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January 28, 2012 | Veterinary Record
Papers
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Evaluation of spinosad for the oral treatment
and control of flea infestations on dogs in Europe
S. Wolken, M. Franc, E. Bouhsira, S. Wiseman, B. Hayes,
B. Schnitzler, D. E. Jacobs
The novel ectoparasiticide spinosad is a naturally occurring mixture of spinosyns A and D
formed during a fermentation process. The spinosyns are tetracyclic macrolides with a
unique ring system. Their mode of action differs from that of other commercially available
insecticides. Laboratory and field trials were conducted to evaluate the use of spinosad in
a chewable tablet at a dose range of 45 to 70 mg/kg for the treatment and control of flea
infestations on dogs in Europe. Laboratory studies with artificially infested dogs confirmed
persistent activity against Ctenocephalides felis of higher than 99 per cent at three weeks
post-treatment with values of 96.5 to 97.8 per cent at four weeks. Two multicentric field trials
with naturally infected client-owned animals in five European countries used selamectin
as comparator. Monthly doses were given during the summer when many homes were
heavily infested. Households with spinosad-treated dogs showed cumulative benefits with
flea burdens reduced by about 97 per cent at 14 and 30 days and by 99.6 per cent at 60
and 90 days. Corresponding figures for selamectin were significantly lower (P<0.05) at all
time points: between 88.5 and 91 per cent at 14 and 30 days, then 97.8 and 98.2 per cent
at 60 and 90 days. Thus, the performance of spinosad compared favourably with that of the
established reference product.
DESPITE the introduction over the past 10 to 15 years of a number
of highly effective long-acting topically applied pulicidal compounds
such as imidacloprid, fipronil, selamectin, pyriprole and metaflumi-
zone (Dryden 2009), fleas continue to be a frequent cause of discom-
fort and canine disease throughout much of Europe (Farkas and others
2009). The so-called ‘cat flea’, Ctenocephalides felis, feeds on humans as
well as on a variety of domesticated and wild animals, and is the com-
monest species found on dogs. Fleas mostly cause minor irritation,
unless present in large numbers, but some dogs may develop hyper-
sensitivity reactions (flea-allergic dermatitis) of greater or lesser sever-
ity. Fleas may also transmit other potential pathogens such as the tape-
S. Wolken, DrMedVet,
University of Veterinary Medicine
Hannover, Institute for Parasitology,
Buenteweg 17, 30559 Hannover,
Germany
M. Franc, PhD, DVM, DipEVPC,
E. Bouhsira, DVM,
Université de Toulouse, INP, ENVT-
Parasitologie-Dermatologie, Ecole
Nationale Vétérinaire, 23 chemin des
capelles, 31076 Toulouse cedex, France
S. Wiseman, PhD,
B. Hayes, BSc,
B. Schnitzler, DrMedVet,
Elanco Animal Health, Lilly House,
Priestley Road, Basingstoke, Hampshire,
RG24 9NL, UK
D. E. Jacobs, BVMS, PhD, DipEVPC,
FRCVS, FRCPath,
Department of Pathology and Infectious
Diseases, Royal Veterinary College,
University of London, Hawkshead Lane,
North Mymms, Hatfield, Herts, AL9
7TA, UK
Correspondence to Dr Schnitzler,
e-mail: schnitzler_beate@lilly.com
Provenance: not commissioned;
externally peer reviewed
Accepted October 5, 2011
Published Online First December 2,
2011
Veterinary Record (2012) 170, 99 doi: 10.1136/vr.100211
worm, Dipylidium, and microorganisms including some Bartonella and
Rickettsia species (Rolain and others 2003, Shaw and others 2004). Cat
fleas have shown a propensity to develop resistance to earlier insecti-
cidal classes, such as cyclodienes, carbamates, organophosphates and
pyrethroids. Extending the longevity of currently effective therapies
should be a major goal of the veterinary community (Rust 2005).
