Managing parasite Threats Today

Supplement to Compendium: Continuing Education for Veterinarians Vol. 31, No. 8(A) August 2009 Managing parasite Threats Today Customized Solutions, Comprehensive Treatment

Copyright 2009, Bayer HealthCare LLC, Animal Health Division, Shawnee Mission, KS 66201 Bayer, the Bayer Cross, Advantage, K9 Advantix, Advantage Multi, Drontal, Profender, and Taste Tabs are registered trademarks of Bayer. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any electronic or mechanical means, by photocopying or recording, or otherwise without the prior permission of the copyright owner. Printed in USA. Images 2009 Carolina K. Smith/Shutterstock.com This information has not been peer reviewed and does not necessarily reflect the opinions of, nor constitute or imply endorsement or recommendation by, the Publisher or Editorial Board. The Publisher is not responsible for any data, opinions, or statements provided herein.

Dear Doctor: The threats associated with parasite infection continue to escalate. With tick distribution expanding into new geographic areas, veterinarians are now faced with tickborne diseases that may be new or unfamiliar to their region. As new evidence of feline heartworm disease emerges, practitioners are taking steps to prevent illness in their feline patients. Both ectoparasites and endoparasites continue to cause serious disease in animals, and they can pose serious zoonotic threats to pet owners as well. At Bayer Animal Health, we are committed to providing veterinary professionals with the most current scientific information on important, ongoing threats pertaining to parasitic infections. This publication is designed to bring you insights by leading authorities on contemporary issues that impact your patients and your practice. At the same time, we are dedicated to providing you with best-in-class therapies for the broad range of parasites you deal with on a daily basis. Through Bayer Parasite Solutions, we can provide you with customized solutions and comprehensive treatments and preventives for fleas, ticks, lice, heartworms, intestinal parasites, and more. Bayer products are supported by extensive research as well as hundreds of clinical studies, so you can be confident of the safety and efficacy of the products you recommend. As always, our goal is to help you educate pet owners about parasites and associated diseases, and we make a concerted effort to encourage regular and frequent veterinary visits to safeguard the health of pets. We appreciate our shared partnership with you and invite you to contact our Veterinary Technical Services Department at 800-422-9874 at any time with comments or questions regarding any of our unique parasiticides. Your feedback remains critical to our mission of providing unparalleled healthcare products for your patients. Sincerely, Cristiano von Simson, DVM Director of Veterinary Technical Services Bayer Animal Health Managing Parasite Threats Today 3

About Our Contributors Robert Allen Kennis, DVM, MS, DACVD Dr. Kennis received his DVM from Michigan State University in 1989. After 2 years in private practice, he returned to MSU for residency training in dermatology. He then moved to Oahu, Hawaii, to pursue private specialty practice. Three years later, he was recruited by Texas A&M University as a clinical instructor. While at A&M, he completed his MS in veterinary immunology. In September 2005, he moved to Auburn University, where he is currently an associate professor. Dr. Kennis has presented continuing education seminars at state, national, and international levels. He has also received several teaching awards, including the Norden Distinguished Teacher Award and the Texas A&M Association of Former Students Distinguished Achievement Award. His research interests include canine food allergy and feline bacterial infections. Edward Breitschwerdt, DVM, DACVIM Dr. Breitschwerdt is a professor of medicine and infectious diseases at the North Carolina State University College of Veterinary Medicine and adjunct professor of medicine at Duke University Medical Center. He was associate editor of the Journal of Veterinary Internal Medicine from 1986 to 1991 and served on the ACVIM Board of Regents from 1996 to 2001. He received the Excellence in Canine Research Award from the American Kennel Club in 1995 and appeared in the International Who s Who of Professionals in 1997. Dr. Breitschwerdt s research interests include infectious diseases and immunology, with an emphasis on vector-transmitted intracellular pathogens. He has published more than 130 articles in scientific journals. Byron L. Blagburn, MS, PhD In his role as Distinguished University Professor at the Auburn University College of Veterinary Medicine, Dr. Blagburn instructs veterinary students, directs graduate student research, heads the clinical parasitology diagnostic laboratory, and oversees a research program that focuses on the development of new pharmaceuticals directed against parasites and parasitic diseases of veterinary importance. He is past-president of several regional and national parasitology organizations and has served as editor and editorial board member for various veterinary journals. Dr. Blagburn is the author of more than 250 publications in scientific journals and has served as a speaker at more than 300 national or international meetings. Dwight D. Bowman, MS, PhD Dr. Bowman earned his PhD in parasitology from Tulane University and completed postdoctorate work on ocular larva migrans at the University of Wisconsin School of Veterinary Medicine. Currently, he is a professor of parasitology in the department of microbiology and immunology at Cornell University, where he has held successive positions since 1987. He has obtained continuous corporate and federal funding throughout his career to study animal parasitology. He has published more than 100 research papers in peer-reviewed journals and is the author of five textbooks, including Feline Clinical Parasitology. Dr. Bowman s research interests include soil-transmitted parasites, parasites of wildlife, and visceral larva migrans. 4 Supplement to VLS journals 2009 Kevin R. Kazacos, DVM, PhD Dr. Kazacos is a professor of veterinary parasitology and director of the clinical parasitology laboratory at the Purdue University School of Veterinary Medicine. There, he teaches veterinary and graduate students, oversees diagnostic work in parasitology, and conducts research on parasitic diseases of animals and humans. Dr. Kazacos has received various teaching, research, and faculty awards and is a founding member and past president of the Companion Animal Parasite Council (CAPC). He has done extensive research on zoonotic helminths that cause visceral, ocular, and neural larva migrans, particularly the raccoon ascarid Baylisascaris procyonis. Dr. Kazacos has published more than 120 research papers in scientific journals and nine book chapters or monographs and has given more than 550 presentations at scientific and professional meetings.

