Anticancer role of flubendazole: Effects and molecular mechanisms (Review).

Flubendazole, an anthelmintic agent with a well-established safety profile, has emerged as a promising anticancer drug that has demonstrated efficacy against a spectrum of cancer types over the past decade. Its anticancer properties encompass a multifaceted mechanism of action, including the inhibition of cancer cell proliferation, disruption of microtubule dynamics, regulation of cell cycle, autophagy, apoptosis, suppression of cancer stem cell characteristics, promotion of ferroptosis and inhibition of angiogenesis. The present review aimed to provide a comprehensive overview of the molecular underpinnings of the anticancer activity of flubendazole, highlighting key molecules and regulatory pathways. Given the breadth of the potential of flubendazole, further research is imperative to identify additional cancer types sensitive to flubendazole, refine experimental methodologies for enhancing its reliability, uncover synergistic drug combinations, improve its bioavailability and explore innovative administration methods. The present review provided a foundation for future studies on the role of flubendazole in oncology and described its molecular mechanisms of action.

Therapeutic effects of myrrh extract and myrrh-based silver nanoparticles on Trichinella spiralis-infected mice: parasitological, histopathological, and immunological (IFN-γ, IL-10, and MMP-9) investigations.

Introduction: Trichinellosis, caused by Trichinella spiralis (T. spiralis), remains a prevalent parasitic zoonosis. Developing new drugs targeting and understanding the immune response against the infection is imperative. Previous research has inadequately explored the efficacy of crude myrrh extract and myrrh-based silver nanoparticles (AgNPs) against trichinellosis, as well as their impact on histopathological, and immunological factors. Methods: This study evaluated the effects of silver nanoparticles biosynthesized using myrrh, crude myrrh extracts, and albendazole on the intestinal phase of T. spiralis. It also examined the associated histopathological changes and alterations in key immunological markers, including Interferon-gamma (IFN-γ), Interleukin-10 (IL-10), and Matrix Metalloproteinase-9 (MMP-9). Five groups of 12 mice were allocated as follows: group 1: non-infected, non-treated (negative control), group 2: infected, non-treated (positive control), group 3: infected and treated with biosynthesized silver nanoparticles (40 µg/mL), group 4: infected and treated with myrrh crude extract (800 mg/kg), and group 5: infected and treated with albendazole (50 mg/kg). Treatment was orally administered starting on the 2nd day post-infection and continued for three successive days. Mice of all groups were euthanized on the 6th day post-infection, and the intestine of each was isolated for parasitological, histopathological, and immunohistochemistry evaluation of MMP-9, as well as assessment of cytokines level (IFN-γ and IL-10 gene expressions) via Real-time PCR technique. Results: The present study showed a considerable reduction in adult worm count among the treated groups. The mortality rates of adult worms were 88.64% in the silver nanoparticles treated group, 85.17% in the myrrh crude extract group, and 94.07% in the albendazole-treated group. Histopathological examination revealed prominent alterations in the intestine of the infected non-treated mice, which were markedly restored by treatment. Immunohistochemical examination accompanied by significant reduction in MMP-9 expression in the infected mice treated with AgNPs compared to the infected non-treated group, reflecting the role of AgNPs in downgrading the inflammatory reaction in the intestine of infected mice. Conclusion: Collectively, this study demonstrates the novel antiparasitic potential of silver nanoparticles biosynthesized with myrrh against T. spiralis in infected mice. The treatment was associated with moderate rise in IFN-γ gene expression and IL-10 expression, highlighting its therapeutic efficacy against T. spiralis.

Effectiveness of benzimidazole treatments against Haemonchus contortus in sheep and goats - Do they produce similar responses?

