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Helminth infections are detrimental to the overall health of dogs; therefore, this study aimed to identify antiparasitic-resistant helminths and evaluate the infection rate and risk factors for parasitism in canines. For this purpose, a parasitological evaluation of 38 randomly selected animals was performed, followed by the evaluation of the anthelminthic efficacy of three drugs: pyrantel pamoate with praziquantel (Canex Composto®), fenbendazole (Fenzol Pet®), and milbemycin oxime with praziquantel (Milbemax C®). Among the evaluated animals, 22/38 (57.89%) tested negative and 16/38 (42.71%) tested positive for Ancylostoma caninum infection. Evaluation of the efficacy of antiparasitic drugs showed that 12/16 (75%) dogs were infected with helminths that were susceptible to pyrantel pamoate with praziquantel. Among those for which pyrantel pamoate with praziquantel was not effective, 3/4 (75%) were susceptible to fenbendazole, while the remaining case resistant to both pyrantel pamoate with praziquantel and fenbendazole was sensitive to milbemycin oxime with praziquantel (100%). The odds ratio of infection in dogs inhabiting environments containing soil or grass was 6.67 times higher than that in dogs inhabiting impermeable environments. Mixed-breed dogs (SRD) were 6.54 times more likely to be infected compared to purebred dogs. A. caninum resistant to pyrantel pamoate with praziquantel (4/16, 25%) and fenbendazole (1/4, 25%) were detected. The results of this study demonstrated the importance of coproparasitological monitoring by professionals before and after treatments to assess antiparasitic drug effectiveness, ensure animal health and welfare, and minimize animal exposure to risk factors.

Pinworm ova were discovered on lesser hedgehog tenrec (Echinops telfairi) fecal exams. Ova were passthrough pseudoparasite pinworms originating from feeder roaches (Blaptica dubia). Roaches were maintained as a feeder colony and offered to tenrecs as a portion of their diet. Pinworms were identified as Leidynema appendiculata. This study aimed to determine if these pinworms could be eliminated from the roaches. Roaches were randomly assigned into groups (n = 24), including a control (A) and four treatment groups (B–E). Treatment group roaches received oral dosing of anthelmintic pyrantel pamoate at four concentrations (mg/g as offered): 3.5 (Group B), 14.0 (Group C), 26.0 (Group D), and 35.0 (Group E). Roach diets were made weekly and offered to roaches 2 consecutive days per week for 3 consecutive weeks. The total pinworm ova per gram of roach feces examined were visually reduced in all treatment groups compared to controls at the end of the feed dosing period (Day 23). Post-treatment pinworm numbers were visually reduced in all treatment groups compared to controls on Day 29 and Day 65. Groups receiving higher concentrations of the oral dosing (C–E) significantly differed from controls at Day 29 (p = 0.0086, p = 0.0045, and p = 0.0013, respectively) with a concentration-dependent response. Parasites were not eliminated in any group at Day 29 or 65 post-treatment, with an increasing visual trend indicating recontamination. This is the first report confirming a passthrough pseudoparasite in tenrecs from dubia roaches, and anthelmintic dosage research is warranted.

Helminthiasis is an important parasitic disease, many of which are zoonotic, particularly common in developing countries and, in countries with hot and humid climates. Intestinal parasites can cause significant manifestations at all levels of the gastrointestinal tract, as well as anemia and growth retardation. This study aims to demonstrate the anti-helminthic effect of Consolida orientalis on Caenorhabditis elegans, which is a helminth model, and introduce new chemotherapeutic candidate substances with anti-helminthic effect to the literature by identifying possible active ingredients with GC-MS analysis. In our study, flower, leaf, stem and aerial part plant extracts of Consolida orientalis were used at 40 mg/mL, 20 mg/mL, 10 mg/mL, 5 mg/mL, 2.5 mg/mL, 1.25 mg/mL concentrations. In addition, possible active ingredients found in plant extracts were determined by GC-MS analysis. As a result of the study, it was determined that the aerial part, leaf and stem extract of the first four concentrates (40 mg/mL, 20 mg/mL, 10 mg/mL, 5 mg/mL) of Consolida orientalis were more effective than pyrantel pamoate at a concentration of 5 mg/mL. According to our study findings, chemotherapeutics such as Dihidrocarvone and 2(3H)-Benzoxazolone with new antihelmintic-antiparasitic activity are thought to contribute to further research.

Soil-transmitted helminths (Ascaris lumbricoides, hookworm and Trichuris trichiura) infect about one-fifth of the world’s population. The currently available drugs are all highly efficacious against A. lumbricoides. However, they are only moderately efficacious against hookworm and poorly efficacious against T. trichiura. Oxantel, a tetrahydropyrimidine derivative discovered in the 1970s, has recently been brought back to our attention given its high efficacy against T. trichiura infections (estimated 76% cure rate and 85% egg reduction rate at a 20 mg/kg dose). This review summarizes the current knowledge on oxantel pamoate and its use against T. trichiura infections in humans. Oxantel pamoate acts locally in the human gastrointestinal tract and binds to the parasite’s nicotinic acetylcholine receptor (nAChR), leading to a spastic paralysis of the worm and subsequent expulsion. The drug is metabolically stable, shows low permeability and low systemic bioavailability after oral use. Oxantel pamoate was found to be safe in humans, with only a few mild adverse events reported. Several clinical trials have investigated the efficacy of this drug against T. trichiura and suggest that oxantel pamoate is more efficacious against T. trichiura than the currently recommended drugs, which makes it a strong asset to the depleted drug armamentarium and could help delay or even prevent the development of resistance to existing drugs. We highlight existing data to support the use of oxantel pamoate against T. trichiura infections. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-021-01505-1.

Dioctophymosis is the disease caused by Dioctophyma renale, a large nematode, popularly known as giant kidney worm, and whose definitive hosts are the domestic dog and many wild mammal species. There are some reports of maned wolf parasitism by D. renale, however, in most cases the reports are restricted to the finding of the parasite during necropsy, without clinical assessment. The present report aimed to describe the clinical-therapeutic, ultrasonographic and pathological aspects of D. renale parasitism in a free-ranging maned wolf, emphasizing the treatment with an association of doramectin, praziquantel, pyrantel pamoate, and febantel that resulted in complete elimination of the parasite.

Drug repurposing from veterinary to human medicine has been the main strategy to develop the four recommended human anthelminthics, albendazole, mebendazole, levamisole, and pyrantel pamoate, for the treatment of soil-transmitted helminthiasis. A systematic, head-to-head comparison of the anthelminthic activity profile of derivatives of these drugs and other anthelminthics developed in succession has not been conducted to date. We studied eight benzimidazoles, five macrocyclic lactones, tribendimidine, levamisole, and pyrantel pamoate in laboratory models of human intestinal nematode infections. In vitro studies were performed on Trichuris muris L1 larval stage and adults, as well as Ancylostoma ceylanicum, Necator americanus, Heligmosomoides polygyrus, and Strongyloides ratti L3 larvae and adults. The benzimidazoles showed pronounced differences against larval and adult stages, with low activity against larvae and the highest activity observed against adult N. americanus (IC50 of flubendazole 1.1 μM). The macrocyclic lactones, on the other hand, revealed a higher activity on the larval stages, with the lowest IC50 values observed against N. americanus L3 (IC50 values of 0.03-3 μM). In vivo studies were performed in the T. muris and H. polygyrus mice models, with moxidectin and milbemycin oxime showing the highest activity against H. polygyrus (ED50 values of 0.009 and 0.006 mg/kg, respectively) and moxidectin and abamectin being the most effective drugs against T. muris (ED50 values of 0.2 and 0.5 mg/kg, respectively). Laboratory models for soil-transmitted helminthiasis can assist characterizing potential drug candidates. Drugs should be evaluated against different species, and both the adult and larval stages as activities could differ considerably.

BACKGROUND: Soil-transmitted helminths (STHs) infection (i.e., Ascaris lumbricoides, Trichuris trichiura, and hookworm) are commonly found as a single infection as well as a mixture of the three kinds of helminths that requires a broad anthelmintic spectrum. Some study revealed that combination of anthelmintic provides better efficacy. AIM: The objective of the study was to compare the efficacy of combination treatment of albendazole-mebendazole, albendazole-pyrantel pamoate, and mebendazole alone in treating STHs infection as well as the rate of reinfection post-treatment. METHODS: In 2018, a randomized controlled trial was conducted in Batubara district, North Sumatera. School-aged children diagnosed for STH were randomly allocated to (1) albendazole-mebendazole; (2) albendazole-pyrantel pamoate; or (3) mebendazole treatment groups. Here, we report the efficacy (cure rates [CRs] and egg-reduction rates [ERR]) and reinfection rates determined 12 weeks post-treatment. Chi-square test was used to compare the drug efficacy and reinfection rate between three groups. RESULTS: A total of 309 children complete baseline and follow-up data. The efficacy was determined after 4 weeks post-treatment albendazole-pyrantel pamoate showed a significant higher efficacy against A. lumbricoides (CR: 93.5%; ERR: 100%) and T. trichiura (CR: 81.4%; ERR: 99%). For hookworm infection, results showed higher efficacy between the three groups after treatment. The reinfection rates 12 weeks after treatment for A. lumbricoides infection (Group 1: 3.1%; 2: 3%; 3: 1.3%) with p > 0.05 and for T. trichiura infection (Group 1: 19.2%; 2: 25%; 3: 1.5%) with p < 0.05. CONCLUSION: This study showed the excellent efficacy of an albendazole-pyrantel pamoate combination against STHs infections. The highest reinfection rate was found in albendazole-pyrantel pamoate group for T. trichiura infection.

