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Frontiers in Cellular and Infection... 2024The lethal zoonosis alveolar echinococcosis is caused by tumour-like growth of the metacestode stage of the tapeworm within host organs. We previously demonstrated that...
The lethal zoonosis alveolar echinococcosis is caused by tumour-like growth of the metacestode stage of the tapeworm within host organs. We previously demonstrated that metacestode proliferation is exclusively driven by somatic stem cells (germinative cells), which are the only mitotically active parasite cells that give rise to all differentiated cell types. The gene repertoire required for germinative cell maintenance and differentiation has not been characterised so far. We herein carried out Illumina sequencing on cDNA from metacestode vesicles, from metacestode tissue depleted of germinative cells, and from primary cell cultures. We identified a set of ~1,180 genes associated with germinative cells, which contained numerous known stem cell markers alongside genes involved in replication, cell cycle regulation, mitosis, meiosis, epigenetic modification, and nucleotide metabolism. Interestingly, we also identified 44 stem cell associated transcription factors that are likely involved in regulating germinative cell differentiation and/or pluripotency. By hybridization and pulse-chase experiments, we also found a new general stem cell marker, , and we provide evidence implying the presence of a slow cycling stem cell sub-population expressing the extracellular matrix factor . RNA-Seq analyses on primary cell cultures revealed that metacestode-derived stem cells display an expanded differentiation capability and do not only form differentiated cell types of the metacestode, but also cells expressing genes specific for protoscoleces, adult worms, and oncospheres, including an ortholog of the schistosome praziquantel target, EmTRPM. Finally, we show that primary cell cultures contain a cell population expressing an ortholog of the tumour necrosis factor α receptor family and that mammalian TNFα accelerates the development of metacestode vesicles from germinative cells. Taken together, our analyses provide a robust and comprehensive characterization of the germinative cell transcriptome, demonstrate expanded differentiation capability of metacestode derived stem cells, and underscore the potential of primary germinative cell cultures to investigate developmental processes of the parasite. These data are relevant for studies into the role of stem cells in parasite development and will facilitate the design of anti-parasitic drugs that specifically act on the parasite germinative cell compartment.
Topics: Animals; Echinococcus multilocularis; Parasites; Larva; Gene Expression Profiling; Cell Culture Techniques; Stem Cells; Mammals
PubMed: 38333034
DOI: 10.3389/fcimb.2024.1335946 -
Parasite Epidemiology and Control Feb 2024Pediatric schistosomiasis has been recognized as a public health concern in schistosomiasis endemic areas of sub-Saharan Africa, including Tanzania. However, there is...
Where will pediatric praziquantel be needed in Tanzania? Geographical variation in prevalence, and risk factors of in pre-school aged children in southern and north-western Tanzania.
BACKGROUND
Pediatric schistosomiasis has been recognized as a public health concern in schistosomiasis endemic areas of sub-Saharan Africa, including Tanzania. However, there is limited epidemiological information relating to pediatric schistosomiasis in Tanzania. Therefore, this current focused on assessing the geographical prevalence of infection and its associated risk factors in pre-school children (PreSAC) in southern and north-western Tanzania.
METHODS
A total of 1585 PreSAC aged 1-6 years were enrolled in a cross-sectional study. A single urine and stool sample were obtained from each child and processed using point-of-care circulating cathodic (POC-CCA) antigen and Kato Katz (K-K) technique. The overall prevalence of infection based on K-K technique and POC-CCA test were 18.6% (95%CI:16.7-20.6) and 28.3% (95%CI:26.1-30.6), respectively. The overall geometrical mean eggs per gram of faeces was 110.38epg (95% CI:97.3-125.3). The age group 4-6 years had the highest prevalence ( < 0.01) of in both diagnostic tests and infection intensity ( = -2.8398, < 0.005) using K-K technique. On multivariable analysis, only Ukerewe district was associated with infection based on K-K technique (aOR = 2.8 (95%CI:2.1-3.9), < 0.001). Based on POC-CCA test, age group (4-6 years), aOR = 1.7, 95%CI:1.3-2.2, < 0.001), Nyasa (aOR = 6.2, 95%CI:3.0-12.5, < 0.001), Geita (aOR = 4.2, 95%CI:2.1-8.2, < 0.001) and Ukerewe (aOR = 28.9, 95%CI:15.0-55.8, < 0.001) districts remained independently associated with infection.
CONCLUSION
is a public health concern among PreSAC in the study districts and its prevalence varies from one geographical setting to another. These findings strongly support the need to include pre-school aged in preventive chemotherapy.
PubMed: 38323193
DOI: 10.1016/j.parepi.2024.e00337 -
Parasite (Paris, France) 2024Feline pulmonary capillariosis is a significant disorder due to its distribution and clinical impact. This study evaluated the safety and efficacy of two administrations...
