Pharmacodynamics of mefloquine and praziquantel combination therapy in mice harbouring juvenile and adult Schistosoma mansoni (original) (raw)
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PLoS Neglected Tropical Diseases, 2014
Background: Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel. Hence, there is a pressing need to develop additional therapeutics against schistosomiasis. The antimalarial drug mefloquine shows antischistosomal activity in animal models and clinical trials, which calls for further investigations. Methodology: We comparatively assessed the efficacy and tolerability of the following treatments against Schistosoma haematobium in school-aged children in Cô te d'Ivoire: (i) praziquantel (40 mg/kg; standard treatment); (ii) mefloquine (25 mg/kg) combined with praziquantel (40 mg/kg); and (iii) mefloquine-artesunate (36 (100 mg artesunate +250 mg mefloquine)) combined with praziquantel (40 mg/kg) (treatments administered on subsequent days). Two urine samples were collected before, and on days 21-22 and 78-79 after the first dosing.
Bulletin of the World Health Organisation
Objective To evaluate the therapeutic efficacy of oxamniquine and praziquantel, the two most clinically important schistosomicide drugs, and to compare the accuracy of faecal examination with the accuracy of oogram in testing for Schistosoma mansoni infection. Methods In a triple-masked and randomized controlled trial, 106 patients infected with S. mansoni were randomly allocated to one of three statistically homogeneous groups. One group was given 60 mg/kg praziquantel per day for three consecutive days, another was given two daily doses of 10 mg/kg oxamniquine, and the placebo group received starch. Faecal examinations (days 15, 30, 60, 90, 120, 150, and 180 after treatment) and biopsy of rectal mucosa by quantitative oogram (days 30, 60, 120, and 180) were used for the initial diagnosis and for evaluating the degree of cure. The w 2 test and the Kruskal-Wallis test were used to compare variables in the three groups. Survival analysis (Kaplan-Meier) and the log-rank test were used to evaluate the efficacy of the treatments. Findings The sensitivity of stool examinations ranged from 88.9% to 94.4% when patients presented with >5000 S. mansoni eggs per gram of tissue (oogram); when the number of eggs dropped to <1000 eggs per gram, sensitivity was reduced (range, 22.7-34.0%). When cure was evaluated by stool examination, oxamniquine and praziquantel had cure rates of 90.3% and 100%, respectively. However, when the oogram was used as an indicator of sensitivity, the oxamniquine cure rate dropped dramatically (to 42.4%), whereas the rate for praziquantel remained high, at 96.1%. Conclusion Praziquantel was significantly more effective than oxamniquine in treating S. mansoni infection. The oogram was markedly more sensitive than stool examinations in detecting S. mansoni eggs and should be recommended for use in clinical trials with schistosomicides.
PLOS Neglected Tropical Diseases
Background One of the considerable challenges of schistosomiasis chemotherapy is the inefficacy of praziquantel (PZQ) at the initial phase of the infection. Immature schistosomes are not susceptible to PZQ at the curative dose. Here, we investigated the efficacy of different PZQ regimens administered during the initial stage of Schistosoma mansoni infection in mice. Methodology/Principal findings Two months-old mice were individually infected with 80 S. mansoni cercariae and divided into one infected-untreated control group (IC) and four PZQ-treated groups: PZQ at 100 mg/kg/day for five consecutive days (group PZQ1), PZQ at 100 mg/kg/day for 28 days (group PZQ2), PZQ at 18 mg/kg/day for 28 days (group PZQ3) and a single dose of PZQ at 500 mg/kg (group PZQ4). The treatment started on day one post-infection (p.i), and each group of mice was divided into two subgroups euthanized on day 36 or 56 p.i, respectively. We determined the mortality rate, the parasitological burden, the hepatic...
2018
Host immune response against Schistosoma mansoni is a major contributor in the process of resistance or susceptibility to re-infection, as well as the therapeutic response towards different antischistosomal drugs. This study evaluated the role of IgG &IgG4 as immune-logical marker of cure and their effect on anti-schistosomal mefloquine efficacy. Sixty swiss albino mice were infected with Schistosoma cercaria and divided into four groups; non-infected, infected not treated, infected treated with praziquantel and infected treated with mefloquine. The effect of drugs was assessed parasitologically using Kato-Katz technique and immunologically by measuring the serum level of anti-Schistosoma IgG & IgG4 subclass. The results showed 83.5% significant egg count reduction in MFQ-treated infected group. Also, serum anti-soluble egg antigen (SEA) total IgG & IgG4 subclass levels in MFQ treated group were significantly different from infected control group & PZQ-treated infected group.
