Impact of Strongyloides stercoralis infection on complement activation in Type 2 diabetes mellitus: Insights from a clinical and anthelmintic intervention study.

BACKGROUND: Numerous studies indicate a potential protective role of helminths in diabetes mellitus (DM) progression. The complement system, vital for host defense, plays a crucial role in tissue homeostasis and immune surveillance. Dysregulated complement activation is implicated in diabetic complications. We aimed to investigate the influence of the helminth, Strongyloides stercoralis (Ss) on complement activation in individuals with type 2 DM (T2D). METHODOLOGY: We assessed circulating levels of complement proteins (C1q, C2, C3, C4, C4b, C5, C5a, and MBL (Lectin)) and their regulatory components (Factor B, Factor D, Factor H, and Factor I) in individuals with T2D with (n = 60) or without concomitant Ss infection (n = 58). Additionally, we evaluated the impact of anthelmintic therapy on these parameters after 6 months in Ss-infected individuals (n = 60). RESULTS: Ss+DM+ individuals demonstrated reduced levels of complement proteins (C1q, C4b, MBL (Lectin), C3, C5a, and C3b/iC3b) and complement regulatory proteins (Factor B and Factor D) compared to Ss-DM+ individuals. Following anthelmintic therapy, there was a partial reversal of these levels in Ss+DM+ individuals. CONCLUSION: Our findings indicate that Ss infection reduces complement activation, potentially mitigating inflammatory processes in individuals with T2D. The study underscores the complex interplay between helminth infections, complement regulation, and diabetes mellitus, offering insights into potential therapeutic avenues.

New benzimidazole derivative compounds with in vitro fasciolicidal properties.

BACKGROUND: Control of the zoonotic food-borne parasite Fasciola hepatica remains a major challenge in humans and livestock. It is estimated that annual economic losses due to fasciolosis can reach US$3.2 billion in agriculture and livestock. Moreover, the wide distribution of drug-resistant parasite populations and the absence of a vaccine threaten sustainable control, reinforcing the need for novel flukicides. METHODS: The present work analyses the flukicidal activity of a total of 70 benzimidazole derivatives on different stages of F. hepatica. With the aim to select the most potent ones, and screenings were first performed on eggs at decreasing concentrations ranging from 50 to 5 µM and then on adult worms at 10 µM. Only the most effective compounds were also evaluated using a resistant isolate of the parasite. RESULTS: After the first screenings at 50 and 10 µM, four hit compounds (BZD31, BZD46, BZD56, and BZD59) were selected and progressed to the next assays. At 5 µM, all hit compounds showed ovicidal activities higher than 71% on the susceptible isolate, but only BZD31 remained considerably active (53%) when they were tested on an albendazol-resistant isolate, even with values superior to the reference drug, albendazole sulfoxide. On the other hand, BZD59 displayed a high motility inhibition when tested on adult worms from an albendazole-resistant isolate after 72 h of incubation. CONCLUSIONS: BZD31 and BZD59 compounds could be promising candidates for the development of fasciolicidal compounds or as starting point for the new synthesis of structure-related compounds.

Intestinal cell diversity and treatment responses in a parasitic nematode at single cell resolution.