Ancylostoma caninum is the most prevalent intestinal nematode of dogs, and has a zoonotic potential. Multiple-drug resistance (MDR) has been confirmed in a number of A. caninum isolates, including isolate Worthy 4.1F3P, against all anthelmintic drug classes approved for hookworm treatment in dogs in the United States (US). The cyclooctadepsipeptide emodepside is not registered to use in dogs in the US, but in a number of other countries/regions. The objective of this study was to evaluate the efficacy of emodepside + praziquantel, as well as three commercial products that are commonly used in the US for treatment of hookworms, against a suspected (subsequently confirmed) MDR A. caninum isolate Worthy 4.1F3P. 40 dogs infected on study day (SD) 0 with 300 third-stage larvae, were randomly allocated to one of five treatment groups with eight dogs each: pyrantel pamoate (Nemex®-2), fenbendazole (Panacur® C), milbemycin oxime (Interceptor®), emodepside + praziquantel tablets and non-treated control. Fecal egg counts (FEC) were performed on SDs 19, 20, 22, 27, 31 and 34. All treatments were administered as per label requirements on SD 24 to dogs in Groups 1 through 4. Two additional treatments were administered on SDs 25 and 26 to dogs in Group 2 as per label requirements. Dogs were necropsied on SD 34 and the digestive tract was removed/processed for worm recovery and enumeration. The geometric mean (GM) worm counts for the control group was 97.4, and for the pyrantel pamoate, fenbendazole, milbemycin oxime, and emodepside + praziquantel groups were 74.8, 72.0, 88.9, and 0.4, respectively. These yielded efficacies of 23.2%, 26.1%, and 8.8%, and 99.6%, respectively. These data support previous findings of the MDR status of Worthy 4.1F3P as treatments with pyrantel pamoate, fenbendazole and milbemycin oxime lacked efficacy. In sharp contrast, Worthy 4.1F3P was highly susceptible to treatment with emodepside + praziquantel., Graphical abstract Image 1

Background Soil transmitted helminths (STH) are intestinal nematodes and constitute one of the most neglected tropical diseases to exist. Objective: This study determined the efficacy of albendazole-pyrantel pamoate compared to albendazole in 8-12 years old children with Trichuris trichiura infection. Methods A randomised controlled trial was conducted between October 2017 and February 2018 on participants whose stool examinations confirmed the presence of Trichuris trichiura infection. The subjects were randomised into two groups. The statistical analysis used Chi-square test. Results There were 392 of 600 children at five public elementary schools in Bangli and Bali and were infected with Trichuris trichiura. The cure rate of Trichuris trichiura infection seven days following treatment was lower with the combination of albendazole and pyrantel pamoate compared to that of albendazole. The egg reduction rate of Trichuris trichiura infection was lower with the combination of albendazole and pyrantel pamoate compared to albendazole. Conclusion The study indicated that a combination of albendazole and pyrantel pamoate does not improve cure rate or egg reduction rate in 8-12 years old children with Trichuris trichiura infection.

The efficacy of pyrantel pamoate, pyrvinium pamoate, ivermectin, and piperazine citrate against pinworm in cockroach was evaluated. Laboratory-reared German cockroaches naturally infected with Blatticola blattae were treated with the anthelmintics and necropsied at 3 to 35 days after treatment. Ivermectin at over 5 ppm and piperazine citrate at over 2000 ppm killed all the treated cockroaches. Pinworms were still detected in cockroaches given lower concentration of the aforementioned drugs. Administration of pyrantel pamoate (100-1000 ppm) and pyrvinium pamoate (2000 ppm) did not kill the cockroaches, and no pinworms were detected at 3 and 17 days after treatment. Thus, pyrantel pamoate and pyrvinium pamoate were found to be effective for deworming B. blattae in the German cockroaches, without causing mortality for the host. Our results showed that anthelmintics selection is essential for eradication of pinworms in cockroaches because of the toxicity for the host such as ivermectin or piperazine citrate. This is the first report of piperazine citrate toxicity in cockroaches.

Indian star tortoise (Geochelone elegans Schoepff, 1795) is a terrestrial herbivorous reptile that is classified under the vulnerable species of IUCN-Red List. The present communication reports the successful management of gastrointestinal parasitism due to co-infection with oxyurids and ascarid nematodes in the captive population of Indian star tortoise maintained at Zoological Garden, Thiruvananthapuram, Kerala, India. The diseased tortoise exhibited clinical signs like diarrhea, anorexia, and weight loss. Direct microscopic examination of pooled fecal sample identified the presence of oxyurid and ascarid ova. Therapeutic management involved a two-dose regimen of pyrantel pamoate given in a 2 week interval at a dose rate of 5 mg/kg body weight per orally. Complete parasitological clearance was observed 2 weeks after initiating the therapy without any recurrence. The two-dose pyrantel pamoate protocol was found to be effective in controlling the parasitic burden of captive Indian star tortoise. Chemotherapy can be combined with managemental changes to nullify the possibility of re-infection.

Rat lungworm (Angiostrongylus cantonensis) is a neurotropic nematode, and the leading cause of eosinophilic meningitis worldwide. The parasite is usually contracted through ingestion of infected gastropods, often hidden in raw or partially cooked produce. Pharmaceutical grade pyrantel pamoate was evaluated as a post-exposure prophylactic against A. cantonensis. Pyrantel pamoate is readily available over-the-counter in most pharmacies in the USA and possesses anthelmintic activity exclusive to the gastrointestinal tract (GIT). Administering pyrantel pamoate immediately after exposure should theoretically paralyze the larvae in the GIT, causing the larvae to be expelled via peristalsis without entering the systemic circulation. In this study, pyrantel pamoate (11 mg/kg) was orally administered to experimentally infected rats at 0, 2-, 4-, 6-, or 8-h post-infection. The rats were euthanized six weeks post-infection, and worm burden was evaluated from the heart-lung complex. This is the first in vivo study to evaluate its efficacy against A. cantonensis. This study demonstrates that pyrantel pamoate can significantly reduce worm burden by 53-72% (P = 0.004), and thus likely reduce the severity of infection that is known to be associated with worm burden. This paralyzing effect of pyrantel pamoate on the parasite may also be beneficial for delaying the establishment of infection until a more suitable anthelmintic such as albendazole is made available to the patient.

Objective: To review the literature regarding the epidemiology and treatment of intestinal helminthic infections. Data Sources: A literature search of MEDLINE (1946-January 2014), EMBASE (1980-January 2014), International Pharmaceutical Abstracts (1970-January 2014), and the Cochrane Library (1996-January 2014) was performed using the following terms: intestinal, helminthic, humans, United States, and individual drug names (albendazole, ivermectin, mebendazole, nitazoxanide, praziquantel, pyrantel pamoate). Secondary and tertiary references were obtained by reviewing related articles. Study Selection and Data Extraction: All English-language articles identified from the data sources and clinical studies using anthelmintic agents were included. Data Synthesis: The 2011 removal and continued absence of mebendazole from the market has left limited options for helminth infections. For hookworm, albendazole has a 72% cure rate compared to 32% for pyrantel pamoate. Albendazole, ivermectin, and nitazoxanide appear to be effective for Ascaris with cure rates of 88%, 100%, and 91%, respectively. Both albendazole and pyrantel pamoate have been evaluated for pinworm with cure rates of 94.1% and 96.3%, respectively. Combination therapy with ivermectin and albendazole produces cure rates of 38% to 80% for whipworm. For Strongyloides stercoralis, ivermectin cure rates are 93.1% to 96.8% compared with 63.3% for albendazole. Praziquantel is effective for intestinal trematode infections with cure rates of 97% to 100% while its efficacy against tapeworm ranges from 75% to 85%. Conclusions: Albendazole is the drug of choice for hookworm, Ascaris lumbricoides, and pinworm. In combination with ivermectin, it is the first-line agent for whipworm. Ivermectin is preferred for Strongyloides stercoralis, and praziquantel is effective against most nematodes and trematodes.

