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Following the emergence of highly pathogenic avian influenza (H5N8) in France in early December 2020, we used duck mortality data from the index farm to investigate within-flock transmission dynamics. A stochastic epidemic model was fitted to the daily mortality data and model parameters were estimated using an approximate Bayesian computation sequential Monte Carlo (ABC-SMC) algorithm. The model predicted that the first bird in the flock was infected 5 days (95% credible interval, CI: 3–6) prior to the day of suspicion and that the transmission rate was 4.1 new infections per day (95% CI: 2.8–5.8). On average, ducks became infectious 4.1 h (95% CI: 0.7–9.1) after infection and remained infectious for 4.3 days (95% CI: 2.8–5.7). The model also predicted that 34% (50% prediction interval: 8%–76%) of birds would already be infectious by the day of suspicion, emphasizing the substantial latent threat this virus could pose to other poultry farms and to neighbouring wild birds. This study illustrates how mechanistic models can help provide rapid relevant insights that contribute to the management of infectious disease outbreaks of farmed animals. These methods can be applied to future outbreaks and the resulting parameter estimates made available to veterinary services within a few hours. ISSN:1865-1674 ISSN:1865-1682

Phylodynamic methods have successfully been used to describe viral spread history but their applications for assessing specific control measures are rare. In 2016-17, France experienced a devastating epidemic of a highly pathogenic avian influenza virus (H5N8 clade 2.3.4.4b). Using 196 viral genomes, we conducted a phylodynamic analysis combined with generalised linear model and showed that the large-scale preventive culling of ducks significantly reduced the viral spread between départements (French administrative division). We also found that the virus likely spread more frequently between départements that shared borders, but the spread was not linked to duck transport between départements. Duck transport within départements increased the within-département transmission intensity, although the association was weak. Together, these results indicated that the virus spread in short-distances, either between adjacent départements or within départements. Results also suggested that the restrictions on duck transport within départements might not have stopped the viral spread completely. Overall, by testing specific hypothesis related to different control measures, we demonstrated that phylodynamics methods are capable of investigating the impacts of control measures on viral spread.

Highlights • Maternally-derived neutralizing antibodies impair PRRS vaccination immune responses in piglets. • Maternally-derived neutralizing antibodies reduce PRRS vaccine efficacy in piglets. • IFNa may also interfere with PRRS vaccination., Modified live virus (MLV) vaccines are commonly used to reduce the impact of porcine reproductive and respiratory syndrome (PRRS) but limited efficacy is achieved in field conditions. Here, we evaluated the impact of maternally-derived neutralizing antibodies (MDNAs) on vaccine efficacy after PRRS virus (PRRSV) challenge. Piglets with low (A−) or high (A+) MDNA levels derived from a commercial pig herd were moved to experimental facilities to be vaccinated (V+) or not (V−) with a PRRSV-1 MLV vaccine at 3 weeks of age (woa). Because of unexpectedly low vaccine detection in A−V+ piglets post-vaccination (pv), all V+ piglets received a second vaccination at 4 woa. Five weeks (W5) pv, piglets were inoculated with a PRRSV-1 field strain to evaluate vaccine protection, and were mingled 24 h later with non-inoculated piglets of similar immune status to assess viral transmission. Vaccine strain was detected at W2 pv in 69% and 6% of A−V+ and A+V+ piglets, and at W5 pv in 50% and 25% of A−V+ and A+V+ piglets, respectively. At W5 pv, 94% of A−V+ and 44% of A+V+ piglets seroconverted, with a significant IFNg response induction in the A−V+ group only. After challenge, compared to the V− inoculated group, viremia was 100-fold lower at 10 days post-infection in A−V+ whereas viremia was not significantly reduced in A+V+ piglets. A lower transmission rate was estimated for the A−V+ group: 0.15 [0.07–0.29] versus 0.44 [0.18–1.76] and 0.32 [0.14–0.68] for the A+V+ and V− groups, respectively. Investigations about the low vaccine strain detection after the first vaccination suggested a relationship between IFNa levels and vaccine strain detection in A−V+ piglets. We showed that MDNAs impair vaccine efficacy against PRRSV both in inoculated and contact piglets, probably by reducing vaccine replication. IFNa may also interfere with PRRSV vaccination. These new data could help improving vaccination protocols.

