Canine and Feline Heartworm Notes PDF

CLINICAL PATHOLOGY I – Lecture Dirofilaria immitis (“heartworm”) in Dogs Etiologic Species = Dirofilaria immitis o Another nematode o Life cycle is indirect o Transmission is indirect o IH is mosquito o Prepatent period ▪ Dogs = 6 to 7 mo...

CLINICAL PATHOLOGY I – Lecture Dirofilaria immitis (“heartworm”) in Dogs Etiologic Species = Dirofilaria immitis o Another nematode o Life cycle is indirect o Transmission is indirect o IH is mosquito o Prepatent period ▪ Dogs = 6 to 7 months ▪ Cats ~ 8 months Definitive Host o Dog most common, but has been found in ▪ Cats ▪ Ferrets o Also in wild animals ▪ Foxes (not particularly good host) ▪ Coyotes (very good host) ▪ Sea lions Zoonotic Potential o Humans can be infested with Dirofilaria immitis, though patent infestation does not develop o Immature D. immitis worms may reach pulmonary artery, triggering inflammatory response resulting in death of worms o Pulmonary nodules (“coin lesions”) sometimes develop, and can be mistaken for lung cancer Regarding Cats o This information covers most common host, the dog. Cats** will be addressed in separate lecture. (**They’re special, you know) Distribution of HWD o Originally found along Atlantic and Gulf coasts, but... o Now across U.S., number of cases low in ▪ Rocky Mountain west ▪ Desert southwest states o However, currently moving up Colorado River Valley from Grand Junction Life Cycle o Adult worms found primarily in ▪ Pulmonary arteries ▪ Right heart (ventricle first, then atrium) ▪ Occasionally vena cava o Females produce offspring (L1 = microfilariae) Microfilariae o First stage larvae (L1) ▪ Microfilaria = Singular ▪ Microfilariae = Plural o Circulate in DH’s blood o Tiny -- 0.3mm long IH = Mosquito o Mosquito takes blood meal from infested DH and ingests L1 o Larvae develop to L3 inside IH. Takes 10 – 30 days (average 14 days), depending on ambient temperature (ideally > 70 degrees Fº) o L3 migrate to mosquito mouthparts o Mosquito takes blood meal from another host, deposits larvae onto skin of DH, larvae enter bite wound Definitive Host o L3 develop into L4 o L4 migrate through host’s subcutaneous tissue for ~ 2 months, molt to L5 o L5 (immature adults) enter vascular system and migrate to heart o L5 arrive at heart, another 4 to 5 months to ▪ Reach sexual maturity ▪ Females begin producing microfilariae and antigen o Prepatent period = 6 to 7 months Adult D. immitis o In pulmonary arteries (and right heart if worm burden is high) o Typically live 5 to 7+ years if untreated o Responsible for pathology and clinical signs ▪ Male worms ~ 180 mm (7”) in length ▪ Female worms ~ 300 mm (12”) in length VERY IMPORTANT o **Entire life cycle in dog takes 6 – 7 months** ▪ ~ 2 months in SQ tissues ▪ ~ 4 to 5 months maturing in pulmonary arteries o Host will not have adults or circulating microfilaria until 6 – 7 months post-infestation o Host will test negative on BOTH antigen test and microfilariae test until at least 6 months post- infestation Transmission Rate of Heartworm is Directly Related to Density of Mosquitoes o Requires environment conducive to breeding of mosquitoes; i.e., hot and wet (Florida) o Warm temperatures for incubation of larvae in mosquito (Florida) o What’s good for mosquitoes is good for heartworms (Florida) Clinical Signs of HWD o Decreased exercise tolerance, lethargy o Cough: Dry, non-productive o Dyspnea: Labored breathing o Syncope: Fainting due to diminished blood flow to brain  o Distended abdomen: Ascites o Cachexia: Profound, marked state of constitutional disorder; general ill health and malnutrition; emaciation Pathogenesis o Parasite causes arteritis, damages pulmonary endothelium o Increased permeability of vessels permits leakage of fluid into tissues o Vessel walls thicken and lumen narrows o Arteries enlarge and become tortuous o Right ventricular hypertrophy develops Cardiac Signs o Physical obstruction of ▪ Vessels ▪ Heart chambers ▪ Valves o Right-sided CHF ▪ Reverse “D”-shaped heart ▪ Ascites ▪ Hepatomegaly Respiratory Signs o Non-productive cough o Pulmonary embolism ▪ Pulmonary vessels plugged with worms ▪ Blood supply to lung tissue is decreased o Pulmonary crackles: Alveoli collapse and stick together o Hemoptysis: Coughing up blood from the respiratory tract Caval Syndrome o Heartworms packed into ▪ Right ventricle ▪ Right atrium ▪ Vena cava o Acute onset o Lethal if not treated o Only treatment is surgical removal o Basket retrieval device introduced through jugular vein into vena cava and right atrium to physically remove adult worms o Supportive care ▪ Fluids ▪ Steroids ▪ Antibiotics o Adulticide treatment initiated 2 – 4 weeks following removal of worms Diagnosis o Three acceptable methods ▪ Modified Knott test: Microfilariae ▪ Millipore filter test: Microfilariae ▪ Antigen (Ag) test: