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Ngwa, Victor Ngu, 2006. Evolution of Liver Fibrosis During Long-term Experimental Schistosoma japonicum Infection in Pigs. Second cycle, A1N, A1F or AXX ( AXX). Uppsala: SLU, Dept. of Biomedical Sciences and Veterinary Public Health

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Abstract

Schistosomiasis japonica, caused by the zoonotic trematode Schistosoma japonicum, is a highly debilitating parasitic disease endemic in China, the Philippines and Indonesia. The disease is a serious threat to public health and a major cause of liver fibrosis in humans. The tissue damage caused by the host tissue reaction to schistosome eggs trapped in the portal system of the liver leads to portal fibrosis and hypertension. The fibrosis is characterised by excessive deposition of extra-cellular matrix (ECM), especially collagen types 1 and 3 in various proportions, in portal areas. The pig is a natural host for S. japonicum and has several anatomical, physiological and immunological similarities with man, which has led to the exploration of the pig as a large animal model of human schistosomiasis japonica. In pigs, pronounced portal and septal fibrosis develops at the early stage of infection, when egg excretion is high and then gradually regresses over time as the pigs undergo self-cure. This makes the pig a useful animal model for studies of the pathogenesis of the development and resolution of liver fibrosis, including any qualitative changes in the ECM that may occur during the infection period.

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In the present study, liver fibrosis during the course of long-term S. japonicum infection in pigs was investigated. Three groups of pigs were infected with 1000 S. japonicum cercariae and necropsied at 8, 16 and 24 weeks post infection (p.i.). Parasitological variables included faecal egg and miracidial counts and liver tissue egg counts(TEC). The degree of fibrosis was assessed in Masson’s trichrome-stained liver sections, using both semi-quantitative histopathological scoring and quantitative area measurement by image analysis. The number of perioval granulomas per area unit in the same sections was determined. Collagen type 1 was detected by immunohistochemistry and the area fraction in selected areas of interlobular septa was measured by image analysis. The relationship between fibrosis and parasitological variables was investigated.

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Faecal egg and miracidial counts peaked at 8 weeks p.i. and declined rapidly thereafter to low levels at 24 weeks p.i. Liver TEC and granuloma density were also highest at 8 weeks p.i. and decreased at the later time points. The liver lesions were characterised by perioval granulomas, diffuse inflammatory cell infiltration, and portal and septal fibrosis. Scores for both portal and septal fibrosis were highest at 8 weeks p.i. and were reduced at the later time points, and similar results were obtained for the area of fibrosis. Collagen type 1 was present in portal and septal areas in proportion to the degree of fibrosis in the infected pigs. The area fraction for collagen type 1 in septa was significantly higher in infected than in control pigs, but no difference was found between the different time points in infected pigs. There was a correlation between the area of fibrosis and faecal miracidial counts and between granuloma density and faecal egg counts. Fibrosis was strongly correlated with granuloma density, but not with liver TEC. The two methods used for assessment of liver fibrosis were found to be well correlated.

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In conclusion, this study confirmed the results from other studies that marked liver fibrosis develops at the acute stage and is reduced at later stages of S. japonicum infection in pigs, and that the degree of fibrosis is related to granuloma density in the liver. The results suggest that faecal egg excretion could be used as a marker of liver pathology. Quantitative image analysis gave comparable results to semi-quantitative histopathological scoring and is thus a useful, additional tool for assessment of the degree of liver fibrosis in this animal model. Finally, the study showed that the area fraction of collagen type 1 in fibrous septa was increased in the infected pigs, but did not change in connection with the resolution of fibrosis that occurred during the course of infection.

Main title:Evolution of Liver Fibrosis During Long-term Experimental Schistosoma japonicum Infection in Pigs
Authors:Ngwa, Victor Ngu
Supervisor:UNSPECIFIED
Examiner:UNSPECIFIED
Series:Report / International Master of Science Programme, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences
Volume/Sequential designation:63
Year of Publication:2006
Level and depth descriptor:Second cycle, A1N, A1F or AXX
Student's programme affiliation:MSCVE Master of Science Programme in Veterinary Medicine 90 HEC
Supervising department:(VH) > Dept. of Biomedical Sciences and Veterinary Public Health
Keywords:Schistosoma japonicum, liver fibrosis, pig, granuloma density, histopathological scores, image analysis, collagen type 1
URN:NBN:urn:nbn:se:slu:epsilon-s-710
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-s-710
Subject. Use of subject categories until 2023-04-30.:Animal diseases
Language:English
Deposited On:09 Nov 2011 10:13
Metadata Last Modified:07 Oct 2012 19:53

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