Difference between revisions of "Dirofilaria immitis"

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[[Image:Dirofilaria immitus.jpg|thumb|right|250px|''Dirofilaria immitis'' - Courtesy of the Laboratory of Parasitology, University of Pennsylvania School of Veterinary Medicine]]
 
  
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Also known as: '''Heartworm Disease — Dirofilariasis
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==Description==
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[[Image:Dirofilaria immitus.jpg|thumb|right|150px|''Dirofilaria immitus'' - Courtesy of the Laboratory of Parasitology, University of Pennsylvania School of Veterinary Medicine]]
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[[Image:dirofilariasis.jpg|right|thumb|125px|<small><center>'''Dirofilariasis'''. Courtesy of T. Scase</center></small>]]
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[[Image:dirofilariasis 2.jpg|right|thumb|125px|<small><center>'''Dirofilariasis'''. Courtesy of T. Scase</center></small>]]
  
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Beware confusing with: ''[[Angiostrongylus vasorum]]'', [[angiostrongylosis]].
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Dirofilaria is a filarial worm. Female worms measure up to 30cm in length and males up to 15cm. The worms have a life-span of 5-7 years. Up to 250 worms may establish in the heart and [[Respiratory Parasitic Infections - Pathology#Dirofilaria immitis|pulmonary arteries]] of dogs and cats.
 +
Dirofilaria worms produce microfilariae, not eggs.
  
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==Introduction==
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'''Microfilariae''':
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''Dirofilaria immitis'' is a nematode parasite that causes heartworm disease in dogs, cats and ferrets. Heartworm disease is transmitted by [[Culicidae|mosquito]] bites and there are more than 70 species of mosquito that are able to transmit infection; ''Aedes, Anopheles'' and ''Culex'' are the most common vector species. Heartworm disease has been reported in many countries with temperate climate and is particularly prevalent in the USA, Canada, and southern Europe. The introduction of the PETS travel scheme has increased the concern over Dirofilariasis in the UK.
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*in peripheral circualtion
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*periodicity - maximum numbers in blood evening/night
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*greater than 300µm long
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*life-span 2years
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*present in approximately 60% of infected dogs
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*microfilariae are absent from the circulating blood if:
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**only immature worms present
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**only one worm present
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**only one sex
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**microfilariae killed by immune response (in 15% of dogs)
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**females sterilised by chemotherapy (e.g. ivermectin).
  
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''Dirofilaria'' does have zoonotic potential: infected mosquitos can transmit ''D. immitis'' to humans, but the infection does not become patent. The infective larvae instead reach the lungs, become encapsulated, and die causing granulomatous reactions called "coin lesions" in the process. These are only important because they may be confused with neoplastic metastasis to the lungs on radiography<sup>1</sup>.
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'''Intermediate hosts''':
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*many, but not all, species of mosquito.
  
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==Life Cycle==
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'''Local Epidemiology''':
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''Dirofilaria immitis'' adults reach maturity and sexually reproduce in the '''pulmonary arteries''' and '''right ventricle'''. Adult males are around 15cm in length, and females are around 25cm<sup>1</sup>. After mating, female worms release larvae known as microfilariae (or L1) into the circulation. When a mosquito takes a blood meal from the infected dog or cat, microfilariae are ingested. Mosquitoes are true intermediate hosts for ''Dirofilaria immitis'', since microfilariae require a period of maturation to L2 then L3 in the vector. The duration of this development depends upon environmental conditions. For example, maturation at 30&deg;C takes around 8 days, but when temperatures are down to 18&deg;C, this takes around one month<sup>2</sup>. Below 14&deg;C, development is halted and resumes when temperatures rise. In cooler climates, this means that transmission of heartworm disease to new canine or feline hosts can only occur in warmer months.  
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*determined by feeding preferences of local species, and population density.
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*up to 45% of non-protected dogs infected in some parts of USA.
  
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Once matured, L3 in the mosquito migrate to the labium, from which they erupt onto the host's skin as the mosquito feeds. Larvae then migrate into the bite wound and, as most dogs are highly susceptible to heartworm disease, most L3 then establish infection. It takes 2-3 days for L3 to moult to L4, which remain in the subcutaneous tissues for up to two months before becoming young adults (L5) and migrating to the pulmonary arteries.  
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'''In mosquito''':
 +
*microfilariae → L1 → L2 → infective L3
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*this takes 1week at 30°C, or 4weeks at 18°C - there is no development below 14°C.
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*when mosquito next feeds:
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**L3 moves to mouthparts
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**up to 12 L3 deposited on skin
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**enter body via puncture wound.
  
