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*''Dirofilaria immitis'' live in heart and [[Respiratory Parasitic Infections - Pathology#Dirofilaria immitis|pulmonary arteries]] of dogs and cats
*''Dirofilaria immitis'' live in heart and [[Respiratory Parasitic Infections - Pathology#Dirofilaria immitis|pulmonary arteries]] of dogs and cats
== Nematodes of Dogs - CANINE HEARTWORM ==
*''Dirofilaria immitis'' is one of the most important causes of morbidity and mortality in dogs in many regions of the world that have a warm, humid climate, including parts of southern Europe, USA and Australia.
*The presenting signs are usually those of heart failure, but sudden collapse may occur in heavily infected dogs.
*The endemic zone for canine heartworm disease is spreading as people increasingly travel with their pets.
*Strains of ''D. immitis'' are adapting to cooler climates.
*It is not endemic in the UK, but more infected dogs are likely to be imported now that the quarantine regulations have been relaxed.
*It has a very long prepatent period, so clinical signs may not appear for many months after importation.
*Although primarily a canine parasite, cats and ferrets can become infected.
*Owners taking their pets into endemic regions require advice on how the disease can be prevented.
'''''Dirofilaria immitis''''':
*a filarial worm
*females: up to 30cm long; males: up to 15cm long
*life-span 5-7years
*up to 250 worms may establish in the heart and pulmonary arteries
*produce microfilariae, not eggs.
'''Microfilariae''':
*in peripheral circualtion
*periodicity - maximum numbers in blood evening/night
*greater than 300µm long
*life-span 2years
*present in approximately 60% of infected dogs
*microfilariae are absent from the circulating blood if:
**only immature worms present
**only one worm present
**only one sex
**microfilariae killed by immune response (in 15% of dogs)
**females sterilised by chemotherapy (e.g. ivermectin).
'''Intermediate hosts''':
*many, but not all, species of mosquito.
'''Local Epidemiology''':
*determined by feeding preferences of local species, and population density.
*up to 45% of non-protected dogs infected in some parts of USA.
'''In mosquito''':
*microfilariae → L1 → L2 → infective L3
*this takes 1week at 30°C, or 4weeks at 18°C - there is no development below 14°C.
*when mosquito next feeds:
**L3 moves to mouthparts
**up to 12 L3 deposited on skin
**enter body via puncture wound.
'''In dog''':
*larvae migrate through connective tissues and moult twice
*immature adults (L5) are 1-5cm long → caudal distal pulmonary arteries in 4months → diffuse eosinophilic reaction in lung parenchyma, then migrate back towards right ventricle
*start producing microfilariae 6-7months post-infection.
'''Zoonotic hazard''':
*human infection can occur, but few cases are diagnosed
*this usually happens when a radio-opaque plaque is detected in the lung, and further investigation shows it to be caused by a trapped ''D. immitis'' larva.
=== Pathology ===
'''Worms produce''':
*substances that are:
**antigenic
**immunomodulatory
**pharmacologically active.
'''Lesions are''':
*'''not''' confined to the location of the worms
*also caused by shear stress of high blood flow.
'''Severity''':
*not associated with the number of worms
*exacerbated by exercise (i.e. by high blood flow rate)
*sedentary dogs often asymptomatic - symptoms most commonly associated with racing greyhounds.
'''Acute prepatent disease''':
*immature adult worms in caudal distal pulmonary arteries
*leads to intense diffuse eosinophilic reaction, which in turn leads to coughing.
'''Chronic disease''':
*mature worms in right heart and pulmonary arteries
*endothelial swelling and sloughing
*increased permeability → inflammation → periarteritis
*platelets/white blood cells activated → thrombosis
*proliferation of smooth muscle, thickening of media:
→ impairment of blood flow
→ pulmonary hypertension
→ right ventricular strain
→ right ventricular hypertrophy and right-sided heart failure
*insufficient blood pumped through pulmonary capillary bed → insufficient preload for left ventricle.
'''Post Caval Syndrome (Dirofilarial haemoglobinuria)''':
*can be acute or chronic
*heavy heartworm infestation:
**entangled clumps of worms → impaired closure of tricuspid valve → post-caval stagnation → hepatic congestion and hepatic failure
*this is accompanied by increased red blood cell fragility, haemolytic anaemia and haemolobinuria.
