Randomized comparison of low-dose versus standard-dose praziquantel therapy in treatment of urinary tract morbidity due to Schistosoma haema tobium infection.
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At present, anthelmintic therapy with praziquantel at a dose of 40 mg/kg of body weight is the recommended treatment for control of urinary tract morbidity caused by Schistosoma haematobium. Although this standard regimen is effective, drug cost may represent a significant barrier to implementation of large-scale schistosomiasis control programs in developing areas. Previous comparison trials have established that low-dose (20-30 mg/kg) praziquantel regimens can effectively suppress the intensity of S. haematobium infection in endemic settings. However, the efficacy of these low-dose regimens in controlling infection-related morbidity has not been determined in a randomized field trial. The present random allocation study examined the relative efficacy of a 20 mg/kg dose versus a 40 mg/kg dose of praziquantel in control of hematuria and bladder and renal abnormalities associated with S. haematobium infection in an endemic area of Coast Province, Kenya. After a nine-month observation period, the results indicated an advantage to the standard 40 mg/kg praziquantel dose in terms of reduction of infection prevalence and hematuria after therapy (P < 0.01 and P < 0.005, respectively). However, the two treatment groups were equally effective in reducing structural urinary tract morbidity detected on ultrasound examination. We conclude that in certain settings, a 20 mg/kg dose of praziquantel may be sufficient in providing control of morbidity due to urinary schistosomiasis in population-based treatment programs. (+info)
Synthesis of a new antischistosomally active and toxicologically tolerant C-12 monothione surrogate of the universal antihelmintic praziquantel.
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A new C-12 monothione mimic (III) of the universal antihelmintic Praziquantel (I) namely, 2-cyclohexylthiocarbonyl( 1,2.3,6,7,11b)-hexahydro-4H-pyrazino[2-1a] isoquinoline-4-one was chemically synthesized and structurally elucidated (Elemental analysis. El-Mass, 13C-NMR and IR spectroscopy). Antischistosomal potency in the order of -76% comparable to that for our newly reported C-12 and C-4 dithion mimic II (-70%) and Praziquantel. Praziquantel (100%, mice infected with S. mansoni cercariae), was realized. Toxicological evaluation (mice liver and kidney functions) and biochemical parameters (cholesterol, triglycerides, albumin, total serum proteins and amino acid profile of liver protein homogenate) were also assayed. Comparable to the parent drug, general insignificant toxicological diferences could be attributed for III. Interestingly, III exhibited intermediate biological figures between I and II. An order of IIIII>I, for the other tested biochemical parameters was observed. A consideration of obtained results could indicate that, structurally, an intact glycine amide segment of the pyrazine moiety, as it is the case in both I and III, and not in II (glycine thioamide) seemed now more crucial for exhibiting an optimum antihelmintic potency as well as a more tolerant toxicity characteristics. Additionally, the obtained comparable amino acid profile of mice liver protein homogenate after the treatment by III, could suggest similar biochemical, lethal mechanistic and metabolic routes for II, III and I. The new lipophilic candidatee III seems to merit more profound chemical, biological, and pharmaceutical investigations. (+info)
Lymphatic filariasis elimination and schistosomiasis control in combination with onchocerciasis control in Nigeria.
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This paper describes a pilot initiative to incorporate lymphatic filariasis (LF) elimination and urinary schistosomiasis (SH) control into a mature onchocerciasis control program based on community-directed ivermectin treatment in central Nigeria. In the same districts having onchocerciasis we found LF (as determined by blood antigen testing in adult males) in 90% of 149 villages with a mean prevalence of 22.4% (range 0-67%). Similarly, SH, as determined by dipstick reagent testing for blood in urine from school children, was found in 91% of 176 villages with a mean orevalence in school age children of 24.4% (range 0-87%). Health education and treatment interventions for SH resulted in 52,480 cumulative praziquantel treatments, and 159,555 combined onchocerciasis and LF treatments (with ivermectin and albendazole) as of the end of 2000. Treatments for onchocerciasis and LF were separated by at least 1 week from treatments for SH. There was no negative impact on the coverage of the onchocerciasis program by the addition of LF and SH activities. (+info)
The effect of treatment on the age-antibody relationship in children infected with Schistosoma mansoni and Schistosoma haematobium.
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The effect of praziquantel treatment on the age-antibody relationship was studied in 174 children aged between 6 and 17 years from a schistosome endemic area in Zimbabwe. The children were co-infected with Schistosoma mansoni and S. haematobium with infection prevalences of 74% and 53% respectively. Antibody levels for the isotypes IgA, IgE, IgM, IgG1, IgG2, IgG3 and IgG4, directed against soluble egg antigen were measured using an indirect ELISA assay. Treatment resulted in a significant increase in levels of IgG2 and IgG3 while levels of IgA decreased significantly. In untreated children there were significant decreases in levels of IgG4. Treatment also resulted in significant alteration in the age-antibody profiles for the isotypes IgE, IgM, IgG1 and IgG2 in treated children but not in untreated children. The results are discussed in the context of factors believed to give rise to the age-antibody relationship; i.e. age-related exposure patterns, age-related development of acquired immunity, age-related hormonal changes and age-related changes in innate susceptibility to infection. (+info)
Hematospermia due to schistosome infection in travelers: diagnostic and treatment challenges.
