I was skimming through some journals yesterday and came across an incredibly disturbing case report. The paper, titled "Macrocyclic lactone resistance in Dirofilaria immitis," appeared in the September 27, 2011 issue of Veterinary Parasitology.

First, some translation: Macrocyclic lactones are the drugs used to prevent heartworm infections and kill baby heartworms (i.e., microfilariae) in the blood stream during heartworm treatment. Ivermectin and milbemycin oxime are macrocyclic lactones. Dirofilaria immitis is the scientific name for heartworms.

And now for some history. Rumors of a small number of dogs coming down with heartworm infections while on heartworm preventative have been circulating for years, but these cases have been incredibly difficult to confirm. It is next to impossible to determine whether a dog received and absorbed his heartworm prevention every month all year round, particularly since the lapse in question had to have occurred at least six months previously. (It takes six months for the juvenile heartworms passed through the bite of an infected mosquito to mature into the adults that are responsible for a positive heartworm test and most clinical signs of heartworm disease.)

Veterinarians have been starting to suspect that some populations of heartworms were in the process of developing resistance to heartworm preventatives, but we haven’t had any definitive proof … until now.

The case report I mentioned above details the case of a dog that was rescued in New Orleans after Hurricane Katrina. The dog tested positive for and had symptoms consistent with heartworm disease. It was treated with four doses of melarsomine dihydrochloride, which killed the adult worms living in its heart and lungs. So far so good, but an equally important part of treatment is the use of a macrocyclic lactone to kill the microfilariae circulating in the blood stream. The microscopic worms can cause damage to the kidneys and other organs and are responsible for the transmission of heartworm disease from animal to animal through mosquito bites.

The dog in question received three treatments (one should suffice) with high doses of macrocyclic lactones — once with milbemycin oxime and twice with ivermectin, all to no avail. The researchers performed a genetic analysis on the surviving microfilariae and identified the mutation that is most likely responsible for this case of drug resistance. It looks like the heartworms have mutated so that the proteins in their cell membranes no longer allow macrocyclic latones to enter their cells.

This paper should strike fear into the heart (no pun intended) of every dog and cat owner. Genetic mutations like this can spread quickly among parasite populations, meaning that our current heartworm preventatives may become less effective as time goes on. If this occurs, the only solution is for new drugs to come to market, and since this is quite a long process, drug companies need to get on the ball now.

Dr. Jennifer Coates

http://www.petmd.com/blogs/fullyvetted/2011/dec/resistance_to_heart...