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

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

Apport de la modélisation à l'étude de la dynamique de transmission de virus dans des populations : application aux virus influenza de type A en élevage porcin.

Modelling in epidemiology can be used for parameter estimation, understanding infectious process or control strategies evaluation, and is based on a mathematical model representing the infectious process derived from the SIR model (susceptible-infectious-removed). This model is further adapted to the disease under study with additional health statuses to represent more precisely the characteristics of the infectious agent and to couple the infection dynamics with the population dynamics of the studied system. This adaptation is documented by descriptive and analytic epidemiological studies to obtain a model representing the infectious process in a realistic way. Risk assessment and/or evaluation of control strategies can be proposed by the model simulation. The use of a modelling approach to understand the determinisms of a viral infectious process within a structured animal population is further illustrated by the example of swine influenza A viruses persistence in pig farms. The model set up to this aim is used to better understand the mechanisms related to viruses persistence within the herd and identify potential control measures that could be applied in farm conditions.

Maternally-derived antibodies do not prevent transmission of swine influenza A virus between pigs.

A transmission experiment involving 5-week-old specific-pathogen-free (SPF) piglets, with (MDA(+)) or without maternally-derived antibodies (MDA(-)), was carried out to evaluate the impact of passive immunity on the transmission of a swine influenza A virus (swIAV). In each group (MDA(+)/MDA(-)), 2 seeders were placed with 4 piglets in direct contact and 5 in indirect contact (3 replicates per group). Serological kinetics (ELISA) and individual viral shedding (RT-PCR) were monitored for 28 days after infection. MDA waning was estimated using a nonlinear mixed-effects model and survival analysis. Differential transmission rates were estimated depending on the piglets' initial serological status and contact structure (direct contact with pen-mates or indirect airborne contact). The time to MDA waning was 71.3 [52.8-92.1] days on average. The airborne transmission rate was 1.41 [0.64-2.63] per day. The compared shedding pattern between groups showed that MDA(+) piglets had mainly a reduced susceptibility to infection compared to MDA(-) piglets. The resulting reproduction number estimated in MDA(+) piglets (5.8 [1.4-18.9]), although 3 times lower than in MDA(-) piglets (14.8 [6.4-27.1]), was significantly higher than 1. Such an efficient and extended spread of swIAV at the population scale in the presence of MDAs could contribute to swIAV persistence on farms, given the fact that the period when transmission is expected to be impacted by the presence of MDAs can last up to 10 weeks.

Maternally-derived antibodies do not inhibit swine influenza virus replication in piglets but decrease excreted virus infectivity and impair post-infectious immune responses.

Maternally-derived antibodies (MDA) reduce piglet susceptibility to swine influenza A virus, but interfere with post-infectious immune responses, raising questions about protection after waning of passive immunity. We therefore analysed the impact of different levels of residual MDA on virus excretion and immune responses in piglets born to vaccinated sows (MDA+) and infected with H1N1 at 5, 7 or 11 weeks of age, in comparison to piglets born to unvaccinated sows (MDA-). Subsequent protection against a second homologous infection occurring 4 weeks after the primo-infection was also investigated. MDA- pigs showed clinical signs, shed the virus, and developed specific immune responses despite some age-dependent differences: 7-week-old pigs were less affected clinically, showed a 2-day delayed excretion peak and excreted less virus than younger pigs. In MDA+ animals, clinical signs increased together with the decrease of MDA levels related to the age at infection-time. Virus shedding was not prevented and genome quantification profiles were similar to those obtained in MDA- piglets. However, viral particles excreted by 5-week-old MDA+ piglets appeared to be less infectious than those shed by MDA- piglets at the same age. Humoral response was affected by MDA as illustrated by the absence of HI and neutralizing response regardless the infection age, but anti-NP/M responses were less affected. Proliferative T cell responses were slightly delayed by high MDA levels. Nevertheless, MDA+ animals were all protected from a second infection, like MDA- piglets. In conclusion, responses of pigs to H1N1 were affected by both the physiological development of animals at infection and the MDA level.

Maternally Derived Immunity Extends Swine Influenza A Virus Persistence within Farrow-to-Finish Pig Farms: Insights from a Stochastic Event-Driven Metapopulation Model.

Swine Influenza A Viruses (swIAVs) have been shown to persist in farrow-to-finish pig herds with repeated outbreaks in successive batches, increasing the risk for respiratory disorders in affected animals and being a threat for public health. Although the general routes of swIAV transmission (i.e. direct contact and exposure to aerosols) were clearly identified, the transmission process between batches is still not fully understood. Maternally derived antibodies (MDAs) were stressed as a possible factor favoring within-herd swIAV persistence. However, the relationship between MDAs and the global spread among the different subpopulations in the herds is still lacking. The aim of this study was therefore to understand the mechanisms induced by MDAs in relation with swIAV spread and persistence in farrow-to-finish pig herds. A metapopulation model has been developed representing the population dynamics considering two subpopulations-breeding sows and growing pigs-managed according to batch-rearing system. This model was coupled with a swIAV-specific epidemiological model, accounting for partial passive immunity protection in neonatal piglets and an immunity boost in re-infected animals. Airborne transmission was included by a between-room transmission rate related to the current prevalence of shedding pigs. Maternally derived partial immunity in piglets was found to extend the duration of the epidemics within their batch, allowing for efficient between-batch transmission and resulting in longer swIAV persistence at the herd level. These results should be taken into account in the design of control programmes for the spread and persistence of swIAV in swine herds.