Mutations in GluCl associated with field ivermectin-resistant head lice from Senegal

Abstract

Through its unique mode of action, ivermectin represents a relatively new and very promising tool to fight against human lice, especially in cases of resistance to commonly used pediculicides. However, ivermectin resistance in the field has already begun to be reported. Therefore, understanding the mechanisms involved is a key step in delaying and tackling this phenomenon.In this study, field head lice with confirmed clinical resistance to ivermectin in rural human populations from Senegal were subjected to genetic analysis targeting the GluCl gene, the primary target of ivermectin known to be involved in resistance. Through DNA-polymorphism analysis, three relevant non-synonymous mutations in GluCl which were found only in ivermectin-resistant head lice (76 head lice tested), were identified. The A251V mutation found in the TM3 transmembrane domain was the most prevalent (allelic frequency of 0.33), followed by the S46P mutation (0.28) located at the N-terminal extracellular domain. The H272R was in the M3–M4 linker transmembrane region of GluCl and has shown the lowest frequency (0.18). Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) diagnostic assays were also developed for their accurate genotyping.Our study is the first to report the presence of GluCl point mutations in clinical ivermectin-resistant head lice occurring in rural human populations of Senegal.