-
PLoS Pathogens Jul 2023Schistosomiasis, a severe parasitic disease, is primarily caused by Schistosoma mansoni, Schistosoma japonicum, or Schistosoma haematobium. Currently, praziquantel is... (Review)
Review
Schistosomiasis, a severe parasitic disease, is primarily caused by Schistosoma mansoni, Schistosoma japonicum, or Schistosoma haematobium. Currently, praziquantel is the only recommended drug for human schistosome infection. However, the lack of efficacy of praziquantel against juvenile worms and concerns about the emergence of drug resistance are driving forces behind the research for an alternative medication. Schistosomes are obligatory parasites that survive on nutrients obtained from their host. The ability of nutrient uptake depends on their physiological structure. In short, the formation and maintenance of the structure and nutrient supply are mutually reinforcing and interdependent. In this review, we focus on the structural features of the tegument, esophagus, and intestine of schistosomes and their roles in nutrient acquisition. Moreover, we introduce the significance and modes of glucose, lipids, proteins, and amino acids intake in schistosomes. We linked the schistosome structure and nutrient supply, introduced the currently emerging targets, and analyzed the current bottlenecks in the research and development of drugs and vaccines, in the hope of providing new strategies for the prevention and control of schistosomiasis.
Topics: Animals; Humans; Praziquantel; Schistosomiasis; Schistosoma japonicum; Schistosoma haematobium; Schistosoma mansoni; Eating
PubMed: 37498810
DOI: 10.1371/journal.ppat.1011498 -
International Journal of Pharmaceutics Sep 2023In this paper we report a successful example of combining drugs through cocrystallization. Specifically, the novel solid is formed by two anthelminthic drugs, namely...
In this paper we report a successful example of combining drugs through cocrystallization. Specifically, the novel solid is formed by two anthelminthic drugs, namely praziquantel (PZQ) and niclosamide (NCM) in a 1:3 molar ratio, and it can be obtained through a sustainable one-step mechanochemical process in the presence of micromolar amounts of methanol. The novel solid phase crystallizes in the monoclinic space group of P2/c, showing one PZQ and three NCM molecules linked through homo- and heteromolecular hydrogen bonds in the asymmetric unit, as also attested by SSNMR and FT-IR results. A plate-like habitus is evident from scanning electron microscopy analysis with a melting point of 202.89 °C, which is intermediate to those of the parent compounds. The supramolecular interactions confer favorable properties to the cocrystal, preventing NCM transformation into the insoluble monohydrate both in the solid state and in aqueous solution. Remarkably, the PZQ - NCM cocrystal exhibits higher anthelmintic activity against in vitro S. mansoni models than corresponding physical mixture of the APIs. Finally, due to in vitro promising results, in vivo preliminary tests on mice were also performed through the administration of minicapsules size M.
Topics: Animals; Mice; Praziquantel; Niclosamide; Antiparasitic Agents; Pharmaceutical Preparations; Spectroscopy, Fourier Transform Infrared; Anthelmintics; Schistosoma mansoni
PubMed: 37579827
DOI: 10.1016/j.ijpharm.2023.123315 -
Trends in Parasitology Apr 2013The occurrence of schistosomiasis within African infants and preschool children has been much better documented in recent years, revealing an important burden of disease... (Review)
Review
The occurrence of schistosomiasis within African infants and preschool children has been much better documented in recent years, revealing an important burden of disease previously overlooked. Despite mounting evidence showing that treatment with praziquantel is safe, beneficial, and could be delivered within ongoing public health interventions, young children still do not have satisfactory access to this drug, and a significant treatment gap exists. Progress towards resolution of this unfortunate health inequity is highlighted, including the development of an appropriate paediatric praziquantel formulation, and present blocks are identified on securing this issue within the international health agenda.
Topics: Africa; Animals; Anthelmintics; Child, Preschool; Humans; Infant; Praziquantel; Prevalence; Public Health; Schistosomiasis
PubMed: 23465781
DOI: 10.1016/j.pt.2013.02.001 -
Ui Sahak Aug 2021The Korean parasite control program is regarded as one of the most successful examples of health care movement in Korea. This 'Parasite Eradication Program' which was...