The presented study describes the development, optimization, and validation of a method for the determination of four structurally different anthelmintics (benzimidazole, diphenyl sulfide, imidazothiazole, hexahydropyrazine, and tetrahydropyrimidine) in water samples. The studied compounds were albendazole, febantel, levamisole, praziquantel, and pyrantel pamoate. The method involves solid-phase extraction and preconcentration of the anthelmintics, separation by thin-layer chromatography (TLC), and quantification by videodensitometry. TLC and preparative TLC separation was performed on silica gel 60 F254 plates with chloroform—methanol—formic acid as the mobile phase. Spots were detected and quantified at λ = 254 nm by videodensitometry. The method provides a linear response over a concentration range of 200–1500 μg L-1, depending on the anthelmintic with a correlation coefficient of 0.9888 in most cases, except for albendazole (0.9634) and pamoic acid (0.9654) as a secondary component of pyrantel pamoate. Also, the method has revealed limits of detection (100–300 μg L-1), good precision (intra- and inter-day) with a relative standard deviation below 13%, and recoveries above 95% for all investigated pharmaceuticals. The developed method has been successfully applied to the analysis of anthelmintics in production wastewater samples obtained from the local pharmaceutical industry. In order to determine the structures of two compounds detected by TLC of pyrantel pamoate, the spots were separated by preparative TLC, and the structures of the isolated samples were analyzed using 1H and 13C nuclear magnetic resonance (NMR) spectroscopy.

Ninety-seven children with Ascariasis were treated at randomly with Piperazine, Tetramisole, and Pyrantel pamoate in a single dose with cure rates of 59%, 62%, and 88%, respectively. In the children who were not cured, a reduction in egg count of nearly 80% was found in all three treatment groups. The results of this study showed that Pyrantel pamoate is the most effective of the three drugs.

Objective: To develop a simple, accurate and precise reverse-phase high-performance liquid chromatography (RP-HPLC) method and subsequently validate for the simultaneous estimation of praziquantel (PZQ) and pyrantel pamoate (PP) in the pharmaceutical dosage form. Methods: The chromatographic separation was achieved on Phenomenex Luna C18 column (250 mm × 4.6 mm, 5 μm) as stationary phase maintained at an ambient temperature with a mobile phase comprising of water: acetonitrile (20: 80) at a flow rate of 1.0 ml/min and UV detection at 220 nm. Results: The retention time of PZQ and PP was found to be 3.897 min and 1.697 min respectively. The method was validated in terms of specificity, accuracy, precision, linearity and robustness as per ICH guidelines. Linearity was obtained in the concentration range of 20–60 μg/ml for both PZQ and PP with correlation coefficients of 0.987 and 0.998 respectively. The accuracy of the method was determined using a recovery test and found as 98.44 % to 100.35 %. All parameters are found to be within the acceptable limit. Conclusion: The developed RP-HPLC method was simple, rapid, accurate, precise for the simultaneous estimation of PZQ and PP in bulk and tablet dosage form.

Problema: En Colombia no hay informes sobre efectos en humanos del tratamiento periódico antihelmíntico-vitamina A. Objetivo: Evaluar efectos de albendazol/pamoato de pirantelvitamina A trimestrales sobre Ascaris lumbricoides, Trichuris trichiura, Necator americanus y sobre niveles séricos de retinol y hemoglobina, en niños del Urabá antioqueño. Metodología: Estudio clínico, aleatorio, con grupos paralelos, cerrado, intervenidos y evaluados cada 3-4 meses por 4 veces, seguidos 12 meses. Intervención: suministro de pamoato de pirantel (pamoato) (< 2 años) o albendazol (≥ 2 años), con o sin vitamina A oral. Resultados: Ingreso: 25% presentó desnutrición crónica y hemoglobina (g/L), 106 g/L en < 2 años y 115 g/L en ≥ 2 años. A) Prevalencias: estrongiloides 7%, uncinarias 29%, áscaris 45%, tricocéfalos 45%. Cambios postratamiento: pamoato únicamente causó reducción de áscaris y, en general, aumentó tricocéfalos y uncinarias. Albendazol: redujo cada helminto, como lo hicieron tratamientos sin este medicamento, pero fue mayor con albendazol. B) Cambio en carga parasitaria: únicas diferencias significativas fueron para tricocéfalos con pamoato-vitamina y albendazolvitamina, por aumento, y áscaris con albendazolvitamina, por reducción. No hubo diferencia significativa entre ingreso y egreso en niveles de hemoglobina ni retinol en ninguno de los cuatro tratamientos. Conclusiones: En general, no hubo efecto del albendazol sobre la carga helmintiana, pero sí efecto moderado sobre la prevalencia de uncinarias, áscaris y tricocéfalos. Quizás la desparasitación de solo parte de la población < 15 años, sin tratar el resto de convivientes, y el mantenimiento de muy deficientes condiciones de vida expliquen estos resultados. Problem:, There are no reports about the effect of periodic anthelminthic-vitamin A treatment in humans In Colombia. Objective: To evaluate effects of albendazole/ pamoate pyrantel-vitamin A administered quarterly on Ascaris lumbricoides, Trichuris trichiura, Necator americanus, and on serum retinol and hemoglobin levels in children from Urabá (Antioquia, Colombia). Methodology: Clinical, randomized, controlled trial with parallel groups intervened and evaluated each 3-4 months for 4 times, followed 12 months. Intervention: administration of pyrantel pamoate (pamoate) (< 2 years) or albendazole (≥ 2 years), with or without oral vitamin A. Results: Entry: 25% presented chronic malnutrition and hemoglobin, 10.6 g/L (< 2 years) and 11.5 g/L (≥ 2 years). A) Prevalence: strongyloides 7%, uncinaria 29%, ascaris 45%, whipworms 45%. Post-treatment changes: pamoate only caused reduction of ascaris and, in general, increased whipworms and uncinarias. Albendazole: reduced the prevalence of each helminth, as treatments without this medication did, but it was higher in treatments with albendazole.. B) Change in parasite load: only significant differences were for whipworms with pamoate-vitamin and albendazole-vitamin, because of increase, and ascaris with albendazole-vitamin, because of reduction. No significant difference between entry and leave in hemoglobin or retinol levels in any of the four treatment groups. Conclusions: Overall, there was no effect of albendazole on helminth communities, but there was moderate effect on prevalence of uncinaria, ascaris and whipworms. Possibly deworming only part of the population < 15 years without treating the rest of cohabitants, and the maintenance of very poor living conditions can explain these results.

In Ukraine, about 100,000 cases of geohelminthiasis are registered annually, 80%of which are children under 17 years of age. Symptoms of helminthiasis are mild orcompletely absent, but harmful to the body, however, infection of the child's body isespecially dangerous.Objective - to conduct a marketing study of drugs, used for treatment, and identify themain problems of this pathology prevention.Material and methods. A marketing research and analysis of the trade names’ market,analysis of 52 medical records of inpatients and outpatients (children aged 12 to 17years) for worm infestations and medical records of medical institutions in Chernivtsihave been carried out.Results. At the first stage of the research, a statistical study of invasive diseases state wasconducted and the main risk factors for infection were identified. We studied the rangeof antiparasitic drugs available on the domestic pharmaceutical market. Albendazole ismost often used as an active anthelmintic agent, 75% of which are domestic and 25% ofimported production. Preparations with the active substance pyrantel pamoate accountfor 42.8% of domestic production, all others are imported. According to the results of theprocessed medical records of patients several of the most common treatment regimens,which include anthelmintic therapy, the use of enterosorbents and the appointment ofa 5-day course prescription of H1-histamine receptor blockers were chosen. Havinganalyzed the average cost of the day treatment of nematode infestations, we came to theconclusion that the most available complex of group II drugs, the main antihelmintic drugis Zentel.One of the measures to prevent helminthiasis is the use of phytopreparations anddietary supplements based on medicinal plant materials, which, unlike chemicals, arecharacterized by milder properties and less toxicity, the ability not only to affect thepathogen directly, but also to restore the functional state of the organs and systemsaffected by worm infestation.Conclusions. From the offered schemes of pharmacotherapy the most accessible is theuse of a complex which structure includes Сarbowhite, Rolinoz, Zentel. It is promising tostudy the use of phytomedicines both during medical therapy and for prevention.

Angiostrongylus cantonensis is the leading cause of eosinophilic meningitis worldwide, with life-threatening complications if not managed correctly. Previous in vitro studies have utilized change in motility patterns of adult female worms to assess the efficacy of anthelmintics qualitatively. However, it is the third stage larvae (L3) that are infectious to humans. With differential staining using propidium iodide penetration as the indicator of death, we can distinguish between dead and live larvae. This assay has enabled us to quantify the in vitro efficacy of nine clinically established anthelmintics on A. cantonensis L3. All drugs were tested at a 1 mm concentration. Piperazine and niclosamide were ineffective in inducing larval death; however, albendazole sulfoxide, pyrantel pamoate, diethylcarbamazine, levamisole and praziquantel were effective as compared to unexposed controls (P < 0.05). Ivermectin and moxidectin did not induce significant levels of mortality, but they considerably reduced larval motility almost immediately. This study indicates the need for further in vivo studies to determine the optimal dose and time frame for post-infection treatment with anthelmintics that demonstrated efficacy.