The primary aim of this study was to compare the in vivo responses to orally administered doses of albendazole (5 mg/kg body weight) between experimentally infected sheep and goats. Fifty-four Improved Valachian lambs and 54 Saanen goat kids were split into six groups of nine animals. The sheep and goats were infected with larvae of the gastrointestinal nematode parasite Haemonchus contortus containing 10, 20, 30, 40, 60, and 80 % of the isotype-1 ß-tubulin gene codon 200 alleles previously shown to be associated with benzimidazole (BZ)-resistance. All groups of goats generally had higher mean eggs per gram (EPG) before treatment, which was significant (p<0.05) only for the group with 80 % resistance alleles. An in vivo faecal egg reduction test (FECRT) was used to determine the efficacy of albendazole (ABZ) eight days after treatment. Anthelmintic treatment significantly reduced the EPGs in the groups with 10, 20, and 80 % resistance alleles in sheep and with 10, 20, 30, and 40 % resistance alleles in goats. Differences in efficacy between the sheep and goats after the application of doses of ABZ recommended for sheep mostly ranged from 2 % to 10 %. The largest variation was in the group infected with worms containing 60 % resistance alleles, where the efficacy was 13 % higher in goats. Our secondary aims were to evaluate the data obtained from an in vitro egg hatch test (EHT) in sheep and goats and to compare these data with the results from the isotype-1 ß-tubulin gene codon 200 pyrosequencing and the FECRT. The percentages of the BZ-resistance alleles were comparable with the mean hatching obtained in the EHT and were also supported by the FECRT data for all groups. The results of the in vivo tests should be verified in the future using in vivo surveys conducted in mixed breeds and infections in multiple species.

The effect of Momordica charantia extract on sheep infected with Haemonchus contortus.

Bitter melon (Momordica charantia) has several biological properties including anthelmintic activity. Presented in vivo study evaluated the anthelmintic activity of the hydroalcoholic extract of M. charantia Presented in vivo study (HEMC) and its effect on animal performance, carcass characteristics and lamb meat quality in animals infected by Haemonchus contortus. The HEMC demonstrated effectiveness against the parasite. Lambs treated with HEMC showed a significant reduction in egg count per gram of faeces and in the number of parasites in the abomasum. However, nutrient intake decreased with increasing doses of HEMC, leading to reductions in final live weight and carcass weight. No significant effects were observed on meat quality. Therefore, it is concluded that HEMC presents anthelmintic action, but it also impairs animal performance, highlighting the need to assess the benefits and impacts of HEMC use for H. contortus control.

Exploring alternative anthelmintic compounds: Impact of peruvin, hentriacontane/1-nonacosanol and their synergistic effect on the health of Meriones unguiculatus infected with Haemonchus contortus.

Haemonchus contortus is a highly pathogenic blood-feeding parasite affecting sheep and goats, leading to significant economic losses. With increasing resistance to conventional anthelmintics, exploring plant-based alternatives is crucial. In vitro, studies suggest that peruvin and hentriacontane/1-nonacosanol, isolated from Artemisia cina (Asteraceae), may synergistically control Haemonchus contortus. However, their in vivo efficacy and safety are unestablished. This study evaluated these compounds' anthelmintic activity and health effects and their synergistic mixture in Meriones unguiculatus (gerbils). The compounds were isolated using open-column chromatography and identified by spectroscopic techniques. Gerbils were artificially infected with H. contortus following dexamethasone treatment to enhance infection. Anthelmintic activity was assessed by larval reduction in the stomach, blood biochemical parameters using a blood chemistry analyzer, and the anatomopathological changes in kidney and liver tissues. Peruvin (0.4 mg/kg) and hentriacontane/1-nonacosanol (2.60 mg/kg) achieved larvicidal reductions of 84.86 % and 74.05 %, respectively, while their synergistic mixture (0.08/0.0017 mg/kg) resulted in a 100 % reduction. Histopathological analysis revealed minor inflammation and albuminous degeneration, primarily affecting the liver. The peruvin-treated group showed notable kidney damage, while hepatic alterations were similar across both compounds. Although effective, further research is needed to optimize dosing and ensure safety.

Reduced anthelmintic use on 13 New Zealand sheep farms: farmer motivations and practical implementation.