Table of Contents Alleviate Clinical Signs of Flea Bite Hypersensitivity Robert Allen Kennis, DVM, MS, DACVD...6 Prevention of Transmission of Ehrlichia spp Edward Breitschwerdt, DVM, DACVIM...8 Feline Heartworm Disease: Puzzling and Poorly Understood Byron L. Blagburn, MS, PhD... 10 Three Treatments Needed to Eliminate Whipworm Infections Dwight D. Bowman, MS, PhD... 12 Feline Tapeworms: Difficult to Diagnose, Easy to Treat Kevin R. Kazacos, DVM, PhD... 14 Bayer Parasite Solutions: Customized Comprehensive Parasite Programs for Each of Your Patients... 16 Product Information Summaries... 17 Managing Parasite Threats Today 5

Alleviate Clinical Signs of Flea Bite Hypersensitivity Robert Kennis, DVM, MS, DACVD Associate Professor of Dermatology Auburn University College of Veterinary Medicine Flea bite hypersensitivity (FBH), also known as flea allergy dermatitis, is the most common allergic skin disease in dogs in climates that are conducive to fleas. 1 While cats are also affected by FBH, the true prevalence in cats is unknown. Antigens in flea saliva are the primary causative agents of this pruritic condition in flea-sensitive dogs and cats. For these patients, inhibition of flea feeding and elimination of the antigen source are critical to the prevention and resolution of FBH. Pathogenesis and Clinical Signs Once on the animal, fleas bite quickly. Studies show that more than 97% of fleas are engorged within 1 hour of being placed on the host. 2 Antigenic and inflammatory components in flea saliva, transferred during flea bites, trigger an immune response in sensitive animals, ranging from immediate to delayed hypersensitivity reactions. 1 As a result, pets experience pruritus, which leads to scratching, licking, chewing, trauma-induced alopecia, and excessive grooming. Dogs with FBH typically present with papules or crusts. Lesions are commonly found on the back half of the body, including the dorsal lumbosacral area, ventral abdomen, caudomedial thighs, and flanks. Chronic pruritus can lead to Imidacloprid alleviates FBH signs in dogs* Signs of FBH decreased after imidacloprid treatment, study shows 5 Percentage 100-90- 80-70- 60-50- 40-30- 20-10- 0-0 1 14 21 28 DAYS AFTER TREATMENT SIGNS Absent Mild Moderate Severe *FBH in 688 dogs from multiple-animal households. 6 Supplement to VLS journals 2009 alopecia, hyperpigmentation, pyotraumatic dermatitis ( hot spots ), and secondary bacterial or yeast infections. Atopic dogs may be predisposed to FBH. 1 Cats with FBH may present with crusted papules (miliary crusting dermatitis) in the dorsal lumbosacral area, face and neck, caudomedial thighs, ventral abdomen, and flanks. Excessive grooming may lead to symmetric trauma-induced alopecia. Eosinophilic granuloma complex lesions may also occur. Not All Products Require Feeding While there are many treatments that help eliminate fleas, some products require fleas to bite and ingest the insecticide in order to be killed. Imidacloprid works differently. As a neonicotinoid insecticide, imidacloprid penetrates the intersegmental membranes of the flea on contact, behaving as an agonist at the postsynaptic nicotinic acetylcholine receptor sites on the insect s motor neurons. The net effect is neuronal hyperstimulation and rapid death of the flea without feeding and ingestion of the chemical being required. An in vivo study showed that on dogs treated with imidacloprid, fleas stopped feeding within 3 to 5 minutes and died within an hour of exposure. 3 In another study comparing the speed of kill of selamectin, imidacloprid, and fipronil (S)-methoprene spot-on formulations in cats, only imidacloprid demonstrated a significant reduction in adult fleas on treated cats versus untreated controls within 6 hours of initial application. 4 Imidacloprid Reduces Clinical Signs of FBH In a field study, 688 of the dogs and 323 of the cats in multiple-pet households had FBH. A single topical treatment of imidacloprid was shown to significantly reduce the clinical signs of FBH in these dogs and cats. 5 Within days of treatment, there was a rapid improvement in clinical signs. By the end of the study, only 7.8% of these dogs and 5.1% of these cats showed signs of FBH. Another study showed that topical use of imidacloprid markedly reduced the clinical signs of FBH in cats. 6 Twenty-two cats were treated with a topical formulation of imidacloprid every 28 days for 3 months. During the study, total scores for each clinical sign fell dramatically. Pruritus severity scores dropped by 68% within the first 2 weeks of the study and by 94% by the end of the study. Signs of miliary dermatitis improved by 38% within 2 weeks and were

