title: Effect of heterogeneous mixing and vaccination on the dynamics of anthelmintic resistance: a nested model.
abstract: Anthelmintic resistance is a major threat to current measures for helminth control in humans and animals. The introduction of anthelmintic vaccines, as a complement to or replacement for drug treatments, has been advocated as a preventive measure. Here, a computer-based simulation, tracking the dynamics of hosts, parasites and parasite-genes, shows that, depending on the degree of host-population mixing, the frequency of totally recessive autosomes associated with anthelmintic resistance can follow either a fast dynamical regime with a low equilibrium point or a slow dynamical regime with a high equilibrium point. For fully dominant autosomes, only one regime is predicted. The effectiveness of anthelminthic vaccines against resistance is shown to be strongly influenced by the underlying dynamics of resistant autosomes. Vaccines targeting adult parasites, by decreasing helminth fecundity or lifespan, are predicted to be more effective than vaccines targeting parasite larvae, by decreasing host susceptibility to infection, in reducing the spread of resistance. These results may inform new strategies to prevent, monitor and control the spread of anthelmintic resistance, including the development of viable anthelmintic vaccines.
authors.affiliation: Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America. lsabatel@fhcrc.org
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Sabatelli
mesh_terms: D000483:Alleles; D000818:Animals; D000871:Anthelmintics / Q000276:immunology*; D004351:Drug Resistance / Q000276:immunology*; D005787:Gene Frequency / Q000235:genetics; D006790:Host-Parasite Interactions / Q000235:genetics; D018448:Models, Immunological; D016052:Protozoan Vaccines / Q000276:immunology; D012680:Sensitivity and Specificity; D014611:Vaccination
chemical_list: D000871:Anthelmintics; D016052:Protozoan Vaccines