In November 1999, four (two male and two female) wild-caught, captive-reared, North American river otters (Lontra canadensis), approximately 3 years of age, entered quarantine in a large southern zoo. These animals had been caught as pups and hand-reared in Louisiana. Routine quarantine health screen revealed all animals positive for Dirofilaria immitis infection based on serum antigen detected by ELISA (PetChek, IDEXX, Westbrook, ME, USA) and morphologic evaluation of the circulating microfilaria. These animals were classified as stabilized class 1 heartworm infection based on the following criteria: asymptomatic, no cardiopulmonary radiographic signs, normal packed cell volume, and no loss of body condition. Adulticidal treatment was elected to eliminate or control the heartworm infection in these young animals before clinical signs appeared. Melarsomine (Immiticide, Merial, Duluth, GA, USA) at 2.5 mg/kg injected intramuscularly deep in the left lumbar epaxial musculature. Twenty-four hours after administration, one female was found dead, the other showed clinical signs of respiratory distress, coughing, and a stretched posture with head extended upward to compensate for dyspnea. At this time, the two males appeared normal, but progressed to similar clinical signs over the ensuing hours. The animals did not respond to aggressive steroid and diuretic therapy and died spontaneously following short courses of coughing and respiratory distress. The last animal died approximately 36 hours after melarsomine administration.
Gross necropsy exam revealed excellent body condition in all four animals. A single dead adult heartworm was identified in the right atrium of two animals. Two adult worms were identified in the right atrium of one animal. No adult heartworms were identified in the heart or great vessels of one animal. All animals had wet lungs that oozed clear fluid on cut surface and thoracic connective tissues were edematous. Histopathologic findings were similar for the four animals. Pulmonary parenchyma was markedly congested and diffusely edematous. Adrenal glands had congestion of blood vessels with swelling and vacuolation of cortical epithelial cells. Adult nematodes and microfilaria did not appear particularly degenerated in examined sections. Death of the otters was attributed to acute shock, predominantly targeting the lungs and adrenal gland.
The margin of safety of melarsomine is narrow. The therapeutic dose in domestic canids is 2.5 mg/kg, with tremors, respiratory distress, stupor, and death occurring at 7.5 mg/kg. Melarsomine is safe in healthy, heartworm-free cats at doses up to 3.5 mg/kg, but death occurs at 4 mg/kg. One study documented that healthy ferrets tolerated melarsomine administration at doses up to 9.75 mg/kg with no ill effects; melarsomine at 3.25 mg/kg twice, 24 hours apart, provides 80% efficacy as a heartworm adulticide in ferrets.2 However, one practitioner who treated five heartworm-positive ferrets at 2.5 mg/kg reported that two animals died within 12 hours of drug administration.1 It is believed that the death of the otters following melarsomine administration (2.5 mg/kg) was due to direct drug toxicity, rather than to a thromboembolic shower of dead D. immitis antigen. In these otters, death occurred within 12–36 hours. Death secondary to antigenic showering can be acute, but more commonly takes days to weeks of progressive pulmonary disease, even in cats. Histology demonstrated only pulmonary edema without evidence of thromboembolism or inflammatory reaction. The microfilaria and adult nematodes seen on cut section did not appear to be particularly degenerated. The adult nematodes seen in the otter necropsies likely died shortly after the otters died, not because of the effect of the melarsomine. Death of adult worms due to melarsomine usually takes a period of days (J.W. McCall, personal communication).
Melarsomine has been tested on a narrow range of species, including the domestic dog, domestic cat, and domestic ferret. Based on this report, it appears that wide species differences exist in the direct toxic effects of this drug. The North American river otter seems to have a much lower safety margin than the other species tested, including the ferret that is in the same taxonomic family. Investigation into the progression of heartworm disease in infected otters, as well as alternatives to arsenical adulticidal therapy should be initiated.
1. Kemmerer, D.W. 1998. Heartworm disease in the domestic ferret. D.W. Kemmerer, Proc., Recent Advances in Heartworm Disease, American Heartworm Society, Tampa, Florida.
2. Supakorndej P., J.W. McCall, N. Supakorndej, M.T. Dzimianski, L. Neuwirth, R.E. Roberts, and A.E. Mansour. 2001. Evaluation of melarsomine dihydrochloride as a heartworm adulticide for ferrets. In: Seward, L. (ed). State of the Heartworm Symposium, American Heartworm Society, Batavia, Illinois.