Search Results (163)

Neglected diseases significantly impact the world, and there is a lack of effective treatments, requiring therapeutic alternatives. Thus, the study of the phytochemical and schistosomicidal activity evaluation of Copaifera oblongifolia leaves’ crude extract was conducted. The quercitrin (1) and afzelin (2) were isolated from the crude extract. In the in vitro schistosomicidal activity test, the isolated compounds demonstrated promising results, with 75% mortality at a concentration of 12.5 µM after 72 h. Molecular docking calculations indicated that compounds 1 and 2 could potentially interact with the amino acids of the FAD binding site in the TGR enzyme, a crucial enzyme for the survival of Schistosoma mansoni. These interactions could have binding energies comparable to praziquantel, a preferred drug for treating schistosomiasis. Therefore, in silico and in vitro investigations are crucial for developing new studies that can reveal the antiparasitic potential of compounds of plant origin. Full article

Cat owners are involved in their cats’ healthcare, including the prevention of parasitic diseases. However, a comprehensive understanding of their preferences for feline antiparasitics is lacking. This study addresses this gap through a multifaceted methodology comprising three phases. In Phase 1, the physical properties and usability aspects of seven topical antiparasitic formulations were assessed. Within Phase 2, an ease-of-use study was conducted to evaluate the cat owners’ application experience with deidentified products representing three topical antiparasitics. Phase 3 included the identification and validation of product attributes most valued by pet owners through interviews with cat owners and veterinary experts. The product attributes identified informed the subsequent quantitative discrete choice experiment (DCE), which involved 1040 cat owners from different countries (Australia/New Zealand, Canada, Greece/Spain, and the UK) and aimed to analyze their preferences based on choices among product profiles mirroring four topical antiparasitics: selamectin–sarolaner, moxidectin–fluralaner, moxidectin–imidacloprid, and eprinomectin–esafoxolaner–praziquantel. Phase 1 showed that the selamectin–sarolaner formulation exhibits minimal odor, less stickiness, and less drying time. The ease-of-use study (Phase 2) showed that the blinded product representing the selamectin–sarolaner formulation was characterized by seamless application, rapid dispensing, and a sense of control during application. The quantitative DCE study (Phase 3) indicated a preference for the product profile mirroring the selamectin–sarolaner formulation among a global sample of cat owners. Demographic characteristics such as gender, age, and insurance status influenced their preferences. Key predictors for preferring the selamectin–sarolaner formulation over at least one comparator treatment included the ability to confirm successful administration, age restrictions, ease of application, and the time before the cat could sit on furniture following administration. These findings suggest that cat owners prioritize ease of use, safety, and overall user experience, providing valuable guidance for veterinary practitioners to make informed treatment recommendations. Full article

Sparganosis is a neglected food- and water-borne zoonotic disease caused by members of the tapeworm genus Spirometra. More than 1600 human cases have been reported in the literature, primarily in Korea and China; however, the clinical significance of sparganosis is likely underestimated. The control of this disease is challenging in endemic regions because of the complexity of its lifecycle and the involvement of many animal host species, and treatment of clinical disease in humans and animals with selected drugs (e.g., mebendazole and/or praziquantel), even at elevated doses, is often ineffective, such that novel interventions are needed. It is anticipated that the use of molecular technologies should allow the identification of new intervention targets in crucial biological processes and/or pathways of Spirometra spp. While some draft genomes of Spirometra have been produced, their assemblies are incomplete. Here, we employed an advanced DNA sequencing–informatic approach to assemble and annotate the first high-quality genome of an isolate of Spirometra from Australia, with chromosome-level contiguity and a curated gene set. This improved genome provides a useful resource to support fundamental and applied molecular investigations of Spirometra species and should assist in the design of new tools for the intervention against sparganosis of companion animals (including dogs and cats) and humans. Full article

Schistosomiasis mansoni is a neglected tropical disease caused by the parasite Schistosoma mansoni, affecting approximately 200 million people annually. Currently, treatment relies primarily on a single drug, praziquantel (PZQ), which shows limited efficacy against the parasite’s immature forms. As a result, Thioredoxin Glutathione Reductase from S. mansoni (SmTGR) has emerged as a promising target for novel drug development. This study presents the development of integrated in silico methods to identify alkaloids from medicinal plants with potential activity against S. mansoni. Fourteen alkaloids were identified, with predicted activity ranging from 61.3 to 85.2%. Among these, lindoldhamine and daibucarboline A demonstrated, for the first time, potential SmTGR inhibition, with probabilities of 85.2% and 75.8%, respectively. These findings highlight the potential of these alkaloids as promising candidates for the development of new therapies against schistosomiasis. Full article