BACKGROUND: Parasitic nematodes, significant pathogens for humans, animals, and plants, depend on diverse organ systems for intra-host survival. Understanding the cellular diversity and molecular variations underlying these functions holds promise for developing novel therapeutics, with specific emphasis on the neuromuscular system's functional diversity. The nematode intestine, crucial for anthelmintic therapies, exhibits diverse cellular phenotypes, and unraveling this diversity at the single-cell level is essential for advancing knowledge in anthelmintic research across various organ systems. RESULTS: Here, using novel single-cell transcriptomics datasets, we delineate cellular diversity within the intestine of adult female Ascaris suum, a parasitic nematode species that infects animals and people. Gene transcripts expressed in individual nuclei of untreated intestinal cells resolved three phenotypic clusters, while lower stringency resolved additional subclusters and more potential diversity. Clusters 1 and 3 phenotypes displayed variable congruence with scRNA phenotypes of C. elegans intestinal cells, whereas the A. suum cluster 2 phenotype was markedly unique. Distinct functional pathway enrichment characterized each A. suum intestinal cell cluster. Cluster 2 was distinctly enriched for Clade III-associated genes, suggesting it evolved within clade III nematodes. Clusters also demonstrated differential transcriptional responsiveness to nematode intestinal toxic treatments, with Cluster 2 displaying the least responses to short-term intra-pseudocoelomic nematode intestinal toxin treatments. CONCLUSIONS: This investigation presents advances in knowledge related to biological differences among major cell populations of adult A. suum intestinal cells. For the first time, diverse nematode intestinal cell populations were characterized, and associated biological markers of these cells were identified to support tracking of constituent cells under experimental conditions. These advances will promote better understanding of this and other parasitic nematodes of global importance, and will help to guide future anthelmintic treatments.

Machine learning prediction of multiple anthelmintic resistance and gastrointestinal nematode control in sheep flocks.

The high prevalence of Haemonchus contortus and its anthelmintic resistance have affected sheep production worldwide. Machine learning approaches are able to investigate the complex relationships among the factors involved in resistance. Classification trees were built to predict multidrug resistance from 36 management practices in 27 sheep flocks. Resistance to five anthelmintics was assessed using a fecal egg count reduction test (FECRT), and 20 flocks with FECRT < 80% for four or five anthelmintics were considered resistant. The data were randomly split into training (75%) and test (25%) sets, resampled 1,000 times, and the classification trees were generated for the training data. Of the 1,000 trees, 24 (2.4%) showed 100% accuracy, sensitivity, and specificity in predicting a flock as resistant or susceptible for the test data. Forage species was a split common to all 24 trees, and the most frequent trees (12/24) were split by forage species, grazing pasture area, and fecal examination. The farming system, Suffolk sheep breed, and anthelmintic choice criteria were practices highlighted in the other trees. These management practices can be used to predict the anthelmintic resistance status and guide measures for gastrointestinal nematode control in sheep flocks.

Anthelmintic efficacy of nitazoxanide in dogs naturally infected with Toxocara canis.

Toxocara canis (T. canis) is a gastrointestinal nematode in dogs, and its larvae also infect humans, causing severe larval migratory disease. Anthelmintic drugs have become the primary means to combat T. canis. In this study, the efficacy of nitazoxanide (NTZ) was tested against all the internal stages of T. canis, including L3 larval stage in vitro experiments and gastrointestinal worm in vivo experiments. In the in vitro experiment, after treatment with NTZ at 7.81 and 62.5 µg/mL for 12 h, the larval mortality efficacy reached 90.0 and 100.0%, respectively. In the in vivo experiments, 100 mg/kg NTZ possessed good anthelmintic efficacy against T. canis, with an egg per gram (EPG) reduction of 99.19%, and 90.00% of dogs cleared with residual worms. These results were comparable to those of the positive control drug. The highest anthelmintic efficacy was observed in the group treated with 150 mg/kg NTZ. Based on faecal egg counts, the number of T. canis eggs decreased by 100.00%, and the percentage of dogs cleared with residual worms achieved 90.00% after 7 days of treatment in the 150-mg/kg NTZ treatment group. In general, NTZ showed great potential to be applied as an anthelmintic against T. canis.

Getting around the roundworms: Identifying knowledge gaps and research priorities for the ascarids.

