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Scientific Reports Oct 2022This study aimed to assess the toxicity of praziquantel (anthelmintic drug) in different developmental stages of common carp (Cyprinus carpio) based on mortality, early...
This study aimed to assess the toxicity of praziquantel (anthelmintic drug) in different developmental stages of common carp (Cyprinus carpio) based on mortality, early ontogeny, growth, oxidative stress, antioxidant enzymes, histology and behaviour. Praziquantel at all tested concentrations ranging from 1 to 4 mg/L showed no significant adverse effects on mortality, the early ontogeny and behaviour locomotory (activity, moved distance and velocity) of carp after 35-day exposure. Concentrations of 3 and 4 mg/L caused significantly (P < 0.01) lower growth, total superoxide dismutase and catalase activities compared with controls. Praziquantel is safe for the early life of carp in concentrations ≤ 2 mg/L.
Topics: Animals; Antioxidants; Carps; Catalase; Embryo, Nonmammalian; Larva; Praziquantel; Superoxide Dismutase; Water Pollutants, Chemical
PubMed: 36241766
DOI: 10.1038/s41598-022-21679-2 -
PLoS Neglected Tropical Diseases Jul 2014Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel. Hence, there is a pressing need to develop additional therapeutics against... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel. Hence, there is a pressing need to develop additional therapeutics against schistosomiasis. The antimalarial drug mefloquine shows antischistosomal activity in animal models and clinical trials, which calls for further investigations.
METHODOLOGY
We comparatively assessed the efficacy and tolerability of the following treatments against Schistosoma haematobium in school-aged children in Côte d'Ivoire: (i) praziquantel (40 mg/kg; standard treatment); (ii) mefloquine (25 mg/kg) combined with praziquantel (40 mg/kg); and (iii) mefloquine-artesunate (3× (100 mg artesunate +250 mg mefloquine)) combined with praziquantel (40 mg/kg) (treatments administered on subsequent days). Two urine samples were collected before, and on days 21-22 and 78-79 after the first dosing.
PRINCIPAL FINDINGS
Sixty-one children were present on all examination time points and had complete datasets. No difference in efficacy was observed between the three treatment groups on either follow-up. On the 21-22 day posttreatment follow-up, based on available case analysis, cure rates of 33% (95% confidence interval (CI) 11-55%), 29% (95% CI 8-50%), and 26% (95% CI 5-48%) were observed for praziquantel, mefloquine-artesunate-praziquantel, and mefloquine-praziquantel, respectively. The corresponding egg reduction rates were 94% and above. On the second follow-up, observed cure rates ranged from 19% (praziquantel) to 33% (mefloquine-artesunate-praziquantel), and egg reduction rates were above 90%. Praziquantel monotherapy was the best tolerated treatment. In the mefloquine-artesunate-praziquantel group, adverse events were reported by 91% of the participants, and in the mefloquine-praziquantel group, 95% experienced adverse events. With the exception of abdominal pain at moderate severity, adverse events were mild.
CONCLUSIONS/SIGNIFICANCE
The addition of mefloquine or mefloquine-artesunate does not increase the efficacy of praziquantel against chronic S. haematobium infection. Additional studies are necessary to elucidate the effect of the combinations against acute schistosomiasis.
Topics: Adolescent; Animals; Anthelmintics; Artemisinins; Artesunate; Child; Cote d'Ivoire; Drug Therapy, Combination; Female; Humans; Male; Mefloquine; Praziquantel; Schistosoma haematobium; Schistosomiasis haematobia
PubMed: 25033291
DOI: 10.1371/journal.pntd.0002975 -
International Surgery Jan 2015Hydatid disease is caused by infection with the metacestode stage of Echinococcus tapeworms of the family Taeniidae. The primary carriers are dogs and wolves, and humans... (Review)
Review
Hydatid disease is caused by infection with the metacestode stage of Echinococcus tapeworms of the family Taeniidae. The primary carriers are dogs and wolves, and humans are accidental hosts that do not contribute to the normal life cycle of this organism. The liver is the most commonly involved organ in the body by cystic echinococcosis (CE) secondary to infection with Echinococcus granulosus . Management options for CE should depend on the World Health Organization (WHO) diagnostic classification. Small (<5 cm) WHO stage CE1 and CE3a cysts may be primarily treated with benzimidazoles; the first-choice drug is albendazole. In some situations the combination of albendazole and praziquantel may be preferred. Chemotherapy with a benzimidazole or albendazole plus praziquantel is also used as adjunctive treatment to surgery and percutaneous treatment. Drug treatments have been the indispensable therapeutic modalities for cystic echinococcosis.