Thus, there is a continuing need to develop improved flea-control
methodologies and to expand the chemotherapeutic options available
to the veterinarian for this purpose.
The latest addition to the range of commercially available long-
acting pulicides is spinosad (Comfortis, Elanco) which is character-
ised by oral rather than topical administration and a rapid speed of
kill (Blagburn and others 2010). Spinosad is a naturally occurring
mixture of spinosyns A and D formed during a fermentation process
employing the soil-dwelling actinomycete, Saccharopolyspora spinosa.
Structurally, spinosyns are tetracyclic macrolides with a unique ring
system. They exhibit a novel mode of action primarily involving
nicotinic acetylcholine receptor binding sites (nAChRs) that are
distinct from those targeted by other insecticides (Sparks and oth-
ers 2001). The outcome is disruption of the flea’s nervous system.
A secondary effect on γ-aminobutyric acid (GABA) may potenti-
ate this pulicidal activity. The low mammalian toxicity associated
with spinosad is likely to be due to a lack of homology between
insect and mammalian nicotinic and/or GABA receptors. Spinosad
is presented for flea-control as a ‘chewable’ tablet (ie, a tablet that
is efficacious whether swallowed whole or after being chewed or
bitten). Preliminary dog studies indicated that effective flea-control
over a four-week period could be obtained with dose rates of 30 mg
spinosad/kg bodyweight or above (Snyder and others 2007). A mini-
mum dose of 45 mg/kg was selected for European laboratory studies
to ensure compliance with all local regulatory requirements (EMEA/
CVMP 2007). As is the case with all medicines presented in tablet
form, any combination of tablet sizes has to cover a range of body-
weights and tablet strengths are therefore designed to provide dosag-
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and females in each. The second, in France (study 3), was similar but
with an additional female in the control group bringing the total of
untreated dogs to nine. Whole spinosad tablets (Comfortis, Elanco) or
placebo tablets were given on day 0. Treated dogs weighing less than
12.5 kg received a tablet containing 560 mg spinosad, whereas those
over this weight received 810 mg spinosad. Fleas were placed on the
animals on the day before treatment (day –1) in the French study and
on days 7, 14, 21 and 28 in both studies.
Field studies
Study design
Field investigations included a one-month trial (study 4) covering five
European countries (UK, Netherlands, France, Germany and Italy)
and a three-month trial (study 5) confined to France but spanning
both Atlantic and Mediterranean climatic zones. Each was a blinded
positive-control multicentre study using a randomised complete block
design. Data collection was standardised using preprinted forms and
questionnaires. The experimental unit was the household represented
by one dog. Ethical considerations did not permit the use of nega-
tive (untreated) controls, and thus spinosad treatments were compared
with an established reference product. Because no alternative long-act-
ing oral pulicide was commercially available, selamectin (Stronghold,
Pfizer) was selected for this purpose. Although chemically unrelated
and topically applied, selamectin (like spinosad) is a long-acting puli-
cide with systemic activity (Sarasola and others 2002). As the two
products are so different in formulation and presentation, their iden-
tity could not be masked, but trial blinding was achieved by ensuring
that personnel conducting flea-counts were unaware of which treat-
ment had been given. In accordance with current guidelines, the ran-
domised allocation procedure allowed one positive control for every
two spinosad test homes.
Animals
For enrolment, dogs at first inspection had to be naturally infested
with at least 10 fleas but otherwise healthy, over six weeks old and
with a minimum bodyweight of 1 kg. They were not accepted if
intended for breeding within six months or if any flea treatment had
been used within a specified time period (dependent on the nature of
the product used), or if their disposition or hair-coat precluded accurate
flea-counting. Cooperating dog owners were fully informed and pro-
vided a written consent.