Hepatitis E virus is a zoonotic pathogen for which pigs have been identified as the main reservoir in industrialised countries. HEV infection dynamics in pig herds and pigs are influenced by several factors, including herd practices and possibly co-infection with immunomodulating viruses. This study therefore investigates the impact of porcine circovirus type 2 (PCV2) on HEV infection and transmission through experimental HEV/PCV2 co-infection of specific-pathogen-free pigs. No statistical difference between HEV-only and HEV/PCV2-infected animals was found for either the infectious period or the quantity of HEV shed in faeces. The HEV latency period was shorter for HEV/PCV2 co-infected pigs than for HEV-only infected pigs (11.6 versus 12.3 days). Its direct transmission rate was three times higher in cases of HEV/PCV2 co-infection than in cases of HEV-only infection (0.12 versus 0.04). On the other hand, the HEV transmission rate through environmental accumulation was lower in cases of HEV/PCV2 co-infection (4.3.10(-6) versus 1.5.10(-5) g/RNA copies/day for HEV-only infected pigs). The time prior to HEV seroconversion was 1.9 times longer in HEV/PCV2 co-infected pigs (49.4 versus 25.6 days for HEV-only infected pigs). In conclusion, our study shows that PCV2 affects HEV infection and transmission in pigs under experimental conditions.

Live animal movements generate direct contacts (via the exchange of live animals) and indirect contacts (via the transit of transport vehicles) between farms, which can contribute to the spread of pathogens. However, most analyses focus solely on direct contacts and can therefore underestimate the contribution of live animal movements in the spread of infectious diseases. Here, we used French live duck movement data (2016–2018) from one of the largest transport companies to compare direct and indirect contact patterns between duck farms and evaluate how these patterns were associated with the French 2016–2017 epidemic of highly pathogenic avian influenza H5N8. A total number of 614 farms were included in the study, and two directed networks were generated: the animal introduction network (exchange of live ducks) and the transit network (transit of transport vehicles). Following descriptive analyses, these two networks were scrutinized in relation to farm infection status during the epidemic. Results showed that farms were substantially more connected in the transit network than in the animal introduction network and that the transit of transport vehicles generated more opportunities for transmission than the exchange of live animals. We also showed that animal introduction and transit networks’ statistics decreased substantially during the epidemic (January–March 2017) compared to non-epidemic periods (January-March 2016 and January-March 2018). We estimated a probability of 33.3 % that a farm exposed to the infection through either of the two live duck movement networks (i.e. that was in direct or indirect contact with a farm that was reported as infected in the following seven days) becomes infected within seven days after the contact. However, we also demonstrated that the level of exposure of farms by these two contact patterns was low, leading only to a handful of transmission events through these routes. As a consequence, we showed that live animal movement patterns are efficient transmission routes for HPAI but have been efficiently reduced to limit the spread during the French 2020–2021 epidemic. These results underpin the relevance of studying indirect contacts resulting from the movement of animals to understand their transmission potential and the importance of accounting for both routes when designing disease control strategies.

Following the emergence of highly pathogenic avian influenza (H5N8) in France in early December 2020, we used duck mortality data of the index case to investigate within-flock transmission dynamics. A stochastic epidemic model was adjusted to the daily mortality data and model parameters were estimated using an approximate Bayesian computation sequential Monte Carlo (ABC-SMC) algorithm. Results suggested that the virus was introduced 4 days (95% credible interval: 3 – 5) prior to the day suspicion was reported and that the transmission rate was 3.7 day-1 (95%CI: 2.6 – 5.3). On average, ducks started being infectious 3.1 hours (95%CI: 0.4 – 8.0) after infection and remained infectious for 4.4 days (95%CI: 3.1 – 5.6). Model outputs also suggested that the number of infectious ducks was already 3239 (95%CI: 26 – 3706) the day before suspicion, emphasising the substantial latent threat this virus could pose to other poultry farms and to neighbouring wildlife. These estimations can be applied to upcoming outbreaks and made available to veterinary services within few hours. This study illustrates how mechanistic models can provide rapid relevant insights to contribute to the management of infectious disease outbreaks of farmed animals.

Hepatitis E virus (HEV) is a zoonotic agent with pigs as the main reservoir in industrialised countries. Recent studies conducted on pig farms, in experimental conditions or through modelling approaches, have led to a better understanding of the spread of HEV on pig farms. The findings have also made it possible to define a set of measures to reduce HEV prevalence and the risk of marketing contaminated products. The objective of this study was to assess the feasibility of a set of HEV control strategies on pig farms. Individual semi-structured interviews were conducted with farmers, veterinarians and farming advisors to collect general data, their level of knowledge of HEV, their opinion on the technical feasibility of certain changes in practices, their perception of the respective responsibilities of the different stakeholders, and their feelings about the importance of the issue, following the framework of the Theory of Planned Behaviour. The interviews made it possible to highlight potential barriers and preferred motivators for the implementation of on-farm risk mitigation strategies. Barriers included lack of knowledge, scientific gaps, perceived inability to control HEV, and low perception of the importance of the issue. Motivators included professional satisfaction, family recognition, and the opportunity to achieve higher quality standards. Three clusters of stakeholders were also identified, with a group of leaders who could help unlock reluctance and disseminate innovations. This type of behavioural approach appeared useful to help risk managers facilitate zoonotic control on pig farms.

