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PubMed1975

[Experimental erysipelas in different species as a model for systemic connective tissue disease. I. Systemic vascular processes during organ manifestation (author's transl)].

INTRODUCTION: The similarities between erysipelas in animals and rheumatic diseases in man have been discussed since the work of Nieberle (1931). The present work sets out to investigate the course of organ manifestations in pigs, rats, and mice using germ-free or specific pathogen-free experimental animals. Particular consideration will be given to the initial systemic vascular processes as well as to the significance of the erysipelas antigen. MATERIAL AND METHODS: In several experiments, a total of 166 pigs--partly gnotobiotic or specific pathogen-free animals--37 specific pathogen free Wistar rats and 57 albino mice were orally and/or parenterally infected with standardized erysipelas strains of serotype B. Clinical examination post infection were carried out with the EKG and by x-raying the joints of the extremities. All large parenchymatous organs, as well as heart valves, aorta and synovia were examined histologically in paraffin sections. In mice and rats, joints of the extremities were embedded in toto in metracrylate. Besides various histological staining methods, histochemical reactions were used to demonstrate mucopolysaccharides and fibrin. The myocardium, central nervous system and synovia of several joints were examined with the electron microscope. In the pig, immunohistological methods demonstrating the presence of fibrin, complement and IgG, as described by Seidler et al. (1971) and Trautwein et al. (1972), were used. RESULTS: The most important changes in joints, heart valves heart musculature and blood vessels occur during the early bacteriemic phase. A distinct sticking effect develops in the mouse 3.5 hours p.i., in the rat 24 hours p.i., and in the pig 36 hours p.i. Simultaneously, hyaline thrombi occur in capillaries and venules; these are seen as parallel, loosely-packed fibrin fibers in the electron microscope. With the aid of immunofluorescence fibrin, IgG and complement C3 can also be demonstrated here. Exudates rich in fibrin develop parallel to the microthrombosis. In pigs and rats vascular and myocardial necroses develop to 3 days p.i. The mice do not survive the 3rd p.i. 39% of the pigs showed edema and mesenchymal activation of varying intensity in the heart valves between the 3rd and 8th day p.i. Besides the insudation of the valves, endocardial thromboses developed in 80% of the mice. Endocarditis, aand in addition large aortic thromboses were recognized in more than 50% of the rats. As early as the 4th day p.i., coagulopathy, angionecrosis and exudation led to acute arthritic symptoms..

Animals↗
PubMed1975

Preweaning mortality in pigs. 7. Polyarthritis.

The incidence and causes of polyarthritis in sucking pigs were studied in herds with 2,936 litters during a 2-year period. Among pigs more than 3 days old, the average morbidity rate was 3.3 per cent and the mortality rate amounted to 1.5 per cent (Table I). Among herds the morbidity ranged from 0.9 to 7.0 per cent and the mortality due to polyarthritis from 0.5 to 2.8 per cent. The incidences of polyarthritis were higher in the progeny of gilts than in the progeny of sows of other age groups (Table II). No consistens correlation between litter size at birth and the mortality rate due to polyarthritis was found (Table III). Cases of polyarthritis were observed in 17.8 per cent of the examined litters. Death due to polyarthritis occurred in 10.8 per cent of the litters (Table I); 67.3 per cent of the fatal cases occurred sporadically with only one pig lost per litter (Table IV). The mortality due to polyarthritis appeared to be higher in male pigs (Table V). An analysis of some possible contributory factors showed that the frequency of polyarthritis was adversely affected by new introduction of female breeding stock, clipping of the canine teeth and tail docking in the new-born, and by occurrence of skin diseases in individual piglets (Table VI, IX & XII). No obvious relation was found with such factors as: season of the year, sow's health condition, herd size (Table I), or hygiene level in the individual herds (Table VIII). Death due to polyarthritis occurred most frequently in pigs 2--4 weeks of age (Table X). The pathological lesions, which varied according to the duration of the inflammation and to the aetiology, are described. Arthritis was most frequently observed in the larger limb joints, although every joint may be affected (Table XI). In the majority of the cases a meningoencephalitis was present. A survey of other concomitant, complicating or possible predisposing lesions are presented (Table XII). The bacteriological examination of joints and other organs Table XIII) showed that haemolytic streptococci by far dominated as causative organism. Staphylococci species and E. coli were isolated from affected joints in 6.4 per cent and 4.3 per cent of the pigs, respectively. C. pyogenes and E. rhusiopathiae were rarely encountered in these sucking pigs with polyarthritis. Aspects of the epidemiology and pathogenesis are discussed in regard of minimizing the losses due to polyarthritis/meningitis in sucking pigs.

Animals↗
PubMed1975

[Experimental erysipelas in different species as a model for systemic connective tissue disease. II. The chronic phase with special reference to polyarthritis (author's transl)].

