into rural household poultry AI vaccination by the Egyptian government, village CAFI is unlikely to be maintained at the levels required to significantly reduce the virus load and restrict transmission. In HPAI-endemic countries that consider AI vaccination as one of the disease control options, the high cost of mass AI vaccination campaigns and their achievable benefits must be compared with other available control measures, which may include targeted vaccination. Achievable vaccination coverage, VE and the different characteristics of commercial and household (village) poultry production are key parameters determining the feasibility and cost-effectiveness of different AI vaccination strategies.

Background: Systems for animal disease mitigation involve both surveillance activities and interventions to control the disease. They are complex organizations that are described by partial or imprecise data, making it difficult to evaluate them or make decisions to improve them. A mathematical method, called loop analysis, can be used to model qualitatively the structure and the behavior of dynamic systems; it relies on the study of the sign of the interactions between the components of the system. This method, currently widely used by ecologists, has to our knowledge never been applied in the context of animal disease mitigation systems. The objective of the study was to assess whether loop analysis could be applied to this new context. We first developed a generic model that restricted the applicability of the method to event-based surveillance systems of endemic diseases, excluding the emergence and eradication phases. Then we chose the mitigation system of highly pathogenic avian influenza (HPAI) H5N1 in Cambodia as an example of such system to study the application of loop analysis to a real disease mitigation system., Results: Breaking down the generic model, we constructed a 6-variables model to represent the HPAI H5N1 mitigation system in Cambodia. This construction work improved our understanding of this system, highlighting the link between surveillance and control which is unclear in traditional representations of this system. Then we analyzed the effect of the perturbations to this HPAI H5N1 mitigation system that we interpreted in terms of investment in a given compartment. This study suggested that increasing intervention at a local level can optimize the system's efficiency. Indeed, this perturbation both decreases surveillance and intervention costs and reduces the disease's occurrence., Conclusion: Loop analysis can be applied to disease mitigation systems. Its main strength is that it is easy to design, focusing on the signs of the interactions. It is a simple and flexible tool that could be used as a precursor to large-scale quantitative studies, to support reflection about disease mitigation systems structure and functioning.

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.

East and Southeast Asia are important pig- and poultry-producing areas, where the majority of production takes place on small-scale farms with low biosecurity levels. This systematic review synthesizes data on swine influenza virology, serology and epidemiology in East and Southeast Asia. A total of 77 research articles, literature reviews and conference papers were selected and analyzed from 510 references retrieved from PubMed and ISI Web of KnowledgeSM. The number of published articles increased in the last 3 years, which may be attributed to improvement in monitoring and/or a better promotion of surveillance data. Nevertheless, large inequalities in surveillance and research among countries are underlined. Virological results represent the largest part of published data, while the serological and epidemiological features of swine influenza in East and Southeast Asia remain poorly described. The literature shows that there have been several emergences of swine influenza in the region, and also considerable evidence of multiple introductions of North American and avian-like European strains. Furthermore, several avian-origin strains are isolated from pigs, including H5 and H9 subtypes. However, their low seroprevalence in swine also shows that pigs remain poorly infected by these subtypes. We conclude that sero-epidemioligical investigations have been neglected, and that they may help to improve virological surveillance. Inter- and intra-continental surveillance of gene flows will benefit the region. Greater investment is needed in swine influenza surveillance, to improve our knowledge of circulating strains as well as the epidemiology and disease burden in the region.

Vaccination of domestic poultry against avian influenza (AI) has been used on a large-scale in South East Asia since 2003 and in Egypt since 2006 to fight H5N1 highly-pathogenic avian influenza (HPAI) epidemics. The decision to use mass vaccination against HPAI in Egypt was taken as an emergency measure based on positive impact of such control measures in Vietnam and the People's Republic of China. However, three years on, the impact on disease control of AI vaccination in Egypt has been very limited. Despite the continuous vaccination of poultry against HPAI, poultry outbreaks and human cases are reported regularly. A recent assessment study highlighted substantial weaknesses in the current immunisation programme and its lack of positive impact on the spread of infection or the maintenance of public health safety. The shortcomings of the vaccination strategy may be attributed in part to a lack of sufficient support in terms of funding and communication, the absence of an efficient monitoring system, and inadequate training of field technicians. The difficulties of blanket vaccinations in semi-commercial farms and household poultry sectors are well known, however, improvements in the industrial sector should be possible though better government controls and greater collaboration with the private sector. AI vaccination should be regarded as just one control tool within a broader disease control program integrating surveillance, outbreak investigation, disease management systems, and the rigorous implementation of bio-security measures. If incorrectly implemented, AI vaccination has a limited impact as a disease control measure. Moreover, without strict bio-security precautions undertaken during its application, farm visits to vaccinate poultry could facilitate the spread of the virus and therefore become a risk factor with important implications on the maintenance of the virus and potential risk for human exposure.