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Hematospermia associated with schistosomal infection is a new topic of clinical interest. The features and incidence of this rare complication and the difficulties associated with its treatment have yet to be characterized. We describe 4 patients with hematospermia due to schistosome infection acquired during travel to an area of endemicity. (+info)
Lack of C3 affects Th2 response development and the sequelae of chemotherapy in schistosomiasis.
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The role of the third component of complement (C3) during schistosome infection was investigated using mice deficient in C3. While no effect was observed 8 wk after infection on worm development or liver pathology, Ag-specific Th2-associated cytokine production (IL-13, IL-5, IL-6, and IL-10) was significantly reduced, and IFN-gamma production was enhanced in the absence of C3. IgG1 and IgE, but not IgG2a or IgM, Ab responses were also significantly impaired in infected C3(-/-) mice, suggesting that C3 may play a role in IL-4-mediated Th2 response enhancement during schistosome infection. Furthermore, C3-deficient mice could not effectively clear adult worms after praziquantel (PZQ) treatment and suffered increased morbidity due to the overproduction of proinflammatory mediators following drug administration. However, the ischemic liver damage that normally accompanies PZQ administration in infected wild-type mice was substantially reduced in treated C3-deficient mice, probably due to the absence of dead or dying worms in the livers of these animals. Together these results indicate that C3 enhances Th2 responses during schistosome infection, potentiates PZQ-mediated parasite clearance, and reduces chemotherapy-induced proinflammatory mediator production. (+info)
Effects of pentoxifylline on the hepatic content of TGF-beta1 and collagen in Schistosomiasis japonica mice with liver fibrosis.
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AIM: To study the effects of pentoxifylline (PTX) on the content of hepatic TGF-beta1, type I and type III collagen in schistosomiasis japonica mice with liver fibrosis and its mechanism of anti-fibrosis. METHODS: Forty mice with schistosomiasis were divided into four groups: one group as control without any treatment, other three were treated with Praziquantel 500 mg/(kg x d)for 2 d, high dose PTX 360 mg/(kg x d) for 8 wk, and low dose PTX 180 mg/(kg x d) for 8 wk respectively. Immunohistochemical technique and multimedia color pathographic analysis system were applied to observe the content change of hepatic TGF-beta1, type I and type III collagen in schistosomiasis japonica mice with liver fibrosis before and after PTX treatment. RESULTS: Effects of PTX on the content change of hepatic TGF-beta1, type I and type III collagen in schistosomiasis japonica mice with liver fibrosis were related to the dosage of PTX, high dose PTX treated group could significantly reduce the content of TGF-beta1 (0.709+/-0.111), type I (0.644+/-0.108) and type III (0.654+/-0.152) collagen compared with those of control group (0.883+/-0.140, 0.771+/-0.156, 0.822+/-0.129) with statistical significance (P<0.05). Low dose PTX could also reduce the hepatic content of TGF-beta1 (0.752+/-0.152), type I (0.733+/-0.117) and type III (0.788+/-0.147) collagen, but without statistical significance (P>0.05). Both high dose and low dose PTX groups have significant differences on the content of TGF-beta1, type I and type III collagen (P<0.05, P<0.05, P<0.01, respectively). CONCLUSION: High dose of PTX treatment could reduce the content of hepatic TGF-beta1, type I and type III collagen significantly in schistosomiasis japonica mice with liver fibrosis, and thus plays its role of antifibrosis. (+info)
Infection status of Clonorchis sinensis in residents of Hamyang-gun, Gyeongsangnam-do, Korea.
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Oriental liver fluke (Clonorchis sinensis) infection was surveyed among residents of Hamyang-gun, Gyeongsangnam-do, Korea during the period of January 2001 to March 2002. Total 1,041 stool samples were collected from residents who visited Public Health Center and its branches in Hamyang-gun and examined using formalin-ether sedimentation method. The overall egg positive rate was 16%, male showing higher positive rate (21%) than female (10%). The age group of 30 to 50 years had the highest egg positive rate of C. sinensis from 20% to 22%. The positive examinees were treated with praziquantel and educated individually to prevent reinfection. Egg positive rate in this area was decreased when compared with results recorded in the past, however, still remained more than 10%. This study suggests that periodic examination, treatment as well as education of residents should be continued and systematized. (+info)