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Journal of Parasitic Diseases :... Jun 2024Echinochasmidae are considered one of the digenean intestinal parasites of carnivorous mammals and humans. Some larvicidal medications, such as praziquantel and...
Echinochasmidae are considered one of the digenean intestinal parasites of carnivorous mammals and humans. Some larvicidal medications, such as praziquantel and albendazole, were employed to interrupt the life cycle of Echinochasmidae, which may cause harmful and serious effects on the domestic fish, ducks, and humans in our ecosystem. Cercariae of sp. (gymnocephalus type) were harvested by exposing snails to strong artificial illumination. The emerging cercariae were exposed in vitro to different concentrations of praziquantel and albendazole at the same period of incubation 12 h. Using probit analysis in SPSS version 25, the lethal concentrations 50 and 95% were determined. They were 0.036 and 0.82 ppm, respectively, for praziquantel and 5.3 and 9.2 ppm, respectively, for albendazole. The ultrastructural changes using scanning electron microscope on the tegumental surface of the treated cercariae with the two drugs were compared to the untreated cercariae. The untreated cercariae have a pear-shaped body with a long tail. The oral sucker is armed with a spiny collar and decorated with ciliated and unciliated sensory papillae. The cardinal ventral sucker has a thick, muscular wall. The cercarial tail is decorated with parallel longitudinal tegumental processes and spherical, unciliated papillae. In comparisons, cercariae treated with both drugs lost all healthy morphological features, but in varying degrees and effects between the two drugs. Our findings suggest that the use of both drugs can be recommended during the design of control strategies to combat this type of intestinal parasite.
PubMed: 38840870
DOI: 10.1007/s12639-024-01670-6 -
European Journal of Medical Research Jul 2023Infection with Schistosoma sp. during pregnancy can cause low birth weight of the newborn. To allow a better differentiation between newborns with low birth weight and...
Infection with Schistosoma sp. during pregnancy can cause low birth weight of the newborn. To allow a better differentiation between newborns with low birth weight and those with normal weight, the terms of intrauterine growth restriction (IUGR), small for gestational age (SGA) or fetal growth restriction (FGR) should be used. FGR describes the relationship between birth weight and gestational age and is defined as the incapability of a fetus to achieve expected growth with birth weight below the 10th percentile for gestational age. Additional investigations of the proportion of newborns with FGR should obtain more certainty about the effect of praziquantel and schistosomiasis on fetal growth.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Praziquantel; Birth Weight; Schistosomiasis; Fetus
PubMed: 37434209
DOI: 10.1186/s40001-023-01202-7 -
PLoS Neglected Tropical Diseases Feb 2024The drug praziquantel (PZQ) has served as the long-standing drug therapy for treatment of infections caused by parasitic flatworms. These encompass diseases caused by... (Review)
Review
The drug praziquantel (PZQ) has served as the long-standing drug therapy for treatment of infections caused by parasitic flatworms. These encompass diseases caused by parasitic blood, lung, and liver flukes, as well as various tapeworm infections. Despite a history of clinical usage spanning over 4 decades, the parasite target of PZQ has long resisted identification. However, a flatworm transient receptor potential ion channel from the melastatin subfamily (TRPMPZQ) was recently identified as a target for PZQ action. Here, recent experimental progress interrogating TRPMPZQ is evaluated, encompassing biochemical, pharmacological, genetic, and comparative phylogenetic data that highlight the properties of this ion channel. Various lines of evidence that support TRPMPZQ being the therapeutic target of PZQ are presented, together with additional priorities for further research into the mechanism of action of this important clinical drug.
Topics: Praziquantel; Anthelmintics; Phylogeny; Transient Receptor Potential Channels
PubMed: 38358948
DOI: 10.1371/journal.pntd.0011929 -
Scientific Reports May 2024Metabolism of praziquantel (PZQ), a racemic mixture and the only drug approved to treat S. mansoni infection, is mediated by genetically polymorphic enzymes. Periodic...
