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Brazilian Journal of Biology = Revista... 2023Schistosomiasis, caused by Schistosoma mansoni Sambon, 1907, is a severe and widely distributed parasitic disease, affecting about 200 million people worldwide. The...
The schistosomicidal activity of ethanolic extracts from branches, leaves, flowers and fruits of Handroanthus impetiginosus (Mart. ex DC.) Mattos (Bignoniaceae) plant and metabolic profile characterization by UPLC-ESI-QTOF analysis.
Schistosomiasis, caused by Schistosoma mansoni Sambon, 1907, is a severe and widely distributed parasitic disease, affecting about 200 million people worldwide. The disease is recognized by elevated mortality rates, especially among those living in areas of poor sanitation. Currently, the chemotherapeutic treatment is solely based on using the praziquantel drug. Therefore, there is a need for the discovery of new medicines for the treatment of this parasitosis. Thus, this work aimed to evaluate the schistosomicidal activity of ethanolic crude extracts from the branches, leaves, flowers, and fruits of Handroanthus impetiginosus (Mart ex DC.) Masttos and characterize its metabolic profile by UPLC-ESI-QTOF analysis. Evaluation of plant extract on S. mansoni was carried out in adult worms in vitro, in which the mortality rate was quantified, and the damages in the tegument of the worms were monitored. All extracts induced changes in the viability of adult males of S. mansoni, causing the death of the parasites, which was directly dependent of the concentration.
Topics: Humans; Male; Schistosomicides; Tabebuia; Bignoniaceae; Fruit; Ethanol; Flowers; Plant Extracts
PubMed: 37970906
DOI: 10.1590/1519-6984.275824 -
ACS Medicinal Chemistry Letters Nov 2023The anthelmintic drug praziquantel remains a key clinical therapy for treating various diseases caused by parasitic flatworms. The parasite target of praziquantel has...
The anthelmintic drug praziquantel remains a key clinical therapy for treating various diseases caused by parasitic flatworms. The parasite target of praziquantel has remained undefined despite longstanding usage in the clinic, although a candidate ion channel target, named TRPM, has recently been identified. Intriguingly, certain praziquantel derivatives show different activities against different parasites: for example, some praziquantel analogs are considerably more active against cestodes than against schistosomes. Here we interrogate whether the different activities of praziquantel analogs against different parasites are also reflected by unique structure-activity relationships at the TRPM channels found in these different organisms. To do this, several praziquantel analogs were synthesized and functionally profiled against schistosome and cestode TRPM channels. Data demonstrate that structure-activity relationships are closely mirrored between parasites and their TRPM orthologs, providing further support for TRPM as the therapeutically relevant target of praziquantel.
PubMed: 37970586
DOI: 10.1021/acsmedchemlett.3c00350 -
PLoS Neglected Tropical Diseases Nov 2023Over 290 million people are infected by schistosomes worldwide. Schistosomiasis control efforts focus on mass drug treatment with praziquantel (PZQ), a drug that kills...
Over 290 million people are infected by schistosomes worldwide. Schistosomiasis control efforts focus on mass drug treatment with praziquantel (PZQ), a drug that kills the adult worm of all Schistosoma species. Nonetheless, re-infections have continued to be detected in endemic areas with individuals living in the same area presenting with varying infection intensities. Our objective was to characterize the transcriptome profiles in peripheral blood of children between 10-15 years with varying intensities of Schistosoma mansoni infection living along the Albert Nile in Uganda. RNA extracted from peripheral blood collected from 44 S. mansoni infected (34 high and 10 low by circulating anodic antigen [CAA] level) and 20 uninfected children was sequenced using Illumina NovaSeq S4 and the reads aligned to the GRCh38 human genome. Differential gene expression analysis was done using DESeq2. Principal component analysis revealed clustering of gene expression by gender when S. mansoni infected children were compared with uninfected children. In addition, we identified 14 DEGs between S. mansoni infected and uninfected individuals, 56 DEGs between children with high infection intensity and uninfected individuals, 33 DEGs between those with high infection intensity and low infection intensity and no DEGs between those with low infection and uninfected individuals. We also observed upregulation and downregulation of some DEGs that are associated with fibrosis and its regulation. These data suggest expression of fibrosis associated genes as well as genes that regulate fibrosis in S. mansoni infection. The relatively few significant DEGS observed in children with schistosomiasis suggests that chronic S. mansoni infection is a stealth infection that does not stimulate a strong immune response.
Topics: Adult; Animals; Humans; Child; Schistosoma mansoni; Anthelmintics; Uganda; Schistosomiasis mansoni; Schistosomiasis; Gene Expression Profiling
PubMed: 37967122
DOI: 10.1371/journal.pntd.0011455 -
Frontiers in Veterinary Science 2023Milbemycin oxime (MBO) and praziquantel (PZQ) have a broad spectrum of biological activity and are commonly used to treat the parasitic infection in the veterinary...
