J.A. Stegeman

The use of marker vaccines in eradication of herpesviruses

Marker vaccines are vaccines that allow serological differentiation between infected and vaccinated individuals. This differentiation is based on the absence of one or more microbial proteins in the vaccine that are present in the wild-type micro-organism. Consequently, after infection, but not after vaccination, an antibody response against that specific protein(s) can be detected. With a protein-specific antibody test infected individuals can thus be distinguished from vaccinated individuals. Marker vaccines against pseudorabies virus (PRV) and against bovine herpesvirus 1 (BHV1) infections have been developed, along conventional routes and by recombinant DNA technology. These vaccines have been shown to be efficacious in reducing (a) clinical signs after infection, (b) wild-type virus replication after infection, and (c) transmission of wild-type virus in the laboratory and in the field. At present, PRV vaccines that lack the gene for the glycoprotein gE are used worldwide in novel eradication programmes. The first phase of such a programme consists of systematic vaccination of pigs on a farm, in a region or an entire country. Experiences in the Netherlands show that it is feasible to eradicate PRV by the intensive use of marker vaccines. Whether, this also holds true for BHV1 is now under investigation.

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.

Classical swine fever in The Netherlands 1997–1998: a description of organisation and measures to eradicate the disease

The central and regional organisation of the campaign to eradicate the CSF epidemic in The Netherlands in 1997/1998 is described. The main instruments used in the campaign were based on stamping-out and movement restrictions specified by the European Union. Additional instruments were used for the first time, namely, pre-emptive culling of contact and neighbouring farms, compartmentalisation of transport, monthly serological screening in established surveillance areas and supervised repopulation of all farms in the former surveillance zone. Two other measures, the killing of very young piglets and a breeding ban were introduced to reduce production in established surveillance zones. Several factors complicated the eradication campaign, for instance, the late detection of the first infection; artificial insemination as a source of infection; the organisation of pig farming in The Netherlands, with its highly concentrated production and dependence on the transport of stock from one unit to another; insufficient rendering capacity; decreasing sensitivity of clinical inspection; and extremely high costs.

The role of backyard poultry flocks in the epidemic of highly pathogenic avian influenza virus (H7N7) in the Netherlands in 2003

In recent years, outbreaks of highly pathogenic avian influenza (HPAI) viruses have caused the death of millions of poultry and of more than 200 humans worldwide. A proper understanding of the transmission dynamics and risk factors for epidemic spread of these viruses is key to devising effective control strategies. The aim of this study was to quantify the epidemiological contributions of backyard flocks using data from the H7N7 HPAI epidemic in the Netherlands in 2003. A dataset was constructed in which flocks in the affected area were classified as susceptible (S), infected but not yet infectious (E), infectious (I), and removed (R). The analyses were based on a two-type SEIR epidemic model, with the two types representing commercial poultry farms and backyard poultry flocks. The analyses were aimed at estimation of the susceptibility (g) and infectiousness (f) of backyard flocks relative to commercial farms. The results show that backyard flocks were considerably less susceptible to infection than commercial farms (g = 0.014; 95%CI = 0.0071-0.023), while estimates of the relative infectiousness of backyard flocks varied widely (0 < or = f < or =5). Our results indicate that, from an epidemiological perspective, backyard flocks played a marginal role in the outbreak of highly pathogenic avian influenza in the Netherlands in 2003.

Quantifying Transmission of Campylobacter spp. among Broilers

ABSTRACT Campylobacter species are frequently identified as a cause of human gastroenteritis, often from eating or mishandling contaminated poultry products. Quantitative knowledge of transmission of Campylobacter in broiler flocks is necessary, as this may help to determine the moment of introduction of Campylobacter in broiler flocks more precisely. The aim of this study was to determine the transmission rate parameter in broiler flocks. Four experiments were performed, each with four Campylobacter-inoculated chicks housed with 396 contact chicks per group. Colonization was monitored by regularly testing fecal samples for Campylobacter. A mathematical model was used to quantify the transmission rate, which was determined to be 1.04 new cases per colonized chick per day. This would imply that, for example, in a flock of 20,000 broilers, the prevalence of Campylobacter would increase from 5% to 95% within 6 days after Campylobacter introduction. The model and the estimated transmission rate parameter can be used to develop a suitable sampling scheme to determine transmission in commercial broiler flocks, to estimate whether control measures can reduce the transmission rate, or to estimate when Campylobacter was introduced into a colonized broiler flock on the basis of the time course of transmission in the flock.