AIMS: To describe the personal drivers, sources of information and gastro-intestinal parasite control methods used by a group of New Zealand sheep farmers identified as low users of anthelmintic (AHC), and their perception of the efficacy and impacts of this approach. METHODS: A convenience sample of 13 sheep farmers farming with a policy of reduced AHC use (no pre-determined routine treatments of ewes >19 months old and/or lambs not routinely treated at pre-determined intervals from weaning through to late autumn) were identified. Semi-structured interviews were conducted regarding their farming philosophy, motivations for reducing AHC use, perceptions of the impacts of farming with reduced AHC use, and parasite control practices. Semi-quantitative data were analysed using descriptive statistics for demographic data and categorising participants' use of AHC and non-chemical control methods. Qualitative data regarding participants' motivations, approaches and rationale were analysed by systematic analysis of the transcripts and distillation of key concepts. RESULTS: Participants had been operating with reduced AHC use for 3 to ≥20 years. Key motivators for reducing AHC use were a diagnosis of anthelmintic resistance (AR) or concerns about AR developing. Parasite management information came from a wide range of sources. All respondents expressed overall positive views regarding the impacts of reduced AHC use but detailed information was not available.All identified that regular monitoring, based primarily on subjective animal and non-animal factors was important for their parasite control strategy. Most used faecal egg counts (FEC), often in an ad hoc manner. Five never treated adult ewes, two routinely treated ewes prior to lambing with short-acting AHC and the remainder occasionally treated a small number in low body condition. Four routinely treated some or all lambs at 28-30-day intervals from weaning to late autumn while the remainder based their treatment decisions for lambs on monitored information. All placed heavy emphasis on feeding sheep well, ensuring high post-grazing residuals, and cross-grazing. CONCLUSIONS: AR was a key motivator for participants to reduce AHC use, and a range of information sources and decision-making processes were used. Key parasite management practices were monitoring, primarily using subjective assessments, emphasis on feeding stock well and cross-grazing. CLINICAL RELEVANCE: The rising prevalence of AR will likely result in increasing the motivation for sheep farmers to reduce their AHC use. Veterinarians will play a key role in providing advice and assistance to facilitate changes in parasite management.

Effect of green tea dust as a dietary additive and anthelminthic on performance, digestibility, and fecal egg counts in Priangan ewe lambs infected with Strongyles worms.

Despite green tea dust (GTD) is a by-product of green tea fabrication, it has the potential as natural additive and anthelmintic in ruminant diets due to its high protein and bioactive contents. This study aimed to compare the effect of 3 different doses [0% (control), 0.75% (GTD-0.75), and 1.5% (GTD-1.5)] of GTD supplementation on dry matter intake (DMI, g/kg DM), average daily gain (ADG, g/kg DM), nutrient digestibility (%), and fecal egg counts (FEC, eggs/g feces) of local ewe lambs infected with Strongyles worms during 84 days feeding trial using a completely randomized design and six replicates (n = 6). The results showed that all lamb groups decreased body weight; however, GTD-1.5 supplemented lambs tended (P = 0.061) to have better ADG at the end of the trial compared to the other groups. In addition, GTD-1.5 supplemented lambs had lower (P < 0.05) FEC at day 42 and day 56 than those the control lambs. About 1.5% GTD supplementation in a diet has the potential as dietary additive and anthelmintic to maintain the productivity, health, and welfare in rearing lambs.

Application potential of albendazole as an aquatic animal drug based on its safety, efficacy, and residue profiles.

The number of available drugs for treating aquatic animals is insufficient, given the occurrence of a variety of parasites and difficulties in developing appropriate treatments, such as vaccines or immunostimulants. Consequently, repurposing livestock drugs for treating aquatic animals is a viable alternative. Several studies have demonstrated that albendazole (ABZ) is a good anthelmintic for humans and animals such as ruminants, poultry, and honeybees. Therefore, we investigated the toxicological studies, metabolic and residue depletion studies, and efficacy trials of ABZ in aquatic animals to identify its application potential as a drug for aquatic animals. ABZ was depleted within 24 h in the muscle tissues of hybrid striped bass, rainbow trout, and tilapia. In muscle tissue with adhering skin obtained from tilapia and largemouth bass, a significant quantity of the amino-sulfone metabolite of ABZ (ABZ-SO2NH2) was present, while no ABZ-SO2NH2 was detected in hybrid striped bass, channel catfish, and patinga. Fish exposed only to high doses of ABZ showed reduced red blood cell counts and hemoglobin levels and increased lymphocytes. Such signs of toxicity have also been observed in human patients and animal studies. At a dose of 100 mg/L, ABZ showed 100% efficacy in eels. In addition, albendazole sulfoxide (ABZSO) demonstrated efficacies of 96.1% and 100% in pirapatinga and ray-finned fish, respectively, at a dose 500 mg/L. ABZ was also highly effective in treating an intracellular parasite E. hepatopenaei in white shrimp. The application of ABZ in aquatic animals under the low-dose and short-term conditions is considered a reasonable solution to manage parasite infections. The types and residual periods of degradation products differed among fish species, suggesting dissimilar metabolic pathways. With a high demand for new alternative veterinary drugs in aquaculture by fish farmers, this review offers important evidence for considering the use of ABZ in Korean farmed fish, taking food safety issues into account.

