Spotlight on research: How residual speed of kill affects flea control in dogs and cats (Sponsored by Merck Animal Health)

Residual speed of kill: Understanding its importance in eliminating fleas from a household

When it comes to controlling flea infestations, one thing more important than the initial speed of kill of a flea adulticide is the residual speed of kill of the adulticide. That is, the adulticide's speed of kill throughout the entire treatment interval — on every day between the initial application of and retreatment with the product. The speed of kill and resulting efficacy of the product at the end of the treatment interval is likely more important than the product's efficacy at the start of treatment. If a flea adulticide loses significant speed of kill throughout the month after its application, it allows fleas to feed long enough that they could elicit an allergic reaction in pets and, if the fleas live for 24 hours, they could lay eggs that repopulate the environment.

Michael W. Dryden, DVM, MS, PhD, DAVCM (Parasitology)

To appreciate the differences in residual adulticide flea control treatments for dogs and cats, it's helpful to understand the experimental methods used in flea treatment studies. Two important, distinct evaluations of flea adulticides are initial speed of kill studies and residual speed of kill studies. 1-5 Initial speed of kill studies measure how quickly a flea adulticide kills fleas when it is first administered; these studies do not indicate the speed of flea kill of the product at other times during the treatment period. In contrast, residual speed of kill studies are more clinically relevant and provide flea kill information for the entire post-treatment interval.

In addition, a third type of study, which can be combined with a residual speed of kill study, is a reproductive breakpoint study. 6-9 This type of study measures whether a residual flea control treatment can prevent a flea population from maintaining itself.

In this Spotlight on Research, I will explain the different studies and discuss which results are most important in evaluating the efficacy of flea-control products.

Typical study protocols

Speed of kill studies of a product tend to follow the same pattern, whether they are designed to examine the time from product administration to statistically significant efficacy against resident fleas or the time to significant efficacy against newly arriving fleas. Efficacy of the product against fleas is calculated by comparing the number of fleas remaining on animals in a treated group compared with the number of fleas remaining on animals in a negative control group at preselected time points. Often a different group of treated animals and control animals is used for each of the preselected time points. Less commonly, repeated measurements are made using the same animals at the preselected time points.

Dr. Dryden’s viewpoint: The clinical relevance of speed of kill

The typical speed of kill experimental protocol involves these steps:

• Dogs or cats that are known to be good flea hosts are selected for inclusion in the study. Some individual animals are not good flea hosts, and including these animals in a study can bias the results.

• Animals in the control and treatment groups are initially infested with a known number of fleas before application of the product, so that the time to significant efficacy of a product can be determined. The day that the animals are treated is usually called Day 0.

• Live fleas are carefully counted on animals in the treatment and control groups at preselected time points (4, 8, 12, 24, and 48 hours; more or fewer time points can be chosen). Efficacy is calculated at each time point based on the number of live fleas on control animals compared with the number of live fleas on treated animals. This portion of the study gives an indication of how quickly a flea-infested animal becomes flea-free after the first product application. This is an initial speed of kill study and indicates the time to potential therapeutic efficacy of a flea product.

• At selected intervals thereafter (typically weekly) throughout the entire post-treatment period, control and treatment group animals are reinfested with a known number of new fleas, and the process of counting live fleas is repeated at each preselected time point (4, 8, 12, 24, and 48 hours; 12 and 24 hours or 24 and 48 hours are often selected because of cost constraints). For a monthly flea treatment, efficacy could be measured every week (on Days 0, 7, 14, 21, and 28) or possibly even beyond the monthly treatment interval. Because speed of kill typically slows with time, this portion of the study gives an indication of the time required to kill newly arriving fleas throughout the treatment period. For example, a flea treatment that kills 100% of fleas within eight hours on Day 7 post-treatment likely will not kill newly arriving fleas with the same speed 30 days later. This is the residual speed of kill portion of the study.

To get a true picture of flea treatment efficacy, you need to understand a few facts about the reproduction of the cat flea, Ctenocephalides felis. Cat fleas initiate feeding within seconds to minutes of acquiring a host, mate within the first 12 hours, and females typically start producing eggs at 24 hours post-infestation.10 These females will continue to produce eggs every day for several months, producing up to 40 eggs/day/female flea.11

Therefore, a topical or systemic flea treatment that has a rapid residual speed of kill, dispatching every flea within 24 hours, can prevent egg production. Preventing flea reproduction means that the environmental flea population load will steadily decrease.12 If a population cannot reproduce, it will go extinct within one generation. However, this rapid 24-hour kill rate must be maintained at 100% throughout the post-treatment period, otherwise fleas will survive and egg-laying will start. Then the only way a product can stop reproduction is if it also has ovicidal properties.7,9 If the reproduction inhibition drops below 100% before the 24-hour mark on any day during the treatment interval, then fleas will reproduce and will reseed the environment with eggs. A topical or systemic flea treatment succeeds or fails based on its ability to control or not control flea reproduction. If fleas can reproduce in spite of the flea treatment, then no amount of treating can ever eliminate fleas from the household.

Does the product prevent fleas from reproducing?

We evaluate a product's ability to prevent reproduction between treatment applications with a reproductive break point study. This study assesses the time following product administration when residual speed of kill slows sufficiently, or ovicidal activity drops below 100%, to allow viable egg production.7-9 In this study design, treated and control animals are reinfested with a known number of fleas at specific intervals after treatment (often weekly, such as on Day 7, 14, 21, 28, 35, or 42). Forty-eight to 72 hours after each reinfestation, researchers carefully collect and count any flea eggs falling from the treated and control animals. These eggs are then incubated to determine their viability, as indicated by the percentage of eggs emerging to adult fleas. Thus we can determine when efficacy of a residual flea adulticide drops below 100% within 24 hours of flea reinfestation and whether the product has additional ovicidal activity. The study identifies the approximate time post-treatment when viable flea eggs are first produced from fleas that reinfest treated animals. This time post-treatment is considered the reproductive break point.