The ascarids are a large group of parasitic nematodes that infect a wide range of animal species. In humans, they cause neglected diseases of poverty; many animal parasites also cause zoonotic infections in people. Control measures include hygiene and anthelmintic treatments, but they are not always appropriate or effective and this creates a continuing need to search for better ways to reduce the human, welfare and economic costs of these infections. To this end, Le Studium Institute of Advanced Studies organized a two-day conference to identify major gaps in our understanding of ascarid parasites with a view to setting research priorities that would allow for improved control. The participants identified several key areas for future focus, comprising of advances in genomic analysis and the use of model organisms, especially Caenorhabditis elegans, a more thorough appreciation of the complexity of host-parasite (and parasite-parasite) communications, a search for novel anthelmintic drugs and the development of effective vaccines. The participants agreed to try and maintain informal links in the future that could form the basis for collaborative projects, and to co-operate to organize future meetings and workshops to promote ascarid research.

Efficacy of a Single Oral Dose of Artesunate plus Sulfalene-Pyrimethamineversus Praziquantel in the Treatment of Schistosoma mansoni in Kenyan Children: An Open-Label, Randomized, Exploratory Trial.

Unlike praziquantel, artemisinin derivatives are effective against juvenile schistosome worms. We assessed the efficacy and safety of a single oral dose of artesunate plus sulfalene-pyrimethamine versus praziquantel in the treatment of Schistosoma mansoni. Seventy-three schoolchildren (aged 9-15 years) with confirmed S. mansoni infection in Rarieda, western Kenya, were randomly assigned to receive either a single oral dose of artesunate plus sulfalene-pyrimethamine (n = 39) or a single dose of praziquantel (n = 34). The cure and egg reduction rates at 4 weeks posttreatment were 69.4% (25/36) versus 80.6% (25/31) (P = 0.297) and 99.1% versus 97.5% (P = 0.607) in the artesunate plus sulfalene-pyrimethamine group versus praziquantel group, respectively. Fourteen children developed adverse events, and there were no serious adverse events. A single oral dose of artesunate plus sulfalene-pyrimethamine has efficacy comparable to that of praziquantel in the treatment of S. mansoni, but these results should be confirmed in larger randomized controlled trials.

Adolescents' Perspective Regarding a Community-Wide Mass Drug Administration Program for Soil-Transmitted Helminths in India.

This study was undertaken to understand the perspective of adolescents in endemic communities of India regarding soil-transmitted helminth (STH) infections and community-wide mass drug administration (cMDA). A multicountry community-based cluster-randomized trial, the Deworm3 trial, tested the feasibility of interrupting STH transmission with cMDA, where all individuals aged 1-99 are treated empirically with albendazole. Using a guideline based on the Consolidated Framework for Implementation Research, eight focus group discussions were conducted among 57 adolescents from the trial site in India and analyzed on ATLAS.ti 8.0 software using an a priori thematic codebook. Adolescents believed that adults could be a source of STH infection because they were not routinely dewormed like the children through the national deworming program. Perceived benefits of cMDA for all were better health and increased work efficiency. Perceived barriers to adults' participation in cMDA was their mistrust about the program, fear of side effects, perceived low risk of infection, and absence during drug distribution. To encourage adult participation in cMDAs, adolescents suggested community outreach activities, engaging village influencers and health workers, and tailoring drug distribution to when adults would be available. Adolescents were confident in their ability to be change agents within their households for treatment compliance. Adolescents provided insights into potential barriers and solutions to improve adult participation in cMDA, identified best practices of cMDA delivery, and suggested that they have unique roles as change agents to increase their household participation in cMDA.

A molecular assessment of Ostertagia leptospicularis and Spiculopteragia asymmetrica among wild fallow deer in Northern Ireland and implications for false detection of livestock-associated species.

