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

BACKGROUND

Hepatosplenic 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.

METHODS

The 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.

RESULTS

Abnormal 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.

CONCLUSIONS

We 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.