Development and validation of an LC-MS/MS method for the simultaneous quantification of milbemycin oxime and praziquantel in plasma: application to a pharmacokinetic study in cats.
INTRODUCTION
Milbemycin oxime (MBO) and praziquantel (PZQ) have a broad spectrum of biological activity and are commonly used to treat the parasitic infection in the veterinary clinic. In this study, a fast and efficient LC-MS/MS method was established and validated for the simultaneous determination of MBO, PZQ, cis-4-hydroxylated-PZQ (C-4-OH-PZQ) and trans-4-hydroxylated-PZQ (T-4-OH-PZQ) and in cat plasma.
METHODS
Extraction of analytes and internal standards from cat plasma by acetonitrile protein precipitation, allows rapid processing of large batches of samples. MBO, PZQ, C-4-OH-PZQ, T-4-OH-PZQ, and internal standard (IS) were eluted for 13.5 min on a C column with a 0.1% formic acid water/acetonitrile mixture as the mobile phase.
RESULTS
Results showed that the method had good precision, accuracy, recovery, and linearity. The linearity range was 2.5-250 ng/mL for MBO, and 10-1000 ng/mL for PZQ, C-4-OH-PZQ, and T-4-OH-PZQ. The intra-day and inter-day precision CV values of the tested components were within 15%. The extraction recoveries of the four components ranged from 98.09% to 107.46%. The analytes in plasma remained stable for 6 h at room temperature, 26 h in the autosampler (4 °C), after freeze-thaw (-20°C) cycles, and 60 days in a -20°C freezer. Method sensitivity sufficed for assessing pharmacokinetic parameters of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ in plasma samples with LLOQ of 2.5 ng/mL for MBO and 10 ng/mL for PZQ, C-4-OH-PZQ, and T-4-OH-PZQ.
CONCLUSION
In this study, a selective and sensitive LC-MS/MS method for the simultaneous quantification of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ in cat plasma was developed and validated.This method had been successfully applied to evaluate the pharmacokinetics of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ after a single oral administration of 8 mg MBO and 20 mg PZQ in cats.
PubMed: 37964913
DOI: 10.3389/fvets.2023.1285932 -
Pharmacogenomics and Personalized... 2023This study aimed to discern the association between PLP2 expression, its biological significance, and the extent of immune infiltration in human GBM.
OBJECTIVE
This study aimed to discern the association between PLP2 expression, its biological significance, and the extent of immune infiltration in human GBM.
METHODS
Utilizing the GEPIA2 and TCGA databases, we contrasted the expression levels of PLP2 in GBM against normal tissue. We utilized GEPIA2 and LinkedOmics for survival analysis, recognized genes co-expressed with PLP2 via cBioPortal and GEPIA2, and implemented GO and KEGG analyses. The STRING database facilitated the construction of protein-protein interaction networks. We evaluated the relationship of PLP2 with tumor immune infiltrates using ssGSEA and the TIMER 2.0 database. An IHC assay assessed PLP2 and PDL-1 expression in GBM tissue, and the Drugbank database aided in identifying potential PLP2-targeting compounds. Molecular docking was accomplished using Autodock Vina 1.2.2.
RESULTS
PLP2 expression was markedly higher in GBM tissues in comparison to normal tissues. High PLP2 expression correlated with a decrease in overall survival across two databases. Functional analyses highlighted a focus of PLP2 functions within leukocyte. Discrepancies in PLP2 expression were evident in immune infiltration, impacting CD4+ T cells, neutrophils, myeloid dendritic cells, and macrophages. There was a concomitant increase in PLP2 and PD-L1 expression in GBM tissues, revealing a link between the two. Molecular docking with ethosuximide and praziquantel yielded scores of -7.441 and -4.295 kcal/mol, correspondingly.
CONCLUSION
PLP2's upregulation in GBM may adversely influence the lifespan of GBM patients. The involvement of PLP2 in pathways linked to leukocyte function is suggested. The positive correlation between PLP2 and PD-L1 could provide insights into PLP2's role in glioma modulation. Our research hints at PLP2's potential as a therapeutic target for GBM, with ethosuximide and praziquantel emerging as potential treatment candidates, especially emphasizing the potential of these compounds in GBM treatment targeting PLP2.
PubMed: 37964785
DOI: 10.2147/PGPM.S425251 -
BioRxiv : the Preprint Server For... Nov 2023We previously performed a genome-wide association study (GWAS) to identify the genetic basis of praziquantel (PZQ) response in schistosomes, identifying two quantitative...
