Human Ectoparasites and Other Potential Targets for Ivermectin

Animal lice and mites are often treated successfully with ivermectin (see Chapters 6 and 7). The theoretical utility of ivermectin against human lice was suggested in one study from Israel in which human body lice feeding on rabbits were killed in the first 3 days after the rabbits were treated with a single dose of 200 g kg-1 ivermectin (Mumcuoglu et al., 1990). Glaziou et al. (1994) failed to effect a complete cure of head lice with a single dose of ivermectin in 26 patients, using 200 g...

Info

Di, Dirofilaria immitis Tc, Toxocara canis Tct, Toxocara cati Tl, Toxascaris leonina Ac, Ancylostoma caninum Ab, Ancylostoma braziliense At, Ancylostoma tubaeforme Us, Uncinaria stenocephala Tv, Trichuris vulpis Cf, Ctenocephalides felis Ss, Sarcoptes scabiei Oc, Otodectes cynotis Dv, Dermacentor variabilis. 100 against D. immitis larvae, adult Toxascaris leonina and adult Ancylostoma caninum 99.3 against adult Uncinaria stenocephala and 88.2 against adult Toxocara canis. These investigators...

Electrophysiology of ivermectin in nematode parasites

Avermectin-sensitive sites in A. suum have been identified on pharyngeal muscle using a two-microelectrode current clamp technique (Fig. 3.2). Avermectins produce hyperpolarization and an increase in Cl- conductance when either bath-applied or pressure-ejected on to the pharyngeal preparation, and usually the response is irreversible. Figure 3.3 illustrates electrophysiological traces from an experiment demonstrating the effects of glutamate and ivermectin. Glutamate and MLs increase the total...

Nematodes

Efficacy of ivermectin against gastrointestinal nematodes of water buffalo was investigated by Gill et al. (1989). Water buffalo naturally infected with gastrointestinal nematodes were treated subcutaneously with ivermectin at 200 g kg-1 or left untreated. Efficacy was evaluated based on faecal egg counts. Nematodes expelled in the faeces were identified to genus. No CAB International 2002. Macrocyclic Lactones in Antiparasitic Therapy (eds J. Vercruysse and R.S. Rew) gastrointestinal nematode...

Molecular structure and formulation

The naturally occurring avermectin and milbemycin compounds are closely related 16-membered macrocyclic lactones (MLs) (Burg et al., 1979 Takiguchi et al., 1980). Both chemical classes of endectocides are produced through fermentation by soil actinomycetes from the genus Streptomyces and have similar spectra of activity. The major difference between avermectins and milbemycins is a disaccharide group attached at the C-13 of avermectin whereas that position is unsubstituted in milbemycins. The...

Effect of Selamectin Against Ectoparasites of Dogs and Cats

At the dose recommended for heartworm prevention in dogs and cats (6 mg kg-1), selamectin is also effective in preventing and controlling cat flea (C.felis) and dog flea infestations (C. canis) (Benchaoui et al, 2000 Boy et al., 2000 McTier et al., 2000b,c,d Shanks et al., 2000a). Selamectin has demonstrated a larvicidal effect on fleas (McTier et al., 2000d) and is also effective for treatment and control of ear mites (Otodectes cynotis) and sarcoptic mange in dogs (Sarcoptes scabiei) (Shanks...

References

Allen, J.L., Kollias, G.V., Griener, E.C. and Boyce, W. (1985) Subcutaneous filarisis (Pelecitus sp.) in a yellow collared macaw. Avian Diseases 29, 891-894. Ambu, S., Mak, J.W. and Ng, C.S. (1992) Efficacy of ivermectin against Parastrongylus malayensis infection in rats. Journal ofHelminthology 66,293-296. Barten, S. (1993) The medical care of iguanas and other common pet lizards. Veterinary Clinics of North America Small Animal Practice 23, 6. Battles, A.H., Adams, S.W., Courtney, C.H. and...

Pharmacokinetics safety and residues

Determination of ivermectin residues in bison has been reported (Marley et al., 1995). For ivermectin pour-on at 500 g kg-1, residue levels of 22,23 dihydroavermectin Bia (ivermectin marker residue) in liver (6.5-54.8 ppb mean 32.1 5.4 ppb) and adipose tissue (1.5-16.7 ppb mean 6.8 1.7 ppb) at 18 days post-treatment, as measured by highperformance liquid chromatography, are similar to those seen in cattle. Soll (1989) reporting on the work of Schillhorn van Veen, Sikarskie and Braselton,...

Safety and Toxicology

It is likely that the entire family of avermectins and milbemycins shares a common mode of action, but most studies have been conducted with either avermectin B1a or 22,23-dihydroavermectin B1a (the major component of ivermectin). The mode of action of these molecules was reviewed by Turner and Schaeffer (1989) and further investigated by Arena et al. (1992, 1995) and by Cully et al. (1996). In target organisms, the mode of action is receptor mediated, and ligand-gated chloride channels are the...