Treatments
Spinosad-treated dogs received an appropriate combination of whole
chewable tablets to provide a dose within the range of 30 to 90 mg/
kg (although only animals receiving 45 to 70 mg/kg were used for
efficacy evaluation, see statistical analysis section below). Their
owners, after appropriate instruction, administered the treatments
at home together with food. Selamectin was applied as per label
instructions (ie, topically as a spot-on preparation to provide a mini-
mum dose of 6 mg/kg). All dogs in multi-pet homes were treated
with the same product. Cats in participating households received
selamectin irrespective of the dog treatment (since no spinosad for-
mulation suitable for cats was available and flea-control in the home
depends on all pets being treated). The use of any other medicament,
shampoo, food supplement, environmental treatment etc contain-
ing any ingredient efficacious against fleas was prohibited during the
course of the trial.
After the initial flea-count and allocation, recruited dogs were
dosed on day 0 in the one-month study (study 4) and at monthly
intervals on days 0, 30 and 60 in the three-month study (study 5).
Flea-counts
A standardised flea-combing procedure taking at least 15 minutes was
performed by trained practice staff using a separate flea-comb for each
dog. Only live, viable fleas were recorded (ie, those demonstrating nor-
mal movement and behaviour, with an ability to maintain an upright
posture and cling onto hair). In study 4, flea-counts were performed
on days 14 and 30 (with a discretionary period of ±2 days to encour-
age owner compliance) and on days 14, 30, 60 and 90 (±three days)
in study 5. Observations were completed before dosing on treatment
es within strictly defined limits. This paper describes laboratory and
field investigations evaluating a dose range of 45 to 70 mg spinosad/
kg bodyweight for the oral treatment and control of flea infestations
on dogs in Europe.
Materials and methods
Three laboratory and two multicentric field studies are reported.
They complied with internationally accepted guidelines and stand-
ards for trial design and animal welfare (EMEA/CVMP 2000, 2007,
Marchiondo and others 2007) as well as all relevant local regulations
and ethical requirements.
Laboratory studies
Study design
Laboratory investigations included a preliminary dose-demonstration
study using unformulated spinosad powder and two dose-confirma-
tion studies with chewable tablets. All were designed as randomised
complete block studies and partly blinded to minimise the risk of
unintentional bias. The dose-confirmation studies were conducted
independently at separate locations.
Animals and infestations
Individually housed laboratory beagles with bodyweights between
10 and 17 kg were used. As part of the allocation procedure, all dogs
were infested with 100 newly emerged unfed fleas about one week
before the scheduled treatment date to account for variation in indi-
vidual susceptibility. Insecticidal activity was evaluated by a similar
application of fleas on the days indicated for each study. Fleas were
counted and removed 48 hours after each infestation. To do this, dogs
were combed systematically with a fine-toothed comb until no more
fleas were detectable. Personnel conducting flea-counts were unaware
of which treatment had been given.
Treatment
An earlier observation (Snyder and others 2007) had suggested that
feeding around the time of dosing improves spinosad bioavailability.
On the day of treatment, therefore, all dogs were offered 25 per cent of
their daily canned ration no more than 30 minutes before they were
dosed. Control dogs received a placebo identical to the spinosad pres-
entation but without an active ingredient. To ensure that the whole
dose was swallowed, the capsule or tablet was placed over the back of
the tongue with a small volume of water. The remainder of the daily
meal was given after dosing.
Statistical analysis
Before each analysis of results, a logarithmic transformation
(ln(count+1)) was applied to the live flea-counts for each animal at
each scheduled time point. This transformation addressed the skew-
ness of the data and also allowed for zero counts. Back-transformed
geometric means were calculated as
e
x
–1
, where x was the arithme-
tic treatment mean of log-transformed counts at a given time point.
Efficacy based on the reduction of flea-counts attributable to treatment
was calculated using the following formula:
Efficacy (per cent) = C–T
C x 100
Where, C is the geometric mean of the flea-counts of the con-
trol group and T is the corresponding geometric mean for the treated
group.
