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.

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.

Mathematical modeling of COVID-19 transmission dynamics in Uganda: Implications of complacency and early easing of lockdown.

BACKGROUND: Uganda has a unique set up comprised of resource-constrained economy, social-economic challenges, politically diverse regional neighborhood and home to long-standing refuge crisis that comes from long and protracted conflicts of the great lakes. The devastation of the on-going global pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is likely to be escalated by these circumstances with expectations of the impact of the disease being severe. MATERIALS AND METHODS: In this study, we formulate a mathematical model that incorporates the currently known disease characteristics and tracks various intervention measures that the government of Uganda has implemented since the reporting of the first case in March 2020. We then evaluate these measures to understand levels of responsiveness and adherence to standard operating procedures and quantify their impact on the disease burden. Novel in this model was the unique aspect of modeling the trace-and-isolate protocol in which some of the latently infected individuals tested positive while in strict isolation centers thereby reducing their infectious period. RESULTS: The study findings show that even with elimination of all imported cases at any given time it would take up to nine months to rid Uganda of the disease. The findings also show that the optimal timing of easing of lockdowns while mitigating the possibility of re-emergence of a second epidemic wave requires avoiding the scenario of releasing too-many-too-soon. It is even more worrying that enhancing contact tracing would only affect the magnitude and timing of the second wave but cannot prevent it altogether. CONCLUSION: We conclude that, given the prevailing circumstances, a phased-out lifting of lockdown measures, minimization of COVID-19 transmissibility within hospital settings, elimination of recruitment of infected individuals as well as enhanced contact tracing would be key to preventing overwhelming of the healthcare system that would come with dire consequences.

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.

Mortality-Based Triggers and Premovement Testing Protocols for Detection of Highly Pathogenic Avian Influenza Virus Infection in Commercial Upland Game Birds.

Outbreaks involving avian influenza viruses are often devastating to the poultry industry economically and otherwise. Disease surveillance is critically important because it facilitates timely detection and generates confidence that infected birds are not moved during business continuity intended to mitigate associated economic losses. The possibility of using an abnormal increase in daily mortality to levels that exceed predetermined thresholds as a trigger to initiate further diagnostic investigations for highly pathogenic avian influenza (HPAI) virus infection in the flock is explored. The range of optimal mortality thresholds varies by bird species, trigger type, and mortality thresholds, and these should be considered when assessing sector-specific triggers. The study uses purposefully collected data and data from the literature to determine optimal mortality triggers for HPAI detection in commercial upland game bird flocks. Three trigger types were assessed for the ability to detect rapidly both HPAI (on the basis of disease-induced and normal mortality data) and false alarm rate (on the basis of normal mortality data); namely, 1) exceeding a set absolute threshold on one day, 2) exceeding a set absolute threshold on two consecutive days, or 3) exceeding a multiple of a seven-day moving average. The likelihood of disease detection using some of these triggers together with premovement real-time reverse transcription PCR (rRT-PCR) testing was examined. Results indicate that the performance of the two consecutive days trigger had the best metrics (i.e., rapid detection with few false alarms) in the trade-off analysis. The collected normal mortality data was zero on 66% of all days recorded, with an overall mean of 0.6 dead birds per day. In the surveillance scenario analyses, combining the default protocol that relied only on active surveillance (i.e., premovement testing of oropharyngeal swab samples from dead birds by rRT-PCR) together with either of the mortality-based triggers improved detection rates on all days postexposure before scheduled movement. For exposures occurring within 8 days of movement, the protocol that combined the default with single-day triggers had slightly more detections than that with two consecutive days triggers. However, all assessed protocol combinations were able to detect all infections that occurred more than 10 days before scheduled movement. These findings can inform risk-based decisions pertaining to continuity of business in the commercial upland game bird industry.