'''Clinical signs''':
*often sudden onset severe lethargy and weakness, but:
*signs variable, reflecting multiple system dysfunction - pulmonary circulation, heart, liver and kidneys:
**lung damage (severe pulmonary hypertension; thromboembolism)
**heart failure (right-sided congestive)
*therefore, '''not''' pathognomonic
*acute prepatent = coughing
*chronic = exercise intolerance, sometimes with ascites
*acute post caval syndrome = collapse (dyspnoea, pale mucous membranes or jaundice, haemoglobinuria)
'''Diagnosis''':
*Physical examination:
**signs of heart disease
**lung involvement
*Radiography:
**enlargement of right heart, main pulmonary arteries; arteries in lung lobes with thickening and tortuosity; inflammation in surrounding tissues
*ECG:
**right axis deviation → deep S waves
*Echocardiography:
**if post caval syndrome suspected - right ventricular enlargement with worms in ventricle appearing as parallel lines.
'''Clinical pathology''':
*needed alongside physical examination and other tests to determine treatment strategy and prognosis.
'''Parasite detection''':
*methods for demonstrating microfilariae in blood:
**wet blood smear (okay for quick look, but insensitive) = ''D. immitis'' not progressively motile
**Knott's test = red blood cells lysed; stained sediment examined
**micropore filter = blood forced through; microfilariae held on filter; stained and examined
**antibody detection ELISA = not reliable in dogs, but it is the best for cats (although some false positives)
**antigen detection ELISA (using specific antigen from adult female worm) = reliable positives from 5-7months post-infection in dogs; although occasional false negatives occur → '''not''' useful for cats
*the immunochromatographic test (ICT) uses coloured gold colloidal particles tagged to monoclonal antibodies to visualise the presence of adult worm antigen - performance similar to antigen detection ELISA, but quicker and easier to do (but not as quantitative as some ELISAs are)
*operator error can give false positives, therefore best to confirm result with another test.
'''Chemotherapy''':
*three treatment objectives needing different approaches:
1) '''Adulticidal'''
*risk that dead worms → thromboembolism → respiratory failure
*therefore, hospitalise and strict exercise restriction for at least 3weeks post-treatment
*organic arsenicals for adulticidal therapy:
**'''Thiacetarsamide''' (2.2mg/kg IV bid for 2days) - hepatotoxic; skin sloughing
**'''Melarsomine''' (2.5mg/kg IM sid for 2days) - generally safer, but greater risk of thromboembolism
NB - Ivermectin preventative doses over 16months reduces adult worm numbers
2) '''Microfilaricidal'''
*start 3-6weeks after adulticidal therapy:
**'''Ivermectin''' (50µg/kg)
**'''Milbemycin oxime''' (0.5mg/kg)
NB - risk of reaction to dead microfilariae in sensitised animals (lethargy, retching, tachycardia, circulatory collapse) - observe for 8hours post-treatment
3) '''Preventative (prophylactic)'''
*objective = kill migrating L4 before they reach the heart
*monthly treatments are 100% effective and safe if used properly, but often fail because of inadequate owner compliance
*test for adult infection/microfilarie before start and annually thereafter:
**'''Ivermectin''' (6µg/kg monthly) - blocks maturation of larvae; these die only after several months
**'''Selamectin''' (6mg/kg monthly)
**'''Moxidectin''' (injectable formulation - 0.17mg/kg gives 6months protection)
**'''Milbemycin oxime''' (0.5mg/kg monthly) - care → kills microfilarie, therefore risk of reaction
**'''DEC (diethylcarbamazine)''' daily - care → kills microfilarie, therefore severe risk of reaction
'''Treatment of Post Caval Syndrome''':
*surgical removal with forceps via jugular vein
*usually very successful, but:
*do not crush or fragment worms
→ massive release of antigen
→ cardiac failure and acute respiratory distress
→ rapid death
'''A typical therapy protocol''':
1) Pre-treatment evaluation
2) Adulticide: 4-6weeks restricted exercise
3) Microfilaricide: 3weeks after adulticide
4) Initiation of monthly preventative treatments
5) Check for microfilariae after 2weeks
6) Check for adults (ELISA) 4-6months after adulticide, and before start of each subsequent mosquito season.
[[Category:Filarioidea]]
[[Category:Filarioidea]]
[[Category:Dog_Nematodes]]