BACKGROUND: Wild deer populations utilizing livestock grazing areas risk cross-species transmission of gastrointestinal nematode parasites (GINs), including GINs with anthelmintic resistance (AR) traits. Wild deer have been shown to carry problematic GIN species such as Haemonchus contortus and Trichostrongylus species in the UK, but the presence of livestock GINs in Northern Ireland deer populations is unknown. Also, is it not known whether AR traits exist among GINs of deer such as Ostertagia leptospicularis and Spiculopteragia asymmetrica in pastureland where anthelmintics are heavily used. METHODS: Adult-stage GIN samples were retrieved from Northern Irish wild fallow deer abomasa. Individual specimens were subject to a species-specific PCR analysis for common sheep and cattle GIN species with ITS-2 sequence analysis to validate species identities. In addition, the beta-tubulin gene was subject to sequencing to identify benzimidazole (BZ) resistance markers. RESULTS: ITS-2 sequencing revealed O. leptospicularis and S. asymmetrica, but species-specific PCR yielded false-positive hits for H. contortus, Teladorsagia circimcincta, Trichostrongylus axei, T. colubriformis, T. vitrinus and Ostertagia ostertagi. For beta-tubulin, O. leptospicularis and S. asymmetrica yielded species-specific sequences at the E198 codon, but no resistance markers were identified in either species at positions 167, 198 or 200 of the coding region. DISCUSSION: From this report, no GIN species of significance in livestock were identified among Northern Ireland fallow deer. However, false-positive PCR hits for sheep and cattle-associated GINs is concerning as the presence of deer species in livestock areas could impact both deer and livestock diagnostics and lead to overestimation of both GIN burden in deer and the role as of deer as drivers of these pathogens. ITS-2 sequences from both O. leptospicularis and S. asymmetrica show minor sequence variations to geographically distinct isolates. AR has been noted among GINs of deer but molecular analyses are lacking for GINs of wildlife. In producing the first beta-tubulin sequences for both O. leptospicularis and S. asymmetrica, we report no BZ resistance in this cohort. CONCLUSIONS: This work contributes to genetic resources for wildlife species and considers the implications of such species when performing livestock GIN diagnostics.

Epidemiology and field efficacy of anthelmintic drugs associated with gastrointestinal nematodes of sheep in Nejo district, Oromia, Ethiopia.

Gastrointestinal nematodes (GINs) are major constraints to health and productivity of small ruminants. Methods of their control relies mainly on anthelmintic drugs; however, the indiscriminate use of these drugs could lead to the development of anthelmintic resistance (AR). This study aimed to investigate the epidemiology of GINs infection, and field evaluation of anthelmintic efficacy in sheep. The epidemiological data were collected using a cross-sectional study design while a farm-based field study design was employed for the evaluation of anthelminthic efficacy. Furthermore, standard parasitological techniques were employed for qualitative and quantitative worm identification. The overall prevalence indicated 50.3%. Six genera of GINs (Haemonchus, Trichostrongylus, Oesophagostomum/Chabertia, Trichuris, Teladosargia/Ostertagia and Nematodirus) were identified. Among the identified genera, Haemonchus (25.4%) and Trichostrongylus (24.8%) were the dominant genera followed by mixed infection (21.8%), Oesophagostomum/Chabertia (10.4%), Trichuris (7.8%), Teladosargia (Ostertagia) (5.7%) and Nematodirus (4.1%). Mixed infections consisted either of double infections with Haemonchus and Trichostrongylus, or triple infections with Haemonchus, Trichostrongylus and Trichuris. The McMaster egg counting results showed that the mean EPG of infected sheep was 845.6. The results also showed 66 (34.2%), 101 (52.3%) and 26 (13.5%) sheep had low, moderate and heavy worm burden, respectively. Albendazole and Ivermectin showed low efficacy (percentage reductions = 90% and 92%; 95% lower confidence limit = 82.1% and 83.6% respectively) whereas Tetramisole was effective (FECR% = 96.8%; 95% LCL = 93.4%). Factors such as age, body condition, management system and past deworming history of sheep were found to have a statistically significant (p < 0.05) influence on the occurrence and burden of the worms. This is further explained as the highest prevalence and worm burden was detected in sheep of young age (p = 0.008; OR = 0.58; 95% CI = 0.39-0.87), poor body condition (p = 0.001; OR = 0.08; 95% CI = 0.04-0.16) and sheep kept under semi-intensive (p = 0.04; OR = 1.53; 95% CI = 1.02-2.29) with no deworming history for the last two months (p = 0.001; OR = 2.97; 95% CI = 1.94-4.56). The study results revealed that nematode infections were among sheep health constraints that could hurt their productivity while low efficacy of Albendazole and Ivermectin were detected. Therefore, the appropriate management techniques of GIN infections should be designed and implemented. Moreover, a further study involving more sensitive techniques (e.g. Mini-FLOTAC, molecular, and serological techniques) should be conducted by considering different host and environmental risk factors such as production level and seasons.