Infection with the stomach worm Physaloptera spp. in dogs can cause chronic vomiting, although the diagnosis is often difficult owing to a low worm burden, single-sex infections, a failure to produce ova, or ova that are of greater density than solutions routinely used for qualitative fecal flotation. A retrospective evaluation was performed of 27 dogs that had gastric Physaloptera spp. infection confirmed endoscopically. In 23 of 27 dogs (85.2%), chronic vomiting was the chief complaint, and Physaloptera was an incidental finding in 3 dogs with esophageal or gastric foreign bodies. The worm burden was low (1–3 worms) in 21 dogs (77.8%), but 2 dogs were infected with large numbers (>50 worms). Prior therapy with routine doses of anthelmintics was ineffective in eight dogs prior to endoscopy. A higher dose and longer duration of fenbendazole in combination with pyrantel pamoate is recommended for treatment of suspected or confirmed infections. Reinfection is common in some dogs and should not be viewed as treatment failure.

Background A novel chewable oral tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) has recently been developed to provide persistent protection against flea and tick infections for a month, treatment of hookworm and roundworm infections and prevention of heartworm and lungworm disease in dogs. Two field studies were conducted to evaluate the safety and efficacy of Simparica Trio™ against natural flea and tick infestations on dogs in Europe. Methods Dogs with natural flea or tick infestations were allocated randomly to treatment on Day 0 with either Simparica Trio™ tablets (flea study: n = 297; tick study: n = 189) to provide 1.2–2.4 mg/kg sarolaner, 24–48 µg/kg moxidectin and 5–10 mg/kg pyrantel (as pamoate salt) or with NexGard® Spectra (afoxolaner + milbemycin oxime) according to the label instructions (flea study: n = 164; tick study: n = 91). Efficacy was calculated based on the mean percent reduction in live parasite counts compared to the respective pre-treatment counts on Days 14 and 30 in the flea study and on Days 7, 14, 21 and 30 in the tick study. To count the fleas, the dog’s entire coat was systematically combed using an extra fine-tooth flea comb until all fleas were removed. For the tick counts, the dog’s entire coat was searched manually. Resolution of the clinical signs of flea allergy dermatitis (FAD) was assessed in flea allergic dogs in the flea study. Palatability was assessed in both studies. Results Simparica Trio™ was well tolerated in both studies. Efficacy against fleas was ≥ 97.9% in the Simparica Trio™ group and ≥ 96.1% in the NexGard® Spectra group. Efficacy against ticks was ≥ 94.8% in the Simparica Trio™ group and ≥ 94.4% in the NexGard® Spectra group. Clinical signs of flea allergy dermatitis improved following treatment with Simparica Trio™. Simparica Trio™ tablets were voluntarily and fully consumed on ≥ 78% of the 485 occasions they were offered. Conclusions A single oral dose of Simparica Trio™ was safe and highly efficacious against naturally occurring flea and tick infestations for 1 month on dogs. Clinical signs of FAD improved following treatment. Simparica Trio™ was voluntarily and readily consumed by most dogs.

We describe the case of a 7-year-old girl with repeated vaginal Enterobius vermicularis infection, never detected as a digestive tract infection. Two-dose pyrantel pamoate or 2-dose albendazole could not suppress recurrence. Finally, 3-dose albendazole after 2-week intervals was successful in preventing relapse.

Srikaya ( Annona squamosa L.) is a fruit that has been widely known to the people of Indonesia that have effective properties as traditional medicine. Srikaya seeds and leaves are known as a medicinal plant worm exterminator. This study aims to determine the anthelmintic influence of extract juice and srikaya leaf infused against roundworm of chicken in vitro, to determine the effect of concentration of extract juice and infuse of the srikaya leaf to the time of death of roundworm of chicken in vitro and to determine the most effective concentration of the extract juice and infuse of the srikaya leaf that has anthelmintic influence. This research is an experimental research design with Post test only controlled group design consisting of 150 of A. galli worms and were divided into 4 groups of treatments. Group 1 were put in NaCl 0.9 % liquid; group 2 was in srikaya leaves juice extract at a concentration of 25, 50, and 75 g/100 ml; group 3 was in srikaya leaves infuse with a concentration of 25, 50, and 75 g/100 ml, and group 4 was given 0.5 % pyrantel pamoate liquid. Each treatments containing 5 worms in 25 ml were done at 3 replication and incubated at 37 o C. The data were obtained from the observation of A. galli time of death every 15 minutes. The data were analyzed using One Way Anova test followed by the Post Hoc LSD test. There was an increasing of the death of A. galli correlating with the increase of the juice extract and infuse the srikaya leaf concentrations. The result showed there was a significant difference of NaCl 0.9 % and pyrantel pamoate 0.5 % treatments and there was no significant difference of the juice extract and infuse the srikaya leaf on worm death time. Extract juice and srikaya leaf infusion has anthelmintic influence against A . galli in vitro. The greater the concentration of the treatments, the greater anthelmintic influence visible on the death time acceleration of A . galli . Concentration of 75 g/100 ml is the most effective treatments of extract juice and srikaya leaf infusion but still lower than that of 0.4 % pyrantel pamoate. Key words : srikaya, A. squamosa , anthelmintic influence and A. galli

Albendazole and mebendazole are commonly used to control hookworm, but have shortcomings in their efficacy profiles. We assessed whether triple drug therapy (TDT) with albendazole, pyrantel pamoate, and oxantel pamoate was more effective than the co-administration of two drugs for the treatment of hookworm infections.A randomised, single-blind trial was done from Sept 27 until Nov 17, 2017, in Laos. Children (6-15 years) from six schools were invited to participate. Hookworm-positive children were randomly assigned (2:2:1:1) by a computer stratified list (block sizes of six and 12) to TDT with albendazole (400 mg), pyrantel pamoate (20 mg/kg), and oxantel pamoate (20 mg/kg); albendazole plus oxantel pamoate; pyrantel pamoate plus oxantel pamoate; or mebendazole (500 mg) combined with both pyrantel pamoate and oxantel pamoate (used as proof of concept to compare the two TDTs). Two stool samples were collected at baseline and follow-up (17-30 days after treatment) and analysed with the Kato-Katz method. The primary outcome was the proportion of hookworm egg-negative children at follow-up in all Kato-Katz slides (cure rate [CR]) in the TDT with albendazole, pyrantel pamoate, and oxantel pamoate group compared with the albendazole plus oxantel pamoate and pyrantel pamoate plus oxantel pamoate groups. Secondary outcomes were tolerability 3 h and 24 h after treatment, egg reduction rates (ERRs) against hookworm, and efficacy against concomitant soil-transmitted helminth infections. Participating children and field and laboratory technicians were masked to treatment allocation. All children with follow-up data were included in the primary analysis. This trial is registered with ClinicalTrials.gov, number NCT03278431.1529 children were assessed for eligibility, of whom 533 provided complete baseline data and 414 provided complete outcome data. The CR was higher for the TDT albendazole, pyrantel pamoate, and oxantel pamoate (116 [84%] of 138) than with albendazole plus oxantel pamoate (73 [53%] of 138; odds ratio 4·7, 95% CI 2·7-8·3; p0·0001) and pyrantel pamoate plus oxantel pamoate (36 [52%] of 69; 4·8, 2·5-9·3; p0·0001). The geometric ERR of the TDT albendazole, pyrantel pamoate, and oxantel pamoate (99·9%) was higher than that for albendazole plus oxantel pamoate (99·0%; difference in ERR 0·9 percentage points, 95% CI 0·5-1·4), and pyrantel pamoate plus oxantel pamoate (99·2%; 0·7 percentage points, 0·3-1·3). Adverse events were reported by six (1%) children 3 h and none 24 h after treatment, without any difference across treatment groups.TDT with albendazole, pyrantel pamoate, and oxantel pamoate could make a difference, in particular in the context of soil-transmitted helminth elimination. Pyrantel pamoate might be a useful alternative to prevent benzimidazole resistance; however, larger trials are needed to confirm this finding.Swiss National Science Foundation.