International audience; Abstract African swine fever (ASF) has affected Romania since July 2017, with considerable economic and social consequences, despite the implementation of control measures mainly based on stamping out of infected pig populations. On the basis of the 2973 cumulative recorded cases up to September 2019 among wild boars and domestic pigs, analysis of the epidemiological characteristics could help to identify the factors favoring the persistence and spread of ASF. A statistical framework, based on a random forest methodology, was therefore developed to assess the spatiotemporal features of the epidemics and their relationships with environmental, human, and agricultural factors. The landscape of Romania was associated with the infection dynamics, particularly concerning forested and wetland areas. Waterways were also identified as a pivotal factor, raising questions about possible waterborne transmission since these waterways are often used as a water supply for backyard holdings. However, human activity was clearly identified as the main risk factor for the spread of ASF. Although the situation in Romania cannot be directly transposed to intensive pig farming countries, the findings of this study highlight the need for strict biosecurity measures on farms, and during transportation, to avoid ASF transmission at large geographic and temporal scales.

Co-infection by a type 1 modified live vaccine-like strain (MLV1-like) of porcine reproductive and respiratory syndrome virus (PRRSV) and a type 2 porcine circovirus (PCV2) was identified on a French pig farm with post-weaning multisystemic wasting syndrome (PMWS). An in vivo experiment was set up to characterize the virulence level of the MLV1-like strain compared with the parental MLV1 strain, and to assess the impact of PCV2 co-infection on the pathogenicity of both PRRSV strains. Six groups of six pigs each were inoculated only with either one of the two PRRSV strains or with PCV2, or co-inoculated with PCV2 and MLV1 or PCV2 and MLV1-like strains. Six contact pigs were added to each inoculated group to assess viral transmission. The animals were monitored daily for 35 days post-inoculation for clinical symptoms. Blood and nasal swabs were sampled twice a week, and tissue samples were collected during necropsy for viral quantification. Compared to MLV1-infected pigs, animals infected with the MLV1-like strain had increased PRRSV viremia and nasal shedding, a higher viral load in the tonsils, and lymph node hypertrophy at microscopic level. PCV2 co-infection did not influence clinical, virologic or transmission parameters for MLV1, but co-infected MLV1-like/PCV2 pigs had the most severe lung lesions, the highest viremia in contact animals and the highest transmission rate. Our study demonstrated that the MLV1 strain tested was safe when co-inoculated with PCV2 in piglets. However, co-infection by the MLV1-like strain and PCV2 resulted in increased virulence compared with that due to a single infection.

Hepatitis E virus is a zoonotic pathogen for which pigs are recognized as the major reservoir in industrialised countries. A multiscale model was developed to assess the HEV transmission and persistence pattern in the pig production sector through an integrative approach taking into account within-farm dynamics and animal movements based on actual data. Within-farm dynamics included both demographic and epidemiological processes. Direct contact and environmental transmission routes were considered along with the possible co-infection with immunomodulating viruses (IMVs) known to modify HEV infection dynamics. Movements were limited to 3,017 herds forming the largest community on the swine commercial network in France and data from the national pig movement database were used to build the contact matrix. Between-herd transmission was modelled by coupling within-herd and network dynamics using the SimInf package. Different introduction scenarios were tested as well as a decrease in the prevalence of IMV-infected farms. After introduction of a single infected gilt, the model showed that the transmission pathway as well as the prevalence of HEV-infected pigs at slaughter age were affected by the type of the index farm, the health status of the population and the type of the infected farms. These outcomes could help design HEV control strategies at a territorial scale based on the assessment of the farms' and network's risk.

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.

