Understanding if the reward is worth the influenza risk: The true cost of showing pigs.

Influenza A virus transmission between pigs and humans has been reported periodically worldwide, and spillover events across the animal-human species barrier could lead to the next influenza pandemic. Swine exhibitions serve as a unique interface conducive to zoonotic disease transmission due to extensive commingling of pigs and humans for prolonged periods of time. The majority of zoonotic influenza A virus transmission in the United States has been linked to swine exhibitions, leading some to suggest additional controls for influenza A virus at the swine-human interface. Determining the value of the exhibition swine industry and gauging the financial impacts influenza A virus outbreaks could have on society, helps to inform adoption decisions of mitigation recommendations. This study estimates the total value of the exhibition swine industry in the United States and calculates the predicted costs of the most extreme mitigation strategy, cancelling swine exhibitions to reduce zoonotic influenza A virus transmission. Mixed methods, including a survey, were used to collect data and inform the study model. We estimated that the direct economic impact of the exhibition swine sector in 2018 was $1.2 billion. If pig shows were to be cancelled for one year, the estimated direct economic impact would be $357.1 million. A permanent, > 3-year ban on swine exhibitions would result in a $665 million economic impact, which is a 45% reduction from baseline. The direct economic impact of cancelling the swine show circuit could not be determined, as youth exhibitors may pursue alternative activities that cannot be precisely accounted for. However, the estimated loss to the swine industry justifies seeking enhanced mitigation to prevent disease transmission. Moreover, economic losses secondary to exhibition cancellations may explain hesitancy to participate in active influenza A virus surveillance efforts.

An economic analysis of a contingency model utilising vaccination for the control of equine influenza in a non-endemic country.

BACKGROUND: Equine influenza (EI) is an infectious respiratory disease of horses that has never been reported in New Zealand (NZ). However, the 2007 EI outbreak in Australia, previously EI free, spurred the NZ government and stakeholders into evaluating alternative EI control strategies in order to economically justify any future decision to eradicate or manage EI. To build on the policy debate, this paper presents an epinomic (epidemiologic and economic) modelling approach to evaluate alternative control strategies. An epidemiologic model to determine how alternative EI control strategies influence the distribution of EI. Model results were then input into a cost-benefit analysis framework, to identify the return and feasibility of alternative EI eradication strategies in NZ. METHODS: The article explores nine alternative eradication scenarios and two baseline strategies. The alternative scenarios consisted of three vaccination strategies (suppressive, protective or targeted) starting at three time points to reflect the commercial breeding-cycle. These alternatives were compared to two breeding-cycle adjusted baselines: movement restriction in the breeding season (August to January) or non-breeding season (February to July). The economic loss parameters were incursion response, impact to the commercial racing industry (breeding, sales and racing), horse morbidity and mortality, and compensation to industry participants. RESULTS AND CONCLUSIONS: Results suggest that the economic viability of the EI eradication programme is dependent on when within the breeding-cycle the EI outbreak occurs. If an outbreak were to occur, the return on each dollar invested for protective or suppressive vaccination strategies would be between NZD$3.67 to NZD$4.89 and between NZD$3.08 to NZD$3.50 in the breeding and non-breeding seasons, respectively. Therefore, protective or suppressive vaccination strategies could be prioritised, regardless of season. As multiple industry stakeholders benefit from these strategies, the study will enable policy development and to better formulate a user-pays eradication programme.

Insertion-responsive microneedles for rapid intradermal delivery of canine influenza vaccine.

In this study, we present transcutaneous influenza vaccination using a novel tip-separable microneedle system called insertion-responsive microneedles (IRMNs). IRMNs are composed of dissolvable hyaluronic acid (HA) tips and biocompatible polycaprolactone (PCL) bases, the tip of which is instantly separated from the base during microneedle insertion and retraction. Vaccine antigens derived from canine influenza virus (A/canine/VC378/2012; H3N2) were successfully coated on HA tips by rapidly freezing the tips prior to coating. An ex vivo porcine skin insertion test showed that IRMNs were capable of penetrating the skin without tip breakage and releasing the coated materials within the skin. The thermal stability of the vaccine as determined by hemagglutination assay revealed that the coated vaccine partially maintained its activity when stored at 50 °C for 3 weeks, whereas the liquid form completely lost the activity. Immunization in guinea pigs showed that hemagglutination inhibition (HI) antibodies induced by IRMNs were two times higher than those induced by intramuscular (IM) injections. When challenged with influenza A/canine/Korea/01/2007 (H3N2) wild-type virus 2 weeks after the second vaccination, viral shedding was completely eliminated at 8 days post infection in both IRMNs and IM injection groups. Our results suggest that IRMNs have great potential for rapid and convenient vaccination, which will be particularly attractive for animal vaccinations.