Rafoxanide negatively modulates STAT3 and NF-κB activity and inflammation-associated colon tumorigenesis.

In the colorectal cancer (CRC) niche, the transcription factors signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB) are hyperactivated in both malignant cells and tumor-infiltrating leukocytes (TILs) and cooperate to maintain cancer cell proliferation/survival and drive protumor inflammation. Through drug repositioning studies, the anthelmintic drug rafoxanide has recently emerged as a potent and selective antitumor molecule for different types of cancer, including CRC. Here, we investigate whether rafoxanide could negatively modulate STAT3/NF-κB and inflammation-associated CRC. The antineoplastic effect of rafoxanide was explored in a murine model of CRC resembling colitis-associated disease. Cell proliferation and/or STAT3/NF-κB activation were evaluated in colon tissues taken from mice with colitis-associated CRC, human CRC cells, and CRC patient-derived explants and organoids after treatment with rafoxanide. The STAT3/NF-κB activation and cytokine production/secretion were assessed in TILs isolated from CRC specimens and treated with rafoxanide. Finally, we investigated the effects of TIL-derived supernatants cultured with or without rafoxanide on CRC cell proliferation and STAT3/NF-κB activation. The results showed that rafoxanide restrains STAT3/NF-κB activation and inflammation-associated colon tumorigenesis in vivo without apparent effects on normal intestinal cells. Rafoxanide markedly reduces STAT3/NF-κB activation in cultured CRC cells, CRC-derived explants/organoids, and TILs. Finally, rafoxanide treatment impairs the ability of TILs to produce protumor cytokines and promote CRC cell proliferation. We report the novel observation that rafoxanide negatively affects STAT3/NF-κB oncogenic activity at multiple levels in the CRC microenvironment. Our data suggest that rafoxanide could potentially be deployed as an anticancer drug in inflammation-associated CRC.

Upcycling Surinam cherry and spine gourd fruit waste: development of anthelmintic jelly candies using fruit extracts.

Under-utilized fruits and vegetables are rich in nutraceuticals and have several medicinal properties. A large group of people widely consumes gummies and jelly candies, which can serve as an excellent vehicle to increase the intake of functional components. In the present study, jelly candies were developed by incorporating fruit extracts from commonly wasted segments of two under-utilized fruits (Surinam cherry and Spine gourd). Jelly candies were evaluated for their anthelmintic efficacy against Caenorhabditis elegans along with various physicochemical, microbial, colour, texture, and sensory parameters immediately after preparation, as well as during 150 days of storage at two conditions (ambient and accelerated). Ready-to-consume jelly candies (5 g) contained 0.21 g of fruit extract in Surinam cherry and 0.35 g of fruit extract in Spine gourd jelly candies. Jelly candies exhibited TSS in the range of 70.40 - 71.37°Brix, pH 2.33 to 2.84, aw 0.70-0.75, moisture 10.57-15.88%, a* value 5.33-1.27, b*value 10.66-1.28, no microbial contamination, and acceptable sensory parameters. Surinam cherry extract candy (4 mg/ml) showed a higher anthelmintic effect than Spine gourd extract candy (6.66 mg/ml) based on egg inhibition, larval death, and average adult worm paralysis time assays. These fruit extract-incorporated candies can be a novel healthier food product with anthelmintic potential, which can be an alternative to commonly used anthelmintic drugs. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-024-05967-5.