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Cats differ from dogs in that they are more resistant to infection with ''Dirofilaria immitis''. A lower percentage of exposed cats develop adult infections, and when this does occur the burden is usually low<sup>1</sup>. L5 in the pulmonary arteries also have a relatively short (2 year) survival time in cats.
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'''Zoonotic hazard''':
 +
*human infection can occur, but few cases are diagnosed
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*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.
  
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==Pathogenesis==
 
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Heartworm disease primarily affects the cardiopulmonary system and the severity and extent of lesions depends on several factors. These include the number and location of adult worms<sup>1, 2</sup>, the duration of infection, and the level of activity of the host<sup>1</sup>. Parasites in the pulmonary arteries cause mechanical irritation, leading to endothelial damage, proliferation of the intima and perivascular cuffing with inflammatory cells. This results in narrowing and occlusion of the vessels which in turn causes pulmonary hypertension. A combination of pulmonary hypertension and inflammatory mediators can lead to an increase in the permeability of pulmonary vessels, giving periarterial oedema and intersitial and alveolar infiltrates. Eventually, irreversible interstitial fibrosis arises.
 
  
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Sequelae to heartworm infection include pulmonary thromboembolism, which can either occur due to the death and metastasis of adult worms, or due to platelet aggregation induced by the parasite. In severe cases, live nematodes can migrate to the right ventricle, right atrium and caudal vena cava. The resulting incompetence of the tricuspid valve, augmented by concurrent pulmonary hypertension, leads to signs of right-sided heart failure. Flow of erythrocytes through the mass of parasites formed can also cause haemolysis and thus haemoglobinaemia. This combination of acute right-sided heart failure and intravascular haemolysis is referred to as "caval syndrome", which in severe cases can also be characterised by thromboembolic events and [[Disseminated Intravascular Coagulation|disseminated intravascular coagulation]]. Due to the smaller numbers of adult worms, caval syndrome is less common in cats<sup>2</sup>.
 
  
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In cats, heartworm disease generally causes a diffuse pulmonary infiltrate and an eosinophilic pneumonia<sup>2</sup>. Adult worms may die and embolise to the lungs, resulting in severe haemorrhage and oedema of the affected lobe. Immature nematodes have also been known to migrate to sites other than the pulmonary arteries and heart such as the CNS, eye and subcutaneous tissues. These ectopic infections are far more common in cats than in dogs, suggesting that ''D. immitis'' is not well adapted to feline hosts.
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=== Feline Heartworm Disease===
 +
 
 +
 
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*A canine parasite - see under Dog Nematodes for life-cycle etc.
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*Cats are abnormal hosts, and so ''D. immitis'' is not very infective for cats.
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*Nevertheless, feline infection is common (up to 25%) in some heavily endemic areas.
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*But only small numbers of adult worms (1-3) establish.
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*The prepatent period is longer (approximately 8months) than in the dog.
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*Few, if any, microfilariae are produced (<20% of cases positive).
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*The life-span of the worm is shorter (2-3years).
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*However: one dead adult → acute pulmonary crisis (thromboembolism).
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*Lung pathology similar to dog, but little heart pathology.
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*Coughing starts 4-6months post-infection.
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*Antibody-detection ELISA used for diagnosis, but false positives occur (antigen ELISA cannot be used as antigen rarely expressed in cats).
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*There is no licensed adulticidal therapy, and treatment may be fatal for the cat as well as the worm.
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*Ivermectin or selamectin can be used for prevention.
  
 
==Signalment==
 
==Signalment==
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''Dirofilaria immitis'' infection affects dogs more commonly than cats, and risk is greatest in outdoor animals. Dogs of any age may be affected, but infections are most common in 3 to 8 year old dogs, and medium and large breeds are over-represented<sup>1, 3</sup>. In cats, there are no breed or age predispositions, but males are more frequently affected<sup>3</sup>. Ferrets may also contract dirofilariasis; there are no age or sex predilections<sup>1</sup>.
 