Host immune response against Schistosoma mansoni is a major contributor in the process of resistance or susceptibility to re-infection, as well as the therapeutic response towards different antischistosomal drugs. This study evaluated the role of IgG &IgG4 as immune-logical marker of cure and their effect on anti-schistosomal mefloquine efficacy. Sixty Swiss albino mice were infected with Schistosoma cercaria and divided into four groups; non-infected, infected not treated, infected treated with praziquantel and infected treated with mefloquine. The effect of drugs was assessed parasitologically using Kato-Katz technique and immunologically by measuring the serum level of anti-Schistosoma IgG & IgG4 subclass. The results showed 83.5% significant egg count reduction in MFQ-treated infected group. Also, serum anti-soluble egg antigen (SEA) total IgG & IgG4 subclass levels in MFQ treated group were significantly different from infected control group & PZQ-treated infected group.
Schistosomiasis is a parasitic disease, second to malaria, affecting human's tropics and sub-tropics. The disease condition varies in severity depending on parasite species and strain, organ system infected, geographical region, genetic constitution of the individual and nutritional status. The drug praziquantel has been the choice of drug for the treatment of schistosomisias; however, the effective dose, 450 mg/kg body weight, which is currently being used, is not able to clear the worms completely. This work sought to determine the effective dose of praziquantel in different mouse strains of which the results can be applied in human treatment. Experimental groups comprising of twelve mice and eighteen for the infected control groups were designed for both BALB/c and Swiss mice. At four weeks post infection, mice were treated with varying dosages of praziquantel namely PZQ 1350, PZQ 900, PZQ 450 mg/kg body weight. At week 6, all mice were perfused to recover adult worms. Gross pathology and histopathology of the liver tissue were examined. Serum samples were collected to determine immunological responses in all the groups at week 4 and 6. Schistosomule soluble protein (SSP) and schistosomule warm antigen preparation (SWAP) specific antibody ELISA were done. Results indicated that in the experimental groups PZQ 1350 mg/kg body weight had few numbers of worms recovered in BALB/c and Swiss mice, that is, 30.30 and 34.08%, respectively, and a high worm reduction, that is, 69.70 and 65.92% respectively. The SSP and SWAP specific IgG responses were high due to synergistic effect between the drug and immune responses. Granuloma formation was greatly reduced in PZQ 1350 mg/kg body weight group in comparison to other treatments. The findings of this study imply that the higher the dosage of praziquantel, the more the protection against Schistosoma mansoni infection, since PZQ 1350 indicated better responses in worm recovery, worm reduction, immunological response and pathology compared to other dosages. These results may be incorporated into the design of a more effective dose; however, the toxicity of the high dose should be investigated. The findings also indicate that Swiss mouse was a better permissive host than BALB/c, as it allowed more parasites to mature instead of destroying them. Hence, it is a better model in schistosomiasis experimental studies.
Schistosomicidal activity of the antimalarial drug, mefloquine, in Schistosoma mansoni-infected mice
Travel Medicine and Infectious Disease, 2008
Therapeutic effects of racemic mefloquine were assessed in Schistosoma mansoniinfected mice, and evaluated by recording worm burden, the status of egg maturation and viability, and intestinal mast cell recruitment. Age-matched mice were divided into four groups, of which two were infected. At 8 weeks postinfection, one group of infected and one group of uninfected mice were treated with a single dose of mefloquine (150 mg/kg). Ten days after treatment, all animals were killed. Mefloquine at 150 mg/kg had no effect on worm burden, but significantly reduced the number of eggs in the first three developmental egg stages. Analysis of intestinal mast cell numbers showed that mefloquine induced mastocytosis both in infected and control animals. In conclusion, mefloquine significantly reduces egg production in S. mansoni-infected mice, suggesting a therapeutic potency in schistosomiasis therapy. Mefloquine also exerts a significant proinflammatory effect on the intestine. Through its effect on egg production, mefloquine may be a cause of silent schistosomiasis in travelers using mefloquine for malaria chemoprophylaxis. Further study of the anti-schistosomal activity of mefloquine is warranted, as its activity against other helminths.