Modern Parasitology For The Cat:

Modern Parasitology For The Cat: Fleas, Mites, and Worms, Oh My! Annette Litster BVSc PhD FACVSc (Feline Medicine) MMedSci (Clinical Epidemiology) Senior Veterinary Specialist, Zoetis Chris Adolph DVM, MS, DACVM (Parasitology) Veterinary Specialist, Zoetis All trademarks are the property of Zoetis Services LLC or a related company or a licensor unless otherwise noted. 2017 Zoetis Services LLC. All rights reserved. 1 Document No. TI-02839

FELINE HEARTWORM INFECTION RISK FACTORS AND LIFE CYCLE

4 McKay et. al., 2013. Journal of Medical Entomology 50 (4): 871-878. Ledesma, N., and L. Harrington, 2015. Veterinary Parasitology 209(1-2):93-100.

Environmental Risk NE AK Frequency of D. immitis-infected Mosquitoes SHELTER + 5 RESIDENTIAL AREAS INSIDE KENNEL OF 1 HW-INFECTED DOG 7.3% 10X 73.7% A single heartworm-positive dog potentially increases infection pressure on susceptible animals sharing mosquito exposure At colder temperatures, average daily temperature models underestimate L3 development; modeling hourly temperature more accurately predicted D. immitis development to infective L3 s. (Ledesma and Harrington, 2015) McKay et. al., 2013. Journal of Medical Entomology 50 (4): 871-878. Ledesma, N., and L. Harrington, 2015. Veterinary Parasitology 209(1-2):93-100. 5

LIFE CYCLE OF DIROFILARIA IMMITIS IN THE CAT Microfilaria 6

LIFE CYCLE OF DIROFILARIA IMMITIS IN THE CAT L 1 Microfilaria L 3 L 2 7

LIFE CYCLE OF DIROFILARIA IMMITIS IN THE CAT L 1 Microfilaria L 3 L 2 X MF (L 1 ) 6 months L 3 Adults Immature Adult L4 8

LIFE CYCLE OF DIROFILARIA IMMITIS IN THE CAT L 1 Microfilaria L 3 L 2 X MF (L 1 ) 6 months L 3 Mosquito infects cat with L3 Adults Immature Adult L4 Stages Susceptible to Preventatives L3 L4 Immature Adult Adult 9 0 30 60 90 120 150 180 D A Y S 210 240

CLINICAL SIGNS CATS INSIST ON BEING DIFFERENT 10

HEARTWORM DISEASE FELINE VS. CANINE 1 Cats more resistant to infection True prevalence? Mosquito vectors Worm burden High larval mortality rate Microfilaremia Host suppression and clearance Aberrant larval migration Reduced lifespan 1. Litster and Atwell, 2008. Journal of Feline Medicine and Surgery 10:137-144. 11

CLINICAL SIGNS ASSOCIATED WITH IMMUNE RESPONSE TO Larval arrival into pulmonary vasculature Antibody mediated response Pulmonary arteritis HARD Death of adult worms Acute death syndrome 12

FELINE HEARTWORM DISEASE: CLINICAL TIMELINE Microfilariae? Ab Ag? 13 0 3 6 9-24 mos Months after Infection

FELINE HEARTWORM DISEASE: CLINICAL TIMELINE Eosinophilia Microfilariae? Ab HARD Bronchitis Ag? Adult HW- PA Lesion Cat +/- Clinical Signs 14 0 3 6 9-24 mos Months after Infection

FELINE HEARTWORM DISEASE: CLINICAL TIMELINE Eosinophilia Microfilariae? Ab HARD Bronchitis Ag? Adult HW- PA Lesion Cat +/- Clinical Signs 15 0 3 6 9-24 mos Months after Infection

BLAGBURN & DILLON HARDs STUDY 1 16 1. Blagburn BL, Dillon AR. Feline heartworm disease: solving the puzzle. Veterinary Medicine (supplement) 2007; March: 7-14.

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18 EVEN CATS WITH HEARTWORM INFECTION THAT NEVER DEVELOPED ADULT WORMS INCURRED SIGNIFICANT BRONCHIAL AND PARENCHYMAL DISEASE

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FELINE HEARTWORM INFECTION THE ACUTE DEATH SYNDROME IN FELINE HEARTWORM DISEASE

THE ACUTE DEATH SYNDROME 1 Prevalence Unknown but estimates range from 10% to 47% of infected cats Clinical presentations Necropsy findings Hypotheses Acute pulmonary thromboembolism associated with death of adult filariae (Dillon 1998) Acute systemic anaphylaxis (Brown et al 1999) worm breakage during extraction procedures Role of Wolbachia? 1. Litster et al., 2008. Veterinary Parasitology 158:196-203. 21

FELINE HEARTWORM INFECTION DIAGNOSIS

FELINE HEARTWORM DIAGNOSIS ANTIBODY AND ANTIGEN TEST (Ab- & Ag-) Preventative 23

FELINE HEARTWORM DIAGNOSIS ANTIBODY AND ANTIGEN TEST (Ab- & Ag-) (Ab+ & Ag-) Preventative +/- Thoracic radiographs +/- Echocardiography +/- Angiography L4-Early Adult infection/ Previous Adult infection Preventative Discuss Potential Complications 24

