Real-time observation of pathophysiological processes during murine experimental Schistosoma japonicum infection using high-resolution ultrasound imaging

Katsumi Maezawa,Akio Yasukawa,Shiro Iwanaga,Rieko Furushima-Shimogawara,Nobuo Ohta,Nobuo Ohta

doi:10.1186/s41182-017-0082-5

Katsumi Maezawa, Akio Yasukawa + Show 4 more

Open Access

https://doi.org/10.1186/s41182-017-0082-5

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Abstract

BackgroundHepatosplenic lesion formation is one of the typical clinical symptoms of schistosomiasis japonica. Although it is established that circum-oval granuloma formation mediated by T lymphocytes is the key event triggering the formation of hepatic lesions, the time-course kinetics of disease progression remains to be fully elucidated.MethodsThe real-time process of the pathophysiology of schistosomiasis japonica from the early to late clinical phase was non-invasively observed in a murine experimental infection model using high-resolution ultrasonography. Together with clinical parameters, including body weight and the levels of serum markers of hepatic damage or fibrosis, ultrasonography was used to assess changes in the liver parenchyma and diameter of the portal vein and portal blood flow velocity. In parallel, parasitological parameters were observed, including egg number in the feces and maturation of parasites.ResultsAbnormal high-echo spot patterns in the liver parenchyma, reflecting hepatic fibrosis in ultrasonography, appeared in the liver at 4 weeks post-infection and the pattern became more enlarged and severe over time. This finding was concordant with parasite maturation and initial egg excretion. The serum M2BPGi level markedly increased from 8 weeks post-infection, suggesting sharp deterioration of hepatic fibrosis. At the same time, the diameter of the portal vein, reflecting portal hypertension, became enlarged and reached the peak level at 8 weeks post-infection. Ascites were apparent around the spleen at 9 weeks post-infection, and dilatation of the splenic vein was noted at 10 weeks post-infection. Live adult worms seemed to be detected in the portal vein at 4 weeks post-infection by ultrasonography.ConclusionsWe obtained real-time imaging of the development of hepatosplenic lesions of schistosomiasis japonica in mice. The time-course kinetics of the onset, development, and modulation of each symptom was uncovered. These results are expected to provide new clues for understanding the pathophysiology of human schistosomiasis japonica.

Highlights

Hepatosplenic lesion formation is one of the typical clinical symptoms of schistosomiasis japonica
Schistosomiasis japonica is characterized by severe hepatosplenic lesions with circum-oval granuloma formation, hepatic fibrosis, portal hypertension, and so forth [3,4,5]
Body weight and egg number per gram (EPG) There was no difference in body weight up to 6 weeks PI, but differences in body weight became apparent between infected mice and control mice as of 7 weeks PI (Fig. 1)

Summary

Introduction

Hepatosplenic lesion formation is one of the typical clinical symptoms of schistosomiasis japonica. Schistosomiasis japonica is characterized by severe hepatosplenic lesions with circum-oval granuloma formation, hepatic fibrosis, portal hypertension, and so forth [3,4,5]. Continuous changes during the infection process have not yet been studied because of the lack of available non-invasive equipment for small experimental animals. As a non-invasive approach, it is possible to conduct continuous observations of disease progress in the same mouse using high-resolution ultrasonography [13, 14]. There is no direct evidence that the clinicopathological changes observed in a mouse model are comparable to those in human infection; the pathophysiology of schistosomiasis in humans seems to be similar to findings in the murine model. Research on the pathophysiology of human schistosomiasis would be greatly promoted with the possibility to conduct longitudinal, but not cross-sectional, observations in mice

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