title: Amphidial structure of ivermectin-resistant and susceptible laboratory and field strains of Haemonchus contortus.
abstract: The development of anthelmintic resistance by nematode parasites is a growing problem for veterinarians, pet owners, and producers. The intensive use of the macrocyclic lactones for the treatment of a variety of parasitic diseases has hastened the development of resistance to this family of parasiticides. As a result, resistance to ivermectin, moxidectin, nemadectin, and doramectin by Haemonchus contortus has been documented throughout the world. Sensory neurons located in the cephalic end of nematodes are in close contact with the external environment. Through these neurons, important chemical and thermal cues are gathered by the parasite. Examination of serial electron micrographs of ivermectin-susceptible and ivermectin-resistant H. contortus allows for comparison of neuronal structure, arrangement of neurons within the amphidial channel, and distance of the tip of the dendritic processes to the amphidial pore. The latter of these characteristics provides a useful means by which to compare the association between the neurons and the external environment of the worm. Comparison of parental laboratory strains of ivermectin-susceptible strains of H. contortus with related selected, ivermectin-resistant strains and with a wild-type ivermectin-susceptible field strain of H. contortus from Louisiana reveal that the ivermectin-resistant worms examined have markedly shorter sensory cilia than their ivermectin-susceptible parental counterparts. Additionally, the amphidial neurons of ivermectin-resistant worms are characterized by generalized degeneration and loss of detail, whereas other neurons outside of the channels, such as the labial and cephalic neurons, are normal in structure. These findings raise a number of questions regarding the relationship between amphidial structure and ivermectin resistance as well as the role of amphids as a means of entry for ivermectin. While shortened amphidial sensilla are associated with ivermectin resistance, it remains unclear if such a structural modification facilitates survival of nematodes exposed to macrocyclic lactones.
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Freeman
authors.forename: Catherine
authors.initials: C
authors.lastname: Nghiem
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Francis T
authors.initials: FT
authors.lastname: Ashton
authors.forename: Jorge
authors.initials: J
authors.lastname: Guerrero
authors.forename: Wesley L
authors.initials: WL
authors.lastname: Shoop
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Schad
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D004351:Drug Resistance; D006189:Haemonchus / Q000033:anatomy & histology* / Q000187:drug effects* / Q000648:ultrastructure; D007559:Ivermectin / Q000494:pharmacology*; D012679:Sense Organs / Q000033:anatomy & histology / Q000648:ultrastructure
chemical_list: D000871:Anthelmintics; D007559:Ivermectin