Feline pulmonary capillariosis is a significant disorder due to its distribution and clinical impact. This study evaluated the safety and efficacy of two administrations 28 days apart of a topical solution containing esafoxolaner, eprinomectin and praziquantel (NexGard Combo) in treating Eucoleus aerophilus (syn. Capillaria aerophila) infection in naturally infected cats. Cats were allocated to two groups: G1 cats (n = 23) received two treatments at study days (SDs) 0 and 28 (±2) and were evaluated for 6 weeks, and G2 cats (n = 17) served as a negative control for 6 weeks and were then treated twice on SDs 42 (±2) and 70 (±2), allowing for an additional 6-week assessment of efficacy. Each cat was subjected to McMaster coproscopy at SDs -7/0, 28 (±2) and 42 (±2) for both groups, 70 (±2) and 84 (±2) only for G2. Clinical examination and chest radiographic images were performed at SDs 0, 28 (±2) and 42 (±2) for G1 and G2, 70 (±2) and 84 (±2) only for G2. The comparison of EPG (eggs per gram of feces), clinical (CS), and radiographic scores (RS) at each time-point was used as a criterion. The efficacy based on the EPG reduction was 99.5% (G1) and 100% (G2) after two administrations of NexGard Combo 2 weeks apart. At SD 0, no significant differences for CS and RS were recorded between G1 and G2, while a significant reduction (p < 0.05) was observed post-treatment for CS, RS, oculo-nasal discharge, auscultation noises, and cough. Two doses of NexGard Combo 28 days apart stopped egg shedding and significantly improved clinical alterations in cats infected by E. aerophilus.
Topics: Animals; Cats; Praziquantel; Ivermectin; Nematode Infections; Enoplida Infections; Cat Diseases; Treatment Outcome
PubMed: 38315065
DOI: 10.1051/parasite/2024005 -
Antimicrobial Agents and Chemotherapy Mar 2024We 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 situated on chromosomes 2 and 3. We reanalyzed this GWAS using the latest (version 10) genome assembly showing that a single locus on chromosome 3, rather than two independent loci, determines drug response. These results reveal that PZQ response is monogenic and demonstrates the importance of high-quality genomic information.
Topics: Animals; Praziquantel; Schistosoma mansoni; Genome-Wide Association Study; Drug Resistance; Schistosomiasis mansoni; Anthelmintics
PubMed: 38289079
DOI: 10.1128/aac.01432-23 -
Chemistry & Biodiversity Mar 2024Schistosomiasis is a major neglected disease that imposes a substantial worldwide health burden, affecting approximately 250 million people globally. As praziquantel...
Schistosomiasis is a major neglected disease that imposes a substantial worldwide health burden, affecting approximately 250 million people globally. As praziquantel is the only available drug to treat schistosomiasis, there is a critical need to identify new anthelmintic compounds, particularly from natural sources. To enhance the activity of different natural products, one potential avenue involves its combination with silver nanoparticles (AgNP). Based on this approach, a one-step green method for the in situ preparation of dehydrodieugenol (DHDG) by oxidation coupling reaction using silver and natural eugenol is presented. AgNP formation was confirmed by UV-Vis spectroscopy due to the appearance of the surface plasmon resonance (SPR) band at 430 nm which is characteristic of silver nanoparticles. The nanoparticles were spherical with sizes in the range of 40 to 50 nm. Bioassays demonstrated that the silver nanoparticles loaded with DHDG exhibited significant anthelmintic activity against Schistosoma mansoni adult worms without toxicity to mammalian cells and an in vivo animal model (Caenorhabditis elegans), contributing to the development of new prototypes based on natural products for the treatment of schistosomiasis.
Topics: Animals; Humans; Silver; Metal Nanoparticles; Anthelmintics; Schistosomiasis; Anti-Infective Agents; Schistosoma mansoni; Biological Products; Mammals; Eugenol; Lignans
PubMed: 38278761
DOI: 10.1002/cbdv.202301929 -
PLoS Neglected Tropical Diseases Jan 2024Malaria and schistosomiasis are two important parasitic diseases that are a particular threat to young children and pregnant women in sub-Saharan Africa. Malaria and... (Review)
Review
Malaria and schistosomiasis are two important parasitic diseases that are a particular threat to young children and pregnant women in sub-Saharan Africa. Malaria and schistosomiasis prevention and control strategies primarily focus on the distribution of long-lasting insecticidal nets and the delivery of praziquantel tablets to at-risk populations in high burden settings through mass drug administration, respectively. The objective of this scoping review was to identify previous efforts to integrate malaria and schistosomiasis prevention and control programs in the literature and to summarize the strategies and approaches used in these programs following the PRISMA-ScR guidelines. We reviewed published and grey literature using a combination of keywords and search terms following themes surrounding "malaria", "Plasmodium falciparum", "Anopheles", "schistosomiasis", "Schistosoma haematobium", "Schistosoma mansoni", and "snails". Neither a date limit nor relevant terms for prevention and control were used. Out of 6374, eight articles were included in the scoping review-three articles investigated the integration of mass drug administration for schistosomiasis with the administration of antimalarials, four articles investigated the effect of administering antimalarials on malaria, schistosomiasis, and their co-infection, and one article assessed the impact of an educational intervention on malaria and schistosomiasis knowledge and preventative behaviors. Our findings suggest that there is an opportunity to link disease control programs to increase access and coverage of interventions to improve outcomes for malaria, schistosomiasis, and their co-infection. Further research is needed on the potential benefits, feasibility, and cost-effectiveness of integrating malaria and schistosomiasis prevention and control programs.