In a field study, a single topical treatment of imidacloprid was shown to significantly reduce the clinical signs of FBH in dogs and cats in multiple-pet households. 5 Imidacloprid alleviates FBH signs in cats Signs of FBH markedly reduced during 3-month study 6 % CATS WITH MODERATE/SEVERE FBH SIGNS 100-90- 80-70- 60-50- 40-30- 20-10- 0- SIGNS 0* Adult fleas Moist dermatitis *Treatment administered on these days. 14 28* DAYS of study Flea excreta Alopecia Pruritus Papules 56* 84* Miliary dermatitis Eosinophilic granuloma virtually eliminated by day 84. Secondary signs of erythema, moist dermatitis, maculae, and eosinophilic granuloma complex were completely resolved by the end of the study. Use of imidacloprid before flea season may help reduce clinical signs of FBH and decrease or eliminate the need for adjunct anti-inflammatory therapy. 6 References 1. Scott DW, Miller WH Jr, Griffin CE. Skin immune system and allergic skin diseases. In: Scott DW, Miller WH Jr, Griffin CE, eds. Muller & Kirk s Small Animal Dermatology. 6th ed. Philadelphia: WB Saunders; 2001:543-566. 2. Cadiergues MC, Hourcq P, Cantaloube B, Franc M. First bloodmeal of Ctenocephalides felis felis (Siphonaptera: Pulicidae) on cats: time to initiation and duration of feeding. J Med Entomol 2000;37(4):634-636. 3. Mehlhorn H. Mode of action of imidacloprid and comparison with other insecticides (i.e., fipronil and selamectin) during in vivo and in vitro experiments. Compend Contin Educ Pract Vet 2000;22(suppl 4A):4-8. 4. Dryden MW, Smith V, Payne PA, McTier TL. 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. 5. Genchi C, Traldi G, Bianciardi P. Efficacy of imidacloprid on dogs and cats with natural infestations of fleas, with special emphasis on flea hypersensitivity. Vet Ther 2000;1(2):71-80. 6. Keil K, Wellington J, Ciszewski D. Efficacy of Advantage in controlling flea allergy dermatitis in cats. Compend Contin Educ Pract Vet 2002;24(suppl 4B):6-9. 7. Rust MK. Advances in the control of Ctenocephalides felis (cat flea) on cats and dogs. Trends Parasitol 2005;21(5):232-236. Advantage : The Flea Specialist advantage offers fast speed of kill: Fleas are killed on contact and don t need to bite to die. Systemic treatments, such as spinosad, require fleas to bite in order to ingest insecticide and die. On dogs treated with Advantage, fleas stopped feeding within 3 to 5 minutes. 3 advantage is gentle enough for puppies as young as 7 weeks and kittens as young as 8 weeks of age. Multiple studies have shown that Advantage is proven to reduce the clinical signs of FBH. 5 7 Your Patients, Your Choice Dosing form Indications Age restrictions Mode of action Imidacloprid Topical Prevents and treats flea infestations on dogs and cats Kills adult fleas on dogs and cats and flea larvae in pet s environment Treats and prevents lice on dogs Puppies 7 weeks and older Kittens 8 weeks and older Acts on contact (e.g., skin, hair) Fleas do not have to bite to die Acts as an agonist on insect postsynaptic nicotinic acetylcholine receptors of motor neurons Spinosad Chewable tablet Prevents and treats flea infestations on dogs Kills adult fleas on dogs Puppies 14 weeks and older Acts systemically (e.g., biting) Fleas have to ingest a blood meal to be killed Primary target of action in insects is activation of nicotinic acetylcholine receptors (DOGS ONLY) Managing Parasite Threats Today 7

Prevention of Transmission of Ehrlichia spp Edward Breitschwerdt, DVM, DACVIM Professor of Medicine and Infectious Diseases North Carolina State University While at least three Ehrlichia species E. canis, E. chaffeensis, and E. ewingii can infect dogs and humans in North America, 1 E. canis produces the most common and severe form of ehrlichiosis in dogs. 2 However, the latter two species may become more important than in the past due to the expanded geographic distribution of Amblyomma americanum, the principal vector of E. chaffeensis and E. ewingii. E. chaffeensis and E. ewingii typically produce mild disease in dogs, but more serious signs, such as epistaxis and anterior uveitis with E. chaffeensis 3 and acute polyarthropathy and meningitis with E. ewingii, 4,5 have been documented. Simultaneous infection with multiple Ehrlichia spp, or other tickborne organisms, may cause more serious disease. Of equal importance, E. chaffeensis is the primary cause of human monocytic ehrlichiosis, and E. ewingii has been linked to human granulocytic ehrlichiosis. 6 While transmission between dogs and people is not known to occur, veterinarians should recognize the possibility for human infection and realize that dogs may serve as a disease reservoir or may carry infective ticks into the home environment. The judicious use of effective acaricides, with knockdown effect and fast speed of kill to prevent tick attachment and feeding, is an important means of preventing disease transmission to our canine patients. Ehrlichiosis found throughout US* Transmission and Pathogenesis Currently, the most common form of canine ehrlichiosis, canine monocytotropic ehrlichiosis, is caused by E. canis. Unless diagnosed and treated early, infection can lead to chronic, insidious, and fatal disease in dogs. E. canis is transmitted in tick saliva when the brown dog tick, Rhipicephalus sanguineus, ingests a blood meal. In experimental studies, Dermacentor variabilis, the American dog tick, has also been shown to transmit the etiologic agent between dogs. 7 During the incubation period, which lasts 8 to 20 days, 8 the gram-negative organisms invade mononuclear cells and are disseminated to peripheral tissues. The infection provokes inflammatory and immune responses leading to hematologic abnormalities, most commonly thrombocytopenia, which can be found in all phases of the disease. Clinical Signs and Laboratory Abnormalities Clinically, canine monocytotropic ehrlichiosis is a multisystemic disorder that occurs in three phases. During the acute phase, which lasts 2 to 4 weeks, dogs may present with fever, anorexia, depression, oculonasal discharge, lymphadenopathy, petechiae, and ecchymoses. 8 Laboratory abnormalities may include thrombocytopenia, mild anemia, and mild leukopenia. When diagnosed early, and with proper treatment, most dogs recover. In the subclinical phase, which can last for months to years, dogs may appear clinically normal. Some dogs may eliminate the rickettsiae, or they may become carriers. Laboratory tests may reveal thrombocytopenia, anemia, hyperglobulinemia, or no abnormalities. During the chronic phase, dogs may show mild or severe signs. In severe cases, bone marrow suppression leads to pancytopenia. 8 Dogs may present with hemorrhagic disorders, anemia, ocular signs (anterior uveitis, retinal detachment), and central nervous system signs (ataxia, seizures). 8 In addition to hematologic abnormalities, laboratory tests may reveal hyperglobulinemia. The prognosis is grave in these patients, and dogs often die due to uncontrolled bleeding or secondary infections. 8 NUMBER OF REPORTED CASES OF EHRLICHIOSIS 500+ 251 500 101 250 1 100 No reported cases Reported positives from more than 10,000 veterinary clinics, telephone surveys, and Idexx Reference Laboratories results from 2001 to March 2007. *For more details, including county-level data, visit dogsandticks.com/us-map-lyme-disease-dogs. Prevention of Disease Transmission In a recent study, the spot-on formulation of imidacloprid 10%/permethrin 50% was shown to be effective at preventing the transmission of E. canis under natural conditions in tick-endemic areas. 9 8 Supplement to VLS journals 2009