FELINE HEARTWORM DIAGNOSIS ANTIBODY AND ANTIGEN TEST (Ab- & Ag-) (Ab+ & Ag-) Preventative +/- Thoracic radiographs +/- Echocardiography +/- Angiography L4-Early Adult infection/ Previous Adult infection Preventative Discuss Potential Complications Positive HW Diagnosis No Approved or Recommended Treatment Supportive Care and Preventative 25

FELINE HEARTWORM DIAGNOSIS ANTIBODY AND ANTIGEN TEST (Ab- & Ag-) (Ab+ & Ag-) (Ab+ & Ag+) Preventative +/- Thoracic radiographs +/- Echocardiography +/- Angiography L4-Early Adult infection/ Previous Adult infection Preventative Discuss Potential Complications Positive HW Diagnosis No Approved or Recommended Treatment Supportive Care and Preventative 26

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Antigen-antibody complexes interfere with antigen detection Heat treatment at 103 C for 10 minutes breaks up complexes Six HW-infected cats with low worm burdens Before heat treatment 0/6 specimens Ag+ After heat treatment 5/6 specimens Ag+ 28

TOTAL # CATS # POSITIVE BEFORE HEAT TREATMENT # POSITIVE AFTER HEAT TREATMENT Shelter cats 220 1 13 (6%) Free-roaming cats 165 4 13 (8%) 29

TOTAL # CATS # POSITIVE BEFORE HEAT TREATMENT # POSITIVE AFTER HEAT TREATMENT Shelter cats 220 1 13 (6%) Free-roaming cats 165 4 13 (8%) 30

FELINE HEARTWORM INFECTION VD VIEW Right PA Rib 9 Left PA Photo: Dr. S. Foster 31

FELINE HEARTWORM INFECTION TREATMENT

FELINE HEARTWORM DISEASE TREATMENT 1 ASYMPTOMATIC CATS Wait for self-cure? 6-12 monthly monitoring Ag + Ab testing, thoracic radiographs Most cats become Ag negative 4-5 months after infection clears good prognostic sign Timing to Ab negative state indeterminate (months-years) Seroconversion to negative, regression of radiographic signs indicate risk period has probably passed 1. American Heartworm Society Current Feline Guidelines 2014 http://www.heartwormsociety.org/ 33

FELINE HEARTWORM DISEASE TREATMENT 1 CATS WITH EVIDENCE OF RADIOGRAPHIC DISEASE Prednisolone in diminishing doses 2mg/kg q24h declining to 0.5mg/kg q48h over 2 wks, discontinue after a further 2 wks Reassessment after prednisolone based on clinical response and radiographic signs Repeat if clinical signs recur Regular monitoring important Aspirin and NSAIDs Failed to produce benefits may exacerbate pulmonary parenchymal disease 1. American Heartworm Society Current Feline Guidelines 2014 http://www.heartwormsociety.org/ 34

FELINE HEARTWORM DISEASE TREATMENT 1, 2 ACUTELY ILL CATS O 2 via nasal catheter/airway Epinephrine 0.01mg/kg 1:1000 solution IM, SC, sublingually Isotonic crystalloid fluid bolus (45-60 ml/kg) Antihistamines e.g. Diphenhydramine 0.5-2.0 mg/kg IM q8h High-dose IV glucocorticoids after circulatory collapse is reversed Bronchodilators e.g. Terbutaline 0.01 mg/kg SC Diuretics inappropriate Anti-serotonin drugs Cyproheptadine? 1. American Heartworm Society Current Feline Guidelines 2014 https://www.heartwormsociety.org/images/pdf/2014_ahs_feline_guidelines.pdf (Accessed August 15 2017) 2. Dhupa 2005 http://www.ivis.org/proceedings/navc/2005/sae/060.pdf?la=1 (Accessed August 15 2017) 35

Intravenous Basket Catheter Accidental Worm Transection Acute Death 36

FELINE HEARTWORM DISEASE TREATMENT 1 ADULTICIDAL THERAPY Physical obstruction by worm burden not a problem for most cats Anaphylactic reaction on worm death fatal MELARSOMINE Toxic to cats in doses as low as 3.5mg/kg Use in cats is not approved 1. American Heartworm Society Current Feline Guidelines 2014 http://www.heartwormsociety.org/ 37

FELINE HEARTWORM DISEASE TREATMENT 1 SELAMECTIN/MOXIDECTIN/IVERMECTIN AS ADULTICIDES Given over 2 years reduces worm burden Slow kill thought to reduce chances of acute reaction Might be used in combination with 30 day course of doxycycline to increase effectiveness of adulticidal action Use of macrocyclic lactones for treatment of heartworm disease in cats is not approved. BOTTOM LINE PREVENTION SHOULD BE PRIORITIZED While there is no published evidence that any form of adulticide therapy increases survival in HW-infected cats, the Blagburn and Dillon studies demonstrated that monthly selamectin will prevent further infections and HARDs 1. American Heartworm Society Current Feline Guidelines 2014 http://www.heartwormsociety.org/ 38