Schistosomiasis is a parasitic disease caused by helminth parasites of the genus Schistosoma, affecting >200 million people worldwide. Current schistosomiasis treatment relies on a single drug, praziquantel, highlighting the urgent need for new therapies. We have identified a non-neuronal tegumental acetylcholinesterase from Schistosoma mansoni (SmTAChE) as a rational and molecularly defined drug target. Molecular modeling reveals significant structural differences between SmTAChE and human AChE, suggesting the potential for identifying parasite-specific inhibitors. Here, we screened recombinant SmTAChE (rSmTAChE) against two chemical libraries: the Broad Institute Drug Repurposing Hub (5440 compounds) and the Diversity-Oriented Synthesis (DOS)-A library (3840 compounds). High-throughput screening identified 116 hits from the Repurposing Hub (2.13% hit rate) and 44 from the DOS-A (1.14% hit rate) library that inhibited rSmTAChE ≥60% at 20 µM. Dose–response assays using both rSmTAChE and recombinant human AChE (rHsAChE) revealed 19 Repurposing Hub compounds (IC₅₀: 0.4–24 µM) and four DOS-A scaffolds (IC₅₀: 13–29 µM), with higher selectivity for rSmTAChE. Selective inhibitors such as cepharanthine, primaquine, mesalazine, and embelin emerged as promising candidates for further evaluation in schistosomiasis treatment. These 23 newly identified selective hits provide a foundation for the further development of novel anti-schistosome therapies. Full article

Background/Objectives: Taeniasis, a zoonotic infection, is a common foodborne disease. Niclosamide and praziquantel have proven to be effective in treating it, but the use of the same drugs can lead to resistance, so alternative drugs need to be explored. This study investigated the anthelmintic potential of derived fractions from hydroethanolic extracts (HEs) of Aframomum melegueta (AM) and Xylopia aethiopica (XA), two medicinal plants known for their diverse bioactive properties. Methods: AM-HE fractions (dichloromethane fraction (DCMF), ether fraction (EF), aqueous fraction (AF)) and XA-HE fractions (chloroform fraction (CF), ether fraction (EF), and aqueous fraction (AF)) were used, and in vitro anthelmintic activity was assessed against Taenia spp. by using an adult motility assay for the worm’s paralysis time determination. The parasiticidal and parasitostatic activity was also tested on Taenia spp. adult worms. Cell viability was further evaluated using propidium iodide (PI) staining, with albendazole (20 mg/mL) as the reference drug. Results: The three fractions of each plant exhibited significant, dose-dependent anthelmintic activity, with AM-HE and XA-CF showing the greatest effects at 20 mg/mL. AM-EF demonstrated significant activity at 0.4% and 0.8%. Irreversibility tests revealed that most of the treated worms remained paralysis, except those exposed to the AF of both plants. PI staining confirmed the dose-dependent mortality of Taenia cells treated with HE, DCMF, and AF of AM. Conclusions: These results underscore the potential of AM and XA extracts and fractions as alternative treatments for helminth infections. Further, in vivo studies are warranted to confirm their safety and therapeutic efficacy. Full article

Introduction: One of the global strategies for the elimination of schistosomiasis is by Mass Drug Administration (MDA) of a single oral dose of praziquantel (40 mg/kg) without a prior individual diagnosis, with a target of >75% treatment coverage among school-aged children. This study was conducted to determine the endemicity of schistosomiasis among school-aged children and adults in Abuja, Nigeria. Methods: A total of 1370 participants were recruited, which consisted of 667 (48.67%) males and 703 (51.31%) females. Urine and stool specimens were collected from each participant and analyzed using standard procedures. Results: The overall prevalence of schistosomiasis was 27.5% in this study with Abuja Municipal having the highest prevalence of 49%, while the least (6.1%) was reported in Bwari LAC. The prevalence of schistosomiasis significantly differs (p < 0.05) between the area councils. The location of communities significantly affected the prevalence of schistosomiasis in Abaji, AMAC, and Gwagwalada LACs (p < 0.005). The Schistosoma recovered in this study were S. haematobium and S. mansoni. The prevalence of schistosomiasis increased from the baseline of 21.1% to 49% in Gwagwalada LAC. Gender significantly affected the prevalence of schistosomiasis as more males were infected (33.1%) than their female counterparts (22.2%) (p < 0.05). The prevalence of schistosomiasis was 31% and 23.9% among SAC and adults, respectively. The participants’ activities in the river significantly affected the prevalence of schistosomiasis in this study (p < 0.05). Conclusions: The clamour for urgent government and non-government intervention through alternate sources of water like boreholes or pipe-borne water, as well as implementing a behavioural change campaign across the communities to prevent the recurrence, are advocated. Full article