The judicious use of effective acaricides is an important means of preventing disease transmission to our canine patients. The study included 535 kennel-confined dogs that tested negative for E. canis by serology and PCR. Dogs were randomized to one of three groups: Group A was treated with the topical formulation once a month; group B was treated with the topical formulation every 2 weeks; and group C consisted of untreated control dogs. During the 14-month study, dogs were monitored at 9 and 13 months for E. canis infection by serology and PCR. By the end of the study, 26 dogs in the untreated control group tested positive for E. canis. No dogs in group A tested positive, and one dog in group B tested positive. The protective efficacy for the imidacloprid 10%/permethrin 50% formulation was 100% and 95.57% for groups A and B, respectively. This study reinforces the importance of effective acaricides to prevent transmission of tickborne disease in regions where dogs are at risk. References 1. Walker DH. Rickettsiae and rickettsial infections: the current state of knowledge. Clin Infect Dis 2007;45(suppl 1):S39-S44. 2. Stich RW, Schaefer JJ, Bremer WG, et al. Host surveys, ixodid tick biology and transmission scenarios as related to the tick-borne pathogen, Ehrlichia canis. Vet Parasitol 2008;158:256-273. 3. Breitschwerdt EB, Hegarty BC, Hancock SI. Sequential evaluation of dogs naturally infected with Ehrlichia canis, Ehrlichia chaffeensis, Ehrlichia equi, Ehrlichia ewingii, or Bartonella vinsonii. J Clin Microbiol 1998;36(9):2645-2651. 4. Cowell RL, Tyler RD, Clinkenbeard KD, Meinkoth JH. Ehrlichiosis and polyarthritis in three dogs. JAVMA 1988; 192(8):1093-1095. 5. Maretzki CH, Fisher DJ, Greene CE. Granulocytic ehrlichiosis and meningitis in a dog. JAVMA 1994;205(11):1554-1556. 6. Buller RS, Arens M, Hmiel SP, et al. Ehrlichia ewingii, a newly recognized agent of human ehrlichiosis. N Engl J Med 1999;341:148-155. 7. Johnson EM, Ewing SA, Barker RW, et al. Experimental transmission of Ehrlichia canis (Rickettsiales: Ehrlichieae) by Dermacentor variabilis (Acari: Ixodidae). Vet Parasitol 1998;74(2-4):277-288. 8. Greene CE. Ehrlichiosis, neorickettsiosis, anaplasmosis, and Wolbachia infection. In: Greene CE, ed. Infectious Diseases of the Dog and Cat. 3rd ed. Philadelphia: WB Saunders Elsevier; 2006:203-232. 9. Otranto D, Paradies P, Testini G, et al. Application of 10% imidacloprid/50% permethrin to prevent Ehrlichia canis exposure in dogs under natural conditions. Vet Parasitol 2008;153:320-328. 10. Dryden MW, Payne PA, Smith V, Hostetler J. Evaluation of an imidacloprid (8.8% w/w)-permethrin (44.0% w/w) topical spot-on and a fipronil (9.8% w/w)-(s)-methoprene (8.8% w/w) topical spot-on to repel, prevent attachment, and kill adult Rhipicephalus sanguineus and Dermacentor variabilis ticks on dogs. Vet Ther 2006:7(3):187-198. K9 Advantix : Repels and Kills Ticks K9 Advantix repels and kills ticks, including: - Brown dog ticks (vector of ehrlichiosis) - Lone star ticks (vector of ehrlichiosis) - Deer ticks (vector of Lyme disease and anaplasmosis) - american dog ticks (vector of Rocky Mountain spotted fever) a repelled tick doesn t bite. If a tick doesn t bite, it can t transmit disease-causing pathogens. With K9 Advantix, a repelled tick quickly dies. 10 K9 Advantix is supported by well over 100 Bayer-sponsored and third-party studies outlining target animal safety, efficacy, and chemistry. K9 Advantix : 5-Way Repel-and-Kill Pest Protection Repels fleas Kills fleas Repels ticks Kills ticks Repels mosquitoes Kills mosquitoes Repels biting flies Prevents and kills lice Managing Parasite Threats Today 9