Highlights • A method is proposed to explore the role of pig movements on pathogen epidemiology. • Pig farm centrality in the network is associated with higher HEV seroprevalence. • Some local areas are more at risk for HEV due to incoming pig movements. • Animal movements should be included in risk-based surveillance strategies., Animal movements between farms are a major route of pathogen spread in the pig production sector. This study aimed to pair network analysis and epidemiological data in order to evaluate the impact of animal movements on pathogen prevalence in farms and assess the risk of local areas being exposed to diseases due to incoming movements. Our methodology was applied to hepatitis E virus (HEV), an emerging foodborne zoonotic agent of concern that is highly prevalent in pig farms. Firstly, the pig movement network in France (data recorded in 2013) and the results of a nation-wide seroprevalence study (data collected in 178 farms in 2009) were modelled and analysed. The link between network centrality measures of farms and HEV seroprevalence levels was explored using a generalised linear model. The in-degree and ingoing closeness of farms were found to be statistically associated with high HEV within-farm seroprevalence (p

Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans, an emerging zoonosis mainly transmitted via food in developed countries and for which domestic pigs are recognised as the main reservoir. It therefore appears important to understand the features and drivers of HEV infection dynamics on pig farms in order to implement HEV surveillance programmes and to assess and manage public health risks. The authors have reviewed the international scientific literature on the epidemiological characteristics of HEV in swine populations. Although prevalence estimates differed greatly from one study to another, all consistently reported high variability between farms, suggesting the existence of multifactorial conditions related to infection and within-farm transmission of the virus. Longitudinal studies and experimental trials have provided estimates of epidemiological parameters governing the transmission process (e.g. age at infection, transmission parameters, shedding period duration or lag time before the onset of an immune response). Farming practices, passive immunity and co-infection with immunosuppressive agents were identified as the main factors influencing HEV infection dynamics, but further investigations are needed to clarify the different HEV infection patterns observed in pig herds as well as HEV transmission between farms. Relevant surveillance programmes and control measures from farm to fork also have to be fostered to reduce the prevalence of contaminated pork products entering the food chain. Electronic supplementary material The online version of this article (doi:10.1186/s13567-017-0436-3) contains supplementary material, which is available to authorized users.

Livestock-associated methicillin resistantStaphylococcus aureus(LA-MRSA) colonizes livestock animals worldwide, especially pigs and calves. Although frequently carried asymptomatically, LA-MRSA can cause severe infections in humans. It is therefore important to better understand LA-MRSA spreading dynamics within pig farms and over pig farms networks, and to compare different strategies of control and surveillance. For this purpose, we propose a stochastic meta-population model of LA-MRSA spread along the French pig-farm network (n=10,542 farms), combining within- and between-farms dynamics, based on detailed data on breeding practices and pig exchanges between holdings. We calibrate the model using French epidemiological data. We then identify farm-level factors associated with the spreading potential of LA-MRSA in the network. We also show that, assuming control measures applied in a limited (n=100) number of farms, targeting farms depending on their centrality in the network is the only way to significantly reduce LA-MRSA global prevalence. Finally, we investigate the scenario of emergence of a new LA-MRSA strain, and find that the farms with the highest indegree would be the best sentinels for a targeted surveillance of such a strain’s introduction.

Colistin resistance associated with plasmidic resistance genes is a serious public health issue. We aimed at studying the transmission of an mcr-1 colistin- and rifampicin-resistant Escherichia coli strain between inoculated pigs and sentinels in different controlled conditions. Three groups of four pigs were bred in separated animal rooms and inoculated on Day 0 (D0). In each inoculated group, six contact pigs were introduced on D2. The first inoculated-and-contact group was left untreated. The ten pigs in the second inoculated-and-contact group received colistin (100 000 IU/kg) before inoculation or contact (D-7 to D-5), simulating prophylactic administration. Pigs in the third inoculated-and-contact group were treated just after inoculation or before transfer (D0 to D2), simulating metaphylactic administration. Faecal samples were regularly collected and segments of intestinal tracts were obtained at necropsy, on D20-D22. Samples were cultured on rifampicin-supplemented media, and PCR was used to detect the mcr-1 gene. The kinetics of infection, based on culture results, were analysed using an SIR model. The inoculated strain was detected in all inoculated and contact pigs. The SIR model showed that one infected pig could transmit the resistant bacteria to one susceptible individual in less than 3 h on average. Prophylactic administration significantly enhanced the transmission rate and resulted in more samples containing the mcr-1 resistance gene at necropsy. No effect of metaphylactic administration could be detected on the transmission rate, nor on the carriage of the resistant strain. Our study confirms that colistin should not be used in a prophylactic manner.

In Europe, modified live vaccines (MLV) are commonly used to control porcine reproductive and respiratory syndrome virus (PRRSV) infection. However, they have been associated with safety issues such as reversion to virulence induced by mutation and/or recombination. On a French pig farm, we identified a field recombinant strain derived from two PRRSV-1 MLV (MLV1). As a result, we aimed to evaluate its clinical, virological, and transmission parameters in comparison with both parental strains. Three groups with six pigs in each were inoculated with either one of the two MLV1s or with the recombinant strain, six contact pigs were then added into each inoculated group. The animals were monitored daily for 35 days post-inoculation (dpi) for clinical symptoms, blood samples and nasal swabs were collected twice a week. PRRS viral load in inoculated pigs of recombinant group was higher in serum, nasal swabs, and tonsils in comparison with both vaccine groups. The first viremic contact pig was detected as soon as 2 dpi in the recombinant group compared to 10 and 17 dpi for vaccine groups. Estimation of transmission parameters revealed fastest transmission and longest duration of infectiousness for recombinant group. Our in vivo study showed that the field recombinant strain derived from two MLV1s demonstrated high viremia, shedding and transmission capacities.

