THE EFFECTIVENESS OF LEVAMISOLE HYDROCHLORIDE IN THE TREATMENT OF ADULT DIROFILARIA IMMITIS

Dogs infected with D. immitis were treated with oral levamisole hydrochloride at various dose rates over different durations. Clinical toxicity, haematological and biochemical parameters, body weight and food intake were recorded and filarial mortality estimated at autopsy. All filariae were dead in dogs treated at 10 mg/kg body weight twice daily (12 hourly) for 14 days, with minimal clinical toxicity being seen during the treatment period.     

Limited efficacy of levamisole against adults of Dirofilaria immitis in a dog

A dog with chronic dirofilariasis (Dirofilaria immitis) was given 15 doses of 12 or 24 mg of levamisole/kg of body weight in 6 treatments within 96 days. Concentration of microfilariae in the blood was determined before and after treatment, and Aedes triseriatus mosquitoes were fed on the dog 1 to 5 days after each treatment and examined for D immitis larvae. Several adult worms were recovered from the dog 160 days after the end of the treatments.     

Efficacy of avermectin B1a against microfilariae of Dirofilaria immitis

Avermectin B1a given at a dose level of 0.05 or 0.1 mg/kg of body weight caused rapid removal of Dirofilaria immitis microfilariae from the blood of dogs with heartworm infections. If the adult worms were also killed with an arsenical (melarsoprol), the removal of microfilariae was permanent.     

Clinical and parasitological evaluations of levamisole as a treatment for bovine stephanofilariasis

Field trials were carried out with two formulations of levamisole for treatment of chronic inflammatory lesions on the muzzle and teats of cattle, caused by Stephanofilaria okinawaensis in the enzootic area of the disease, Ishigaki Island, Okinawa Prefecture, Japan.Cattle were treated orally with levamisole hydrochloride (10% powder) at a dose of 7.5 g/100 kg of body weight once (64 cattle) or twice with an interval of 3 or 4 weeks (five cattle each). Lesions on the muzzle and tests disappeared or were reduced within 4 weeks of the first medication. In some cattle a sign of recurrence was observed 8 weeks after medication.Parasitological and histological examinations were carried out 1 week carried out 1 week (10 cattle), 4 weeks (12 cattle), and 8 weeks (13 cattle) after single oral administration of levamisole hydrochloride. No Stephanofilaria worms were detected at 1 week after medication. A small number of worms were detected at 4 weeks and more were observed 8 weeks after medication.A levamisole phosphate solution (18.2%) was injected subcutaneously once into one teat of each of three cattle, or twice into the neck with a 4-week interval between treatments (five cattle). The dose was 2 ml/teat (364 mg of active ingredient) or 2 ml/45 kg of body weight for the side of the neck. There was marked improvement as with oral medication with levamisole hydrochloride powder.     

Toxicity and tissue residue depletion of levamisole hydrochloride in young goats

Toxicity and tissue residue depletion studies were conducted in young goats, using an oral drench formulation of levamisole hydrochloride. In the target animal toxicity study, 3 groups of 5 goats each were given levamisole orally to provide approximately 11.88, 23.76, or 35.64 mg of levamisole HCl/kg/d for 3 consecutive days; a fourth group of 5 goats served as untreated controls. Blood samples were taken for analysis of levamisole 1 day prior to dosing and 1, 2, 3, 4, and 7 days following the third dose. At the 35.64-mg/kg dose, 2 of 5 goats responded with typical cholinergic signs of toxicosis on each of the 3 days of dosing. The times for the onset of clinical signs of toxicosis ranged from 18 to 63 minutes, with an average duration of 32 minutes. Administration of 23.76 mg of levamisole HCl/kg resulted in hyperactive behavior in 1 of 5 goats only on the first day of dosing; no abnormal behavior was observed in any of the 5 goats following the second or third dose of levamisole HCl at 23.76 mg/kg. Untoward effects were not seen in the 5 goats dosed at 11.88 mg of levamisole HCl/kg or in the controls during the 3-day dosing period or in the following 7-day observation period. Overall, the observed signs of toxicosis did not become more severe, affect more goats, or persist for a longer period on subsequent dosing days.(ABSTRACT TRUNCATED AT 250 WORDS)     

The efficacy of levamisole, and a mixture of oxfendazole and levamisole, against the arrested stages of benzimidazole-resistant Haemonchus contortus and Ostertagia circumcincta in sheep

