Efficacy of Selamectin in the Treatment of Nasal Mite (Pneumonyssoides caninum) Infection in Dogs
In a laboratory study to evaluate the efficacy of selamectin for treatment of canine nasal mite infection, 12 purpose-bred beagles were experimentally infected with Pneumonyssoides caninum (P. caninum). Six of the dogs were treated with selamectin applied to the skin of the back at dosages of 6 to 24 mg/kg for three times at 2-week intervals. The remaining six dogs were an untreated control group. At necropsy 39 to 46 days after inoculation, no P. caninum mites were found in any of the treated dogs. In contrast, nasal mites were found in five of the untreated dogs. This difference was statistically significant at P=0.015.
Introduction
The canine nasal mite, Pneumonyssoides caninum (P. caninum), is a parasite that dwells in the nasal cavity and sinuses of the dog.1 It was first described in 1940 in Michigan.2 Since then, the presence of P. caninum has been reported from many parts of the world.3–11 A recent survey in Sweden showed that 95 (20%) of 474 dogs examined at necropsy were infected with the parasite.12
The P. caninum female is 1.0 to 1.5 mm long and 0.6 to 0.9 mm wide.2 Male mites and larvae are slightly smaller.1314 The life cycle and mode of transmission of the parasite are not fully known. Pneumonyssoides caninum infection in dogs causes nonspecific clinical signs of the upper respiratory tract, such as sneezing, reverse sneezing, rhinitis, and impaired scenting ability.1516 To diagnose P. caninum infection in the living dog is difficult, and a definitive diagnosis cannot be made unless the mites are visualized. There is also no examination method that can definitively exclude the presence of nasal mites. In Scandinavia where the canine nasal mite is endemic, dogs with clinical signs compatible with P. caninum infection are often treated presumptively, with amelioration of signs confirming the diagnosis.
At present, there is no drug licensed for the treatment of P. caninum infection in dogs. In the past, different therapeutic regimens have been tried, such as a mixture of ether and mineral oil applied as nasal drops, rotenone solution applied into the nasal passages, inhalation of dichlorvos, and oral administration of an organophosphorus compound.71718 These treatments have been either ineffective or potentially harmful to the animal. More recently, macrocyclic lactones such as ivermectin,a milbemycin oxime,b and selamectinc have been reported to be clinically effective in the treatment of this condition.81019–23 However, no controlled, experimental studies have been published that confirm the efficacy of these drugs.
Selamectin is an endectocide with a wide margin of safety for all dog breeds. It has been administered at up to five times the recommended dose to avermectin-sensitive breeds without adverse effects.24 Selamectin is easy to administer since it is available in a topical “spot-on” formulation. In dogs, selamectin is licensed to treat infections caused by Ctenocephalides spp., Trichodectes canis, Sarcoptes scabiei, Toxocara canis, and Otodectes cynotis. It is also registered as a heartworm preventative. The product can be used in dogs as early as 6 weeks of age.
This paper reports the results of a laboratory study to evaluate the efficacy of selamectin in the treatment of P. caninum in experimentally infected dogs.
Materials and Methods
Study Subjects
Twelve 4-month-old, purpose-bred beagles (six females and six males) were used in this study. On arrival at the Swedish National Veterinary Institute (SVA) in Uppsala, Sweden, the dogs were thoroughly examined and found to be clinically healthy. During the entire experiment, they were kept behind barriers in the animal facility of the SVA. At the beginning of the experiment, the dogs were housed in groups of three. Following experimental inoculation with nasal mites, the inoculated dogs were housed separately from the noninoculated dogs in groups of two for a period of 6 to 11 days, after which they were assigned either to a selamectin-treated or an untreated control group. After the first treatment, four of the treated dogs were housed alone and two were housed together for a period of 33 to 35 days; then they were euthanized. During the same period, one of the control dogs was housed alone, two were housed together, and the remaining three were also housed together. The dogs were fed standard dry dog food and had free access to water. The experiment was approved by the Swedish National Board for Laboratory Animals and was conducted in compliance with good laboratory practice standards.
