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.

Surveillance and Sequestration Strategies to Reduce the Likelihood of Transporting Highly Pathogenic Avian Influenza Virus Contaminated Layer Manure.

Movement and land application of manure is a known risk factor for secondary spread of avian influenza viruses. During an outbreak of highly pathogenic avian influenza (HPAI), movement of untreated (i.e., fresh) manure from premises known to be infected is prohibited. However, moving manure from apparently healthy (i.e., clinically normal) flocks may be critical, because some egg-layer facilities have limited on-site storage capacity. The objective of this analysis was to evaluate targeted dead-bird active surveillance real-time reverse transcriptase polymerase chain reaction (rRT-PCR) testing protocols that could be used for the managed movement of manure from apparently healthy egg-layer flocks located in an HPAI control area. We also evaluated sequestration, which is the removal of manure from any contact with chickens, or with manure from other flocks, for a period of time, while the flock of origin is actively monitored for the presence of HPAI virus. We used stochastic simulation models to predict the chances of moving a load of contaminated manure, and the quantity of HPAI virus in an 8 metric ton (8000 kg) load of manure moved, before HPAI infection could be detected in the flock. We show that the likelihood of moving contaminated manure decreases as the length of the sequestration period increases from 3 to 10 days (e.g., for a typical contact rate, with a sample pool size of 11 swabs, the likelihood decreased from 48% to <1%). The total quantity of feces from HPAI-infectious birds in a manure load moved also decreases. Results also indicate that active surveillance protocols using 11 swabs per pool result in a lower likelihood of moving contaminated manure relative to protocols using five swabs per pool. Simulation model results from this study are useful to inform further risk evaluation of HPAI spread through pathways associated with manure movement and further evaluation of biosecurity measures intended to reduce those risks.

Artículo regular­Estrategias de vigilancia y aislamiento para reducir la probabilidad de transportar gallinaza de aves de postura contaminada con virus de influenza aviar altamente patógeno. El movimiento y la aplicación de gallinaza a la tierra es un factor de riesgo conocido para la propagación secundaria de los virus de la influenza aviar (IA). Durante un brote de influenza aviar altamente patógena (IAAP), se prohíbe el movimiento de gallinaza sin tratar (es decir, fresco) de las instalaciones que se conoce que están infectadas. Sin embargo, el traslado de gallinaza de parvadas aparentemente sanas (es decir, clínicamente normales) puede ser fundamental, porque algunas instalaciones de producción de huevo tienen una capacidad limitada de almacenamiento en el lugar. El objetivo de este análisis estaba evaluar los protocolos de la prueba de transcriptasa reversa y reacción en cadena de la polimerasa en tiempo real (rRT-PCR) utilizados en la vigilancia activa dirigida a aves muertas, que podrían usarse para el movimiento controlado de gallinaza de parvadas de postura aparentemente sanas ubicadas en un área de control para influenza aviar de alta patogenicidad. También se evaluó el aislamiento, que es la remoción de gallinaza y prevenir cualquier contacto con pollos, o con gallinaza de otras parvadas, durante un período de tiempo, mientras que la parvada de origen es monitoreada activamente para detectar la presencia del virus de la influenza aviar altamente patógeno. Se utilizaron modelos de simulación estocástica para predecir las posibilidades de trasladar una carga de estiércol contaminado y la cantidad de virus de la influenza aviar altamente patógeno en una carga de ocho toneladas métricas (8000 kg) de gallinaza trasladada, antes de que se pudiera detectar la infección por influenza aviar altamente patógena en la parvada. Se demostró que la probabilidad de mover gallinaza contaminada disminuye a medida que la duración del período de aislamiento aumenta de tres a diez días (por ejemplo, para una tasa de contacto típica, con un tamaño de muestra de 11 hisopos, la probabilidad disminuyó de 48% a <1 %). La cantidad total de heces de aves infectadas por la influenza aviar altamente patógena en una carga de gallinaza transportada también disminuye. Los resultados también indican que los protocolos de vigilancia activa que utilizan 11 hisopos como muestra agrupada dan como resultado una menor probabilidad de mover gallinaza contaminada en comparación con los protocolos que utilizan cinco hisopos por muestra agrupada. Los resultados del modelo de simulación de este estudio son útiles para una evaluación adicional del riesgo de la propagación de la influenza aviar altamente patógena a través de vías asociadas con el movimiento de gallinaza y una evaluación adicional de las medidas de bioseguridad destinadas a reducir esos riesgos.

