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Ugeskrift For Laeger May 2024
Topics: Humans; Male; Testicular Diseases; Schistosomiasis; Anthelmintics; Praziquantel; Adult
PubMed: 38808760
DOI: 10.61409/V72026 -
Cureus May 2024The incidence of human diphyllobothriasis is expected to rise amidst the current global popularity of Japanese cuisine, such as sushi, which contains raw fish. We report...
The incidence of human diphyllobothriasis is expected to rise amidst the current global popularity of Japanese cuisine, such as sushi, which contains raw fish. We report a case of a 10-year-old boy with a diphyllobothriasis infection acquired via sushi consumption. The patient was otherwise healthy, exhibited no symptoms, and was successfully treated with a single dose of 10 mg/kg praziquantel. In Japan, this parasite is known as "Sanada-mushi" because it resembles a Sanada cord. Prompt recognition of this parasite by evoking the Sanada cord's appearance may facilitate early diagnosis and treatment and increase public awareness to prevent diphyllobothriasis.
PubMed: 38803400
DOI: 10.7759/cureus.61147 -
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 -
Frontiers in Pharmacology 2024Schistosomiasis is a parasitic disease that endangers human health and social development. The granulomatous reaction of Schistosoma eggs in the liver is the main cause... (Review)
Review
Schistosomiasis is a parasitic disease that endangers human health and social development. The granulomatous reaction of Schistosoma eggs in the liver is the main cause of hepatosplenomegaly and fibrotic lesions. Anti liver fibrosis therapy is crucial for patients with chronic schistosomiasis. Although Praziquantel is the only clinical drug used, it is limited in insecticide treatment and has a long-term large-scale use, which is forcing the search for cost-effective alternatives. Previous research has demonstrated that plant metabolites and extracts have effective therapeutic effects on liver fibrosis associated with schistosomiasis. This paper summarizes the mechanisms of action of metabolites and some plant extracts in alleviating schistosomiasis-associated liver fibrosis. The analysis was conducted using databases such as PubMed, Google Scholar, and China National Knowledge Infrastructure (CNKI) databases. Some plant metabolites and extracts ameliorate liver fibrosis by targeting multiple signaling pathways, including reducing inflammatory infiltration, oxidative stress, inhibiting alternate macrophage activation, suppressing hepatic stellate cell activation, and reducing worm egg load. Natural products improve liver fibrosis associated with schistosomiasis, but further research is needed to elucidate the effectiveness of natural products in treating liver fibrosis caused by schistosomiasis, as there is no reported data from clinical trials in the literature.
PubMed: 38770001
DOI: 10.3389/fphar.2024.1332027 -
BMC Veterinary Research May 2024Although ultrasonography (US) has been widely used in the diagnosis of human diseases to monitor the progress of cystic echinococcosis (CE) control, the screening method...
BACKGROUND
Although ultrasonography (US) has been widely used in the diagnosis of human diseases to monitor the progress of cystic echinococcosis (CE) control, the screening method for hepatic CE in sheep flocks requires adjustment. In this study, we used a US scanner to screen sheep flocks and evaluated the efficacy of dosing dogs once a year with praziquantel for 7 years from 2014 to 2021.
METHODS
All sheep in the three flocks were screened using an ultrasound scanner in 2014 and compared with the prevalence of infection in 2021 in Bayinbuluke, Xinjiang, China. Sheep age was determined using incisor teeth. Cyst activity and calcification were determined using US images. The dogs were dewormed with praziquantel once a year to control echinococcosis in the community.
RESULTS
Three flocks had 968 sheep in 2014, with 13.22%, 22.62%, 18.7%, 27.27%, 11.88%, and 6.3% of sheep aged 1, 2, 3, 4, 5, and ≥ 6 years old, respectively. US scanning revealed that the overall CE prevalence was 38.43% (372/968), with active cysts and calcified cysts present in 9.40% (91/968) and 29.02% (281/968) of the sheep, respectively. For the young sheep aged 1 and 2 years, the prevalence of active and calcified cysts was: 1.56% and 0.91%, and 10.94% and 18.72%, respectively. Approximately 15.15% and 16.52% of the 4- and 5-year-old sheep, respectively, harbored active cysts. There was no significant difference in the infection rates of sheep between 2014 and 2021 (P > 0.05).
CONCLUSIONS
US is a practical tool for the field screening of CE in sheep flocks. One-third of the sheep population in the flocks was 1-2 years old, and these sheep played a very limited role in CE transmission, as most of the cysts were calcified. Old sheep, especially culled aged sheep, play a key role in the transmission of CE. Dosing dogs once a year did not affect echinococcosis control.