An Insight into Practices Associated with the Control of Internal Parasites in the Dairy Goat Herds of Romania: A Questionnaire Survey.

The widespread and uncontrolled use of anthelmintic products has contributed to the emergence of anthelmintic resistance (AR). This phenomenon globally threatens the productivity and welfare of small ruminants. A questionnaire consisting of 34 questions was handed to 234 goat farmers across Romania to gain insight into control practices against internal parasites and the farmers' perception of the parasitic infections present in their herds and the efficacy of anthelmintic treatments. The majority of farmers (88.5%) admitted they had never submitted fecal samples for parasitological laboratory analysis, and 77.4% had treated the animals on their own. In general, the farmers dewormed their goats based on visual body weight estimation. Prophylactic anthelmintic treatment was practiced by more than 85% of the farmers. A traditional control approach based on treating the entire herd at fixed time intervals is widespread among Romanian goat and sheep farmers. The most commonly used anthelmintic drugs in the previous 3 years (2021-2023) were benzimidazoles (85.5%) and macrocyclic lactones (81.6%). Poor anthelmintic efficacy was suspected by 14.5% of farmers, and the minority (18.0%) considered internal parasites as a problem in their herds. Regarding the farmers' perception of the presence of parasites, there was a significant level of uncertainty. This is the first survey carried out in Romanian goat herds, and it provides up-to-date information on practices aimed at controlling internal parasites.

Sustainable approach to control gastrointestinal nematodes using pelargonium quercetorum Agnew in goats.

The use of medicinal plants as a means of combating parasites is becoming increasingly popular due to general resistance to synthetic anthelmintics. Goats typically respond less well to anthelminthic treatments, which may increase their resistance to nematodes. For this purpose, the anthelmintic effect of Pelargonium quercetorum Agnew (P. quercetorum) extract was tested in an in vivo study against gastrointestinal parasites of goats. A total of 40 goats naturally infected with mixed gastrointestinal nematode species were divided into four groups: the first group was treated with albendazole (7.5 mg/kg), the second group received a single dose of closantel (7.5 mg/kg), the third group received plant extract (7.5 mg/kg), and the fourth group served as an untreated control. Fecal egg counts (FEC) were carried out on day 14, as well as day 0, which was prior to the first treatment dose. According to the results, maximum reduction in FEC percentage was observed in P. quercetorum treated group (63.41%). Furthermore, nematode parasites responded poorly to synthetic drugs, although there was a 4.72% and 45.54% decrease in FEC in the albendazole and closantel-treated groups, respectively. Although no significant difference was found between the treatment groups, the P. quercetorum treated group showed a significant reduction in fecal egg count after treatment. Based on findings, a P. quercetorum based anthelmintic could be a sustainable alternative to combat parasite infestation. Therefore, further studies are needed to determine the optimal dose rate and frequency of doses required for effective control of gastrointestinal parasites in goats.

Occurrence of fenbendazole resistance in Parascaris spp. on breeding farms in Sweden.

Anthelmintic resistance is an increasing problem in many gastrointestinal parasites of grazing animals. Among these, the equine roundworm, Parascaris spp., has developed wide-spread resistance to macrocyclic lactones over the past decades. Additionally, there are recent observations of emerging treatment failure of both tetrahydropyrimidine and fenbendazole. Therefore, the aims of this study were to further investigate the occurrence of fenbendazole resistance on breeding farms and to explore potential management-related risk factors associated with resistance in Parascaris spp. in Sweden. Eleven farms with 92 foals positive for Parascaris spp. were included in a faecal egg count reduction test during the years 2021-2023. According to the clinical protocol of the guidelines of the World Association for the Advancement of Veterinary Parasitology, fenbendazole resistance was present on four farms with efficacies varying from 45 % to 96 %. Having previously reported reduced efficacy on one of these farms, we can now confirm that fenbendazole resistance in Parascaris spp. has established. Farms with more than 40 yearly born foals had a significantly higher probability of having resistant Parascaris spp. Populations compared with smaller farms, (generalized linear model (GLM), t = 70.39, p < 0.001). In addition, there was a correlation between the number of foals on the farm and the frequency of yearly treatments showing that farms with < 20 foals were notably inclined to administer treatments twice during the first year (GLM, t=2.76, p < 0.05) in contrast to larger farms with > 40 foals that were using more frequent treatment intervals. In conclusion, this study confirms the establishment of fenbendazole resistance in Parascaris spp. populations on Swedish stud farms with the number of foals on the farm identified as a risk factor for development of anthelmintic resistance.

