-
Trends in Parasitology Dec 2023The World Health Organization (WHO) recently proposed a new operational definition which designates communities with ≥10% prevalence of Schistosoma spp. infection as a... (Review)
Review
The World Health Organization (WHO) recently proposed a new operational definition which designates communities with ≥10% prevalence of Schistosoma spp. infection as a persistent hotspot, when, after at least two rounds of high-coverage annual preventive chemotherapy, there is a lack of appropriate reduction. However, inconsistencies and challenges from both biological and operational perspectives remain, making the prescriptive use of this definition difficult. Here, we present a comprehensive analysis of the use of the term 'hotspot' across schistosomiasis research over time, including both literature searches and opinions from a range of stakeholders, to assess the utility and generalisability of the new WHO definition of a persistent hotspot. Importantly, we propose an updated definition based on our analyses.
Topics: Animals; Praziquantel; Anthelmintics; Schistosoma haematobium; Schistosomiasis; Schistosoma mansoni
PubMed: 37806786
DOI: 10.1016/j.pt.2023.09.006 -
Trends in Parasitology Nov 2023Long-term intensive use of anthelmintics for parasite control of livestock, companion animals, and humans has resulted in widespread anthelmintic resistance, a problem... (Review)
Review
Long-term intensive use of anthelmintics for parasite control of livestock, companion animals, and humans has resulted in widespread anthelmintic resistance, a problem of great socioeconomic significance. But anthelmintic therapy may also select for other biological traits, which could have implications for anthelmintic performance. Here, we highlight recent examples of changing parasite dynamics following anthelmintic administration, which do not fit the definition of anthelmintic resistance. We also consider other possible examples in which anthelmintic resistance has clearly established, but where coselection for other biological traits may have also occurred. We offer suggestions for collecting more information and gaining a better understanding of these phenomena. Finally, we propose research questions that require further investigation and make suggestions to help address these knowledge gaps.
PubMed: 37633759
DOI: 10.1016/j.pt.2023.08.002 -
Molecules (Basel, Switzerland) Jul 2023Plant tannins are known for their anthelmintic and antiparasitic activities and have been increasingly studied to battle the ever-growing problem of anthelmintic...
Plant tannins are known for their anthelmintic and antiparasitic activities and have been increasingly studied to battle the ever-growing problem of anthelmintic resistance. While tannins have been shown to exhibit these activities on their own, one approach would be to use them as complementary nutrients alongside commercial anthelmintics. So far, research on the interactions between tannins and anthelmintics is limited, and few studies have reported both synergistic and antagonistic effects depending on the type of tannin and the method used. These interactions could either strengthen or weaken the efficacy of commercial anthelmintics, especially if tannin-rich diets are combined with anthelmintics used as oral drenches. To study these interactions, a series of hydrolysable tannins (HTs) was selected, and their direct interactions with thiabendazole (TBZ) were evaluated by isothermal titration calorimetry (ITC), which allowed the detection of the exothermic interaction but also the roles and significances of different structural features of HTs in these interactions. Our results show that HTs can have a direct interaction with the benzimidazole anthelmintic TBZ and that the interaction is strengthened by increasing the number of free galloyl groups and the overall molecular flexibility of HTs.
Topics: Tannins; Anthelmintics; Plant Extracts; Hydrolyzable Tannins; Thiabendazole; Calorimetry
PubMed: 37446937
DOI: 10.3390/molecules28135261 -
BMC Complementary Medicine and Therapies May 2024Highlighting affordable alternative crops that are rich in bioactive phytoconstituents is essential for advancing nutrition and ensuring food security. Amaranthus blitum...
BACKGROUND
Highlighting affordable alternative crops that are rich in bioactive phytoconstituents is essential for advancing nutrition and ensuring food security. Amaranthus blitum L. (AB) stands out as one such crop with a traditional history of being used to treat intestinal disorders, roundworm infections, and hemorrhage. This study aimed to evaluate the anthelmintic and hematologic activities across various extracts of AB and investigate the phytoconstituents responsible for these activities.
METHODS
In vitro anthelmintic activity against Trichinella spiralis was evaluated in terms of larval viability reduction. The anti-platelet activities were assessed based on the inhibitory effect against induced platelet aggregation. Further, effects on the extrinsic pathway, the intrinsic pathway, and the ultimate common stage of blood coagulation, were monitored through measuring blood coagulation parameters: prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT), respectively. The structures of isolated compounds were elucidated by spectroscopic analysis.
RESULTS
Interestingly, a previously undescribed compound (19), N-(cis-p-coumaroyl)-ʟ-tryptophan, was isolated and identified along with 21 known compounds. Significant in vitro larvicidal activities were demonstrated by the investigated AB extracts at 1 mg/mL. Among tested compounds, compound 18 (rutin) displayed the highest larvicidal activity. Moreover, compounds 19 and 20 (N-(trans-p-coumaroyl)-ʟ-tryptophan) induced complete larval death within 48 h. The crude extract exhibited the minimal platelet aggregation of 43.42 ± 11.69%, compared with 76.22 ± 14.34% in the control plasma. Additionally, the crude extract and two compounds 19 and 20 significantly inhibited the extrinsic coagulation pathway.