International audience; Hepatitis E virus (HEV) is a zoonotic pathogen, in particular genotype 3 HEV is mainly transmitted to humans through the consumption of contaminated pork products. This study aimed at describing HEV infection patterns in pig farms and at assessing the impact of immunomodulating co-infections namely Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and Porcine Circovirus Type 2 (PCV2), as well as other individual factors such as piglets' immunity and litters' characteristics on HEV dynamics. A longitudinal follow-up was conducted in three farrow-to-finish farms known to be HEV infected. Overall, 360 piglets were individually monitored from birth to slaughter with regular blood and faecal sampling as well as blood and liver samples collected at slaughterhouse. Virological and serological analyses were performed to detect HEV, PCV2 and PRRSV genome and antibodies. The links between 12 explanatory variables and four outcomes describing HEV dynamics were assessed using cox-proportional hazard models and logistic regression. HEV infection dynamics was found highly variable between farms and in a lower magnitude between batches. HEV positive livers were more likely related to short time-intervals between HEV infection and slaughter time (

Hepatitis E virus (HEV) is a zoonotic agent of which domestic pigs have been recognised as the main reservoir in industrialised countries. The great variability in HEV infection dynamics described on different pig farms may be related to the influence of other pathogens, and in particular viruses affecting pigs’ immune response. The objective of this study was to develop a multi-pathogen modelling approach to understand the conditions under which HEV spreads and persists on a farrow-to-finish pig farm taking into account the fact that pigs may be co-infected with an intercurrent pathogen. A stochastic individual-based model was therefore designed that combines a population dynamics model, which enables us to take different batch rearing systems into account, with a multi-pathogen model representing at the same time the dynamics of both HEV and the intercurrent pathogen. Based on experimental and field data, the epidemiological parameters of the HEV model varied according to the pig’s immunomodulating virus status. HEV spread and persistence was found to be very difficult to control on a farm with a 20-batch rearing system. Housing sows in smaller groups and eradicating immunomodulating pathogens would dramatically reduce the prevalence of HEV-positive livers at slaughter, which would drop from 3.3% to 1% and 0.2% respectively (p-value

International audience; Hepatitis E virus (HEV) is an emerging zoonotic pathogen mainly transmitted via food in developed countries, and for which domestic pigs are recognised as the main reservoir. To implement an efficient HEV surveillance and control plan in the pig production sector, it is first necessary to assess the level of knowledge of pig-farming main actors about this pathogen. To this aim, an online survey was conducted between September and October 2017 to evaluate pig farmers’ and veterinarians’ knowledge about HEV epidemiology and its zoonotic potential. The questionnaire was filled in by 383 pig farmers and 46 pig veterinarians. Of this population, 77.8% of farmers and 8.7% of veterinarians had never heard of HEV. Our results highlight knowledge gaps among responding farmers, especially regarding the clinical and epidemiological features of HEV, while veterinarians appear to be well-informed about this pathogen. These findings indicate significant room for further improvement and the need for more information aimed at French pig farmers, with veterinarians acting as a priority channel through which information may be transferred from scientists to farmers. These educational efforts will facilitate farmers’ involvement in future HEV surveillance and control plans.

International audience; Although hepatitis E virus (HEV) transmission has been demonstrated after consumption of products containing infected pig liver, human cases can be also associated with other pig meat products, such as sausages. Data on HEV viremia and dissemination in muscle meat of infected animals are still sparse, especially during long-term infection. Previously, we have shown that experimental co-infection of pigs with HEV and porcine reproductive and respiratory syndrome virus (PRRSV) lengthens HEV infection up to 49 days and increases the likelihood of the presence of HEV RNA in the liver of the pig at a later stage of infection. In the present study, we show that during experimental HEV-PRRSV co-infection, prolonged HEV viremia, up to 49 days post-inoculation (dpi), is detected. The long-term viremia observed was statistically associated with the absence of HEV seroconversion. HEV RNA was also frequently detected, at a late stage of infection (49 dpi), in the three different types of muscle tested: femoral biceps, psoas major or diaphragm pillar. The HEV RNA load could reach up to 1.10(6) genome copies per gram of muscle. Detection of HEV in muscle meat was statistically associated with high HEV loads in corresponding liver and fecal samples. The presence of HEV in pig blood, femoral biceps and major psoas, corresponding to ham and tenderloin muscles respectively, is of concern for the food industry. Hence, these results indicate new potential risks for consumers and public health regarding pork products.

