Sei sulla pagina 1di 4
Efficacy of Imidacloprid on Rabbits Naturally or Experimentally Infested with the Cat Flea, Ctenocephalides felis

Efficacy of Imidacloprid on Rabbits Naturally or Experimentally Infested with the Cat Flea, Ctenocephalides felis

Dennis E. Jacobs, BVMS, PhD, FRCVS, FRCPath a Melanie J. Hutchinson, BSc, HND(Agric) a Tohru Fukase, PhD b Olaf Hansen, DVM, PhD c

a The Royal Veterinary College (University of London), North Mymms, UK b Faculty of Pharmacy, Meiji Pharmaceutical University, Noshio, Kiyose-shi, Tokyo, 204-8588, Japan c Bayer AG, BG-Animal Health, Monheim Agricultural Center, D-51368 Leverkusen, Germany

Introduction

From a veterinary viewpoint, rabbits may be placed into four cat- egories, each associated with a different environment and with dif- ferent risk factors determining their exposure to parasitic disease. This grouping encompasses rabbits living in the wild, those farmed commercially, those kept in laboratory colonies, or those kept as pets in a domestic setting.

Fleas on Pet Rabbits

There are few published reports describing flea populations on pet rabbits, but infestations with Spilopsyllus cuniculi, Cediopsylla simplex, or Odontopsyllus multispinus are likely to occur only when there is direct or indirect contact with wild rabbits. Pet rabbits in the home are, however, often exposed to another, almost ubiquitous pest of the domestic environment—the cat flea (Ctenocephalides felis felis). Despite its name, C. felis is the most common flea of dogs as well as cats in many countries. It also feeds on a wide variety of other hosts. 1 In the U.S. state of Kansas, some 60% of opossums and 20% of rac- coons trapped in urban areas are infested with this flea. 2 Reproduction of C. felis differs in several important aspects from that of the rabbit hostadapted flea species described above. First, it is independent of the physiological state of the host and egg production is therefore a continuous process. Second, cat fleas tend to remain on the host, lay- ing their eggs on the animal. These eggs, nevertheless, soon fall to the ground and can be widely disseminated throughout the home by infested cats, dogs, or other pets. A reservoir of C. felis eggs, larvae, and pupae is thereby established in the domestic environment, 3 and pet rabbits are vulnerable to attack by the hungry, host-seeking cat fleas. As the number of rabbits kept as pets increases, greater demands are made on the veterinarian for advice and treatment.

Treating Rabbits

Few animal health products are specifically licensed for use on

TNAVC, January 2001

rabbits. Caution is needed when extrapolating from recommenda- tions designed for the cat or dog, as rabbits obviously differ with regard to skin and haircoat type. Differences in drug distribution and metabolism can potentially influence efficacy and safety. It is there- fore of value to have sound scientific data to support the use of par- asiticides on this species. Recognition of the need for an easily applied topical preparation for use on flea-infested rabbits stimulat- ed the series of five studies conducted in the U.K., Germany, and Japan described in this article. The studies investigated the efficacy and safety of imidacloprid for this purpose. Imidacloprid was chosen

as it is a highly effective insecticide already in widespread use for flea control on cats and dogs. A single topical application with a 10% spot-on formulation (Advantage ® , Bayer) provides 100% efficacy against a resident C. felis population and at least 95% protection against reinfestation for 4 weeks on both cats 4 and dogs. 5

Efficacy Studies—Experimental Infestation

Two studies were conducted to measure the efficacy and duration of action of imidacloprid against C. felis on artificially infested rab- bits: a pilot study at the Bayer laboratories in Monheim, Germany (Study 1) and a carefully controlled experimental study at the Roy-

al Veterinary College, London, England (Study 2). Each used two

groups of six individually caged rabbits. Allocation to groups was made randomly in the German study, while in the British trial the rabbits were first ranked according to their susceptibility to fleas. This was ascertained by counting the fleas that were established on

each rabbit after a uniform pre-trial (Day 8) infestation. Rabbits in the treatment groups were given a single spot-on treatment on Day 0. As all the rabbits weighed less than 4 kg, each received 0.4 ml of

a 10% topical formulation from a prepackaged applicator (Advan-

tage ® 40 for Cats, Bayer) applied directly onto the skin of the neck just behind the base of the skull (Figure 1). This provided a mini- mum dose of 10 mg/kg.