Follicular larva migrans.

Follicular larva migrans (FLM) is a rare and atypical clinical presentation of hookworm-related cutaneous larva migrans (HrCLM). FLM is characterized clinically by follicular, round, small, erythematous papules that are sometimes topped by vesicles or pustules. These lesions are usually located on the abdomen, back, buttocks and thighs and are accompanied by more or less severe pruritus. Some typical and/or short and fragmented tracks may also be visible. FLM is more resistant to anti-helminthic drugs than classical HrCLM: this is likely due to the deep location of larvae in hair follicles. We present two cases of FLM and a review of the literature.

PHARMACOKINETICS AND EFFICACY OF A SINGLE TOPICAL DOSE OF EPRINOMECTIN IN GIRAFFE (GIRAFFA SPP.).

Growing resistance to current antiparasitic medications, both in livestock and in zoological species under human care, makes it imperative to evaluate available drugs on the market, such as eprinomectin. In this prospective study, five males and one female of reticulated (Giraffa reticulata; n = 2), Masai (Giraffa tippelskirchii; n = 1), Nubian (Giraffa camelopardalis; n = 2), and hybrid subspecies (n = 1) of giraffe, received 1.5 mg/kg eprinomectin topically along the dorsum. Using high-performance liquid chromatography, concentrations of eprinomectin in plasma samples collected at 0, 4, 24, and 48 h, and 7, 14, 21, and 28 d were evaluated following drug administration. Complete blood cell counts and biochemistry panels were performed before (n = 6) and after (n = 3) eprinomectin administration. Samples for modified double centrifugal fecal flotation (n = 6) were evaluated prior to eprinomectin administration to evaluate for endoparasites and were repeated after the study (n = 5). Noncompartmental pharmacokinetic analysis was applied to the data. The observed maximum plasma concentration was 11.45 ng/ml and the time of observed maximum concentration was 2.67 d. The mean terminal half-life was 5.16 d. No adverse effects were observed related to eprinomectin administration and no blood work changes were observed. Parasite loads decreased (n = 3) or did not change (n = 2) after eprinomectin administration. The mean peak plasma concentration of eprinomectin in giraffe was similar to that achieved in cattle, despite using three times the dose.

The effectiveness of albendazole against hookworm infections and the impact of bi-annual treatment on anaemia and body mass index of school children in the Kpandai district of northern Ghana.