Activadores basados en la mortalidad y protocolos de pruebas de premovimiento para la detección de la infección del virus de influenza aviar altamente patógena en aves de caza de tierras altas comerciales Los brotes que involucran virus de influenza aviar a menudo son económicamente devastadores para la industria avícola. La vigilancia de enfermedades es de importancia crítica porque facilita la detección oportuna y genera confianza en que las aves infectadas no serán movilizadas para continuar con la operación de las industrias avícolas para mitigar las pérdidas económicas asociadas. Se explora la posibilidad de utilizar un aumento anormal en la mortalidad diaria a niveles que excedan umbrales predeterminados como un desencadenante para iniciar investigaciones de diagnóstico para la infección del virus de la influenza aviar altamente patógena en la parvada. El rango de umbrales de mortalidad óptimos varían según la especie de ave, el tipo de activador y los umbrales de mortalidad y estos deben considerarse al evaluar los activadores específicos del sector. El estudio utiliza datos recopilados de manera planeada y datos de la literatura para determinar los desencadenantes de mortalidad óptimos para la detección de la influenza aviar altamente patógena en las parvadas comerciales de aves de caza de tierras altas. Se evaluaron tres activadores de acuerdo a su capacidad de detectar rápidamente influenza aviar altamente patógena (en función de los datos de mortalidad normal e inducida por la enfermedad) y la tasa de falsa alarma (en función de los datos de mortalidad normal); como son, 1) que se exceda un umbral absoluto establecido en un día, 2) que se exceda un umbral absoluto establecido en dos días consecutivos, o 3) que excede un múltiplo de un promedio móvil de siete días. Se examinó la probabilidad de detección de la enfermedad utilizando algunos de estos desencadenantes junto con la prueba de transcripción reversa y PCR en tiempo real (rRT-PCR). Los resultados indicaron que el rendimiento del disparador de dos días consecutivos tuvo los mejores resultados (es decir, detección rápida con pocas falsas alarmas) en el análisis costo-beneficio. Los datos de mortalidad normal recopilados fueron cero en el 66% de todos los días registrados, con una media general de 0.6 aves muertas por día. En los análisis de escenarios de vigilancia, la combinación del protocolo predeterminado que se basó únicamente en la vigilancia activa (por ejemplo pruebas antes de movilizaciones con muestras de hisopos orofaríngeos por rRT-PCR de aves muertas) a la par con cualquiera de los desencadenantes basados en la mortalidad mejoraron las tasas de detección en todos los días posteriores a la exposición antes del movimiento programado. Para las exposiciones que ocurrieron dentro de los ocho días de movimiento, el protocolo que combinó el valor predeterminado con los activadores de un solo día tuvo un poco más de detecciones que el de los activadores de dos días consecutivos. Sin embargo, todas las combinaciones de protocolos evaluadas pudieron detectar todas las infecciones que ocurrieron por más de 10 días antes del movimiento programado. Estos hallazgos pueden proveer información para la toma de decisiones basadas en el riesgo relacionadas con la continuidad de operaciones en la industria comercial de aves de caza de tierras altas.

Evaluating the Effect of the Within-Flock Disease Transmission Rate on Premovement Active Surveillance in Low Pathogenicity Avian Influenza-Infected Flocks.

Premovement active surveillance for low pathogenicity avian influenza (LPAI) may be a useful risk management tool for producers during high-risk periods, such as during an LPAI outbreak, or in areas where there is a recognized high risk for LPAI spread. The effectiveness of three active-surveillance protocols in mitigating LPAI spread risk related to the movement of spent broiler breeders to processing was evaluated in this study. Each protocol differed in the amount of real-time reverse transcription polymerase chain reaction (RRT-PCR) and serology testing conducted. The protocols were evaluated with the use of disease transmission and active surveillance simulation models parametrized specifically for broiler breeders to estimate the probability of detecting a current or past infection and the mean proportion of infectious birds at the time of sampling in houses where the infection remains undetected at the time of movement after exposure to the virus. The two values were estimated considering flock infection for 1-28 days prior to the day of scheduled movement. A distribution for the adequate contact rate, a parameter that controls the rate of within-house spread in the disease transmission model, was estimated for this study by a novel forward simulation approach with the use of serology data from three LPAI-infected broiler breeder flocks in the United States. The estimated distribution suggests that the lower contact-rate estimates from previously published studies were not a good fit for the serology results observed in these U.S. flocks, though considerable uncertainty remains in the parameter estimate. The results for the probability of detection and mean proportion of infectious, undetected birds suggest that RRT-PCR testing is most beneficial during the early stages of infection postexposure, and serology testing is most beneficial during the later stages of infection, results that are expected to hold for flocks outside the United States as well. Thus, protocols that combine RRT-PCR and serology testing can offer a more balanced approach with good performance over the disease course in a flock.

