Studies on the pathogenesis of ovine fascioliasis and schistomiasis

The pathogenesis of the disease caused by the liver fluke, Fasciola hepatica, and the blood fluke, Schistosoma mattheei, were studied in sheep. The relationship between host nutrition and fascioliasis was investigated by comparing the course of the disease, firstly, in animals given the same number of F. hepatica metacercariae and fed rations containing 6% or 13% crude protein and, secondly, in chronically infected sheep transferred from high to low protein diets. In the first experiment, it was found that sheep on the lower protein ration experienced more rapidly developing anaemia and hypoalbuminaemia, more severe losses in body weight and died earlier than their better fed counterparts. Since, the fluke burdens were comparable in both groups it was concluded that the advantages displayed by the latter reflected their greater capacity to withstand the parasites' pathogenic effects rather than a superior ability to limit infection. This was supported by the results of the second experiment demonstrating a faster development of disease in infected sheep when switched from high to low protein diets. The development of the anaemia and hypoalbuminaemia in these animals was studied using radioisotopic techniques. An excessive expansion of plasma volume was responsible for the early reductions reductions in PCV's and serum albumin levels in heavy infections but the principle cause of the major reductions was the biliary haemorrhage arising from the feeding activities of the adult flukes. Although the hypervolaemia occurred at an earlier stage of the infection in protein-restricted sheep, the ultimate severity of the decline in PCV and serum albumin level depended on the ability of the host to replace the blood constituents lost into the gut, and this feature was improved by the provision of a better diet. The impairment to the erythropoietic response of the infected sheep on the poorer plane of nutrition was found to result from a deficiency of iron. The worm-free controls used in these studies were "pair-fed" to infected sheep, and this system showed that inappetence, although not the only factor, was the major cause of the weight loss following infection. Nitrogen balance measurements revealed that a reduction in the protein content of the body made up some of the loss in liveweight resulting from factors other than inappetence. The excessive nitrogen excretion was also found to occur in the urine and not in the faeces as might have been expected from the. enteric blood loss. The measurement of water balance revealed that the water intake of sheep increased following infection and there was a tendency for animals to retain water particularly during the later stages of the disease. The apparent digestibility coefficients determined for a number of dietary constituents suggested that F. hepatica has no effect on the digestive function of sheep. Suffolk X Border Leicester sheep exposed to S. mattheei cercariae were found to exhibit almost no clinical signs of disease during the 12 months following infection. This finding was in marked contrast to the acute infections reported by other workers using similar levels of exposure and was all the more remarkable in view of the large numbers of worms and eggs present in the tissues of these sheep at necropsy. There was, however, an absence of parasite eggs in the faeces of these sheep and a lack of intestinal bleeding; an observation which implies that the major factor in the aetiology of the severe disease in sheep is the passage of eggs through the bowel wall and its associated haemorrhage. The parasite used in this study had originated from a strain of S. mattheei which had produced acute experimental schistosomiasis in Romney Marsh sheep some years previously. In addition to the fact that different breeds of sheep were used in the two studies the parasite had also been maintained in the laboratory during the intervening years by passage through hamsters. To determine the factor responsible for this reduced pathogenicity Romney Marsh sheep were infected with 10,000 cercariae of either the hamster- passaged parasite or a strain which had been exclusively passaged through sheep. The "sheep" strain pi-oved lethal within 13 weeks of infection whereas the "hamster" strain produced a symptomless infection. Twice as many worms of the "sheep" strain were recovered at necropsy and these worms not only produced many more eggs, but larger numbers were excreted in the faeces of their hosts. Clearly, "attenuation" of the parasite had taken place as a result of hamster passage. In a further study, it was shown that prior exposure of sheep to the relatively non-pathogenic "hamster" strain of parasite largely protected them from the manifestations of acute schistosomiasis which developed in worm-free sheep also challenged with the virulent "sheep" strain of S. mattheei. The results showed that this was partly due to a reduction in the establishment of the challenge worm population but the main factor was probably a reduction in the fecundity of these worms