INTRODUCTION: In part I of this paper (Schulz et al., 1975) it was shown that in the initial phase of experimental erysipelas a transition from the vascular processes to a systemic connective tissue reaction can be demonstrated in different species. It is the purpose of this paper to describe the chronic phase of the disease with special emphasis on polyarthritis. MATERIALS AND METHODS: 12 spontaneously diseased and 22 experimentally infected pigs were used in experiments to study the pathogenesis of the disease. In addition, 74 Wistar rats and 148 Sprague-Dawley rats were used in the experiments. All experimental animals were specific-pathogen-free and were parenterally infected with the standardized E. insidiosa serotype B strain T 28. The observation period for the pigs was up to 2 years, for the rats up to 11 months. The methods used for pathohistological and electron microscopical studies are described in part I. Immunihistological studies were carried out on synovial tissue with peroxidase-conjugates of goat-anti-pig-IgG, goat-anti-pig-IgM, pig-collagen, E. insidiosa-homogenate and heat-aggregated-pig-IgG. Furthermore, goat-anti-pig-IgG and rabbit-anti-pig-C3 conjugated with FITC were used. Passive hemagglutination tests and Latex agglutination test (Singer and Plotz) were performed to demonstrate rheumatoid factors and collagen antibodies. RESULTS: Polyarthritis occurred in pigs between the 4th and 10th day p.i. and between the 4th and 8th day p.i. in nearly 100% of the infected rats. Fibrinous exudation, proliferation and destruction with pannus formation are marked in most of the joints examined during the first three months. Fibrosis begins 30 days p.i. in the rats' joints and is most severe in both species between the 5th and 8th month. 3 types of lining cells may be differentiated electron microscopically: A (M) cells, B (F) cells and an intermediate form which is found in both species most frequently. Swelling of the endothelial cells together with constriction of the lumen and thickening of the basal membrane occurs in the capillaries. DISCUSSION: A comparison of chronic erysipelas polyarthritis in pigs and rats with rheumatoid arthritis of men reveals many morphological and immunological similarities between the two diseases. Systemic connective tissue activation manifests itself in organs predilected for rheumatic changes, such as heart valves, endocardium and joints. The possible prepetuation of the processes by specific or nonspecific immunomechanisms or by deposits of fibrin is discussed. In addition, experimental erysipelas is reproducible in nearly 100% of the animals given one single subcutaneous application of one defined bacteria strain. Therefore too, erysipelas is suited as an animal model for human rheumatic diseases.

Animals↗
PubMed2001

[100 years of erysipelas prophylaxis: significance and reduction of animal experiments].

The history of erysipelas prophylaxis began in 1882 when Pasteur first discovered the attenuating effect of rabbit passages on the erysipelas bacterium. Ten years later, the German veterinarian Lorenz demonstrated the protecting effect of erysipelas antiserum. He developed a method of serovaccination which was successfully used in Germany for more than 50 years. Both scientists employed laboratory animals for the development of their live vaccines. Lorenz additionally recommended an animal model with grey mice to control the potency of erysipelas sera. In 1944, Fortner and Dinter published the results of their investigation on a skin scarification test in swine. This modus of infection was the basis of the first reliable model for efficacy testing of erysipelas vaccines in domestic animals. Shortly after World War II, the first inactivated erysipelas vaccines were being developed. At that time, also a strict quality control was introduced for this product group which required extensive animal experiments in laboratory mice and pigs for the determination of efficacy. WHO established International Standards for erysipelas vaccines and antisera concerning potency testing in mice. These animal models were finally incorporated in pharmacopoeia monographs. Animal experiments have played an important role in the development and quality control of erysipelas vaccines. And the success of this quality control based on animal experiments has had a significant impact on the quality control systems for veterinary vaccines in general. Today, we have a far more detailed knowledge about pathogenesis and immunology of swine erysipelas. This knowledge now allows the introduction of alternative methods according to the 3R concept. With these new methods, animal numbers can be decreased and suffering caused by challenge infection can be reduced. The ultimate goal, i.e. quality control of erysipelas vaccines carried out without routine performance of animal experiments, should be achieved in the near future.

Animal Testing Alternatives↗
PubMed1975

[Erysipeloid on the islands of the Sea of Okhotsk. I. The sources and vectors of the causative agent of erysipeloid].

The foci of the causative agent of erysipeloid at the islands of the Okhotsk sea were of the polyvector and polyhostal character. There were recorded 92 species of the naturally infected by the erysipeloid causative agent invertebrate inhabitants of the sea, fish, amphibia, reptilia, birds, mammals and ectoparasites of the warm-blooded animals. Gamazoid and ixodes ticks, mosquitoes, horse-flies and flees were found to be naturally infected with erysipelotrix. Ixodes persulcatus were found to be capable of infecting albino mice during blood sucking.

Animals↗
PubMed2003

Humane endpoints in the efficacy testing of swine erysipelas vaccines.

For licensing the efficacy of vaccines for veterinary use has to be demonstrated by well-controlled laboratory experiments in which vaccinated and untreated animals of the target species are challenged. Erysipelas challenge tests cause extreme suffering of the unprotected animals with high fever, apathy, large skin lesions, and even death. This paper describes a standardised procedure for the vaccination challenge test and gives due consideration to the welfare of the animals. By monitoring and using clinical signs observed during the test it is possible to minimise animal pain and distress, thus preventing unnecessary animal suffering.

Animal Testing Alternatives↗