Topics: Animals; Sheep Diseases; Sheep; China; Ultrasonography; Echinococcosis, Hepatic; Prevalence; Dogs; Praziquantel; Anthelmintics; Female
PubMed: 38760783
DOI: 10.1186/s12917-024-04074-z -
PloS One 2024Hundreds of millions of doses of Praziquantel (PZQ) have been administered to persons with and without schistosomiasis living in schistosomiasis endemic settings,...
Praziquantel-related visual disorders among recipients in mass drug administration campaigns in schistosomiasis endemic settings: Systematic review and meta-analysis protocol.
BACKGROUND
Hundreds of millions of doses of Praziquantel (PZQ) have been administered to persons with and without schistosomiasis living in schistosomiasis endemic settings, through the mass drug administration (MDA) strategy which started in the early 2000s. A recent publication suggested high risk of PZQ-related visual disorders, raising public health concerns. We aim to systematically synthesize evidence on the magnitude of PZQ-related visual disorders.
METHODS
We will search PubMed, Google Scholar, CINAHL, SCOPUS, CENTRAL and LILACS from 1977 (when the first human clinical trials on PZQ started) to 31st May 2024, with no language restrictions. The key search terms will include "Praziquantel", "PZQ", "visual disorder", "adverse events", "side effects", "blurry vision" and "visual impairment" together with alternative terms and synonyms. All the countries endemic for schistosomiasis will be included as search terms. We will also search HINARI, Africa Journals Online, Thesis Databases and Preprint Repositories. Where necessary, we will contact expert researchers working in the field of schistosomiasis, UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), pharmaceutical industries, country-specific Food and Drug Authorities (FDAs) and the European Medicines Agency databases. We will search Conference Proceedings and reference lists of relevant studies for additional studies. At least two authors will independently select studies, extract data and assess risk of bias in the included studies. Any disagreements or discrepancies will be resolved through discussion between the reviewers. Heterogeneity will be explored graphically, and statistically using the I2-statistic. We will conduct random-effects meta-analysis when heterogeneity is appreciable, and express dichotomous outcomes (visual adverse events including excessive lacrimation, blurry vision and visual impairments) as risk ratio (RR) or Odds Ratio (OR) with their 95% confidence interval (CI). We will perform subgroup analysis to assess the impact of heterogeneity, and sensitivity analyses to test the robustness of the effect estimates. The overall level of evidence will be assessed using GRADE.
EXPECTED OUTCOMES
The present review expects to identify and categorize visual disorders occurring after administration of PZQ, alone or in combination with other drugs. By synthesizing the data from multiple studies, the review aims to present a quantitative assessment of the risk or odds of experiencing a visual disorder in different populations after ingesting PZQ. The review will also generate insights into whether PZQ in combination with other drugs are associated with increased odds of visual disorders and whether the occurrence of visual disorders correlates with dosage or treatment duration. Policymakers, public health experts and stakeholders could rely on the review findings to deliver context-sensitive preventive chemotherapy programs by adjusting drug combinations or dosing schedules to reduce risk of visual adverse effects in populations treated with PZQ. The review aims to identify gaps in the current evidence regarding visual disorders following PZQ administration in schistosomiasis endemic settings which can serve as the basis for future research on important but unanswered questions.
DISSEMINATION AND PROTOCOL REGISTRATION
The findings of this study will be disseminated through stakeholder forums, conferences, and peer-review publications. The review protocol has been registered in the International Prospective Register for Systematic Reviews (PROSPERO)- CRD42023417963.
Topics: Humans; Schistosomiasis; Praziquantel; Vision Disorders; Systematic Reviews as Topic; Mass Drug Administration; Meta-Analysis as Topic; Endemic Diseases; Anthelmintics
PubMed: 38758736
DOI: 10.1371/journal.pone.0300384 -
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 -
Respiratory Medicine Case Reports 2024Katayama syndrome is an acute manifestation of schistosomiasis, a parasitic infection that manifests itself through a hypersensitivity reaction to migrating larvae and...
BACKGROUND
Katayama syndrome is an acute manifestation of schistosomiasis, a parasitic infection that manifests itself through a hypersensitivity reaction to migrating larvae and early egg deposition. Left undiagnosed and untreated, acute schistosomiasis can develop into chronic schistosomiasis which can lead to debilitating morbidity such as pulmonary hypertension. This case highlights that Katayama syndrome can also been seen in regions where the parasite is not endemic, as it occurs in travelers returning from endemic regions or in immigrants.