Antigen o Both microfilariae and antigen are produced by adult female heartworm ▪ Microfilariae production requires presence of adult male and adult female ▪ Antigen production requires presence of adult female  “The Imposter” Acanthocheilonema reconditum (formerly Dipetalonema reconditum) Nonpathogenic, filarioid nematode in subcutaneous tissue of dog A. reconditum microfilariae circulate in peripheral blood IH = Flea (and sometimes biting louse) Similar to D. immitis on microfilariae tests but can be visually differentiated o Antigen Tests ▪ ELISA-Enzyme-Linked Immunosorbant Assay Other Diagnostic Aids o Radiography o ECG o Echocardiogram Testing Details o Dogs < 6 months of age will be both antigen and microfilariae negative ▪ No need to test ▪ Safe to begin any heartworm preventative ▪ Begin HW preventatives by 8 weeks of age ▪ Perform HW test 6 months later to confirm dog was NOO / NAD at time preventative meds started o Dogs > 6 months of age should have an antigen test ▪ NAD antigen or NOO microfilariae does not mean dog heartworm “negative” ▪ Infestation may too recent for detectable antigen level (or circulating microfilariae); i.e., during prepatent period ▪ If test appears NAD / NOO, dog may be started on HW preventative ▪ Repeat HW test 6 months later to confirm dog was NAD / NOO at time preventative meds were started Treatment o Pretreatment evaluation to determine dog’s ability to handle treatment ▪ Urinalysis ▪ CBC and chemistry profile ▪ Chest radiographs o Treatment sequence 1. Microfilaricide: Two monthly treatments beginning 60 days prior to adulticide 2. Doxycycline: Administer BID for 30 days beginning with first dose of microfilaricide a. Reduce Wolbachia spp. numbers b. Decrease pulmonary pathology c. Increase adulticide effectiveness 3. Adulticide**: Melarsomine dihydrochloride; three-dose protocol 3a. One IM injection; wait 30 days 3b. Two IM injections, 24 hours apart Administered IM in epaxial (lumbar) muscles No problem with tissue damage and sloughing Often causes pain and swelling at injection site Does not kill microfilaria, L3, L4, or immature L5 **Post-adulticide complication: Pulmonary thromboembolism 7 – 10 days post-treatment (but can occur up to 30 days later). May lead to death of patient.  Coughing Dyspnea Hemoptysis Anorexia Lethargy Extremely important to restrict exercise for minimum of 4 to 6 weeks post-treatment Perform Ag test 6 months following adulticide treatment to confirm elimination of adults Prevention: Cheaper & Safer o Monthly oral or topical dosing of any macrocyclic lactones ("macrolides"). Do not prevent infestation with L3 but kill L3 and early-stage L4 on day medication is administered. ▪ Ivermectin: PO ▪ Milbemycin oxime: PO ▪ Selamectin: Topical ▪ Moxidectin: Topical Parenteral (SQ every 6 months) o AHS recommends year-round prevention ▪ Monthly preventatives kill L3 and early-stage L4 (up to about 45 days of age) on day of administration – “reach back” effect ▪ Lapse in monthly dosing of more than 2 weeks puts patient at risk for development of adult Dirofilaria immitis ▪ Parenteral moxidectin is formulated as sustained-release medication CLINICAL PATHOLOGY I – Lecture Heartworm Terminology 1. Antigen: A substance that the body recognizes as “foreign”; antigens are capable of inducing a specific immune response and binding with a specific antibody 2. Dyspnea: Labored breathing 3. Syncope: A temporary suspension of consciousness due to insufficient blood flow to the brain; i.e., fainting 4. Ascites: Abnormal accumulation of serous fluid within the peritoneal cavity 5. Anorexia: Loss or lack of appetite for food 6. Cachexia: Profound and marked state of constitutional disorder; general ill health and malnutrition 7. Hemoptysis: Coughing and/or spitting of blood as a result of bleeding from any part of the respiratory tract 8. Thrombus/thrombi (singular/plural): A clot that is attached to the vessel wall; may partially or completely occlude flow of blood through the vessel 9. Embolus/emboli (singular/plural): A clot or other plug not attached to the vessel wall (usually part or all of a thrombus), brought by the blood from another vessel and forced into a smaller vessel, thereby obstructing circulation  10. Thromboembolus/thromboemboli (singular/plural): Thrombotic material transported in the bloodstream to another site to form an embolus 11. ELISA: Enzyme-Linked Immunosorbent Assay; a type of primary binding test used to detect and measure either antigen or antibody 12. Infarction: Death of tissue due to loss of arterial blood supply 13. Hemoglobinuria: Free hemoglobin in urine 14. Hemoglobinemia: Free hemoglobin in circulating plasma. 