Dr. Ray M. Kaplan

The primary research focus of my laboratory is to measure, understand, and solve the problems presented by drug-resistant parasites. Over the past forty years, the availability of cheap and effective anthelmintic drugs has led to an almost complete reliance on these chemicals for parasite control in animals. Chemical-based parasite control was extremely effective for many years, but we now know that this strategy has turned out to be shortsighted and unsustainable. Parasite drug resistance is now recognized globally as one of the greatest health threats to grazing livestock. Also, in recent years there has been a dramatic increase in the use of mass drug administration to reduce the morbidity associated with helminth infections of humans, raising the likelihood that anthelmintic resistance may become a public health concern in the near future.

To address this problem, my laboratory pursues research projects with four different areas of emphasis:

1. Measuring the prevalence of drug resistance
2. Studying the molecular basis of anthelmintic resistance
3. Developing in vitro and molecular diagnostic assays to detect emerging resistance in nematode populations
4. Studying and developing novel and sustainable approaches to parasite control that deemphasize chemical control

Over the past several years, a major focus of my research program has been the investigation of the molecular basis of anthelmintic resistance in cyathostomins (small strongyles) of horses. However, of current great interest to our laboratory is the impact of mass anthelmintic treatment programs for soil-transmitted helminths and for lymphatic filariasis on the selection for drug resistance. To address this interest we have initiated several projects to investigate the population biology and the molecular basis of anthelmintic resistance in the human parasites Brugia malayi, Ancylostoma duodenale and Necator americanus. Approaches we are using include targeted single gene studies as well as multi-gene studies using microarrays.

We are also involved in studies investigating novel and sustainable approaches to nematode parasite control in sheep and goats. This work is being conducted under the auspices of the Southern Consortium for Small Ruminant Parasite Control (www.scsrpc.org) in collaboration with a multi-disciplinary team of veterinarians, scientists, farmers and extension personnel from institutions throughout the southern United States as well as the University of Pretoria and the Onderstepoort Veterinary Institute in South Africa. One of the most promising approaches for the control of Haemonchus contortus is the FAMACHA© method for identifying anemic animals in need of treatment. Using this method, a selective treatment program can be instituted, which permits the maintenance of a large refugia, thereby reducing the selection pressure for resistance. FAMACHA© is having an immediate impact and is being warmly embraced by farmers. My laboratory, under the auspices of the Southern Consortium for Small Ruminant Parasite Control, is currently serving as the US distributor for the FAMACHA© anemia color cards (see www.scsrpc.org or contact for more information). Other control methods under study include the feeding of condensed tannin containing plants, the administration of copper wire particle boluses, and the feeding of nematophagous fungi (Duddingtonia flagrans) as a biological control agent.

Finally, our laboratory also maintains constant surveillance for the detection of new occurrences of anthelmintic resistance (and multiple-drug resistance) in parasites that have not been recognized previously to be drug-resistant (and/or multiple-drug resistant) in the U.S.

- Principal investigator for the NIH-funded Filariasis Research Reagent Resource Center
- Detection of anthelmintic resistance using in vitro assays
- Evaluation of nematocidal activity of experimental compounds using in vitro assays
- Statistical considerations in diagnosing anthelminitc resistance using fecal egg count reduction tests

- Drug-resistant parasites are maintained and data on many other drug-resistant field isolates are available
- Novel anthelmintic compounds in development must be tested for in vitro activity before conducting expensive in vivo studies
- Novel classes of anthelmintic compounds in development must be tested against drug-resistant isolates to be sure that there is no cross resistance