Diclidophoridae and Capsalidae are families of monogenean parasites that include some of the most pathogenic species for cultured finfish. In this study, the efficacy of praziquantel (PZQ) and a combination anthelmintic (PZQ, ivermectin, pyrantel pamoate and fenbendazole) commercialized under the name of Adecto® (Adler Pharma) were evaluated in vitro against adults and eggs of the diclidophorid Tagia ecuadori and the capsalid Neobenedenia melleni. Freshwater and formalin immersions were also evaluated against T. ecuadori for comparative purposes. In addition, the efficacy in vivo of Adecto® as a bath treatment to eliminate mixed infections as well as the median lethal concentration (LC50) of this drug in juvenile, healthy bullseye puffer fish (Sphoeroides annulatus) were determined. Triglycerides, hemoglobin, total protein and glucose levels were measured in three groups of fish: uninfected, infected and infected/treated with Adecto®. At the doses tested, PZQ did not have a concentration-dependent effect. Thus, 2.5 mg/L PZQ was 100% effective against adults of T. ecuadori after 20 h, and 3 mg/L killed 87% of N. melleni after 12 h. Adecto® had a concentration-dependent effect. The concentration required to kill all parasites in the minimum time was 20 mg/L Adecto® (12 h for T. ecuadori, and 16 h for N. melleni). Neither PZQ nor Adecto® were effective at inhibiting egg hatching. Adults of T. ecuadori were highly tolerant to freshwater; mortality was

Cyathostomins are the most common parasites of adult horses worldwide. Currently, the three classes of anthelmintics used to treat cyathostomin infections includes benzimidazoles, pyrimidines and macrocyclic lactones. However, due to widespread overuse, cyathostomins have developed varying degrees of resistance to all classes of anthelmintics. Fecal egg count reduction tests (FECRT) are currently used to determine the presence of anthelmintic resistance (AR), while egg reappearance periods (ERP) are used to investigate early macrocyclic lactone resistance. The objective of this study was to investigate the prevalence of cyathostomin pyrantel pamoate and ivermectin resistance, and to determine ERP at Prince Edward Island (PEI), Canada horse farms. In addition, fecal cultures and larval identification were performed to evaluate the prevalence of small and large strongyle egg shedding in PEI. Fecal egg counts (FEC) were performed on 270 horses on 14 horse farms across PEI. Horses with≥ 200 eggs per gram (EPG) met the inclusion criteria and were enrolled in the study (n = 101). The median (range) horses per farm was 7.5 (4–11) and 6.0 (4–8) for pyrantel pamoate and ivermectin groups, respectively. Horses were initially treated with 6.6 mg/kg of pyrantel pamoate orally (n = 101). Fecal egg counts were conducted every two weeks for 8 weeks post treatment. Once individual FEC were ≥ 200 EPG, horses were dewormed with 0.2 mg/kg of ivermectin orally (n = 80), and FEC were performed every 2–3 weeks for seven weeks. In this study the ERP was defined as the week the mean FECR were 10% below the initial mean two-week post treatment FECR. Fecal egg count reduction tests and ERP were used to evaluate the efficacy of each anthelmintic. Fecal culture was performed to confirm the shedding of cyathostomin eggs. Fecal egg count reduction tests detected pyrantel pamoate resistance on 5/14 farms. No signs of ivermectin AR were detected, while reappearance of eggs occurred at 4–6 weeks and 7–9 weeks for pyrantel pamoate and ivermectin, respectively. Fecal culture detected large strongyles on 5/14 farms, which accounted for 0.3% of strongyle type eggs cultured. The prevalence of Strongylus vulgaris among individual horses in this study was 2.8% and was detected on 2/14 farms. These findings will allow us to educate owners and veterinarians on appropriate anthelmintic protocols in PEI and can be used as a baseline for continued monitoring of ERP and anthelmintic resistance in this region.

Millions of people are treated with anthelmintics to control soil-transmitted helminth infections; yet, drug distribution in the plasma and gastrointestinal tract compartments and the pathway of drug uptake into gastrointestinal nematodes responsible for the pharmacological effect are unknown. We assessed the distribution and uptake of albendazole, albendazole sulfoxide, albendazole sulfone in the hookworm Heligmosomoides polygyrus in vitro and in vivo as well as the distribution and uptake of albendazole, mebendazole, and oxantel pamoate in the whipworm Trichuris muris in vitro and in vivo. Oral and intraperitoneal treatments (100 mg/kg) were studied. Drug quantities in helminths and host compartments (stomach, the contents and mucosa of the small and large intestine, and the plasma) were determined using HPLC-UV/vis and anthelmintic activities were recorded using phenotypic readout. The influence of 1-aminobenzotriazole (ABT), an irreversible and unspecific cytochrome P450 inhibitor, on albendazole disposition in mice harboring H. polygyrus was evaluated. In vivo, albendazole was found in quantities up to 10 nmol per ten H. polygyrus and up to 31 nmol per ten T. muris. ABT did not change the levels of albendazole or its metabolites in the plasma of mice harboring H. polygyrus or in H. polygyrus, whereas drug levels in the gastrointestinal tract of host mice doubled. Mebendazole and oxantel pamoate quantities per ten T. muris were as high as 21 nmol and 34 nmol, respectively. Albendazole revealed a very dynamic distribution and high rate of metabolism, hence, H. polygyrus and T. muris are exposed to albendazole and both metabolites via multiple pathways. Diffusion through the cuticle seems to be the crucial pathway of oxantel pamoate uptake into T. muris, and likely also for mebendazole. No relationship between concentrations measured in helminths and concentrations in plasma, intestinal content and mucosa of mice, or drug efficacy was noted for any of the drugs studied., Graphical abstract Image 1, Highlights • No correlation was found between drug amounts in helminths versus plasma or gastric content. • Metabolism and disposition of albendazole in H. polygyrus was not influenced by a CYP-inhibitor. • Oxantel pamoate enters T. muris likely from the gastrointestinal tract. • Albendazole revealed a dynamic distribution and high rate of metabolism regardless of mode of administration.

Ganestya S, Djumarga S, Utari CRS. 2012. Anthelmintic effects of pumpkin (Cucurbita moschata) seed extract on Ascaris suum in vitro. Biofarmasi 10: 1-6. The aim of this research was to determine the effect of pumpkin seed extract towards the Lethal Death Time of Ascaris suum Goeze in vitro. The type of this research was an quasi-experiment using a post-test only controlled group design. The subject of this research was the actively motile adult Ascaris suum Goeze. A purposive sampling technique was used to collect the samples by considering the length of each worm without noticing the sex of worm. The subjects were divided into four groups, each group consisted of 10 worms, with 5 times replication. Physiological saline solution and pyrantel pamoate 0.236% were used as the negative and positive control groups, respectively, while the pumpkin seed extracts used for the treatment groups were at the concentrations of 54.5% and 70.5%. The observation and checking towards the dead worm were performed once an hour. The data obtained were analyzed by using a Kruskal-Wallis test, continued with Mann-Whitney and Spearman Correlation tests. The Lethal Death Time of A. suum by pumpkin seed extracts at a concentration of 54.5% was 11 hour 48 minutes, while at a concentration of 70.5%, the Lethal Death Time was 7 hours 48 minutes. The result of Kruskal-Wallis test showed a significant difference among all of the groups (p

Semi-intensive equine breeding system favors gastrointestinal nematode infections. The treatment of these infections is based on the use of anthelmintics. However, the inappropriate use of these drugs has led to parasitic resistance to the available active principles. The objective of this study was to evaluate the efficacy of the main classes of antiparasitic (ATP) used in control in adult and young animals, including: benzimidazoles (fenbendazole), pyrimidines (pyrantel pamoate), macrocyclic lactones (ivermectin and moxidectin), as well as the combination of active ingredients (ivermectin + pyrantel pamoate). The study was carried out in two military establishments, located in Rio Grande do Sul (RS), from January to December, 2018. The intervals between the treatments of the animals were performed from 30 to 90 days. Coproparasitological evaluations were determined by the egg count reduction in the faeces. Cyatostomine larvae were identified in pre and post-treatment cultures. The results demonstrated the multiple parasitic resistance of cyathostomins to fenbendazole, moxidectin in young animals, and to fenbendazole, pyrantel pamoate in adult animals. Thus, it is necessary to define or diagnose parasitic resistance to assist in the creation of prophylactic parasitic control, using suppressive treatment with ATP associated with integrated alternatives. The progress of parasitic resistance can be slowed. Resumo O sistema semi-intensivo de criação de equinos favorece infecções por nematoides gastrointestinais. O tratamento dessas infecções é baseado no uso de anti-helmínticos. No entanto, o uso inadequado desses medicamentos levou à resistência parasitária aos princípios ativos disponíveis. O objetivo deste estudo foi avaliar a eficácia das principais classes de antiparasitários (ATP), utilizados no controle em animais adultos e jovens, incluindo: benzimidazois (fenbendazol), pirimidinas (pamoato de pirantel), lactonas macrocíclicas (ivermectina e moxidectina), bem como a combinação de ingredientes ativos (ivermectina + pamoato de pirantel). O estudo foi realizado em dois estabelecimentos militares, localizados no Rio Grande do Sul (RS), de janeiro a dezembro de 2018. Os intervalos entre os tratamentos foram realizados de 30 a 90 dias. As avaliações coproparasitológicas foram determinadas pela redução da contagem de ovos nas fezes. Foram identificadas larvas de ciatostomíneos nas coproculturas pré e pós tratamentos. Os resultados demonstraram a resistência parasitária múltipla dos ciatostomíneos ao fenbendazol, moxidectina em animais jovens, febendazole e pamoato de pirantel em animais adultos. Estabelecer o diagnóstico da resistência parasitária auxiliará na elaboração de um controle parasitário profilático, reduzindo o tratamento supressivo com ATP juntamente com alternativas de controle integrado. Dessa forma, o avanço da resistência parasitária poderá ser retardado.