Ability of Massachusetts-type infectious bronchitis virus to increase colibacillosis susceptibility incommercial broilers: A comparison between vaccine and virulent field virus

The abilities of Massachusetts-type vaccine virus and virulent infectious bronchitis (IB) field virus to increase colibacillosis susceptibility were compared. In four experiments, 29-day-old female commercial broilers housed in isolators, were infected intratracheally and oculonasally with IB vaccine strains (HI20 and H52) or virulent IB field strains (D387 and M41) (4.8 or 6.8 log10 median embryo infective dose, per broiler). Five days later, Escherichia coli 506 strain was given intratracheally (5.6 to 8.8 log10 colony forming units/broiler). The incidence of nasal discharge at 3 and 5 days after IB virus infection was used to assess the clinical effect of the IB infection, while mortality, body weight uniformity and E. coli lesions at 7 days following E. coli inoculation were used as parameters for colibacillosis. Nasal discharge was observed in 61/117 (5%), 26/119 (22%), 35/119 (29%) and 115/120 (96%) of broilers infected with H120, H52, D387 and M41 virus, respectively. Apart from H52 and D387, differences between IBV strains were significant. IB vaccine and virulent IB viruses did not generally differ significantly in their ability to induce colibacillosis susceptibility. Mean colibacillosis lesion scores of H52-infected birds even significantly exceeded those of birds infected with the other IB viruses. The ability of H120 virus to induce colibacillosis susceptibility tended to be the weakest. The practical consequences of these findings are discussed.

Factors associated with the introduction of classical swine fever virus into pig herds in the central area of the 1997/98 epidemic in the Netherlands

A matched case-control study of 135 infected and 99 uninfected pig herds from the central area of the 1997 to 1998 epidemic of classical swine fever (CSF) in The Netherlands was undertaken to identify factors associated with the introduction of the virus. The herds were matched on the basis of herd type and the shortest geographical distance between pairs of herds. Data on management, hygienic measures, experiences during the depopulation of an infected nearest neighbour, and the frequency of contact with professionals and other agencies were collected by means of a questionnaire taken by personal interview. There were no significant differences between the infected and uninfected herds in the median total number of contacts per year with professionals and other agencies either with or without contact with the pigs. On the basis of a multivariable analysis, five variables were found to be significantly associated with an increased risk of infection: (1) the presence of commercial poultry on the premises; (2) visitors entering the pig units without wearing an overcoat or overalls and boots supplied by the farm; (3) the driver of the lorry transporting pigs for the Pig Welfare Disposal Scheme (PWDS) using his own boots instead of boots supplied by the farm; (4) herds of moderate size (500 to 1000 animals) and very large herds (>7000 animals) were at greater risk than small herds (<500 animals); and (5) an aerosol, produced during high-pressure cleaning of the electrocution equipment used to kill the pigs on a neighbouring infected herd less than 250 m away was carried by the wind on to the premises. Two variables were significantly associated with a decreased risk of csFv-infection: (1) more than 30 years of experience in pig farming; and (2) additional cleaning of the lorries used to transport pigs for the PWDS before they were allowed on to the premises. In the opinion of the cooperating farmers, airborne transmission of the virus and its transmission during the depopulation of an infected neighbour were among the most important routes of infection.