  
 
==Diagnosis==
 
==Diagnosis==
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===Clinical Signs===
 
  
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In dogs, historical findings at the time of presentation can vary. Some animals are asymptomatic, or cough only occasionally. In countries where heartworm is endemic, animals may be routinely tested for dirofilariasis six months after the end of the high-risk season<sup>3</sup>. Therefore, positive laboratory testing may be the first indication of disease<sup>1</sup>. More obvious signs may be seen depending on the severity of disease. Generally, the onset of heartworm disease is insidious, and clinical signs are related either to a high parasite burden, or to an allergic response to the parasite<sup>2</sup>. Affected dogs most often show coughing, and dyspnoea/tachypnoea, exercise intolerance, loss of condition and syncope may also be seen. In severe cases the pulmonary vessels may rupture, leading to haemoptysis or epistaxis. There is a tendency for signs to only manifest during exercise, and so patients with a sedentary lifestyle may never show overt disease. Right-sided congestive heart failure may ensue when worm burden is high, and signs can include jugular distension, ascites, marked exercise intolerance and hepatomegaly. A systolic murmur is sometimes audible on cardiac auscultation.
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'''Diagnosis''':
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*Physical examination:
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**signs of heart disease
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**lung involvement
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*Radiography:
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**enlargement of right heart, main pulmonary arteries; arteries in lung lobes with thickening and tortuosity; inflammation in surrounding tissues
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*ECG:
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**right axis deviation → deep S waves
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*Echocardiography:
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**if post caval syndrome suspected - right ventricular enlargement with worms in ventricle appearing as parallel lines.
  
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A classification system for the presentation of heartworm disease exists<sup>1</sup>, outlined in the table below.
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'''Clinical pathology''':
 +
*needed alongside physical examination and other tests to determine treatment strategy and prognosis.
  
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{| class="wikitable collapsible"
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'''Parasite detection''':
−
|-
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*methods for demonstrating microfilariae in blood:
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!width="8%"|<center><u>'''Class '''</u></center>
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**wet blood smear (okay for quick look, but insensitive) = ''D. immitis'' not progressively motile
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!width="92%"|<center><u>'''Clinical Signs'''</u></center>
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**Knott's test = red blood cells lysed; stained sediment examined
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|-
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**micropore filter = blood forced through; microfilariae held on filter; stained and examined
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|<center>'''Class I'''</center> 
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**antibody detection ELISA = not reliable in dogs, but it is the best for cats (although some false positives)
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|'''Asymptomatic or mild disease'''
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**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
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*Weight loss, reduced exercise tolerance or an occasional cough may be seen.
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*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)
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*No radiographic signs or laboratory abnormalities.
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*operator error can give false positives, therefore best to confirm result with another test.
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|-
 
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|<center>'''Class II'''</center>
 
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|'''Moderate disease'''
 
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*Animal coughs occasionally and shows mild-to-moderate exercise intolerance.
 
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*Lung sounds may be increased
 
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*Radiography may show mild-to-moderate changes, e.g. right ventricular enlargement.
 
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*Anaemia and proteinuria may be present.
 
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|-
 
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|<center>'''Class III'''</center>
 
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|'''Severe disease'''
 
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*Signs are variable but may include weight loss, exercise intolerance, tachypnoea, dyspnoea, severe/persistent coughing, haemoptysis, syncope, or ascites.
 
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*Radiographs appear abnormal: right ventricular hypertrophy, enlargement of the main pulmonary artery, and diffuse pulmonary densities. ECG often shows right ventricular hypertrophy.
 
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*Anaemia, thrombocytopenia, and proteinuria are seen.
 
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|-
 
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|<center>'''Class IV'''</center>
 
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|'''Caval syndrome'''
 
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*Sudden onset of collapse, haemoglobinuria, and respiratory distress.
 
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*Usually fatal without immediate surgery.
 
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|-
 
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|}
 
  
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'''Caval syndrome''' is a very severe form of heartworm disease that can occur in dogs and cats. It is characterised by respiratory distress, signs of right-sided heart failure, intravascular haemolysis and haemoglobinuria. Disseminated intravascular coagulation frequently occurs, and the syndrome is often fatal.
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===Clinical Signs===
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'''Clinical signs''':
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*often sudden onset severe lethargy and weakness, but:
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*signs variable, reflecting multiple system dysfunction - pulmonary circulation, heart, liver and kidneys:
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**lung damage (severe pulmonary hypertension; thromboembolism)
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**heart failure (right-sided congestive)
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*therefore, '''not''' pathognomonic
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*acute prepatent = coughing
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*chronic = exercise intolerance, sometimes with ascites
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*acute post caval syndrome = collapse (dyspnoea, pale mucous membranes or jaundice, haemoglobinuria)
  