Topics: Albendazole; Animals; Anthelmintics; Benzimidazoles; Drug Therapy, Combination; Echinococcosis, Hepatic; Echinococcus granulosus; Humans; Praziquantel; Treatment Outcome
PubMed: 25594649
DOI: 10.9738/INTSURG-D-14-00068.1 -
International Journal For Parasitology.... Apr 2022Parasitic diseases are major constraints in fish mariculture. The anthelmintic praziquantel (PZQ) can effectively treat a range of flatworm parasites in a variety of... (Review)
Review
Parasitic diseases are major constraints in fish mariculture. The anthelmintic praziquantel (PZQ) can effectively treat a range of flatworm parasites in a variety of fish species and has potential for broader application than its current use in the global aquaculture industry. In this review we report on PZQ's current use in the aquaculture industry and discuss its efficacy against various flatworm parasites of fish. Routes of PZQ administration are evaluated, along with issues related to palatability, pharmacokinetics and toxicity in fish, while PZQ's effects on non-target species, environmental impacts, and the development of drug-resistance are discussed.
Topics: Animals; Anthelmintics; Aquaculture; Platyhelminths; Praziquantel
PubMed: 35220160
DOI: 10.1016/j.ijpddr.2022.02.001 -
Non-covalent inhibitors of thioredoxin glutathione reductase with schistosomicidal activity in vivo.Nature Communications Jun 2023Only praziquantel is available for treating schistosomiasis, a disease affecting more than 200 million people. Praziquantel-resistant worms have been selected for in the...
Only praziquantel is available for treating schistosomiasis, a disease affecting more than 200 million people. Praziquantel-resistant worms have been selected for in the lab and low cure rates from mass drug administration programs suggest that resistance is evolving in the field. Thioredoxin glutathione reductase (TGR) is essential for schistosome survival and a validated drug target. TGR inhibitors identified to date are irreversible and/or covalent inhibitors with unacceptable off-target effects. In this work, we identify noncovalent TGR inhibitors with efficacy against schistosome infections in mice, meeting the criteria for lead progression indicated by WHO. Comparisons with previous in vivo studies with praziquantel suggests that these inhibitors outperform the drug of choice for schistosomiasis against juvenile worms.
Topics: Animals; Mice; Schistosomicides; Praziquantel; Schistosoma; NADH, NADPH Oxidoreductases; Schistosomiasis; Schistosoma mansoni
PubMed: 37349300
DOI: 10.1038/s41467-023-39444-y -
Current Opinion in Pharmacology Oct 2018The commitment to eliminate schistosomiasis as a public health problem has mobilized the expansion of praziquantel treatment to meet the London Declaration targets. New... (Review)
Review
The commitment to eliminate schistosomiasis as a public health problem has mobilized the expansion of praziquantel treatment to meet the London Declaration targets. New research has thus sought to elucidate praziquantel's safety and efficacy in key demographics such as preschoolers and pregnant women, as well as novel elements of its pharmacokinetics and pharmacodynamics. At the same time, reliance on praziquantel ad infinitum would place schistosomiasis control at risk, should resistance occur. In response, the academic community has been filling the pre-clinical drug discovery pipeline with novel or resurrected drug candidates against schistosomiasis. In this review, we highlight the latest research on praziquantel treatment dynamics, which aims to improve the utility of this important drug. Moreover, we present the most promising preclinical antischistosomal candidates, which should be studied further to achieve the ultimate goal- an alternative antischistosomal drug in the near future.
Topics: Drug Discovery; Female; Humans; Praziquantel; Pregnancy; Schistosomiasis; Schistosomicides
PubMed: 30077117
DOI: 10.1016/j.coph.2018.06.004 -
International Journal of Infectious... Jan 2017Mass drug administration utilising a single oral dose of 40mg/kg of praziquantel (PZQ) has been endorsed and advocated by the World Health Organisation (WHO) for the...
Mass drug administration utilising a single oral dose of 40mg/kg of praziquantel (PZQ) has been endorsed and advocated by the World Health Organisation (WHO) for the global control and elimination of schistosomiasis. However, this strategy is failing primarily because the drugs are not getting to the people who need them the most. The current global coverage is 20%, the drug compliance rate is less than 50%, and the drug efficacy is approximately 50%. Thus in reality, only about 5% of the reservoir human population is actually receiving intermittent chemotherapy. Despite claims that more of the drug will soon be made available the current strategy is inherently flawed and will not lead to disease elimination. We discuss the many practical issues related to this global strategy, and advocate for an integrated control strategy targeting the life cycle and the most at-risk. Moreover, we discuss how an integrated control package for schistosomiasis should fit within a larger integrated health package for rural and remote villages in the developing world. A holistic health system approach is required to achieve sustainable control and ultimately disease elimination.
Topics: Anthelmintics; Global Health; Humans; Infection Control; Population Groups; Praziquantel; Rural Population; Schistosomiasis
PubMed: 27939558
DOI: 10.1016/j.ijid.2016.09.023 -
Food Additives & Contaminants. Part A,... Apr 2022Praziquantel (PZQ) is a pyrazino-isoquinoline compound with broad spectrum of activity against parasitic trematodes and cestodes, and a key veterinary drug in the...