Background Diagnosis of soil-transmitted helminths (STHs) in developing countries is commonly based on microscopic detection of eggs in stool samples, using the Kato-Katz (KK) method, which has a poor sensitivity for detecting light intensity infections. We compared the performance of the KK method and real-time PCR in the framework of a randomized trial, which evaluated four novel treatments against Trichuris trichiura and concomitant STH infections. Results Two stool samples obtained from 320 participants were examined at baseline and follow-up with quadruplicate KK and PCR analyses of one of the two samples using “bead-beating” for DNA extraction. At follow-up, 80 samples were negative according to both PCR and KK and 173 were positive with both methods for any of the STHs. Relative to PCR, the calculated sensitivity of KK at follow-up was 83.6%, 43.0% and 53.8% for T. trichiura, for hookworm and for Ascaris lumbricoides, respectively. The sensitivity of PCR compared with KK at this time point was 89.1% for T. trichiura, 72.7% for hookworm and 87.5% for A. lumbricoides. Cure rates (CRs) for T. trichiura and A. lumbricoides were slightly lower with the PCR method. For hookworm CRs with KK were mostly significantly lower, namely 36.7%, 91.1%, 72.2% and 77.8% for moxidectin, moxidectin in combination with tribendimidine, moxidectin in combination with albendazole and albendazole in combination with oxantel pamoate, respectively, whereas with PCR the CRs were 8.3%, 82.6%, 37.1% and 57.1%, respectively. Conclusions In conclusion, a single real-time PCR is as sensitive as quadruplicate KK for T. trichiura and A. lumbricoides detection but more sensitive for hookworm, which has an influence on the estimated treatment efficacy. PCR method with DNA extraction using the “bead-beating protocol” should be further promoted in endemic areas and laboratories that can afford the needed equipment. The study is registered at ISRCTN (no. 20398469).

Background The efficacy of a novel oral combination product, Simparica Trio™, containing sarolaner, moxidectin and pyrantel was evaluated against five tick species that commonly infest dogs in the USA, Amblyomma americanum, Amblyomma maculatum, Dermacentor variabilis, Ixodes scapularis and Rhipicephalus sanguineus. Methods Laboratory studies were conducted against two different strains of each tick species. In each study, 10 purpose-bred Beagle or mixed-breed dogs were randomly allocated to one of two treatment groups based on pre-treatment host-suitability tick counts. Dogs were infested with approximately 50 (45–55) unfed adult ticks on Days -2, 5, 12, 19, 26 and 33. On Day 0, dogs received either a single oral dose of Simparica Trio™ at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) or placebo. Tick counts were conducted at 48 h post-treatment and after each subsequent weekly re-infestation for A. maculatum, D. variabilis, I. scapularis and R. sanguineus studies and at 48 hours or at 72 h post-treatment and after weekly re-infestation in the first and second A. americanum studies, respectively. Results No treatment-related adverse reactions occurred in any study. In all studies, placebo-treated dogs maintained infestations throughout the entire study duration, and dogs treated with Simparica Trio™ had significantly lower (P ≤ 0.0010) mean live tick counts than placebo-treated dogs at all time-points. Against A. maculatum, D. variabilis, I. scapularis and R. sanguineus, a single oral dose of Simparica Trio™ evaluated at 48 h post-treatment provided ≥ 98.9% efficacy against existing infestations, and within 48 h of re-infestation efficacy was ≥ 90.4% through at least Day 28 (except for R. sanguineus on Day 14 in a single study with an efficacy of 89.7%). Against A. americanum, Simparica Trio™ provided ≥ 99.4% efficacy at ≤ 72 h after treatment of existing infestations and maintained ≥ 98.4% efficacy at ≤ 72 h after re-infestation through at least Day 35. Conclusions A single dose of Simparica Trio™ administered orally at the minimum label dosage of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel provided treatment and control of the common tick species infesting dogs in the USA for at least one month.

Background Soil transmitted helminths (STH) are intestinal nematodes and constitute one of the most neglected tropical diseases to exist. Objective: This study determined the efficacy of albendazole-pyrantel pamoate compared to albendazole in 8–12 years old children with Trichuris trichiura infection. Methods A randomised controlled trial was conducted between October 2017 and February 2018 on participants whose stool examinations confirmed the presence of Trichuris trichiura infection. The subjects were randomised into two groups. The statistical analysis used Chi-square test. Results There were 392 of 600 children at five public elementary schools in Bangli and Bali and were infected with Trichuris trichiura. The cure rate of Trichuris trichiura infection seven days following treatment was lower with the combination of albendazole and pyrantel pamoate compared to that of albendazole. The egg reduction rate of Trichuris trichiura infection was lower with the combination of albendazole and pyrantel pamoate compared to albendazole. Conclusion The study indicated that a combination of albendazole and pyrantel pamoate does not improve cure rate or egg reduction rate in 8–12 years old children with Trichuris trichiura infection.

The immune system represents a host’s main defense against infection to parasites and pathogens. In the wild, a host’s response to immune challenges can vary due to physiological condition, demography (age, sex), and coinfection by other parasites or pathogens. These sources of variation, which are intrinsic to natural populations, can significantly impact the strength and type of immune responses elicited after parasite exposure and infection. Importantly, but often neglected, a host’s immune response can also vary within the individual, across tissues and between local and systemic scales. Consequently, how a host responds at each scale may impact its susceptibility to concurrent and subsequent infections. Here we analyzed how characteristics of hosts and their parasite infections drive variation in the pro-inflammatory immune response in wild wood mice (Apodemus sylvaticus) at both the local and systemic scale by experimentally manipulating within-host parasite communities through anthelmintic drug treatment. We measured concentrations of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) produced in vitro in response to a panel of toll-like receptor agonists at the local (mesenteric lymph nodes [MLNs]) and systemic (spleen) scales of individuals naturally infected with two gastrointestinal parasites, the nematode Heligmosomoides polygyrus and the protozoan Eimeria hungaryensis. Anthelmintic-treated mice had a 20-fold lower worm burden compared to control mice, as well as a four-fold higher intensity of the non-drug targeted parasite E. hungaryensis. Anthelmintic treatment differentially impacted levels of TNF-α expression in males and females at the systemic and local scales, with treated males producing higher, and treated females lower, levels of TNF-α, compared to control mice. Also, TNF-α was affected by host age, at the local scale, with MLN cells of young, treated mice producing higher levels of TNF-α than those of old, treated mice. Using complementary, but distinct, measures of inflammation measured across within-host scales allowed us to better assess the wood mouse immune response to changes in parasite infection dynamics after anthelmintic treatment. This same approach could be used to understand helminth infections and responses to parasite control measures in other systems in order to gain a broader view of how variation impacts the immune response.

Gastrointestinal parasites, Parascaris sp. and strongyles, are common in young horses worldwide and control of these parasites is challenged by increasing anthelmintic resistance. Our aim was to identify risk factors for these infections as well as to assess the efficacy of fenbendazole (dose 7.5 mg/kg) and pyrantel embonate (dose 19 mg/kg) against Parascaris sp. We also evaluated association between owner observed symptoms and patent infections with these parasites. Fecal samples were collected from 367 young horses in Finland and a questionnaire study was conducted. Fecal egg counts were performed by Mini-FLOTAC (R) method. Univariable logistic regression models using patent infection status (Yes/No), separately for Parascaris sp. and strongyle infections as an outcome were run initially to screen potential risk factors collected by the questionnaire. After the initial screening, multiple logistic regression models were constructed and run to account for correlated data structure, risk factors and potential confounders simultaneously. Two significant risk factors for a patent Parascaris sp. infection were found: breeding farm size (p = 0.028) and frequency of horse movements (p = 0.010). Horses originating from large breeding farms were more likely (OR = 2.47, 95% confidence interval (CI) 1.10-5.51) to shed Parascaris sp. eggs upon relocation to training stables compared to horses originating from small breeding farms. Horses living in farms with frequent horse movements to other premises had higher odds (OR = 3.56, 95% CI: 1.35-9.39) of a patent Parascaris sp. infection compared to farms with less frequent horse movements. Risk factors for patent strongyle infection included age (p

Anthelmintic resistance in equine cyathostomin parasites is widespread. A surveillance-based parasite control program using fecal egg counts (FECs) and fecal egg count reduction tests (FECRTs) to decrease anthelmintic use and monitor treatment efficacy is recommended. The purpose of this study was to examine shifts in equine parasite control program management practices via a short course presented by the Penn State Extension, and to highlight how data collected from these programs is useful for monitoring anthelmintic efficacy on a large scale. Horse owners were enrolled after participating in a short course and filled out questionnaire surveys about their parasite management programs pre and post study, horse information, and farm information. FECs were performed at three time points, and horses above a 300 strongyle eggs per gram cut-off were treated with pyrantel pamoate, fenbendazole, or ivermectin. Two weeks post-treatment, FECRTs were performed to determine treatment efficacy, which included 29 farms with 513 individual treatments. Prior to the study, only 30.6% of farms used FECs, but after the study, 97.3% of farms said they would use FECs in the future. Horses were given an average of 4.1 anthelmintic treatments per year before the study, and post study 89.2% of farms were able to reduce the number of anthelmintic treatments used. Fenbendazole was effective on zero farms, pyrantel pamoate on 7.4% of farms, and ivermectin on 92.9% of farms. This outreach project helped generate information about anthelmintic efficacy levels, causing a shift in practices on participating farms, and collected useful anthelmintic resistance data.