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In cats, most infections are asymptomatic. However, sudden death can occasionally occur. This may be preceded by an acute respiratory crisis, thought to be due to parasitic thromboembolism and obstruction of a major pulmonary artery<sup>1, 2</sup>. When clinical signs are less acute, they are vague and may include anorexia, weight loss and lethargy. Intermittent coughing and dyspnoea can appear similar to feline asthma. Syncope may also occur, and cats may vomit. The cause of this vomiting is undetermined<sup>3</sup>.
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===Diagnostic Imaging===
  
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===Radiography===
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===Laboratory Tests===
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In dogs, thoracic radiography provides good information on disease severity and is useful for screening dogs showing clinical signs compatible with ''D. immitis'' infection<sup>1</sup>. However, thoracic radiograph do not necessarily reflect the current worm burden: radiographic signs of advanced disease can persist long after an infection has run its course<sup>4</sup>. Conversely, dogs with high burdens may be inactive and thus show few clinical signs or radiographic changes. Radiographic signs are mild-to-moderate in class II disease, but become more obvious in class III infections. The main pulmonary artery is enlarged<sup>1, 4</sup>, and the caudal lobar vessels appear tortuous<sup>1</sup>. Ill-defined, fluffy infiltrates are apparent, and often surround the caudal lobar vessels. Right-sided cardiomegaly may be appreciated, and pleural and peritoneal effusions can be noted in right-sided congestive heart failure<sup>4</sup>.
 
  
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Cardiac changes on thoracic radiography are less common in cats than dogs. The caudal lobar veins are enlarged (greater than 1.5 times the width of the ninth rib), and the pulmonary arteries are blunted and tortuous<sup>3, 5</sup>. Patchy parenchymal infiltrates may be seen in the region of vessels in animals showing respiratory signs<sup>1, 3</sup>. Enlargement of the main pulmonary artery cannot normally be seen in cats, as it has a relatively midline position and is thus obscured by the cardiac silhouette<sup>1, 5</sup>. Right-sided cardiomegaly is not considered a typical finding in the cat<sup>5</sup>.
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===Pathology===
 +
'''Worms produce''':
 +
*substances that are:
 +
**antigenic
 +
**immunomodulatory
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**pharmacologically active.
  
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===Echocardiography===
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'''Lesions are''':
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In dogs, echocardiography is not particularly useful as a diagnostic tool for heartworm disease. In severe, chronic pulmonary hypertension, right ventricular hypertrophy, septal flattening, underloading of the left heart, and high-velocity tricuspid and pulmonic regurgitation may be seen<sup>1</sup>. With caval syndrome or high-burden infections, worms may be visualised in the right heart and vena cava.
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*'''not''' confined to the location of the worms
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*also caused by shear stress of high blood flow.
  
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Echocardiography is more important in cats than dogs because of the increased difficulty of diagnosis and the fact that this test can have a high sensitivity depending on operator experience<sup>1</sup>. Specificity is 100%<sup>5</sup>, and the test can help exclude or confirm other primary cardiac diseases such as hypertrophic cardiomyopathy<sup>3</sup>. Worms can be visualised as parallel hyperechoic lines<sup>1</sup>, and are seen in the right atrium and ventricle and main pulmonary artery<sup>1, 3, 5</sup>.
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'''Severity''':
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*not associated with the number of worms
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*exacerbated by exercise (i.e. by high blood flow rate)
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*sedentary dogs often asymptomatic - symptoms most commonly associated with racing greyhounds.
  
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===Electrocardiography===
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'''Acute prepatent disease''':
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The ECG of infected dogs is usually normal. Right ventricular hypertrophy patterns may be seen in chronic ,severe pulmonary hypertension and are associated with impending or apparent right-sided congestive heart failure<sup>4</sup>. Arrhythmias do not normally occur, buy atrial fibrillation is is occasionally seen in Class III disease.
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*immature adult worms in caudal distal pulmonary arteries
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*leads to intense diffuse eosinophilic reaction, which in turn leads to coughing.
  
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Electrocardiography is less useful in the cat, as involvement of the heart chambers does not occur as frequently as in the dog<sup>5</sup>.
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'''Chronic disease''':
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*mature worms in right heart and pulmonary arteries
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*endothelial swelling and sloughing
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*increased permeability → inflammation → periarteritis
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*platelets/white blood cells activated → thrombosis
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*proliferation of smooth muscle, thickening of media:
  
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===Laboratory Tests===
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→ impairment of blood flow
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In both dogs and cats, '''routine haematology, biochemistry and urinalysis''' should be performed. Most parameters are usually within normal limits, but an anaemia can often be seen. Eosinophilia and basophilia are also common<sup>1, 3</sup>. Eosinophilia peaks as L5 enter the pulmonary arteries and subsequently varies. An inflammatory leukogram is possible<sup>3</sup>. Hyperglobulinaemia due to antigenic stimulation is an inconsistent finding<sup>1, 3</sup>. Right-sided heart failure or immune-complex glomerulonephritis can lead to hypoalbuminaemia and, very occasionally, nephrotic syndrome<sup>1</sup>. Because of this, it is possible for urinalysis to reveal proteiunuria<sup>1, 3</sup>. Haemoglobinaemia and haemoglobinuria are associated with caval syndrome<sup>3</sup>.
 
