Efficacy of Imidacloprid
Jacobs, BVMS, PhD, FRCVS,
on Rabbits Naturally or
Experimentally Infested
with the Cat Flea,
Ctenocephalides felis
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
host–adapted 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
Dennis E.
FRCPatha
Melanie J. Hutchinson, BSc, HND(Agric)a
Tohru Fukase, PhDb
a
Olaf Hansen, DVM, PhDc
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
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 cats4 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
 counts between treated and control groups are statistically
significant (P < .002).

Efficacy Studies—Natural 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 owner’s 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
Figure 1—Application of imidacloprid spot-on formulation (Advantage ) to and 7. Small numbers of fleas (<5) were found on one rabbit
®

rabbits. 2 weeks posttreatment and on three rabbits at 4 weeks. Thus,

the Japanese clinical observations closely mirror the pattern
In the British study, fleas were placed on the rabbits on Days –8, of results seen in the British experimental study with substantial,
–1, 7, 14, 21, and 28. An infestation of 100 C. felis gave a consistent although incomplete, protection against reinfestation persisting for
and adequate level of infestation without excessive discomfort to at least 1 month.
the rabbit. Live fleas were observed on the floor of the cages of the
untreated controls. This contrasts sharply with experience in the Safety Studies
same laboratory with C. felis infestations on cats, as in this case the Ancillary safety studies were conducted in Japan (Study 4) and
fleas are almost invariably found only on the host. Similar infesta- Germany (Study 5). In the Japanese study,6 groups of six laboratory
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 Control
is not known if the difference between establish- Treated
ment rates in the British and German studies 40 -
reflects the strain of cat flea used, the breed of 35 -
Mean Flea Counts

rabbit, or other unknown factors.

30 -
To measure curative efficacy against an
established C. felis population, flea counts were 25 -
performed 8 and 24 hours after treatment in the 20 -
British trial and after 24 hours in the German 15 -
study. Flea burdens were reduced by 96% within
10 -
8 hours of treatment and 100% efficacy was
recorded at 24 hours (Figure 2, Table 1). For
5-
evaluation of residual protective activity, counts 0-
were made 24 hours after each subsequent infes- –7 0 1 8 15 22 29
(8 hr) (24 hr)
tation in the British study. Flea counts following Day
reinfestation 1, 2 , 3, and 4 weeks posttreatment
were reduced by 95%, 81%, 79%, and 68%, Figure 2—Mean flea counts of a group of six rabbits treated with imidacloprid on Day
respectively (Figure 2). These differences in flea 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 TABLE 3
MEAN FLEA COUNTS AND PARAMETERS MEASURED IN
PERCENTAGE REDUCTION FOLLOWING SAFETY EVALUATION.
IMIDACLOPRID TREATMENT ON DAY 0 (STUDY 4: JAPAN)
(STUDY 1: ARTIFICIAL
HEMATOLOGY
INFESTATION, GERMANY) • Erythrocyte count • Leukocyte count
• Hematocrit value • Leukocyte differentiation
Pretreatment Posttreatment • Hemoglobin concentration • Platelet count
Day 0 Day 1 • Mean corpuscular volume • Blood cell morphology
• Mean corpuscular
Control 11.2 11.2 hemoglobin concentration
Treated 10.8 0
BIOCHEMISTRY
% reduction — 100 • Sodium • Total protein
• Potassium • Albumin
• Chlorine • Alkaline phosphatase activity
• Calcium • γ-glutamyl transferase
rabbits, weighing 1.2 to 1.5 kg, were kept either as untreated con- • Magnesium (γ-glutamyl transpeptidase)
• Inorganic phosphorus • Lactate dehydrogenase
trols or dosed at 10 mg/kg, 100 mg/kg, or 10 mg/kg daily for 3 con-
• Glucose • Aspartate aminotransferase
secutive days. No clinical abnormalities were detected and no sig- • Total cholesterol (glutamic oxaloacetic
nificant differences were found between groups when hematological • Triglyceride transaminase)
• Urea nitrogen • Alanine aminotransferase
and biochemical parameters were compared (Table 3). Similarly, in (glutamic pyruvic
• Creatinine
German dermal toxicity tests,7 doses of 1, 3, and 5 times the recom- transaminase)
• Uric acid
• Leucine aminopeptidase
mended minimum failed to induce any observable abnormality in • Total bilirubin
pairs of rabbits with body weights of 2.5 to 2.9 kg. No ill effect
URINE
resulted when 0.1 ml of the 10% imidacloprid spot-on formulation • Color • Ketone bodies
was administered orally to a rabbit to mimic possible intake by lick- • Specific gravity • Bilirubin
• pH • Blood
ing and grooming after topical application. • Protein • Nitrate
• Glucose • Urobilinogen
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 References
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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 5 7 14 28

Controla 30 30 30 30 30 29 — —
Treateda 30 3 0 0 0 0 1 3

a30 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
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Second International Flea Control Symposium