Control of endemic swine flu persistence in farrow-to-finish pig farms: a stochastic metapopulation modeling assessment.

Swine influenza viruses (swIAVs) are known to persist endemically in farrow-to-finish pig farms, leading to repeated swine flu outbreaks in successive batches of pigs at a similar age (mostly around 8 weeks of age). This persistence in European swine herds involves swIAVs from European lineages including H1avN1, H1huN2, H3N2, the 2009 H1N1 pandemic virus and their reassortants. The specific population dynamics of farrow-to-finish pig farms, the immune status of the animals at infection-time, the co-circulation of distinct subtypes leading to consecutive or concomitant infections have been evidenced as factors favouring swIAV persistence within herds. We developed a stochastic metapopulation model representing the co-circulation of two distinct swIAVs within a typical farrow-to-finish pig herd to evaluate the risk of reassortant viruses generation due to co-infection events. Control strategies related to herd management and/or vaccination schemes (batch-to-batch or mass vaccination of the sow herd and vaccination of growing pigs) were implemented to assess their relative efficacy regarding viral persistence. The overall probability of a co-infection event for France, possibly leading to reassortment, was evaluated to 16.8%. The export of consecutive piglets batches was identified as the most efficient measure facilitating swIAV infection fade-out. Although some vaccination schemes (batch-to-batch vaccination) had a beneficial effect in breeding sows by reducing the persistence of swIAVs within this subpopulation, none of vaccination strategies achieved swIAVs fade-out within the entire farrow-to-finish pig herd.

Yeast Surface-Displayed H5N1 Avian Influenza Vaccines.

Highly pathogenic H5N1 avian influenza viruses pose a pandemic threat to human health. A rapid vaccine production against fast outbreak is desired. We report, herein, a paradigm-shift influenza vaccine technology by presenting H5N1 hemagglutinin (HA) to the surface of yeast. We demonstrated, for the first time, that the HA surface-presented yeast can be used as influenza vaccines to elicit both humoral and cell-mediated immunity in mice. The HI titer of antisera reached up to 128 in vaccinated mice. A high level of H5N1 HA-specific IgG1 and IgG2a antibody production was detected after boost immunization. Furthermore, we demonstrated that the yeast surface-displayed HA preserves its antigenic sites. It preferentially binds to both avian- and human-type receptors. In addition, the vaccine exhibited high cross-reactivity to both homologous and heterologous H5N1 viruses. A high level production of anti-HA antibodies was detected in the mice five months after vaccination. Finally, our animal experimental results indicated that the yeast vaccine offered complete protection of mice from lethal H5N1 virus challenge. No severe side effect of yeast vaccines was noted in animal studies. This new technology allows for rapid and large-scale production of influenza vaccines for prepandemic preparation.

Characterization of a novel oil-in-water emulsion adjuvant for swine influenza virus and Mycoplasma hyopneumoniae vaccines.

Vaccines consisting of subunit or inactivated bacteria/virus and potent adjuvants are widely used to control and prevent infectious diseases. Because inactivated and subunit antigens are often less antigenic than live microbes, a growing need exists for the development of new and improved vaccine adjuvants that can elicit rapid and long-lasting immunity. Here we describe the development and characterization of a novel oil-in-water emulsion, OW-14. OW-14 contains low-cost plant-based emulsifiers and was added to antigen at a ratio of 1:3 with simple hand mixing. OW-14 was stable for prolonged periods of time at temperatures ranging from 4 to 40°C and could be sterilized by autoclaving. Our results showed that OW-14 adjuvanted inactivated swine influenza viruses (SIV; H3N2 and H1N1) and Mycoplasma hyopneumoniae (M. hyo) vaccines could be safely administered to piglets in two doses, three weeks apart. Injection sites were monitored and no adverse reactions were observed. Vaccinated pigs developed high and prolonged antibody titers to both SIV and M. hyo. Interestingly, antibody titers were either comparable or greater than those produced by commercially available FluSure (SIV) or RespiSure (M. hyo) vaccines. We also found that OW-14 can induce high antibody responses in pigs that were vaccinated with a decreased antigen dose. This study provides direct evidence that we have developed an easy-to-use and low-cost emulsion that can act as a powerful adjuvant in two common types of swine vaccines.

Immunologic characterization of a rhesus macaque H1N1 challenge model for candidate influenza virus vaccine assessment.