Metabolism of praziquantel (PZQ), a racemic mixture and the only drug approved to treat S. mansoni infection, is mediated by genetically polymorphic enzymes. Periodic school-based mass drug administration (MDA) with PZQ is the core intervention to control schistosomiasis. However data on the impact of pharmacogenetic variation, nutrition, and infection status on plasma PZQ exposure is scarce. We investigated genetic and non-genetic factors influencing PZQ plasma concentration and its metabolic ratios (trans-4-OH-PZQ/PZQ and cis-4-OH-PZQ/PZQ). Four hundred forty-six school children aged 7-15 years from four primary schools in southern Ethiopia who received albendazole and PZQ preventive chemotherapy through MDA campaign were enrolled. Genotyping for common functional variants of CYP3A4 (*1B), CYP3A5 (*3, *6), CYP2C19 (*2, *3, *17), CYP2C9 (*2, *3), and CYP2J2*7 was performed. Plasma concentrations of PZQ, trans-4-OH-PZQ, and cis-4-OH-PZQ were quantified using UPLCMS/MS. Carriers of CYP2C19 defective variant alleles (*2 and *3) had significantly higher mean PZQ plasma concentration than CYP2C19*1/*1 or *17 carriers (p = 0.005). CYP2C19*1/*1 and CYP2C19*17 carriers had higher trans-4-OH-PZQ/PZQ and cis-4-OH-PZQ/PZQ metabolic ratios compared with CYP2C19*2 or *3 carriers (p < 0.001). CYP2J2*7 carriers had lower mean PZQ plasma concentration (p = 0.05) and higher trans-4-OH-PZQ/PZQ and cis-4-OH-PZQ/PZQ metabolic ratios. Male participants had significantly higher PZQ concentration (p = 0.006) and lower metabolic ratios (p = 0.001) than females. There was no significant effect of stunting, wasting, S. mansoni or soil-transmitted helminth infections, CYP3A4, CYP3A5, or CYP2C9 genotypes on plasma PZQ or its metabolic ratios. In conclusion, sex, CYP2C19 and CYP2J2 genotypes significantly predict PZQ plasma exposure among Ethiopian children. The impact of CYP2C19 and CYP2J2 genotypes on praziquantel treatment outcomes requires further investigation.
Topics: Humans; Praziquantel; Child; Male; Female; Ethiopia; Adolescent; Cytochrome P-450 CYP2C19; Genotype; Cytochrome P-450 Enzyme System; Anthelmintics; Schistosomiasis mansoni
PubMed: 38778126
DOI: 10.1038/s41598-024-62669-w -
ACS Medicinal Chemistry Letters May 2024To investigate the physicochemical properties of anti-schistosomal compounds reported between 2008 and 2023, a simple but extensive literature scrutiny was conducted....
To investigate the physicochemical properties of anti-schistosomal compounds reported between 2008 and 2023, a simple but extensive literature scrutiny was conducted. Keywords were searched in Chemical Abstracts Service (CAS) SciFinder and primary medicinal chemistry and pharmacology literature to locate publications with compounds displaying and/or anti-schistosomal activity. A total of 57 repurposed U.S. Food and Drug Administration (FDA)-approved drugs, hits and their derivatives were manually extracted, curated and compared to known anti-schistosomal oral drugs in view of establishing trends of calculated critical molecular properties. From this analysis, it was determined that more than 65% of the compounds display cLogD > 3 values, whereas oxamniquine, metrifonate and praziquantel (PZQ), previous and currently used oral anti-schistosomal drugs, possess lower cLogD values (≤2.5). Furthermore, the lipophilicity associated with PZQ corresponds to a highly permeable and sparingly soluble compound, characteristics that favor drug absorption and compound penetration in the parasite. These physicochemical properties together with PZQ's anti-schistosomal activity make PZQ an essential medicine for the treatment of schistosomiasis and demonstrate the importance of finding the right balance among potency (e.g., EC < 5 and 0.5 μM), cell permeability (e.g., > 2 × 10 cm/s) and kinetic aqueous solubility (e.g., >10 μM) to provide high-quality hits and/or leads for the discovery of new oral anti-schistosomal therapeutics.
PubMed: 38746890
DOI: 10.1021/acsmedchemlett.4c00026 -
Veterinarni Medicina Feb 2024The study aimed to evaluate and compare the routes and rates of the depletion of the antiparasitic praziquantel (PZQ), a derivative of pyrazinoisoquinoline,...
The study aimed to evaluate and compare the routes and rates of the depletion of the antiparasitic praziquantel (PZQ), a derivative of pyrazinoisoquinoline, following its oral administration in grass carp (). We focused on the depletion of PZQ and its major metabolites - -hydroxy praziquantel (CPZQ) and -hydroxy praziquantel (TPZQ), in water, the plasma, hepatopancreas, kidney, muscle, and skin, following a single oral administration of PZQ in a concentration of 50 mg/kg. Fish were sampled before the drug administration and then eight times in the course of the 30-day-long experiment. Our results indicate the rapid absorption and elimination of PZQ and its metabolites in all the analysed matrices. The most PZQ-burdened tissue was the hepatopancreas, the gill and the skin. In all the samples, the concentration of the drug and its metabolites consistently declined over time. The residue of the parent compound was detected for the longest time in all the tissues. During the study, a significant ( < 0.01) correlation was found within the concentration of PZQ, CPZQ, and TPZQ in the water and all the biological matrices. It was also found that the PZQ residue was not detected below the maximum residue levels (i.e., 20 μg/kg) until 16 days after exposure in the muscle and skin.
PubMed: 38550621
DOI: 10.17221/109/2023-VETMED -
Immunotherapy Advances 2023Control of schistosomiasis depends on a single drug, praziquantel, with variable cure rates, high reinfection rates, and risk of drug resistance. A vaccine could...