Sheep were allowed to graze pasture that had been seeded with benzimidazole-resistant Haemonchus contortus and Ostertagia circumcincta in order to acquire a burden of arrested larvae. Following housing, sheep were dosed orally with either oxfendazole at a dose rate of 4.7 mg/kg (to confirm the benzimidazole-resistant status of the species of nematode), levamisole at a dose rate of 7.5 mg/kg, or an oxfendazole/levamisole mixture at a dose rate of 4.6 mg/kg oxfendazole and 8.1 mg/kg levamisole. The efficacies of the treatments were assessed by estimation of the arrested larval burden in the abomasum of each sheep, either at 10 or 11 days (oxfendazole and oxfendazole/levamisole mixture), or 12 or 13 days (levamisole), after treatment. Compared to the untreated controls, the protection afforded by a single dose of either levamisole or the oxfendazole/levamisole mixture was >99% against the arrested stages of both Haemonchus contortus and Ostertagia circumcincta. Treatment with oxfendazole confirmed the benzimidazole-resistance status of the two species.     

Chemoprophylactic effects of milbemycin oxime against larvae of Dirofilaria immitis during prepatent development.

Three studies were conducted to determine the efficacy of milbemycin oxime in the prevention of Dirofilaria immitis infection in dogs. Dogs were given single or multiple experimental inoculations with infective third-stage D immitis larvae and were treated with milbemycin oxime at a target dosage of 0.5 mg/kg of body weight either once or at monthly intervals at various times after inoculation. The compound was effective in preventing infection when 1 dose was administered 30 or 45 days after inoculation. Significant, but incomplete, protection was achieved when single treatments were administered 60 or 90 days after inoculation. Multiple monthly treatments beginning 60 days after inoculation appeared to provide additive effects that resulted in restoration of complete efficacy.     

LEVAMISOLE AS A MICROFILARICIDAL AGENT IN THE CONTROL OF CANINE DIROFILARIASIS

The effectiveness of levamisole hydrochloride as a microfilaricidal agent when used 3 weeks after thiacetarsamide sodium therapy for canine dirofilariasis, was studied in 6 experimental dogs and 20 clinical cases. The drug, when administered orally in gelatine capsules daily, cleared microfilariae from the circulation in the experimental dogs in 7 to 11 days. A dose rate of 10mg/kg appeared as effective as 15mg/kg. In the clinical group 70% of dogs had zero microfilarial counts after 4 to 8 doses at 10mg/kg daily. Vomiting, diarrhoea and inappetence were observed in some animals, but were not a significant problem. Elevations in plasma GPT and AP levels were recorded during the administration of levamisole in some dogs while GOT levels rose in 1 dog only. Urea and creatinine levels were unaffected in all dogs. The only haematological parameter affected was the eosinophil count which rose during levamisole administration. All levamisole-treated animals, were successfully commenced on daily DEC, as a prophylactic measure, while an anaphylactic-type reaction occurred when this drug was administered to 1 of the 2 control animals.     

Efficacy of levamisole alone and in combination with mebendazole against Gongylonema pulchrum infection in rabbits

Gongylonema pulchrum is an important parasite of captive primates. Twelve rabbits were infected with 30 third-stage larvae of G. pulchrum. At 4–7 months post-infection, animals were administered levamisole at a single dose of 12 mg/kg, levamisole at 8 mg/kg three times at 2-day intervals, levamisole at a single dose of 8 mg/kg after administration of mebendazole at 70 mg/kg for 3 days or 8 ml of distilled water for 3 days (control). Necropsy at 14 days after treatment revealed that single and multiple dosages of levamisole reduced nematode burdens by 68.4% and 89.5%, respectively. The combined regimen of mebendazole and levamisole exhibited high efficacy for treating G. pulchrum located widely within the upper digestive tract, with a reduction of 98.2%. These results suggest that this combined chemotherapy treatment may be effective against G. pulchrum infection, including buccal and lingual gongylonemiasis in primates.     

