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Susceptibility of Fleas Michael W.

Dryden, DVM, PhD


Associate Professor of Veterinary Parasitology
Department of Diagnostic Medicine/Pathobiology

to Control Agents: College of Veterinary Medicine


Kansas State University
Manhattan, KS, USA

Development of Alberto B. Broce, PhD


Professor of Entomology

a Monitoring System Department of Entomology


Kansas State University
Manhattan, KS, USA

Determining the Cause of Product Failures


T
he development and marketing of highly effective, residual
insecticides/insect growth regulators during the past few Because it is understood that development of resistance in cat
years has dramatically changed the way pet owners treat flea populations is always a possibility, veterinarians should not be
their pets for fleas. The increased reliance on single-compound, on- quick to blame resistance for all perceived control failures. Veteri-
animal, or oral application systems to control fleas has been accom- narians must always be aware that several factors other than resist-
panied by a corresponding decrease in the treatment of premises and ance may be involved when treatment is perceived to have failed.
an indifferent attitude toward flea biology and epidemiology. In clinical practice it may be difficult or impossible to deter-
Although these compounds are remarkably effective, there is a con- mine if a particular product failed because of resistance. Perceived
cern that an overreliance on any single compound to control insects failure in practice situations could be from lack of owner compliance,
may lead to the development of insecticide resistance. environmental burden of the pest, presence of untreated hosts,
Resistance to insecticides was defined by the World Health bathing of the treated pet, vomiting of oral medications, or actual
Organization (WHO) as the development of an ability in a strain of resistance. It can be difficult to determine the reason for perceived
some organism to tolerate doses of a toxicant that would prove product failure without considerable investigation. Even in the labo-
lethal to a majority of individuals in a normal population of the ratory a number of factors can affect the results of a laboratory bioas-
same species.1 Resistance has a genetic basis and is the result of a say, such as rearing conditions, immobilization method, age of organ-
change in the genetic composition of a population as a direct result ism, shipping stresses, treated substrate, temperature, or humidity.
of the selective effects of a toxicant.
Terminology for Describing Product Failures
History of Insecticide Resistance Another problem practitioners encounter is a misunderstanding
In 1951 Pulex irritans was suggested as becoming resistant to of terms used to describe failures. One such term is reduced suscep-
DDT after sprays were applied to control malarial mosquitoes.2 tibility. The reasons for reduced susceptibility may vary depending
Soon thereafter, many locations, mainly in the tropics, reported upon whether one is referring to a laboratory bioassay, an on-animal
control failures. Laboratory bioassays confirmed that insecticide efficacy trial, or a field event. This term simply refers to a popula-
selection pressure had forced genetic evolution of flea populations tion of organisms that has a higher survival rate than expected when
with resistance as the outcome.2 By 1983, eight species of fleas, exposed to a particular compound, regardless of the cause.
including the fleas of public health importance Ctenocephalides felis, Tolerance refers to the response by a population of organisms to
P. irritans, and Xenopsylla cheopis, had demonstrated resistance to a toxicant relative to other species. It is the innate genetic predispo-
many of the insecticides used in flea control.3 In addition, labora- sition of a population. Examples of tolerance include ticks being
tory selection studies have produced resistance ratios (the ratio of more tolerant of imidacloprid than fleas are, and Trichuris vulpis being
lethal doses of a resistant strain to lethal doses of a susceptible more tolerant of pyrantel pamoate than is Ancylostoma caninum.
strain) of 12 and 108 over unselected controls against malathion in These are conditions that exist irrespective of selection pressure.
two separate experiments.4,5 A field-collected strain of cat fleas Insecticide resistance is the ability of an insect population to sur-
from Florida had resistance ratios of 26 and 28 over a laboratory vive doses and concentrations of an insecticide that previously were
strain from California for malathion and bendiocarb, respectively.6,7 lethal to that population. Insecticide resistance is a genetic change in
Cat fleas are thought to be resistant to more chemical families than a population caused by the elimination of the susceptible individuals,
any other flea.8 leaving only the resistant individuals to breed. Resistance is a form of

