Vaccination of Poultry Against Influenza.

The complexity of influenza A virus (IAV) infections in avian hosts leads to equally complex scenarios for the vaccination of poultry. Vaccination against avian influenza strains can be used to prevent infections from sources with a single strain of IAV. It has been used as a part of outbreak control strategies as well as a way to maintain production for both low and high pathogenicity outbreaks. Unlike other viral pathogens of birds, avian influenza vaccination when used against highly pathogenic avian influenza virus, is tied to international trade and thus is not freely available for use without specific permission.

Vacunación de aves comerciales contra la influenza aviar. La complejidad de las infecciones por el virus de la influenza A en las aves hospedadoras conduce a escenarios igualmente complejos para la vacunación en la avicultura. La vacunación contra cepas de influenza aviar se puede utilizar para prevenir infecciones provenientes de fuentes con una sola cepa del virus de influenza. Se ha utilizado como parte de las estrategias de control de brotes, así como como una forma de mantener la producción tanto en brotes de baja como de alta patogenicidad. A diferencia de otros patógenos virales de las aves, la vacunación contra la influenza aviar, cuando se usa contra el virus de la influenza aviar altamente patógeno, está vinculada al comercio internacional y por lo tanto, no está disponible para su uso sin un permiso específico.

Cross-protection of commercial vaccines against Chilean swine influenza A virus using the guinea pig model as a surrogate.

Influenza A virus poses a significant threat to public health and the swine industry. Vaccination is the primary measure for controlling the disease, but the effectiveness of vaccines can vary depending on the antigenic match between vaccine strains and circulating strains. In Chile, H1N1pdm09 and other lineages H1N2 and H3N2 have been detected in pigs, which are genetically distinct from the strains included in commercial vaccines. This study aimed to evaluate the cross-protection by commercial vaccines against strains circulating in Chile using the guinea pig model. For this study, four circulating strains [A/swine/Chile/H1A-7/2014(H1N2), A/swine/Chile/H1B-2/2014(H1N2), A/swine/Chile/H1P-12/2015(H1N1), and A/swine/Chile/H3-2/2015(H3N2)] were selected. Guinea pigs were divided into vaccinated and control groups. The vaccinated animals received either a multivalent antigenically heterologous or monovalent homologous vaccine, while the control animals remained unvaccinated. Following vaccination, all animals were intranasally challenged, and nasal wash samples were collected at different time points post-infection. The results showed that the homologous monovalent vaccine-induced hemagglutinin-specific antibodies against the Chilean pandemic H1N1pdm09 strain. However, the commercial heterologous multivalent vaccine failed to induce hemagglutinin-specific antibody titers against the H1N2 and H3N2 challenge strains. Furthermore, the homologous monovalent vaccine significantly reduced the duration of viral shedding and viral titers specifically against the Chilean pandemic H1N1pdm09 strain and heterologous multivalent vaccine only partial. These findings highlight the importance of regularly updating vaccine strains to match the circulating field strains for effective control of swine influenza. Further research is needed to develop vaccines that confer broader protection against diverse strains of swine influenza A virus.

Rational approach to vaccination against highly pathogenic avian influenza in Nigeria: a scientific perspective and global best practice.

Since 2006, highly pathogenic avian influenza (HPAI) subtypes H5Nx have adversely affected poultry production in Nigeria. Successive waves of infections in the last two decades have raised concerns about the ability to contain infections by biosecurity alone, and evidence of recurrent outbreaks suggests a need for adoption of additional control measures such as vaccination. Although vaccination can be used to control virus spread and reduce the morbidity and mortality caused by HPAI, no country using vaccination alone as a control measure against HPAI has been able to eliminate or prevent re-infection. To inform policy in Nigeria, we examined the intricacies of HPAI vaccination, government regulations, and scientific data regarding what kind of vaccines can be used based on subtype, whether inactivated or live attenuated should be used, when to deliver vaccine either proactively or reactively, where to apply vaccination either in disease control zones, regionally, or nationally, and how to vaccinate the targeted poultry population for optimum success. A resurgence of HPAI outbreaks in Nigeria since 2018, after the country was declared free of the epidemic following the first outbreak in 2006, has led to enhanced intervention. Controlled vaccination entails monitoring the application of vaccines, the capacity to differentiate vaccinated from infected (DIVA) flocks, and assessing seroconversion or other immune correlates of protection. Concurrent surveillance for circulating avian influenza virus (AIV) and analyzing AIV isolates obtained via surveillance efforts for genetic and/or antigenic mismatch with vaccine strains are also important. Countries with high investment in commercial poultry farms like Nigeria may identify and zone territories where vaccines can be applied. This may include ring vaccination to control HPAI in areas or production systems at risk of infection. Before adoption of vaccination as an additional control measure on commercial poultry farms, two outcomes must be considered. First, vaccination is an admission of endemicity. Secondly, vaccinated flocks may no longer be made accessible to international poultry markets in accordance with WOAH trade regulations. Vaccination must therefore be approached with utmost caution and be guided by science-based evidence throughout the implementation strategy after thorough risk assessment. Influenza vaccine research, development, and controlled application in addition to biosecurity may be a precautionary measure in the evolving HPAI scenario in Nigeria.