Seasonal variation in anthelmintic response by cattle to dermally applied levamisole

Four experiments in 1978-79, and 2 in 1982 designed to define the optimum dose rate of dermally applied formulations of levamisole are described. These experiments showed that the absorption of levamisole with resultant blood levels and anthelmintic activity is strongly influenced by temperature. In warm to hot conditions percutaneous absorption is rapid and high blood levels with high anthelmintic activity against Haemonchus placei, Ostertagi sp, Trichostrongylus sp, Cooperia sp, Oesophagostomum radiatum, O. venulosum and Dictyocaulus viviparus result from dose rates of 10 mg/kg or more. In cold weather the high efficacy against H. placei, Cooperia sp, and Oesophagostomum sp is unchanged, but efficacy against Ostertagia sp, T. axei and D. viviparus decreases to the extent that a mean dose rate of 20 mg/kg (range 15 to 25 mg/kg) is necessary if the anthelmintic activity of dermally applied levamisole is to match that of either parenterally or orally administered material. These anthelmintic data are supported by the levamisole blood profile which in winter months, peaks at a figure of one quarter or less of that obtained from a similar dose rate in warm conditions. The implications of this variability in action are discussed.     

Activity of an injectable, sustained-release formulation of moxidectin administered prophylactically to mixed-breed dogs to prevent infection with Dirofilaria immitis.

OBJECTIVE: To test the ability of a single injection of a sustained-release formulation of moxidectin (moxidectin SR) to protect dogs against heartworm infection for 180 days after inoculation with infective third-stage larvae (L3) of Dirofilaria immitis. ANIMALS: 32 adult mixed-breed dogs. PROCEDURE: Dogs were allocated to 4 groups on the basis of weight and sex. Dogs were injected SC with saline (0.9% NaCl) solution or moxidectin SR at the rate of 0.06, 0.17, or 0.5 mg/kg of body weight (day 0). Each dog was inoculated SC with 50 D immitis L3 180 days later. On days 330 and 331, dogs were euthanatized. The heart, lungs, and thoracic cavity were examined, and number and sex of heartworms were determined. RESULTS: A mean of 35.9 heartworms was recovered from untreated control dogs. Fourteen worms were recovered from 1 of 8 dogs given moxidectin SR at the lowest dosage, and none of the dogs in the 2 highest moxidectin treatment groups were infected. Small barely palpable granulomas were detected at injection sites of moxidectin-treated dogs. Frequency and size of granulomas were positively correlated with dose of moxidectin administered. CONCLUSIONS AND CLINICAL RELEVANCE: A single dose of moxidectin SR at a dosage as low as 0.17 mg/kg can safely and reliably confer complete protection against infection after challenge-exposure with D. immitis L3, and protection lasts for at least 180 days. This mode of prophylactic treatment against infection with heartworms effectively eliminates failure of prophylaxis that results from erratic administration of medications designed for monthly administration.     

Levamisole toxicosis in a dog

A single oral dose of levamisole hydrochloride given at the rate of 12 mg/kg was believed responsible for bradycardia, tachypnea, hypothermia, cerebrocortical depression, and diarrhea in a dog. Supportive treatment and symptomatic treatment for the bradycardia were required for 4 days. In addition to these previously reported abnormalities associated with levamisole toxicosis, cerebrocortical depression and multiple foci of irritation were characterized by electroencephalography.     

Efficacy of ivermectin and pyrantel pamoate combined in a chewable formulation against heartworm, hookworm, and ascarid infections in dogs.

Eight trials were conducted in dogs to document the efficacy of ivermectin (6 micrograms/kg of body weight) and pyrantel pamoate (5 mg of active pyrantel/kg) in a beef-based chewable formulation against Dirofilaria immitis, Ancylostoma caninum, Uncinaria stenocephala, Toxocara canis, and Toxascaris leonina. Three studies involved induced infection with D immitis, and 5 studies involved induced or natural infection with hookworms and ascarids. In 3 intestinal parasite trials, the efficacy of the combination chewable tablet was compared with each of its components. Results indicated that 1 component did not interfere with the activity of the other. In 1 heartworm and 2 intestinal parasite trials, the efficacy of pyrantel, ivermectin/pyrantel combination, or ivermectin with pyrantel dosage of 10 mg/kg was evaluated. The ivermectin/pyrantel combination was 100% effective in preventing development of D immitis larvae. Efficacy of the combined product against T canis, Toxascaris leonina, A caninum, and U stenocephala was 90.1, 99.2, 98.5, and 98.7%, respectively. In the intestinal parasite trials, each individual component was found not to interfere with the anthelmintic action of the other. Increasing the dosage of pyrantel to 10 mg/kg (2 x that in the combination) did not interfere with the efficacy of ivermectin against heartworm or increase the activity of pyrantel against intestinal parasites.     

The effect of fenbendazole on nematode parasites in experimentally infected lambs.

