M.C.M. de Jong

Bayesian estimation of hepatitis E virus seroprevalence for populations with different exposure levels to swine in The Netherlands.

Hepatitis E virus (HEV) is ubiquitous in pigs worldwide and may be zoonotic. Previous HEV seroprevalence estimates for groups of people working with swine were higher than for control groups. However, discordance among results of anti-HEV assays means that true seroprevalence estimates, i.e. seroprevalence due to previous exposure to HEV, depends on choice of seroassay. We tested blood samples from three subpopulations (49 swine veterinarians, 153 non-swine veterinarians and 644 randomly selected individuals from the general population) with one IgM and two IgG ELISAs, and subsets with IgG and/or IgM Western blots. A Bayesian stochastical model was used to combine results of all assays. The model accounted for imperfection of each assay by estimating sensitivity and specificity, and accounted for dependence between serological assays. As expected, discordance among assay results occurred. Applying the model yielded seroprevalence estimates of approximately 11% for swine veterinarians,approximately 6% for non-swine veterinarians and approximately 2% for the general population. By combining the results of five serological assays in a Bayesian stochastical model we confirmed that exposure to swine or their environment was associated with elevated HEV seroprevalence.

Comparison of the transmission characteristics of low and high pathogenicity avian influenza A virus (H5N2).

Low pathogenicity avian influenza A strains (LPAI) of the H5 and H7 type are noted for their ability to transform into highly pathogenic counterparts (HPAI). Here we compare the transmission characteristics in poultry of LPAI H5N2 (A/Chicken/Pennsylvania/83) and corresponding HPAI virus by means of transmission experiments. In the experiments, five inoculated animals are placed in a cage with five contact animals, and the infection chain is monitored by taking blood samples, and samples from the trachea and cloaca. The data are analysed by final size methods and a generalized linear model. The results show that HPAI virus is more infectious and induces a longer infectious period than LPAI. In fact, fully susceptible animals are invariably infected when confronted with HPAI virus and die within six days after infection. Animals previously infected with LPAI virus, on the other hand, survive an infection with HPAI virus or escape infection all together. This implies that a previous infection with LPAI virus effectively reduces susceptibility of the host to infection and decreases transmission of HPAI virus. We discuss the implications of these conclusions for the control and evolution of avian influenza viruses.

Determination of the onset of the herd-immunity induced by the E2 sub-unit vaccine against classical swine fever virus.

For a recently developed E2 subunit vaccine against classical swine fever (CSF), the reduction in transmission, at different moments after vaccination, was assessed by animal experiments and statistical calculations. Two experiments were performed to estimate the reproduction ratio R. Experiment 1 consisted of three groups and experiment 2 of two groups each of 10 pigs. In four of these groups, all pigs were vaccinated intramuscularly with the vaccine. The pigs in the fifth group remained unvaccinated (control group). After treatment, half of each group was intranasally inoculated with the virulent CSFV strain Brescia. In the vaccine groups, the following vaccination-challenge intervals were applied: 14, 14, 10, and 7 days, respectively. The occurrence of (contact-) infection was determined using the E(rns) ELISA. In the 7-days interval group and in the control group, virus transmission to all contact pigs occurred, indicating R1. Neither in the two 2-week interval groups nor in the 10-day interval group did contact-infections occur. Hence, the estimated R is less than one, which indicates that an epidemic would fade out. Therefore, the E2 subunit vaccine may be an efficacious tool in a control program during an outbreak of CSF as from 10 days after vaccination.

Transmission of pseudorabies virus within pig populations is independent of the size of the population

Abstract Epidemic models are often used to analyse the transmission of infectious diseases. These models, however, differ in whether they assume that transmission of a pathogen increases with population size or not. The purpose of this study was to investigate whether the transmission of pseudorabies virus—expressed as the reproduction ratio R -depends on population size. Experimental groups of either ten or 40 vaccinated pigs per group were housed at equal density. We inoculated half of each group, and we estimated the transmission of the virus from the number of contact-infections, using a stochastic Susceptible-Infectious-Recovered model. We calculated that if the transmission depended on population size, the transmission in the group of 40 pigs would be four times as high as the transmission in the group of ten pigs. However, the transmission of the virus did not differ significantly between the groups, and thus we concluded that the transmission was not influenced by the size of the population. This finding suggests that control measures should not be aimed at reducing the size of the herd.

QUANTIFICATION OF THE TRANSMISSION OF CLASSICAL SWINE FEVER VIRUS BETWEEN HERDS DURING THE 1997-1998 EPIDEMIC IN THE NETHERLANDS

In this study, we describe a method to quantify the transmission of Classical Swine Fever Virus (CSFV) between herds from data collected during the 1997-1998 epidemic in The Netherlands. From the contacts between infected herds and the serological findings shortly before depopulation, we estimated the week of virus introduction and the length of the period over which the herd emitted virus for each CSFV-infected herd. From these data, we estimated the infection-rate parameter beta (the average number of herds infected by one infectious herd during one week) and the herd reproduction ratio, Rh (the average total number of secondary outbreaks caused by one infectious herd, i.e. in its entire infectious period), using a SIR-model for different sets of CSF control measures. When Rh > 1, an epidemic continues to grow. On the other hand, when Rh < 1 an epidemic will fade out. During the phase before the first outbreak was diagnosed and no specific measures had been implemented, beta was estimated at 1.09 and Rh at 6.8. In the subsequent phase infected herds were depopulated, movement restrictions were implemented, infected herds were traced forward and backward and the herds in the protection and surveillance zones were clinically inspected by the veterinary authorities (regional screening). This set of measures significantly reduced beta to 0.38. However, Rh was 1.3 and thus still > 1. Consequently, the number of outbreaks continued to grow. After a number of additional measures were implemented, the value of Rh was reduced to 0.5 and the epidemic came to an end. These measures included pre-emptive slaughter of herds that had been in contact with infected herds or were located near an infected herd, increased hygienic procedures, replacement of transports of pigs for welfare reasons by killing of young piglets and a breeding ban, and regional screening for CSF-infected herds by local veterinary practitioners.