The Korean parasite control program is regarded as one of the most successful examples of health care movement in Korea. This 'Parasite Eradication Program' which was conducted from 1969 to 1995, involved testing and treating of 300 million people. In cooperation with Japan, parasitologists and activists who participated in the parasite control program formed a common system called the 'Mass Testing, Mass Treatment.' This study focuses on the localization process of Praziquantel, Clonorchiasis treatment production and its application in Clonorchiasis control program. Parasitologists rapidly introduced newly developed Praziquantel, and Korean chemists quickly reverse engineered the compound to evade patent issues. This allowed for the mass production of Praziquantel at a lower price, which in turn enabled a nationwide Clonorchiasis control program. At the same time, low price and stable supply opened the private market for Praziquantel. However, acceptance and understanding of the Praziquantel differed significantly among the stakeholders. For the government, it was a means for policy propaganda, and for the health agencies, it was a means for mass scale control program, while for the public, it was a means for maintaining conventional eating habits without risk of infection. This study reveals how the material end of a disease control policy is accepted and interpreted by different actors.
Topics: Animals; Clonorchiasis; Clonorchis sinensis; Humans; Japan; Praziquantel; Republic of Korea
PubMed: 34663774
DOI: 10.13081/kjmh.2021.30.317 -
International Journal For Parasitology.... Aug 2021Human schistosomiasis is a debilitating, life-threatening disease affecting more than 229 million people in as many as 78 countries. There is only one drug of choice... (Review)
Review
Human schistosomiasis is a debilitating, life-threatening disease affecting more than 229 million people in as many as 78 countries. There is only one drug of choice effective against all three major species of Schistosoma, praziquantel (PZQ). However, as with many monotherapies, evidence for resistance is emerging in the field and can be selected for in the laboratory. Previously used therapies include oxamniquine (OXA), but shortcomings such as drug resistance and affordability resulted in discontinuation. Employing a genetic, biochemical and molecular approach, a sulfotransferase (SULT-OR) was identified as responsible for OXA drug resistance. By crystallizing SmSULT- OR with OXA, the mode of action of OXA was determined. This information allowed a rational approach to novel drug design. Our team approach with schistosome biologists, medicinal chemists, structural biologists and geneticists has enabled us to develop and test novel drug derivatives of OXA to treat this disease. Using an iterative process for drug development, we have successfully identified derivatives that are effective against all three species of the parasite. One derivative CIDD-0149830 kills 100% of all three human schistosome species within 5 days. The goal is to generate a second therapeutic with a different mode of action that can be used in conjunction with praziquantel to overcome the ever-growing threat of resistance and improve efficacy. The ability and need to design, screen, and develop future, affordable therapeutics to treat human schistosomiasis is critical for successful control program outcomes.
Topics: Animals; Drug Discovery; Humans; Oxamniquine; Praziquantel; Schistosoma mansoni; Schistosomiasis
PubMed: 34111649
DOI: 10.1016/j.ijpddr.2021.05.002 -
Clinical Medicine (London, England) Oct 2011
Topics: Animals; Anthelmintics; Endemic Diseases; Humans; Life Cycle Stages; Praziquantel; Schistosoma; Schistosomiasis; Travel
PubMed: 22034712
DOI: 10.7861/clinmedicine.11-5-479 -
Molecules (Basel, Switzerland) Sep 2023It is estimated that 250 million people worldwide are affected by schistosomiasis. Disease transmission is related to the poor sanitation and hygiene habits that affect... (Review)
Review
It is estimated that 250 million people worldwide are affected by schistosomiasis. Disease transmission is related to the poor sanitation and hygiene habits that affect residents of impoverished regions in tropical and subtropical countries. The main species responsible for causing disease in humans are , , and , each with different geographic distributions. Praziquantel is the drug predominantly used to treat this disease, which offers low effectiveness against immature and juvenile parasite forms. In addition, reports of drug resistance prompt the development of novel therapeutic approaches. Natural products represent an important source of new compounds, especially those obtained from plant sources. This review compiles data from several in vitro and in vivo studies evaluating various compounds and essential oils derived from plants with cercaricidal and molluscicidal activities against both juvenile and adult forms of the parasite. Finally, this review provides an important discussion on recent advances in molecular and computational tools deemed fundamental for more rapid and effective screening of new compounds, allowing for the optimization of time and resources.
Topics: Humans; Animals; Anthelmintics; Schistosoma haematobium; Biological Products; Schistosomiasis; Praziquantel; Schistosoma mansoni
PubMed: 37836650
DOI: 10.3390/molecules28196807 -
Journal of Feline Medicine and Surgery Oct 2018Objectives The pharmacokinetics of praziquantel and pyrantel pamoate has never been reported in cats. The present study was designed to establish the plasma...