Evaluación del efecto de la tasa de transmisión dentro de la parvada en la vigilancia activa previa al movimiento de parvadas infectadas por influenza aviar de baja patogenicidad. La vigilancia activa para la influenza aviar de baja patogenicidad (LPAI) previa al movimiento puede ser una herramienta útil en el manejo de riesgos para los productores durante períodos de alto riesgo, como durante un brote de influenza aviar de baja patogenicidad o en áreas donde se reconoce que existe un alto riesgo de propagación de esta enfermedad. En este estudio, se evaluó la efectividad de tres protocolos de vigilancia activa para mitigar el riesgo de propagación de la influenza aviar de baja patogenicidad relacionado con el movimiento de los reproductores pesados de desecho a la planta de procesamiento. Los protocolos diferían en la cantidad de muestras procesadas por la transcriptasa reversa y reacción en cadena de la polimerasa en tiempo real (rRT-PCR) y por las pruebas serológicas realizadas. Los protocolos se evaluaron utilizando modelos de simulación de vigilancia activa y transmisión de la enfermedad con parámetros específicamente para reproductores pesados, para estimar la probabilidad de detectar una infección actual o pasada y la proporción media de aves con infección activa al momento del muestreo en casetas donde la infección permanecía sin detectar al momento del movimiento después de la exposición al virus. Los dos valores se estimaron considerando la infección de la parvada de uno a 28 días antes de la fecha programada para el movimiento. Una distribución para la tasa de contacto adecuada, un parámetro que controla la tasa de propagación dentro de la caseta en el modelo de transmisión de la enfermedad, se estimó para este estudio mediante un novedoso enfoque de simulación directa utilizando datos serológicos de tres parvadas reproductores pesados infectados con influenza aviar de baja patogenicidad en los Estados Unidos. La distribución estimada sugiere que las estimaciones de la tasa de contacto más baja obtenida de los estudios publicados previamente no fueron una buena opción para los resultados serológicos observados en estas parvadas en los Estados Unidos, aunque sigue existiendo una gran incertidumbre en la estimación del parámetro. Los resultados de la probabilidad de detección y la proporción media de aves con infección no detectadas sugieren que la prueba rRT-PCR es más beneficiosa durante las primeras etapas de la infección después de la exposición, mientras que la serología es más beneficiosa durante las últimas etapas de la infección, resultados que se espera apliquen también para parvadas fuera de los Estados Unidos. Por lo tanto, los protocolos que combinan rRT-PCR y las pruebas de serología pueden ofrecer un enfoque más equilibrado con un buen rendimiento durante el curso de la enfermedad en una parvada.

Assessment of replicate numbers for titrating avian influenza virus using dose-response models.

Embryonating chicken eggs (ECEs) are among the most sensitive laboratory host systems for avian influenza virus (AIV) titration, but ECEs are expensive and require space for storage and incubation. Therefore, reducing ECE use would conserve resources. We utilized statistical modeling to evaluate the accuracy and precision of AIV titration with 3 instead of 5 ECEs for each dilution by the Reed-Muench method for 50% endpoint calculation. Beta-Poisson and exponential dose-response models were used in a simulation study to evaluate observations from actual titration data from 18 AIV isolates. The reproducibility among replicates of a titration was evaluated with one AIV isolate titrated in 3 replicates with the beta-Poisson, exponential, and Weibull dose-response models. The standard deviation (SD) of the error between input and estimated virus titers was estimated with Monte Carlo simulations using the fitted dose-response models. Good fit was observed with all models that were utilized. Reducing the number of ECEs per dilution from 5 to 3 resulted in the width of the 95% confidence interval increasing from ±0.64 to ±0.75 log10 50% ECE infectious doses (EID50) and the SD of the error increased by 0.03 log10 EID50. Our study suggests that using fewer ECEs per dilution is a viable approach that will allow laboratories to reduce costs and improve efficiency.

Analysis of geographic location and pathways for influenza A virus infection of commercial upland game bird and conventional poultry farms in the United States of America.

BACKGROUND: Avian influenza (AI) is an infectious viral disease that affects several species and has zoonotic potential. Due to its associated health and economic repercussions, minimizing AI outbreaks is important. However, most control measures are generic and mostly target pathways important for the conventional poultry farms producing chickens, turkeys, and eggs and may not target other pathways that may be specific to the upland game bird sector. The goal of this study is to provide evidence to support the development of novel strategies for sector-specific AI control by comparing and contrasting practices and potential pathways for spread in upland game bird farms with those for conventional poultry farms in the United States. Farm practices and processes, seasonality of activities, geographic location and inter-farm distance were analyzed across the sectors. All the identified differences were framed and discussed in the context of their associated pathways for virus introduction into the farm and subsequent between-farm spread. RESULTS: Differences stemming from production systems and seasonality, inter-farm distance and farm densities were evident and these could influence both fomite-mediated and local-area spread risks. Upland game bird farms operate under a single, independent owner rather than being contracted with or owned by a company with other farms as is the case with conventional poultry. The seasonal marketing of upland game birds, largely driven by hunting seasons, implies that movements are seasonal and customer-vendor dynamics vary between industry groups. Farm location analysis revealed that, on average, an upland game bird premises was 15.42 km away from the nearest neighboring premises with birds compared to 3.74 km for turkey premises. Compared to turkey premises, the average poultry farm density in a radius of 10 km of an upland game bird premises was less than a half, and turkey premises were 3.8 times (43.5% compared with 11.5%) more likely to fall within a control area during the 2015 Minnesota outbreak. CONCLUSIONS: We conclude that the existing differences in the seasonality of production, isolated geographic location and epidemiological seclusion of farms influence AI spread dynamics and therefore disease control measures should be informed by these and other factors to achieve success.

