moxidectin and Helminthiasis

Ivermectin and moxidectin, two macrocyclic lactones, are potent antiparasitic drugs currently registered and mainly used against filarial diseases; however, their potential value for improved soil-transmitted helminth (STH) control has been acknowledged. This review provides insights on recent studies evaluating the efficacy of ivermectin and moxidectin as single or coadministered therapy against human soil-transmitted helminthiases (including Strongyloides stercoralis infections) and on pharmacokinetic/pharmacodynamic parameters measured in treated populations. Furthermore, we discuss current gaps for research, highlight advantages - but also existing challenges - for uptake of ivermectin and/or moxidectin treatment schemes into routine STH control in endemic countries.

Topics: Animals; Anthelmintics; Feces; Helminthiasis; Helminths; Humans; Ivermectin; Soil

Diseases caused by helminth infections affect more than a quarter of the population of the world, but the therapeutic arsenal is limited. The approval of moxidectin in 2018 and triclabendazole in 2019 by the FDA marked an important moment in the fight against diseases of poverty, such as helminthiases.

Topics: Animals; Anthelmintics; Drug Approval; Helminthiasis; Humans; Macrolides; Triclabendazole; United States; United States Food and Drug Administration

The avermectins and, to a lesser extent, the milbemycins, have revolutionized antiparasitic and antipest control over the last decade. Both avermectins and milbemycins have macrocyclic lactone structures that are superimposable, they are produced by the same genus of soil dwelling organisms, they have the same mode of action, they exert this action against the same nematode/acarine/insect spectrum of targets, and they show the same mechanism-based toxicity in mammals. Reports suggesting that milbemycins have a different mode of action from avermectins with implications that there will be no mutual resistance to the groups have been shown to be false. Contributing to the belief that there were differences in mode of action between the two groups are the vague definitions of resistance presently in use which rely on the ability of the parasite to survive treatment at the manufacturer's recommended use level. More appropriately, drug resistance should be defined as 'a change in gene frequency of a population, produced by drug selection, which renders the minimal, effective dosage previously used to kill a defined portion (e.g. 95%) of the population no longer equally effective'. This type of definition would allow us to detect changes in susceptibility of a population earlier and is essential when comparing different chemicals to determine if there is mutual resistance to them. It is concluded that much effort has been expended by pharmaceutical, government, and academic scientists searching for broad-spectrum second generation avermectin and milbemycin products, but none has exceeded the original avermectin in any fundamental way. The newer avermectin and milbemycin compounds that have appeared claim niches in the market place based on emphasis of certain narrow parts of the overall spectrum. Consequently, there are no second generation avermectins and milbemycins at present and all newer compounds from this mode of action class are viewed as siblings of the first generation.

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Antiprotozoal Agents; Dog Diseases; Dogs; Helminthiasis; Helminthiasis, Animal; Ivermectin; Macrolides; Molecular Structure; Parasitic Diseases; Parasitic Diseases, Animal; Sheep; Sheep Diseases; Structure-Activity Relationship

The milbemycins are the only novel broad spectrum anthelmintic chemicals to reach the market place in the last 10 years. Many new systems for delivery and strategies for rational use have, however, been introduced. Boluses which are retained by virtue of specific gravity and by variable geometry are now available. They contain benzimidazoles, morantel, ivermectin and levamisole. Their release mechanisms involve preferential corrosion of a retaining metal core, constant diffusion from a laminated ethylene acetate sandwich, and a hydrostatic pump driven by osmotic pressure. Some are biodegradable. Experimental delivery systems have been developed incorporating ear implants and liposomes. The anthelmintic efficacy of some drugs has been potentiated by the synergistic action of metabolic inhibitors and these combinations hold promise for the future. Much new information is now available on those factors which affect anthelmintic efficacy such as concurrent administration with food and the presence of the target parasites themselves. This knowledge provides a sound basis for the rational use of anthelmintic drugs.

