Contributing to the Emergence of Heartworm Disease

Resistance Resistance to current preventive medications is considered a very prominent topic. All major heartworm preventives are in the macrocyclic lactone class of antiparasiticides. Those approved for use in dogs and cats include ivermectin, moxidectin, milbemycin, selamectin, and milbemycin. They demonstrate excellent lethality to the L3 and L4 stages of Dirofilaria immitis. Based upon increased reports to the Food and Drug Administration, which monitors adverse events of approved animal products, questions related to resistance have been raised (Hampshire 2005). Perceived prevention failure reports occurred in most categories of heartworm prevention products. A majority of reported events stemmed from heartworm endemic states. The process for reporting adverse events from heartworm preventives began in 1998. An increasing trend of adverse (lack of effectiveness) event reports related to heartworm prevention products demonstrated a rise from 2000 (n=405) to 2002 (n=951), a 57 percent increase. The event numbers rose again in 2003 (n=1503) and then fell in 2004 (n=393). The information evaluated was found to be extremely deficient relative to quantity and quality of details related to the patient and event. Information relative to previous heartworm prevention product administration, heartworm testing history, as well as breed, sex, or age distribution pattern was insufficient. In 2004, the FDA attempted to delineate the information to evaluate product events appropriately. The true incidence of product failure is difficult to evaluate based upon the data collected prior to 2004 (Hampshire 2005). Previous reports indicated that no evidence of resistance was noted in the avermectin or milbemycin classes of parasiticide medications. In fact, the genetic selection was likely to be low for resistance based upon the number of genes involved, complexity of the resistance mechanism, treatment coverage, and extent of suitable habitat (Prichard 2005). It was felt that with the current heartworm control practices, overt resistance was extremely unlikely. A factor that could offer better control may lie in the recommendations by the veterinary community regarding frequency of dosing. Dr. Byron Blagburn, a parasitologist from Auburn University, said in his report, “In reality, failure of any of the preventives to prevent heartworm infection in dogs is extremely rare (estimated to be less than 0.0001 percent)” (Blagburn, et al. 2007). However, genetic mapping has demonstrated that heartworms with different genetic makeup appear to exist, suggesting that a change has occurred in the heartworm parasite. Blackburn evaluated strains of heartworms collected in the Mississippi Delta. LD95 and LD99 for macrocyclic lactones data was evaluated, and Blackburn Resistance and Selection Issues