The impact of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) (initiated in 2000 in Ghana and ran for 12 years) in mitigating soil-transmitted helminth (STH) infections in LF-endemic areas is unknown. During a 1-year hiatus which ensued between 2011 and 2012, a longitudinal study was conducted to determine GPELF effect on hookworm infections in selected communities involved in the programme since its inception, while measuring the effectiveness of biannual ALB treatments on schoolchildren living in such communities. A total of 399 school children aged 3 to 18 years were randomly selected from four communities in the Kpandai district of northern Ghana. Each presented a single stool sample at baseline, 21 days post-treatment, at the 3rd and 6th months, 21 days post-second intervention (i.e. following sample collection and treatment with ALB in the 6th month), and in the ninth month of the study period. Haemoglobin (hb) levels were also measured at all time points using finger prick blood samples and a URIT digital test kit. Each participant submitting a sample, was treated with a single-dose ALB (400mg) at baseline and in the sixth month. Stool samples were processed by preparing duplicate Kato-Katz slides per sample, and examined by microscopy. The Body Mass Index-for-age z-scores (BAZ) of participants were assessed following the determination of BMIs at each time point by measuring their height and weight with a stadiometer and weighing scale. Overall hookworm prevalences were 25.68% (95% CI = 20.51-31.75) at baseline, 11.18% (95% CI = 7.87-15.41) 21 days post-treatment, 11.78% (95% CI = 8.38-16.11) and 6.95% (95% CI = 4.41-10.43) in the 3rd and 6th months, 0.91% (95% CI = 0.19-2.65) 21 days post-second intervention, and 8.46% (95% CI = 5.62-12.23) in the ninth month. Observed overall faecal egg count reduction rates (ERRs) were 94.21% (95% CI = 81.50%- 100.00%) 21 days after baseline treatment, 97.70% (95% CI = 85.08-100.00) and 96.95% (95% CI = 84.18%- 100.00%) in the 3rd and 6th months, 99.98% (95% CI = 86.42%- 100.00%) 21 days post-second intervention, and 17.18% (95% CI = 14.07%- 20.67%) in the 9th month. Respective cure rates (CRs) were 62.35% (95% CI = 46.71-81.56%), 85.88% (95% CI = 67.32-100.00%), 87.06% (95% CI = 68.36%- 100.00%), 98.82% (95% CI = 78.83%- 100.00%), and 36.36% (95% CI = 9.91%- 93.11%). Additionally, increases in the percent frequency of 'normal hb' (p < 0.01) were observed across the study time points, whilst 'normal BAZ' cases remained high (from 94.87% to 98.87%) throughout the study period. These findings primarily indicate satisfactory effectiveness of ALB which may be maintainable in mass drug administration programmes by the modification of treatment strategies from annual to bi-annual regimes. This could minimize the likelihood of emerging poorly-responding hookworm phenotypes in Ghana. Additionally, a positive impact of bi-annual treatment on participant anaemia status is herein indicated with particular regard to the school children in our cohort.

Egg excretion patterns of soil-transmitted helminth infections in humans following albendazole-ivermectin and albendazole treatment.

BACKGROUND: Control efforts of soil-transmitted helminthiases rely primarily on large scale administration of anthelminthic drugs. The assessment of drug efficacies and understanding of drug behavior is pivotal to the evaluation of treatment successes, both in preventive chemo-therapy programs as well as in research of novel treatment options. The current WHO guidelines recommend an interval of 14-21 days between the treatment and follow-up, yet no in-depth analysis of egg excretion patterns of Trichuris trichiura after treatment has been conducted to date. METHODS: Within the framework of a multi-country trial to assess the efficacy and safety of albendazole-ivermectin combination therapy vs albendazole monotherapy against T. trichiura infections, we conducted a study collecting daily stool samples over the period of 28 days post-treatment in 87 participants in Pak Khan, Lao PDR. Egg counts were derived by duplicate Kato-Katz on-site for T. trichiura, hookworm and Ascaris lumbricoides and stool sample aliquots were subsequently analyzed by qPCR for the detection of T. trichiura infections. Sensitivity and specificity was calculated for each day separately using data derived by Kato-Katz to determine the optimal timepoint at which to assess drug efficacy. RESULTS: Egg excretion patterns varied across treatment arms. For T. trichiura, only the albendazole-ivermectin treatment led to a considerable reduction in mean egg counts, whereas both treatments reduced hookworm egg counts and A. lumbricoides were cleared in all participants after day 7. For T. trichiura, we found sensitivity to be highest at days 18 and 22 when using egg counts as outcome and days 19 and 24 when using qPCR. Specificity was high (>0.9) from day 14 onwards. For hookworm, the highest sensitivity and specificity were found at days 17 and 25, respectively. CONCLUSIONS: Based on our study, the ideal time period to assess drug efficacy for soil-transmitted helminth infections would be between day 18 and 24. The current WHO recommendation of 14 to 21 days is likely to yield acceptable outcome measures for soil-transmitted helminth infections. TRIAL REGISTRATION: NCT03527732.

