| Schistosomiasis, caused by infection with blood flukes of the genus Schistosoma,is a serious infectious disease which severely damages human health and hinderssocioeconomic development. In China, schistosomiasis japonica remains a majorpublic-health concern. After long-term comprehensive control, currently, the mainendemic foci are concentrated in5provinces of Hunan, Hubei, Jiangxi, Anhui andJiangsu along the middle and lower reaches of the Yangtze River, and somemountainous areas of Yunnan and Sichuan provinces. About326000cases wereestimated to be infected with the parasite in2010. Chemotherapy is an importantstrategy to reduce morbidity and control the transmission of the disease. Praziquantelis currently the only drug of choice for treatment of human S. japonicum infections.Since it was introduced in1970s, it has played a critical role in schistosomiasiscontrol. However, it is worrying about that drug resistance may emerge afterlong-term, repeated use.Since1980s, over50million residents have been given praziquantel treatment inthe endemic foci of China. There is currently no direct evidence to prove theresistance of S. japonicum to praziquantel, however, it has been detected that the drugsensitivity reduces in susceptible populations in some highly endemic regions. Giventhat large-scale use of praziquantel has been implemented in areas with high andmoderate endemicities of China, with the increase in frequency of repeated use of thedrug in the same susceptible population, and the increased probability of subcurativedose used in mass chemotherapy, it is worrying about that following long-termsubcurative treatment, praziquantel sensitivity may reduce or S. japonicum maydevelop resistance to praziquantel under drug selection pressure. It should be noted that, under laboratorial conditions, it is possible to induce praziquantel resistance in S.japonicum following multiple uses of subcurative doses. It is, therefore, of greatimportance to determine the current sensitivity of S. japonicum to praziquantel inmainland China, establish the techniques to monitor and detect drug sensitivity in S.japonicum, and assess the current efficacy of praziquantel and monitor the emergenceof praziquantel resistance in endemic field.The present study included the following4aspects.1The sensitivity of adult S. japonicum to praziquantel in mainland ChinaObjective: To determine and compare the sensitivity to praziquantel of adult wormsof different isolates of S. japonicum in mainland China, of S. japonicum and S.mansoni, and of praziquantel-susceptible and-resistant isolates of S. japonicum.Methods: Mice infected with Huarong isolate, Hunan susceptible isolate, Gong’anisolate, Hubei isolate, Nanchang isolate, Anhui isolate, Jiangsu susceptible isolate,laboratorial passage isolate, Hunan and Jiangsu resistant isolates of S. japonicum andS. mansoni, were grouped, and treated with praziquantel at single oral doses of37.5,75,150,300and600mg/kg. The worm burden reductions caused by praziquanteltreatment were observed, and the50%effective dose (ED50value) was calculated.Results: The praziquantel ED50values against different isolates of S. japonicumranged from134.4to187.0mg/kg, and no significant differences of praziquantelED50values were detected among different isolates (P>0.05). The praziquantel ED50value against S. mansoni was96.3mg/kg, which was not significantly from those of S.japonicum (P>0.05). The praziquantel ED50values against Hunan and Jiangsupraziquantel-susceptible and-resistant isolates of S. japonicum were134.4and165.4mg/kg, and468.8and554.9mg/kg, and there were significant differences ofpraziquantel ED50values observed between the praziquantel-susceptible and-resistantisolates (P <0.05).Conclusions: There were no significant differences of praziquantel sensitivity againstS. japonicum in mainland China. No significant difference of ED50values wasobserved between S. japonicum and S. masoni. Praziquantel ED50value againstschistosomes, as a quantitative index, can truly reflect the sensitivity of schistosome populations to praziquantel, which can be used to assess the risk of emergence ofpraziquantel resistance in schistosomes.2The sensitivity of S. japonicum cercariae to praziquantel in mainland ChinaObjective: To determine and compare the sensitivity to praziquantel of cercariae ofdifferent isolates of S. japonicum in mainland China, of S. japonicum and S. mansoni,and of praziquantel-susceptible and-resistant isolates of S. japonicum.Methods: Some cercariae of Huarong isolate, Hunan susceptible isolate, Gong’anisolate, Hubei isolate, Nanchang isolate, Anhui isolate, Jiangsu susceptible isolate,laboratorial passage isolate, Hunan and Jiangsu resistant isolates of S. japonicum andS. mansoni, were exposed to praziquantel at concentrations of10-5,5×10-6,10-6,5×10-7mol/L and10-7mol/L for20,40,60,80min and100min. The tail-shedding ofcercariae were observed under a microscopy, the tail-shedding rates were calculated,and the50%lethal concentration (LC50value) of praziquantel at40min wascalculated.Results: After treatment with praziquantel at the same concentration for the sametime, there was no significant difference of tail-shedding rates of cercariae of differentisolates of S. japonicum (P>0.05), while the tail-shedding