No foot-and-mouth disease virus transmission between individually housed calves

The foot-and-mouth disease outbreak in The Netherlands in 2001 most likely started on a mixed veal-calf/dairy-goat farm. The outbreak among the 74 calves on this farm appeared to be limited to four animals, and no clinical signs of FMD were reported. Also on a second veal-calf farm minor clinical signs and limited virus transmission were observed. Since FMD is known to be a very contagious disease, and can cause severe lesions, these observations were disputed. Therefore, we carried out two experiments to determine whether the Dutch FMD virus isolate from 2001 does spread among individually housed calves with limited contacts, either indirect (experiment 1) or direct (experiment 2). In experiment 1, four pairs of calves were housed in an individual box at 1m distance from each other. In experiment 2, two groups of three calves were housed in individual boxes, directly bordering each other. We infected one animal per pair in experiment 1, and the calf in the middle in experiment 2. We recorded clinical signs, virus shedding in saliva and the development of antibodies. In addition, we determined whether the virus was transmitted from the inoculated calves to the neighbour(s). All inoculated calves showed mild signs of FMD--fever, and some vesicles on hooves and/or in the mouth--but only one calf showed signs that were visible without physical examination. All inoculated calves shed virus in the saliva and developed neutralising antibodies. None of the contact animals seroconverted, indicating that virus transmission did not occur. These experiments showed that no virus transmission among individual housed calves can occur. This finding supports the hypothesis of the route of virus introduction to The Netherlands in 2001 and show that the observations on the two veal-calf farms were not impossible.     

A decision-tree to optimise control measures during the early stage of a foot-and-mouth disease epidemic

A decision-tree was developed to support decision making on control measures during the first days after the declaration of an outbreak of foot-and-mouth disease (FMD). The objective of the tree was to minimise direct costs and export losses of FMD epidemics under several scenarios based on livestock and herd density in the outbreak region, the possibility of airborne spread, and the time between first infection and first detection. The starting point of the tree was an epidemiological model based on a deterministic susceptible–infectious–recovered approach. The effect of four control strategies on FMD dynamics was modelled. In addition to the standard control strategy of stamping out and culling of high-risk contact herds, strategies involving ring culling within 1 km of an infected herd, ring-vaccination within 1 km of an infected herd, and ring-vaccination within 3 km of an infected herd were assessed. An economic model converted outbreak and control effects of farming and processing operations into estimates of direct costs and export losses. Ring-vaccination is the economically optimal control strategy for densely populated livestock areas whereas ring culling is the economically optimal control strategy for sparsely populated livestock areas.     

Quantification of transmission of foot-and-mouth disease virus caused by an environment contaminated with secretions and excretions from infected calves

Foot-and-mouth disease virus (FMDV) infected animals can contaminate the environment with their secretions and excretions. To quantify the contribution of a contaminated environment to the transmission of FMDV, this study used calves that were not vaccinated and calves that were vaccinated 1 week prior to inoculation with the virus in direct and indirect contact experiments. In direct contact experiments, contact calves were exposed to inoculated calves in the same room. In indirect contact experiments, contact calves were housed in rooms that previously had held inoculated calves for three days (either from 0 to 3 or from 3 to 6 days post inoculation). Secretions and excretions from all calves were tested for the presence of FMDV by virus isolation; the results were used to quantify FMDV transmission. This was done using a generalized linear model based on a 2 route (2R, i.e. direct contact and environment) SIR model that included information on FMDV survival in the environment. The study shows that roughly 44% of transmission occurs via the environment, as indicated by the reproduction ratio R^02Renvironment that equalled 2.0, whereas the sum of R^02Rcontact and R^02Renvironment equalled 4.6. Because vaccination 1 week prior to inoculation of the calves conferred protective immunity against FMDV infection, no transmission rate parameters could be estimated from the experiments with vaccinated calves. We conclude that a contaminated environment contributes considerably to the transmission of FMDV therefore that hygiene measures can play a crucial role in FMD control.

Electronic supplementary material

The online version of this article (doi:10.1186/s13567-015-0156-5) contains supplementary material, which is available to authorized users.     