Objectives The pharmacokinetics of praziquantel and pyrantel pamoate has never been reported in cats. The present study was designed to establish the plasma concentration-time profile and to derive pharmacokinetic data for a combined formulation of praziquantel and pyrantel in cats, after a single, oral administration. Methods Twenty-two clinically healthy adult cats were used, each receiving a single oral dose of praziquantel (8.5 mg/kg) and pyrantel (100 mg/kg). Blood samples were collected at regular time points up to 48 h post-dosing. Plasma concentrations of praziquantel and pyrantel were measured using a liquid chromatography-mass spectrometry-high-throughput screening method. Results Clinical examination of all cats did not reveal any side effects after oral administration of these medications. The terminal half-life for praziquantel and pyrantel was 1.07 and 1.36 h, respectively. Praziquantel peak concentration (C) was 1140 μg/ml, reached at 1.22 h. The plasma concentrations of pyrantel after oral administration were low with a mean C of 0.11 μg/ml, reached at a T of 1.91 h. Pyrantel showed a very limited absorption as pamoate salt, suggesting permanence and efficacy inside the gastrointestinal tract, where the adult stages of most parasitic nematodes reside. Conclusions and relevance Pyrantel showed a very limited absorption as pamoate salt. Praziquantel was rapidly absorbed following oral administration and the concentrations achieved suggest that praziquantel could be an effective and safe medication in cats. Although some resistance problems are arising as a result of their long use, these anthelminthic products can still play a major role in parasitic control, especially in geographical areas where the high cost of newer treatments or necessity of parenteral administration could decrease the number of treated animals.
Topics: Administration, Oral; Animals; Anthelmintics; Area Under Curve; Cats; Drug Combinations; Female; Male; Praziquantel; Pyrantel Pamoate; Random Allocation; Treatment Outcome
PubMed: 29017390
DOI: 10.1177/1098612X17734065 -
Antimicrobial Agents and Chemotherapy May 2017Schistosomiasis, a major neglected tropical disease, affects more than 250 million people worldwide. Treatment of schistosomiasis has relied on the anthelmintic drug... (Review)
Review
Schistosomiasis, a major neglected tropical disease, affects more than 250 million people worldwide. Treatment of schistosomiasis has relied on the anthelmintic drug praziquantel (PZQ) for more than a generation. PZQ is the drug of choice for the treatment of schistosomiasis; it is effective against all major forms of schistosomiasis, although it is less active against juvenile than mature parasites. A pyrazino-isoquinoline derivative, PZQ is not considered to be toxic and generally causes few or transient, mild side effects. Increasingly, mass drug administration targeting populations in sub-Saharan Africa where schistosomiasis is endemic has led to the appearance of reduced efficacy of PZQ, which portends the selection of drug-resistant forms of these pathogens. The synthesis of improved derivatives of PZQ is attracting attention, e.g., in the (i) synthesis of drug analogues, (ii) rational design of pharmacophores, and (iii) discovery of new compounds from large-scale screening programs. This article reviews reports from the 1970s to the present on the metabolism and mechanism of action of PZQ and its derivatives against schistosomes.
Topics: Africa South of the Sahara; Animals; Drug Resistance; Humans; Praziquantel; Schistosoma; Schistosomiasis; Schistosomicides
PubMed: 28264841
DOI: 10.1128/AAC.02582-16 -
Infectious Diseases of Poverty Mar 2017The current approach of morbidity control of schistosomiasis, a helminth disease of poverty with considerable public health and socioeconomic impact, is based on... (Review)
Review
The current approach of morbidity control of schistosomiasis, a helminth disease of poverty with considerable public health and socioeconomic impact, is based on preventive chemotherapy with praziquantel. There is a pressing need for new drugs against this disease whose control entirely depends on this single drug that has been widely used over the past 40 years. We argue that a broader anthelminthic approach supplementing praziquantel with new antischistosomals targeting different parasite development stages would not only increase efficacy but also reduce the risk for drug resistance. Repositioning drugs already approved for other diseases provides a shortcut to clinical trials, as it is expected that such drugs rapidly pass the regulatory authorities. The antischistosomal properties of antimalarial drugs (e.g., semisynthetic artemisinins, synthetic trioxolanes, trioxaquines and mefloquine) and of drugs being developed or registered for other purposes (e.g., moxidectin and miltefosin), administered alone or in combination with praziquantel, have been tested in the laboratory and clinical trials. Another avenue to follow is the continued search for new antischistosomal properties in plants. Here, we summarise recent progress made in schistosomiasis chemotherapy, placing particular emphasis on repositioning of existing drugs against schistosomiasis.
Topics: Animals; Anthelmintics; Antimalarials; Drug Repositioning; Drug Resistance; Drug Therapy, Combination; Humans; Praziquantel; Public Health; Schistosoma; Schistosomiasis
PubMed: 28351414
DOI: 10.1186/s40249-017-0286-2