  
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[[Image:dirofilariasis.jpg|right|thumb|200px|Dirofilariasis. Courtesy of T. Scase]]
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→ pulmonary hypertension
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There are several methods for the specific demonstration of ''Dirofilaria immitis'' in the animal. Firstly, direct '''microscopic examination''' allows rapid identification of microfilariae in a drop of fresh blood, as their movements can vigorously displace the surrounding red blood cells<sup>2</sup>. Despite being quick, simple and inexpensive, this test is not sufficiently sensitive to provide a definitive diagnosis, particularly when there is a low concentration of microfilariae in the bloodstream. '''Filtration methods''' therefore exist to facilitate the microscopic demonstration of microfilariae<sup>2, 3</sup>. These include the '''modified Knott's test''', which involves haemolysis, centrifugation and staining with methylene blue before direct examination. Tests such as this are more sensitive than merely examining a drop of blood, and the morphology of microfilariae can be clearly seen. However, sensitivity in comparison to other methods is still low and so microfilarial identification tests are often reserved for confirmation of weak positive antigen tests and determination of microfilarial status prior to treatment with a microfilaricide<sup>3</sup>. Cats frequently lack circulating microfilariae, and so direct microscopic examination is of little use in this species.
 
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[[Image:dirofilariasis 2.jpg|right|thumb|200px|'''Dirofilariasis'''. Courtesy of T. Scase]]
 
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Tests exist to detect ''D. immitis'' antigens. '''ELISAs''' specific for proteins released from the reproductive tract of adult female worms are available for in-house use<sup>2</sup>. Sensitivity and specificity are excellent, but small worm burdens and the presence of immature female- or male-only infections can give low antigen titres hence false negatives. This is especially common in cats. '''Specific agglutination and immunochromatography''' techniques are also available for use in dogs. Any antigen test performed in the first six months of infection may give false negative results as levels of circulating antigen are initially low while female worms mature. '''In-house tests''' are also available to detect antibody against ''Dirofilaria immitis''. The presence of antibodies confirms exposure, but does not necessarily provide information about current infection. These tests are therefore most useful for ruling out infection. ''D. immitis'' antibody tests have a low specificity<sup>2</sup> and so have largely been superceded by tests for antigen.
 
  
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'''PCR-based tests''' are highly sensitive and specific for the diagnosis of immature and adult heartworms, and are especially useful in unconventional (e.g. wildlife) hosts<sup>2</sup>. At present, these tests are not widely available for the diagnosis of ''Dirofilaria immitis''.
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→ right ventricular strain
  
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===Pathology===
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→ right ventricular hypertrophy and right-sided heart failure
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*insufficient blood pumped through pulmonary capillary bed → insufficient preload for left ventricle.
  
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On post-mortem examination, ''Dirofilaria immitis'' worms are apparent in the pulmonary artery and possibly the right side of the heart. The right side of the heart is found to be enlarged and there is proliferation of the pulmonary arterial myointima. Pulmonary thromboembolism and haemorrhage may be seen. If right-sided congestive heart failure was present in life, hepatomegaly and hepatic congestion will be apparent.
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'''Post Caval Syndrome (Dirofilarial haemoglobinuria)''':
 +
*can be acute or chronic
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*heavy heartworm infestation:
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**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.
  
