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artesunate, artemether) constitute the standard of care for malaria treatment that is an artemisinin-based combination therapy (ACT). However, given together with PZQ, all life cycle stages in humans could be targeted. Differences in the design and quality of the studies carried out make it difficult to draw an overall conclusion on the antischistosomal efficacy of artemisinins and mefloquine. Of particular interest is their activity against young schistosomes, as identified in preclinical studies. Indeed, antimalarials such as artesunate, artemether, and mefloquine have been tested, as a monotherapy or in combination, in clinical trials for their antischistosomal potency. Antiplasmodial compounds approved for use in humans may serve as “low hanging fruits” for the development of new antischistosomal interventions either as antimalarial treatments with an add-on effect against schistosomes or as a starting point for a schistosomiasis drug development program. since both parasites have a large geographical overlap in endemicity. In Africa, individuals are often co-infected with Schistosoma spp. Interestingly, schistosomes and malaria parasites both degrade blood/hemoglobin and depend on intracellular mechanisms to protect themselves from heme toxicity a molecular pathway inhibited by several antimalarial compounds. The need for a new antischistosomal compound is urgent, optimally exhibiting broad activity against all stages of the parasite’s life cycle present in humans.ĭrug repurposing is a rapid and efficient strategy to identify compounds with new therapeutic targets. Resistance to PZQ has not been confirmed and its existence remains controversial, yet, clinical schistosome isolates with reduced sensitivity have been identified in Egypt and Senegal after PZQ deployment in mass drug administration programs.
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Schistosomes in the prepatent period of up to eight weeks are not affected which is a limit to schistosomiasis control and elimination efforts by PZQ mass administration. japonicum, is exclusively active against the adult life cycle stage. Praziquantel (PZQ), the only drug for the treatment of all Schistosoma spp., including Schistosoma mansoni, S. WHO estimated that approximately 100 million people were treated for schistosomiasis in 2018, with about 90% of cases occurring in Africa, and approximately 290 million people receiving preventive treatment. Schistosomiasis is an infectious disease caused by parasitic flatworms of the genus Schistosoma. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. AK and PGK received funding from the DZIF. NZ and AK received intramural funding via the Interdisziplinäres Promotionskolleg Medizin IZKF (grant number PK ) of the University of Tübingen. The data is provided in S1 Data excel file.įunding: The project was supported by the University Hospital Tübingen, Germany. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All relevant data are within the manuscript and its Supporting information files. Received: JanuAccepted: Published: June 24, 2021Ĭopyright: © 2021 Koehne et al. PLoS Negl Trop Dis 15(6):Įditor: Geoffrey Gobert, Queen’s University Belfast, UNITED KINGDOM (2021) Evidence for in vitro and in vivo activity of the antimalarial pyronaridine against Schistosoma.
Ic50 graphpad prism 6 trial#
A pilot trial with pyronaridine-artesunate done in Gabon showed the first promising results against Schistosoma infections.Ĭitation: Koehne E, Zander N, Rodi M, Held J, Hoffmann W, Zoleko-Manego R, et al.
Ic50 graphpad prism 6 series#
After testing a series of antiplasmodial compounds, the authors found that several compounds also exhibited antischistosomal activity at various life cycle stages of the worms, including pyronaridine and methylene blue, both compounds already approved for human use. The need for a new antischistosomal compound is urgent, ideally exhibiting broad activity against all stages of the parasite’s life cycle present in humans. Although resistance to praziquantel has not been confirmed and its existence remains controversial, some countries have identified clinical schistosome isolates with reduced sensitivity to praziquantel, after deployment in mass drug administration programs. and is exclusively active against the adult life cycle stage, since schistosomes in the prepatent period of up to eight weeks are not affected by the drug.
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Praziquantel is still the only drug in use for the treatment of all Schistosoma spp.