Feline parasitism affects animals’ health and welfare. Faeces from 472 client-owned cats from Greece were examined to provide updated data on the epizootiology of metazoan endo- and ectoparasites (namely, Toxocara cati, Ancylostomatidae, Dipylidium caninum, lungworms, Toxascaris leonina, Otodectes cynotis, fleas, ticks and Notoedres cati). All positive animals received a topical formulation containing esafoxolaner, eprinomectin and praziquantel (NexGard^® Combo, Boehringer Ingelheim), and its efficacy was evaluated. The overall prevalence of parasitism was 22.9%, while that of multiparasitism was 16.3%. Toxocara cati (18.4%) was the most prevalent endoparasite, followed by Ancylostomatidae (10.8%), D. caninum (4.7%), lungworms (2.5%) and T. leonina (0.4%). Regarding ectoparasites, O. cynotis (3.2%), fleas (2.3%), ticks (0.6%) and N. cati (0.4%) were found. To estimate the efficacy of treatment, the geometric means of the number of parasitic elements before the first treatment and post-treatment, (i) 14 days for intestinal helminths, (ii) 28 and 56 days for lungworms and (iii) 28 days for O. cynotis and fleas, were estimated and compared. Following statistical analyses (paired t-test and McNemar’s test), an efficacy of 100% was recorded against the most commonly detected parasites (gastrointestinal helminths and mites) and a notable statistically significant effect against fleas and lungworms after one dose, while 100% efficacy against lungworms was achieved after two doses of the product. No adverse effects were reported. The prevalence of parasitism in owned cats in Greece remains high, highlighting the demand for targeted preventive antiparasitic schemes. This study demonstrated high-level efficacy and tolerance of NexGard^® Combo against common endoparasites and ectoparasites of household cats in Greece. Full article

Background: Schistosomiasis (SCH) and soil transmitted helminthiasis (STH) have been targeted for elimination as a public health problem (EPHP) within the World Health Organization (WHO)’s Roadmap for Neglected Tropical Diseases (NTDs) 2021–2030. One of the global strategies for the control and elimination of these diseases is the mass administration of praziquantel and albendazole/mebendazole without prior individual diagnosis. To measure the progress towards the 2030 target, we conducted an assessment to determine the impact of the 3–5 rounds of annual mass drug administration among school age children in Ekiti State. Such scientific insights into the impact of these treatments will facilitate improved planning and targeting of resources towards reaching the last mile. Methodology: This assessment was conducted in 16 local government areas (LGAs) of Ekiti State between October and November 2023. Samples were collected from pupils in 166 primary and junior secondary schools across 166 wards of the State. Urine and stool samples were collected from 7670 pupils of ages 5 to 14 years, following standard laboratory procedures. Urine membrane filtration techniques were used for urine preparation while the Kato–Katz technique was used for stool preparation. A novel AiDx digital microscope was used to examine the presence of any ova in the prepared specimen. Parasite ova in urine were reported as the number of ova/10 mL of urine, and were categorized as light infection (˂50 ova/10 mL of urine) or heavy infection (>50 ova/10 mL of urine) while ova of parasites in stool samples were reported as eggs per gram of stool (EPG) and categorized into light, moderate and heavy infection. Results: Overall, 0.76% (0.56–0.95) at 95% CI of the 7670 respondents were infected with Schistosomia haematobium. No Schistosoma mansoni infection was recorded in the study. Similarly, 3.9% (3.43–4.29) at 95% CI were infected with STHs. The overall prevalence of schistosomiasis had significantly reduced from 8.2% in 2008 to 0.8%, while the overall prevalence of STHs significantly reduced from 30.9% to 3.9% with Ascaris lumbricoides being the dominant species of STH. In the 16 LGAs assessed, Ekiti West had the highest S. haematobium prevalence of 4.26%. Ise/Orun and Oye ranked second and third with a prevalence of 3.48% and 2.40% respectively, while all other LGAs had <1% prevalence. The prevalence of STHs was highest in Ekiti-West with a prevalence of 10.45% while Emure and Ikole Local Governments had the lowest prevalence of 0.31% and 0.38%, respectively. There was no significant difference in the prevalence of schistosomiasis between male (0.76%) and female (0.75%) as p ≥ 0.05. Similarly, the difference in prevalence for STH among males (3.95%) was not significantly different from their female counterparts (3.77%), p ≥ 0.05. Conclusions: Based on the WHO guidelines, this study demonstrated that only three LGAs require continued MDA every 2/3 years, seven require only surveillance while six are now non-endemic for schistosomiasis. Similarly, two of the LGAs require one round of MDA yearly, eight LGAs need one round of MDA every two to three years and six LGAs are now below the treatment threshold and no longer require treatment for STH. Full article