We previously performed a genome-wide association study (GWAS) to identify the genetic basis of praziquantel (PZQ) response in schistosomes, identifying two quantitative trait loci (QTL) situated on chromosome 2 and chromosome 3. We reanalyzed this GWAS using the latest (v10) genome assembly showing that a single locus on chromosome 3, rather than two independent loci, determines drug response. These results reveal that praziquantel response is monogenic and demonstrates the importance of high-quality genomic information.
PubMed: 37961217
DOI: 10.1101/2023.11.01.565202 -
Malaria Journal Nov 2023The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that... (Randomized Controlled Trial)
Randomized Controlled Trial
Feasibility and safety of integrating mass drug administration for helminth control with seasonal malaria chemoprevention among Senegalese children: a randomized controlled, observer-blind trial.
BACKGROUND
The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that may help to achieve elimination of malaria and helminths. A randomized, controlled, observer-blind trial was conducted to assess the feasibility and safety of combining mass drug administration (MDA) for schistosomiasis and soil transmitted helminths (STH) with seasonal malaria chemoprevention (SMC) among children living in Senegal.
METHODS
Female and male children aged 1-14 years were randomized 1:1:1, to receive Vitamin A and Zinc on Day 0, followed by SMC drugs (sulfadoxine-pyrimethamine and amodiaquine) on Days 1-3 (control group); or praziquantel and Vitamin A on Day 0, followed by SMC drugs on Days 1-3 (treatment group 1); or albendazole and praziquantel on Day 0, followed by SMC drugs on Days 1-3 (treatment group 2). Safety assessment was performed by collecting adverse events from all children for six subsequent days following administration of the study drugs. Pre- and post-intervention, blood samples were collected for determination of haemoglobin concentration, malaria microscopy, and PCR assays. Stool samples were analyzed using Kato-Katz, Merthiolate-iodine-formalin and PCR methods. Urine filtration, PCR and circulating cathodic antigen tests were also performed.
RESULTS
From 9 to 22 June 2022, 627 children aged 1-14 years were randomized into the three groups described above. Mild, transient vomiting was observed in 12.6% (26/206) of children in treatment group 2, in 10.6% (22/207) in group 1, and in 4.2% (9/214) in the control group (p = 0.005). Pre-intervention, the geometric mean value of Plasmodium falciparum parasite density was highest among children who received albendazole, praziquantel with SMC drugs. Post-intervention, the parasite density was highest among children who received SMC drugs only. Children who received praziquantel and SMC drugs had a lower risk of developing severe anaemia than their counterparts who received SMC drugs alone (OR = 0.81, 95% CI 0.13-5.00, p = 0.63).
CONCLUSIONS
Integration of MDA for helminths with SMC drugs was safe and feasible among Senegalese children. These findings support further evaluation of the integrated control model.
TRIAL REGISTRATION
The study is registered at Clinical Trial.gov NCT05354258.
Topics: Animals; Humans; Child; Male; Female; Antimalarials; Praziquantel; Albendazole; Mass Drug Administration; Seasons; Feasibility Studies; Vitamin A; Malaria; Helminths; Chemoprevention
PubMed: 37957702
DOI: 10.1186/s12936-023-04784-z -
Current Research in Parasitology &... 2023The miticide efficacy of a single treatment with Felpreva® (tigolaner, emodepside and praziquantel) spot-on solution for cats was evaluated in two European field...
Field efficacy and safety of Felpreva® (tigolaner, emodepside and praziquantel) spot-on for the treatment of natural ear mite infestations () and notoedric mange () in cats.
The miticide efficacy of a single treatment with Felpreva® (tigolaner, emodepside and praziquantel) spot-on solution for cats was evaluated in two European field studies. One study was conducted in cats naturally infested with . The other study was conducted in cats naturally infested with . In both studies, the presence of viable mites was confirmed prior to treatment (Day -1/Day 0) and re-evaluated on Day 14 ( study) and on Day 28 (both studies). Efficacy was calculated based on the number of viable mites found after treatment. In the study, the primary criterion was the percentage of mite-free cats after treatment with Felpreva® compared to a sarolaner/selamectin combination (Stronghold® Plus, Zoetis) as a positive control. In the study, the primary criterion was the difference between arithmetic mean mite counts of cats treated with Felpreva® and cats treated with a placebo formulation (solketal). Secondary criteria in both studies were changes in clinical lesion scores after treatment. In both studies, all Felpreva®-treated cats were mite-free (100% parasitological cure) on Day 28, 4 weeks after treatment. Signs of mange on Day 28 were clinically improved in all -infested cats (100%) and clinically cured in all -infested cats (100%). There were no records of any adverse events or application site reactions in Felpreva®-treated cats.