Farm management practices associated with influenza A virus contamination of people working in Midwestern United States swine farms.

Indirect transmission of influenza A virus (IAV) contributes to virus spread in pigs. To identify farm management activities with the ability to contaminate farmworkers' hands and clothing that then could be a source of virus spread to other pigs, we conducted a within-farm, prospective IAV surveillance study. Hands and clothes from farmworkers performing the activities of piglet processing, vaccination, or weaning were sampled before and after the activities were performed. Samples were tested by IAV rRT-PCR and virus viability was assessed by cell culture. A multivariate generalized linear model was used to detect associations of the activities with IAV contamination. Of the samples collected for IAV rRT-PCR testing, there were 16% (12/76) collected immediately after processing, 96% (45/48) collected after vaccination, and 94% (29/31) collected after weaning that tested positive. Samples collected immediately after vaccination and weaning, i.e., activities that took place during the peri-weaning period when pigs were about 3 weeks of age, had almost 6 times higher risk of IAV detection and had more samples IAV positive (p-value < 0.0001) than samples collected after processing, i.e., an activity that took place in the first few days of life. Both, hands and clothes had similar contamination rates (46% and 55% respectively, p-value = 0.42) and viable virus was isolated from both. Our results indicate that activities that involve the handling of infected piglets close to weaning age represent a significant risk for IAV dissemination due to the high level of IAV contamination found in farmworkers' hands and coveralls involved in the activities. Biosecurity protocols that include hand sanitation and changing clothing after performing activities with a high-risk of influenza contamination should be recommended to farmworkers to control and limit the mechanical spread of IAV between pigs.

Influenza A viruses in gulls in landfills and freshwater habitats in Minnesota, United States.

Introduction: The unpredictable evolution of avian influenza viruses (AIVs) presents an ongoing threat to agricultural production and public and wildlife health. Severe outbreaks of highly pathogenic H5N1 viruses in US poultry and wild birds since 2022 highlight the urgent need to understand the changing ecology of AIV. Surveillance of gulls in marine coastal environments has intensified in recent years to learn how their long-range pelagic movements potentially facilitate inter-hemispheric AIV movements. In contrast, little is known about inland gulls and their role in AIV spillover, maintenance, and long-range dissemination. Methods: To address this gap, we conducted active AIV surveillance in ring-billed gulls (Larus delawarensis) and Franklin's gulls (Leucophaeus pipixcan) in Minnesota's natural freshwater lakes during the summer breeding season and in landfills during fall migration (1,686 samples). Results: Whole-genome AIV sequences obtained from 40 individuals revealed three-lineage reassortants with a mix of genome segments from the avian Americas lineage, avian Eurasian lineage, and a global "Gull" lineage that diverged more than 50 years ago from the rest of the AIV global gene pool. No poultry viruses contained gull-adapted H13, NP, or NS genes, pointing to limited spillover. Geolocators traced gull migration routes across multiple North American flyways, explaining how inland gulls imported diverse AIV lineages from distant locations. Migration patterns were highly varied and deviated far from assumed "textbook" routes. Discussion: Viruses circulating in Minnesota gulls during the summer breeding season in freshwater environments reappeared in autumn landfills, evidence of AIV persistence in gulls between seasons and transmission between habitats. Going forward, wider adoption of technological advances in animal tracking devices and genetic sequencing is needed to expand AIV surveillance in understudied hosts and habitats.

Modeling the accuracy of a novel PCR and antibody ELISA for African swine fever virus detection using Bayesian latent class analysis.

Introduction: Diagnostic test evaluation for African swine fever (ASF) in field settings like Vietnam is critical to understanding test application in intended populations for surveillance and control strategies. Bayesian latent class analysis (BLCA) uses the results of multiple imperfect tests applied to an individual of unknown disease status to estimate the diagnostic sensitivity and specificity of each test, forgoing the need for a reference test. Methods: Here, we estimated and compared the diagnostic sensitivity and specificity of a novel indirect ELISA (iELISA) for ASF virus p30 antibody (Innoceleris LLC.) and the VetAlert™ ASF virus DNA Test Kit (qPCR, Tetracore Inc.) in field samples from Vietnam by assuming that disease status 1) is known and 2) is unknown using a BLCA model. In this cross-sectional study, 398 paired, individual swine serum/oral fluid (OF) samples were collected from 30 acutely ASF-affected farms, 37 chronically ASF-affected farms, and 20 ASF-unaffected farms in Vietnam. Samples were tested using both diagnostic assays. Diagnostic sensitivity was calculated assuming samples from ASF-affected farms were true positives and diagnostic sensitivity by assuming samples from unaffected farms were true negatives. ROC curves were plotted and AUC calculated for each test/sample combination. For comparison, a conditionally dependent, four test/sample combination, three population BLCA model was fit. Results: When considering all assumed ASF-affected samples, qPCR sensitivity was higher for serum (65.2%, 95% Confidence Interval [CI] 58.1-71.8) and OF (52%, 95%CI 44.8-59.2) compared to the iELISA (serum: 42.9%, 95%CI 35.9-50.1; OF: 33.3%, 95%CI 26.8-40.4). qPCR-serum had the highest AUC (0.895, 95%CI 0.863-0.928). BLCA estimates were nearly identical to those obtained when assuming disease status and were robust to changes in priors. qPCR sensitivity was considerably higher than ELISA in the acutely-affected population, while ELISA sensitivity was higher in the chronically-affected population. Specificity was nearly perfect for all test/sample types. Discussion: The effect of disease chronicity on sensitivity and specificity could not be well characterized here due to limited data, but future studies should aim to elucidate these trends to understand the best use of virus and antibody detection methods for ASF. Results presented here will help the design of surveillance and control strategies in Vietnam and other countries affected by ASF.