CONCLUSIONS
These findings extend awareness about the nutritional value of AB as a food, with thrombosis-preventing capabilities and introducing a promising source for new anthelmintic and anticoagulant agents.
Topics: Amaranthus; Animals; Anthelmintics; Plant Extracts; Phytochemicals; Platelet Aggregation Inhibitors; Anticoagulants; Larva
PubMed: 38704537
DOI: 10.1186/s12906-024-04478-2 -
Parasites & Vectors Jul 2023Helminth infections are an important public health problem in humans and have an even greater impact on domestic animal and livestock welfare. Current readouts for...
BACKGROUND
Helminth infections are an important public health problem in humans and have an even greater impact on domestic animal and livestock welfare. Current readouts for anthelmintic drug screening assays are stage development, migration, or motility that can be subjective, laborious, and low in throughput. The aim of this study was to apply and optimize a fluorometric technique using resazurin for evaluating changes in the metabolic activity of Ascaris suum third-stage larvae (L3), a parasite of high economic relevance in swine.
METHODS
Ascaris suum L3 were mechanically hatched from 6- to 8-week embryonated and sucrose-gradient-enriched eggs. Resazurin dye and A. suum L3 were titrated in 96-well microtiter plates, and resazurin reduction activity was assessed by fluorometry after 24 h of incubation. Fluorescence microscopy was used to localize the resazurin reduction site within the larvae. Finally, we exposed A. suum L3 to various stress conditions including heat, methanol, and anthelmintics, and investigated their impact on larval metabolism through resazurin reduction activity.
RESULTS
We show that the non-fluorescent dye resazurin is reduced inside vital A. suum L3 to fluorescent resorufin and released into the culture media. Optimal assay parameters are 100-1000 L3 per well, a resazurin concentration of 7.5 µg/ml, and incubation at 37 °C/5% CO for 24 h. An intact L2 sheath around the L3 of A. suum completely prevents the uptake of resazurin, while in unsheathed L3, the most intense fluorescence signal is observed along the larval midgut. L3 exposed to methanol or heat show a gradually decreased resazurin reduction activity. In addition, 24 h exposure to ivermectin at 0.625 µM, mebendazole at 5 µM, and thiabendazole from 10 to 100 µM significantly decreased larval metabolic activity by 55%, 73%, and 70% to 89%, respectively.
CONCLUSIONS
Together, our results show that both metabolic stressors and anthelmintic drugs significantly and reproducibly reduce the resazurin reduction activity of A. suum L3, making the proposed assay a sensitive and easy-to-use method to evaluate metabolic activity of A. suum L3 in vitro.
Topics: Humans; Animals; Swine; Ascaris suum; Methanol; Anthelmintics; Xanthenes; Ascariasis; Larva
PubMed: 37468906
DOI: 10.1186/s13071-023-05871-5 -
Veterinary Medicine (Auckland, N.Z.) 2023Anthelmintic resistance (AR) in gastrointestinal nematodes (GINs) is currently present worldwide and a major challenge to goat production. However, no updated...
BACKGROUND AND AIM
Anthelmintic resistance (AR) in gastrointestinal nematodes (GINs) is currently present worldwide and a major challenge to goat production. However, no updated information is available on this topic in the study area. Thus, this study evaluated the efficacy of commonly used anthelmintics on GINs in naturally-infected goats and assessed farmers' perception of anthelmintic utilization practices in Humbo district, Southern Ethiopia.
MATERIALS AND METHODS
The field experiments for routinely used anthelmintics, namely, albendazole, ivermectin, and tetramisole, were conducted from September 2022 to April 2023. Sixty naturally-infected goats with nematodes were selected based on egg count (≥150 eggs per gram of feces) and allocated randomly into four groups (15 animals per group). Then, fecal samples were collected pre- and post-treatment and examined for fecal egg count reduction (FECRT) to determine the AR status of goat GINs. The modified McMaster technique using standard floatation was used for quantifying the eggs. In addition, a questionnaire survey was conducted to assess anthelmintic utilization practices among goat owners.
RESULTS
The FECR levels for albendazole, ivermectin, and tetramisole were 94.6, 95.9, and 97.3%, respectively. By coproculture, the nematode genera identified before treatment were Haemonchus, Trichostrongylus, Teladorsagia, Oesophagostomum, Bunostomum, and Chabertia Species. However, post-treatment fecal cultures showed that some Haemonchus, Trichostrongylus, and Strongyloides spp. did not respond to the treatments. The questionnaire survey revealed that albendazole was the most commonly used anthelmintic to treat nematode infection in goats. Respondents expressed that anthelmintic treatment was utilized based on veterinarian prescription (59%), availability (32%), efficacy (4%), and affordability (5%).