In vitro anthelmintic activity and colocalization analysis of hydroxycinnamic acids obtained from Chamaecrista nictitans against two Haemonchus contortus isolates.

This study assessed the in vitro anthelmintic activity of ethyl acetate extract (Cn-EtOAc) and its bioactive fractions (CnR3 and CnR5) obtained from Chamaecrista nictitans aerial parts against two Haemonchus contortus (Hc) isolates, one resistant (strain HcIVM-R) and another susceptible (strain HcIVM-S) to ivermectin. Ferulic acid and p-coumaric acid were identified in the bioactive fractions; therefore, their commercial standards were also assessed. A colocalization analysis between the ferulic acid commercial standard and eggs of the HcIVM-R strain was performed using confocal laser scanning microscopy and the ImageJ program. The ovicidal effects of the Cn-EtOAc extract, bioactive fractions and commercial compounds were tested through the egg hatching inhibition (EHI) assay on H. contortus isolates HcIVM-R and HcIVM-S. The Cn-EtOAc caused 88 % and 92 % EHI at 5000 µg/mL on HcIVM-R and HcIVM-S, respectively. Fractions CnR3 and CnR5 displayed the highest ovicidal activity against HcIVM-S, with effective concentrations (EC90) of 2134 and 601 µg/mL, respectively. Meanwhile, the commercial standards ferulic acid and p-coumaric acid also resulted in higher effectiveness on the same strain, with EC90 of 57.5 and 51.1 µg/mL. A colocalization analysis of ferulic acid and eggs of HcIVM-R revealed that this compound is localized to the cuticle surface of the embryo inside the egg parasite. The results demonstrated that both ferulic and p-coumaric acids interrupt the egg-hatching processes of the two Hc isolates. Both phenolic acids isolated from C. nictitans and commercial standards exhibited the best anthelmintic effect on HcIVM-S. These findings indicate that the phenolic acids were less effective in egg hatch inhibiting on the HcIVM-R strain compared to the HcIVM-S strain.

Development of non-sedating benzodiazepines with in vivo antischistosomal activity.

The neglected tropical disease schistosomiasis infects over 200 million people worldwide and is treated with just one broad-spectrum antiparasitic drug (praziquantel). Alternative drugs are needed in the event of emerging praziquantel resistance or treatment failure. One promising lead that has shown efficacy in animal models and a human clinical trial is the benzodiazepine meclonazepam, discovered by Roche in the 1970s. Meclonazepam was not brought to market because of dose-limiting sedative side effects. However, the human target of meclonazepam that causes sedation (GABAARs) is not orthologous to the parasite targets that cause worm death. Therefore, we were interested in whether the structure of meclonazepam could be modified to produce antiparasitic benzodiazepines that do not cause host sedation. We synthesized 18 meclonazepam derivatives with modifications at different positions on the benzodiazepine ring system and tested them for in vitro antiparasitic activity. This identified five compounds that progressed to in vivo screening in a murine model, two of which cured parasite infections with comparable potency to meclonazepam. When these two compounds were administered to mice that were run on the rotarod test, both were less sedating than meclonazepam. These findings demonstrate the proof of concept that meclonazepam analogs can be designed with an improved therapeutic index and point to the C3 position of the benzodiazepine ring system as a logical site for further structure-activity exploration to further optimize this chemical series.

P-glycoproteins in anthelmintic safety, efficacy, and resistance.

P-glycoprotein (PGP) is a pivotal transmembrane transporter governing the cellular flux of diverse substances shielding mammals from toxics. It can thwart the effectiveness of medicines such as ivermectin (IVM) and other macrocyclic lactone (ML) anthelmintics, undermining therapeutic efforts. We analyze the role of PGPs in limiting the toxicity of these drugs in hosts, and their potential contribution to anthelmintic resistance in nematodes. Targeting nematode PGPs to increase drug sensitivity to MLs seems interesting, but is hampered by the lack of selective inhibitors. The nuclear hormone receptor (NHR)-8 should be seriously considered as a target because it upregulates multiple PGPs involved in anthelmintic resistance and it is specific to nematodes. This would advance our understanding of host-pathogen dynamics and foster innovative therapeutic strategies.