Despite the availability of annually formulated vaccines, influenza virus infection remains a worldwide public health burden. Therefore, it is important to develop preclinical challenge models that enable the evaluation of vaccine candidates while elucidating mechanisms of protection. Here, we report that naive rhesus macaques challenged with 2009 pandemic H1N1 (pH1N1) influenza virus do not develop observable clinical symptoms of disease but develop a subclinical biphasic fever on days 1 and 5 to 6 postchallenge. Whole blood microarray analysis further revealed that interferon activity was associated with fever. We then tested whether type I interferon activity in the blood is a correlate of vaccine efficacy. The animals immunized with candidate vaccines carrying hemagglutinin (HA) or nucleoprotein (NP) exhibited significantly reduced interferon activity on days 5 to 6 postchallenge. Supported by cellular and serological data, we conclude that blood interferon activity is a prominent marker that provides a convenient metric of influenza virus vaccine efficacy in the subclinical rhesus macaque model.

Controlling equine influenza: policy networks and decision-making during the 2007 Australian equine influenza outbreak.

Rapid, evidence-based decision-making is critical during a disease outbreak response; however, compliance by stakeholders is necessary to ensure that such decisions are effective - especially if the response depends on voluntary action. This mixed method study evaluated technical policy decision-making processes during the 2007 outbreak of equine influenza in Australia by identifying and analysing the stakeholder network involved and the factors driving policy decision-making. The study started with a review of the outbreak literature and published policy documents. This identified six policy issues regarding policy modifications or differing interpretations by different state agencies. Data on factors influencing the decision-making process for these six issues and on stakeholder interaction were collected using a pre-tested, semi-structured questionnaire. Face-to-face interviews were conducted with 24 individuals representing 12 industry and government organizations. Quantitative data were analysed using social network analysis. Qualitative data were coded and patterns matched to test a pre-determined general theory using a method called theory-oriented process-tracing. Results revealed that technical policy decisions were framed by social, political, financial, strategic and operational considerations. Industry stakeholders had influence through formal pre-existing channels, yet specific gaps in stakeholder interaction were overcome by reactive alliances formed during the outbreak response but outside the established system. Overall, the crisis management system and response were seen as positive, and 75-100% of individuals interviewed were supportive of, had interest in and considered the outcome as good for the majority of policy decisions, yet only 46-75% of those interviewed considered that they had influence on these decisions. Training to increase awareness and knowledge of emergency animal diseases (EADs) and response systems will improve stakeholder participation in emergency disease management and preparedness for future EAD incursions.

Innovative zoning to support equine influenza eradication from New South Wales, Australia.

Following detection of equine influenza (EI) in New South Wales, a complete standstill was imposed the next morning on the movement of all horses and donkeys within the state. Premises' biosecurity guidelines became progressively more stringent with time in an effort to stop local spread. The standstill was highly effective as a primary response to stop EI becoming widespread across Australia, but did not prevent spread to properties contiguous to infected premises in areas of high horse density and small property size, nor transmission by fomites nor possible local airborne transmission. Within 2 weeks of the start of the outbreak, a zoning system of Purple (Special Restricted), Red (Restricted), Amber (Control), and Green (Protected) Zones was implemented, and progressively modified as disease distribution changed. The colour coding system proved to be an easy way to communicate zone changes, the approximate level of disease risk and the stringency of movement restrictions to the general public and should be adopted more generally in AUSVETPLAN.

One health approach to influenza: assessment of critical issues and options.

A task force of experts on influenza, public health, and animal health met at the conference One Health Approach to Influenza: Assessment of Critical Issues and Options in Washington, DC, on December 1-2, 2009. These experts discussed the role of the One Health approach in preparing for and responding to an influenza pandemic or other emerging zoonotic disease by using pandemic (H1N1) 2009 as a case study. The meeting was convened by the US Department of Homeland Security National Center for Foreign Animal and Zoonotic Disease Defense, and the National Institute of Allergy and Infectious Diseases/National Institutes of Health Western Regional Center of Excellence for Biodefense and Emerging Infectious Diseases.

Vaccine Manufacturing--Second Annual visiongain Conference.

The Vaccine Manufacturing--Second Annual visiongain Conference, held in London, included topics covering new technological developments in the field of influenza vaccine research. This conference report highlights selected presentations on influenza vaccine development in mammalian, insect and avian embryonic cells, regulatory considerations for cell culture-based influenza vaccine production, an improved animal model for influenza infection, and considerations for designing vaccine manufacturing facilities. Investigational drugs discussed include FluBiovax (Immunobiology Ltd) and FluBlok (Protein Sciences Corp/UMN Pharma Inc).

H1N1 Swine Flu: The 2010 Perspective--A New York Academy of Sciences Meeting.

