Multiple anthelmintic drug resistance in hookworms (Ancylostoma caninum) in a Labrador breeding and training kennel in Georgia, USA

Abstract

OBJECTIVE To evaluate the efficacy of the 3 major classes of anthelmintics used for the treatment of hookworms in dogs in the US and an extralabel treatment with an FDA-approved product for use in cats in a Labrador kennel with a history of persistent hookworm infections. ANIMALS 22 dogs housed in a single kennel comprised of the following breeds: 19 Labrador Retrievers, 1 English Cocker Spaniel, 1 Chesapeake Bay Retriever, and 1 Boykin Spaniel. PROCEDURES We performed a fecal egg count (FEC) reduction test using 22 dogs that were allocated randomly to 1 of 5 treatment groups: pyrantel pamoate (Pyrantel pamoate suspension), fenbendazole (Safe-Guard suspension 10%), milbemycin oxime (Interceptor), moxidectin plus imidacloprid (Advantage Multi), and emodepside plus praziquantel (Profender topical solution for cats). FEC was performed on samples collected on days 0 and 11. RESULTS FEC reductions for the milbemycin oxime, moxidectin plus imidacloprid, and emodepside plus praziquantel groups were 43.9%, 57.4%, and 100%, respectively. The FEC increased following treatment for the pyrantel and fenbendazole groups. CLINICAL RELEVANCE These data demonstrate that the Ancylostoma caninum infecting the dogs in this kennel are highly resistant to all major anthelmintic classes approved for use in dogs in the US but are susceptible to emodepside. This was the first report of multiple anthelmintic drug–resistant A caninum in a dog kennel that does not involve Greyhounds.

Reflecting on the past and fast forwarding to present day anthelmintic resistant Ancylostoma caninum–A critical issue we neglected to forecast

“…Later reports of both fenbendazole and macrocyclic lactone resistant worms were reported ( Kitchen et al, 2019 ; Jimenez Castro et al, 2019 ), but the chronological order for selective resistance to fenbendazole and/or macrocyclic lactone in A. caninum remains unknown. Nonetheless, the well characterized case reports of known MADR A. caninum isolates that are non-Greyhounds breeds, serve as a warning for the potential selection and dispersal of additional A. caninum isolates resistant to pyrantel, fenbendazole, and macrocyclic lactones ( Jimenez Castro et al, 2023 ). The presence of viable, reproducing worms remaining after selective anthelmintic treatment or the acquisition of drug resistant worms with an ongoing less than 100% effective anthelminthic treatment, sets the stage for the dominant selection of a resistant isolate or isolates.…”

“…Data from the historical trends and selection of drug-resistant nematodes in livestock and equine could have forecasted the current MADR A. caninum situation in USA Greyhound kennels and the present dissemination of these parasites into the pet dog population. Unfortunately, this warning did not occur, and the event has happened: anthelmintic resistant or MADR resistant A. caninum isolates are no longer limited to Greyhounds as detection of these parasites are occurring in other susceptible dogs ( Jimenez Castro et al, 2023 ). Identification using appropriate ante-mortem testing for these drug resistant parasites is key to avoid further dissemination.…”

“…This drug is available for use in dogs in the European Union, as Profender® (formulated with praziquantel) but is not currently marketed for dogs in the USA or Australia. Therefore, when the triple dewormer protocol fails to clear a dog of hookworm egg shedding, emodepside or in the USA extra-label emodespide-praziquantel combination product (available in the USA and Australia, as Profender® for cats) may be used by the veterinarian ( Jimenez Castro et al, 2023 , Jimenez Castro and Kaplan, 2020 ). An experimental trial using emodepside demonstrated excellent efficacy, 99.6%, as calculated by worm recovery counts ( Jimenez Castro et al, 2020b ).…”

“…In the USA, there are at least two MADR A. caninum published case reports, characterized through both in vivo and in vitro studies ( Jimenez Castro et al, 2019 ; Kitchen et al, 2019 ; Jimenez Castro et al, 2020b ). However, using standard clinical parasitology testing (monitoring fecal egg counts following anthelmintic treatment) investigators documented additional multi-drug resistant parasites in 21 dogs of different breeds (non-Greyhound) within the same kennel located in southeastern USA ( Jimenez Castro et al, 2023 ). This is not an anomaly as a similar hookworm infection, lack of response to at least two drugs (pyrantel and fenbendazole) was seen in a Siberian Husky kennel (18 dogs) in the northeastern USA (personal observation).…”

“…Dogs with a MDR1 genetic mutation are unusually sensitive to drugs, including ivermectin and other macrocyclic lactones ( Mealey et al, 2001 ). The AAVP hookworm task force discussed concerns regarding acronym confusion with the canine MDR1 gene, drugs, and genetic testing components; therefore, the AAVP hookworm task force agreed to use “MADR” to describe canine hookworms that “fail to respond to two or more dewormers.” This term, MADR was used in a recent publication ( Jimenez Castro et al, 2023 ). The drug resistant A. caninum case reports, the development of terminology, and the organization of industry and researchers are reminiscent of early work, regarding drug resistant nematodes in the livestock and equine industries.…”