Suppl Compend Contin Educ Pract Vet Vol. 23, No. 4(A), 2001

Figure 1— Application of imidacloprid spot-on formulation (Advantage ® ) to rabbits. In the British

Figure 1—Application of imidacloprid spot-on formulation (Advantage ® ) to

rabbits.

In the British study, fleas were placed on the rabbits on Days 8, 1, 7, 14, 21, and 28. An infestation of 100 C. felis gave a consistent and adequate level of infestation without excessive discomfort to the rabbit. Live fleas were observed on the floor of the cages of the untreated controls. This contrasts sharply with experience in the

same laboratory with C. felis infestations on cats, as in this case the fleas are almost invariably found only on the host. Similar infesta- tions on rabbits in Germany resulted in much

lower establishment rates; thus two infestations with 100 fleas were given on Days 3 and 1. It is not known if the difference between establish- ment rates in the British and German studies reflects the strain of cat flea used, the breed of rabbit, or other unknown factors. To measure curative efficacy against an established C. felis population, flea counts were performed 8 and 24 hours after treatment in the British trial and after 24 hours in the German study. Flea burdens were reduced by 96% within 8 hours of treatment and 100% efficacy was recorded at 24 hours (Figure 2, Table 1). For evaluation of residual protective activity, counts were made 24 hours after each subsequent infes- tation in the British study. Flea counts following reinfestation 1, 2 , 3, and 4 weeks posttreatment were reduced by 95%, 81%, 79%, and 68%, respectively (Figure 2). These differences in flea

counts between treated and control groups are statistically significant (P < .002).

Efficacy StudiesNatural Infestation

The third efficacy study (Study 3) was a clinical field tri- al conducted at the Meiji Pharmaceutical University, Tokyo, Japan, 6 in which 30 naturally infested rabbits treated with the 10% spot-on formulation at 10 mg/kg were compared with 30 untreated controls. Infestations were mostly C. felis, but a few additional dog fleas (Ctenocephalides canis) were noted on two of the rabbits. Initial flea burdens numbered 5 to 10 on most animals, but some had between 10 and 20. Flea counts were performed 1, 2, 3, 5, and 7 days posttreat- ment, and treated animals were also combed after 2 and 4 weeks. Each rabbit returned to its owners home after each visit to the clinic. With the exception of one animal on one occasion, fleas were found on all of the controls at every count (Table 2). This confirms that the rabbits were contin- ually exposed to reinfestation in their home environment. In contrast, only 3 of 30 treated rabbits harbored fleas one day posttreatment, and all were free from fleas between Days 2 and 7. Small numbers of fleas (<5) were found on one rabbit

2 weeks posttreatment and on three rabbits at 4 weeks. Thus, the Japanese clinical observations closely mirror the pattern of results seen in the British experimental study with substantial, although incomplete, protection against reinfestation persisting for at least 1 month.

Safety Studies

Ancillary safety studies were conducted in Japan (Study 4) and Germany (Study 5). In the Japanese study, 6 groups of six laboratory

Control Treated 40 - 35 - 30 - 25 - 20 - 15 - 10
Control
Treated
40
-
35
-
30
-
25
-
20
-
15
-
10
-
5
-
0
-
–7
0
1 8
15
22
29
(8 hr)
(24 hr)
Day
Mean Flea Counts

Figure 2Mean flea counts of a group of six rabbits treated with imidacloprid on Day 0 and a similar group kept as untreated controls (Study 2: Artificial Infestation, Britain).