Fenbendazole given orally to experimentally infected lambs at a dose rate of 5 mg per kg was found to be 100 per cent effective against three and 10-day larave and also against 20-day adults of H contortus, O circumcincta, N battus and T colubriformis. The same dose was also 100 per cent effective against 10-day, 17-day larvae and 27-day adult D filaria.     

Effect of first-pass hepatic metabolism on the disposition of levamisole after intravenous administration in rabbits

OBJECTIVE: To evaluate the contribution of first-pass hepatic metabolism of levamisole on levamisole disposition in rabbits. ANIMALS: 30 male New Zealand White rabbits. PROCEDURES: Rabbits were randomly placed into 2 groups. Rabbits in the first group received levamisole via the marginal ear vein at the following 3 doses: 12.5, 16, and 20 mg/kg (5 rabbits for each dose). Rabbits of the second group received levamisole via the jejunal vein at the same doses (5 rabbits each). During the following 240-minute period, plasma samples were obtained and quantified for levamisole concentrations by reversed-phase high-performance liquid chromatography. RESULTS: No significant differences were found between pharmacokinetic parameters calculated by compartmental or noncompartmental analysis. Mean hepatic extraction ratio ranged from -0.044 to 0.017 and from 0.020 to 0.081 when area under the plasma concentration-time curve values were obtained after compartmental or noncompartmental analysis, respectively. After compartmental analysis, plasma concentration decreased bi-exponentially. Mean pharmacokinetic parameter values were as follows for each dose (12.5, 16, and 20 mg/kg, respectively): after levamisole administration via the marginal ear vein, volume of distribution at steady state (Vss) = 4.26, 4.33, and 3.20 L/kg; total body clearance (CI) = 49.04, 43.77, and 39.26 mL/kg x min; and half-life associated with beta-phase (t1/2beta) = 77.93, 85.39, and 69.79 minutes. After levamisole administration via the jejunal vein, Vss = 4.38, 2.85, and 2.97 L/kg; CI = 48.14, 42.40, and 39.69 mL/kg x min; and t1/2b = 101.9, 76.71, and 76.13 minutes. CONCLUSIONS: Levamisole has a low degree of hepatic extraction in rabbits.     

Effect of levamisole on lymphocyte blastogenesis and neutrophil function in dexamethasone-treated cattle

Levamisole was evaluated at 6 dose levels for its ability to prevent the dexamethasone-induced suppression of in vitro lymphocyte blastogenesis or neutrophil function in cattle. Dexamethasone (0.4 mg/kg of body weight, IM) and levamisole hydrochloride (0.5, 1.0, 2.0, 4.0, or 8.0 mg/kg orally) were administered to groups of 4 cattle daily for 3 days. Another group of 4 cattle were given the 3-day dexamethasone treatment and 6.0 mg/kg of levamisole (the recommended anthelmintic dose) was given only once on the 1st day that dexamethasone was given. Results obtained from the dexamethasone-levamisole-treated cattle were compared with results obtained from cattle that were given only dexamethasone. Levamisole had no apparent consistent ability to enhance lymphocyte blastogenic responsiveness (to the mitogens phytohemagglutinin, concanavalin A, or pokeweed mitogen or in a 1-way mixed lymphocyte reaction) or to enhance neutrophil function (random migration, nitroblue tetrazolium reduction, iodination, or antibody-dependent cell-mediated cytotoxicity) in dexamethasone-treated cattle.     

Effects of treatment with ticlopidine in heartworm-negative, heartworm-infected, and embolized heartworm-infected dogs.

Ticlopidine hydrochloride was evaluated for its effectiveness in inhibiting platelet aggregation and serotonin release in 5 laboratory Beagles before and after heartworm implantation with 7 adult Dirofilaria immitis, and after embolization with 7 dead heartworms to mimic what happens after heartworm adulticide treatment. Five other laboratory Beagles, similarly implanted and embolized with heartworms, were used as nonmedicated controls. During the heartworm-negative stage, the dosage of ticlopidine that inhibited adenosine diphosphate (ADP)-induced platelet aggregation in 5 dogs by at least 50% after 5 days of treatment was 62 mg/kg of body weight once a day. In the same dogs implanted with 7 adult heartworms 21 days previously, mean (+/- SD) ticlopidine dosage required to obtain similar results was 71 (+/- 13) mg/kg given once daily. During the 21 days after dead heartworms were implanted in heartworm-infected dogs, mean ticlopidine dosage was 108 (+/- 35) mg/kg (range, 62 to 150 mg/kg). Ticlopidine treatment was associated with increased platelet numbers in all 5 dogs during the heartworm-negative stage and in 4 of 5 dogs during the heartworm implantation and heartworm embolization stages. Mean platelet volume tended to decrease as platelet numbers increased. At necropsy, gross and histologic pulmonary lesions were less severe in ticlopidine-treated dogs than in nonmedicated control dogs.     