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. Electronic supplementary material The online version of this article (doi:10.1186/s13567-017-0462-1) contains supplementary material, which is available to authorized users.

The outputs of epidemiological models are strongly related to the structure of the model and input parameters. The latter are defined by fitting theoretical concepts to actual data derived from field or experimental studies. However, some parameters may remain difficult to estimate and are subject to uncertainty or sensitivity analyses to determine their variation range and their global impact on model outcomes. As such, the evaluation of immunity duration is often a puzzling issue requiring long-term follow-up data that are, most of time, not available. The present analysis aims at characterizing the kinetics of antibodies against Porcine Reproductive and Respiratory Syndrome virus (PRRSv) from longitudinal datasets. The first dataset consisted in the serological follow-up of 22 vaccinated gilts during 21 weeks post vaccination. The second one gathered the maternally derived antibody (MDA) kinetics in piglets from 3 different farms up to 14 weeks of age. The peak of the post-vaccination (PV) serological response against PRRSv was reached 6.9 weeks post-vaccination on average withan average duration of antibodies persistence of 26.5 weeks. In the monitored cohort of piglets, the duration of passive immunity was found relatively short, with an average duration of 4.8 weeks. The level of PRRSv-MDAs was found correlated with the dams’ antibody titer at birth and the antibody persistence was strongly related to the initial MDAs titers in piglets. These results evidenced the importance of PRRSv vaccination schedule in sows, to optimize the delivery of antibodies to suckling piglets. These estimates of the duration of active and passive immunity could be further used as input parameters of epidemiological models to analyze their impact on the persistence of PRRSV within farms.

Numerous viruses, mostly in mixed infections, have been associated worldwide with poult enteritis complex (PEC). In 2008 a coronavirus (Fr‐TCoV 080385d) was isolated in France from turkey poults exhibiting clinical signs compatible with this syndrome. In the present study, the median infectious dose (ID 50), transmission kinetics and pathogenicity of Fr‐TCoV were investigated in 10‐day‐old SPF turkeys. Results revealed a titre of 104.88 ID 50/ml with 1 ID 50/ml being beyond the limit of genome detection using a well‐characterized qRT‐PCR for avian coronaviruses. Horizontal transmission of the virus via the airborne route was not observed however, via the oro‐faecal route this proved to be extremely rapid (one infectious individual infecting another every 2.5 hr) and infectious virus was excreted for at least 6 weeks in several birds. Histological examination of different zones of the intestinal tract of the Fr‐TCoV‐infected turkeys showed that the virus had a preference for the lower part of the intestinal tract with an abundance of viral antigen being present in epithelial cells of the ileum, caecum and bursa of Fabricius. Viral antigen was also detected in dendritic cells, monocytes and macrophages in these areas, which may indicate a potential for Fr‐TCoV to replicate in antigen‐presenting cells. Together these results highlight the importance of good sanitary practices in turkey farms to avoid introducing minute amounts of virus that could suffice to initiate an outbreak, and the need to consider that infected individuals may still be infectious long after a clinical episode, to avoid virus dissemination through the movements of apparently recovered birds.

Dengue is the world's major arbovirosis and therefore an important public health concern in endemic areas, The availability of weekly reports of dengue cases in Singapore offers the opportunity to analyze the transmission dynamics and the impact of vector control strategies. Based on a previous model studying the impact of vector control strategies in Singapore during the 2005 outbreak, a simple vector-host model accounting for seasonal fluctuation in vector density was developed to estimate the parameters governing the vector population dynamics using dengue fever incidence data from August 2003 to December 2007. The impact of vector control, which consisted principally of a systematic removal of actual and potential breeding sites during a six-week period in 2005, was also investigated. Although our approach does not account for the complex life cycle of the vector, the good fit between data and model outputs showed that the impact of seasonality on the transmission dynamics is highly important. Moreover, the periodic fluctuations of the vector population were found in phase with temperature variations, suggesting a strong climate effect on the vector density and, in turn, on the transmission dynamics. (c) 2013 Elsevier Inc. All rights reserved.

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. Electronic supplementary material The online version of this article (doi:10.1186/s13567-016-0365-6) contains supplementary material, which is available to authorized users.