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.

Surveillance and sequestration strategies to reduce the likelihood of transporting HPAIV contaminated layer manure.

Movement and land application of manure is a known risk factor for secondary spread of avian influenza (AI) viruses. During an outbreak of highly pathogenic avian influenza (HPAI), movement of untreated (i.e., fresh) manure from premises known to be infected would be prohibited. However, moving manure from apparently healthy (i.e., clinically normal) flocks may become critical, because some egg-layer facilities have limited on-site storage capacity. The objective of this analysis was to evaluate targeted dead-bird active surveillance rRT-PCR (real-time reverse transcriptase polymerase chain reaction) testing protocols that could be used for the managed movement of manure from apparently healthy egg-layer flocks located in a HPAI Control Area. We also evaluated sequestration, which is the removal of manure from any contact with chickens, or with manure from other flocks, for a period of time, while the flock of origin is actively monitored for the presence of HPAI virus. We used stochastic simulation models to predict the chances of moving a load of contaminated manure, and the quantity of HPAI virus in an 8 metric ton (8000 kg) load of manure moved, before HPAI infection would be detected in the flock. We show that the likelihood of moving contaminated manure would decrease as the length of the sequestration period increased from 3 to 10 days (e.g., for a typical contact rate, with a sample pool size of 11 swabs, the likelihood decreased from 48% to <1%). The total quantity of feces from HPAI infectious birds in a manure load moved would also decrease. Results also indicate that active surveillance protocols using 11 swabs per-pool result in a lower likelihood of moving contaminated manure relative to protocols using 5 swabs per pool. Simulation model results from this study are useful to inform further risk evaluation of HPAI spread through pathways associated with the manure movement, and further evaluation of biosecurity measures intended to reduce those risks.

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.

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.

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.

Mortality and Egg Production Patterns in the United States Prior to HP/LPAI H7N9 Detection.

In March 2017, two commercial broiler breeder operations were confirmed with H7N9 highly pathogenic avian influenza (HPAI), and an additional six commercial broiler breeder operations were found positive with an H7N9 low pathogenicity avian influenza virus (LPAIV) or an H7 LPAIV (N type not identified). To better understand conditions leading up to testing positive for AI, egg production and mortality data for the 6 mo before the outbreak were obtained from five case farms (two HPAIV-infected farms and three LPAIV-infected farms) and two control farms. Both HPAI farms experienced a sudden spike in mortality immediately before testing positive. Two LPAI farms experienced drops in egg production along with slight increases in mortality that occurred after a negative serologic test and before a positive PCR test. The third LPAI farm also had a notable drop in egg production with a coinciding increase in mortality before testing positive for AIV (last negative test date not available). Additionally, both HPAI farms and two LPAI farms reported mild respiratory illnesses in the weeks prior to testing positive for AI. Control farms did not experience similar drops in production or increase in mortality. Clinical signs on LPAI farms were mild and easily confused with background health patterns, suggesting the need for improved sensitivity to identify LPAI quickly. Applying a trigger of a 2% drop in egg production along with a mortality of 8 per 10 000 hens in individual barns showed that all case farms would be identified and uninfected farms would be falsely triggered on 1% of days monitored.

