Schistosomiasis was discovered in Malaysia in 1975 in an autopsy case. Since 1975 autopsies, surveys, and resurveys have been carried out to identify animal hosts, snail intermediate hosts, and reservoir hosts. Seroepidemiologic tests involving enzyme-linked immunosorbent and circumoval precipitin methods have been used to determine the true incidence and prevalence of this protean disease among the Orang Aslis (aborigines) in Malaysia. With the use of better epidemiologic and parasitologic tools, more cases of schistosomiasis are being reported.
In hepatic schistosomiasis, pathology arises when schistosome eggs become lodged in the host liver, evoking an interleukin 4 (IL-4)- and IL-13-mediated dominant CD4(+) Th2 immune response. This response leads to the development of granulomas and fibrosis, with eosinophils, neutrophils, macrophages, hepatic stellate cells, and lymphocytes all identified as major cellular contributors to these events. This review outlines the cellular and molecular mechanisms of hepatic schistosomiasis, with an emphasis on the major cellular components and their release of chemokines. The differences between Schistosoma mansoni- and Schistosoma japonicum-induced hepatic granuloma are also discussed. This comprehensive overview of the processes associated with hepatic schistosomiasis may provide new insights into improved treatment for both schistosomiasis and other granulofibrotic diseases.
Schistosomiasis is a neglected tropical disease that affects more than 200 million people worldwide. The main disease-causing agents, Schistosoma japonicum, S. mansoni and S. haematobium, are blood flukes that have complex life cycles involving a snail intermediate host. In Asia, S. japonicum causes hepatointestinal disease (schistosomiasis japonica) and is challenging to control due to a broad distribution of its snail hosts and range of animal reservoir hosts. In China, extensive efforts have been underway to control this parasite, but genetic variability in S. japonicum populations could represent an obstacle to eliminating schistosomiasis japonica. Although a draft genome sequence is available for S. japonicum, there has been no previous study of molecular variation in this parasite on a genome-wide scale. In this study, we conducted the first deep genomic exploration of seven S. japonicum populations from mainland China, constructed phylogenies using mitochondrial and nuclear genomic data sets, and established considerable variation between some of the populations in genes inferred to be linked to key cellular processes and/or pathogen-host interactions. Based on the findings from this study, we propose that verifying intraspecific conservation in vaccine or drug target candidates is an important first step toward developing effective vaccines and chemotherapies against schistosomiasis.
S. mansoni and S. japonicum complex schistosomes cause hepatosplenic and hepatointestinal schistosomiasis. The prevalence and incidence of this disease is increasing in all the endemic areas. Hepatosplenic schistosomiasis is seen in a small subset of clinically infected patients and represents a good model of intrahepatic portal hypertension characterised by a presinusoidal portal block and a well preserved liver parenchyma. Symmers' fibrosis is seen in a significant proportion of patients with high worm load. While the pathogenesis of Symmers' pipe stem fibrosis has not been well established, experimental and clinical data point to egg induced granulomata. The main consequences are presinusoidal portal hypertension, oesophageal varices and hepatosplenomegaly. The most striking symptoms are haematemesis or melena secondary to variceal and gastrointestinal bleeding. Cofactors associated with the pathogenesis include aflatoxins, malnutrition, alcoholism, hepatitis B and C virus. While stool examination is the best technique for diagnosis, a number of immunological tests though sensitive are not specific. Ultrasonography is sensitive for detection of Symmer's fibrosis. Praziquantel and oxaminiquine are drugs found to be effective in the treatment of hepatosplenic schistosomiasis. Recently beta-blockers have been found to be effective in the treatment of gastrointestinal rebleeding. Endoscopic sclerotherapy has been found to be effective for treatment of bleeding oesophageal varices. The treatment of choice for portal hypertension is oesophagogastric devascularization with splenectomy (EGDS).
Schistosomiasis is a widely prevalent disease in the world and usually involves the gastro-intestinal and urinary tract. The involvement of the female genital tract has been well-established in S. haematobium infections and is rare with S. japonicum infections. This case involves a Filipino female who was admitted to the University Hospital Kuala Lumpur for right iliac fossa pain and was diagnosed initially as acute appendicitis. Ultrasound showed a multi-septated pelvic cyst leading to a provisional diagnosis of ovarian torsion. Intraoperatively a right parovarian cyst was detected and removed. Histology revealed a congested cyst wall with areas of haemorrhage with several viable and calcified eggs of S. japonicum measuring 85 microns x 62 microns. Within the cystic cavity blood admixed with eggs were seen. Confirmation was carried out by using the indirect haemagglutination (IHA) test. This is a first report of upper genital schistosomiasis mimicking an ovarian tumour.
For hepatic schistosomiasis the egg-induced granulomatous response and the development of extensive fibrosis are the main pathologies. We used a Schistosoma japonicum-infected mouse model to characterise the multi-cellular pathways associated with the recovery from hepatic fibrosis following clearance of the infection with the anti-schistosomal drug, praziquantel. In the recovering liver splenomegaly, granuloma density and liver fibrosis were all reduced. Inflammatory cell infiltration into the liver was evident, and the numbers of neutrophils, eosinophils and macrophages were significantly decreased. Transcriptomic analysis revealed the up-regulation of fatty acid metabolism genes and the identification of Peroxisome proliferator activated receptor alpha as the upstream regulator of liver recovery. The aryl hydrocarbon receptor signalling pathway which regulates xenobiotic metabolism was also differentially up-regulated. These findings provide a better understanding of the mechanisms associated with the regression of hepatic schistosomiasis.