Avian Influenza in the U.S. Commercial Upland Game Bird Industry: An Analysis of Selected Practices as Potential Exposure Pathways and Surveillance System Data Reporting.

Producing a smaller yield of higher-value birds compared to conventional poultry production, the U.S. commercial upland game bird industry deals primarily in the sale of live birds for recreational hunting. In this study, our aims were to gain insights into the occurrence of avian influenza (AI) in the U.S. commercial upland game bird industry in comparison to other poultry sectors, to identify the presence of the specific AI risk factors in the practices of raising ducks on site and having connections to live bird markets (LBMs), and to assess how AI surveillance systems may have played a role in the reporting of the presence of exposure pathway-related information. We found that 23 AI epizootics involving upland game bird premises were reported, compared to 485 epizootics in the other poultry industries, and 86% of epizootics involving upland game birds were limited to only one premises. Regarding specific AI risk factors, 70% of upland game bird epizootics involved one of the two examined practices. In assessing the impact of surveillance systems, data framed around the implementation of surveillance systems revealed that the introduction of active surveillance coincided with the more thorough reporting of both the raising of ducks on site and premises having connections to LBMs. Our results suggest the need for more thorough data collection during epizootics and the need to assess additional exposure pathways specific to the commercial raise-for-release upland game bird industry.

Quantifying the effect of swab pool size on the detection of influenza A viruses in broiler chickens and its implications for surveillance.

BACKGROUND: Timely diagnosis of influenza A virus infections is critical for outbreak control. Due to their rapidity and other logistical advantages, lateral flow immunoassays can support influenza A virus surveillance programs and here, their field performance was proactively assessed. The performance of real-time polymerase chain reaction and two lateral flow immunoassay kits (FluDETECT and VetScan) in detecting low pathogenicity influenza A virus in oropharyngeal swab samples from experimentally inoculated broiler chickens was evaluated and at a flock-level, different testing scenarios were analyzed. RESULTS: For real-time polymerase chain reaction positive individual-swabs, FluDETECT respectively detected 37% and 58% for the H5 and H7 LPAIV compared to 28% and 42% for VetScan. The mean virus titer in H7 samples was higher than for H5 samples. For real-time polymerase chain reaction positive pooled swabs (containing one positive), detections by FluDETECT were significantly higher in the combined 5- and 6-swab samples compared to 11-swab samples. FluDETECT detected 58%, 55.1% and 44.9% for the H7 subtype and 28.3%, 34.0% and 24.6% for the H5 in pools of 5, 6 and 11 respectively. In our testing scenario analysis, at low flock-level LPAIV infection prevalence, testing pools of 11 detected slightly more infections while at higher prevalence, testing pools of 5 or 6 performed better. For highly pathogenic avian influenza virus, testing pools of 11 (versus 5 or 6) detected up to 5% more infections under the assumption of similar sensitivity across pools and detected less by 3% when its sensitivity was assumed to be lower. CONCLUSIONS: Much as pooling a bigger number of swab samples increases the chances of having a positive swab included in the sample to be tested, this study's outcomes indicate that this practice may actually reduce the chances of detecting the virus since it may result into lowering the virus titer of the pooled sample. Further analysis on whether having more than one positive swab in a pooled sample would result in increased sensitivity for low pathogenicity avian influenza virus is needed.

Preparing for a Foreign Animal Disease Outbreak Using a Novel Tabletop Exercise.