In developed countries, most of hepatitis E human cases are of zoonotic origin. Swine is a major hepatitis E virus (HEV) reservoir and foodborne transmissions after pork product consumption have been described. The risk for HEV-containing pig livers at slaughter time is related to the age at infection and to the virus shedding duration. Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is a virus that impairs the immune response; it is highly prevalent in pig production areas and suspected to influence HEV infection dynamics. The impact of PRRSV on the features of HEV infections was studied through an experimental HEV/PRRSV co-infection of specific-pathogen-free (SPF) pigs. The follow-up of the co-infected animals showed that HEV shedding was delayed by a factor of 1.9 in co-infected pigs compared to HEV-only infected pigs and specific immune response was delayed by a factor of 1.6. HEV shedding was significantly increased with co-infection and dramatically extended (48.6 versus 9.7 days for HEV only). The long-term HEV shedding was significantly correlated with the delayed humoral response in co-infected pigs. Direct transmission rate was estimated to be 4.7 times higher in case of co-infection than in HEV only infected pigs (0.70 and 0.15 per day respectively). HEV infection susceptibility was increased by a factor of 3.3, showing the major impact of PRRSV infection on HEV dynamics. Finally, HEV/PRRSV co-infection – frequently observed in pig herds – may lead to chronic HEV infection which may dramatically increase the risk of pig livers containing HEV at slaughter time. Electronic supplementary material The online version of this article (doi:10.1186/s13567-015-0207-y) contains supplementary material, which is available to authorized users.

International audience; Passive immunity (PI), acquired through colostrum intake, is essential for piglet protection against pathogens. Maternally-derived antibodies (MDAs) can decrease the transmission of pathogens between individuals by reducing shedding from infected animals and/or susceptibility of naive animals. Only a limited number of studies, however, have been carried out to quantify the level of protection conferred by PI in terms of transmission. In the present study, an original modeling framework was designed to estimate parameters governing the transmission of infectious agents in the presence and absence of PI. This epidemiological model accounts for the distribution of PI duration and two different forces of infection depending on the serological status of animals after colostrum intake. A Bayesian approach (Metropolis-Hastings algorithm) was used for parameter estimation. The impact of PI on hepatitis E virus transmission in piglets was investigated using longitudinal serological data from six pig farms. A strong impact of PI was highlighted, the efficiency of transmission being on average 13 times lower in piglets with maternally-derived antibodies than in fully susceptible animals (range: 5-21). Median infection-free survival ages, based on herd-specific estimates, ranged between 8.7 and 13.8 weeks in all but one herd. Indeed, this herd exhibited a different profile with a relatively low prevalence of infected pigs (50% at slaughter age) despite the similar proportions of passively immune individuals after colostrum intake. These results suggest that the age at HEV infection is not strictly dependent upon the proportion of piglets with PI but is also linked to farm-specific husbandry (mingling of piglets after weaning) and hygiene practices. The original methodology developed here, using population-based longitudinal serological data, was able to demonstrate the relative impact of MDAs on the transmission of infectious agents.

International audience; The aim of this study was to investigate the fitness of macrolide resistant Campylobacter coli and Campylobacter jejuni. The in vitro growth, the survival on food matrix, and the in vivo colonization of C. jejuni and C. coli susceptible isolates and their isogenic resistant mutants were studied. In vitro experiments demonstrated that macrolide resistance imposed a fitness cost when the susceptible strains and their isogenic resistant mutants were cultured in competition. When inoculated in food matrix, the resistant C. jejuni mutant was no longer detectable after 3 to 5 days but the susceptible strain remained detectable for over 18 days. No difference in survival in food matrix was observed between susceptible and resistant C. coli. When inoculated in vivo in chickens, the macrolide susceptible and resistant C. coli displayed similar levels of colonization, both in separated inoculations and during competitive assays. Strikingly, when mono-inoculated or co-inoculated into chickens, macrolide susceptible C. jejuni outcompeted the macrolide resistant population. However, a spontaneous mutant that evolved in vivo showed a colonization capacity similar to the susceptible strain. Our findings demonstrate the effect of macrolide resistance on the fitness of Campylobacter but suggest that evolved mutants may be as fit as susceptible strains.

Antimicrobial resistance is of primary importance regarding public and animal health issues. Persistence and spread of resistant strains within a population contribute to the maintenance of a reservoir and lead to treatment failure. An experimental trial was carried out to study the horizontal transmission of a fluoroquinolone-resistant Escherichia coli strain from inoculated to naïve pigs. All naïve contact pigs had positive counts of fluoroquinolone-resistant E. coli after only two days of contact. Moreover, re-infections of inoculated pigs caused by newly contaminated animals were suspected. A maximum likelihood method, based on a susceptible-infectious-susceptible (SIS) model, was used to determine the transmission parameters. Two transmission levels were identified depending on the quantity of bacteria shed by infected individuals: (i) low-shedders with bacterial counts of resistant E. coli in the faeces between 5*103 and 106 CFU/g (βL = 0.41 [0.27; 0.62]), (ii) high shedders with bacterial counts above 106 CFU/g (βH = 0.98 [0.59; 1.62]). Hence, transmission between animals could be pivotal in explaining the persistence of resistant bacteria within pig herds.

