Case report: C57BL/6NTac and C57BL/6NCrl mice displaying neurological signs after deworming with ivermectin.

Abstract

For over 40 years, ivermectin has served as an effective anti-parasitic drug used in human and veterinary medicine. In laboratory animal facilities it is used prophylactically or therapeutically to maintain the health status of the colony or experimentally in studies. Although ivermectin is generally safe to use, there are reports of neurotoxicity associated with ivermectin crossing the blood-brain barrier due to overdosing or blood-brain barrier dysfunction. In mice, P-glycoprotein maintains the blood-brain barrier and mice with a mutation in the P-glycoprotein encoding gene mdr1a are 50-100 times more sensitive to ivermectin. Signs of neurotoxicity include ataxia, bradypnea, recumbency, tremor, and death. We report neurotoxicity after ivermectin administration was used for the purpose of eradicating the murine-specific intestinal nematode Heligmosomoides polygyrus in C57BL/6NTac and C57BL/6NCrl mice. The mice were dewormed by subcutaneous administration of 10 or 20 mg/kg ivermectin to eradicate all stages of Heligmosomoides polygyrus. At 24-48h after deworming, 5% (n = 4) of the mice presented with tremor, ataxia, and/or head tilt. The affected mice were euthanised and gross pathological findings were found in one of the four mice (left-sided hydronephrosis). We assume that the observed neurological effects were due to defects in the blood-brain barrier, overdosing or individual sensitivity. This report provides a reason for caution when deworming laboratory mice subcutaneously with ivermectin at doses of 10 mg/kg or higher.