rates of S. mansonicercariae were higher than those of S. japonicum, and the tail-shedding rates ofcercariae of praziquantel-susceptible isolates of S. japonicum were significantlyhigher than those of praziquantel-susceptible isolates (P <0.05). There were nosignificant differences of praziquantel LC50values at40min against cercariae ofdifferent isolates of S. japonicum (P>0.05), and no significant differences ofpraziquantel LC50values were detected between S. japonicum and S. mansoni (P>0.05). The praziquantel LC50values against cercariae of praziquantel-resistant isolatesof S. japonicum were significantly higher than those of praziquantel-susceptibleisolates (P <0.05).Conclusions: There were no significant differences of praziquantel sensitivity againstcercariae of different isolates of S. japonicum in mainland China. Following treatmentof praziquantel at the same concentration for the same time, the tail-shedding rates of S. mansoni cercariae were higher than those of S. japonicum; however, no significantdifference of praziquantel LC50values at40min was observed between S. japonicumand S. masoni. Praziquantel LC50value against schistosome cercariae, as aquantitative index, can truly reflect the sensitivity of schistosome populations topraziquantel, which can be used to detect and monitor the emergence of praziquantelresistance in the snail host of schistosomes.3The sensitivity of S. japonicum miracidia to praziquantel in mainland ChinaObjective: To determine and compare the sensitivity to praziquantel of miracidia ofdifferent isolates of S. japonicum in mainland China, of S. japonicum and S. mansoni,and of praziquantel-susceptible and-resistant isolates of S. japonicum.Methods: Some miracidia of Huarong isolate, Hunan susceptible isolate, Gong’anisolate, Hubei isolate, Nanchang isolate, Anhui isolate, Jiangsu susceptible isolate,laboratorial passage isolate, Hunan and Jiangsu resistant isolates of S. japonicum andS. mansoni, were exposed to praziquantel at concentrations of10-5,5×10-6,10-6,5×10-7mol/L and10-7mol/L for1,3min and5min. The morphological changes ofmiracidia were observed under a microscopy, and the morphological change rateswere calculated.Results: After exposure to praziquantel at the same concentration for the same time,the miracidia of different isolates of S. japonicum changed their morphology, but therewas no significant difference of morphological change rates of miracidia of differentisolates of S. japonicum (P>0.05), while the morphological change rates of S.mansoni miracidia were higher than those of S. japonicum (P <0.05), and themorphological change rates of miracidia of praziquantel-susceptible isolates of S.japonicum were significantly higher than those of praziquantel-susceptible isolates (P<0.05).Conclusions: There were no significant differences of praziquantel sensitivity againstmiracidia of different isolates of S. japonicum in mainland China. Following exposureto praziquantel at the same concentration for the same time, the morphological changerates of S. mansoni miracidia were higher than those of S. japonicum. The morphological change rate of schistosome miracidium after exposure to praziquantelcan quantitatively reflect the sensitivity of schistosome populations to praziquantel,which can be used to detect and monitor the emergence of praziquantel resistance indefinitive host of schistosomes.4Assessment of praziquantel sensitivity against S. japonicum in areas with lowendemicity in ChinaObjective: To assess the efficacy of praziquantel against S. japonicum in areas withlow endemicity of China.Methods: During the period from November,2010, through March,2011, theresidents aged6–65years old from two villages with low endemicity of S. japonicum,namely Sanshan and Xuguang of Wucheng Township, Yongxiu County, JiangxiProvince, were detected for schistosome infections using the miracidial hatching test.The infected residents in Sanshan Village were treated with praziquantel at a singleoral dose of40mg/kg, while those infected in Xuguang Village were treated withpraziquantel at a single oral dose of30mg/kg for two successive days (total dose of60mg/kg). Six weeks after the treatment, the cases were detected again, the infectionrate in residents were calculated, and the praziquantel efficacy in treatment ofschistosomiasis japonica was assessed.Results: A total of1242residents were detected in both villages, and43infectedcases were observed, with an infection rate of3.46%. Of the1242residents examined,417were living in Sanshan Village, with13cases infected;825were living inXuguang Village, with30cases infected. All43subjects were treated withpraziquantel at a single oral dose of40mg/kg or a single oral dose of30mg/kg fortwo successive days (total dose of60mg/kg); six weeks later, the subjects wereexamined using miracidial hatching test, and no infections were detected.Conclusions: The sensitivity of praziquantel against S. japonicum does not decreaseand the current efficacy is still high, which has not changed after more than threedecades of repeated, expanded chemotherapy in main endemic areas of China. It isalso suggested that no evidence of tolerance or resistance to praziquantel in S. japonicum is detected in China. |
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