Inoculum
Living P. caninum mites were obtained from naturally infected dogs that had been submitted to the Department of Pathology, SVA, for necropsy. One day after euthanasia, nasal mites were collected, cleaned of mucus and debris, and kept in 0.01 molar phosphate-buffered saline (pH 7.0) at +20°C, until the following day when the experimental inoculation was performed. One beagle (case no. 2) was not inoculated until 2 days after the mites had been collected. At the time of inoculation, all mites (based on microscopic visualization) appeared to be viable and moved without difficulty.
Experimental Infection
The 12 dogs to be inoculated were sedated with medetomidined (40 μg/kg intramuscularly [IM]). Inoculation was done when the dogs no longer responded to manipulation of the nose, using a procedure described previously by Gunnarsson, et al [Figure 1].25 When possible, the same relative proportion of mites as was found at necropsy in the naturally infected dogs was inoculated into the study subjects. The inoculum included mainly females, then larvae, and then males.12 The dogs were each inoculated with 24 to 41 P. caninum mites [Table 1]. Ten of the dogs were inoculated only once, whereas two dogs (case nos. 11, 12) were inoculated twice, 3 days apart. Case no. 11 initially received 29 females, and on the second occasion was inoculated with seven females, two larvae, and two males. Case no. 12 was first inoculated with 29 females and one male, and on the second inoculation received eight females, two larvae, and one male. Because the supply of P. caninum varied, inoculation was not performed simultaneously in all dogs but at six different times over a period of 8 weeks. On 5 days, two dogs were inoculated simultaneously. On one occasion, four dogs were inoculated at the same time.
Treatment and Observations
Six to 11 days postinoculation, the dogs were randomly assigned either to a selamectin-treated or an untreated control group. Study day 0 was defined for each dog as the day on which the dog was first treated with selamectin or assigned to the control group. The six dogs in the treatment group (case nos. 1, 3, 5, 7, 9, 11) were treated on days 0, 14, and 28 with selamectin. Four dogs (case nos. 1, 3, 5, 7) were treated with a dosage of 24 mg/kg, and two dogs (case nos. 9, 11) received 6 mg/kg. Treatment was applied topically to the skin of the animal’s back between the shoulder blades. Treated and nontreated dogs were kept separated.
The dogs treated with selamectin were observed for periods of approximately 10 minutes at 2, 4, and 24 hours after dosing for signs of local or systemic adverse effects. The staff attending the dogs also observed them daily for clinical signs compatible with nasal mite infection, such as sneezing, reverse sneezing, rhinitis, and impaired scenting ability.1516
Necropsy Examinations
The dogs were euthanized between days 33 and 35 and were submitted for necropsy to the Department of Pathology, SVA. The skulls were split with a band saw along the median line. Septae were removed, and the sinuses were opened. The skulls were then placed under a 100-W infrared light and were examined macroscopically by a blinded investigator (Zakrisson) at regular intervals for a 2-hour period. All P. caninum mites found were collected in Petri dishes filled with phosphate-buffered saline and were examined under a stereomicroscope for verification, as described by Gunnarsson, et al.25
Statistical Analysis
Because the dogs were randomly assigned to treatment groups rather than sampled randomly, a permutation test was used for statistical analysis.26 Fisher’s exact test was applied to the mite counts found at necropsy in infected dogs.e
Results
No clinical signs compatible with nasal mite infection were observed in any of the dogs. Two dogs (case nos. 5, 7) that had been treated with selamectin at a dosage of 24 mg/kg developed mild alopecia at the application site. Case no. 5 started to show alopecia on day 28, and case no. 7 developed alopecia on day 14. Histological examination of skin biopsies taken in connection with necropsy examination showed focal alopecia. No other abnormal clinical signs or adverse effects were observed.