Feline Heartworm Disease: puzzling and poorly understood Byron L. Blagburn, MS, PhD Distinguished University Professor Auburn University College of Veterinary Medicine Despite recent research, improved diagnostic tests, and increasing reports of feline heartworm disease, many veterinarians remain skeptical of the prevalence of heartworm in cats. Skepticism is fueled by reports that many veterinarians have not diagnosed a case of feline heartworm infection. The fewer confirmed cases can be explained by the differences between heartworm infections in cats and dogs. 1 3 Feline Heartworm: A Difficult Diagnosis Infected cats usually harbor few adult heartworms. Fewer worms in cats often result in male-only infections or too few female worms to trigger a positive antigen test. Because mature female heartworms are smaller in cats, antigen tests are more likely to be negative. In addition, recent research has confirmed that heartworm-infected cats may develop respiratory disease without developing adult heartworms. These cats, although suffering from heartworm-induced disease, will always test negative with antigen tests and many times with antibody tests as well. Consequently, positive antibody tests cannot confirm that asymptomatic cats are infected with heartworms or that heartworms are responsible for the clinical signs in a symptomatic cat. To add even more confusion, neither the hemogram/ chemistry panel nor pulmonary radiographic lesions are specific for feline heartworm disease. Also, lesions and clinical signs in heartworm-infected cats may be similar to those of other allergic (e.g., feline asthma), infectious, or parasitic diseases. 4 Although echocardiography can confirm infections, ultrasonographic detection of adult heartworms in cats depends on the size and location of the worm(s) and the skill of the ultrasonographer. Because confirming feline heartworm infection is difficult, many cases remain undiagnosed. This leads to underdiagnosis and difficulty in establishing true prevalence. We now know that feline heartworm infections occur wherever canine heartworm infections occur. However, veterinarians often cannot document the risk of feline infection in their practice areas and may be reluctant to recommend heartworm prevention in cats. A Currently, less than 5% of cats in the United States are given heartworm preventives. 5 The 3-Month Feline Heartworm Disease Cycle and HARD In cats, most immature adult worms arrive in the lungs 70 to 90 days after infection. However, because of the cat s unique pulmonary response, most of these immature adult worms are killed in the lungs and do not survive to the adult stage. The intense inflammation caused by the death of these immature adult heartworms results in respiratory disease characterized by coughing and dyspnea. Because these signs correspond to the death of these worms about 90 days after infection, resulting disease is referred to as the 3-month disease cycle. 6 Figure 1. Histopathology sections of alveoli from cats exposed to heartworms. (A) A cross section of healthy alveolar tissue from a cat on heartworm preventive medication. (B) Alveoli from a cat with an abbreviated juvenile heartworm infection. Lesions include interstitial hypertrophy and diffuse inflammation. Similar lesions of comparable severity are found in cats with mature heartworm infection. (Courtesy of Drs. Byron Blagburn and Ray Dillon, Auburn University, Alabama) B In a laboratory model of feline heartworm disease, Blagburn and Dillon reproduced the 3-month disease cycle. 4,7 They did so by strategically treating experimentally infected cats to eliminate 70- to 90-day-old heartworms. Results demonstrated that experimentally induced death of immature adult heartworms in the lungs can cause clinical disease identical to the naturally occurring 3-month disease. This syndrome was named heartworm-associated respiratory disease (HARD) to demonstrate the potential for immature heartworms to cause severe respiratory disease and to Events in the heartworm life cycle in cats 1 2 3 4 5 6 7 L3 larvae are deposited by a mosquito. The L3 larvae molt to L4 larvae (1 to 3 days) in subcutaneous tissues. The L4 larvae molt to immature adult heartworms (50 to 70 days) during migration to the heart. The immature adult heartworms arrive in the heart (70 to 90 days) and are carried with the cardiopulmonary blood flow to the main pulmonary arteries of the lungs. Many immature adults die (90 to 180 days), inciting pulmonary signs and lesions the 3-month disease cycle. A small number of immature heartworms mature to adult heartworms in the lungs and heart. Adult heartworms die, inciting pulmonary signs and lesions the 6-month or longer disease cycle. 10 Supplement to VLS journals 2009

Advantage Multi for Cats : Heartworm Prevention and Much More Inflamed, edematous feline lungs secondary to heartworm infection. (Courtesy of Dr. Ray Dillon, Auburn University, Alabama) illustrate that HARD can be similar clinically and radiographically to other feline respiratory diseases. In a study in naturally infected shelter cats, Browne and colleagues 8 obtained antigen, antibody, necropsy, and histopathologic results that correlated well with test results in the laboratory HARD study. 8 The similarities in the two studies indicate that experimentally induced HARD is similar to the 3-month disease cycle in naturally infected cats. These studies should alert veterinarians that feline heartworm disease is often difficult to diagnose and that even early disease can cause serious disease or death. Occasionally, heartworms do mature to adult worms in the heart and lungs of cats. These cats will likely remain asymptomatic until the adult worms die. Their death can trigger a severe response consisting of coughing, dyspnea, vomiting, and even sudden death. Elimination of adult heartworms using adulticidal strategies practiced in dogs is not recommended in cats. 9 Also, specific therapies for HARD are unknown at this time. Consequently, cats suffering from death of adult heartworms and/or HARD can only be treated symptomatically with oxygen, glucocorticoids, bronchodilators, fluid therapy, and thermal support. Even with adequate emergency care, it is expected that 10% to 20% of cats with symptomatic heartworm infections will die from their respiratory complications. 10 The availability of convenient broadspectrum preventives for cats can eliminate heartworm risks and provide the benefits of additional internal and external parasite control. Both the American Heartworm Society and the Companion Animal Parasite Council recommend heartworm prevention in cats. References 1. Litster AL, Atwell RB. Feline heartworm disease: a clinical review. J Feline Med Surg 2008;10(2):137-144. 2. Atkins C. Feline heartworm disease. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. 6th ed. St. Louis: Elsevier; 2005:1137-1144. 3. Mannella C, Donoghue AR. Feline heartworm disease: facts and myths. Vet Forum 1999;16:50-65. 4. Blagburn BL, Dillon AR. Feline heartworm disease: solving the puzzle. Vet Med 2007;102(3 suppl):7-14. 5. Pfizer Animal Health. Independent market research; 2005. 6. Dillon R. Feline heartworm disease: assessing the danger for owners. In: DVM Best Practices. DVM Newsmagazine 2003;34(suppl):23-26. 7. Dillon AR, Blagburn BL, Tillson DM, et al. Immature heartworm infection produces pulmonary parenchymal, airway, and vascular disease in cats [abstract #133]. J Am Vet Int Med 2007;21:608-609. 8. Browne LE, Carter TD, Levy JK, et al. Pulmonary arterial disease in cats seropositive for Dirofilaria immitis but lacking adult heartworms in the heart and lungs. Am J Vet Res 2005;66(9):1544-1549. 9. Nelson CT. Dirofilaria immitis in cats: diagnosis and management. Compend Contin Educ Pract Vet 2008;30(7):393-400. 10. Genchi C, Venco L, Ferrari N, et al. Feline heartworm (Dirofilaria immitis) infection: a statistical elaboration of the duration of the infection and life expectancy in asymptomatic cats. Vet Parasitol 2008;158:177-182. 11. Freedom of Information Summary. NADA 141-254, Advantage Multi for Cats. Advantage Multi for Cats is 100% effective in the prevention of heartworm disease, as seen in clinical trials. 11 Advantage Multi for Cats also kills adult fleas and treats and controls hookworms and roundworms. After five consecutive monthly treatments, Advantage Multi for Cats provides continuous control of hookworms with continued monthly use. Advantage Multi for Cats treats ear mites with one topical dose. Monthly use will control any subsequent ear mite infestations. 11 capc recommends that cat owners use a monthly broad-spectrum heartworm preventive year-round. the convenient topical application of Advantage Multi for Cats helps improve owner compliance with recommended treatment. Indications Parasite Species Activity Against Heartworms Dirofilaria immitis Migrating Larvae (L3 and L4) Fleas Ctenocephalides felis Adults Flea Infestations Intestinal Stages Adults/ L4 Larvae Roundworms Toxocara cati Hookworms Ancylostoma tubaeforme Ear mites Otodectes cynotis Adults Immature Adults Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian. Do not use on sick, debilitated, or underweight cats. Avoid oral ingestion. Do not use on cats younger than 9 weeks of age or less than 2 lb body weight. Children should not come in contact with the application site for 30 minutes after application. Please refer to the label section for full prescribing information. Managing Parasite Threats Today 11