Background/Objectives: Pork tapeworm Taenia solium is the causative agent of cysticercosis which may develop in muscle tissue, skin, eyes, and the central nervous system (neurocysticercosis). It is estimated by the World Health Organization (WHO) that about 2.56–8.30 million are infected worldwide. Praziquantel and albendazole are used for anthelminthic treatment of neurocysticercosis; however, not all patients have a complete elimination of cysts, which makes it necessary to seek new and improved treatment options. Methods: In this study, methyl, ethyl, n-propyl, and iso-propyl quinoxaline-7-carboxylate-1,4-di-N-oxide derivatives were evaluated in vitro against Taenia crassiceps (T. crassiceps) cysts. Additionally, to know their potential mode of action, a molecular docking analysis on T. solium triosephosphate isomerase (TsTIM) and an enzyme inactivation assay on recombinant TsTIM were carried out. Results: Nine compounds had time- and concentration-dependent cysticidal activity. Particularly, compounds TS-12, TS-19, and TS-20 (EC₅₀ values 0.58, 1.02, and 0.80 µM, respectively) were equipotent to albendazole sulfoxide (EC₅₀ = 0.68 µM). However, TS-12 compounds only cause a slight inhibition of TsTIM (<40% at 1000 µM), suggested that another drug target is implicated in the biological effects. Conclusions: These results demonstrated that quinoxaline 1,4-di-N-oxide is a scaffold to develop new and more potent antitaeniasis agents, although it is necessary to explore other pharmacological targets to understand their mode of action. Full article

Drug resistance is the main challenge in treating parasitic diseases, including cystic echinococcosis (CE). Hence, the current study aims to investigate the effect of nanocapsules containing albendazole (ABZ), mebendazole (MBZ), and praziquantel (PZQ) on treating hydatid cysts in mice using these high-potency drugs. A total of 78 female white laboratory mice (BALB/C mice), 8 weeks old and weighing 25 g, were intraperitoneally injected with 1500 live protoscoleces of Echinococcus granulosus. The first group received ABZ nanocapsules, group 2 received MBZ nanocapsules, group 3 received PZQ nanocapsules, group 4 received ABZ + MBZ nanocapsules, group 5 received ABZ + PZQ nanocapsules, and group 6 received MBZ + PZQ nanocapsules. Each group also had a control group, which received the non-nanocapsulated drugs (group 7–12). Group 13 received no treatment and served as the negative control, just receiving phosphate-buffered saline (PBS). A thorough examination of the cysts’ physical properties, including size, quantity, and weight, was carried out. According to our results, the polymeric nanocapsules are sphere-like and of different sizes. The total number of cysts in all nanocapsule groups significantly decreased compared to the control group. In the total weight of the cysts, ABZ + MBZ nanocapsules, ABZ + PZQ nanocapsules, and MBZ + PZQ nanocapsules had the least total cyst weight, showing that the use of the medicinal combination had a better effect on the penetration and weight reduction of the cysts. In conclusion, the findings showed that ABZ, MBZ, and PZQ significantly reduced the size, weight, and number of hydatid cysts in the mouse model used in this study. Full article

Schistosomiasis, a parasitic disease caused by worms of the genus Schistosoma, affects >250 million people worldwide. With no available vaccine, treatment relies solely on one drug—praziquantel—underscoring the urgent need for new therapies. We identified a tegumental, non-neuronal acetylcholinesterase (AChE) from Schistosoma mansoni—SmTAChE—as a promising drug target. RNA interference confirmed its essential role in parasite survival, as gene suppression significantly reduced parasite recovery from infected animals. Here, we produced functionally active recombinant SmTAChE by using a mammalian expression system. Biochemical characterization confirmed its identity as a true acetylcholinesterase, with the highest turnover rate (K_cat = 373 ± 39 s⁻¹) and catalytic efficiency (K_cat/K_m = 1.17 × 10⁶ M⁻¹·S⁻¹) for acetylthiocholine. Additionally, rSmTAChE was inhibited by classical AChE-specific inhibitors but not by a butyrylcholinesterase-specific inhibitor. To identify novel SmTAChE inhibitors, we developed a high-throughput chemical screening protocol (Z′ factor > 0.9) and screened a 1894-compound validation library. Twelve compounds reproducibly inhibited rSmTAChE by >30% at 7.5 µM, including known AChE inhibitors like physostigmine and new selective inhibitors. Notably, compound #2 preferentially inhibited rSmTAChE (IC₅₀ = 0.74 µM) over human AChE (IC₅₀ = 151 µM), thus providing a foundation for developing parasite-specific therapies targeting SmTAChE and potentially leading to new treatments for schistosomiasis. Full article