Prevalence of Taenia solium cysticercosis in domestic pigs following albendazole deworming intervention in rural communities of Mbulu district, Tanzania.

Taeniosis and cysticercosis are infections caused by cestodes, Taenia solium is among them. T.solium neurocysticercosis accounts for 30% of acquired epilepsy in human in developing countries. This study was carried out to determine the prevalence of cysticercosis among domestic pigs in Mbulu district following deworming intervention. The study was conducted among three rural communities monitoring community intervention in Mbulu district between March 2020 and September 2021. Live pigs were diagnosed by lingual examination for the presence of T. solium cysticerci, and pig-rearing practices were recorded. Logistic regression was performed to determine the role of risk factors on pig infection outcome. We conveniently sampled 510 pigs; 267 (52.4%) were sampled in the year 2020 and 243 (47.6%) in 2021. All pigs were examined by lingual examination for the presence of pork tapeworm larvae, and 43 (8.4%) pigs were found to be infected. Twenty-one (48.8%) of the infected pigs were males and 22 (51.2%) were females, and the overall annual prevalence of tapeworm larvae was 9% and 7.8% for 2020 and 2021, respectively. The pigs were twice more likely to be found infected during the rainy season compared to the dry season in 2020 (OR = 2.27, 95%CI of 1.16-7.22). The reported pig-rearing practices were free-range, penned, and tethered, 141 (52.8%), 64 (24%), and 62 (23.2%), respectively. Of the 94 visited households in 2020, 78 (83%) reported drinking water without boiling, and 59 (62.8%) household leaders reported having heard about taeniosis/cysticercosis. The prevalence of cysticercosis among domestic pigs in this study was high, with seasonal variations. Despite the ongoing national school deworming and community deworming program, there was no significant change in the prevalence of cysticercosis over two consecutive years. The reported pig infections imply fecal-oral transmission with humans tapeworm eggs released from infected humans. Most households reported consuming unboiled drinking water that might be contaminated. Integrating pig vaccination and deworming, health education and school or community deworming along with improved pig management practice and general community water sanitation hygiene (WASH) are recommended to reduce the burden of pork tapeworm in the study communities.

Eco-friendly Regioselective Synthesis, Biological Evaluation of Some New 5-acylfunctionalized 2-(1H-pyrazol-1-yl)thiazoles as Potential Antimicrobial and Anthelmintic Agents.

The present study describes an eco-friendly NBS-assisted regioselective synthesis of new 5-acylfunctionalized 5-acylfunctionalized 2-(1H-pyrazol-1-yl)thiazoles by condensation of 3,5-dimethyl-1H-pyrazole-1-carbothioamide with unsymmetrical 1,3-diketones under solvent-free conditions. The structural elucidation of the newly synthesized compounds was accomplished using various spectroscopic techniques viz. FTIR, NMR and mass spectrometry. All the newly synthesized compounds were examined for their in vitro antimicrobial potential against both pathogenic gram positive and gram negative bacterial and fungal species as well as anthelmintic activity against Pheretima posthuma earthworms. The results of antimicrobial activity revealed that all tested compounds 3 a-j showed excellent antimicrobial potential particularly against S. aureus. It was also observed that compounds 3 e and 3 i (MIC=62.5 µg/mL) showed greater potency against E. coli, whereas compounds 3 a and 3 h (MIC=50 µg/mL and 62.5 µg/mL) demonstrated better activity against P. aeruginosa and compound 3 i (MIC=62.5 µg/mL) exhibited superior activity against S. pyogenus when compared to standard drug Ampicillin (MIC=100µg/mL). Compound 3 e and 3 j revealed remarkable antifungal and anthelmintic activities. To find out binding interactions of target compounds with target proteins and pharmacokinetic parameters of the compounds, in silico investigations involving molecular docking studies and ADMET predictions were also performed.