Evaluation of internal farm biosecurity measures combined with sow vaccination to prevent influenza A virus infection in groups of due-to-wean pigs.

BACKGROUND: Influenza A virus (IAV) is an important respiratory pathogen of pigs that affects pig health, well-being and productivity, has zoonotic potential, and has significant economic impact for producers. The ultimate goal is to maintain herds free from IAV. Due to the probability of IAV introduction into the herds, it is also desirable for herds to have some immunity to the virus. In this study, we evaluated a protocol that combined sow vaccination with the implementation of internal biosecurity practices during the pre-weaning period with the goal to wean IAV negative pigs. Five IAV positive breeding herds were vaccinated twice, 3 weeks apart with a herd-specific autogenous vaccine. For the subsequent 8 weeks, a biosecurity protocol was maintained, consisting of no pig movements after 3 days of age, no use of nurse sows, workers changing disposable gloves between litters, workers not stepping into farrowing crates, and daily disinfection of tools and materials used to handle pigs. RESULTS: Following these interventions, four of the five treatment farms had significant reductions in IAV detection (p value < 0.05). Three of the farms tested negative at all sampling points post-intervention and one farm had a 21% reduction in IAV positivity. CONCLUSIONS: This study indicates that a protocol that combines sow vaccination and enhanced biosecurity practices may limit IAV transmission among piglets and enable the weaning of groups of pigs free from the virus.

Senecavirus A seroprevalence and risk factors in United States pig farms.

Senecavirus A (SVA) is a non-enveloped, single-stranded, positive-sense RNA virus belonging to the Picornaviridae family. Senecavirus A is constantly associated with outbreaks of vesicular disease in pigs and has been reported in several countries since its first large-scale outbreak in 2014. Senecavirus A's clinical disease and lesions are indistinguishable from other vesicular foreign animal diseases (FAD). Therefore, an FAD investigation needs to be conducted for every SVA case. For this reason, SVA has been attributed as the cause of an alarming increase in the number of yearly FAD investigations performed by the United States Department of Agriculture (USDA). The objectives of this study were to estimate the seroprevalence of SVA antibodies in breeding and growing pig farms in the United States and to determine the farm-level risk factors associated with seropositivity. A total of 5,794 blood samples were collected from 98 and 95 breeding and growing pig farms in 17 states. A farm characteristics questionnaire was sent to all farms, to which 80% responded. The responses were used to conduct logistic regression analyses to assess the risk factors associated with SVA seropositivity. The estimated farm-level seroprevalences were 17.3% and 7.4% in breeding and growing pig farms, respectively. Breeding farms had 2.64 times higher odds of SVA seropositivity than growing pig farms. One key risk factor identified in breeding farms was the practice of rendering dead animal carcasses. However, the adoption of a higher number of farm biosecurity measures was associated with a protective effect against SVA seropositivity in breeding farms.

Evaluation of dam parity and internal biosecurity practices in influenza infections in piglets prior to weaning.