15. Microfilaremia: Presence of microfilariae in the bloodstream 16. Antigenemia: Presence of antigens in the bloodstream 9/25/2020 1  CLINICAL PATHOLOGY I – Lecture Feline Heartworm Disease The same... only very different. Cats are a resistant, but susceptible, host for Dirofilaria immitis ▪ Cats in heartworm enzootic areas are consistently diagnosed with heartworm disease ▪ Clinical signs and diagnostic approach are very different in cats than in dogs Biology of Infestation ▪ Because cats are somewhat resistant, it takes greater exposure for infestation to occur in cats. When 100 infective L3s are introduced into a population of dogs and cats o 100% of dogs infested with L3s will develop ~ 75 adult worms o 75% of cats infested with L3s will develop ~ 3 to 10 adult worms ▪ Prepatent period is ~ 8 months ▪ Worm burden is smaller -- typically 1 to 5 worms (but up to 65 adults have been observed) ▪ Worms can reach significant size (4.5 to 8.25 inches), but development is slower in cat ▪ Single-sex infestations appear to be much more common in the cat due to low worm burdens ▪ Infective larvae in cat are poorly oriented, so ectopic sites for adult worm are more common (body cavities, CNS / brain, systemic arteries). Ectopic = Located away from normal position. ▪ Microfilariae are rarely observed in bloodstream of cats; only about 20% of infested cats will be microfilaremic o Feline immune system suppresses production of microfilariae o If present, microfilariae live only few months in cats o As a result, infested cats are poor reservoir of parasite ▪ Adult worms live ~ 2 to 3 years in cats Pathology ▪ Some cats never manifest clinical signs ▪ Increased immunologic response of cat explains clinical signs that are observed ▪ If evident, clinical signs most commonly appear during two stages of parasite’s life cycle o #1) When L5 arrive in pulmonary arteries, lungs respond with intense inflammation and “asthma-like” signs; i.e., “chronic” clinical signs o #2) After mature worms develop, clinical signs may be intermittent or absent until death of the worm; i.e., “acute” clinical signs #1) Chronic Clinical Signs: “HARD” ▪ Arrival of L5 in pulmonary vasculature stimulates activity of PIMs (pulmonary intravascular macrophages) ▪ PIMs release inflammatory mediators that cause intense reaction in lungs and death of many L5s ▪ Signs may be intermittent and often misdiagnosed as asthma or allergic bronchitis o Coughing o Dyspnea o Lethargy o Intermittent vomiting o Anorexia +/- weight loss #2) Acute Clinical Signs: “HARD” ▪ Death of adult worm(s) reinitiates PIM activity, leading to severe, intense inflammation of entire lung accompanied by thromboembolism ▪ Acute collapse including death may occur with or without previous clinical signs ▪ As few as one worm has been found in cases of acute collapse and pulmonary infarction  o Convulsions o Vomiting / Diarrhea o Collapse o Blindness o Anorexia o Tachycardia / Tachypnea o Syncope o Sudden death: Due to circulatory collapse and respiratory failure from acute pulmonary infarction and lung injury Medical Terminology ▪ HARD: Heartworm Associated Respiratory Disease ▪ Pulmonary thromboembolism: Obstruction of pulmonary artery by a clot or foreign material ▪ Pulmonary infarction: Localized necrosis of lung tissue due to obstruction of arterial blood supply; most often due to a pulmonary thromboembolism Diagnostic Testing ▪ Serologic tests often inconclusive ▪ Ag tests not as definitively diagnostic in cats as in dogs o Single sex, male only infestations more common o Clinical signs present during pre-patent period ▪ Ab tests are more sensitive in cats due to their strong immune response to larvae o May detect Ab two months post-infestation o BUT, Ab + only means cat has been exposed to D. immitis at some time during cat’s life ▪ Microfilaremia rarely present, so microfilariae testing is unreliable in cats o Occult infestations are common o Feline immune system suppresses production of microfilariae o Microfilariae live only few months in cats **AHS recommends use of both Ag and Ab testing in cats ▪ Other tests that may aid in diagnosis include o Radiography o Echocardiography o NECROPSY Treatment ▪ NO treatment: Treat clinical signs and wait for spontaneous cure (natural death of adult worms) o Death of adult worms can cause severe respiratory signs o Cat may develop peracute signs and die ▪ Physical removal of adult worms with basket retrieval instrument ▪ Chemotherapy: Currently no products approved for use in cats o Caparsolateâ and Immiticideâ have been used experimentally o Serious post-treatment complications have been reported in up to 33% of treated cats o Considered treatment of last resort An Ounce of Prevention... ▪ Controversy over testing prior to beginning prophylaxis – recommended though not always practical ▪ Safe to begin monthly preventative without testing as early as 8 weeks of age o Ivermectin: PO o Milbemycin oxime: PO o Selamectin: Topical o Moxidectin: Topical 9/25/2020 1