The environmental safety of eprinomectin to earthworms.

A study was conducted to assess the environmental safety of the endectocide eprinomectin to the earthworm Lumbricus terrestris under conditions mimicking typical product use on pasture. The LC50 value of eprinomectin in artificial soil after 28 days of exposure is higher than the levels expected in feces from dosed cattle or in soil fertilized with manure from dosed cattle, which indicates a wide margin of safety for this compound to earthworms. However, the no-observed-effect concentration has not been established. Therefore, the current study was conducted to determine whether there would be any effects on earthworms from feces from cattle treated with the commercial formulation of eprinomectin. Feces were collected rectally from grazing cattle on Day 0 before treatment and on Days 2, 4, 7 and 14 after treatment with EPRINEX (eprinomectin) Pour-On for Beef and Dairy Cattle (Merial Limited) at 0.5 mg eprinomectin per kg bodyweight. Assays of eprinomectin B1a (the major component of eprinomectin) were 0, 0.427, 0.152, 0.0512 and 0.00185 mg kg-1 wet weight of feces (equivalent to 0, 3.34, 1.19, 0.40 and 0.010 mg kg-1 on a dry weight basis, respectively). No significant differences (p>0.05) were observed at any day post-treatment in the survival or behavioral effects of any worms fed post-dose feces relative to the worms fed control feces. All post-dose comparisons of weight changes of living earthworms to the control group were not significantly different (p>0.05), indicating that treatment of cattle with EPRINEX (eprinomectin) Pour-On for Beef and Dairy Cattle did not affect feeding or weight gain of the earthworms. The LC50 value and the results of this study establish the wide margin of safety afforded to earthworms by eprinomectin under typical usage conditions.

Productivity effects of bovine mange and control with ivermectin.

A randomised block design study was conducted to evaluate the effects of mange on cattle. Twenty-four Simmentaler Fleckvieh bulls were formed into eight replicates of three bulls based on Day -56 body weight (288-414 kg). Within replicates bulls were randomly allocated to groups G1: uninfested control, G2: infested control or G3: infested, treated with 0.2mg ivermectin/kg (1% ivermectin injection; IVOMEC, Merial) on Day 0. The G2 and G3 bulls were infested with Sarcoptes/Chorioptes mites on Days -56 and -49. Feed consumption was recorded daily throughout the study (Days -56 to 56). Body weights were measured and serum samples collected. Mites were counted at bi-weekly intervals from Day -14 on. The carcasses of the bulls and the leather produced from their hides were evaluated. Differences between variables were declared significant if P

Persistent efficacy of doramectin injectable against artificially induced infections with Cooperia punctata and Dictyocaulus viviparus in cattle.

Three studies were conducted to evaluate the persistent efficacy of doramectin injectable solution against experimental challenges with infective larvae of Cooperia punctata and Dictyocaulus viviparus. In each study, four groups of ten randomly-assigned calves, negative for trichostrongyle-type eggs on fecal examination, were treated subcutaneously in the midline of the neck with saline (1 ml/50 kg) on Day 0 or doramectin (200 microg/kg = 1 ml/50 kg) on Day 0, 7, or 14. Two additional calves from the same pool of animals were randomly assigned as larval-viability monitors and received no treatment. On Days 14-28, approximately 1000 and 50 infective larvae of Cooperia spp. and D. viviparus, respectively, were administered daily by gavage to each animal in Groups T1-T4. On Day 28, the two larval-viability monitor calves were inoculated in a similar manner with a single dose of approximately 30000 and 2000 larvae of Cooperia spp. and D. viviparus, respectively. Equal numbers of calves from each treatment group were killed on Days 42-45, as well as the two viability monitor animals to enumerate worm numbers. A 2% or 5% aliquot of small intestinal contents and washings were examined for worm quantification and identification, while 100% of the lung recoveries were quantified and identified. For each study and across the three studies, geometric mean worm recoveries for each treatment group were calculated from the natural log transformed data (worm count + 1) and were used to estimate percentage reduction. In the three studies, doramectin injectable solution was 97.5% efficacious against lungworms for up to 28 days and was 99.8% efficacious in reducing infection resulting from challenge with infective larvae of C. punctata for at least 28 days post-treatment.

Efficacy of topically administered doramectin against eyeworms, lungworms, and gastrointestinal nematodes of cattle.

OBJECTIVE: To evaluate efficacy of topically administered doramectin against eyeworms, lungworms, and gastrointestinal nematodes of cattle. ANIMALS: 400 cattle (20 cattle in each of 20 trials). PROCEDURE: Trials were conducted in North America; natural and experimentally induced infections were used. In each trial, cattle were allocated randomly to control (placebo [saline [0.9% NaCl] solution at 1 ml/10 kg of body weight] or untreated; n = 10) or doramectin-treated (500 microg/kg of body weight; 10) groups. Treatments were applied in a single passage along the midline of the back, from the withers to the tailhead. Cattle were euthanatized > or =14 days after treatment, and worm burdens were determined by use of standard techniques. RESULTS: Efficacy of doramectin was > or =95.3% against adults of Thelazia gulosa, T skrjabini, Dictyocaulus viviparus, Haemonchus contortus, H placei, Ostertagia lyrata, O ostertagi, Trichostrongylus axei, Bunostomum phlebotomum, Capillaria spp, Cooperia oncophora, C pectinata, C punctata, C spatulata, C surnabada, Nematodirus spathiger, Strongyloides papillosus, T colubriformis, Oesophagostomum radiatum, and Trichuris spp. Efficacy was 95.1% against fourth-stage larvae of D viviparus, H placei, O lyrata, O ostertagi, T axei, C oncophora, C punctata, C spatulata, C surnabada, N helvetianus, T colubriformis, O radiatum, and Trichuris spp. In addition, efficacy against inhibited fourth-stage larvae of O ostertagi and Ostertagia spp was > or =98.1%. CONCLUSIONS AND CLINICAL RELEVANCE: A single topical application of doramectin pour-on was efficacious against a broad range of nematode species in cattle.