Transcutaneous immunization (TCI) capitalizes on the accessibility and immunocompetence of the skin, elicits protective immunity, simplifies vaccine delivery, and may be particularly advantageous when frequent boosting is required. In this study we examined the potential of TCI to boost preexisting immune responses to diphtheria in mice. The cross-reacting material (CRM(197)) of diphtheria toxin was used as the boosting antigen and was administered alone or together with either one of two commonly used mucosal adjuvants, cholera toxin (CT) and a partially detoxified mutant of heat-labile enterotoxin of Escherichia coli (LTR72). We report that TCI with CRM(197) significantly boosted preexisting immune responses elicited after parenteral priming with aluminum hydroxide-adsorbed diphtheria toxoid (DTxd) vaccine. In the presence of LTR72 as an adjuvant, toxin-neutralizing antibody titers were significantly higher than those elicited by CRM(197) alone and were comparable to the functional antibody levels induced after parenteral booster immunization with the adsorbed DTxd vaccine. Time course study showed that high levels of toxin-neutralizing antibodies persisted for at least 14 weeks after the transcutaneous boost. In addition, TCI resulted in a vigorous antigen-specific proliferative response in all groups of mice boosted with the CRM(197) protein. These findings highlight the promising prospect of using booster administrations of CRM(197) via the transcutaneous route to establish good herd immunity against diphtheria.

There is increasing concern over the efficacy of existing vaccines for diphtheria and there is interest in the development of a mucosally active formulation which might improve local protection. Lipophilic immune stimulating complexes (ISCOMS) containing Quil A are active by both parenteral and mucosal routes and here we have established methods for incorporating palmitified diphtheria toxoid (DT) into ISCOMS. The resulting formulation was immunogenic by the subcutaneous, oral and intranasal routes, with very low doses of DT inducing systemic humoral immune responses, as well as cell mediated immunity including both gammaIFN and IL5 production. Intranasal immunisation with DT in ISCOMS also stimulated significant local antibody production in tracheal washes, as well as cellular immunity in draining lymphoid tissues and serum neutralising antibodies. Finally, subcutaneous immunisation of guinea pigs with DT in ISCOMS primed protective immunity against challenge with diphtheria holotoxin more efficiently than the equivalent doses of DT in the conventional alum vaccine. ISCOMS based vaccines may provide a novel strategy for mucosal and systemic immunisation against diphtheria.

Biodegradable microspheres may represent a potential tool for the delivery of combination vaccines. We demonstrate strong immunogenicity of five co-encapsulated antigens after a single subcutaneous inoculation in guinea pigs. Tetanus- and diphtheria-specific antibodies were not significantly affected by the presence of either antigen or by the presence of pertussis or Haemophilus influenzae type b (Hib) antigens. Microsphere formulations gave better protection against diphtheria toxin than did two injections of a licensed tetravalent vaccine. Finally, a synthetic malaria peptide antigen (PfCS) also encapsulated in PLGA microspheres increased diphtheria and tetanus-specific immunity and improved protection against diphtheria. These findings demonstrate the potential of microspheres as an alternative and promising strategy for combination vaccines with a further aptitude in reducing the number of inoculations required to gain functional immunity.

We examined the antibody responses elicited in rats after transcutaneous immunization (TCI) with the Haemophilus influenzae type b (Hib)-cross-reacting material (CRM(197)) glycoconjugate vaccine coadministered with cholera toxin or mutants of heat-labile enterotoxin of Escherichia coli (LTK63 and LTR72) as adjuvants. The glycoconjugate vaccine was immunogenic, eliciting high antibody responses to the capsular polysaccharide of Hib and to diphtheria toxin. Passively transferred immune serum protected infant rats against challenge with the Hib Eagan strain and exhibited strong neutralizing activity against diphtheria toxin both in vitro and in vivo. The finding that TCI of rats can elicit antibody responses surpassing the minimum levels required for protective immunity against Hib and diphtheria suggests that this immunization strategy holds a lot of promise for future pediatric use. However, further studies are required to confirm the potential of TCI with glycoconjugate vaccines in humans.