Once the reproductive break point is passed, then the flea treatment will allow fleas to deposit viable eggs into the environment, thereby maintaining the local population. Counting fleas on these treated animals 48 or 72 hours post-infestation may still show excellent efficacy against adult fleas; however, this may be false assurance because the fleas may have laid eggs before dying and reinfested the environment, thus the flea problem will persist.

When evaluating the residual performance of a flea product, an effective product's reproductive break point will occur at some time point after the next labeled reapplication interval. If a product is labeled for once-a-month administration and the reproductive break point occurs around Day 21, then the product will probably not be effective in eliminating a flea infestation. Considering the results of a residual speed of kill and a reproductive break point study together gives the best indication of the real clinical efficacy of a flea treatment. A treatment that can control close to 100% of flea adults within 24 hours for the full duration of its treatment interval (as shown in a speed of kill study) and that also does not allow production of viable flea eggs within its treatment interval can be used to drive fleas to extinction in a household. This is because the treatment will not allow adult fleas to survive long enough to reproduce, and no new viable flea eggs are being added to the environment.

A recent reproductive break point study9 demonstrated that the data generated in the laboratory was then directly applicable in a field study in the high-challenge environment of Tampa, Fla.13 The reproductive break point of an indoxacarb-based flea adulticide product in the laboratory trial was well beyond the 30-day retreatment interval.9 When tested in a field trial, regular monthly applications of the product almost completely eliminated flea infestation on pets and in their home environments within 60 days.13

The use of a flea treatment that eliminates fleas within a household is still not quite the end of the story because there is always the possibility that fleas will be reintroduced into your client's household from flea populations on wildlife or from untreated households. As veterinarians, we need to persuade owners to routinely reapply an effective product at the recommended retreatment interval. In most locations, this needs to be continued year round. A treatment gap will allow fleas to reseed the environment with viable eggs.

Michael W. Dryden, DVM, MS, PhD, DAVCM (Parasitology), University Distinguished Professor of Veterinary Parasitology, Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas.

REFERENCES

1. Dryden MW, McCoy CM, Payne PA. Speed of kill with nitenpyram tablets, compared to imidacloprid spot-on and fipronil spot-on on dogs. Comp Cont Ed Pract Vet. 2001;23(3[A]):24-27.

2. Dryden MW, Smith V, Payne PA, et al. Comparative speed of kill of selamectin, imidacloprid, and fipronil–(s)-methoprene spot-on formulations against fleas on cats. Vet Ther 2005;6(3):228-236.

3. Blagburn BL, Young DR, Moran C, et al. Effects of orally administered spinosad (Comfortis) in dogs on adult and immature stages of the cat flea (Ctenocephalides felis). Vet Parasitol 2010; 168:312–317.

4. Dryden MW, Payne PA, Smith V, et al. Efficacy of imidacloprid + moxidectin and selamectin topical solutions against the KS1 Ctenocephalides felis flea strain infesting cats. Parasites & Vectors 2011;4:174.

5. Dryden MW, Payne PA, Vicki S, et al. Efficacy of topically applied dinotefuran formulations and orally administered spinosad tablets against the KS1 flea strain infesting dogs. Intern J Appl Res Vet Med 20111;9(2):123-128.

6. Payne PA, Dryden MW, Smith V, et al. Effect of 0.29% w/w fipronil spray on adult flea mortality and egg production of three different cat flea, Ctenocephalides felis (Bouche), strains infesting cats. Vet Parasitol 2001;102(4):331-340.

7. Dryden M, Payne P, Smith V. Efficacy of selamectin and fipronil/(s)-methoprene spot-on formulations applied to cats against the adult cat flea, Ctenocephalides felis, flea eggs and adult flea emergence. Vet Ther 2007;8(4):255-262.

8. Dryden M, Payne P, Lowe A, et al. Efficacy of a topically applied formulation of metaflumizone on cats against the adult cat flea, flea egg hatch and adult flea emergence. Vet Parasitol 2007;150:263-267.

9. Dryden MW, Payne PA, Smith V, et al. Efficacy of indoxacarb applied to cats against the adult cat flea, Ctenocephalides felis, flea eggs and adult flea emergence. Parasites & Vectors 2013;6:126. Available at: http://www.parasitesandvectors.com/content/6/1/126

10. Blagburn BL, Dryden MW. Biology, treatment and control of flea and tick infestations. Vet Clin N Am 2009;39(6):1173-1200.

11. Dryden M. Host association, on host longevity and egg production of Ctenocephalides felis. Vet Parasitol 1989;34:117-122.

12. Dryden MW. How you and your clients can win the flea control battle. Vet Med 2009;104(3, suppl):17-26.

13. Dryden MW, Payne PA, Smith V, et al. Evaluation of indoxacarb and fipronil (s)-methoprene topical spot-on formulations to control flea populations in naturally infested dogs and cats in private residences in Tampa FL. USA. Parasites & Vectors 2013;6:366. Available at http://www.parasitesandvectors.com/content/pdf/1756-3305-6-366.pdf

The views expressed are solely those of Dr. Dryden. Dr. Dryden received compensation for his time associated with this project and occasionally collaborates with Merck Animal Health.