Preliminary study
The preliminary dose-demonstration study (study 1) employed two
groups of six dogs, each comprising four males and two females. The
purpose was to confirm the residual insecticidal efficacy of spinosad at
the proposed European minimum dose rate of 45 mg/kg. For this, each
dog was treated on day 0 with an exact dose, based on its bodyweight
of unformulated spinosad powder in a gelatine capsule. Control dogs
received empty capsules. Fleas were applied on days 21 and 28.
Dose-confirmation studies
The first dose-confirmation trial was conducted in Germany (study 2)
and included two groups of eight dogs with equal numbers of males
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days. In the case of multi-pet homes, flea-count data were collected
from only one designated dog.
Statistical analysis
The prescribed spinosad dosage used in these trials was based on
results from early studies (Snyder and others 2007) and as a conse-
quence spanned a broader dose range (30 to 90 mg/kg) than that sub-
sequently selected for European registration (45 to 70 mg/kg). To fulfil
the objective of the current publication, therefore, data from spinosad-
treated dogs receiving less than 45 mg/kg or more than 70 mg/kg were
rejected from the analysis. This constrained the numbers of eligible
spinosad-treated dogs to 93 (of 197) and 43 (of 130) in studies 4 and
5, respectively. These restrictions did not affect the statistical power
or validity of the analysis. The full set of positive control (selamectin)
dogs was kept for comparison.
In the absence of negative (untreated) controls, efficacy values were
calculated by comparing post-treatment flea-counts with baseline data
collected immediately before the first treatment. For reasons outlined
above for the laboratory studies, geometric means were used for this
purpose. Further analysis on the log-transformed (flea-count+1) data
used a repeated measures mixed effects linear model for values on suc-
cessive observation days. In addition to estimating reduction in flea
populations on treated dogs, the proportion of dogs in each treatment
group on which no fleas could be found (the ‘zero-flea’ percentage)
was also recorded.
Results
Laboratory studies
In all cases, pretreatment observations confirmed that flea infestations
could be established on all animals in sufficient numbers to allow valid
statistical analysis. Feeding and treatment procedures were completed
without problem and all animals received their full dose, which in
the dose-confirmation trials ranged from 45.9 to 54.0 mg/kg. Efficacy
values for each observation-point in the three studies are displayed
in Table 1. Flea populations established on dogs in study 3 one day
before treatment were completely eliminated. Residual efficacies in
all three studies were greater than 99 per cent up to three weeks post-
treatment, while day 30 values of 96.5, 96.5 and 97.8 per cent were
recorded in studies 1, 2 and 3, respectively.
Field studies
The clinical phase of each field study was completed between May
and November and encompassed a wide range of geographical, social
and climatic regions. Data from 34 veterinary clinics qualified for
inclusion in study 4, and from 21 clinics in study 5. The test popu-
lation in study 4 comprised female and male dogs in almost equal
proportions (54.5 v 45.5 per cent). They belonged to no fewer than
52 breeds. Longhaired varieties were, however, in a minority (9.6 per
cent). Bodyweight ranged from 1.3 to 65 kg and age from seven weeks
to 17 years. Homes with a single dog, with more than one dog (but
no cat) or with at least one cat were almost equally represented (32.6,
37.9 and 29.5 per cent, respectively). Most (82.7 per cent) lived partly
or fully outdoors. Study 5 was similarly diverse, although a larger pro-
portion (69.3 per cent) was kept indoors.
Flea populations at the time of recruitment were often substantial
and were comparable between treatment groups. The largest initial
flea infestations recorded for spinosad- and selamectin-treated groups,
respectively, were 560 and 229 in the first trial; they were 437 and
394, respectively, in the second trial (Table 2). Pretreatment geometric
mean flea-counts for spinosad- and selamectin-treated groups, respec-
tively, were 36.7 and 29.7 in study 4, and 40.7 and 33.5 in study 5.