Influenza is an important respiratory disease of pigs and humans. Controlling influenza in pigs is challenging due to the substantial genetic diversity of influenza A virus (IAV). In this study, we assessed the impact of internal biosecurity practices directed at limiting exposure of piglets to IAV before weaning; evaluated the association of sow parity with IAV prevalence in piglets and the levels of maternally derived antibodies (MDA), and documented the frequency of detection of IAV on farmworkers' hands and the instruments used when handling pigs. The control group included litters in rooms where no specific changes were made to standard farm procedures. The treatment group included litters in rooms where no cross-fostering or nurse sows use was allowed, and where farmworkers were required to change gloves between litters when handling pigs. Both, younger (≤ Parity 3) and older parity sows (>Parity 3) were represented in all rooms included in the study. Overall, litters in the treatment group had lower IAV prevalence (29.9 %) than litters in the control group (44.2 %) (p < 0.001), and at day 8 of age the litters from the control group had 7.5 times higher IAV prevalence than the litters from the treatment group. However, at weaning differences were not found (77.2 % vs. 81 % for treatment vs. control, respectively, p = 0.41). There were no differences in IAV detection between parity groups at any of the sampling points (p = 0.86) and incidence of detection in sows from farrowing to weaning was 29 %. Piglets that tested ELISA negative were 1.3 times more likely to test IAV positive than piglets that were ELISA positive for IAV antibody test, suggesting that effective colostrum intake may reduce the likelihood of infection. IAV was detected on 46 % of the instruments used when handling piglets and on 58 % of farmworkers' hands, indicating the potential risk for mechanical transmission of IAV in pigs. Overall, we showed that the implementation of internal biosecurity practices that limit IAV exposure to newborn piglets helped delay IAV infections but were not sufficient to reduce the prevalence of IAV infection in litters at weaning.

Vaccination decreases the risk of influenza A virus reassortment but not genetic variation in pigs.

Although vaccination is broadly used in North American swine breeding herds, managing swine influenza is challenging primarily due to the continuous evolution of influenza A virus (IAV) and the ability of the virus to transmit among vaccinated pigs. Studies that have simultaneously assessed the impact of vaccination on the emergence of IAV reassortment and genetic variation in pigs are limited. Here, we directly sequenced 28 bronchoalveolar lavage fluid (BALF) samples collected from vaccinated and unvaccinated pigs co-infected with H1N1 and H3N2 IAV strains, and characterized 202 individual viral plaques recovered from 13 BALF samples. We identified 54 reassortant viruses that were grouped in 17 single and 16 mixed genotypes. Notably, we found that prime-boost vaccinated pigs had less reassortant viruses than nonvaccinated pigs, likely due to a reduction in the number of days pigs were co-infected with both challenge viruses. However, direct sequencing from BALF samples revealed limited impact of vaccination on viral variant frequency, evolutionary rates, and nucleotide diversity in any IAV coding regions. Overall, our results highlight the value of IAV vaccination not only at limiting virus replication in pigs but also at protecting public health by restricting the generation of novel reassortants with zoonotic and/or pandemic potential.

Swine influenza A viruses cause severe illness among pigs and financial losses on pig farms worldwide. These viruses can also infect humans and have caused deadly human pandemics in the past. Influenza A viruses are dangerous because viruses can be transferred between humans, birds and pigs. These co-infections can allow the viruses to swap genetic material. Viral genetic exchanges can result in new virus strains that are more dangerous or that can infect other types of animals more easily. Farmers vaccinate their pigs to control the swine influenza A virus. The vaccines are regularly updated to match circulating virus strains. But the virus evolves rapidly to escape vaccine-induced immunity, and infections are common even in vaccinated pigs. Learning about how vaccination affects the evolution of influenza A viruses in pigs could help scientists prevent outbreaks on pig farms and avoid spillover pandemics in humans. Li et al. show that influenza A viruses are less likely to swap genetic material in vaccinated and boosted pigs than in unvaccinated animals. In the experiments, Li et al. collected swine influenza A samples from the lungs of pigs that had received different vaccination protocols. Next, Li et al. used next-generation sequencing to identify new mutations in the virus or genetic swaps among different strains. In pigs infected with both the H1N1 and H3N2 strains of influenza, the two viruses began trading genes within a week. But less genetic mixing occurred in vaccinated and boosted pigs because they spent less time infected with both viruses than in unvaccinated pigs. The vaccination status of the pig did not have much effect on how many new mutations occurred in the viruses. The experiments show that vaccinating and boosting pigs against influenza A viruses may protect against genetic swapping among influenza viruses. If future studies on pig farms confirm the results, the information gleaned from the study could help scientists improve farm vaccine protocols to further reduce influenza risks to animals and people.

Evidence of influenza A infection and risk of transmission between pigs and farmworkers.

Interspecies transmission of influenza A virus (IAV) between pigs and people represents a threat to both animal and public health. To better understand the risks of influenza transmission at the human-animal interface, we evaluated 1) the rate of IAV detection in swine farmworkers before and after work during two human influenza seasons, 2) assessed risk factors associated with IAV detection in farmworkers and 3) characterized the genetic sequences of IAV detected in both workers and pigs. Of 58 workers providing nasal passage samples during 8-week periods during the 2017/18 and 2018/19 influenza seasons, 33 (57%) tested positive by rRT-PCR at least once. Sixteen (27%) workers tested positive before work and 24 (41%) after work. At the sample level, 58 of 1,785 nasal swabs (3.2%) tested rRT-PCR positive, of which 20 of 898 (2.2%) were collected prior to work and 38 of 887 (4.3%) after work. Although farmworkers were more likely to test positive at the end of the working day (OR = 1.98, 95% CI 1.14-3.41), there were no influenza-like illness (ILI) symptoms, or other risk indicators, associated with IAV detection before or after reporting to work. Direct whole-genome sequencing from samples obtained from worker nasal passages indicated evidence of infection of a worker with pandemic 2009 H1N1 of human-origin IAV (H1-pdm 1A 3.3.2) when reporting to work, and exposure of several workers to a swine-origin IAV (H1-alpha 1A 1.1) circulating in the pigs on the farm where they were employed. Our study provides evidence of 1) risk of IAV transmission between pigs and people, 2) pandemic H1N1 IAV infected workers reporting to work and 3) workers exposed to swine harbouring swine-origin IAV in their nasal passages temporarily. Overall, our results emphasize the need to implement surveillance and transmission preventive protocols at the pig/human interface.