Control of gastrointestinal parasites

In Australia, two distinct climatic zones, the temperate and the tropical subtropical, delineate different gastrointestinal helminth species of cattle based on the epidemiology of their infection and their economic importance (Steele, 1998). In each zone, the prevalence of parasitism in cattle is determined largely by rainfall. The temperate zone can be subdivided further on the basis of summer or winter rainfall dominance. Throughout the temperate (southern New South Wales (NSW), Victoria,...

Arthropods

Gill et al. (1989) evaluated ivermectin administered subcutaneously at 200 g kg-1 against mange mites (Sarcoptes scabiei and or Psoroptes ovis) on water buffalo. Within 2 weeks of treatment, mites were not found in the skin scrapings of most ivermectin-treated animals, and pre-existing skin lesions had improved. A second dose given 28 days after the initial treatment was required to affect a cure in a few buffalo (four of 20) with an extensive amount of body surface affected by mange. All...

Birds

The use of MLs has not been well studied in birds other than poultry, and documentation of the efficacy of these compounds in pet birds is limited. None the less, ivermectin is used routinely as a nematocide and ectoparasiticide in pet birds at a dose of 200 g kg-1 (Greiner and Ritchie, 1994 Ritchie and Harrison, 1994 Tully, 1997 Bowman, 1999 Clyde and Patton, 2000 Samour, 2000). Ivermectin has been used to treat pigeons for Capillaria spp. (1.5 mg per pigeon per os or 300 g per pigeon...

Resistance

Despite the intensive use of IVM on many horse farms since the advent of IVM in the early 1980s, there has never been a demonstration of drug-resistant small strongyles in horses. An explanation proposed for this phenomenon is that the encysted and hypobiotic EL3, LL3 and DL4 stages of cyathostomes represent the majority of the cyathostome gene pool and these stages are not subjected to selection pressure due to the short terminal half-life of IVM following oral administration. These mucosal...

Mange mites

Primarily, three genera of mange mites infect cattle Sarcoptes scabiei var. bovis, Psoroptes ovis and Chorioptes bovis. The female S. scabiei var. bovis mites burrow in the superficial layers of the skin and evidently consume body fluids directly. P. bovis mites do not burrow in the skin but live at the base of hairs and cause irritation by piercing the skin. The mites are believed to feed on the superficial lipid emulsion of lymph, skin cells and skin secretions. C. bovis is a non-invasive...

Metabolism and Tissue Residues

Total residue studies in target species Radiolabelled moxidectin has been used to determine the tissue distribution, biotransformation and elimination of moxidectin in several animal species. Studies have been carried out in cattle dosed subcutaneously or topically, and sheep and horses dosed orally. The metabolic profile in milk taken from cows treated topically with moxidectin has also been studied. These studies were carried out using 14C -moxidectin prepared by chemically modifying its...

Avermectin Leeches

Mahato and Thakur (as reported by Mahato, 1989) observed that nasal leeches (Dinobdella ferox) could be removed from buffalo effectively by first sprinkling water on the nose of the buffalo, which makes the leech protrude from the nose, and subsequently soaking the leech in a 10 ig kg-1 solution of ivermectin. Leeches gradually become flaccid and drop out of the nose within 3 h. Alternatively, the ivermectin can be administered as nasal drops, but subcutaneously or intramuscularly applied...

Future Prospects for Maintaining Parasite Control Despite the Development of Anthelmintic Resistance

Once resistance to use-level anthelmintics has been found, it is difficult to do very much about it. Experience suggests that withdrawal of the use of the anthelmintic to which the worms have become resistant does not lead to reversion to susceptibility in the case of ML or benzimidazole resistance. If another class of anthelmintic remains effective, it can be used to maintain parasite control until resistance eventually also develops to this class. In some parts of South Africa, the management...

Target animal safety

For both dogs (Novotny et al., 2000) and cats (Krautmann et al., 2000), drug tolerance and margin of safety were evaluated together in a single study. For each species, selamectin in the commercial formulation was applied topically at the base of the neck. Unit doses of 0,1, 3, 5, or 10x (0, > 6, > 18, > 30 or > 60 mg kg-1, respectively) the recommended dose were administered once every 28 days for seven treatments to 6-week-old puppies or kittens. No adverse effects were observed...

The Control of Nematodes and Egg Reappearance Periods ERPs of the MLs

Considerable debate has taken place in the equine literature over the strengths and weaknesses of IVM or MOX when used in strategic control programmes for horses. Anthelmintic programmes, once based on fixed intervals of anthelmintic administration during the grazing season (reviewed by Bennett, 1983), more recently have been based on strategic treatments delivered to all horses in a herd and targeted for control of both large and small strongyles (reviewed by Ewert et al., 1991 Klei, 1997...