Revisiting anthelmintic resistance in sheep flocks from São Paulo State, Brazil.

Haemonchus contortus and Trichostrongylus colubriformis are the most important gastrointestinal nematodes causing serious losses in sheep production of tropical and subtropical regions. Prophylaxis of gastrointestinal nematode infections is based on anthelmintics use, but their frequent administration selects multiple-resistant parasites. To evaluate how the situation has changed over the last decades, the anthelmintic resistance status of gastrointestinal nematodes in sheep flocks was assessed in the current study and compared to previous surveys. In each one of the 15 flocks evaluated, animals (n ≥ 7) were allocated into at least five groups and treated as follows: 1) untreated control; 2) albendazole; 3) levamisole; 4) ivermectin; and 5) monepantel. If more animals were available, two additional groups were included: 6) closantel, and 7) moxidectin. The faecal egg count reduction test (FECRT) was carried out to evaluate the pre- and post-treatment using the SHINY tool. Haemonchus spp. was the most prevalent nematode from faecal cultures. The mean efficacy of albendazole was 40%. Only in two farms, levamisole presented a relatively high percentage of reduction in the FECRT about 90%, while ivermectin and moxidectin presented the worst mean efficacy of 34% and 21% among all farms, respectively. Like other anthelmintics, closantel demonstrated low efficacy (63%) across all farms evaluated. Monepantel presented an overall mean efficacy of 79%, but it was the only anthelmintic that presented efficacy ≥95%, in five farms. The results revealed that gastrointestinal nematodes with multiple anthelmintic resistance were prevalent in all 15 sheep herds. The research suggests that nematodes are becoming more and more resistant to various anthelmintic compounds, which has made the problem worse. This circumstance highlights the necessity to put into practice sustainable and long-lasting methods to prevent gastrointestinal nematode infections in sheep husbandry.

Dietary glycemic and energy load differentially modulates Schistosoma mansoni-induced granulomatous inflammation and response to antiparasitic chemotherapy.

The impact of diet composition and energy content on schistosomiasis evolution and treatment efficacy is still controversial. This study compared the impact of sucrose-rich diet and intermittent fasting on Schistosoma mansoni infection and praziquantel (PZQ)-based chemotherapy response in mice. BALB/c mice were infected with S. mansoni and followed for 15 weeks. The animals were randomized into nine groups receiving high glycemic load (high-sucrose diet - HSD), low caloric load (standard chow alternate-day fasting - ADF), and standard chow ad libitum (AL). Eight weeks after S. mansoni infection, these groups remained untreated or were treated with PZQ (300 mg/kg/day) for 3 days. Our results indicated that parasite load (S. mansoni eggs and parasite DNA levels), granulomatous inflammation (granulomas number and size), and liver microstructural damage (reduction in hepatocytes number, increase in nucleus-cytoplasm ratio, connective stroma expansion and fibrosis) were increased in ADF-treated animals. These animals also showed decreased eggs retention, granulomatous inflammation and collagen accumulation in the small intestine. Conversely, HSD diet and PZQ treatment attenuated all these parameters and stimulated hepatic regenerative response. PZQ also stimulated fibrosis resolution in HSD-treated mice, effect that was limited ADF-exposed mice. Our findings indicate that dietary glycemic and energy load can modulate schistosomiasis progression and the severity of hepatic and intestinal granulomatous inflammation in untreated and PZQ-treated mice. Thus, lower intestinal eggs retention may potentially be linked to worsening liver disease in ADF, while attenuation of hepatic and intestinal granulomatous inflammation is consistent with reduced parasite load in HSD- and PZQ-treated animals.

Assessing the effectiveness of fenbendazole supramolecular complexes against schistosomiasis, monieziosis and parabronemosis in sheep.