Predicting the time to detect moderately virulent African swine fever virus in finisher swine herds using a stochastic disease transmission model.

BACKGROUND: African swine fever (ASF) is a highly contagious and devastating pig disease that has caused extensive global economic losses. Understanding ASF virus (ASFV) transmission dynamics within a herd is necessary in order to prepare for and respond to an outbreak in the United States. Although the transmission parameters for the highly virulent ASF strains have been estimated in several articles, there are relatively few studies focused on moderately virulent strains. Using an approximate Bayesian computation algorithm in conjunction with Monte Carlo simulation, we have estimated the adequate contact rate for moderately virulent ASFV strains and determined the statistical distributions for the durations of mild and severe clinical signs using individual, pig-level data. A discrete individual based disease transmission model was then used to estimate the time to detect ASF infection based on increased mild clinical signs, severe clinical signs, or daily mortality. RESULTS: Our results indicate that it may take two weeks or longer to detect ASF in a finisher swine herd via mild clinical signs or increased mortality beyond levels expected in routine production. A key factor contributing to the extended time to detect ASF in a herd is the fairly long latently infected period for an individual pig (mean 4.5, 95% P.I., 2.4 - 7.2 days). CONCLUSION: These transmission model parameter estimates and estimated time to detection via clinical signs provide valuable information that can be used not only to support emergency preparedness but also to inform other simulation models of evaluating regional disease spread.

African swine fever detection and transmission estimates using homogeneous versus heterogeneous model formulation in stochastic simulations within pig premises.

Background: African swine fever (ASF) is one of the most important foreign animal diseases to the U.S. swine industry. Stakeholders in the swine production sector are on high alert as they witness the devastation of ongoing outbreaks in some of its most important trade partner countries. Efforts to improve preparedness for ASF outbreak management are proceeding in earnest and mathematical modeling is an integral part of these efforts. Aim: This study aimed to assess the impact on within-herd transmission dynamics of ASF when the models used to simulate transmission assume there is homogeneous mixing of animals within a barn. Methods: Barn-level heterogeneity was explicitly captured using a stochastic, individual pig-based, heterogeneous transmission model that considers three types of infection transmission, (1) within-pen via nose-to-nose contact; (2) between-pen via nose-to-nose contact with pigs in adjacent pens; and (3) both between- and within-pen via distance-independent mechanisms (e.g., via fomites). Predictions were compared between the heterogeneous and the homogeneous Gillespie models. Results: Results showed that the predicted mean number of infectious pigs at specific time points differed greatly between the homogeneous and heterogeneous models for scenarios with low levels of between-pen contacts via distance-independent pathways and the differences between the two model predictions were more pronounced for the slow contact rate scenario. The heterogeneous transmission model results also showed that it may take significantly longer to detect ASF, particularly in large barns when transmission predominantly occurs via nose-to-nose contact between pigs in adjacent pens. Conclusion: The findings emphasize the need for completing preliminary explorations when working with homogeneous mixing models to ascertain their suitability to predict disease outcomes.

Simulated Flock-Level Shedding Characteristics of Turkeys in Ten Thousand Bird Houses Infected with H7 Low Pathogenicity Avian Influenza Virus Strains.

Understanding the amount of virus shed at the flock level by birds infected with low pathogenicity avian influenza virus (LPAIV) over time can help inform the type and timing of activities performed in response to a confirmed LPAIV-positive premises. To this end, we developed a mathematical model which allows us to estimate viral shedding by 10,000 turkey toms raised in commercial turkey production in the United States, and infected by H7 LPAIV strains. We simulated the amount of virus shed orally and from the cloaca over time, as well as the amount of virus in manure. In addition, we simulated the threshold cycle value (Ct) of pooled oropharyngeal swabs from birds in the infected flock tested by real-time reverse transcription polymerase chain reaction. The simulation model predicted that little to no shedding would occur once the highest threshold of seroconversion was reached. Substantial amounts of virus in manure (median 1.5×108 and 5.8×109; 50% egg infectious dose) were predicted at the peak. Lastly, the model results suggested that higher Ct values, indicating less viral shedding, are more likely to be observed later in the infection process as the flock approaches recovery.