Topics: Pregnancy; Child; Animals; Humans; Female; Child, Preschool; Antimalarials; Coinfection; Malaria; Schistosomiasis; Schistosoma haematobium
PubMed: 38265982
DOI: 10.1371/journal.pntd.0011886 -
Pharmaceutics Dec 2023This review discusses the entire progress made on the anthelmintic drug praziquantel, focusing on the solid state and, therefore, on anhydrous crystalline polymorphs,... (Review)
Review
This review discusses the entire progress made on the anthelmintic drug praziquantel, focusing on the solid state and, therefore, on anhydrous crystalline polymorphs, amorphous forms, and multicomponent systems (i.e., hydrates, solvates, and cocrystals). Despite having been extensively studied over the last 50 years, new polymorphs and the greater part of their cocrystals have only been identified in the past decade. Progress in crystal engineering science (e.g., the use of mechanochemistry as a solid form screening tool and more strategic structure-based methods), along with the development of analytical techniques, including Synchrotron X-ray analyses, spectroscopy, and microscopy, have furthered the identification of unknown crystal structures of the drug. Also, computational modeling has significantly contributed to the prediction and design of new cocrystals by considering structural conformations and interactions energy. Whilst the insights on praziquantel polymorphs discussed in the present review will give a significant contribution to controlling their formation during manufacturing and drug formulation, the detailed multicomponent forms will help in designing and implementing future praziquantel-based functional materials. The latter will hopefully overcome praziquantel's numerous drawbacks and exploit its potential in the field of neglected tropical diseases.
PubMed: 38258039
DOI: 10.3390/pharmaceutics16010027 -
Journal of Zoo and Wildlife Medicine :... Jan 2024Spirorchiidosis, caused by blood flukes of the genus is a disease of great concern for the critically endangered European pond turtle (EPT; ) in Switzerland. The...
Spirorchiidosis, caused by blood flukes of the genus is a disease of great concern for the critically endangered European pond turtle (EPT; ) in Switzerland. The endogenous life cycle of the parasite often leads to systemic inflammatory reactions, thrombosis, and death. Praziquantel (PZQ) is the treatment of choice against adult spp. in green () and in loggerhead () sea turtles and is therefore considered for the treatment of EPT. This study aimed to establish a safe, easily applicable PZQ treatment for EPT, based on pharmacokinetics and tolerability. Three application methods were tested in a total of 12 adult EPT. Each turtle received a total of 75 mg/kg PZQ (three doses of 25 mg/kg in 3-h intervals [q3h × 3]) via IM ( = 3 turtles), SC ( = 3 turtles), or PO ( = 6 turtles) administration. Blood was collected 3, 6, 24, and 48 h after the first administration to determine the plasma concentration of PZQ using high-performance liquid chromatography coupled to mass spectrometry. Maximum measured R-PZQ concentrations (C) were reached after 6 h. The mean C of the total PZQ (sum of R- and S-PZQ) in the PO-treated EPT group was 1,929 ng/ml. Significantly higher concentrations were measured after IM and SC injection (mean C of total PZQ = 12,715 ng/ml and 10,114 ng/ml, respectively). Transient side effects were evident after IM administration (local swelling and lameness), whereas no adverse drug effects were observed after PO and SC administration. Based on these results and the ease of administration to EPT, SC injection of PZQ at 25 mg/kg q3h times 3 serves as promising treatment application for the future.
Topics: Animals; Praziquantel; Turtles; Chromatography, High Pressure Liquid; Gait; Inflammation
PubMed: 38251996
DOI: 10.1638/2023-0031 -
Infectious Diseases of Poverty Jan 2024Mass drug administration (MDA) program of albendazole to at-risk populations as preventive chemotherapy is the core public health intervention to control...
