Collagen capsule and drug access do not explain ivermectin resistance of Trichinella spiralis muscle larvae

Trichinella is a nematode that causes chronic infection via its larvae in muscle cells and remains a global health concern. Drug sensitivity, including to ivermectin (IVM), differs between intestinal adult worms (AW) and muscle larvae (ML): AW are susceptible, whereas ML are not. We tested whether the collagen capsule surrounding ML limits drug entry and thereby explains the poor efficacy of IVM. In mice infected with encapsulated T. spiralis or non-encapsulated T. pseudospiralis, IVM treatment at the ML stage did not reduce ML burdens. In vivo pharmacokinetic analyses detected IVM within ML, regardless of presence or absence of the collagen capsule. These results indicate that the collagen capsule and limited drug access do not account for the ineffectiveness of IVM against ML. Intrinsic, stage-specific factors within ML likely underlie this resistance and warrant further investigation.