Abstract
BackgroundSeveral reports have confirmed that macrocyclic lactone-resistant isolates of Dirofilaria immitis are circulating in the United States; however, the prevalence and potential impact of drug resistance is unknown. We wished to assess computer-aided measurements of motility as a method for rapidly assessing the resistance status of parasite isolates.MethodsBlood containing microfilariae (MF) from two clinical cases with a high suspicion of resistance was fed to mosquitoes and the resultant L3 injected into dogs that were then treated with six doses of Heartgard® Plus (ivermectin + pyrantel; Merial Limited) at 30-day intervals. In both cases patent heartworm infections resulted despite the preventive treatment. Microfilariae isolated from these dogs and other isolates of known resistance status were exposed to varying concentrations of ivermectin in vitro and their motility assessed 24 h later using computer-processed high-definition video imaging.ResultsWe produced two isolates, Yazoo-2013 and Metairie-2014, which established patent infections despite Heartgard® Plus treatments. Measurements of the motility of MF of these and other isolates (Missouri, MP3 and JYD-27) following exposure to varying concentrations of ivermectin did not distinguish between susceptible and resistant heartworm populations. There was some evidence that the method of MF isolation had an influence on the motility and drug susceptibility of the MF.ConclusionsWe confirmed that drug-resistant heartworms are circulating in the southern United States, but that motility measurements in the presence of ivermectin are not a reliable method for their detection. This implies that the drug does not kill the microfilariae via paralysis.
Highlights
Several reports have confirmed that macrocyclic lactone-resistant isolates of Dirofilaria immitis are circulating in the United States; the prevalence and potential impact of drug resistance is unknown
Most reports of macrocyclic lactone (ML) resistance in D. immitis have focused on the Mississippi Delta region of the southern United States, an area of very high parasite challenge, but we do not know the frequency and geographic range of resistant isolates, and so it is difficult to assess the potential impact they might have on canine and feline health [2, 11]
Evans et al used a larval migration inhibition assay to measure the susceptibility of D. immitis L3 to MLs [13], but the concentrations of drug needed to prevent migration were much higher than those to which the larvae would be exposed to in vivo and the assay does not seem to be able to distinguish resistant from susceptible isolates [14]
Summary
Several reports have confirmed that macrocyclic lactone-resistant isolates of Dirofilaria immitis are circulating in the United States; the prevalence and potential impact of drug resistance is unknown. Most reports of ML resistance in D. immitis have focused on the Mississippi Delta region of the southern United States, an area of very high parasite challenge, but we do not know the frequency and geographic range of resistant isolates, and so it is difficult to assess the potential impact they might have on canine and feline health [2, 11]. In large part this is because the confirmation of drug resistance in heartworms is timeconsuming and expensive. The derivation of the IC95, was by extrapolation from a limited number of observations at lower drug concentrations and the assays were dependent on visual observation and assessment of motility by an expert technician, which would limit the wider usefulness of the method
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