Helminth infections pose a significant economic threat to livestock production, causing productivity declines and, in severe cases, mortality. Conventional anthelmintics, exemplified by fenbendazole, face challenges related to low solubility and the necessity for high doses. This study explores the potential of supramolecular complexes, created through mechanochemical modifications, to address these limitations. The study focuses on two key anthelmintics, praziquantel (PZQ) and fenbendazole (FBZ), employing mechanochemical techniques to enhance their solubility and efficacy. Solid dispersions (SD) of PZQ with polymers and dioctyl sulfosuccine sodium (DSS) and fenbendazole with licorice extract (ES) and DSS were prepared. The helminthicidal activity of these complexes was assessed through helminthological dissections of sheep infected with Schistosoma turkestanicum, moniesiasis, and parabronemosis. In the assessment of supramolecular complex of FBZ (SMCF) at doses ranging from 1.0 to 3.0 mg/kg for the active substance (AS), optimal efficacy was observed with the fenbendazole formulation containing arabinogalactan and polyvinylpyrrolidone at a 3.0 mg/kg dosage. At this concentration, the formulation demonstrated a remarkable 100% efficacy in treating spontaneous monieziosis in sheep, caused by Moniezia expansa (Rudolphi, 1810) and M. benedenii (Moniez, 1879). Furthermore, the SMCF, administered at doses of 1.0, 2.0, and 3.0 mg/kg, exhibited efficacy rates of 42.8%, 85.7%, and 100%, respectively, against the causative agent of parabronemosis (Parabronema skrjabini Rassowska, 1924). Mechanochemical modifications, yielding supramolecular complexes of PZQ and FBZ, present a breakthrough in anthelmintic development. These complexes address solubility issues and significantly reduce required doses, offering a practical solution for combating helminth infections in livestock. The study underscores the potential of supramolecular formulations for revolutionizing helminthiasis management, thereby enhancing the overall health and productivity of livestock.

*Inactivation of encysted muscle larvae of Trichinella spiralis in pigs using Mebendazole.

We evaluated the effect of 4 anthelmintic treatments on the viability of Trichinella spiralis encysted muscle larvae (ML) 55 days post infection (PI) in experimentally infected pigs. Muscle larvae were isolated from pig muscle by artificial digestion after oral treatment of pigs with Levamisole (8 mg/kg, daily for 5 days) and Mebendazole (50 mg/kg, daily for 5 days); Doramectin (0.3 mg/kg, single IM injection), and Moxidectin (0.5 mg/kg, single pour on). Isolated larvae from treated pigs were orally inoculated into mice to assess viability of ML from each treatment. Only Mebendazole treatment of pigs significantly reduced ML viability in mice. The effect of timing of the effective Mebendazole treatment on ML from a longer term infection was then examined in a second experiment. Analysis revealed that Mebendazole treatment of pigs with 250 mg/kg over 3 days (83 mg/kg/day) or 5 days (50 mg/kg/day) reduced numbers of ML recovered from pig tissues compared to untreated, infected controls, and rendered ML non-infective to mice; Mebendazole treatment of pigs with 250 mg/kg in a single dose was not effective in reducing ML numbers recovered from pigs or in impacting ML infectivity to mice. An examination of the lowest effective dose of Mebendazole on encysted ML was determined in a third experiment. Mebendazole of pigs with 5, 50, or 100 mg/kg over 3 days demonstrated that 5 or 50 mg/kg over 3 days insufficient to reduce infectivity in recovered ML, while 100 mg/kg (and 83 g from experiment 2) over 3 days significantly reduces infectivity of ML. This procedure provides a means to evaluate the efficacy of various anthelmintic treatments on the viability of Trichinella spiralis ML in pig tissues, and identified Mebendazole, at 83-100 mg/kg administered over a 3-5 day period as an anthelmintic which renders encysted Trichinella spiralis ML from pig tissues non-infective. As risk from Trichinella significantly impacts acceptance of pork from pasture-raised pigs, these data provide a method, especially for producers of these high-risk pigs, to eliminate the potential of Trichinella transmission from infected pork.