Novel therapeutic and prevention approaches for schistosomiasis: review

Schistosomiasis is a debilitating disease affecting approximately 600 million people in 74 developing countries, with 800 million, mostly children at risk. To circumvent the threat of having praziquantel [PZQ] as the only drug used for treatment, several PZQ derivatives were synthesized, and drugs destined for other parasites were used with success. A plethora of plant-derived oils and extracts were found to effectively kill juvenile and adult schistosomes, yet none was progressed to pre- and clinical studies except an oleo-gum resin extracted from the stem of Commiphora molmol, myrrh, which action was challenged in several trials. We have proposed an essential fatty acid, a component of our diet and cells, the polyunsaturated fatty acid arachidonic acid [ARA] as a remedy for schistosomiasis, due to its ability to activate the parasite tegument-bound neutral sphingomyelinase, with subsequent hydrolysis of the apical lipid bilayer sphingomyelin molecules, allowing access of specific antibody molecules, and eventual worm attrition. This concept was convincingly supported using larval and adult Schistosoma mansoni and Schistosoma haematobium worms in in vitro experiments, and in vivo studies in inbred mice and outbred hamsters. Even if ARA proves to be an entirely effective and safe therapy for schistosomiasis, it will not prevent reinfection, and accordingly, the need for developing an effective vaccine remains an urgent priority. Our studies have supported the status of S. mansoni calpain, glutathione-S-transferase, aldolase, triose phosphate isomerase, glyceraldehyde 3-phosphate dehydrogenase, enolase, and 2-cys peroxiredoxin as vaccine candidates, as they are larval excreted-secreted products and, contrary to the surface membrane molecules, are entirely accessible to the host immune system effector elements. We have proposed that the use of these molecules, in conjunction with Th2 cytokines-inducing adjuvants for recruiting and activating eosinophils and basophils, will likely lead to development and implementation of a sterilizing vaccine in a near future

Height as a Surrogate for Bodyweight for Estimating the Dosage of Praziquantel and Artesunate in theTreatment of Urinary Schistosomiasis in School-Age Children

World Health Organization recommends mass treatment of all school children in areas where the prevalence of schistosomiasis is greater than 50. Praziquantel and artesunate are reported to display broad-spectrum antischistosomal activities. Since the susceptibilities of the different stages of schistosomes to the two drugs are distinctively different; it has been established that the use of these two drugs in combination will be beneficial for the treatment of urinary schistosomiasis. Dosage is determined by weight; which can be difficult to determine in field conditions. The use of calibrated height meter with height-based dosage calibration will make the work less cumbersome in field settings. Data on age; weight; and height from 264 school children who were screened and found to be infected with Schistosoma haematobium; diagnosed by the presence of the ova in their urine; were used to predict an alternative to bodyweight and thus the dosage of praziquantel and artesunate required to treat this disease. A very strong positive correlation (r = 0.8) was obtained for the height of treated children measured against weight while a moderately positive correlation coefficient (r = 0.6) was obtained for weight against age measurements; depicting that height can be used in lieu of weight for correct dose determination. A height meter calibrated with the equivalent number of tablets of praziquantel and artesunate could thus be used as a simple measurement to determine the dosage of praziquantel and artesunate needed to treat children in the field. This calibrated height will expedite treating large population of children in mass treatment campaigns in an endemic community

Evaluation of the levels of circulating carbohydrate antigen and anti-SWAP antibodies in patients with active Schistosoma haematobium infection and its relation to morbidity changes

The immune responses of schistosomiasis and its relation to morbidity changes is important to understand the pathogenesis of this disease. The aim of this study is to evaluate the levels of circulating antigen and anti-SWAP antibodies and its relation to morbidity changes in patients with active Schistosoma haemtobium infection. An antigen enzyme-linked immunosorbent assay [ELISA] employing monoclonal [mAb] 128C3/ 3/21 was used to detect circulating parasite-derived antigen in the sera of 35 of actively infected schistosoma haematobium patients [31 males and 4 females, 5 to 25 years of age] seen in the out patient clinic of Assiut University Hospital. AntiSWAP [soluble adultworm antigen preparation] immunoglobulins IgG1. IgG4 and IgE were performed for 25 of them. Patients were treated with praziquantel [PZQ] and re-evaluated after 1, 3, and 6 months. Changes in morbidity were evaluated using ultrasonographic grading of urinary bladder lesions. It was found that all patients had significantly high levels of circulating antigens in their sera i. e. above the cut-off value. The antigen level fell significantly in the follow cup visits [p<0.001]. Although the mean antigen level was still significantly reduced [p<0.001] at 6 months visit, 16 patients had high mean antigen level and 9 had rising levels of antigenaemia, reflecting reinfection in 6 patients and persistence of infection in the others. On the other hand, all patients had positive ELISA reaction for IgG1 and IgG4, while 5 patients had negative reaction for IgE through the different visits before and after treatment. The decrease in the mean levels of IgG1 and IgG4 were statistically significant only after 6 months of treatment, but the mean levels of IgE showed significant drop at 3 and 6 months of treatment. A significant correlation was found between the circulating antigen and the anti SWAP IgE during the active infection, but no significant correlation was found between the antigen level and IgG1 and IgG4. There was a significant correlation between the level of circulating carbohydrate antigens and morbidity changes of the urinary bladder. On the other hand there was no significant correlation between the anti-SWAP antibodies and morbidity changes. We conclude that ELISA assay for detection of circulating carbohydrate antigen of S.haematobium is valuable and sensitive in diagnosis of active infection, measurement of intensity of infection and detection of reinfection as well as evaluation of the efficacy of treatment. Its level correlates with anti-SWAP IgE during active infection. In addition it correlates significantly with