These differences might be related to the sampling procedures

These differences might be related to the sampling procedures. resembled paucibacillary lesions in 23 and multibacillary in 4 goats. LAMC3 antibody Caseous and calcified granulomas predominated in intestinal LNN. BOB and lesion score corresponded well in intestinal mucosa and oGALT but not in intestinal LNN. Conclusions A defined experimental contamination model for the clinically non-apparent phase of paratuberculosis was established in goats as suitable basis for future studies. subsp. (MAP) and affects domestic and wild ruminants worldwide, causing considerable economic losses for the livestock industry [1,2]. Research to improve diagnostic methods and prophylactic steps has been performed for many years, but still many questions remain unanswered. One reason is the extended clinically non-apparent initial phase of the infection and the still insufficient knowledge about the interactions between the host organism and the pathogen during this time period. Despite large numbers of naturally MAP infected animals, elucidation of host-pathogen interactions in the early phase of the disease is only possible using the defined conditions and variables of experimental animal models. This is due to a diagnostic space that allows in SU10944 vivo identification of infected animals only after sero-conversion or after the onset of faecal shedding, which become detectable late in the course of the disease with large inter-individual variance [3]. Experimental SU10944 animal infection models allow the investigation of relevant numbers of animals with defined contamination status and under identical conditions during the clinically non-apparent phase of disease. Experimental infections have been performed in diverse domestic species, and furthermore, in small laboratory animals [4]. Study SU10944 conditions were not standardized among the experiments making comparisons hard. Generally, age at infection, dose and frequency of inoculation, and duration of the experiment are decisive for disease development [4,5]. International guidelines for standardization of animal models for paratuberculosis have been proposed only recently [5]. While cattle, sheep and deer have been used extensively studies in goats are rare and only small numbers of animals were included [6-12]. Since marked individual variations of host immune response and lesions were observed even in the same experiment, the conclusions vary widely. Performing experimental infections in goats has several advantages in comparison to cattle and sheep. Goats are susceptible to the three main groups of MAP, Type I, II and III [13-15]. They are considered the least naturally MAP resistant species due to a rather fast disease progress [16]. This allows a shorter period of experiments. In a study using Angora goats, specific IFN- responses were observed already one month after challenge with MAP positive gut mucosa and sero-conversion as early as four months post contamination (mpi). Clinical indicators occurred between 22 and 29 mpi [17]. In addition, the feeding and housing requirements of goats are easier to fulfil compared to cattle. The aim of the present study was to establish a well characterized experimental animal model for the clinically non-apparent phase of paratuberculosis in goats as a basis for future studies of the early pathogenesis of MAP contamination. Results Clinical indicators Severe clinical indicators of paratuberculosis were observed in three of the MAP-inoculated animals (3/27). One animal each of group V2 and V4 developed non-treatable diarrhea at 37 and 35 wpi, respectively, and had to be necropsied, while the third goat of group V1 was cachectic at 48 wpi. At 37, 38 and 39 wpi, 3 other goats of group V2 died or had to be euthanized because of neurologic indicators. Post mortem examination revealed cerebrocortical necrosis. Shedding of MAP MAP was detected repeatedly in the faeces of most of the animals during the inoculation period (not shown). Shedding halted at 1 wpi in 13 of the 14 early inoculated goats and in eight of the 13 late inoculated goats and re-emerged about 6 wpi in all animals except one goat of group V2. A large inter-individual variability of shedding in terms of intensity (not shown) and time course was observed impartial from inoculation time and dose. Essentially, three different shedding patterns occurred: animals that stopped shedding before 34 wpi (1), animals that shed.