The H1N1 Swine Flu: The 2010 Perspective conference, held in New York City, included topics covering new research developments regarding the H1N1 influenza virus. This conference report highlights selected presentations on high-yield reassortant viral production, virus transmission and pathogenesis in ferret and guinea pig models, and the advantages of virus-like particle vaccines. Fatal pathology findings from the 2009 H1N1 strain in New York, and preparedness for and response to the 2009 pandemic, are also discussed.

Assessment of the efficacy of commercially available and candidate vaccines against a pandemic H1N1 2009 virus.

BACKGROUND: The emergence and global spread of the pandemic H1N1 2009 influenza virus have raised questions regarding the protective effect of available seasonal vaccines and the efficacy of a newly produced matched vaccine. METHODS: Ferrets were immunized with the 2008-2009 formulations of commercially available live attenuated (FluMist; MedImmune) or split-inactivated (Fluviral; GlaxoSmithKline) vaccines, a commercial swine vaccine (FluSure; Pfizer), or a laboratory-produced matched inactivated whole-virus vaccine (A/Mexico/InDRE4487/2009). Adaptive immune responses were monitored, and the animals were challenged with A/Mexico/InDRE4487/2009 after 5 weeks. RESULTS: Only animals that received the swine or matched vaccines developed detectable hemagglutination-inhibiting antibodies against the challenge virus, whereas a T cell response was exclusively detected in animals vaccinated with FluMist. After challenge, all animals had high levels of virus replication in the upper respiratory tract. However, preexisting anti-pandemic H1N1 2009 antibodies resulted in reduced clinical signs and improved survival. Surprisingly, FluMist was associated with a slight increase in mortality and greater lung damage, which correlated with early up-regulation of interleukin-10. CONCLUSIONS: The present study demonstrates that a single dose of matched inactivated vaccine confers partial protection against a pandemic H1N1 2009 virus, and it suggests that a higher dose or prime-boost regimen may be required. The consequences of mismatched immunity to influenza merit further investigation.

A stochastic model for the assessment of the transmission pathways of heart and skeleton muscle inflammation, pancreas disease and infectious salmon anaemia in marine fish farms in Norway.

Salmon farming is threatened, economically and ecologically, by infectious diseases. To reduce the risk of epidemics, authorities have developed regulations. These are based on quantitative understanding of pathways of infection, representing disease specific risks. A stochastic model was fitted to historical data, to estimate risk factors associated with competing spread mechanisms. Three infectious diseases were compared, heart and skeletal muscle inflammation (HSMI), pancreas disease (PD) and infectious salmon anaemia (ISA). This study was based on space-time data, from Norway from 2003 to 2007, describing the susceptible fish cohorts and the reported infections. Particular interest was given to seaway distances between farms and their local management organisation. The parameter measuring the effect of distance to an infectious fish farm was positive and significant for all diseases, implying that the risk involved with proximate infectious fish farms increased with decreasing distance. For HSMI and PD there was a significant effect of sharing a contact network with an infectious farm. For HSMI, but not for PD or ISA, there was a significant effect of previous infected cohorts on the same farm. The relative contribution of each transmission pathway was dominated by seaway distance for PD and HSMI, while other non-defined pathways dominated for ISA. This comparative study highlights that the three diseases have different patterns of spread, with important consequences for disease prevention and management.

[Influenza A (H1N1). fear of a pandemic]. / Influenza A (H1N1): temor a una pandemia.

As of July 1st 2009, 90300 cases of the new Influenza A (H1N1) have been officially reported to the World Health Organization (WHO) in more than 80 countries. Venezuela does not seem to be the exception, but it was not until June 11th 2009, when the first case was reported; however, the Venezuelan sanitary authorities maintain active the epidemiologic monitoring and controls to avoid the propagation of the virus. A positive aspect, in this instance, is that the world is better prepared to confront an influenza pandemic; but it is generally accepted that the preparation against a pandemic requires the participation, not only of the health sector, but of all society. There are many challenges in the present and in the future, for the production of an effective vaccine against this new strain of the virus, which will create a sense of hope for the people who have not yet been affected by this disease.

Development of a vaccine against pandemic influenza viruses: current status and perspectives.

The constant threat of a new influenza pandemic, which may be caused by a highly pathogenic avian influenza virus, necessitates the development of a vaccine capable of providing efficient, long-term, and cost-effective protection. Proven avenues for the development of vaccines against seasonal influenza as well as novel approaches have been explored over the past decade. Whereas significant insights are consistently being made, the generation of a highly efficient and cross-protective vaccine against the future pandemic influenza strain remains as the ultimate goal in the field. In this review, we re-examine these efforts and outline the scientific, political, and economic problems that befall this area of biotechnological research.