A meta-analysis quantifying transmission parameters of FMDV strain O Taiwan among non-vaccinated and vaccinated pigs

Our aim was to provide additional estimates of main parameters for the transmission of foot-and-mouth disease virus (FMDV) strain O Taiwan (3/97). We used the data of previous experiments in non-vaccinated and vaccinated pigs and combined the data of experiments with the same treatment(s). First, we quantified the reproduction ratio R for the various groups using a final-size method. Our final-size results predicted that vaccination with a four-fold vaccine dose (but not with a single dose) at 1 week before inoculation (-7 dpi) would reduce R compared to the non-vaccinated group. Secondly, we used the daily results of virus excretion to quantify the transmission rate beta (by using generalized linear modelling), and the infectious period T (by using survival analysis). We used the estimates of beta and T to estimate R more precisely as compared to the final-size method and also for the groups for which a finite estimate could not be obtained using a final-size method. Our modelling results predicted that beta for non-vaccinated, for single-dose and four-fold-dose groups would be 6.1 (3.7, 10)day(-1), 2.0 (1.0, 4.0)day(-1) and 0.4 (0.1, 1.4)day(-1), T at 6.5 (5.7, 7.3), 5.3 (4.7, 6.0) and 2.3 (0.9, 5.7) days and R at 40 (21, 74), 11 (4.9, 24) and 1.0 (0.1, 7.8), respectively. These results predicted that both vaccination with a four-fold vaccine dose and with a single dose at -7 dpi would reduce beta, T and R significantly as compared to the non-vaccinated pigs, thereby showing that vaccination will reduce transmission of FMDV significantly already 1 week post vaccination.     

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 herd's incubation period.     

Passive immunization of guinea pigs with llama single-domain antibody fragments against foot-and-mouth disease

Foot-and-mouth disease (FMD) is a highly contagious disease that occasionally causes outbreaks in Europe. There is a need for therapies that provide rapid protection against FMD in outbreak situations. We aim to provide such rapid protection by passive immunization with llama single-domain antibody fragments (VHHs). Twenty-four VHHs binding serotype O FMDV in vitro were isolated from immunized llamas by phage display and expressed in bakers yeast for further characterization. They recognized four functionally independent antigenic sites. Six strongly FMDV neutralizing VHHs bound to a peptide representing the GH-loop of viral protein 1 known to be involved in binding to the cellular receptor of FMDV. Clone M8, recognizing this antigenic site, and clone M23, recognizing another antigenic site, showed synergistic in vitro virus neutralization. Three FMDV specific VHHs were PEGylated in order to decrease their rapid blood clearance and thus enable in vivo guinea pig protection experiments. Passive immunization with individual VHHs showed no protection, but a mixture of M8 and M23 showed partial transient protection. The protection afforded by these VHHs was however low as compared to the complete protection afforded by convalescent guinea pig serum. In contrast, these VHHs showed far more efficient in vitro FMDV neutralization than convalescent guinea pig serum. This lack of correlation between in vitro neutralization and in vivo protection lends further credence to the notion that opsonophagocytosis of FMDV is important for protection in vivo.     

An investigation to enhance understanding of the stimulation of weed seedling emergence by soil disturbance

Enhanced understanding of soil disturbance effects on weed seedling recruitment will help guide improved management approaches. Field experiments were conducted at 16 site‐years at 10 research farms across Europe and North America to (i) quantify superficial soil disturbance (SSD) effects on Chenopodium album emergence and (ii) clarify adaptive emergence behaviour in frequently disturbed environments. Each site‐year contained factorial combinations of two seed populations (local and common, with the common population studied at all site‐years) and six SSD timings [0, 50, 100, 150, 200 day‐degrees (d°C, base temperature 3°C) after first emergence from undisturbed soil]. Analytical units in this study were emergence flushes. Flush magnitudes (maximum weekly emergence per count flush) and flush frequencies (flushes year^?1) were compared between disturbed and undisturbed seedbanks. One year after burial, SSD promoted seedling emergence relative to undisturbed seedbanks by increasing flush magnitude rather than increasing flush frequency. Two years after burial, SSD promoted emergence through increased flush magnitude and flush frequency. The promotional effects of SSD on emergence were strongest within 500 d°C following SSD; however, low levels of SSD‐induced emergence were detected as late as 3000 d°C following SSD. Accordingly, stale seedbed practices that eliminate weed seedlings should occur within 500 d°C of disturbance, because few seedlings emerge after this time. However, implementation of stale seedbed practices will probably cause slight increases in weed population densities throughout the year. Compared with the common population, local populations exhibited reduced variance in total emergence measured within sites and across SSD treatments, suggesting that C. album adaptation to local pedo‐climatic conditions involves increased consistency in SSD‐induced emergence.