Modelling Eggs Distribution And Immune System Dynamics In Schistosome Japonicum Infected Hosts

Schistosomiasis japonica is one of the major infectious diseases that still threaten people's health in China. Eggs play an essential role in the pathogenesis of schistosomiasis japonica, mainly are deposited in liver and intestinal in susceptible hosts, only a few are deposited in mesentery lymph node, lung, spleen and central nerve, resulting in granulomas performed. In liver, granulomas are located in the terminal embranchment of portal vein. In case of severe infection, extensive fibrosis in tissue surrounding portal vein and granulomas block anterior sinus vein. The consequences of human Sj infection include hypersplenism and gastrointestinal hemorrhage, which even leads to death. In intestinal, granulomas and consequently repeat fibrosis result in intestinal ulcer and blockage.Schistosome stains and species of the hosts are the 2 main factors affecting eggs distribution in viscera and faeces. In susceptible hosts, Schistosome japonicum (Sj) eggs distribution in the hosts varies with the geographical strains of the worm and host species.In this study, we infected 120 C57BL/6 and 120 BALB/c mices with ten cercariae to establish Sj infected mice model, respectively. From the 3th to the 14th week after Sj infection, we killed ten C57BL/6 and ten BALB/c mices weekly, reclaimed the amount of paired worms by perfusing thoracic aorta, and separated and digested liver, small intestinal and large intestinal to record the amount of eggs. Then we calculated the amount of deposited eggs per paired worm and the percentage of eggs deposited in liver,small intestinal and large intestinal on different timepoints. At the same time, from the 5th to the 11th week after Sj infection, we collected 24h faecal samples of twenty-six C57BL/6 and twenty-six BALB/c mice every week to record the amount of egg counts per gram of faces(EPG), respectively. Based on the established mathematical model for host immune responses following Sj infection, we simulated the dynamics of eight immune factors during the course of infection using Matlab.The main results are as follows:1. After infection with the same amount of Sj (Chinese strain) cercariae, by perfusing thoracic aorta, the amount of paired worms obtained between C57BL/6 and BALB/c mice are no significant (t=1.5670, P=0.1190).2. During 14 weeks after Sj infection, there is no significant difference between C57BL/6 and BALB/c mice regarding the amount of eggs deposited in viscera by each worm pair(t=0.9328, P=0.3782); the amount of eggs deposited in liver of C57BL/6 mice is significantly larger than that of BALB/c (t=4.3190, P=0.0025); there is no significant difference between C57BL/6 and BALB/c mice regarding the amount of eggs deposited in small intestinal by each worm pair (t=0.6150, P=0.5556); the amount of eggs deposited in large intestinal of C57BL/6 mice is significantly fewer than that of BALB/c (t=3.0714, P=0.0153).3. On different timepoints after infection, there is significant difference between two species of mice regarding the percentage of eggs deposited in viscera. In liver, C57BL/6 mice is degressive from the 4th to the 7th week and stabile from the 7th to the 14th week after infection, BALB/c is continually degressive, their peak values are in the 4th week after infection, the percentage of eggs from C57BL/6 is significantly larger than BALB/c (t=5.0547, P=0.001); In small intestinal, they are continually increased and no significant (t=0.9820, P=0.3548); In large intestinal, the percentage of eggs from C57BL/6 mice is significantly smaller than BALB/c (t=4.5621, P=0.0018).4. During the course of infection, there is significant difference between two species of mice regarding the temporal dynamic distribution of deposited eggs, too. The eggs deposited in viscera, the eggs deposited in liver and the eggs deposited in intestinal of C57BL/6 mice are aggregation distributions, which are density-dependent. But the eggs deposited in viscera and the eggs deposited in liver of BALB/c mice are uniform distributions, the eggs deposited in intestinal are aggregation distributions, which are density-dependent.5. In laboratory Sj infected C57BL/6 and BALB/c mice, the within group EPG at all timepoints fit normal distribution. The temporal dynamics of EPG in both C57BL/6 and BALB/c mice faecal samples can be described by negative binomial distribution.6. At the 5th and 6th week after Sj infection, EPG in C57BL/6 mice positive faecal is significantly fewer than BALB/c. From the 7th to14th week after infection , there are no significant between C57BL/6 and BALB/c mice.7. Based on the established mathematical model for host immune responses following Sj infection, we simulated the dynamics of eight immune factors during the course of infection using Matlab. The results suggest, the curve of IgG fitted well, but there was difference comparing the acknowledged characters of immune responses in our model. At the fiftieth day after Sj infection, we intervened to increase or reduce the amount of antigen. The amount of Th1 and Th2 cells ascended or descended a little, and the amount of Macrophage cells, B cells and plasma cells changed no significantly. The curve of antibody descended or ascended fsatly, then ascended or descended slowly to plateau. The results suggested antibody would be an important monitoring index after intervenor.The results enriched the study of the distribution of deposited eggs in viscera and faecal, further supported the experiment data of deposited eggs in viscera and fecal in mice infected Schistosoma japonicum (Chinese strain). Mathematical model to simulate host immune responses was successfully fitted to further wide the study of immune responses in Schistosoma japonicum.