Hospital Study On Combined Treatment Of Praziquantel And Artemether On Patients With Acute Schistosomiasis Japonica

Due to a large amount of eggs laying to the blood steam by female worms, acute schistosomiasis japonica appears with a featured high nocturnal fever on an average of 41.5 days after a first infection or reinfection with high density of cercariae. Not every individual response well to praziquantel 120mg/kg in a 6-day course especially those who had a repeated water exposure before the onset of the disease. Nevertheless, efficacy of praziquantel also partly depends on host immune status. Thus, combining both anti-larva arthemether and anti-adult worm praziquantel would provide higher worm reduction than either drug alone. This hypothesis has been confirmed in previous experimental studies.A total dose of praziquantel 120mg/kg for acute schsitosomiasis is generally considered high by WHO and 60mg/kg in one day time is recommended. In this regard, on rabbit experiment, we test the therapeutic effect of two different doses of praziquantel.Our present work were also carried out to search for a better treatment regime and understand the immune status before treatment on human acute schistosomiasis japonica.Objectives1. To observe the effect of praziquantel (PZQ) at 2 different doses on rabbits infected with S.japonicum so as to provide a basis for clinical use of praziquantel;2. To explore the immune status and the relationship between immune response and age, infection intensity in acute patients with schistosomiasis japonica before parasitological treatment;3. To compare with current monotherapy of praziquantel and evaluate the efficacy and safety of four different treatment regimes in order to find out a more efficient, more convenient, safer treatment regime for acute schistosomiasis japonica patients. Methods1. At 42 days after challenged with S. japonicum cercariae, twelve rabbits were randomly divided into 3 groups, rabbits in group A were treated with a single intragastric (Ig) dose of PZQ 60mg/kg, group B with PZQ 20mg/kg, daily once every day for 6 days and control group left with no treatment. The effect of therapy was assessed by worm, liver and intestine egg count at 22 days later;2. Anti-egg and anti-worm antigen IgE and IgG₄ as well as soluble TNF receptors (sTNFR- I ,sTNFR- II ) and soluble intercellular adhesion molecule-1 (sICAM-1) were tiltered by ELISA in the sera of patients with acute (n=38), chronic(n=41), advanced(n=40) schistosomiasis and uninfected subjects(n=29). One-way ANOVA analysis was carried out to compare levels of markers among clinical phenotypes. The relationships between age, infection intensity and serum specific antibodies and cytokines in acute schistosomiasis patients before parasitological treatment were analyzed;3. Two hundred and five patients with acute schistosomiasis japonica were randomly allocated into four groups with different treatment regimes: 53 patients in group A were treated with praziquantel 60mg/kg plus artemether 6mg/kg; 56 in group B with praziquantel 60mg/kg and placebo; 45 in group C with praziquantel 120mg/kg plus artemether 6mg/kg; 51 in group D with praziquanel 120mg/kg and placebo. The clinical cure rate and stool egg reduction were evaluated 45 days after drugs administration; Drug adverse event was monitored for 20 days.Results1. There was no statistically significance for worm, liver and intestine egg reduction between two groups of different dosage 22 days later in rabbit;2. Anti-SEA and anti-SWA IgG₄ titre in both acute and chronic patients were significantly higher than that in uninfected subjects and advanced cases (P<0.05). There were significantly higher anti-SEA and anti-SWA IgE in acute schistosomiasis patients before anti-schistosome treatment than in chronic, advanced ones and uninfected subjects (P<0.01). sTNFR-I , sTNFR- II, sICAM-1 serum levels in acute patients were significantly higher than that in the chronic, advanced cases and the unifected subjects (P<=0.05) and there is no statistical significance either by age or egg count(P>0.05); serum IgE response to SWA was significantly related to age(P<0.05) and serum IgG₄ response to SEA was significantly related to egg count in acute patients(P<0.05);3. The clinical cure rates of acute schistosomiasis patients were 98.0%, 96.4%, 97.7% and 95.7% from group A to D respectively. Egg count in stool was reduced by 97.8%, 99.1%, 99.1% and 97.7% in group A to D respectively. There was no significant difference in cure rate and stool egg reduction rate among four groups (both P>0.05). Fever decreased 3.9, 5.1, 6.4 and 5.7days after treatment from A to D group respectively (P>0.05). Patients in four groups were hospitalized for 6.4, 7.9, 9.4, 8.9 days respectively. Patients in group A stayed in hospital significantly shorter than those in other groups (P<0.05). No major adverse event and serious side effect was observed besides mild allergy in two cases after artemether administration.Conclusion1. Increasing the dose of praziquantel from 60mg/kg to 120mg/kg does not result in better therapeutical effects in rabbits infected with S. japonica;2. There was apparently a stronger inflammatory reaction in acute schistosomiasis patients before parasitological treatment than in chronic patients. Inflammatory reaction in acute schistosomaisis patients did not show significant difference by egg-count and age from our observation. Specific antibodies response increased and it was related to age and infection intensity in acute schistosomiasis patients;3. The combined therapy of artemether with praziquantel did not have better therapeutical effects than praziquantel alone in patients with acute schistosomiasis japonica. Praziquantel 120mg/kg in 6-day regime was no more efficient in treating acute schistosomiasis than a total dose of 60mg/kg in one day. Combination of praziquantel 60mg/kg with artemether 6mg/kg was better for fever clearance. This study suggested that patient's hospital stay can be significantly shortened. Artemether at a single oral dose of 6mg/kg is safe and well tolerant on acute schistosomiasis patients. Artemether given one day apart from praziquantel was also safe.This work has contributed to improve our knowledge on clinical application of two key anti-schistosomal drugs, praziquantel and artemether, for human acute schistosomiais japonica.