A Retrospective Study of Early vs. Late Virus Detection and Depopulation on Egg Laying Chicken Farms Infected with Highly Pathogenic Avian Influenza Virus During the 2015 H5N2 Outbreak in the United States.

The 2015 highly pathogenic avian influenza (HPAI) H5N2 outbreak affected more than 200 Midwestern U.S. poultry premises. Although each affected poultry operation incurred substantial losses, some operations of the same production type and of similar scale had differences between one another in their ability to recognize evidence of the disease before formal diagnoses and in their ability to make proactive, farm-level disease containment decisions. In this case comparison study, we examine the effect of HPAI infection on two large egg production facilities and the epidemiologic and financial implications resulting from differences in detection and decision-making processes. Each egg laying facility had more than 1 million caged birds distributed among 18 barns on one premises (Farm A) and 17 barns on the other premises (Farm B). We examine how farm workers' awareness of disease signs, as well as how management's immediate or delayed decisions to engage in depopulation procedures, affected flock mortality, levels of environmental contamination, time intervals for re population, and farm profits on each farm. By predictive mathematical modeling, we estimated the time of virus introduction to examine how quickly infection was identified on the farms and then estimated associated contact rates within barns. We found that the farm that implemented depopulation immediately after detection of abnormal mortality (Farm A) was able to begin repopulation of barns 37 days sooner than the farm that began depopulation well after the detection of abnormally elevated mortality (Farm B). From average industry economic data, we determined that the loss associated with delayed detection using lost profit per day in relation to down time was an additional $3.3 million for Farm B when compared with Farm A.

Estudio retrospectivo de detección viral temprana y tardía y despoblación en granjas de gallinas de postura infectadas con el virus de la influenza aviar altamente patógeno durante el brote de H5N2 del año 2015 en los Estados Unidos. El brote de influenza aviar altamente patógena (HPAI) H5N2 del año 2015 afectó a más de 200 granjas avícolas del medio oeste de los Estados Unidos. Aunque cada operación avícola afectada incurrió en pérdidas sustanciales, algunas operaciones del mismo tipo de producción y de escala similar tuvieron diferencias entre sí en su capacidad para reconocer evidencias de la enfermedad antes de los diagnósticos formales y en su capacidad para realizar decisiones proactivas para la contención de la enfermedad a nivel de granja. En este estudio de caso, se examinó el efecto de la infección por influenza aviar altamente patógena en dos instalaciones grandes de producción de huevo y las implicaciones epidemiológicas y financieras que fueron resultado de los diferentes procesos de detección y toma de decisiones. Cada instalación de postura de huevo tenía más de un millón de aves enjauladas distribuidas en 18 casetas en una granja (Granja A) y 17 casetas en las otras instalaciones (Granja B). Se examinó cómo el conocimiento de los trabajadores agrícolas sobre los signos de la enfermedad, así como cómo las decisiones de manejo inmediatas o tardías para establecer procedimientos de despoblación, afectaron la mortalidad de las parvadas, los niveles de contaminación ambiental, los intervalos de tiempo para la repoblación y las ganancias en cada granja. Mediante un modelo matemático predictivo, se estimó el tiempo de introducción del virus para examinar la rapidez con la que se identificó la infección en las granjas y luego se estimaron las tasas de contacto asociadas dentro de las casetas. Se encontró que la granja que implementó la despoblación inmediatamente después de la detección de mortalidad anormal (Granja A) pudo comenzar la repoblación de las casetas 37 días antes que la granja que comenzó la despoblación mucho después de la detección de mortalidad anormalmente elevada (Granja B). A partir de los datos económicos promedio de la industria, se determinó que la pérdida asociada con la detección tardía utilizando las pérdidas de ganancias por día en relación con el tiempo de inactividad fue de $3.3 millones adicionales para la Granja B en comparación con la Granja A.

The Risk of Highly Pathogenic Influenza A Virus Transmission to Turkey Hen Flocks Through Artificial Insemination.

Artificial insemination is a routine practice for turkeys that can introduce pathogens into breeder flocks in a variety of ways. In this manuscript, a risk analysis on the potential transmission of highly pathogenic avian influenza (HPAI) to naïve hens through artificial insemination is presented. A case of HPAI on a stud farm where the potential transmission of the virus to susceptible hens in the 2015 H5N2 HPAI outbreak in Minnesota is described along with documentation of known and potential transmission pathways from the case. The pathways by which artificial insemination might result in the spread of HPAI to susceptible hens were determined by considering which could result in the 1) entry of HPAI virus onto a premises through semen movement; and 2) exposure of susceptible hens to HPAI as a result of this movement. In the reported case, HPAI virus was detected in semen from infected toms, however, transmission of HPAI to naïve hens through semen is unclear since the in utero infectious dose is not known. This means that the early detection of infection might limit but not eliminate the risk of hen exposure. Because of the numerous potential pathways of spread and the close contact with the birds, it is highly likely that if semen from an HPAI-infected tom flock is used, there will be spread of the virus to naïve hens through insemination. If insemination occurs with semen from stud farms in an HPAI control area, receiving hen farms should have restricted movements to prevent outbreak spread in the event that they become infected.