Three Treatments Needed to Eliminate Whipworm Infections Dwight Bowman, MS, PhD Professor of Parasitology Cornell University College of Veterinary Medicine A lthough whipworms are often overlooked parasites of dogs, a recent study reports the average national prevalence of whipworms as 20.5%. 1 It s common for dogs of all ages to be affected by whipworms, according to a national survey of shelter dogs, and older dogs are nearly as susceptible to infection as younger dogs. 2 Still, dogs often go untreated not only because they may be asymptomatic, but also because Trichuris vulpis eggs are difficult to detect on traditional fecal flotation exams. Even with a positive fecal exam, a single treatment may not be enough. Whipworms have a lengthy prepatent period, which means that larvae not susceptible to treatment may continue to develop, leading to chronic infection. As a result, three treatments are recommended to completely eliminate the infection. Pathogenesis and Disease Unembryonated whipworm eggs are passed in the feces and become infective in as few as 9 days under ideal environmental conditions. 3 These eggs are resistant to temperature extremes and ultraviolet radiation, and they can persist in the environment for years, serving as a source for reinfection. Dogs become infected with whipworm by ingesting infective eggs from the soil, usually during grooming or by ingesting soil-contaminated objects. The larvae hatch in T. vulpis national prevalence over 20%, highest in Southeast 1 West 6.1% Midwest 14.1% Northeast 19.5% the intestine and penetrate the intestinal mucosa, eventually making their way to the cecum and, when present in larger numbers, the colon. After a long prepatent period (74 to 90 days), 3 females may produce 4,000 to 8,000 eggs per day. 4 Adult whipworms can live for years, consuming blood, mucosal epithelium, and tissue fluids. 3 While some whipworm-infected dogs may be asymptomatic, others may experience intermittent large bowel diarrhea with mucus and blood. Heavy infection may lead to severe and bloody diarrhea, anemia, dehydration, weight loss, and, rarely, death. 3 Diagnosis: Centrifugal Flotation Is Best Whipworm infections are diagnosed based on history, clinical signs, and the presence of eggs on fecal exam. However, the thick-shelled, double-operculated eggs do not float as readily as other common nematode eggs, so they re easy to miss on standard fecal flotation. For this reason, sugar flotation solution, with a specific gravity of 1.27 to 1.33, is recommended over lighter solutions such as zinc sulfate or sodium nitrate, with specific gravities of 1.2. 5 Centrifugal flotation is the diagnostic technique of choice. In a study by Dryden et al, 5 centrifugal flotation with sugar solution consistently recovered more whipworm eggs than the stationary flotation method and required less time. Even if a solution with the appropriate specific gravity is used with standard flotation, examining the coverslip before the sample has been allowed to stand for 15 minutes can result in a missed diagnosis of T. vulpis. 5 The direct smear method also showed dismal results, with false-negative results occurring 92.61% of the time. 5 Other factors may make fecal exams problematic. With light infections, adult worms may produce eggs intermittently and in small numbers. The prolonged prepatent period also means that dogs may show clinical signs before eggs are shed in feces. 3 Southeast 28.1% PREVALENCE RATE Moderate High Treatment: Now, in 3 Weeks, and in 3 Months Two common treatments for whipworm infection are febantel, formulated with praziquantel and pyrantel, and fenbendazole. Because of the extended prepatent period for T. vulpis, the Companion Animal Parasite Council (CAPC) recommends an initial treatment followed by treatments 3 weeks and 3 months later. Periodic fecal exams may be necessary because of the prolonged viability of infective eggs in the environment. 12 Supplement to VLS journals 2009