Control of schistosomiasis depends on a single drug, praziquantel, with variable cure rates, high reinfection rates, and risk of drug resistance. A vaccine could transform schistosomiasis control. Preclinical data show that vaccine development is possible, but conventional vaccine efficacy trials require high incidence, long-term follow-up, and large sample size. Controlled human infection studies (CHI) can provide early efficacy data, allowing the selection of optimal candidates for further trials. A CHI has been established in the Netherlands but responses to infection and vaccines differ in target populations in endemic countries. We aim to develop a CHI for in Uganda to test candidate vaccines in an endemic setting. This is an open-label, dose-escalation trial in two populations: minimal, or intense, prior exposure. In each population, participants will be enrolled in sequential dose-escalating groups. Initially, three volunteers will be exposed to 10 cercariae. If all show infection, seven more will be exposed to the same dose. If not, three volunteers in subsequent groups will be exposed to higher doses (20 or 30 cercariae) following the same algorithm, until all 10 volunteers receiving a particular dose become infected, at which point the study will be stopped for that population. Volunteers will be followed weekly after infection until CAA positivity or to 12 weeks. Once positive, they will be treated with praziquantel and followed for one year. The trial registry number is ISRCTN14033813 and all approvals have been obtained. The trial will be subjected to monitoring, inspection, and/or audits.
PubMed: 37538934
DOI: 10.1093/immadv/ltad010 -
Journal of Travel Medicine Nov 2023We report on six patients with suspected chronic schistosomiasis and negative microbiological findings at baseline. All patients were treated empirically with...
We report on six patients with suspected chronic schistosomiasis and negative microbiological findings at baseline. All patients were treated empirically with praziquantel and all seroconverted 20 days to two months after treatment. We suggest that seroconversion after praziquantel treatment may be used as a confirmatory diagnostic tool for chronic schistosomiasis.
Topics: Humans; Praziquantel; Seroconversion; Schistosomiasis
PubMed: 37418150
DOI: 10.1093/jtm/taad091 -
Antimicrobial Agents and Chemotherapy May 2024Schistosomiasis, a widespread parasitic disease caused by the blood fluke of the genus , affects over 230 million people, primarily in developing countries....
Schistosomiasis, a widespread parasitic disease caused by the blood fluke of the genus , affects over 230 million people, primarily in developing countries. Praziquantel, the sole drug currently approved for schistosomiasis treatment, demonstrates effectiveness against patent infections. A recent study highlighted the antiparasitic properties of amiodarone, an anti-arrhythmic drug, exhibiting higher efficacy than praziquantel against prepatent infections. This study assessed the efficacy of amiodarone and praziquantel, both individually and in combination, against through comprehensive and experiments. experiments demonstrated synergistic activity (fractional inhibitory concentration index ≤0.5) for combinations of amiodarone with praziquantel. In a murine model of schistosomiasis featuring prepatent infections, treatments involving amiodarone (200 or 400 mg/kg) followed by praziquantel (200 or 400 mg/kg) yielded a substantial reduction in worm burden (60%-70%). Given the low efficacy of praziquantel in prepatent infections, combinations of amiodarone with praziquantel may offer clinical utility in the treatment of schistosomiasis.
PubMed: 38780260
DOI: 10.1128/aac.00114-24 -
[Histone deacetylase and histone acetyltransferase inhibitors as antischistosomal agents: a review].Zhongguo Xue Xi Chong Bing Fang Zhi Za... Mar 2024Schistosomiasis is a neglected zoonotic parasitic disease. Currently, praziquantel is the drug of choice for the treatment of schistosomiasis, and is the only effective... (Review)
Review
Schistosomiasis is a neglected zoonotic parasitic disease. Currently, praziquantel is the drug of choice for the treatment of schistosomiasis, and is the only effective chemical for treatment of schistosomiasis japonica. Since its introduction in the 1970s, praziquantel has been used for large-scale chemotherapy of schistosomiasis for over 40 years. However, there have been reports pertaining to the resistance to praziquantel in schistosomes. Therefore, development of novel antischistosomal agents as alternatives of praziquantel, is of great need. Histone deacetylases and histone acetyltransferases have been recently reported to play critical roles in the growth, development and reproduction of schistosomes, and are considered as potential drug targets for the treatment of schistosomiasis. This review summarizes the latest advances of histone deacetylase and histone acetyltransferase inhibitors in the research on antischistosomal drugs, so as to provide insights into research and development of novelantischistosomal agents.
Topics: Animals; Histone Deacetylase Inhibitors; Histone Acetyltransferases; Humans; Histone Deacetylases; Schistosoma; Schistosomiasis; Schistosomicides
PubMed: 38857968
DOI: 10.16250/j.32.1374.2023178