FELINE HEARTWORM INFECTION PROPHYLAXIS

FELINE HEARTWORM DISEASE PROPHYLAXIS WITH MACROCYTIC LACTONES MONTHLY TOPICALS Selamectin (Revolution ) Moxidectin + imidicloprid (Advantage Multi ) MONTHLY ORAL TABLETS Ivermectin (Heartguard ) Milbemycin (Interceptor ) 40

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42 QUESTION TIME

COMMON FELINE GI HELMINTHS Toxocara cati Ancylostoma tubaeforme Dipylidium caninum Taenia taeniaeformis Photos courtesy of the NCVP 43

LIFE CYCLE OF TOXOCARA CATI Host ingests PH with larvae arrested in tissue Adult ascarids in small intestine Host ingests infective eggs with larvae Larvae may be shed in milk and ingested by neonates Eggs pass in feces and larvate Photos courtesy of the NCVP 44

LIFE CYCLE OF ANCYLOSTOMA TUBAEFORME Host ingests PH with larvae arrested in tissue Adult hookworms in small intestine Host ingests infective larvae Larvae penetrate skin of host Eggs pass in feces and larvate Photos courtesy of the NCVP 45

DIPYLIDIUM CANINUM: LIFE CYCLE Cysticercoid in ingested flea develop into adults in the small intestine Proglottids containing egg packets pass in feces Develop into infective cysticercoids in the developing flea Ingested by flea larvae 46

TAENIA TAENIAEFORMIS: LIFE CYCLE Cat infected by eating intermediate host Tapeworm proglottids containing infective eggs pass in feces Develop into infective cysticercoids in the developing flea 47 Rodent intermediate host ingests eggs Eggs released from proglottids into environment

FELINE PARASITE PREVALENCE STUDY 1 116 adult cats examined Gl tract examined at necropsy, helminths collected Determine the prevalence of intestinal parasites including Toxocara cati Ancylostoma tubaeforme Physaloptera spp. Cestodes Determine the utility of common diagnostics 1. Adolph C., 2013. Prevalence, disease implications, and diagnostic assays for parasites and vector-borne infections of cats in NE Oklahoma. Master s Thesis 48

RESULTS 1 (CONT.) Ascarids in 48/116 (41.4%) Hookworms in 8/116 (6.9%) Physaloptera in 3/116 (2.6%) Photos courtesy of the NCVP 1. Adolph C., 2013. Prevalence, disease implications, and diagnostic assays for parasites and vector-borne infections of cats in NE Oklahoma. Master s Thesis 49

RESULTS (CONT.) Cestodes in 63/116 (54.3%) cats Dipylidium caninum: 40/116 (34.5%) Taenia taeniaeformis: 30/116 (25.9%) Co-infection with both: 7/116 (6.0%) 50

RESULTS: DIAGNOSTIC TESTS 1 T. cati Centrifugation: 37/48 (77.1%) Passive: 33/48 (68.8%) A. tubaeforme Centrifugation 8/8 (100%) Passive 2/8 (25%) Physaloptera Both methods 0/3 (0%) Photos courtesy of the NCVP 1. Adolph C., 2013. Prevalence, disease implications, and diagnostic assays for parasites and vector-borne infections of cats in NE Oklahoma. Master s Thesis 51

RESULTS: DIAGNOSTIC TESTS (CONT.) T. taeniaeformis Centrifugation: 8/30 (26.7%) Passive: 3/30 (10%) Proglottids identified: 6/30 (20%) D. caninum Centrifugation: 0/40 (0%) Passive: 0/40 (0%) Proglottids identified: 6/40 (15%) 52

INTENSITY: HELMINTHS T. cati 7.2 (1-35) D. caninum 10.3 (1-63) 5 cats have over 20 adult D. caninum T. taeniaeformis 12.5 (1-56) 5 cats had over 35 adult T. taeniaeformis Cestode mass in 1 cat weighed 34.4 grams (1.5% of cat s body weight) 53

54 NOW FOR SOMETHING WE CAN SEE

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FLEA; KEY CONSIDERATIONS When an owner reports still seeing fleas despite initiation of insecticidal medications think life cycle first and resistance last How long has therapy been ongoing? What medications are being used? Are ALL pets in the environment on PROPER medications? Environmental factors 62

CONCLUSIONS 1 Helminths very common in cats in this study Detection techniques failed to identify MOST tapeworms Detection techniques failed to identify infections in some cats with T. cati Improved diagnostic techniques may allow detection of infections currently overlooked Fleas are common ectoparasites of cats, but ticks also found Supports importance of routine heartworm and flea prevention for cats 1. Adolph C., 2013. Prevalence, disease implications, and diagnostic assays for parasites and vector-borne infections of cats in NE Oklahoma. Master s Thesis 63