Artículo regular­Riesgo de transmisión del virus de la influenza A altamente patógeno a parvadas de pavos hembras mediante inseminación artificial. La inseminación artificial es una práctica de rutina para los pavos que puede introducir patógenos en las parvadas de reproductores de diversas formas. En este manuscrito, se presenta un análisis de riesgo sobre la posible transmisión de la influenza aviar altamente patógena a gallinas susceptibles mediante inseminación artificial. Un caso de influenza aviar altamente patógena en una granja de machos sementales donde se describe la posible transmisión del virus a gallinas susceptibles en el brote de influenza aviar altamente patógena H5N2 del año 2015 en Minnesota, junto con la documentación de las vías de transmisión conocidas y potenciales del caso. Las vías por las cuales la inseminación artificial podría resultar en la propagación de la influenza aviar altamente patógena a las gallinas susceptibles se determinaron considerando cuáles podrían resultar en 1) la entrada del virus de la influenza aviar altamente patógena en una granja a través del movimiento del semen; y 2) exposición de gallinas susceptibles a la influenza aviar altamente patógena como resultado de este movimiento. Sin embargo, se demostró la detección del virus de la influenza aviar altamente patógena en el semen de machos infectados. Debido a que se desconoce la dosis infecciosa del virus de la influenza aviar administrada en el útero necesaria para transmitir la influenza aviar altamente patógena a las gallinas susceptibles, está claro que la detección de la infección no puede ser la única estrategia de contención. La detección temprana de la infección puede limitar, pero no eliminar, el riesgo de exposición de las gallinas. Debido a las numerosas vías potenciales de propagación y al estrecho contacto con las aves, es muy probable que si se usa semen de una parvada de machos infectados con influenza aviar de alta patogenicidad, se propague el virus a gallinas susceptibles a través de la inseminación. Si la inseminación ocurre con semen de granjas de sementales en un área de control de influenza aviar de alta patogenicidad, las granjas de gallinas receptoras deben tener movimientos restringidos para prevenir la propagación del brote en caso de que se infecten.

Influenza Vaccination of Swine Reduces Public Health Risk at the Swine-Human Interface.

Influenza A viruses (IAV) in swine (IAV-S) pose serious risk to public health through spillover at the human-animal interface. Continued zoonotic transmission increases the likelihood novel IAV-S capable of causing the next influenza pandemic will emerge from this animal reservoir. Because current mitigation strategies are insufficient to prevent IAV zoonosis, we investigated the ability of swine vaccination to decrease IAV-S zoonotic transmission risk. We assessed postchallenge viral shedding in market-age swine vaccinated with either live-attenuated influenza virus (LAIV), killed influenza virus (KV), or sham vaccine (NV). We also assessed postchallenge transmission by exposing naive ferrets to pigs with contact types reflective of those experienced by humans in a field setting. LAIV and KV swine groups exhibited a nearly 100-fold reduction in peak nasal titer (LAIV mean, 4.55 log 50% tissue culture infectious dose [TCID50]/ml; KV mean, 4.53 log TCID50/ml) compared to NV swine (mean, 6.40 log TCID50/ml). Air sampling during the postchallenge period revealed decreased cumulative IAV in LAIV and KV study room air (LAIV, area under the concentration-time curve [AUC] of 57.55; KV, AUC = 24.29) compared to the NV study room (AUC = 86.92). Pairwise survival analysis revealed a significant delay in onset of infection among ferrets exposed to LAIV pigs versus NV pigs (rate ratio, 0.66; P = 0.028). Ferrets exposed to vaccinated pigs had lower cumulative virus titers in nasal wash samples (LAIV versus NV, P < 0.0001; KV versus NV, P= 0.3490) and experienced reduced clinical signs during infection. Our findings support the implementation of preexhibition influenza vaccination of swine to reduce the public health risk posed by IAV-S at agricultural exhibitions. IMPORTANCE Swine exhibited at agricultural fairs in North America have been the source of repeated zoonotic influenza A virus transmission, which creates a pathway for influenza pandemic emergence. We investigated the effect of using either live-attenuated influenza virus or killed influenza virus vaccines as prefair influenza vaccination of swine on zoonotic influenza transmission risk. Ferrets were exposed to the pigs in order to simulate human exposure in a field setting. We observed reductions in influenza A virus shedding in both groups of vaccinated pigs as well as the corresponding ferret exposure groups, indicating vaccination improved outcomes on both sides of the interface. There was also significant delay in onset of infection among ferrets that were exposed to live-attenuated virus-vaccinated pigs, which might be beneficial during longer fairs. Our findings indicate that policies mandating influenza vaccination of swine before fairs, while not currently common, would reduce the public health risk posed by influenza zoonosis.

Shedding and transmission of a live attenuated influenza A virus vaccine in pre-weaned pigs under field conditions.