CONCLUSION
Tetramisole should be used cautiously to prevent the development of resistant strains, as it was still effective in the study area. Additionally, regular monitoring of anthelmintic effectiveness is necessary.
PubMed: 38054011
DOI: 10.2147/VMRR.S434584 -
International Journal of Pharmaceutics Sep 2023In this paper we report a successful example of combining drugs through cocrystallization. Specifically, the novel solid is formed by two anthelminthic drugs, namely...
In this paper we report a successful example of combining drugs through cocrystallization. Specifically, the novel solid is formed by two anthelminthic drugs, namely praziquantel (PZQ) and niclosamide (NCM) in a 1:3 molar ratio, and it can be obtained through a sustainable one-step mechanochemical process in the presence of micromolar amounts of methanol. The novel solid phase crystallizes in the monoclinic space group of P2/c, showing one PZQ and three NCM molecules linked through homo- and heteromolecular hydrogen bonds in the asymmetric unit, as also attested by SSNMR and FT-IR results. A plate-like habitus is evident from scanning electron microscopy analysis with a melting point of 202.89 °C, which is intermediate to those of the parent compounds. The supramolecular interactions confer favorable properties to the cocrystal, preventing NCM transformation into the insoluble monohydrate both in the solid state and in aqueous solution. Remarkably, the PZQ - NCM cocrystal exhibits higher anthelmintic activity against in vitro S. mansoni models than corresponding physical mixture of the APIs. Finally, due to in vitro promising results, in vivo preliminary tests on mice were also performed through the administration of minicapsules size M.
Topics: Animals; Mice; Praziquantel; Niclosamide; Antiparasitic Agents; Pharmaceutical Preparations; Spectroscopy, Fourier Transform Infrared; Anthelmintics; Schistosoma mansoni
PubMed: 37579827
DOI: 10.1016/j.ijpharm.2023.123315 -
Chemosphere Dec 2023Anthelmintics are drugs used for the treatment and prevention of diseases caused by parasitic worms (helminths). While the importance of anthelmintics in human as well... (Review)
Review
Anthelmintics are drugs used for the treatment and prevention of diseases caused by parasitic worms (helminths). While the importance of anthelmintics in human as well as in veterinary medicine is evident, they represent emerging contaminants of the environment. Human anthelmintics are mainly used in tropical and sub-tropical regions, while veterinary anthelmintics have become frequently-occurring environmental pollutants worldwide due to intensive agri- and aquaculture production. In the environment, anthelmintics are distributed in water and soil in relation to their structure and physicochemical properties. Consequently, they enter various organisms directly (e.g. plants, soil invertebrates, water animals) or indirectly through food-chain. Several anthelmintics elicit toxic effects in non-target species. Although new information has been made available, anthelmintics in ecosystems should be more thoroughly investigated to obtain complex knowledge on their impact in various environments. This review summarizes available information about the occurrence, behavior, and toxic effect of anthelmintics in environment. Several reasons why anthelmintics are dangerous contaminants are highlighted along with options to reduce contamination. Negative effects are also outlined.
Topics: Animals; Humans; Ecosystem; Anthelmintics; Environmental Pollutants; Soil; Water
PubMed: 37852376
DOI: 10.1016/j.chemosphere.2023.140446 -
The Journal of General Physiology Jul 2024The TMEM16A calcium-activated chloride channel is a promising therapeutic target for various diseases. Niclosamide, an anthelmintic medication, has been considered a...
The TMEM16A calcium-activated chloride channel is a promising therapeutic target for various diseases. Niclosamide, an anthelmintic medication, has been considered a TMEM16A inhibitor for treating asthma and chronic obstructive pulmonary disease (COPD) but was recently found to possess broad-spectrum off-target effects. Here, we show that, under physiological Ca2+ (200-500 nM) and voltages, niclosamide acutely potentiates TMEM16A. Our computational and functional characterizations pinpoint a putative niclosamide binding site on the extracellular side of TMEM16A. Mutations in this site attenuate the potentiation. Moreover, niclosamide potentiates endogenous TMEM16A in vascular smooth muscle cells, triggers intracellular calcium increase, and constricts the murine mesenteric artery. Our findings advise caution when considering clinical applications of niclosamide as a TMEM16A inhibitor. The identification of the putative niclosamide binding site provides insights into the mechanism of TMEM16A pharmacological modulation and provides insights into developing specific TMEM16A modulators to treat human diseases.
Topics: Niclosamide; Anoctamin-1; Animals; Mice; Humans; Vasoconstriction; HEK293 Cells; Binding Sites; Calcium; Mesenteric Arteries; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Male
PubMed: 38814250
DOI: 10.1085/jgp.202313460 -
Orvosi Hetilap Dec 2023
Topics: Humans; Urinary Bladder; Schistosomiasis; Anthelmintics
PubMed: 38043096
DOI: 10.1556/650.2023.32902