International audience; We assessed, using a modelling approach, the influence of several management practices within a farrow-to-finish farm on the age of PCV-2 infection. The impact of PCV-2 vaccination with different vaccination schemes on infection dynamics, was also tested. A stochastic individual-based model describing the population dynamics in a typical French farrow-to-finish pig farm was built and coupled with an epidemiological model of PCV-2 infection. The parameters of the infectious model were mainly obtained from previous transmission experiments. Results were subjected to a survival analysis of time-toinfection. For each comparison, the reference situation was no vaccination followed by random mixing of piglets after birth and after weaning. The risk of early infection was significantly reduced when mixing of piglets was reduced at different stages (avoiding cross-fostering and grouping piglets by litters in small pens after weaning, hazard ratio (HR) = 0.52 [0.46; 0.59]). Sow-targeted vaccination delayed the infectious process until the waning of passive immunity and piglet-targeted vaccination considerably decreased the force of infection leading to a dramatic decrease of the total number of infections (HR = 0.44 [0.37; 0.54]). The effect was even more pronounced when strict management measures were applied (HR = 0.24 [0.19; 0.31]). Changing from a low (3%) prevalence of PCV-2-infected semen to a higher one (18%) significantly increased the risk of early infections (HR = 1.36 [1.2; 1.53]), whereas reducing replacement rate or changing sow housing from individual crates to group housing had a limited impact on PCV-2 dynamics.

International audience; Hepatitis E virus (HEV) can cause enterically-transmitted hepatitis in humans. The zoonotic nature of Hepatitis E infections has been established in industrialized areas and domestic pigs are considered as the main reservoir. The dynamics of transmission in pig herds therefore needs to be understood to reduce the prevalence of viremic pigs at slaughter and prevent contaminated pig products from entering the food chain. An experimental trial was carried out to study the main characteristics of HEV transmission between orally inoculated pigs and naive animals. A mathematical model was used to investigate three transmission routes, namely direct contact between pigs and two environmental components to represent within-and between-group oro-fecal transmission. A large inter-individual variability was observed in response to infection with an average latent period lasting 6.9 days (5.8; 7.9) in inoculated animals and an average infectious period of 9.7 days (8.2; 11.2). Our results show that direct transmission alone, with a partial reproduction number of 1.41 (0.21; 3.02), can be considered as a factor of persistence of infection within a population. However, the quantity of virus present in the environment was found to play an essential role in the transmission process strongly influencing the probability of infection with a within pen transmission rate estimated to 2 . 10(-6)g ge(-1)d(-1)(1 . 10(-7); 7 . 10(-6)). Between-pen environmental transmission occurred to a lesser extent (transmission rate: 7 . 10(-8)g ge(-1)d(-1)(5 . 10(-9); 3 . 10(-7)) but could further generate a within-group process. The combination of these transmission routes could explain the persistence and high prevalence of HEV in pig populations.

Concomitant infections by different influenza A virus subtypes within pig farms increase the risk of new reassortant virus emergence. The aims of this study were to characterize the epidemiology of recurrent swine influenza virus infections and identify their main determinants. A follow-up study was carried out in 3 selected farms known to be affected by repeated influenza infections. Three batches of pigs were followed within each farm from birth to slaughter through a representative sample of 40 piglets per batch. Piglets were monitored individually on a monthly basis for serology and clinical parameters. When a flu outbreak occurred, daily virological and clinical investigations were carried out for two weeks. Influenza outbreaks, confirmed by influenza A virus detection, were reported at least once in each batch. These outbreaks occurred at a constant age within farms and were correlated with an increased frequency of sneezing and coughing fits. H1N1 and H1N2 viruses from European enzootic subtypes and reassortants between viruses from these lineages were consecutively and sometimes simultaneously identified depending on the batch, suggesting virus co-circulations at the farm, batch and sometimes individual levels. The estimated reproduction ratio R of influenza outbreaks ranged between 2.5 [1.9-2.9] and 6.9 [4.1-10.5] according to the age at infection-time and serological status of infected piglets. Duration of shedding was influenced by the age at infection time, the serological status of the dam and mingling practices. An impaired humoral response was identified in piglets infected at a time when they still presented maternally-derived antibodies.