At both 14 and 30 days post-treatment, flea burdens of spinosad-
treated dogs were reduced by about 97 per cent compared with
pretreatment values (Table 2), while corresponding figures for sela-
mectin were significantly lower (90.7 and 88.5 per cent on day 14;
89.4 and 91.0 per cent on day 30 in studies 4 and 5, respectively). At
the end of the second and third months, reductions of 99.6 per cent
were recorded for the spinosad group, while selamectin values were
again significantly lower at 97.8 and 98.2 per cent on days 60 and 90,
respectively.
The proportion of spinosad-treated dogs on which no fleas could
be found (Table 2) varied during the first month from a low of 39.5
per cent (study 5, day 14) to a high of 59.1 per cent (study 4, day 14).
Corresponding figures for the selamectin animals were 28.6 per cent
(study 5, day 14) to 34.1 per cent (study 4, day 30). Following the sec-
ond monthly dose, the figures for spinosad and selamectin increased
to 77.5 and 62.9 per cent, respectively. By day 90, they had become
significantly different (P=0.042) at 85 and 67.1 per cent, respectively.
Discussion
Laboratory studies are usually designed to isolate and define single
aspects of the biological activity of an experimental compound. They
provide essential building blocks for knowledge and understanding
but rarely do they fully reproduce or reflect the complexities of natural
disease. In this respect, domestic flea infestations present a particu-
larly challenging therapeutic problem (Rust and Dryden 1997). Only
a small part of the total flea population resides on the host animal.
In much greater abundance are off-host life cycle stages such as eggs,
larvae, pupae and newly emerging adults found in locations such as
carpets, furniture and bedding. Flea-control therefore depends on the
overall impact of veterinary and other interventions on the dynam-
ics of this ecological system. Modern veterinary pulicides can influ-
ence this process in a number of ways depending upon their particu-
lar biological characteristics, the nature and spectrum of which vary
between products. Such attributes can include their short-term effect
on adult fleas (knockdown), longer-term residual activity, speed of kill,
TABLE 1: Laboratory studies: percentage reduction in flea-counts
comparing spinosad-treated dogs with placebo-treated controls
48 hours after each infestation
Study Formulation Actual dose given
% Reduction in flea-count
measured on day
mg/kg 1 9 16 23 30
1 Powder 45 - - - 99.8 97.8
2 Tablet 45.9-54.0 - 99.9 100 99.4 96.5
3 Tablet 48.2-53.0 100 100 100 99.1 96.5
TABLE 2: Field trial data: percentage reduction in flea-counts of spinosad and selamectin-treated dogs (compared with pretreatment values
on day 0) and the proportion of flea-free dogs at each observation day
Treatment*
Total number
of dogs
Number of fleas
on day 0
†
% Reduction in flea-counts on day % Dogs with zero fleas on day
14 30 60 90 14 30 60 90
Study 4
‡
Spinosad 93 36.7 (11-560) 97.5 97.2 - - 59.1 54.5 - -
Selamectin 93 29.7 (10-229) 90.7 89.4 - - 33.7 34.1 - -
P values
§
0.001 0.003 - - 0.001 0.006 - -
Study 5
#
Spinosad 43 40.7 (10-437) 97.3 97.4 99.6 99.6 39.5 50.0 77.5 85.0
Selamectin 71 33.5 (10-394) 88.5 91.0 97.8 98.2 28.6 31.4 62.9 67.1
P values
§
<0.001 0.005 0.01 0.035 NS NS NS 0.042
* Spinosad 45 to 70 mg/kg; selamectin 6 to 11.8 mg/kg
†
Geometric mean and range
‡
Treated day 0
#
Treated days 0, 30, 60
§
Comparing spinosad and selamectin groups
NS Not significant (P>0.05)
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anti-feeding potential, repellency and larvicidal effects (Carlotti and
Jacobs 2000). Furthermore, these properties can be modified by factors
such as formulation, dose and method of application. Consequently,
field studies play a particularly important role in evaluating prospec-
tive flea-control agents as they come closest to encompassing the full
scope of these ecological and therapeutic complexities.