An epidemiological and economic simulation model to evaluate the spread and control of infectious bovine rhinotracheitis in the Netherlands

Bovine herpesvirus type I (BHV1), causing infectious bovine rhinotracheitis (IBR), was introduced in the Netherlands in 1971. In 1993, about 42% of the dairy cows had antibodies against BHV1. In the future, stricter requirements are anticipated regarding the health status of exported breeding cows and material. To support policymakers in their decisions on IBR eradication, a simulation model was developed in which the epidemiological and economic consequences of various control strategies were evaluated. This paper describes the model and provides an overview of some important outcomes. In the model, dairy herds were classified into different disease states based on (1) the reproduction ratio of the disease (R, defined as the number of secondary cases caused by one infectious animal) (2) the within-herd prevalence, within each value of R and (3) the expected number of infectious animals in an infectious herd within each prevalence range. The dynamic transition probability of a herd going from one state to another per week depends on direct contacts between animals, and other contacts such as transmission through fomites, indirect transmission through other species, airborne transmission and minor disease-specific routes such as venereal or iatrogenic transmission. Five control strategies, including both a voluntary vaccination program and a compulsory vaccination program for all dairy herds were evaluated. A voluntary vaccination program with 50% participation is not expected to lead to eradication of IBR. It appears that compulsory vaccination would be necessary to reach an IBR-free status.

The effect of inoculation dose of a highly pathogenic avian influenza virus strain H5N1 on the infectiousness of chickens

Highly pathogenic avian influenza is of major concern for the poultry industry, as the virus can spread rapidly in and between flocks, causing high mortality and severe economic losses. The aim of this study was to determine the probability of infection and to determine dose-dependent virus transmission (direct transmission) for various inoculation doses. Two transmission experiments with pair-wise housed layer type chickens were performed, in which one bird per pair was inoculated with an HPAI H5N1 virus and the other contact-exposed. Various inoculation doses were used to determine the susceptibility (ID(50)), and possible relation between ID(50), and infectiousness, expressed as the amount of virus shedding and the probability of contact birds becoming infected. The infectious H5N1 dose (CID(50)) in this study was an estimated 10(2.5) egg infectious dose (EID(50))(.) Increasing the dose increased the probability of infection but survival from infection was independent of dose. In addition, increasing the dose decreased the mean latent period in the inoculated chickens significantly. This could be important for determining the time of onset of infection in a flock and thus allowing more accurate identification of the source of infection. Moreover, the amount of virus shed in trachea and cloaca by the inoculated chickens in the time between inoculation and contact infection, also differed between the various dose groups. Despite differences in latent period and virus shedding, the transmission rate parameter β and reproduction ratio R(0) did not differ significantly between the various dose groups. This implies that in this experiment the amount of virus shedding is not a measure to predict transmission or the infectiousness of chickens.

Foot and mouth disease virus transmission during the incubation period of the disease in piglets, lambs, calves, and dairy cows.

Transmission of foot and mouth disease (FMD) virus by infected animals may already occur before clinical signs are evident. Quantitative data for FMD transmission rates during this so-called high-risk period are currently lacking and would provide useful information to develop surveillance systems in which the number of new outbreaks is an outcome variable. In order to address this, we used experimental data to quantify transmission in cattle, swine and sheep during the non-clinical phase of the disease. Groups consisted of vaccinated or non-vaccinated animals of one species; half of each group was inoculated with FMDV, the other half was contact-exposed. We estimated the reproduction ratio R(nonclin) using a mathematical SIR model. R(nonclin) was defined as the average number of secondary infections caused by one infectious individual in its non-clinical phase. Animals not showing clinical signs shed lower amounts of virus than clinically affected ones. Therefore, we estimated transmission proportionally to the virus excretion. Low estimates for R(nonclin) in groups with non-vaccinated and vaccinated calves; 0.30 [0.03; 3.43] and 1.03x10(-8) [0; infinity] respectively and 0.21 [0.02; 2.48] for the non-vaccinated and 0.16 [0.009; 2.96] for the vaccinated lambs, were observed. These results indicate that only few secondary infections are to be expected from infected calves and lambs when they are not clinically affected. In groups of non-vaccinated piglets estimates were R(nonclin)=13.20 [4.08; 42.68], and in vaccinated piglets R(nonclin)=1.26 [0.18; 8.96]. The estimate for R(nonclin) for non-vaccinated dairy cows was R(nonclin)=176.65 [80.38; 388.24], whereas R(nonclin) in the vaccinated groups could not be estimated. Our findings suggest that a large number of individuals might have been infected before clinical signs are noticed, especially in non-vaccinated swine and dairy herds. These findings suggest that after clinical recognition of FMD, priority should be given to trace back contacts with swine and dairy farms, as they may already have been infectious in the herds incubation period.