Immunostimulatory effects of the muramyl dipeptide analogue LK415 in chickens immunized with a vaccine strain of infectious bursal disease virus

The effects of muramyl dipeptide (MDP) synthetic analogue LK415 on the immune response of chickens immunized with a live vaccine against infectious bursal disease (IBD) were studied in two independent trials, using levamisole hydrochloride as comparative immunostimulant. Groups of five-week-old commercial chickens (Isa Brown) were immunized orally with 10 doses of the vaccine strain of IBDV (Winterfield strain). The chickens were then given four injections of the MDP analogue LK415 in a dosage of either 0.25 mg/kg body weight (b.w.) or 2.5 mg/kg b.w. or levamisole at a daily dose of 15 mg/kg b.w. for four consecutive days, starting from the day of immunization. Histological examinations of bursal tissue collected on days 2, 4 and 7 postimmunization (p.i.) showed a lower degree of destruction of bursal follicles and earlier renewal of bursal tissue in LK415-treated chickens compared to levamisole-treated and untreated immunized groups. Compared to the other groups, the LK415-treated chickens showed a significantly higher antibody response to IBDV on days 14 and 28 p.i. (P < 0.01) as measured by commercial ELISA. The present study indicates some potent immunostimulatory effects of the MDP analogue LK415 on the chicken immune system.     

Anthelmintic effect of levamisole hydrochloride or ivermectin on tissue toxocariasis of mice

Paranatal transmission of Toxocara canis infection could be prevented in pups if an effective drug were administered to pregnant bitches. This drug also could eliminate the larvae in dogs that have been experimentally infected repeatedly to produce protective immunity. For these reasons, we assayed the effect of 2 doses of levamisole hydrochloride or ivermectin on T canis larvae. Mice (5 groups) were infected with 1,000 infective T canis larvae and then treated with 2 different dosages of levamisole hydrochloride (6 mg/kg or 12 mg/kg, given subcutaneously), 2 different dosages of ivermectin (0.2 mg/kg or 0.4 mg/kg, given IM) or 0.15M NaCl (given subcutaneously) once a day from days 15 to 28 of infection. On day 33 of infection, the parasites in liver, lungs, brain, and carcass were obtained and compared between groups. The smaller dosage of levamisole hydrochloride (6 mg/kg) significantly decreased only carcass parasitism to 17% of that in the controls, but did not affect significantly the total parasite load. The larger dosage of levamisole hydrochloride (12 mg/kg) decreased the infection in all organs, but particularly in carcass and brain; total parasitism was only 36% of that in the controls. The smaller dosage of ivermectin (0.2 mg/kg) significantly increased the number of larvae in the lungs to 550% of that in the controls, but it did not significantly affect the total parasite load. The larger dosage of ivermectin (0.4 mg/kg) significantly decreased only brain parasitism, but liver and total parasitism were decreased to 40% and 57%, respectively, compared with that in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Synergetic effects of oral administration of levamisole and Echinacea purpurea on immune response in Wistar rat

This research investigated the effects of levamisole and Echinacea purpurea (EP), separately and together on the immune response of the rat as a laboratory model. In this experiment, 40 male Wistar rats were obtained and divided into four groups (n = 10). These groups received normal saline (10 mg/kg), EP (500 mg/kg), levamisole (2 mg/kg) and EP (500 mg/kg) with levamisole (2 mg/kg) as oral gavages every day for a period of 4 weeks, respectively. After obtaining blood samples (at the end of each week), haematocrit (HCT), differential and total white blood cell (WBC) counts, phagocyte activity (number), total protein, albumin and globulins levels of samples were obtained. The results of the study showed that the gamma globulin level, WBC, neutrophil and monocyte counts and phagocyte activity increased significantly in comparison with normal saline group during the study. According to the results, each of the mentioned agents had a stimulant effect on the immune system separately and together on rats. In the group that received EP and levamisole simultaneously, these effects were synergistically increased. These compounds, by increasing the mentioned factors, will probably affect the immune system.