Effective flea-control is a three-stage process (Carlotti and Jacobs
2000). First, the removal of fleas from an already infested host pro-
vides relief from discomfort and aids the resolution of skin lesions due
to self-trauma or allergy. Secondly, the animal must be protected from
re-infestation since the household environment is likely to be con-
taminated and therefore a continuing source of hungry host-seeking
fleas. Thirdly, the reservoir of off-host life cycle stages must be elimi-
nated as this is the only way a long-term solution can be provided.
Traditionally, this was achieved by the direct application of chemicals
onto flea development ‘hotspots’ around the home (Rust and Dryden
1997). More recently, however, this approach has been largely super-
seded by long-acting animal treatments that halt the deposition of
viable flea-eggs. With no new eggs entering the system, the domestic
reservoir of developing fleas becomes progressively depleted and is
eventually driven towards extinction (Dryden 2009).
Under most household conditions, fleas originating from eggs
deposited before the start of a control programme will have completed
their development and emerged from their cocoons within three to five
weeks, but this process can in some cases be delayed by up to 174 days
(Dryden and Rust 1994) and may influence the results of clinical trials.
Nevertheless, in the current field investigation, a 99.6 per cent reduction
in flea burdens on dogs was observed in spinosad households 60 days
from the start of the monthly dosing programme and the ‘zero-flea’
data suggested that fleas had been eliminated from up to 85 per cent of
these homes by day 90 (Table 2). This compared favourably with the
selamectin controls in which a 97.8 per cent reduction in flea-count
was recorded at day 60 and a ‘zero-flea’ value of 67 per cent at day 90.
These investigations were conducted over the summer season in
a variety of climatic regions including warm, humid areas favouring
flea reproduction. Thus, these results were obtained at a time when
flea populations would normally be increasing in magnitude. Indeed,
the day 14 zero-flea figures indicate the presence of heavy challenge in
many of the households in the early part of the two studies (Table 2)
with evidence of re-infestation taking place on 41 and 60 per cent of
spinsosad dogs, respectively, and on 66 and 71 per cent of the selamec-
tin groups. Nevertheless, the overall number of fleas on the animals
at day 14 had been reduced by 97 per cent in the case of spinosad and
by about 90 per cent for selamectin indicating a high level of protec-
tion in the face of continuing re-infestation. Similar results have been
reported from a comparable trial encompassing 14 sites in the USA
and two in Canada (Robertson-Plouch and others 2008).
The high-performance level of spinosad under challenging clinical
situations in both European and North American field trials can be
ascribed to the summation of its inherent pulicidal attributes, includ-
ing ‘knockdown’, duration of activity, speed of kill and the resultant
impact of these on flea-egg output. At dose rates of 30 mg/kg or more,
the ‘knockdown’ effect of spinosad against a previously established flea
population is virtually 100 per cent (Snyder and others 2007, Blagburn
and others 2010). Thereafter, a high level of residual protection against
re-infestation is maintained for a month (Snyder and others 2007). In
this study, where dose rates in individual dogs ranged from 45 to 54
mg/kg, values higher than 99 per cent were recorded up to day 23 and
of 96.5 per cent at day 30 (Table 1). The speed at which spinosad kills
fleas was investigated by Blagburn and others (2010) using a dose rate
of 30 to 60 mg/kg. Mortality was evident as early as 30 minutes after
treatment with a significant reduction (64.2 per cent, P<0.05) at one
hour. By two hours, efficacy had increased to 85.8 per cent and had
reached 100 per cent by four hours. This is of significance in control
programmes as newly acquired fleas must be killed before they start
to lay eggs, if recontamination of the household environment is to
be avoided. To measure the effect of spinosad-treatment on flea-egg
production, Blagburn and others (2010) collected eggs dropping from
treated dogs and untreated controls that had been infested with fleas at
intervals over a one-month period. They estimated that treatment had
reduced the number of eggs falling to the ground by at least 99.8 per
cent. Extrapolating this result to a domestic setting, monthly spinosad
treatments would therefore be expected to make a major contribution
towards the long-term objective of eliminating the environmental res-
ervoir of off-host life cycle stages. Complementary interventions such
as household vacuum cleaning, particularly of potential hotspots, are of
course invaluable adjuncts for accelerating progress towards this goal.