Previous studies demonstrated in vitro phagocytosis of poly(lactide-co-glycolide) (PLGA) microspheres (MS) by macrophages and dendritic cells and the biodistribution of fluorescent PLGA particles following oral or intranasal administration. In this study, we report the uptake and biodistribution of sub-cutaneously administered fluorescent labelled PLGA MS loaded with diphtheria toxoid (DT). The cell type and percentage of fluorescent positive cells were determined by flow cytometry and confirmed by fluorescent microscopy. Fluorescent particles were detected inside cells of the peritoneal flush as early as 10 min post-inoculation, predominantly in cells of macrophage morphology. In vivo trafficking of PLGA particles following a sub-cutaneous immunisation of mice appeared to be governed by macrophages. However, in the first week after inoculation, dendritic cells played a significant role in the uptake and digestion of the microspheres, thereby triggering the immune response against the antigen. Fluorescent PLGA MS were also observed in cells of lymphoid tissues such as mesenteric lymph nodes (MLN) and spleen (S). However, microsphere fluorescence in lymphoid tissues decreased rapidly, as they were degraded inside the cells, thereby enabling the presentation of the antigen to specific cells of the immune system. To our knowledge, this is the first time the fate of immunogenic PLGA microspheres was studied in vivo following a sub-cutaneous injection route.

In an endeavor towards development of multivalent vaccines based on biodegradable microspheres, we tested the immunologic performance of several divalent microsphere formulations against tetanus and diphtheria. Microspheres were made by separate microencapsulation of tetanus and diphtheria toxoid in poly(lactide-co-glycolide) by either spray-drying or coacervation. Guinea pigs were subcutaneously immunized by a single injection of the divalent vaccines or, for control, an equivalent dose of a licensed vaccine containing both antigens adsorbed on aluminium hydroxide. All microsphere formulations were strongly immunogenic, irrespective of particle size and hydrophobicity. End point titers of ELISA antibodies, mainly of the IgG1 subtype, were comparable to those obtained after immunization with the licensed vaccine. The microspheres provided increasing levels of antibodies, during the 16 weeks of testing, and the antibodies were weakly polarized towards tetanus. The induced antibodies were also toxin neutralizing, as determined for both diphtheria (1-4 IU/mL) and tetanus (5-9 IU/mL) 8 weeks after immunization. These neutralization levels were several orders of magnitude above the level considered minimum for protection (0.01 IU/mL). When the animals were challenged with tetanus or diphtheria toxins 6 weeks after immunization, microsphere vaccines produced protective immunity that was comparable to or better than that induced by the licensed divalent vaccine. In conclusion, this study showed that a single administration of biodegradable microsphere vaccines provided protective immunity against diphtheria and tetanus, and that this immunization approach might be feasible for multivalent vaccines., (Copyright 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:957-966, 2003)

Purpose: With the aim of developing multivalent vaccines for single-injection, we examined the feasibility of combining antigens in biodegradable microspheres. Such vaccines are expected to improve vaccination coverage by reducing the number of vaccination sessions required to generate immunity., Methods: Mono- and multivalent vaccines of Haemophilus influenzae type b (Hib) conjugate, diphtheria toxoid (DT), tetanus toxoid (TT), and pertussis toxin (PT) in poly (lactic acid) and poly(lactic-coglycolic acid) microspheres were prepared by spray drying, and the influence of coencapsulated antigens and excipients on antigen loading, release, and stability was examined. Two tetravalent formulations were tested in guinea pigs., Results: Monovalent Hib and PT vaccines showed loading efficiencies of 10% (Hib) and 30% (PT) in both polymers. The loading efficiencies increased upon addition of trehalose and, even more, when the antigens were coencapsulated in di- and trivalent combinations. Highest loading efficiencies (> 80%) were achieved with trivalent formulations (DT + PT + Hib) that also contained coencapsulated albumin. The percentage of antigen released during 24 h of incubation was typically 10-40% and decreased as loading efficiency increased. Enzyme-linked immunosorbent assay (ELISA) data revealed that TT, DT, and PT remained antigenic throughout the encapsulation and subsequent release processes. Finally, all antigens maintained their immunogenicity, since strong and sustained antibody responses were elicited after a single injection of tetravalent microsphere vaccines (DT + TT + PT + Hib) in guinea pigs., Conclusions: This study reveals technologic benefit as well as an immunological potential of multivalent single-injection microsphere vaccines. The results support our hypothesis that coencapsulation of several antigens may intrinsically improve entrapment of antigenic and immunogenic antigen probably by virtue of increased protein concentration during microencapsulation leading to mutual stabilization of the components.