At necropsy, no nasal mites were found in any of the treated dogs. In contrast, four to 23 live P. caninum mites were recovered from the nasal cavity, sinuses, or both, from five of the six untreated reference dogs [Table 2; Figure 2]. The difference was statistically significant at P=0.015. No macroscopic lesions were observed in the nasal cavities, sinuses, or tonsils in any of the dogs.
Discussion
At necropsy 39 to 46 days after inoculation and 5 to 7 days after the last selamectin treatment, no P. caninum mites were found in any of the treated dogs. In contrast, nasal mites were found in five of the six untreated control dogs. Selamectin applied topically appeared to be effective against P. caninum infection in these experimental dogs. This finding was compatible with results of Bergeaud and Dedenbach, et al., who reported successful treatment of two dogs with P. caninum infection.2223 In both cases, P. caninum mites had been visualized in the nasal cavity by endoscopy. The dogs were subsequently treated topically with selamectin at dosages between 6 and 12 mg/kg for three times at an interval of 4 weeks. The clinical signs disappeared within a few days after the first treatment. Anchierri, et al., reported the unsuccessful treatment of a dog when selamectin was given at a dosage of 5.45 mg/kg three separate times at intervals of 15 days.27 Clinical signs did not abate, and endoscopy of the nasal cavity revealed the presence of P. caninum mites. This latter dog was subsequently treated with milbemycin oxime at 0.5 to 1.0 mg/kg for three times at intervals of 15 days, and all clinical signs resolved. A possible explanation for the selamectin failure in the case reported by Anchierri, et al., may have been the use of an inadequate dosage. Because definitive conclusions cannot be drawn from the few published clinical cases, further studies concerning the efficacy and appropriate dosing of selamectin against P. caninum infection in dogs are needed.
The control dog in which no P. caninum mites were found had, for logistical reasons, been inoculated 3 days after the death of the donor dog (i.e., 1 day later than the other dogs). In previous experiments, seven beagles were experimentally inoculated with P. caninum mites collected from naturally infected dogs at necropsy.28 Those dogs were not medically treated, and at necropsy 14 to 42 weeks postinoculation, P. caninum mites were found in all of them.28 Because the method of inoculation has worked previously, it is likely that case no. 2 did not become infected because the mites given to the dog were not viable.
In the study reported here, selamectin was administered at a dosage of 6 to 24 mg/kg every 2 weeks for 6 weeks. This dosage regimen is higher than the monthly dose of 6 to 12 mg/kg recommended for flea infestations and for heart-worm prevention. Higher dosages were chosen to demonstrate whether or not selamectin had effect against P. caninum in dogs. Based on the results reported here, selamectin was effective against nasal mite infection.
The only adverse effect observed was partial alopecia at the application site that developed in two of four dogs that were treated with a dosage of 24 mg/kg. No discomfort was noted at the alopecic area. According to the manufacturer, selamectin has been administered at 10 times the recommended dose without undesirable effects.24 However, partial alopecia at the application site has been observed in cats, and it usually resolves spontaneously. In some cats, symptomatic treatment may be needed.24 Because the dogs in this study were euthanized within 5 to 7 days after the last treatment, it is unknown whether the alopecia would have resolved spontaneously.
Conclusion
Selamectin applied topically was effective against experimental P. caninum infection in dogs, but further studies are needed to establish the optimal dosage.
Ivomec; Merial, Duluth, GA 30096
Interceptor; Novartis, Greensboro, NC 27419
Stronghold; Pfizer Ltd., Sandwich, Kent, United Kingdom
Domitor; Orion, FL-02101 Espoo, Finland
SYSTAT 9.01; SPSS Inc., Point Richmond, CA 94804
Acknowledgments
The authors thank photographer Bengt Ekberg for providing the photos included in this article.
Citation: Journal of the American Animal Hospital Association 40, 5; 10.5326/0400400
Citation: Journal of the American Animal Hospital Association 40, 5; 10.5326/0400400
Pneumonyssoides caninum mites on the nose of a dog (case no. 4).
Pneumonyssoides caninum mites observed in the nasal cavity at necropsy (case no. 10).