Topics: Alginates; Animals; Anthelmintics; Anti-Bacterial Agents; Benzimidazoles; Drug Combinations; Drug Delivery Systems; Helminthiasis; Helminthiasis, Animal; Ivermectin; Liposomes; Macrolides; Morantel; Pharmaceutical Vehicles

Two dosages of moxidectin oral gel were evaluated and compared to a therapeutic dose of ivermectin oral paste in the control of a spectrum of gastrointestinal parasites of ponies naturally infected in southern Louisiana or Mississippi. Thirty-two mixed-breed ponies ranging in age from one to 21 years were used in this controlled test. Eight weeks prior to the experiment, ponies grazing on contaminated pasture were moved to a paddock and fed a pelleted ration, thus reducing or eliminating the potential for additional infection and ensuring the existence of a population of encysted larvae. Ponies were then allocated to replicates of four animals based on values of fecal strongyle egg counts and percent strongyle larvae composition determined from Baermann sedimentations of fecal cultures. Members of replicates were allocated to one of four treatment groups: moxidectin oral gel administered at 300 micrograms kg-1 body weight, moxidectin oral gel at 400 micrograms kg-1, the oral gel vehicle as negative control, and ivermectin oral paste at 200 micrograms kg-1. Prior to treatment, ponies were confined in pairs to covered concrete runs by treatment group. Two weeks following treatment, necropsy examinations of all animals were performed. Parasites were recovered from the lumen of the stomach, the intestinal tract, the cranial mesenteric artery and its major branches, the peritoneal body wall and from pepsin digests of mucosal scrapings taken from the cecum and large colon. Encysted cyathostome larval burdens were also compared using mural transillumination of segments of the large colon for visualization of the encysted forms. Control ponies were not uniformly infected with the spectrum of parasites; however, moxidectin, at either dosage, compared favorably with ivermectin in the control of the adults of Strongylus vulgaris, Strongylus edentatus, Triodontophorus spp., Oesophagodontus robustus, Trichostrongylus axei, Oxyuris equi, Parascaris equorum, Habronema muscae, as well as both the adult and larval Cyathostominae recovered from the lumen. Moxidectin also appears as efficacious as ivermectin against migrating large strongyle larvae at the two weeks post-treatment evaluation. Moxidectin demonstrated a trend towards greater efficacy against encysted cyathostome larvae than a therapeutic dosage of ivermectin, but this difference was not statistically significant. Moxidectin was less effective than ivermectin against Gasterophilus intestinalis and was equally i

Topics: Administration, Oral; Animals; Anthelmintics; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Female; Gels; Helminthiasis; Helminthiasis, Animal; Horse Diseases; Horses; Ivermectin; Macrolides; Male; Nematode Infections; Ointments; Strongyle Infections, Equine; Strongylus

Moxidectin was tested as an oral gel formulation during a controlled test performed to evaluate dosages against equine gastrointestinal parasites. Four groups of ten ponies were used. Ponies ranged from 1 to 20 years of age and were naturally infected in southern Louisiana or Mississippi. Fecal exams and fecal cultures were performed on all ponies to determine the strongyle egg counts and the percent distributions of large and small strongyles. Following these determinations, ponies were allocated to replicates of four ponies to provide an even distribution of strongyle infection, age, weight and gender. Members of each replicate were then randomly assigned to one of four treatment groups. The doses tested were 300, 400 and 500 micrograms kg-1 body weight. The oral gel vehicle alone served as control. Treatments were administered behind the tongue and the ponies were observed continuously for 4 h for any adverse reactions; thereafter, ponies were observed at least twice daily. Necropsy examinations were performed 14 days post-treatment for the recovery and identification of any parasites present. Moxidectin, at all doses tested, was 100% efficacious against adults of Strongylus vulgaris, Strongylus edentatus, Triodontophorus spp. and 22 species of small strongyles. Moxidectin was also 100% efficacious against larvae of Strongylus edentatus and Oxyuris equi, greater than 94% efficacious against Strongylus vulgaris larvae and Oxyuris equi adults at 14 days post-treatment. Moxidectin proved highly efficacious against luminal small strongyle larvae (> 99.9% against L4 and > 92% against L3) and moxidectin demonstrated some efficacy against encysted small strongyle larvae as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Animals; Anthelmintics; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Equidae; Female; Gastrointestinal Diseases; Gels; Helminthiasis; Helminthiasis, Animal; Macrolides; Male; Oxyuriasis; Strongylida Infections; Strongylus

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Feces; Female; Fenbendazole; Helminthiasis; Helminthiasis, Animal; Intestinal Diseases, Parasitic; Ivermectin; Macrolides; Parasite Egg Count; Pregnancy; Puerperal Infection; Sheep; Sheep Diseases; Time Factors