IntroductionForeign animal disease (FAD) outbreaks can have devastating impacts, but they occur infrequently in any specific sector anywhere in the United States (US). Training to proactively discuss implementation of control and prevention strategies are beneficial in that they provide stakeholders with the practical information and educational experience they will need to respond effectively to an FAD. Such proactive approaches are the mission of the Secure Food System (SFS; University of Minnesota; St. Paul, Minnesota USA). METHODS: The SFS exercises were designed as educational activities based on avian influenza (AI) outbreaks in commercial poultry scenarios. These scenarios were created by subject matter experts and were based on epidemiology reports, risk pathway analyses, local industry practices, and site-specific circumstances. Target audiences of an exercise were the groups involved in FAD control: animal agriculture industry members; animal health regulators; and diagnosticians. Groups of industry participants seated together at tables represented fictional poultry premises and were guided by a moderator to respond to an on-farm situation within a simulated outbreak. The impact of SFS exercises was evaluated through interviews with randomized industry participants and selected table moderators. Descriptive statistics and qualitative analyses were performed on interview feedback. RESULTS: Eleven SFS exercises occurred from December 2016 through October 2017 in multiple regions of the US. Exercises were conducted as company-wide, state-wide, or regional trainings. Nine were based on highly pathogenic avian influenza (HPAI) outbreaks and two focused on outbreaks of co-circulating HPAI and low pathogenicity avian influenza (LPAI). Poultry industry participants interviewed generally found attending an SFS exercise to be useful. The most commonly identified benefits of participation were its value to people without prior outbreak experience and knowledge gained about Continuity of Business (COB)-permitted movement. After completing an exercise, most participants evaluated their preparedness to respond to an outbreak as somewhat to very ready, and more than one-half reported their respective company or farms had discussions or changed actions due to participation. CONCLUSION: Evaluation feedback suggests the SFS exercises were an effective training method to supplement preparedness efforts for an AI outbreak. The concept of using multi-faceted scenarios and multiple education strategies during a tabletop exercise may be translatable to other emergency preparedness needs. LinskensEJ, NeuAE, WalzEJ, St. CharlesKM, CulhaneMR, SsematimbaA, GoldsmithTJ, HalvorsonDA, CardonaCJ. Preparing for a foreign animal disease outbreak using a novel tabletop exercise. Prehosp Disaster Med. 2018;33(6):640-646.

Spatial transmission of H5N2 highly pathogenic avian influenza between Minnesota poultry premises during the 2015 outbreak.

The spatial spread of highly pathogenic avian influenza (HPAI) H5N2 during the 2015 outbreak in the U.S. state of Minnesota was analyzed through the estimation of a spatial transmission kernel, which quantifies the infection hazard an infectious premises poses to an uninfected premises some given distance away. Parameters were estimated using a maximum likelihood method for the entire outbreak as well as for two phases defined by the daily number of newly detected HPAI-positive premises. The results indicate both a strong dependence of the likelihood of transmission on distance and a significant distance-independent component of outbreak spread for the overall outbreak. The results further suggest that HPAI spread differed during the later phase of the outbreak. The estimated spatial transmission kernel was used to compare the Minnesota outbreak with previous HPAI outbreaks in the Netherlands and Italy to contextualize the Minnesota transmission kernel results and make additional inferences about HPAI transmission during the Minnesota outbreak. Lastly, the spatial transmission kernel was used to identify high risk areas for HPAI spread in Minnesota. Risk maps were also used to evaluate the potential impact of an early marketing strategy implemented by poultry producers in a county in Minnesota during the outbreak, with results providing evidence that the strategy was successful in reducing the potential for HPAI spread.

A Mathematical Model that Simulates Control Options for African Swine Fever Virus (ASFV).

A stochastic model designed to simulate transmission dynamics of African swine fever virus (ASFV) in a free-ranging pig population under various intervention scenarios is presented. The model was used to assess the relative impact of the timing of the implementation of different control strategies on disease-related mortality. The implementation of biosecurity measures was simulated through incorporation of a decay function on the transmission rate. The model predicts that biosecurity measures implemented within 14 days of the onset of an epidemic can avert up to 74% of pig deaths due to ASF while hypothetical vaccines that confer 70% immunity when deployed prior to day 14 of the epidemic could avert 65% of pig deaths. When the two control measures are combined, the model predicts that 91% of the pigs that would have otherwise succumbed to the disease if no intervention was implemented would be saved. However, if the combined interventions are delayed (defined as implementation from > 60 days) only 30% of ASF-related deaths would be averted. In the absence of vaccines against ASF, we recommend early implementation of enhanced biosecurity measures. Active surveillance and use of pen-side diagnostic assays, preferably linked to rapid dissemination of this data to veterinary authorities through mobile phone technology platforms are essential for rapid detection and confirmation of ASF outbreaks. This prediction, although it may seem intuitive, rationally confirms the importance of early intervention in managing ASF epidemics. The modelling approach is particularly valuable in that it determines an optimal timing for implementation of interventions in controlling ASF outbreaks.