PubMed: 37954512
DOI: 10.1016/j.crpvbd.2023.100146 -
PLoS Neglected Tropical Diseases Nov 2023Schistosomiasis is a neglected tropical disease (NTD) that is endemic in Uganda, despite several interventions to eliminate it. It is transmitted when people infected...
INTRODUCTION
Schistosomiasis is a neglected tropical disease (NTD) that is endemic in Uganda, despite several interventions to eliminate it. It is transmitted when people infected with it pass on their waste matter into fresh water bodies used by others, consequently infecting them. Several studies have demonstrated gender and age differences in prevalence of schistosomiasis and NTDs such as lymphatic filariasis and soil transmitted helminths. However, few intersectional gender analysis studies of schistosomiasis have been undertaken. Using the World Health Organisation (WHO)'s intersectional gender analysis toolkit, this study was undertaken to identify which social stratifiers most intersected with gender to influence vulnerability to and access to treatment for schistosomiasis disease, to understand how best to implement interventions against it.
METHODOLOGY
This was a qualitative study comprising eight focus group discussions (FGDs) of community members, disaggregated by age, sex and location, and 10 key informant interviews with health care providers and community leaders. The Key informants were selected purposively while the community members were selected using stratified random sampling (to cater for age, sex and location). The data was analysed manually to identity key themes around gender, guided by a gender and intersectionality lens.
RESULTS
The study established that while the River Nile provided livelihoods it also exposed the community to schistosomiasis infection. Gender relations played a significant role in exposure to and access to treatment for schistosomiasis. Traditional gender roles determined the activities men and women performed in the private and public spheres, which in turn determined their exposure to schistosomiasis and treatment seeking behaviour. Gender relations also affected access to treatment and decision making over family health care. Men and some women who worked outside the home were reported to prioritise their income earning activities over seeking health care, while women who visited the health facilities more regularly for antenatal care and to take sick children were reported to have higher chance of being tested and treated in time, although this was undermined by the irregular and infrequent provision of praziquantel (PZQ) mass drug administration. These gender relations were further compounded by underdevelopment and limited economic opportunities, insufficient health care services, as well as the respondent's age and location.
CONCLUSIONS
The study concludes that vulnerability to schistosomiasis disease and treatment occurred within a complex web of gender relations, culture, poverty, limited economic opportunities and insufficient health services delivery, which together undermined efforts to eliminate schistosomiasis. This study recommends the following: a) increased public health campaigns around schistosomiasis prevention and treatment; b) more regular PZQ MDA at home and schools; c) improved health services delivery and integration of services to include vector control; d) prioritising NTDs; e) providing alternative economic activities; and f) addressing negative gender norms that promote social behaviours which negatively influence vulnerability, treatment seeking and decision making for health.
Topics: Pregnancy; Male; Child; Humans; Female; Uganda; Intersectional Framework; Schistosomiasis; Praziquantel; Delivery of Health Care
PubMed: 37948453
DOI: 10.1371/journal.pntd.0010639 -
PLoS Neglected Tropical Diseases Nov 2023Schistosomiasis is one of the most important neglected tropical diseases, with a great impact on public health and more than 200,000 deaths annually. Schistosoma...
BACKGROUND
Schistosomiasis is one of the most important neglected tropical diseases, with a great impact on public health and more than 200,000 deaths annually. Schistosoma haematobium causes urinary tract (UT) morbidity. Since schistosomiasis morbidity control programs focus on children older than 5 years, pre-school age children (PSAC) morbidity is not well known.
METHODS
We conducted a cross-sectional study in Cubal (Angola) among 245 PSAC with the objective of evaluating the prevalence of S. haematobium infection, the intensity of infection, and associated morbidity. For this purpose, urine filtration test followed by microscopic visualization and ultrasound examinations were performed.
RESULTS
The estimated overall prevalence of urogenital schistosomiasis was 30.2% (CI 95%; 24.5-35.9), with 20.3% (CI 95%; 15.3-25.3) of the samples analysed showing a high intensity of infection. A total of 54.5% (CI 95%; 47.6-61.8) of infected children presented UT lesions, showing a significant association between schistosomiasis infection and UT morbidity (p-value < 0.001). Bladder wall thickening was the most common lesion, being present in 100% of abnormal ultrasounds. We found that anaemia and severe malnutrition were not significantly associated with the development of UT lesions.
CONCLUSIONS
S. haematobium infection in PSAC causes great UT detectable morbidities. Therefore, there is an evident need of including them in mass drug administration (MDA) campaigns and consequently the development of an adapted praziquantel treatment dosage for children under 2 years of age.
Topics: Animals; Humans; Child; Child, Preschool; Infant; Schistosomiasis haematobia; Prevalence; Angola; Cross-Sectional Studies; Morbidity; Schistosoma haematobium
PubMed: 37939154
DOI: 10.1371/journal.pntd.0011751