The fast onset of flea mortality following oral dosing observed by
Blagburn and others (2010) can be explained by rapid absorption of
spinosyns A and D from the canine gastrointestinal tract, with maxi-
mum plasma concentrations occurring about two to four hours after
treatment (Anon 2007). The systemic activity of spinosad has other
potentially beneficial consequences. For example, newly acquired fleas
start to feed within minutes of jumping onto their host (Dryden and
Gaafar 1991, Cadiergues and others 2000) and may thereby assimilate
a lethal dose of a systemic pulicide more quickly than by absorption
of a topical contact insecticide through the cuticle (McCoy and others
2008). Furthermore, as spinosad is not known to be present in sebum,
shed hair or skin flakes (Blagburn and others 2010), direct transfer
from treated animals onto animal handlers or into the household
environment is unlikely.
In conclusion, the rapid absorption and fast speed of kill of spinosad
ensure that infested dogs respond quickly to treatment and that fleas
acquired subsequently are killed before they start to lay eggs, thereby
breaking the flea life cycle in contaminated households. A monthly
dosing programme using client-owned dogs, many of which would
have been kept under conditions of heavy natural challenge, reduced
parasite burdens on dogs by 97 per cent during the first month and
drove the flea population close to extinction in the majority of homes
within 60 days. In comparative field studies, efficacy values for spinosad
were higher than those obtained for the reference product, selamectin.
Thus, laboratory and field trials have confirmed that spinosad chewable
tablets administered to dogs at a dose rate of 45 to 70 mg/kg are highly
effective for the treatment and control of flea infestations.
Acknowledgements
The authors express their gratitude to all personnel involved in the
independent laboratory studies and to the dog owners and staff of
veterinary clinics taking part in the field investigations. J. Stoker, A.
K. Nissen and other members of the Elanco team are thanked for
their participation, as is Dr Dan Snyder for his constant support and
encouragement.
References
ANON (2007) Freedom of Information Summary. NADA. September 25 2007.
pp 141-277
BLAGBURN, B. L., YOUNG, D. R., MORAN, C., MEYER, J. A., LEIGH-HEFFRON,
A., PAARLBERG, T., ZIMMERMANN, A. G., MOWREY, D., WISEMAN, S. &
SNYDER, D. E. (2010) Effects of orally administered spinosad (Comfortis) in dogs on
adult and immature stages of the cat flea (Ctenocephalides felis). Veterinary Parasitology
168, 312-317
CADIERGUES, M. C., HOURCQ, P., CANTALOUBE, B. & FRANC, M. (2000) First
bloodmeal of Ctenocephalides felis felis (Siphonaptera: Pulicidae) on cats: time to initia-
tion and duration of feeding. Journal of Medical Entomology 37, 634-636
CARLOTTI, D. N. & JACOBS, D. E. (2000) Review: therapy, control and prevention of
flea allergy dermatitis in dogs and cats. Veterinary Dermatology 11, 83-98
DRYDEN, M. W. & GAAFAR, S. M. (1991) Blood consumption by the cat flea,
Ctenocephalides felis (Siphonaptera: Pulicidae). Journal of Medical Entomology 28, 394-400
DRYDEN, M. W. (2009) Flea and tick control in the 21st century: challenges and oppor-
tunities. Veterinary Dermatology 20, 435-440
DRYDEN, M. W. & RUST, M. K. (1994) The cat flea: biology, ecology and control.