Praziquantel (PZQ) is a pyrazino-isoquinoline compound with broad spectrum of activity against parasitic trematodes and cestodes, and a key veterinary drug in the parasitic disease control field. However, PZQ residues caused by non-conforming or excessive use in food-producing animals may pose a serious threat to human health. Herein, a simple, sensitive and reproducible LC-MS/MS method was developed for the simultaneous determination of praziquantel and - and -4-hydroxypraziquantel in black goat tissues to guide the reasonable use of PZQ. The mean recoveries for three target analytes were 71.2 ∼ 117.6%, and the limits of quantification were 1.0 μg/kg. Twenty-five healthy black goats were administered a single dose of praziquantel tablets at a dose of 35 mg/kg of body weight for residue elimination study, The results revealed that praziquantel and 4-hydroxypraziquantel were rapidly depleted in goat tissues and the elimination half-lives did not exceed 1 day in all tissues except for muscle and lung. It provides guidance for the establishment of maximum residue limit of praziquantel in goat.
Topics: Animals; Anthelmintics; Chromatography, Liquid; Goats; Muscles; Praziquantel; Tandem Mass Spectrometry
PubMed: 35394409
DOI: 10.1080/19440049.2022.2032380 -
Expert Opinion on Drug Delivery Apr 2022Infections caused by parasitic flatworms impose a considerable worldwide health burden. Recently, World Health Organization launched its roadmap for neglected diseases... (Review)
Review
INTRODUCTION
Infections caused by parasitic flatworms impose a considerable worldwide health burden. Recently, World Health Organization launched its roadmap for neglected diseases for the period 2021 to 2030 and oral treatment with praziquantel (PZQ) in tablet form is the main drug therapy for combating these diseases, but its use is limited by many drawbacks, including the high therapeutic dose due to the drug's low solubility and bioavailability. Among the strategies to improve PZQ performance, the use of drug nanocarriers has been cited as an interesting approach to overcome these pharmacological issues.
AREAS COVERED
This review focuses on the various types of nanomaterials (polymeric, lipidic, inorganic nanoparticles, and nanocrystals) which have been recently used to improve PZQ therapy. In addition, recent advances in PZQ nanoformulations, developed to overcome the barriers of the conventional drug are described.
EXPERT OPINION
Considering the poor rate of discovery in the anthelmintic segment observed in recent decades, the effective management of existing drugs has become essential. The application of new strategies based on nanotechnology can extend the useful life of PZQ in new and more effective formulations. Pharmaceutical nanotechnology can solve the pharmacokinetic challenges characteristic of PZQ and improve its solubility and bioavailability.
Topics: Anthelmintics; Biological Availability; Helminthiasis; Humans; Praziquantel; Solubility
PubMed: 35264036
DOI: 10.1080/17425247.2022.2051477 -
Antimicrobial Agents and Chemotherapy Aug 2018There is a growing consensus to include preschool-aged children in preventive chemotherapy programs with praziquantel to improve schistosomiasis control. However,...
There is a growing consensus to include preschool-aged children in preventive chemotherapy programs with praziquantel to improve schistosomiasis control. However, pharmacokinetic data, crucial to establish a safe and effective dose for this age group, are sparse. The objective of this study was to establish and compare the pharmacokinetic parameters of praziquantel in preschool- and school-aged children with schistosomiasis. Two pharmacokinetic trials in school- and preschool-aged children infected with or were conducted in Côte d'Ivoire. Dried blood spot samples were taken from 492 children at 10 time points following a single oral dose of 20, 40, or 60 mg/kg of body weight of praziquantel and analyzed using liquid chromatography-mass spectrometry. Noncompartmental analysis (NCA) was performed to obtain the pharmacokinetic parameters of -praziquantel (RPZQ), -praziquantel (SPZQ), and -4-hydroxy-praziquantel. No significant differences in pharmacokinetic parameters between species-specific infections were observed. While pharmacokinetic parameters differed significantly between age groups for , this trend was not observed with Neither the area under the curve (AUC) nor the maximal blood concentration () presented clear dose proportionality for R- and SPZQ. Logistic regression indicated a relationship between the RPZQ AUC and and the probability of cure. Praziquantel is subject to complex metabolic processes following erratic absorption. While the results of NCA are a very informative base for a better understanding of the drug, a more targeted approach in the form of population modeling is needed to quantify the factors influencing metabolic processes and draw conclusions.
Topics: Adolescent; Animals; Child; Child, Preschool; Chromatography, Liquid; Humans; Praziquantel; Schistosoma haematobium; Schistosoma mansoni; Schistosomiasis mansoni; Tandem Mass Spectrometry
PubMed: 29866859
DOI: 10.1128/AAC.02253-17