Because of the extended prepatent period for T. vulpis, CAPC recommends an initial treatment followed by treatments 3 weeks and 3 months later. Whipworms: Cycle begins when dog ingests infective eggs Dog ingests infective eggs from the soil or vegetation. Whipworms mature in the intestine. Drontal Plus: The Most Trusted, Broad-Spectrum Dewormer for Dogs 6 Drontal Plus provides up to 94% efficacy against T. vulpis in a single dose 7 Drontal Plus offers 100% efficacy against four species of tapeworms: 7 - Echinococcus multilocularis - Echinococcus granulosus - Taenia pisiformis - Dipylidium caninum Drontal Plus is also up to 99.7% effective against Toxocara canis and up to 100% effective against Ancylostoma caninum. 7 To treat whipworms as they emerge during the prepatent period, the industry-standard protocol 8 includes 3 monthly doses of an anthelmintic indicated for T. vulpis. Follow-Up Follow-Up Dosing in 3 Dosing in 3 Product Initial Dose Weeks Months Whipworm eggs can remain infective in the environment for several years. Eggs are shed in feces, contaminating the environment. Eggs in the environment become infective in 1 month. Fenbendazole Day 1 Day 2 Day 3 Day 1 Day 2 Day 3 Day 1 Day 2 Day 3 References 1. Blagburn BL. National parasite prevalence survey: an interim report. Proc NAVC 2009;26:1168-1171. 2. Blagburn BL, Lindsay DS, Vaughan JL, et al. Prevalence of canine parasites based on fecal flotation. Compend Contin Educ Prac Vet 1996;18(5):483-509. 3. Companion Animal Parasite Council. CAPC Recommendations: Intestinal Parasites: Nematodes: Whipworms. Available at: www.capcvet. org/recommendations/whipworms.html. Accessed 5/29/09. 4. Campbell BG. Trichuris and other trichinelloid nematodes of dogs and cats in the United States. Compend Contin Educ Pract Vet 1991;13(5):769-773, 776-778. 5. Dryden MW, Payne PA, Ridley R, Smith V. Comparison of common fecal flotation techniques for the recovery of parasite eggs and oocysts. Vet Ther 2005;6(1):15-28. 6. Bayer Animal Health. Data on file. 7. Freedom of Information Summary. NADA 141-007, Drontal Plus Broad Spectrum Anthelmintic Tablets. 8. Bowman DD. Georgis Parasitology for Veterinarians. 9th ed. Philadelphia: Saunders Elsevier; 2008:225. Federal (U.S.A.) law restricts this drug to use on or by the order of a licensed veterinarian. Drontal Plus is not for use in puppies less than 3 weeks of age or weighing less than 2 lb. Do not use in pregnant animals. Of 40 dogs treated with Drontal Plus Taste Tabs, two dogs vomited and two had diarrhea. Dogs given up to 5x the label dosage for 3 consecutive days had doserelated vomiting and loose stools. Please refer to the label section for full prescribing information. Managing Parasite Threats Today 13

Feline Tapeworms: Difficult to Diagnose, Easy to Treat Kevin R. Kazacos, DVM, PhD Professor of Veterinary Parasitology Purdue University School of Veterinary Medicine Feline tapeworm infections are challenging to diagnose on fecal flotation. Adult tapeworms shed segments intermittently, and proglottids are not evenly distributed in fecal material. Unless a segment has ruptured, eggs won t appear on fecal flotation, leading to false-negative results. Consequently, fecal flotation is not a reliable screening method for tapeworm infections in cats. More often than not, the diagnosis is made by finding proglottid segments on the perineum. The elusive nature of tapeworm segments and eggs may explain why the reported prevalence of feline tapeworm infections ranges from 1.8% to 52.7%. 1 Data based on fecal flotation probably underestimate the true prevalence of tapeworm infections in cats. shed in cat feces as early as 2 weeks post-infection. For Taenia spp, the prepatent period is about 5 to 6 weeks. Clinical Signs, Zoonotic Risks Infected cats may be asymptomatic unless large numbers of tapeworms are present. Heavy infections in kittens may result in constipation or diarrhea. Occasionally, cats may groom the perineum excessively as a result of anal irritation caused by passing segments. In general, the zoonotic risk to humans is relatively low. People can become infected with Dipylidium by accidental ingestion of a flea containing infective larvae. Children are most at risk and may show nonspecific signs of gastrointestinal disturbance and perianal irritation if infected. Infected by Intermediate Hosts The most common tapeworms in cats are Dipylidium caninum and Taenia taeniaeformis. Cats are infected when they ingest infective intermediate hosts, either fleas (D. caninum) or rodents (T. taeniaeformis). Once the intermediate host is digested, the infective larval stages are released into the intestine. At this point, they attach to the wall of the small intestine and form proglottids. In the case of D. caninum, gravid segments may be Dipylidium caninum life cycle 5) Cats pass adult tapeworm segments containing tapeworm eggs into the environment. 4) Tapeworms grow to maturity within the cat s intestinal tract. 1) Flea larvae ingest tapeworm eggs found in the environment. 14 Supplement to VLS journals 2009 3) Cat eats flea containing tapeworm larvae. 2) A tapeworm embryo emerges from the egg inside the flea and forms a larva. Diagnostic Considerations Diagnosis of tapeworm infection can be made by finding proglottids on the animal s perineum or in its feces or bedding. Specific identification is made by examining proglottids and/or eggs microscopically. Dipylidium segments taper slightly at both ends, have a genital pore on each side, and contain many packets of eggs. Taenia proglottids, on the other hand, are stouter, wider at the posterior end, and have a single lateral genital pore and a characteristically branched uterus containing individual eggs. On fecal flotation, packets containing 5 to 30 thin-walled spherical eggs with six-hooked embryos are indicative of Dipylidium infection, while individual, thick-walled, spherical eggs may be either Taenia or Echinococcus spp. If a cat has fleas, there is a good chance that it may also be infected with D. caninum. Since many cats are fastidious groomers, the absence of fleas does not necessarily rule out a flea infestation. If Dipylidium infection is diagnosed, a flea control program should be instituted at the same time as tapeworm treatment. Treatment Is Simple The drug of choice for treatment of tapeworms in cats is praziquantel, which is highly efficacious against both D. caninum and T. taeniaeformis. One new formulation that has been shown to be effective against both of these tapeworms is an emodepside/praziquantel combination. In studies of naturally infected cats, this topical solution demonstrated 100% efficacy against these tapeworms. 2 5 A multi-clinic field study validated these results by achieving 99.1% efficacy in household cats infected with D. caninum. 6