Mortalidad y patrones de producción de huevos en los Estados Unidos antes de la detección del virus de la influenza aviar H7N9 de baja y alta patogenicidad. En marzo del 2017, se confirmaron dos operaciones de reproductores pesados comerciales con influenza aviar altamente patógena H7N9 (HPAI) y adicionalmente se encontraron seis operaciones de reproductores pesados comerciales con un virus de influenza aviar de baja patogenicidad H7N9 (LPAIV) o con un virus de baja patogenicidad H7 con un subtipo de neuraminidasa no identificado. Para comprender mejor las condiciones que condujeron a un resultado positivo de influenza aviar, se recolectaron los datos de producción de huevo y mortalidad de cinco granjas que presentaron casos (dos granjas infectadas con el virus de alta patogenicidad y tres granjas infectadas con el virus de baja patogenicidad) y dos granjas control durante los seis meses anteriores al brote. Las dos grajas infectadas con el virus de alta patogenicidad experimentaron un aumento repentino en la mortalidad inmediatamente antes de que se determinaran como positivas. Dos granjas con el virus de baja patogenicidad experimentaron caídas en la producción de huevo junto con un ligero aumento en la mortalidad que se produjo después de que mostraran respuesta negativa a las pruebas serológicas y antes de resultar positivas mediante pruebas de RT-PCR. La tercera granja infectada con el virus de baja patogenicidad también tuvo una caída importante en la producción de huevo con un aumento coincidente en la mortalidad antes de que mostraran un resultado positivo para influenza aviar (la fecha de la última prueba negativa no se encontró disponible). Además, tanto las dos granjas con influenza aviar de alta patogenicidad como dos granjas con influenza aviar de baja patogenicidad reportaron enfermedades respiratorias leves en las semanas previas a la fecha cuando mostraron resultados positivos para la influenza aviar. Las granjas control no experimentaron caídas similares en la producción de huevo o aumento en la mortalidad. Los signos clínicos en las granjas de baja patogenicidad fueron leves y se confundieron fácilmente con los patrones de salud normales de la parvada, lo que sugiere la necesidad de mejorar la sensibilidad para identificar rápidamente la a la influenza aviar de baja patogenicidad. Con la aplicación de una alarma que se desencadene con una caída del 2% en la producción de huevo junto con una mortalidad de ocho por cada 10 mil gallinas en casetas individuales mostró que todas las granjas problema serían identificadas y que las granjas no infectadas podrían ser activadas falsamente en el 1% de los días monitoreados.

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.

Modeling the Transmission of Foot and Mouth Disease to Inform Transportation of Infected Carcasses to a Disposal Site During an Outbreak Event.

In the event of a Food and Mouth Disease (FMD) outbreak in the United States, an infected livestock premises is likely to result in a high number of carcasses (swine and/or cattle) as a result of depopulation. If relocating infected carcasses to an off-site disposal site is allowed, the virus may have increased opportunity to spread to uninfected premises and result in exposure of susceptible livestock. A stochastic within-herd disease spread model was used to predict the time to detect the disease by observation of clinical signs within the herd, and the number of animals in different disease stages over time. Expert opinion was elicited to estimate depopulation parameters in various scenarios. Disease detection was assumed when 5% of the population showed clinical signs by direct observation. Time to detection (5 and 95th percentile values) was estimated for all swine farm sizes (500-10,000 head) ranged from 102 to 282 h, from 42 to 216 h for all dairy cattle premises sizes (100-2,000 head) and from 66 to 240 h for all beef cattle premises sizes (5,000-50,000 head). Total time from infection to beginning depopulation (including disease detection and confirmation) for the first FMD infected case was estimated between 8.5-14.3 days for swine, 6-12.8 days for dairy or beef cattle premises. Total time estimated for subsequent FMD cases was between 6.8-12.3 days for swine, 4.3-10.8 days for dairy and 4.5-10.5 days for beef cattle premises. On an average sized operation, a sizable proportion of animals in the herd (34-56% of swine, 48-60% of dairy cattle, and 47-60% of beef cattle for the first case and 49-60% of swine, 55-60% of dairy cattle, 56-59% of beef cattle for subsequent cases) would be viremic at the time of beginning depopulation. A very small fraction of body fluids from the carcasses (i.e., 1 mL) would contain virus that greatly exceeds the minimum infectious dose by oral (4-7x) or inhalation (7-13x) route for pigs and cattle.

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.

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.

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.

A Simulation-Based Evaluation of Premovement Active Surveillance Protocol Options for the Managed Movement of Turkeys to Slaughter During an Outbreak of Highly Pathogenic Avian Influenza in the United States.