Schistosomiasis is a neglected tropical disease that affects over 240 million people worldwide. Currently, praziquantel is the only drug recommended by the World Health Organization for treatment. However, cases of drug resistance have been reported, which indicates an urgent need for new therapeutics. In this context, natural compounds represent valuable sources of pharmacological substances. Plant-derived natural products have been greatly explored for their potential antischistosomal activity, while animal-derived compounds have received little attention. Recent advances in the biotechnology field allow the wide exploration of animal-derived compounds in drug discovery, which may represent a cost-effective option to find bioactive molecules also against Schistosoma mansoni and other parasites. This review highlights the research into animal-derived products and compounds that have already been tested against schistosomes. Phenotypic effects on schistosomes have been observed upon incubation with some of these substances, which may, therefore, represent possible candidates to be used in the development of new drugs. Overall, these studies advance the discovery of antischistosomal compounds by exploring a yet understudied natural resource. The present review also discusses the challenges of testing animal-derived products and provides examples of the experimental in vitro testing of different selected animal natural products against S. mansoni. Full article

This quasi-experimental trial examined the relationship between Schistosoma haematobium infection and nutritional status, and the impact of single dose praziquantel (PZQ) therapy on undernutrition. A total of 353 children were examined, 112 of which were infected with S. haematobium and treated with PZQ. Children’s heights, weights, and mid-upper arm circumferences (MUAC) were measured at baseline and one month post-treatment. Infected children had significantly smaller mean BMI-for-age z-scores (BAZ) (−1.16 vs. 0.11, p < 0.01) and weight-for-age z-scores (WAZ) (−0.61 vs. −0.31, p = 0.03) than the uninfected ones at baseline. S. haematobium infection was associated with underweight (adjusted OR: 1.76, 95% CI: 1.63–1.90). One month after treatment, BAZ, WAZ, height for age z-scores (HAZ), and MUAC scores were comparable between treated and control children. However, there was a significant decrease in the prevalence of underweight among treated children, while no significant change was observed in the control group one month post-treatment. In conclusion, children infected with S. haematobium are likely to suffer from undernutrition; however, single dose PZQ therapy may not improve their nutritional status within one month of treatment. Future studies could have longer follow-up periods to better estimate the drug’s effect on nutrition. Full article

Background: Chronic schistosomiasis can lead to significant morbidity. Serology is highly sensitive; however, its role in assessing treatment response is controversial. This study aimed to analyze serological values following treatment of chronic imported schistosomiasis. Methods: A retrospective observational study was performed including patients treated for chronic imported schistosomiasis from 2018 to 2022 who had at least one serological result at baseline and during follow-up. Demographic, clinical, and laboratory data were evaluated. Generalized estimating equation (GEE) models and Kaplan–Meier curves were used to analyze the evolution of serological values. Results: Of the 83 patients included, 72 (86.7%) were male, and the median age was 26 years (IQR 22–83). Most patients, 76 (91.6%), were migrants from sub-Saharan Africa. While 24 cases (28.9%) presented with urinary symptoms, the majority (59; 71.1%) were asymptomatic. Schistosoma haematobium eggs were observed in five cases (6.2%). Eosinophilia was present in 34 participants (40.9%). All patients had an initial positive Schistosoma ELISA serology, median ODI 2.3 (IQR 1.5–4.4); the indirect hemagglutination (IHA) test was positive/indeterminate in 34 cases (43.1%). Following treatment with praziquantel, serology values significantly decreased: −0.04 (IC95% −0.073, −0.0021) and −5.73 (IC95% −9.92, −1.53) units per month for ELISA and IHA, respectively. A quarter of patients (25%) had negative ELISA results 63 weeks after treatment. All symptomatic cases were clinically cured. Conclusions: Serial serological determinations could be helpful for monitoring chronic schistosomiasis in non-endemic regions. The ideal timing for these follow-up tests is yet to be determined. Further research is needed to determine the factors that influence a negative result during follow-up. Full article