| Schistosomiasis is a major infectious disease which has caused serious risks to human health, impeded economical development, and been considered as one of the ten neglected tropical diseases by the World Health Organization (WHO). Currently, schistosomiasis is epidemic in76countries and regions around the world with nearly800million people in risk of infection, more than200million infected people and20million patients.As a low-toxic oral broad-spectrum antiparasitic, Praziquantel (PZQ) is not only available for treatments of five types of schistosomiasis with high efficacy, short course of treatment (1-2days) and little adverse reactions, but also can be easily and widely used, which has resulted in its recommendation as the preferred oral drug for anti-schistosomiasis by WHO.However, excessive drug usage, inadequate dose or other factors often lead to resistance of pathogens. Concerns have been growing about incidence of drug-resistant schistosoma isolates because of long-term and repeated use of PZQ. In1994, Fallon and Doenhoff induced resistant isolates of Schistosoma mansoni (S mansoni) with sub-therapeutic dose of PZQ in the lab, confirming S. mansoni to be resistant to PZQ due to drug selection.As regards Schistomoma Japonicum (S japonicum) spread in China, PZQ was considered as the specific drug for anti-schistosomiasis in endemic areas since its synthesis in1980. Although direct evidences about incidence of resistant isolates to PZQ have not been yet discovered in endemic areas of China, cases which could not be cured still exist in the susceptible population. In view of wide, repeated or inadequate usage of PZQ in the endemic areas, whether resistant isolate could be induced by long-term sub-therapeutic dose of PZQ has attracted great many attentions. Lately, two PZQ-resistant isolates were successfully induced with sub-therapeutic doses by Liang etal*, which proved that S. japonicum could also be resistant to PZQ. So researching about biological and immunopathological characteristics of S. japonicum PZQ-resistant isolates and comparing concerned differences between homologous PZQ-resistant and-susceptible isolates play important roles in exploring infectious and epidemiological significance of PZQ-resistant isolates.This paper researched biological and immunopathological characteristics of S. japonicum PZQ-resistant isolates, aiming at not only exploring its pathogenicity to host and transmission characteristics, but also predicting and assessing its potential hazards. The mechanism of praziquantel against schistosoma japonicum, praziquantel resistance mechanisms of schistosome and the development of prevention and control strategies for schistosomiasis are of great theoretical and practical significance for this study.The present study included the following3aspects.1Biological Characteristics in mice of Praziquantel-resistant Isolates of Schistomoma JaponicumObjective:To investigate the changes of biological characteristics in mice about praziquantel (PZQ)-resistant isolates of Schistomoma Japonicum(S. japonicum).Methods:Jiangsu laboratory-maintaining isolate and Hunan field-collecting isolate of S. japonicum which were never treated with PZQ were regarded as PZQ-susceptible, while two corresponding, areal and homologous PZQ-induced isolates established via drug-treated passage in laboratory were regarded as PZQ-resistant. Four groups with15mice each were infected with S. japonicum cercariae collected from the above four isolates respectively. Prepatent period of egg, egg excretion, counts of worms and counts of eggs in tissue and length of worms were observed and compared.Results:The prepatent periods in the groups infected with Jiangsu PZQ-susceptible and-resistant isolates were36.1days and36.8days respectively (P=0.371), egg excretions were14.6/100mg faeces and21.2/100mg faeces (P=0.007), worm recoveries were20.5/mouse and25.1/mouse (P=0.042), the mean numbers of eggs in tissue were31,303/worm pair and38,594/worm pair (P=0.040), the mean numbers of eggs in liver were14,810/worm pair and19,715/worm pair (P=0.007), and the mean numbers of eggs in gut were16,493/worm pair and18,879/worm pair (P=0.309). There were no differences between the susceptible and resistant isolates in the length of male (P=0.741), female (P=0.701) and Schistosomes encopula (P=0.744) of recovered worms. The prepatent periods in the groups infected with Hunan PZQ-susceptible and-resistant isolates were35.5days and35.6days respectively (P=0.867), egg excretions were13.3/100mg faeces and18.9/100mg faeces (P=0.001), worm recoveries were17.6/mouse and25.1/mouse (P=0.004), the mean numbers of eggs in tissue were30,932/worm pair and53,903/worm pair (P<0.001), the mean numbers of eggs in liver were12,307/worm pair and26,363/worm pair (P<0.001), and the mean numbers of eggs in gut were18,625/worm pair and27,541/worm pair (P=0.007). There were no differences between the