If a cat has fleas, there is a good chance that it may also be infected with D. caninum. Emodepside/praziquantel 100% effective against tapeworms after a single dose* Profender : The Most Complete Feline Topical Dewormer* 100% effective against tapeworms** 100% effective against roundworms and hookworms (as seen in clinical trials) Convenient topical formulation 90% of cat owners prefer, and feel their cat would prefer, a topical rather than a pill or tablet 7 89% of cat owners feel if the medicine is easier to give, they would be more likely to give it to their cat as prescribed 7 D. caninum - T. taeniaeformis - 100% Profender Topical Solution provides broad coverage effective against adults and 100% multiple larvae stages 2 5 - - 0% 20% 40% 60% 80% 100% *Field trial efficacy against D. caninum 99.1%. 6 Efficacy (%) References 1. Companion Animal Parasite Council. CAPC Recommendations: Intestinal Parasites: Cestodes: Tapeworm. Available at: www.capcvet. org/recommendations/tapeworm1.html. Accessed 5/31/09. 2. Kok D (investigator, unpublished data). Evaluation of the efficacy of different dose levels of a combination of BAY 44-4400 (emodepside) and praziquantel against natural Dipylidium caninum infection in cats. Freedom of Information Summary Report #75625. NADA 141-275, Profender Topical Solution:17-18. 3. Cruthers L (investigator, unpublished data). Evaluation of the efficacy of a combination of BAY 44-4400 (emodepside) and praziquantel against natural Dipylidium caninum infection in cats. Freedom of Information Summary Report #75617. NADA 141-275, Profender Topical Solution:18-19. 4. Kok D (investigator, unpublished data). Evaluation of the efficacy of a combination of BAY 44-4400 (emodepside) and praziquantel against natural Taenia taeniaeformis infection in cats. Freedom of Information Summary Report #75627. NADA 141-275, Profender Topical Solution:14-15. 5. Bowman D (investigator, unpublished data). Evaluation of the efficacy of a combination of BAY 44-4400 (emodepside) and praziquantel against natural Taenia taeniaeformis infection in cats. Freedom of Information Summary Report #75626. NADA 141-275, Profender Topical Solution:15-16. 6. Field Safety and Effectiveness Study (multiple veterinary practices, unpublished data). Clinical evaluation of the safety and efficacy of BAY 44-4400 (emodepside) and praziquantel topical solution against nematode and cestode infections in cats. Freedom of Information Summary Report #75628. NADA 141-275, Profender Topical Solution:19-22. 7. From a survey of 736 cat owners. Data on file. - - - - Tapeworms D. caninum Adult T. taeniaeformis Adult Roundworms T. cati Adult L4 Larvae Hookworms A. tubaeforme Adult L4 Larvae Immature Adults *Profender is labeled for tapeworms, roundworms, and hookworms. **Field trial efficacy against D. caninum 99.1%. 6 Field trial efficacy against T. cati 99.9%. 6 Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian. Not for human use. Keep out of reach of children. To prevent accidental ingestion of the product, children should not come into contact with the application site for 24 hours while the product is being absorbed. Use with caution in sick or debilitated cats. Please refer to the label section for full prescribing information. Managing Parasite Threats Today 15

With Bayer Parasite Solutions, you can customize comprehensive parasite DOGS programs for each of your patients. DOGS Treat monthly, year-round Treat as indicated CATS Treat monthly, year-round Federal (U.S.A.) law restricts Drontal Plus, Profender, Advantage Multi for Cats and Advantage Multi for Dogs to use by or on the order of a licensed veterinarian. Advantage Multi for Cats WARNING: Do not use on sick, debilitated, or underweight cats (see ADVERSE REACTIONS). Do not use on cats less than 9 weeks of age or less than 2 lbs. body weight. HUMAN WARNINGS: Children should not come in contact with the application site for 30 minutes after application. PRECAUTION: Avoid oral ingestion. Advantage Multi for Dogs CONTRAINDICATIONS: Do not administer the product orally. Do not use this product (containing 2.5% moxidectin) on cats. WARNING: For the first 30 minutes after application, ensure that dogs cannot lick the product from application sites on themselves or other treated dogs, and separate dogs from one 16 Supplement to VLS journals 2009 Treat as indicated another and from other pets to reduce the risk of accidental ingestion. Ingestion of this product by dogs may cause serious adverse reactions including depression, salivation, dilated pupils, incoordination, panting and generalized muscle tremors. In avermectin sensitive dogs, the signs may be more severe and may include coma and death. HUMAN WARNINGS: Children should not come in contact with the application site for two (2) hours after application. Drontal Plus Not for use in puppies less than 3 weeks of age or weighing less than 2 lbs. Do not use in pregnant animals. Profender Not for human use. Keep out of the reach of children. Children should not contact application site for twenty-four (24) hours. K9 Advantix is for use on dogs only.

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