Influenza A virus (IAV) is one of the most important respiratory viruses affecting pig health and vaccination is the most common strategy to control influenza infections. In this field study we assessed the onset and duration of shedding of a live attenuated influenza virus (LAIV) vaccine, its ability to transmit to non-vaccinated pigs and whether the LAIV could be aerosolized and detected in the environment. Thirty-three litters (n = 33) of a farm using the LAIV vaccine were selected for the study, a subset of them (n = 12) were left unvaccinated and a subset of piglets (n = 3) in vaccinated litters were also left unvaccinated to serve as sentinels. Selected piglets from the litters were sampled multiple days post vaccination (DPV) by collecting nasal swabs and blood, and were tested using a LAIV vaccine specific RT-PCR assay and hemagglutination inhibition assay against the LAIV strains respectively. Environmental specimens consisting of air and surface wipes were also collected. One hundred percent (21/21) of the vaccinated litters tested LAIV positive 1 DPV and until 6 DPV. In contrast, only five (5/33) of the thirty-three non-vaccinated pigs tested positive during the course of the study. Viable LAIV was confirmed in vaccinated pigs by cell culture and whole genome sequencing. In addition, low levels of LAIV RNA (RT-PCR Ct values ranging between 33 and 38) were detected in all air specimens collected on the day of vaccination and until 6 DPV (3/10). Pigs had maternally derived antibodies reactive against the LAIV strains which may have influenced the degree of shedding observed. Under the conditions of this study, shedding of the LAIV from vaccinated pigs was limited in time, resulted in minimal transmission to non-vaccinated pigs and was detected in low levels in aerosols collected in the vaccinated rooms likely influenced by the presence of maternally derived antibodies against the LAIV strains.

Impact of nurse sows on influenza A virus transmission in pigs under field conditions.

Piglets prior to weaning play a central role in maintaining influenza infections in breeding herds and the use of nurse sows is a common practice to adopt piglets that fall behind and that otherwise would die. Transmission of influenza A virus (IAV) from nurse sows to adopted pigs has been reported experimentally, however, the importance of this route of transmission under field conditions has not yet been elucidated. A cohort study to assess the IAV status in nurse and control sows and their respective litters was carried out in three influenza positive breed-to-wean farms. A total of 94 control and 90 nurse sows were sampled by collecting udder skin wipes and oral swabs at enrollment (∼ 5-7 days after farrowing) and at weaning. Six piglets per litter were sampled randomly at enrollment, 2 days post-enrollment (DPE), 4 DPE, at day 14 of lactation (14DL) and at weaning. At enrollment, 76 % (69/91) of udder wipes and 3 % (3/89) of oral swabs from nurse sows were positive by rRT-PCR compared with 23 % (21/92) of udder wipes and 0 % (0/85) of oral swabs from control sows. Of the 94 control litters sampled, 11.7 %, 14.9 %, 22.9 %, 46.8 % and 63.9 % tested rRT-PCR IAV positive at enrollment, 2DPE, 4DPE, 14 DL and weaning, respectively. Corresponding prevalence for nurse sow litters were 12.2 %, 30.2 %, 37.0 %, 59.4 % and 56.4 %. The odds of IAV positivity were significantly higher (p < 0.05) for litters from nurse sows 2 DPE (odd ratio (OR) = 6.13, 95 % CI = 1.8-21.2), 4 DPE (OR = 5.5, 95 % CI = 1.7-17.8) and 14 DL (OR = 3.7, 95 % CI = 1.1-12.3). However, there were no differences in the proportion of positive samples at weaning. Moreover, approximately 18 % of the control sows and 11 % of nurse sows that tested IAV negative in oral swabs at enrollment, tested IAV positive at weaning. This study indicates that nurse sows can contribute to the transmission and perpetuation of IAV infections in pigs prior to weaning, particularly during the first week after adoption.

Estimating epidemiological parameters using diagnostic testing data from low pathogenicity avian influenza infected turkey houses.

Limiting spread of low pathogenicity avian influenza (LPAI) during an outbreak is critical to reduce the negative impact on poultry producers and local economies. Mathematical models of disease transmission can support outbreak control efforts by estimating relevant epidemiological parameters. In this article, diagnostic testing data from each house on a premises infected during a LPAI H5N2 outbreak in the state of Minnesota in the United States in 2018 was used to estimate the time of virus introduction and adequate contact rate, which determines the rate of disease spread. A well-defined most likely time of virus introduction, and upper and lower 95% credibility intervals were estimated for each house. The length of the 95% credibility intervals ranged from 11 to 22 with a mean of 17 days. In some houses the contact rate estimates were also well-defined; however, the estimated upper 95% credibility interval bound for the contact rate was occasionally dependent on the upper bound of the prior distribution. The estimated modes ranged from 0.5 to 6.0 with a mean of 2.8 contacts per day. These estimates can be improved with early detection, increased testing of monitored premises, and combining the results of multiple barns that possess similar production systems.