Suppl Compend Contin Educ Pract Vet Vol. 23, No. 4(A), 2001

Second International Flea Control Symposium

TABLE 1

MEAN FLEA COUNTS AND PERCENTAGE REDUCTION FOLLOWING

IMIDACLOPRID TREATMENT ON DAY 0

(STUDY 1: ARTIFICIAL

INFESTATION, GERMANY)

Pretreatment

Posttreatment

Day 0

Day 1

Control

11.2

11.2

10.8

0

Treated

100

% reduction

rabbits, weighing 1.2 to 1.5 kg, were kept either as untreated con- trols or dosed at 10 mg/kg, 100 mg/kg, or 10 mg/kg daily for 3 con- secutive days. No clinical abnormalities were detected and no sig- nificant differences were found between groups when hematological and biochemical parameters were compared (Table 3). Similarly, in German dermal toxicity tests, 7 doses of 1, 3, and 5 times the recom- mended minimum failed to induce any observable abnormality in pairs of rabbits with body weights of 2.5 to 2.9 kg. No ill effect resulted when 0.1 ml of the 10% imidacloprid spot-on formulation was administered orally to a rabbit to mimic possible intake by lick- ing and grooming after topical application.

Conclusions

These experimental and clinical field trials demonstrate that imidacloprid spot-on provides excellent efficacy against a resident flea infestation on rabbits. The subsequent residual protective effect is not as complete as that seen on treated cats or dogs but is never- theless substantial, persisting for 4 weeks in the British and Japanese trials. No adverse effects were seen in any treated animal. The safe- ty of topically applied imidacloprid was confirmed by experimental studies in which rabbits were deliberately overdosed without ill effect.

TABLE 3

PARAMETERS MEASURED IN

SAFETY EVALUATION.

(STUDY 4: JAPAN)

HEMATOLOGY

Erythrocyte count

Leukocyte count

Hematocrit value

Leukocyte differentiation

Hemoglobin concentration

Platelet count

Mean corpuscular volume

Blood cell morphology

Mean corpuscular

hemoglobin concentration

BIOCHEMISTRY

Sodium

Total protein

 

Albumin

Potassium

Chlorine

Alkaline phosphatase activity

Calcium

γ-glutamyl transferase

Magnesium

(γ-glutamyl transpeptidase)

 

Lactate dehydrogenase

Inorganic phosphorus

Glucose

Aspartate aminotransferase

Total cholesterol

(glutamic oxaloacetic

Triglyceride

transaminase)

Urea nitrogen

Creatinine

Uric acid

Total bilirubin

Alanine aminotransferase

(glutamic pyruvic

transaminase)

Leucine aminopeptidase

 

URINE

Color

Ketone bodies

Specific gravity

Bilirubin

 

Blood

pH

Protein

Nitrate

Glucose

Urobilinogen

References

1. Rust MK, Dryden MW: The biology, ecology, and management of the cat flea. Ann Rev Entomol 42:451473, 1997.

2. Dryden MW, Broce AB, Cawthra J, Gnad D: Urban wildlife as reservoirs of cat fleas, Ctenocephalides felis [abstract]. Proc 40 th Ann Meet Am Assoc Vet Parasitol, Pittsburgh, 1995.

3. Robinson WH: Distribution of cat flea larvae in the carpeted household. Vet Dermatol 6:145150, 1995.

4. Jacobs DE, Hutchinson MJ, Krieger KJ: Duration of activity of imidaclo-

TABLE 2

NUMBER OF RABBITS INFESTED WITH FLEAS FOLLOWING IMIDACLOPRID

TREATMENT ON DAY 0 (STUDY 3: CLINICAL EFFICACY, JAPAN)

Day Posttreatment

0

1

2

3

7

14

28

5

30

30

30

30

30

29

Control a

30

3

0

0

0

0

1

3

Treated a

a 30 per group.

TNAVC, January 2001

Suppl Compend Contin Educ Pract Vet Vol. 23, No. 4(A), 2001

prid, a novel adulticide for flea control, against Ctenocephalides felis on cats. Vet Rec 140:259260, 1997.

5. Arther RG, Cunningham J, Dorn H, et al: Efficacy of imidacloprid for removal and control of fleas (Ctenocephalides felis) on dogs. Am J Vet Res 58:848850, 1997.

Suppl Compend Contin Educ Pract Vet Vol. 23, No. 4(A), 2001

6. Fukase T, Stanneck D, Mencke N: Efficacy and safety of an imidacloprid spot-on formulation for treating flea infestations in domestic rabbits [abstract]. Proc WSAVA-FECAVA Congr, Amsterdam, April 2529, 2000.

7. Andrews P, unpublished results, 1999.

Second International Flea Control Symposium