Risk management decisions associated with live poultry movement during a highly pathogenic avian influenza (HPAI) outbreak should be carefully considered. Live turkey movements may pose a risk for disease spread. On the other hand, interruptions in scheduled movements can disrupt business continuity. The Secure Turkey Supply (STS) Plan was developed through an industry-government-academic collaboration to address business continuity concerns that might arise during a HPAI outbreak. STS stakeholders proposed outbreak response measure options that were evaluated through risk assessment. The developed approach relies on 1) diagnostic testing of two pooled samples of swabs taken from dead turkeys immediately before movement via the influenza A matrix gene real-time reverse transcriptase polymerase chain reaction (rRT-PCR) test; 2) enhanced biosecurity measures in combination with a premovement isolation period (PMIP), restricting movement onto the premises for a few days before movement to slaughter; and 3) incorporation of a distance factor from known infected flocks such that exposure via local area spread is unlikely. Daily exposure likelihood estimates from spatial kernels from past HPAI outbreaks were coupled with simulation models of disease spread and active surveillance to evaluate active surveillance protocol options that differ with respect to the number of swabs per pooled sample and the timing of the tests in relation to movement. Simulation model results indicate that active surveillance testing, in combination with strict biosecurity, substantially increased HPAI virus detection probability. When distance from a known infected flock was considered, the overall combined likelihood of moving an infected, undetected turkey flock to slaughter was predicted to be lower at 3 and 5 km. The analysis of different active surveillance protocol options is designed to incorporate flexibility into HPAI emergency response plans.

Quantitative Estimation of the Number of Contaminated Hatching Eggs Released from an Infected, Undetected Turkey Breeder Hen Flock During a Highly Pathogenic Avian Influenza Outbreak.

The regulatory response to an outbreak of highly pathogenic avian influenza (HPAI) in the United States may involve quarantine and stop movement orders that have the potential to disrupt continuity of operations in the U.S. turkey industry--particularly in the event that an uninfected breeder flock is located within an HPAI Control Area. A group of government-academic-industry leaders developed an approach to minimize the unintended consequences associated with outbreak response, which incorporates HPAI control measures to be implemented prior to moving hatching eggs off of the farm. Quantitative simulation models were used to evaluate the movement of potentially contaminated hatching eggs from a breeder henhouse located in an HPAI Control Area, given that active surveillance testing, elevated biosecurity, and a 2-day on-farm holding period were employed. The risk analysis included scenarios of HPAI viruses differing in characteristics as well as scenarios in which infection resulted from artificial insemination. The mean model-predicted number of internally contaminated hatching eggs released per movement from an HPAI-infected turkey breeder henhouse ranged from 0 to 0.008 under the four scenarios evaluated. The results indicate a 95% chance of no internally contaminated eggs being present per movement from an infected house before detection. Sensitivity analysis indicates that these results are robust to variation in key transmission model parameters within the range of their estimates from available literature. Infectious birds at the time of egg collection are a potential pathway of external contamination for eggs stored and then moved off of the farm; the predicted number of such infectious birds was estimated to be low. To date, there has been no evidence of vertical transmission of HPAI virus or low pathogenic avian influenza virus to day-old poults from hatching eggs originating from infected breeders. The application of risk analysis methods was beneficial for evaluating outbreak measures developed through emergency response planning initiatives that consider the managed movement of hatching eggs from monitored premises in an HPAI Control Area.

Risk Reduction Modeling of High Pathogenicity Avian Influenza Virus Titers in Nonpasteurized Liquid Egg Obtained from Infected but Undetected Chicken Flocks.

Control of highly pathogenic avian influenza (HPAI) outbreaks in poultry has traditionally involved the establishment of disease containment zones, where poultry products are only permitted to move from within a zone under permit. Nonpasteurized liquid egg (NPLE) is one such commodity for which movements may be permitted, considering inactivation of HPAI virus via pasteurization. Active surveillance testing at the flock level, using targeted matrix gene real-time reversed transcriptase-polymerase chain reaction testing (RRT-PCR) has been incorporated into HPAI emergency response plans as the primary on-farm diagnostic test procedure to detect HPAI in poultry and is considered to be a key risk mitigation measure. To inform decisions regarding the potential movement of NPLE to a pasteurization facility, average HPAI virus concentrations in NPLE produced from a HPAI virus infected, but undetected, commercial table-egg-layer flock were estimated for three HPAI virus strains using quantitative simulation models. Pasteurization under newly proposed international design standards (5 log10 reduction) is predicted to inactivate HPAI virus in NPLE to a very low concentration of less than 1 embryo infectious dose (EID)50 /mL, considering the predicted virus titers in NPLE from a table-egg flock under active surveillance. Dilution of HPAI virus from contaminated eggs in eggs from the same flock, and in a 40,000 lb tanker-truck load of NPLE containing eggs from disease-free flocks was also considered. Risk assessment can be useful in the evaluation of commodity-specific risk mitigation measures to facilitate safe trade in animal products from countries experiencing outbreaks of highly transmissible animal diseases.