Red Deer Cervus elaphus Nematodes

Andrews and Lancaster (1988) and Andrews et al. (1993) reported, on the basis of field observations, that a single dose of injectable ivermectin at 200 g kg-1 as recommended for cattle, sheep and horses appeared to be insufficient to control nematode infections in red deer, as is the case of goats treated at the sheep dose (reviewed by Conder and Campbell, 1995). Based on egg larval count (Andrews et al., 1993) or egg larval worm count (Mackintosh et al., 1993) data, 400 g kg-1 of ivermectin...

Oh

Chemical structure of doramectin. doramectin is aver-mectin Aia, its molecular formula is C50H74O14, and its molecular weight is 899.14. The commercial name globally is Dectomax . Dectomax injectable is a 1 solution of doramectin in a non-aqueous vehicle of sesame oil and ethyl oleate. Dectomax pour-on is a 0.5 solution of doramectin in a vehicle of cetearyl octanoate and isopropanol. Injectable formulations (1 solutions) of doramectin are licensed for use in cattle, swine, and...

Nr

100 (Campbell et al., 1989) 100 (Monahan et al., 1995c) 100 (Campbell et al., 1989) 100 (Coles et al., 1998) 100 (Campbell et al., 1989) 100 (Costa et al., 1998) 100 (Campbell et al., 1989) 20-99 (see Discussion) aEfficacy is reported in percentage reduction in selected controlled studies. In general, the highest percentage reduction reported is cited. In the case of ivermectin, many of the original papers are cited in the review by Campbell et al. (1989). individual species of cyathostomes are...

Fallow Deer Dama dama Nematodes

Ivermectin administered orally at 200 g kg-1 to fallow deer was ineffective against mixed nematode infections based on faecal egg counts 13 days following treatment (Mylrea et al., 1991). A second treatment of ivermectin (1 ml per deer) given subcutaneously 13 days after the original treatment resulted in egg counts of zero at 40 and 47 days after the second treatment in at least two deer however, at necropsy at the latter time, S. asymmetrica was present in both and O. ostertagi was found in...

Efficacy Cydectin Against Ixodes

Alva-Valdes, R., Wallace, D.H., Holste, J.E., Egerton, J.R., Cox, J.L., Wooden, J.W. and Barrick, R.A. (1986) Efficacy of ivermectin in a topical formulation against induced gastrointestinal and pulmonary nematode infections, and naturally acquired grubs and lice in cattle. American Journal of Veterinary Research 47, 2389-2392. Alvineri, M., Sutra, J.F., Galtier, P. and Toutain, P.L. (1994) Microdose d'ivermectine chez la vache laiti re concentrations plasmatiques et r sidus dans le lait. Revue...

Introduction

The avermectins and related milbemycins here referred to as the macrocyclic lactones MLs are derived from Streptomyces microorganisms. They are a group of very hydrophobic compounds, which have broad-spectrum antinematodal Campbell and Benz, 1984 and antiarthropodal properties. The group includes abamectin, doramectin, eprinomectin, ivermectin, and selamectin, derived from Streptomyces avermitilis milbemycin D, derived from S. hygroscopicus and moxidectin, derived from S. cyanogriseus....

Snakes

Ivermectin is used frequently as a nematocide in snakes at a dose of 200 ig kg-1 administered either orally or by injection. This dose is considered to be safe in most species of snakes, and corn snakes Elapha guttata have tolerated doses of 1000 g kg-1 without apparent adverse effects Teare and Bush, 1983 . However, there are anecdotal reports of ivermectin toxicity in some Australian snakes Jacobson, 1993 . Ivermectin also has been used successfully as an acaricide in many species of snakes....

Heartworm Clinical Prophylaxis in Dogs and Cats

All MLs are completely efficacious against D. immitis larvae, which allows them to be administered every 30 days. For instance, the oral chewable formulation of ivermectin has been found to be 100 effective in preventing development of D. immitis larvae in dogs and cats when administered 30 or 45 days after challenge with infective larvae McTier et al., 1992c Paul et al., 1992a . This characteristic provides a safeguard in the case of omission or delay of a monthly treatment, or when the...

Pharmacokinetics residues and safety

Pharmacokinetic evaluation of subcutaneously administered 200 g kg-1 ivermectin or moxidectin levels following treatment in plasma and milk of lactating camels Oukessou et al., 1999 and for ivermectin in plasma of non-lactating camels Oukessou et al., 1996 yielded area under the curve AUC , Cmax and Tmax values that generally suggested dramatically reduced bioavailability of the two drugs in camels relative to published literature on cattle, but more comparable bioavailability relative to...

Chemoprophylactic Treatment of Feline Heartworm Disease and its Effect on Internal Parasites

Heartworm preventive treatment in cats follows the same regimen established for dogs, that is, monthly dosing should begin within 1 month from the start of the transmission season and the last dose should be given within 1 month from the end of the risk period. Ivermectin is marketed in the USA for use as a prophylactic agent in cats given monthly at the dose of 24 g kg-1 McTier et al, 1992c Paul et al, 1992b . This oral dosage is also highly effective for treatment and control of A. tubaeforme...