TNAVC, January 2000 Suppl Compend Contin Educ Pract Vet Vol. 22, No. 4(A), 2000
time-compressed evolution. Classic evolution is a gradual selection of be combined to establish LC50 and LC95 to be used in a discriminat-
more competitive morphologic, physiologic, or behavioral traits, ing dose bioassay. A discriminating dose bioassay will then be used
whereas resistance selection is a rapid evolutionary process. The appli- for large-scale screening of field populations of cat fleas. A discrim-
cation of the insecticide results in an instantaneous widespread eco- inating dose bioassay will allow for more rapid screening of larger
logic disaster on the population. Individuals with morphologic, physi- numbers of cat flea strains. It is planned that during the first year the
ologic, or behavioral traits that allow survival remain to reproduce. five laboratories will randomly screen up to 150 flea isolates (indi-
Although a great deal of knowledge has been gained concerning vidual collections of fleas from infested dogs or cats in veterinary
insecticide resistance in other insect species, unfortunately in fleas practices) in the United States and 100 in Europe.
the extent, prevalence, or clinical significance of insecticide resist- During this screening process a population will be considered
ance to any particular insecticide has not been determined. Although potentially resistant if the mortality at the discriminating dosage falls
it is apparent that insecticide resistance has been detected in various outside the confidence limits of the normal range for the five baseline
cat flea populations, there currently is no active program to monitor for strains. The numbers of any such field strain determined to be poten-
resistance. In addition, no standard bioassay system has been used to tially resistant will be increased in the laboratory, and their dose-
compare strains, and there are no data to indicate what level of sur- response will be determined in a classic bioassay. A population will be
vivability in a bioassay corresponds to control failure on animals. considered resistant if its LD50 (median lethal dose) and/or LD95 is sig-
nificantly greater (outside the 95% confidence interval) than the
The Flea Susceptibility Monitoring Team LD50 and/or LD95 of the standard value for the combined strains.
In September 1999 a Flea Susceptibility Monitoring Team was Most programs for monitoring insecticide resistance in other
organized by Bayer, Animal Health. The team includes Byron Blagburn species of insects do not attempt to correlate the dose-response data
(Auburn University, USA), Michael Dryden (Kansas State University, to field performance (i.e., efficacy) of the insecticide tested. This is
USA), Dennis Jacobs (Royal Veterinary College, London, UK), an important question when monitoring for the development of
Michael Rust (University of California at Riverside, USA), Ian Den- insecticide resistance, mainly for two reasons: first, there is no infor-
holm and Martin Williamson (Institute of Arable Crops Research mation on how well the dose-response data equate to the on-host
[IACR], Rothamsted, UK), Heinz Mehlhorn (Heinrich Heine Univer- efficacy of the chemical in question; second, the validity of using
sity, Düsseldorf, Germany), and the Research and Development Divi- dose-response of strains reared under laboratory conditions for a
sion of Bayer Animal Health (United States, Germany, Australia). long time is questionable. Therefore, once a strain has been deter-
The team was formed to establish protocols and procedures to mined to be resistant in the classic bioassay, the team will conduct
monitor cat flea susceptibility to imidacloprid, determine clinical on-host efficacy evaluations and simulated home environment trials
significance of reduced susceptibility that may be found in the of the resistant isolate(s) using standard doses of imidacloprid to
future, and formulate plans to steward imidacloprid into the future. determine if resistance levels found in laboratory bioassays have any
clinical significance.
Monitoring for Insecticide Resistance Finally, because virtually nothing is known concerning the
Monitoring for insecticide resistance in wild populations of pests resistance mechanisms of resistance in fleas, the team will attempt
has often been used to describe a continuous inspection of levels of to determine biochemical and genetic mechanism(s) of resistance.
efficacy of an insecticide applied to such populations. The first step
of a monitoring program should be to obtain baseline data before References
1. Ferrari JA: Insecticide resistance, in Beaty BJ, Marguardt WC: The Biolo-
resistance appears and the use of the insecticide is widespread. How-
gy of Disease Vectors. Niwot, Colo, University Press of Colorado, 1996, pp
ever, if baseline data cannot be obtained a priori, then data from sev- 512–529.
eral laboratory strains should be used to establish such a baseline. 2. Brown AWA, Pal R: Insecticide Resistance in Arthropods, ed 2. Geneva,
WHO, 1971, p 491.
Obviously, these should be insecticide-susceptible strains that have 3. Georghiou GP, Mellon RP: Pesticide resistance in time and space, in
not been exposed to insecticides during their laboratory rearing. One Georghiou GP, Saito T (eds): Pest Resistance to Pesticides. New York,
Plenum Press, 1983, pp 1–46.
would hope that the dose-responses of these lab strains would cover 4. Collart MG, Fink WF: Development of resistance to malathion in cat flea
the range of original variability found among wild populations. (Siphonaptera: Pulicidae). J Econ Entomol 79:1570–1572, 1986.
5. Moyses EW: Measurement of insecticide resistance in the adult cat flea,
The first step proposed in establishing baseline data is to estab-
in Meola RW (ed): Proc Third Intl Symp Ectoparasites of Pets, 995. Col-
lish a practical, repeatable, and reliable bioassay system to monitor lege Station, Tex, Texas A&M University, 1999, pp 21–34.
for imidacloprid susceptibility in five separate laboratories. The 6. El-Gazzar LM, Milio J, Koehler PG, Patterson PS: Insecticide resistance in
the cat flea (Siphonaptera: Pulicidae). J Econ Entomol 79:132–134, 1986.
monitoring team will do this by determining the LC50 (median 7. El-Gazzar LM, Patterson RS, Koehler PG: Comparisons of cat flea
lethal concentration) and LC95 of five laboratory strains of cat fleas (Siphonaptera: Pulicidae) adult and larval insecticide susceptibility. Fla
Entomol 71:359–363, 1988.
using a larval development inhibition test. In addition, the team 8. Rust MK: Insecticide resistance in fleas, in Knapp FW (ed): Intl Symp
will establish the range of LC50 and LC95 of the same five strains Ectoparasites of Pets. Lexington, KY, University of Kentucky, 1993, pp 18–26.
using an adult in vitro bioassay. Data from all laboratories will then

Suppl Compend Contin Educ Pract Vet Vol. 22, No. 4(A), 2000 International Flea Control Symposium