Reduced efficacy of single-dose albendazole against Ascaris lumbricoides, and Trichuris trichiura, and high reinfection rate after cure among school children in southern Ethiopia: a prospective cohort study.
BACKGROUND
Mass drug administration (MDA) program of albendazole to at-risk populations as preventive chemotherapy is the core public health intervention to control soil-transmitted helminths (STHs). Achieving this goal relies on drug effectiveness in reducing the parasite reservoirs in the community and preventing reinfection. We assessed the efficacy of albendazole against STH parasite infection and reinfection status after cure.
METHODS
A total of 984 schoolchildren infected with at least one type of STH parasite (hookworm, Ascaris lumbricoides, Trichuris trichiura) in southern Ethiopia were enrolled and received albendazole and praziquantel in MDA campaign conducted from January to March 2019. Stool exams at week-4 and at week-8 of post-MDA were done using Kato Katz technique. The primary outcome was efficacy assessed by cure rate (CR) and fecal egg reduction rates (ERRs) at four weeks of post-MDA. The secondary outcome was reinfection status defined as parasite egg positivity at eight weeks among those who were cured at 4 weeks of post-MDA. Group comparisons in CR and related factors were assessed with chi-square or Fisher's exact tests. Predictors of CR were examined through univariate and multivariate regression analyses.
RESULTS
The overall CR and ERR for hookworm infection were 97.2% (95% CI 94.6-99.4) and 97.02%, respectively. The overall CR and ERR for A. lumbricoides were 71.5% (95% CI 68.3-74.6) and 84.5% respectively. The overall CR and ERR and for T. trichiura were 49.5% (95% CI 44.8-54.2) and 68.3%, respectively. The CR among moderate T. trichiura infection intensity was 28.6%. Among children cured of hookworm, A. lumbricoides and T. trichiura at week 4 post-MDA, 4.6%, 18.3% and 52.4% became reinfected at week-8 post-MDA, respectively. Significantly lower CR (36.6%) and higher reinfection after cure (60.6%) among A. lumbricoides and T. trichiura coinfected children than A. lumbricoides only (CR = 69.6%, reinfection rate = 15.1%) or T. trichiura only infected children (CR = 55.6%, reinfection rate = 47.1%) was observed. Pre-treatment coinfection with ≥ two types of STH parasites was significantly associated with re-infection after cure.
CONCLUSION
Albendazole MDA is efficacious against hookworm but has reduced efficacy against A. lumbricoides and is not effective against T. trichiura. The low drug efficacy and high reinfection rate after cure underscore the need for alternative treatment and integration of other preventive measures to achieve the target of eliminating STHs as a public health problem by 2030.
Topics: Child; Animals; Humans; Ascaris lumbricoides; Trichuris; Albendazole; Ethiopia; Prospective Studies; Reinfection; Coinfection
PubMed: 38246985
DOI: 10.1186/s40249-024-01176-6 -
Scientific Reports Jan 2024Schistosomiasis is caused by parasites of the genus Schistosoma, which infect more than 200 million people. Praziquantel (PZQ) has been the main drug for controlling...
Schistosomiasis is caused by parasites of the genus Schistosoma, which infect more than 200 million people. Praziquantel (PZQ) has been the main drug for controlling schistosomiasis for over four decades, but despite that it is ineffective against juvenile worms and size and taste issues with its pharmaceutical forms impose challenges for treating school-aged children. It is also important to note that PZQ resistant strains can be generated in laboratory conditions and observed in the field, hence its extensive use in mass drug administration programs raises concerns about resistance, highlighting the need to search for new schistosomicidal drugs. Schistosomes survival relies on the redox enzyme thioredoxin glutathione reductase (TGR), a validated target for the development of new anti-schistosomal drugs. Here we report a high-throughput fragment screening campaign of 768 compounds against S. mansoni TGR (SmTGR) using X-ray crystallography. We observed 49 binding events involving 35 distinct molecular fragments which were found to be distributed across 16 binding sites. Most sites are described for the first time within SmTGR, a noteworthy exception being the "doorstop pocket" near the NADPH binding site. We have compared results from hotspots and pocket druggability analysis of SmTGR with the experimental binding sites found in this work, with our results indicating only limited coincidence between experimental and computational results. Finally, we discuss that binding sites at the doorstop/NADPH binding site and in the SmTGR dimer interface, should be prioritized for developing SmTGR inhibitors as new antischistosomal drugs.
Topics: Animals; Child; Humans; Schistosoma mansoni; Crystallography, X-Ray; NADP; Schistosomiasis; Binding Sites; Schistosomiasis mansoni; Multienzyme Complexes; NADH, NADPH Oxidoreductases
PubMed: 38238498
DOI: 10.1038/s41598-024-52018-2