Albendazole is an effective anthelmintic intensively used for decades. However, profound pharmacokinetic (PK) characterization is missing in children, the population mostly affected by helminth infections. Blood microsampling would facilitate PK studies in pediatric populations but has not been applied to quantify albendazole's disposition. Quantification methods were developed and validated using liquid chromatography-tandem mass spectrometry to analyze albendazole and its metabolites albendazole sulfoxide and albendazole sulfone in wet samples (plasma and blood) and blood microsamples (dried-blood spots [DBS]; Mitra). The use of DBS was limited by a matrix effect and poor recovery, but the extraction efficiency was constant throughout the concentration range. Hookworm-infected adolescents were venous and capillary blood sampled posttreatment with 400 mg albendazole and 25 mg/kg oxantel pamoate. Similar half-life (; t; 1/2; = ∼1.5 h), time to reach the maximum concentration (; t; max; = ∼2 h), and maximum concentration (; C; max; = 12.5 to 26.5 ng/ml) of albendazole were observed in the four matrices. The metabolites reached; C; max; after ∼4 h with a; t; 1/2; of ca. 7 to 8 h. A statistically significant difference in albendazole sulfone's; t; 1/2; as determined by using DBS and wet samples was detected.; C; max; of albendazole sulfoxide (288 to 380 ng/ml) did not differ among the matrices, but higher; C; max; of albendazole sulfone were obtained in the two microsampling devices (22 ng/ml) versus the wet matrices (14 ng/ml). In conclusion, time-concentration profiles and PK results of the four matrices were similar, and the direct comparison of the two microsampling devices indicates that Mitra extraction was more robust during validation and can be recommended for future albendazole PK studies.

The present study aims to give a better estimate of the worm burden (ascariasis) to address accurately the impact of intestinal parasitosis on the children growth in Africa. The study was conducted on 20 subjects aged 10 months to 10 years (Mean more or less SD: 5.6 more or less 2.3 years). They were treated with 10 mg/kg of Pyrantel pamoate. The next day, the stools were collected, washed and filtered to harvest all adult ascaris. In total, 141 ascaris (71 males and 70 females) were extracted for 879.9 g of stool. The geometric mean of eggs counted was 29 by 2 mg of stool. The daily eggs laying per female was estimated to 202,500 eggs/days (CI95%: 128,800 and 276,200). Statistical analysis shows that the parasitic worm burden was proportional both to the number eggs counted per unit of stool volume, and to age of infested subject. A regression model based on these two parameters, with a coefficient of determination equal to 59 %, was retained. Thus, for an old subject respectively of 1, 5 and 10 years, at which 1 egg of ascaris in approximately 2 mg of a preparation would lodge a respective parasitic mass of 1, 3 and 9 g. The results are in the form of confidence interval. For example, for a 5 years old subject with an average of 10 eggs (CI95% = 5.6 - 14.4) after reading of 2 separated preparations coming from the same specimen, the estimated parasitic load is laying between 7 and 11 g. KEY-WORDS : Ascaris lumbricoides; estimation of load parasitic; Kinshasa

Nematodes are an important cause of disease and loss of performance in horses. Changes in the parasitic fauna of horses have occurred in the past few decades, making cyathostomins the major parasites in adult horses, while large strongyles have become less prevalent. Parascaris spp. remains the most important parasite infecting foals and weanlings. Anthelmintic resistance is highly prevalent in cyathostomins and Parascaris spp. worldwide and it must be factored into treatment decisions. To assess anthelmintic efficacy in Northern Italy, we sampled 215 horses from 17 sport and horse-breeding farms. Fecal egg count reduction tests (FECRT) were used to assess anthelmintic efficacy. Copromicroscopic analysis was performed using MiniFLOTAC before treatment with fenbendazole, pyrantel pamoate or ivermectin, and repeated 14 days post-treatment. Strongyle-type eggs were detected in 66.91% of horses (CI95% 61.40–73.79%), while Parascaris spp. was detected in 2.79% (CI95% 1.94–5.95%). Reduced efficacy against cyathostomins was observed for fenbendazole in 55.56% of the treated animals (CI95% 41.18– 69.06%), and for pyrantel pamoate in 75% of animals (CI95% 30.06–95.44%). Ground-based actions must be set in place to promote the uptake of state-of-the-art worm control plans that will prevent clinical disease while minimizing the selection pressure of resistant parasites.

Ancylostoma (A.) ceylanicum, one of the most common species of hookworms infecting dogs and cats, also causes patent infections in humans and is now considered to be the second most common hookworm species infecting populations in southeast Asia. A Japanese patient who returned from a visit to Thailand and Lao People's Democratic Republic (PDR) was presented with intermittent watery diarrhea with eosinophilia. Hookworm eggs were found in feces samples, and adult worms were confirmed to be present in the jejunum with capsule endoscopy and double balloon enteroscopy. A diagnosis of A. ceylanicum infection was made based on the morphology of the adult worms along with findings of a PCR-based molecular study using larvae obtained from a fecal sample culture. The infection was considered likely to have been obtained during a 1-month stay in a Laotian village, where the patient had eaten local food, worn sandals on bare feet, and lived as a local native villager, though he had stayed in modern hotels during the visit to Thailand.

Parasitic helminths of equids are capable of causing ill-thrift, clinical disease, and death. Although young horses are the most susceptible to parasitic disease and are the most intensively treated cohort, deworming regimens are rarely evaluated within this age group. This study objectively evaluated the impact of deworming regimen on fecal egg counts (FECs), growth rates, and body-condition scores in young Thoroughbreds. Forty-eight Thoroughbred foals from three central Kentucky farms were randomly allocated to two treatment groups: an interval dose program receiving bi-monthly rotations of pyrantel pamoate and ivermectin and a daily deworming group receiving daily rations of pyrantel tartrate feed additive throughout the study, oxibendazole at two months of age, and moxidectin treatments at 9.5 and 16.5 months of age. Pre- and post-treatment eggs per gram of feces (EPGs) of Parascaris spp. and strongyle family parasites, gel/paste dewormer efficacies, and monthly weights and body condition scores were collected. Ascarid and strongyle FECs were not significantly different between groups but were significantly influenced by horse age with strongyle counts continually increasing and ascarid counts peaking at 4.5 months of age. Reduced strongyle efficacies of ivermectin and moxidectin were observed on two farms with consistently low pyrantel pamoate efficacies on all three farms. Ivermectin also exhibited reduced ascarid efficacy. Average daily gain did not differ significantly between groups and was only significantly influenced by age, mirroring average daily gain reference data for Kentucky Thoroughbreds born in 2013. Body condition scores also did not differ between groups, remaining in the optimal range (5-6) for the duration of the study. Management practices resulting in growth rates matching the reference data and in optimal body condition scores compensate for the negative impacts of parasitism even in cases of reduced drug efficacy. Performance parameters can provide useful information in cases of suboptimal parasite control.

El presente estudio tuvo como objetivo determinar la efectividad de tres principios antihelmínticos comúnmente usados en equinos del Valle de Aburrá, departamento de Antioquia (Colombia), mediante la prueba de reducción de recuento de huevos fecales (FECTR). Se realizó un estudio transversal en 143 caballos con recuentos iniciales de >100 huevos por gramo de heces (HPG). Se evaluaron tres principios antihelmínticos (fenbendazol [FEN], ivermectina [IVM] y pamoato de pirantel [PYR]). Se encontró que la mayoría de los encargados de los animales no recordaban el producto utilizado en la última desparasitación (27.9%; 40/143); que en la población de estudio era común el uso de IVM (25.2%; 36/143) y FEN (23.1%; 33/143); y, que la IVM es el principio activo con la mayor efectividad en la población de estudio (82.7%), seguido del PYR (65.8%). Ninguno de los principios activos evaluados mostró ser efectivo contra parásitos que producen huevos tipo Strongylus, mientras que la IVM y el PYR mostraron ser aún efectivos para el control de Oxyuris equi. Esto permite sospechar del desarrollo de resistencia antihelmíntica en nematodos gastrointestinales que afectan los caballos del área de estudio.