Veterinary Parasitology 52, 1-19
EMEA/CVMP (2000) VICH GL9: guideline on good clinical practices EMEA/CVMP/
VICH/595/98 July 2000
EMEA/CVMP (2007) Testing and evaluation of the efficacy of antiparasitic substances
for the treatment and prevention of tick and flea infestations in dogs and cats. EMEA/
CVMP/005/00 Rev 2 November 2007
FARKAS, R., GYURKOVSZKY, M., SOLYMOSI, N. & BEUGNET, F. (2009) Prevalence
of flea infestation in dogs and cats in Hungary combined with a survey of owner
awareness. Medical and Veterinary Entomology 23, 187-194
MARCHIONDO, A. A., HOLDSWORTH, P. A., GREEN, P., BLAGBURN, B. L.
& JACOBS, D. E. (2007) World Association for the Advancement of Veterinary
Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of parasiticides for the
treatment, prevention and control of flea and tick infestation on dogs and cats. Veterinary
Parasitology 145, 332-344
MCCOY, C., BROCE, A. B. & DRYDEN, M. W. (2008) Flea blood feeding patterns in
cats treated with oral nitenpyram and the topical insecticides imidacloprid, fipronil and
selamectin. Veterinary Parasitology 156, 293-301
group.bmj.com on July 20, 2015 - Published by http://veterinaryrecord.bmj.com/Downloaded from
January 28, 2012 | Veterinary Record
Papers
ROLAIN, J. M., FRANC, M., DAVOUST, B. & RAOULT, D. (2003) Molecular detection
of Bartonella quintana, B. koehlerae, B. henselae, B. clarridgeiae, Rickettsia felis, and Wolbachia
pipientis in cat fleas, France. Emerging Infectious Diseases 9, 338-342
ROBERTSON-PLOUCH, C., BAKER, K. A., HOZAK, R. R., ZIMMERMANN, A. G.,
PARKS, S. C., HERR, C., HART, L. M., JAY, J., HUTCHENS, D. E. & SNYDER, D. E.
(2008) Clinical field study of the safety and efficacy of spinosad chewable tablets for
controlling fleas on dogs. Veterinary Therapeutics 9, 26-36
RUST, M. K. (2005) Advances in the control of Ctenocephalides felis (cat flea) on cats
and dogs. Trends in Parasitology 21, 232-236
RUST, M. K. & DRYDEN, M. W. (1997) The biology, ecology, and management of the
cat flea. Annual Review of Entomology 42, 451-473
SARASOLA, P., JERNIGAN, A. D., WALKER, D. K., CASTLEDINE, J., SMITH, D. G.
& ROWAN, T. G. (2002) Pharmacokinetics of selamectin following intravenous,
oral and topical administration in cats and dogs. Journal of Veterinary Pharmacology and
Therapeutics 25, 265-272
SHAW, S. E., KENNY, M. J., TASKER, S. & BIRTLES, R. J. (2004) Pathogen carriage by
the cat flea Ctenocephalides felis (Bouché) in the United Kingdom. Veterinary Microbiology
102, 183-188
SNYDER, D. E., MEYER, J., ZIMMERMANN, A. G., QIAO, M., GISSENDANNER,
S. J., CRUTHERS, L. R., SLONE, R. L. & YOUNG, D. R. (2007) Preliminary studies
on the effectiveness of the novel pulicide, spinosad, for the treatment and control of
fleas on dogs. Veterinary Parasitology 150, 345-351
SPARKS, T. C., CROUSE, G. D. & DURST, G. (2001) Natural products as insecticides:
the biology, biochemistry and quantitative structure–activity relationships of spinosyns
and spinosoids. Pesticide Management Science 57, 896-905
group.bmj.com on July 20, 2015 - Published by http://veterinaryrecord.bmj.com/Downloaded from
Europe
and control of flea infestations on dogs in
Evaluation of spinosad for the oral treatment
and D. E. Jacobs
S. Wolken, M. Franc, E. Bouhsira, S. Wiseman, B. Hayes, B. Schnitzler
doi: 10.1136/vr.100211
2011 2012 170: 99 originally published online December 2,Veterinary Record
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