Monitoring flea susceptibility to imidacloprid (Sponsored by Bayer Healthcare)

Imidacloprid is still highly effective against both laboratory and field strains of Ctenocephalides felis, according to an international study that was initiated in 1999.1

In January 2008, the latest data were compiled by the International Flea Susceptibility Monitoring (IFSM) group.2 The IFSM group assayed C. felis larvae in the United States and in European countries from 2001 to 2007, and each time the results were the same—nearly all flea isolates assayed for susceptibility to imidacloprid did not survive Step 1 of the bioassay. The few flea eggs that survived to adulthood didn't survive the second step of the bioassay. A very small number of isolates that survived the first step of the bioassay never made it through the second step, a complete dose response assay.

The data on file with the IFSM group suggest that variations in the flea population, location, and compliance issues might contribute to increased client reports of perceived product failure.2 The IFSM group, which was formed in 1999, was charged to scientifically monitor the susceptibility of fleas to imidacloprid and dispel any misinformation that was being generated. They developed a method for monitoring the susceptibility of C. felis to imidacloprid and assayed its efficacy in a controlled laboratory environment. The results definitively show there was no reduced susceptibility of the assayed flea isolates to imidacloprid since the inception of the monitoring group.

Key Points

Purpose

A study was conducted to monitor the susceptibility of C. felis isolates to imidacloprid.

Methodology

From 2001 to 2007, 1150 flea egg isolates were collected and assayed in the United States and Europe. Clinic personnel took flea egg specimens from both dogs and cats in the United States, United Kingdom, and Germany (see Figure 1). Of the isolates collected, 909 contained a sufficient number of eggs to be included in the larval bioassay.

Figure 1. Hosts from which flea eggs were obtained*

Researchers let the eggs hatch, exposing the test group of larvae to flea-rearing media containing a diagnostic dose of imidacloprid. They monitored these larvae for 28 days, at which time live adult fleas in the treated and control groups were counted.

If on day 28 any isolate had adult fleas numbering 5% or more of the number of larvae assayed, the fleas were propagated on laboratory cats before being removed and utilized in Step 2 of the bioassay, a complete dose response test. If the number of surviving fleas in Step 2 was significantly higher than laboratory strains or field isolates, the flea isolate being assayed would be propagated further for evaluation (Step 3) using an in vivo challenge model on cats.

Results

Of the 909 flea isolates assayed through 2007, only 11 isolates had a survival rate of 5% or more. All 11 of these isolates progressed to Step 2, the complete dose response test. Adult survival of these isolates in Step 2 was not significantly different than the laboratory strains or field isolates. Additionally, none of these isolates progressed to Step 3 in the bioassay.

Since the IFSM has never found an isolate showing reduced susceptibility, it has actually never proven or disproven the presence of resistance of C. felis to imidacloprid. The study suggests that if resistance does actually occur, it appears very difficult to find.

Discussion

According to the IFSM,2 clients may develop a false impression about the efficacy of a particular flea-control product because they still see fleas after treatment. But in areas where and years when the flea population is high, these observations will likely occur even if a product is administered properly. A dog or cat could be treated effectively for a month and then contract fleas from an external source after treatment (e.g., from a backyard or another animal).

The IFSM group says the veterinary community should be cautious about presuming that perceived flea product failures are caused by reduced susceptibility. The IFSM group says the capability to identify and document susceptibility to flea-control products will provide for a better understanding of the molecular and biochemical basis of resistance. It also says similar susceptibility monitoring programs on other flea control products may be developed in the future.

References

1. Blagburn BL, Dryden MW, Payne P, et al. New methods and strategies for monitoring susceptibility of fleas to current flea control products. Vet Ther 2006;7:86-98.

2. Data on file, International Flea Susceptibility Monitoring Group, 2007.

From the expert

Byron L. Blagburn, MS, PhD, with Auburn University's College of Veterinary Medicine in Auburn, Ala., shares his opinions on the International Flea Susceptibility Monitoring study.

1. Why are this study's results useful for veterinarians?

Before the development of the procedures described in this study, veterinarians had no valid or convenient laboratory method to differentiate true flea resistance from other causes of perceived flea-control product failure. We have examined the susceptibility of hundreds of isolates of fleas. To date, we have not encountered a flea isolate from pets that we would characterize as resistant to imidacloprid. The study results do not guarantee that resistance to imidacloprid does not exist. However, they suggest that the frequency of resistance to imidacloprid in U.S. and European flea populations is very low—if it exists at all.

The results indicate that factors other than resistance are the cause of most product failure reports. Veterinarians should feel more comfortable knowing that we now have valid methods of monitoring the performance of flea-control products. Having these methods in place is an important first step in developing strategies for dealing with resistance—if or when it develops.

2. What can cause resistance to flea-control products?

Many misconceptions exist about how fleas develop resistance to flea-control products. Resistance actually develops naturally in a population of fleas by random mutation and recombination of genes during reproduction.

One of my favorite quotes regarding resistance is: "Somewhere in the world, a flea already exists that is resistant to a product that hasn't been developed yet." This statement effectively communicates that the development of resistant genes is a powerful and natural phenomenon. Many veterinarians and pet owners are not aware that flea-control products do not cause resistance—they select for resistant fleas over time. Stated differently, flea-control products kill what they can and leave what they can't. If the surviving resistant fleas breed successfully, the previously susceptible population becomes a resistant population over time by the selection process.

The development of a resistant flea population is dependent upon many circumstances: the number of fleas on the pet(s) and in the environment, their rate of reproduction, climatic conditions that favor flea survival and reproduction, prolonged exposure to flea-control products, the efficacy and mode of action of the products, and prior exposure of fleas to the class of insecticide contained in the products.

Many older products that contained organophosphates, carbamates, or chlorinated-hydrocarbon compounds were applied only to the environment that contained fleas in all life stages. Consequently, the likelihood that these products would select for resistant fleas—if they were present—was great. Newer flea-control products applied directly to dogs or cats generally target adult fleas. Because adult fleas represent only 5% of the total flea population, the process of selection would likely require more time.

3. If a client reports a flea-control product failure, what steps should veterinarians tell the client to take?

Almost all cases of perceived flea-control product failure are caused by something other than resistance. The first step to determine why a client reports failure is to review the medical records and ask questions. Does the problem involve just one pet or are multiple pets in the household? Are all of the pets being treated? Are the pets receiving the correct amount of product at the correct intervals? Is the client applying the product properly? Are the pets predominantly indoor, outdoor, or both? Do the pets swim or receive baths frequently? Do the pets have another dermatologic condition that requires topical therapy? Has the client observed the problem only recently or has it escalated over time? A few simple inquiries will usually identify the problem and give you direction.

Some practitioners believe that switching products might produce a more effective result. I usually do not recommend an immediate switch because doing so may result in a new set of compliance problems or subsequent questions about the new product. If the client was initially satisfied with the product, veterinarians should recommend switching to another product only after resistance has been proven via laboratory evaluation of fleas from the pet. The methods described in the imidacloprid study will continue to help us identify resistance and differentiate resistance from other product performance issues.