CASE PRESENTATION
We describe the case of a 26-year-old asthmatic male, who presented with systemic symptoms including fever, myalgia, night sweats as well as gastro-intestinal and pulmonary complaints since five days. At presentation, there was a raised blood eosinophil count and nodular lesions were seen on computed tomography. After considering diagnoses such as tuberculosis, vasculitis and hypereosinophilic syndrome, it was repeated history taking that revealed that the patient had suffered from swimmer's itch during a stay in Guinea. A stool sample showed microscopic presence of Schistosoma mansoni eggs, confirming the diagnosis of Katayama syndrome. The patient was treated with tapered corticosteroids to suppress the hypersensitivity reaction and praziquantel was added to cure the parasitic infection. This led to a complete resolution of the patients' symptoms and radiological abnormalities. Negative stool samples confirmed the eradication of the schistosomes.
CONCLUSIONS
Swimmer's itch and Katayama syndrome are manifestations of acute schistosomiasis. It is important to recognize the syndrome, because early diagnosis and adequate treatment can prevent chronic disease and significant morbidity.
PubMed: 38737518
DOI: 10.1016/j.rmcr.2024.102032 -
Molecules (Basel, Switzerland) Apr 2024The burden of human schistosomiasis, a known but neglected tropical disease in Sub-Saharan Africa, has been worrisome in recent years. It is becoming increasingly...
The burden of human schistosomiasis, a known but neglected tropical disease in Sub-Saharan Africa, has been worrisome in recent years. It is becoming increasingly difficult to tackle schistosomiasis with praziquantel, a drug known to be effective against all , due to reports of reduced efficacy and resistance. Therefore, this study seeks to investigate the antischistosomal potential of phytochemicals from against proteins that have been implicated as druggable targets for the treatment of schistosomiasis using computational techniques. In this study, sixty-three (63) previously isolated and characterized phytochemicals from were identified from the literature and retrieved from the PubChem database. In silico screening was conducted to assess the inhibitory potential of these phytochemicals against three receptors ( Thioredoxin glutathione reductase, dihydroorotate dehydrogenase, and Arginase) that may serve as therapeutic targets for schistosomiasis treatment. Molecular docking, ADMET prediction, ligand interaction, MMGBSA, and molecular dynamics simulation of the hit compounds were conducted using the Schrodinger molecular drug discovery suite. The results show that Andrographolide possesses a satisfactory pharmacokinetic profile, does not violate the Lipinski rule of five, binds with favourable affinity with the receptors, and interacts with key amino acids at the active site. Importantly, its interaction with dihydroorotate dehydrogenase, an enzyme responsible for the catalysis of the de novo pyrimidine nucleotide biosynthetic pathway rate-limiting step, shows a glide score and MMGBSA of -10.19 and -45.75 Kcal/mol, respectively. In addition, the MD simulation shows its stability at the active site of the receptor. Overall, this study revealed that Andrographolide from could serve as a potential lead compound for the development of an anti-schistosomal drug.
Topics: Azadirachta; Molecular Docking Simulation; Dihydroorotate Dehydrogenase; Animals; Schistosomiasis; Oxidoreductases Acting on CH-CH Group Donors; Humans; Phytochemicals; Molecular Dynamics Simulation; Schistosoma mansoni; NADH, NADPH Oxidoreductases; Plant Extracts; Computer Simulation; Schistosomicides; Multienzyme Complexes; Praziquantel
PubMed: 38731401
DOI: 10.3390/molecules29091909 -
BioRxiv : the Preprint Server For... Apr 2024The bitter taste of medicines hinders patient compliance, but not everyone experiences these difficulties because people worldwide differ in their bitterness perception....
The bitter taste of medicines hinders patient compliance, but not everyone experiences these difficulties because people worldwide differ in their bitterness perception. To better understand how people from diverse ancestries perceive medicines and taste modifiers, 338 adults, European and recent US and Canada immigrants from Asia, South Asia, and Africa, rated the bitterness intensity of taste solutions on a 100-point generalized visual analog scale and provided a saliva sample for genotyping. The taste solutions were five medicines, tenofovir alafenamide (TAF), moxifloxacin, praziquantel, amodiaquine, and propylthiouracil (PROP), and four other solutions, TAF mixed with sucralose (sweet, reduces bitterness) or 6-methylflavone (tasteless, reduces bitterness), sucralose alone, and sodium chloride alone. Bitterness ratings differed by ancestry for two of the five drugs (amodiaquine and PROP) and for TAF mixed with sucralose. Genetic analysis showed that people with variants in one bitter receptor variant gene (38) reported PROP was more bitter than did those with a different variant (p= 7.6e-19) and that people with either an or a genotype found sucralose more bitter than did others (p=2.6e-8, p=7.9e-11, resp.). Our findings may help guide the formulation of bad-tasting medicines to meet the needs of those most sensitive to them.
PubMed: 38712219
DOI: 10.1101/2024.04.24.590957