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      Bioactivity of miltefosine against aquatic stages of Schistosoma mansoni, Schistosoma haematobium and their snail hosts, supported by scanning electron microscopy

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      1 , , 2 , 2
      Parasites & Vectors
      BioMed Central

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          Abstract

          Background

          Miltefosine, which is the first oral drug licensed for the treatment of leishmaniasis, was recently reported to be a promising lead compound for the synthesis of novel antischistosomal derivatives with potent activity in vivo against different developmental stages of Schistosoma mansoni. In this paper an in vitro study was carried out to investigate whether it has a biocidal activity against the aquatic stages of Schistosoma mansoni and its snail intermediate host, Biomphalaria alexandrina , thus being also a molluscicide. Additionally, to see whether miltefosine can have a broad spectrum antischistosomal activity, a similar in vitro study was carried out on the adult stage of Schistosoma haematobium, the second major human species, its larval stages and snail intermediate host, Bulinus truncutes. This was checked by scanning electron microscopy.

          Results

          Miltefosine proved to have in vitro ovicidal, schistolarvicidal and lethal activity on adult worms of both Schistosoma species and has considerable molluscicidal activity on their snail hosts. Scanning electron microscopy revealed several morphological changes on the different stages of the parasite and on the soft body of the snail, which further strengthens the current evidence of miltefosine's activity. This is the first report of mollusicidal activity of miltefosine and its in vitro schistosomicidal activity against S.haematobium.

          Conclusions

          This study highlights miltefosine not only as a potential promising lead compound for the synthesis of novel broad spectrum schistosomicidal derivatives, but also for molluscicidals.

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          Most cited references44

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          Resistance to praziquantel: direct evidence from Schistosoma mansoni isolated from Egyptian villagers.

          Recent evidence suggest that resistance to praziquantel (PZQ) may be developing. This would not be surprising in countries like Egypt where the drug has been used aggressively for more that 10 years. The classic phenotype of drug resistance is a significant increase in the 50% effective dose value of isolates retrieved from patients not responding to the drug. In a previous publication, we reported that such phenotypes have been isolated from humans infected with Schistosoma mansoni. Since the action of PZQ may be dependent upon the drug and host factors, most notably the immune system, we analyzed the quantitative effects of PZQ on single worms that differed in their response to PZQ when maintained in mice. Our hypothesis was that the in vitro action of the drug would correlate with it in vivo action. We confirmed this hypothesis and conclude that the in vitro action of the drug is related to its in vivo action. Knowing this relationship will assist in our ability to detect or survey for the PZQ resistant phenotype in human populations.
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            Schistosomiasis: challenges for control, treatment and drug resistance.

            Schistosomiasis is a parasitic disease that has recently attracted increased focus and funding for control. Despite shifts in global health policy towards the implementation of mass chemotherapeutic control programmes at the national scale in sub-Saharan Africa, however, many challenges still exist. Publications reviewed for this article cover: the development of treatment strategies; the planning, implementation and impact of control programmes; the re-evaluation of the burden of schistosomiasis; improved tools for control; new drugs; the safety of treatment during pregnancy; and the development of resistance against praziquantel. The morbidity due to schistosomiasis has been shown to be greater than was previously thought. The reduction in morbidity of schistosomiasis by control programmes has been demonstrated, while new tools include a validated dose pole for delivering the correct treatment, geographical information systems mapping for determining high-risk areas, and Lot Quality Assurance Sampling for determining treatment strategies at the local level. Sustainability and future funding are issues to be addressed. Despite some positive results, myrrh is apparently ineffective against schistosomiasis, but fortunately no resistance to praziquantel has developed. We predict the impact of schistosomiasis control will be a healthier generation of children within 5 years.
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              Praziquantel for the treatment of schistosomiasis: its use for control in areas with endemic disease and prospects for drug resistance.

              Praziquantel became available for the treatment of schistosomiasis and other trematode-inflicted diseases in the 1970s. It was revolutionary because it could be administered orally and had very few unwanted side effects. As a result of marked reductions in the price of praziquantel, the rate at which it is used has accelerated greatly in recent years. For the foreseeable future it will be the mainstay of programs designed to control schistosome-induced morbidity, particularly in sub-Saharan Africa where schistosomiasis is heavily endemic. There is currently no evidence to suggest that any schistosomes have developed resistance to praziquantel as a result of its widespread use. Nevertheless, while resistance may not pose an obvious or immediate threat to the usefulness of praziquantel, complacency and a failure to monitor developments may have serious consequences in the longer term since it will be the only drug that is readily available for large-scale treatment of schistosomiasis.
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                Author and article information

                Journal
                Parasit Vectors
                Parasites & Vectors
                BioMed Central
                1756-3305
                2011
                11 May 2011
                : 4
                : 73
                Affiliations
                [1 ]Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
                [2 ]Department of Medical Malacology, Theodor Bilharz Research Institute, Imbaba, Cairo, Egypt
                Article
                1756-3305-4-73
                10.1186/1756-3305-4-73
                3114006
                21569375
                7831d5ee-cc23-4589-9576-0ec2100b9f02
                Copyright ©2011 Eissa et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 March 2011
                : 11 May 2011
                Categories
                Research

                Parasitology
                Parasitology

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