Estimating the Basic Reproductive Number (R0) for African Swine Fever Virus (ASFV) Transmission between Pig Herds in Uganda.

African swine fever (ASF) is a highly contagious, lethal and economically devastating haemorrhagic disease of domestic pigs. Insights into the dynamics and scale of virus transmission can be obtained from estimates of the basic reproduction number (R0). We estimate R0 for ASF virus in small holder, free-range pig production system in Gulu, Uganda. The estimation was based on data collected from outbreaks that affected 43 villages (out of the 289 villages with an overall pig population of 26,570) between April 2010 and November 2011. A total of 211 outbreaks met the criteria for inclusion in the study. Three methods were used, specifically; (i) GIS- based identification of the nearest infectious neighbour based on the Euclidean distance between outbreaks, (ii) epidemic doubling time, and (iii) a compartmental susceptible-infectious (SI) model. For implementation of the SI model, three approaches were used namely; curve fitting (CF), a linear regression model (LRM) and the SI/N proportion. The R0 estimates from the nearest infectious neighbour and epidemic doubling time methods were 3.24 and 1.63 respectively. Estimates from the SI-based method were 1.58 for the CF approach, 1.90 for the LRM, and 1.77 for the SI/N proportion. Since all these values were above one, they predict the observed persistence of the virus in the population. We hypothesize that the observed variation in the estimates is a consequence of the data used. Higher resolution and temporally better defined data would likely reduce this variation. This is the first estimate of R0 for ASFV in a free range smallholder pig keeping system in sub-Saharan Africa and highlights the requirement for more efficient application of available disease control measures.

Mathematical modelling of the transmission dynamics of contagious bovine pleuropneumonia reveals minimal target profiles for improved vaccines and diagnostic assays.

Contagious bovine pleuropneumonia (CBPP) is a cattle disease that has hampered the development of the livestock sector in sub-Saharan Africa. Currently, vaccination with a live vaccine strain is its recommended control measure although unofficial antimicrobial use is widely practiced. Here, modelling techniques are used to assess the potential impact of early elimination of infected cattle via accurate diagnosis on CBPP dynamics. A herd-level stochastic epidemiological model explicitly incorporating test sensitivity and specificity is developed. Interventions by annual vaccination, annual testing and elimination and a combination of both are implemented in a stepwise manner and their effectiveness compared by running 1000 simulations per intervention over ten years. The model predicts that among the simulated interventions, the ones likely to eliminate the disease from an isolated herd all involved annual vaccination of more than 75% of the animals with a vaccine that protects for at least 18 months combined with annual testing (and elimination of positive reactors) of 75% of the animals every six months after vaccination. The highest probability of disease elimination was 97.5% and this could occur within a median of 2.3 years. Generally, our model predicts that regular testing and elimination of positive reactors using improved tests will play a significant role in minimizing CBPP burden especially in the current situation where improved vaccines are yet to be developed.

Small distances can keep bacteria at bay for days.

Transmission of pathogens between spatially separated hosts, i.e., indirect transmission, is a commonly encountered phenomenon important for epidemic pathogen spread. The routes of indirect transmission often remain untraced, making it difficult to develop control strategies. Here we used a tailor-made design to study indirect transmission experimentally, using two different zoonotic bacteria in broilers. Previous experiments using a single bacterial species yielded a delay in the onset of transmission, which we hypothesized to result from the interplay between diffusive motion of infectious material and decay of infectivity in the environment. Indeed, a mathematical model of diffusive pathogen transfer predicts a delay in transmission that depends both on the distance between hosts and on the magnitude of the pathogen decay rate. Our experiments, carried out with two bacterial species with very different decay rates in the environment, confirm the difference in transmission delay predicted by the model. These results imply that for control of an infectious agent, the time between the distant exposure and the infection event is important. To illustrate how this can work we analyzed data observed on the spread of vancomycin-resistant Enterococcus in an intensive care unit. Indeed, a delayed vancomycin-resistant Enterococcus transmission component was identified in these data, and this component disappeared in a study period in which the environment was thoroughly cleaned. Therefore, we suggest that the impact of control strategies against indirect transmission can be assessed using our model by estimating the control measures' effects on the diffusion coefficient and the pathogen decay rate.