Design and analysis of small-scale transmission experiments with animals

Interactions between pathogens and hosts at the population level should be considered when studying the effectiveness of control measures for infectious diseases. The advantage of doing transmission experiments compared to field studies is that they offer a controlled environment in which the effect of a single factor can be investigated, while variation due to other factors is minimized. This paper gives an overview of the biological and mathematical aspects, bottlenecks and solutions of developing and executing transmission experiments with animals. Different methods of analysis and different experimental designs are discussed. Final size methods are often used for analysing transmission data, but have never been published in a refereed journal; therefore, they will be described in detail in this paper. We hope that this information is helpful for scientists who are considering performing transmission experiments.

Design and analysis of an Actinobacillus pleuropneumoniae transmission experiment

This paper describes a methodology to quantify the transmission of Actinobacillus (A.) pleuropneumoniae from subclinically infected carrier pigs to susceptible contact pigs, and to test the effect of possible interventions on the transmission. The methodology includes the design of a transmission experiment, and a method with which A. pleuropneumoniae transmission can be quantified and with which the effect of an intervention on the transmission can be tested. The experimental design consists of two parts. First, subclinically infected carrier pigs are created by contact exposure of specific-pathogen-free pigs to endobronchially inoculated pigs. Second, transmission is observed from the group of carrier pigs to a second group of susceptible contact pigs after replacing the inoculated pigs by new contact pigs. The presented analytical method is a generalised linear model (GLM) with which the effect of an intervention on the susceptibility and infectivity can be tested separately, if the transmission is observed in heterogeneous populations. The concept of the experimental transmission model is illustrated by describing an A. pleuropneumoniae transmission experiment in which the effect of vaccination on the susceptibility is quantified. Although it could not be demonstrated that vaccination has an effect on the susceptibility of pigs, it was demonstrated that nasal excretion of A. pleuropneumoniae is related to the infectivity of pigs.

Rate of inter-herd transmission of classical swine fever virus by different types of contact during the 1997-8 epidemic in The Netherlands

In this study we quantified the rate at which classical swine fever had been transmitted by several different types of inter-herd contact during the 1997-8 epidemic in The Netherlands. During that epidemic 428 CSFV-infected pig herds were detected, 403 of which were include in this study. The estimated rates of transmission were 0.065 per shipment of live pigs, 0.011 per contact by a pig transportation lorry, 0.0068 per person contact, 0.0007 per dose of semen, 0.0065 per contact with a potentially contaminated pig assembly point, 0.027 per week per infected herd within a radius of 500 metres and 0.0078 per week per infected herd at a distance between 500 and 1000 metres. These transmission rates can be used to optimize the strategy to stop future epidemics of CSF in The Netherlands. In addition, the analysis demonstrated in this paper, can be used to quantify CSFV transmission rates from other epidemics.

Prevalence and risk factor analysis of livestock associated MRSA-positive pig herds in The Netherlands

In 2005, methicillin-resistant Staphylococcus aureus was found in pig herds and in humans in contact with pigs. To determine the prevalence of, this now-called livestock-associated (LA) MRSA among pig herds in The Netherlands and to identify and quantify risk factors, an observational study of 202 pig herds was performed between 2007 and 2008. Five environmental wipes and 60 nasal swabs from each herd were collected, and microbiological analysis was performed on single environmental samples and pooled nasal samples. A herd was considered MRSA-positive if ≥1 sample tested positive. The prevalence of MRSA-positive herds was 67% in breeding herds and 71% in finishing herds. Multivariable logistic regression analysis was then performed on data from 171 breeding herds. The number of MRSA-positive herds increased from ∼30% at the start to ∼75% at the end of the study, most likely due to transmission between herds. The prevalence of MRSA increased with herd size, as ∼40% of smaller herds (<250 sows) were MRSA-positive compared to >80% of larger herds (>500 sows). Other risk factors (e.g. antimicrobial use, purchase of gilts and hygiene measures) were not significantly associated with MRSA, though associated with herd size. Herd size appeared to be a compilation of several factors, which made larger herds more often MRSA positive.

An inactivated gE-negative marker vaccine and an experimental gD-subunit vaccine reduce the incidence of bovine herpesvirus 1 infections in the field.

An inactivated glycoprotein E-negative vaccine and an experimental glycoprotein D-subunit vaccine against bovine herpesvirus 1 (V1) were examined for their effectiveness in a randomized, double-bline, placebo-controlled field trial comprising 130 dairy farms. The use of these marker vaccines enabled us to monitor the incidence of infections in vaccinated populations. The aims of this trial were to evaluate whether these vaccines: (1) reduce the proportion of outbreaks in dairy herds; and (2) reduced virus transmission within dairy herds and to what extent. Vaccination with either of the two vaccines significantly reduced the proportion of herds wherein an outbreak occurred as well as the virus transmission within herds, as compared to placebo-treated herds. The estimated number of secondary cases caused by one infectious animal, expressed as the reproduction ratio R, was for both vaccines significantly > 1. This indicates that when BHV1 is introduced into vaccinated herds, major outbreaks may still occur.