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      Schistosomiasis and soil-transmitted helminthiasis: common drugs for treatment and control

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      Expert Opinion on Pharmacotherapy
      Informa Healthcare

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          Abstract

          Schistosomiasis is a disease caused by parasitic trematode worms (schistosomes) that currently affects 200 million people living in tropical and subtropical environments. It is a chronic disease and the latest estimates for sub-Saharan Africa are that it kills > 200000 people every year. Soil-transmitted helminthiasis (STH) is caused by intestinal nematodes. More than 2 billion people are infected worldwide and the disease burden might approach that of malaria. Recognising the enormous public health significance of schistosomiasis and STH, particularly among the poor, and in view of readily available drugs that are safe, efficacious and inexpensive, the World Health Assembly recently set forth a resolution for a combined approach for morbidity control of both diseases. This review briefly summarises the geographical distribution, life cycle and global burden of schistosomiasis and STH. The current arsenal of drugs available for morbidity control, including discovery, chemistry, pharmacological properties and aspects of therapeutic efficacy and adverse events in clinical human use is then discussed. The emphasis is on praziquantel, oxamniquine and artemisinin derivatives (against schistosomes) and albendazole, mebendazole, levamisole, pyrantel pamoate and other compounds (against intestinal nematodes). The experience gained with combination chemotherapy in schistosomiasis and STH is briefly discussed. Finally, current research needs and the critical importance for development of novel anthelmintic drugs, so that chemotherapy can continue to serve as the backbone of integrated and sustainable control of schistosomiasis and STH, is highlighted.

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          Most cited references68

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          Effects of environmental change on emerging parasitic diseases.

          Ecological disturbances exert an influence on the emergence and proliferation of malaria and zoonotic parasitic diseases, including, Leishmaniasis, cryptosporidiosis, giardiasis, trypanosomiasis, schistosomiasis, filariasis, onchocerciasis, and loiasis. Each environmental change, whether occurring as a natural phenomenon or through human intervention, changes the ecological balance and context within which disease hosts or vectors and parasites breed, develop, and transmit disease. Each species occupies a particular ecological niche and vector species sub-populations are distinct behaviourally and genetically as they adapt to man-made environments. Most zoonotic parasites display three distinct life cycles: sylvatic, zoonotic, and anthroponotic. In adapting to changed environmental conditions, including reduced non-human population and increased human population, some vectors display conversion from a primarily zoophyllic to primarily anthrophyllic orientation. Deforestation and ensuing changes in landuse, human settlement, commercial development, road construction, water control systems (dams, canals, irrigation systems, reservoirs), and climate, singly, and in combination have been accompanied by global increases in morbidity and mortality from emergent parasitic disease. The replacement of forests with crop farming, ranching, and raising small animals can create supportive habitats for parasites and their host vectors. When the land use of deforested areas changes, the pattern of human settlement is altered and habitat fragmentation may provide opportunities for exchange and transmission of parasites to the heretofore uninfected humans. Construction of water control projects can lead to shifts in such vector populations as snails and mosquitoes and their parasites. Construction of roads in previously inaccessible forested areas can lead to erosion, and stagnant ponds by blocking the flow of streams when the water rises during the rainy season. The combined effects of environmentally detrimental changes in local land use and alterations in global climate disrupt the natural ecosystem and can increase the risk of transmission of parasitic diseases to the human population.
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            Artemisinins target the SERCA of Plasmodium falciparum.

            Artemisinins are extracted from sweet wormwood (Artemisia annua) and are the most potent antimalarials available, rapidly killing all asexual stages of Plasmodium falciparum. Artemisinins are sesquiterpene lactones widely used to treat multidrug-resistant malaria, a disease that annually claims 1 million lives. Despite extensive clinical and laboratory experience their molecular target is not yet identified. Activated artemisinins form adducts with a variety of biological macromolecules, including haem, translationally controlled tumour protein (TCTP) and other higher-molecular-weight proteins. Here we show that artemisinins, but not quinine or chloroquine, inhibit the SERCA orthologue (PfATP6) of Plasmodium falciparum in Xenopus oocytes with similar potency to thapsigargin (another sesquiterpene lactone and highly specific SERCA inhibitor). As predicted, thapsigargin also antagonizes the parasiticidal activity of artemisinin. Desoxyartemisinin lacks an endoperoxide bridge and is ineffective both as an inhibitor of PfATP6 and as an antimalarial. Chelation of iron by desferrioxamine abrogates the antiparasitic activity of artemisinins and correspondingly attenuates inhibition of PfATP6. Imaging of parasites with BODIPY-thapsigargin labels the cytosolic compartment and is competed by artemisinin. Fluorescent artemisinin labels parasites similarly and irreversibly in an Fe2+-dependent manner. These data provide compelling evidence that artemisinins act by inhibiting PfATP6 outside the food vacuole after activation by iron.
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              Schistosoma mansoni: chemotherapy of infections of different ages.

              Mice were treated with potassium antimony tartrate, hycanthone, oxamniquine, niridazole, or praziquantel at different times after infection with Schistosoma mansoni. The rate of cure was assessed by perfusion of surviving worms approximately 4 weeks after treatment, and the percentage reduction in worm burden was estimated relative to the number of adult worms perfused from control mice, comparably infected but untreated. All six drugs were relatively inactive against S. mansoni between 3 and 4 weeks after infection when compared with treatment at 5 to 6 weeks. However, the drugs differed in the patterns of cure they achieved in the 2-week period after administration of cercariae and in the period around the onset of patency. Worms that had been subjected to amoscanate or hycanthone in the third week after infection showed evidence of this as adults in having a reduced fecundity. Factors such as worm or host physiology, or host immune status may have had roles in the outcome of chemotherapy at different stages of maturation of S. mansoni.
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                Author and article information

                Journal
                Expert Opinion on Pharmacotherapy
                Expert Opinion on Pharmacotherapy
                Informa Healthcare
                1465-6566
                1744-7666
                March 02 2005
                February 2004
                March 02 2005
                February 2004
                : 5
                : 2
                : 263-285
                Article
                10.1517/14656566.5.2.263
                14996624
                42dd5b93-d371-4826-9f51-16ad687e1bd3
                © 2004
                History

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