Evaluation of selected antiprotozoal drugs in the Babesia microti-hamster model.

The presently used therapy for Babesia microti infections, a combination of quinine and clindamycin, does not always result in parasitologic cures. To identify possible alternative chemotherapeutic agents for such infections, we screened, in the hamster-B. microti system, 12 antiprotozoal drugs that have either recently been released for human use or were in experimental stages of development at the Walter Reed Army Institute of Research for the treatment of malaria and leishmaniasis. Several well-recognized antimalarial drugs, such as mefloquine, halofantrine, artesunate, and artelenic acid, exhibited little or no effect on parasitemia. Two 8-aminoquinolines, WR006026 [8-(6-diethylaminohexylamino)-6-methoxy-4-methylquinoline dihydrochloride] and WR238605 [8-[(4-amino-1-methylbutyl)amino]-2,6-dimethoxy-4-methyl-5 -(3-trifluoromethylphenoxy-7) quinoline succinate], produced clearance of patent parasitemia. Furthermore, blood from infected hamsters treated with WR238605 via an intramuscular injection failed to infect naive hamsters on subpassage, thus producing a parasitologic cure. These two compounds merit further screening in other systems and may prove useful in treating human babesiosis.

Immunopurification and measurement of IgE in serum samples from bancroftian filariasis patients.

Patent infection with Wuchereria bancrofti is associated with increased levels of filaria-specific IgG4 and IgE. In vitro quantification of filaria-specific IgE is hampered by its small proportion in serum relative to other isotypes and by potential competition with IgG4 for the same epitopes on parasite antigens. To determine if IgG4 or other isotypes inhibit the detection of parasite-specific IgE, total IgE was affinity purified prior to filaria-specific IgE enzyme-linked immunosorbent assay. Briefly, anti-human IgE mouse monoclonal antibody 6H10 was coupled to Affigel, and 50 microliters of patient serum was incubated on microcolumns for 16 hr. Total IgE was eluted with 25 mM triethylamine (pH 11.2) and levels of total and filaria-specific IgE and total IgG4 were assessed in the filtrates and eluates. Sera from 14 patients with W. bancrofti microfilaremia (Mf+) and 17 amicrofilaremic patients with chronic pathology (CP) were assayed. Filtrates and eluates were devoid of IgE and IgG4, respectively. The average yield of total IgE in the eluates was 70% (SEM = 6.5; range 21-100%) of that measured in the serum. Antifilarial IgE levels in column eluates were significantly higher in serum samples from CP patients than Mf+ patients. Antibody inhibition of IgE was assessed by comparing the levels of anti-filarial IgE detected in eluates and serum. Evidence for antibody-mediated inhibition of IgE detection was obtained with 2/2 samples from Indian tropical pulmonary eosinophilia patients, but only 2/14 and 4/17 Mf+ and CP patients, respectively.

Reduced antifilarial IgG4 responsiveness in a subpopulation of microfilaremic persons.

Antifilarial IgG4 is a marker of active filarial infection; however, 10% of microfilaremic persons may have low levels of antifilarial IgG4. To gain insight into how persons with microfilaremia with low antifilarial IgG4 levels (< 10 micrograms/mL) differ from those with high levels (> 170 micrograms/mL), total IgG4 and IgE and filaria-specific IgE, IgG1, and IgG2 were measured by ELISA in serum samples collected from 85 microfilaremic Haitians. Persons with lower levels of antifilarial IgG4 had significantly lower total IgG4 and total IgE (P < .01), lower levels of antifilarial IgG1, IgG2, and IgE (P < .01, = .03, and < .01, respectively), and higher antigenemia and microfilaremia (P < .01) than did persons with higher levels of antifilarial IgG4. Increased antigen loads in microfilaremic persons may be associated with a down-regulation of antibody production, which extends to all isotypes.

Efficacy of ivermectin pour-on against Ostertagia ostertagi infection and residues in the American bison, Bison bison.

Sixteen American bison, Bison bison, were artificially infected with 10(5) infective stage larvae of Ostertagia ostertagi on 21 April 1993. At 42 days post-infection eight bison were treated with 0.5% ivermectin pour-on (500 micrograms/kg bodyweight) and eight treated with the carrier only. Bison were necropsied 17 and 18 days post-treatment (21 and 22 June 1993, respectively). Mean (+/- SE) of 5,413 (+/- 1,716) adults and 565 (+/- 305) immature O. ostertagi were recovered at necropsy from bison treated with the carrier. No O. ostertagi were detected in bison treated with ivermectin pour-on. Based on the levels of the ivermectin marker metabolite in liver and adipose tissue 18 days post-treatment, the established bovine withdrawal time of 48 days appears adequate to insure that violative residues do not occur.

Ivermectin cattle pour-on: duration of a single late spring treatment against horn flies, Haematobia irritans (L.) (Diptera: Muscidae) in Missouri, USA.

Late spring treatment of cattle with a single dose of pour-on ivermectin (0.5 mg kg-1 body weight) resulted in reduced horn fly populations for approximately 6 weeks, with percentage efficacy exceeding 80% for at least 26 days post-treatment. Bioassay with house flies of dung from treated cattle demonstrated suppression of fly emergence for 11 days post-treatment. The subsequent increase in horn fly numbers on the treated herd was predicted by a developmental rate equation interpreted by the time of cessation of larval fly inhibition in field dung.