Tablets for oral suspension (TOS) present a convenient alternative dosage form to conventional tablets. Dispersed in a glass of water or on a spoon, such tablets can be easily administered, which can become beneficial for pediatric or geriatric patients. The novel excipient functionalized calcium carbonate (FCC), consisting of calcium carbonate and calcium phosphate, has already shown to be suitable to produce orally disintegrating placebo tablets. In this study, the influence of formulation composition on disintegration time in water and artificial saliva was investigated using caffeine and oxantel pamoate as model drugs, reflecting BCS class 1 and BCS class 4, respectively. The optimized formulation for each model drug underwent a stress test. The results show that the drug content in DTs was not influenced by FCC under stressed conditions, however the disintegration and dissolution performance was affected by temperature and humidity. It can be concluded that it was possible to produce TOS characterized by rapid disintegration complemented by high physical stability of the tablets and chemical stability of the drug.

The aims of this study were to determine the species of Parascaris present in foals in Sweden and to establish whether anthelmintic resistance to pyrantel and fenbendazole is present on Swedish stud farms. Ascarid eggs collected from different regions in Sweden were karyotyped and were all identified as Parascaris univalens, characterized by one chromosomal pair. Faecal egg count reduction tests were performed on a total of 142 foals on 9 farms between September 2016 and May 2017. Healthy foals with at least 150 eggs per gram faeces (EPG) were included in the study and treated with oral pastes of pyrantel embonate or fenbendazole according to manufacturer instructions. The efficacy of the drugs was calculated by a Bayesian model using the R package "eggCounts". In accordance with the American Association of Equine Practitioners, parasites were classified as resistant to pyrantel if the reduction in EPG was ≤ 85% and to fenbendazole if the observed efficacy was ≤ 90%. Four of eleven groups treated with pyrantel had an observed efficacy of ≤ 85%, and as many as 43% of the foals treated with pyrantel excreted eggs 10-16 days after treatment. In contrast, one of the six groups treated with fenbendazole had an observed efficacy of ≤ 90%, and only 6% of all foals were excreting eggs 10-16 days after treatment. Since resistance to ivermectin has earlier been shown to be widespread in Parascaris spp. in Sweden it is likely that multiresistant populations are present on Swedish stud farms. This is the first study showing the existence of pyrantel-resistant Parascaris spp. in Europe, and the first ever study where anthelmintic resistance has been shown in P. univalens.

Soil-transmitted helminths infect 1.5 billion people worldwide. Treatment with anthelminthics is the key intervention but interactions between anthelminthic agents and the gut microbiota have not yet been studied. In this study, the effects of four anthelminthic drugs and combinations (tribendimidine, tribendimidine plus ivermectin, tribendimidine plus oxantel-pamoate, and albendazole plus oxantel-pamoate) on the gut microbiota were assessed. From each hookworm infected adolescent, one stool sample was collected prior to treatment, 24 h post-treatment and 3 weeks post-treatment, and a total of 144 stool samples were analyzed. The gut bacterial composition was analyzed using 16S rRNA gene sequencing. Tribendimidine given alone or together with oxantel-pamoate, and the combination of albendazole and oxantel pamoate were not associated with any major changes in the taxonomic composition of the gut microbiota in this population, at both the short-term post-treatment (24 h) and long-term post-treatment (3 weeks) periods. A high abundance of the bacterial phylum Bacteroidetes was observed following administration of tribendimidine plus ivermectin 24 h after treatment, due predominantly to difference in abundance of the families Prevotellaceae and Candidatus homeothermaceae. This effect is transient and disappears three weeks after treatment. Higher abundance of Bacteroidetes predicts an increase in metabolic pathways involved in the synthesis of B vitamins. This study highlights a strong relationship between tribendimidine and ivermectin administration and the gut microbiota and additional studies assessing the functional aspects as well as potential health-associated outcomes of these interactions are required., Graphical abstract Image 1, Highlights • Tribendimidine in combination with ivermectin modulate the gut microbiota. • Bacteroidetes phylum is more abundant 24 h after treatment. • B vitamins biosynthesis pathways are over-represented 24 h post-treatment. • Tribendimidine/ivermectin effect is transient and disappears within 3 weeks.

In the last decade there have been numerous reports of anthelmintic resistant cyathostomins in many parts of the world. The objective of the present study was to evaluate the efficacy of the commercially available anthelmintics against cyathostomin egg shedding in the Mid-Atlantic region of the United States. A total of 989 horses from 67 different farms located in southeastern Pennsylvania, northern Delaware, and northeastern Maryland were treated with fenbendazole, oxibendazole, pyrantel pamoate, ivermectin, or moxidectin at their recommended dosages. Fecal egg count reduction testing was used to determine the efficacy of each anthelmintic on those horses with fecal egg counts of ≥ 200 eggs per gram on the day of treatment (272 horses). Decreased efficacy (reduction of strongyle-type fecal egg counts by less than 90%) was found for fenbendazole, oxibendazole, and pyrantel pamoate, with only 6%, 21% and 43% of horses showing reductions of greater than 90%, respectively. The macrocyclic lactones showed high efficacy in all horses sampled in this study. The decreased anthelmintic efficacy detected in this study adds further evidence for the existence of resistant cyathostomins throughout much of the eastern United States. Findings from this study can be used to create a more sustainable approach for parasite control programs.

Three simple, rapid, inexpensive, and highly sensitive spectrophotometric methods are described for the quantifi cation of pyrantel pamoate (PYP) in pure drug and formulations. The methods are based on the molecular charge-transfer (CT) complexation reaction involving pyrantel base (PYL) as n-donor and iodine as σ-acceptor (I 2 , method A), and 2,4-dinitrophenol (DNP, method B) or picric acid (PA, method C) as π-acceptors. Spectrophotometrically, the CT complexes showed absorption maxima at 380, 420, and 430 nm, for methods A, B, and C, respectively. Under optimum conditions, Beer's law was obeyed over the concentration ranges 0.12–2.9, 0.12–3.75, and 0.12–2.9 μg/ml for methods A, B, and C, respectively. The apparent molar absorptivity of the CT complexes at the respective λmax are calculated to be 2.63 × 10 5 , 6.91 × 10 4 , and 1.73 × 10 5 l/mol·cm respectively and the corresponding Sandell sensitivity values are 0.0009, 0.003, and 0.0012. The limits of detection (LOD) and quantification (LOQ) are calculated to be (0.02 and 0.07), (0.05 and 0.15), and (0.02 and 0.07) μg/ml with methods A, B, and C, respectively. The intra-day and inter-day accuracy expressed as %RE and precision expressed as %RSD are less than 3%. The methods have been applied to the determination of PYP in tablets, suspensions, and spiked human urine. Parallel assay by a reference method and statistical analysis of the results obtained show no significant difference between the proposed methods and the reference method with respect to accuracy and precision, as evident from the Student’s t and variation ratio tests. The accuracy of the methods has been further ascertained by recovery tests via the standard addition technique.

Baylisascaris procyonis is a common gastrointestinal parasite of raccoons (Procyon lotor) and is a zoonotic helminth with the potential to cause severe or fatal infection. Raccoons thrive in human-dominated landscapes, and the fecal-oral transmission pathway and lack of effective treatment make B. procyonis a serious threat to public health. The distribution of medicinal baits has emerged as a socially acceptable and cost-effective method for managing disease in free-ranging wildlife. We assessed the suitability of a mass-producible anthelmintic bait for B. procyonis mitigation by evaluating the willingness of free-ranging raccoons to consume anthelmintic baits and determining whether bait consumption successfully cleared B. procyonis infections from raccoons. Anthelmintic baits were modified from standard fishmeal polymer baits, the food attractant commonly used in oral rabies vaccine baits, with the introduction of 220 mg of pyrantel pamoate into the fishmeal mixture. We captured 16 naturally infected raccoons, presented one anthelmintic bait, and monitored B. procyonis infection over 90 d by screening feces for eggs. Treatment cleared B. procyonis infections for nine of 12 raccoons that consumed10 g of the 15 g bait. We used remote cameras to monitor in situ patterns of bait consumption for anthelmintic baits relative to standard baits. Both anthelmintic and standard baits were rapidly consumed, with no differences in the rate of consumption between bait types. However, after bait contact, raccoons demonstrated a greater willingness to consume standard baits while ignoring anthelmintic baits more frequently (P = 0.06). Initial trials of anthelmintic baits show promise, although refinement in both dose and palatability is needed. At mass production scales, the addition of pyrantel pamoate to fishmeal polymer baits would be inexpensive, potentially making anthelmintic baits a viable management option when coupled with an oral rabies vaccine or used independently for B. procyonis mitigation.