susceptible and resistant isolates in the length of male (P=0.461), female (P=0.784) and Schistosomes encopula (P=0.397) of recovered worms.Conclusions:Pathogenicity and physiological damages to hosts caused by S. japonicum PZQ-resistant isolates were more serious compared with those caused by PZQ-susceptible isolates, and their dissemination abilities were also expanded.2Biological Characteristics in snails of Praziquantel-resistant Isolates of Schistomoma JaponicumObjective:To investigate the changes of biological characteristics in snails about praziquantel (PZQ)-resistant isolates of Schistomoma Japonicum(S. japonicum).Methods:Jiangsu laboratory-maintaining isolate and Hunan field-collecting isolate of S. japonicum which were never treated with PZQ were regarded as PZQ-susceptible, while two corresponding, areal and homologous PZQ-induced isolates established via drug-treated passage in laboratory were regarded as PZQ-resistant. Four groups with10mice each were infected with S. japonicum cercariae collected from the above four isolates respectively. Then the eggs collected from the mice were hatched for infecting snails. Prepatent period of cercariae, the infection rate of the snails, the survival rates of the snails infected and the total number of cercariae shed from each snail infected were observed and compared.Results:When snails were exposed to a single miracidium per snail, the infection rate of the snails in Jiangsu PZQ-resistant isolate was19.74%while that in Jiangsu PZQ-susceptible isolate was8.99%. There was a significant difference between Jiangsu PZQ-resistant and-susceptible isolate(P=0.047). The infection rate of the snails in Hunan PZQ-resistant isolate was21.52%while that in Hunan PZQ-susceptible isolate was10.00%. There was a significant difference between Hunan PZQ-resistant and-susceptible isolate(P=0.046). The total number of cercariae shed from each snail infected with a single miracidium from Jiangsu PZQ-resistant isolate was1039.3, while that from Jiangsu PZQ-susceptible isolate was1460.2. There was a significant difference between Jiangsu PZQ-resistant and-susceptible isolate(P=0.020). The total number of cercariae shed from each snail infected with a single miracidium from Hunan PZQ-resistant isolate was1003.5, while that from Hunan PZQ-susceptible isolate was1319.4. There was a significant difference between Hunan PZQ-resistant and-susceptible isolate(P=0.017). There was no difference between PZQ-resistant and-susceptible isolate of S. japonicum in the prepatent period of cercariae and the survival rates of the snails infected.Conclusions:The higher infection rate of the snails and the lower of the total number of cercariae shed from each snail infected with PZQ-resistant isolate may be related with praziquantel resistance.3Effect on egg-granulomas in livers and serologic reactions of Praziquantel-resistant and-susceptible Isolates of Schistomoma JaponicumObjective:To compare the effect of praziquantel on the formation of egg-granulomas in the livers of Schistomoma Japonicum worrms between praziquantel-resistant and-susceptible parasite isolates in vivo. To compare the intensity of serologic reactions of Schistomoma Japonicum worrms between praziquantel-resistant and-susceptible parasite isolates in vivo.Methods:Eight groups of mice were infected with cercariae of two praziquantel-resistant isolates and two praziquatel-susceptible isolates of Schistomoma Japonicum respectively. Four groups of them were treated with150mg/kg micronized praziquatel by oral on the day35, then were sacrificed and livers were examined pathologically two weeks later. The untreated groups were sacrificed and livers were examined pathologically on the day42. Liver samples were fixed, embeded in paraffin, cut in sections and stained with haematoxylin and eosin for microscopic observation. Serum was separated from collected blood of the untreated groups for serologic reactions on the day42.Results:There were no differences between praziquantel-resistant and-susceptible parasite isolates of untreated groups, while the size of egg-granulomas in the livers of praziquantel-resistant isolates treated was larger than that of praziquantel-susceptible isolates treated. There were no differences between praziquantel-resistant and-susceptible parasite isolates in the intensity of serologic reactions.Conclusions:. There were significant differences in the effect of praziquantel on the formation of egg-granulomas in the livers of Schistomoma Japonicum worrms between praziquantel-resistant and-susceptible parasite isolates in vivo. The eggs from susceptible control isolates were more sensitive to praziquantel than those from resistant isolates in the livers. There were no significant differences in the level of antibodies induced by Schistomoma Japonicum praziquantel-resistant and-susceptible parasite isolates. |
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