 
==Treatment==
 
==Treatment==
−
Animals with right-sided congestive heart failure require stablisation with diuretics, ACE inhibitors and cage rest before treatment for heartworm disease is implemented. Animals with severe respiratory signs also require stabilisation with oxygen supplementation, anti-inflammatory doses of corticosteroid and anti-thrombotic drugs.
+
'''Chemotherapy''':
 +
*three treatment objectives needing different approaches:
  
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The specific adulticidal treatment for ''Dirofilaria immitis'' is '''melarsomine dihydrochoride''', a new generation arsenical compound. Melarsomine is administered intramuscularly into the epaxial muscles, and pressure should be applied during and after needle withdrawal<sup>3</sup>. A "graded-kill" protocol is recommended: an initial injection is followed one month later with two injections at an interval of 24 hours, given on opposite sides<sup>1-4</sup>. This spreads the killing effects over two treatments, with an aim to reducing the occurrence of thromboembolism after parasite death. Cage rest and anti-inflammatory doses of corticosteroids in the week following melarsomine treatment can also reduce the likelihood of pulmonary thromboembolism. Antigen testing four months after adulticidal treatment will determine whether it is necessary to repeat the therapy<sup>3</sup>.
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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
  
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Adulticidal treatment may be declined by the owner, owing to the risk of thromboembolism. Alternatively, it may not be possible to implement adulticidal treatment if the patient is suffering renal or hepatic failure<sup>3</sup>. In these cases, monthly administration of prophylactic doses of ivermectin is a reasonable treatment option, as it prevents further infection and may kill some adult nematodes<sup>2</sup>.
+
NB - Ivermectin preventative doses over 16months reduces adult worm numbers
  
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Even low grade infections in cats may result in pulmonary thromboembolism with adulticidal treatment. Because of this, symptomatic treatment of sick cats may be followed by surgical or catheter-based extraction of nematodes once the patient is stable<sup>3</sup>. Stablisation is similar to that for feline asthma, and can include cage rest, oxygen supplementation, bronchodilators (e.g. theophylline), tapering doses of prednisolone, and balanced fluid therapy if indicated<sup>3</sup>. Heartworms have a much shorter life-span in cats, and spontaneous remission is seen in some cases. Regular monitoring may therefore be the best course of action in clinically well cats.
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2) '''Microfilaricidal'''
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*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
  
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In '''caval syndrome''', surgery is the treatment of choice. Worms are removed from the right side of the heart and the main pulmonary artery using flexible crocodile or basket-type retrieval forceps<sup>2</sup>. This procedure is complex and requires general anaesthesia and fluoroscopic imaging, but reduces the risk of thromboembolism following subsequent adulticidal treatment. Symptomatic and supportive therapy to stabilise the patient should be continued for around one month after surgery before adulticidal treatment is administered<sup>3</sup>.
+
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
  
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'''No drugs are specifically approved for microfilaricidal treatment''' of ''Dirofilaria immitis'', and successful elimination of adult worms should result in the demise of circulating microfilariae four to six weeks later<sup>2</sup>. '''Single doses of ivermectin, milbemycin oxime, moxidection or selamectin''' are, however, effective at removing microfilariae from the circulation. The sudden death of large numbers of microfilariae may invoke an anaphylactic response, and oral prednisolone may be administered with microfilaricides to help prevent this.
+
'''Treatment of Post Caval Syndrome''':
−
+
*surgical removal with forceps via jugular vein
−
Heartworm prophylaxis should be implemented in all cats and dogs living in or visiting areas in which ''Dirofilaria immitis'' is endemic. Ivermectin or milbemycin oxime can be given ''per os'' on a monthly basis, and selemectin spot-on is effective when applied each month. If animals have already been exposed to ''Dirofilaria immitis'' it may be wise to perform an antigen test before starting treatment. In endemic countries, routine antigen testing six months after the end of the previous heartworm season will detect infections that have slipped through the net, and enable treatment during the mild, early stages of disease<sup>3</sup>.
+
*usually very successful, but:
 +
*do not crush or fragment worms
  
−
==Prognosis==
+
→ massive release of antigen
 +
 
 +
→ cardiac failure and acute respiratory distress
  
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In mildly symptomatic  or asymptomatic animals, the course of dirofilariasis is usually uneventful following treatment and the prognosis is excellent<sup>3</sup>. Animals with severe infection carry a guarded prognosis with a higher risk of complications.
+
→ rapid death
  
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{{Learning
+
'''A typical therapy protocol''':
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|literature search = [http://www.cabdirect.org/search.html?rowId=1&options1=AND&q1=%22Dirofilaria+immitis%22&occuring1=title&rowId=2&options2=AND&q2=&occuring2=freetext&rowId=3&options3=AND&q3=&occuring3=freetext&x=21&y=6&publishedstart=2000&publishedend=yyyy&calendarInput=yyyy-mm-dd&la=any&it=any&show=all Dirofilaria immitis publications since 2000]
 
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|full text = [http://www.cabi.org/cabdirect/FullTextPDF/2010/20103181752.pdf '''A review of American heartworm society guidelines for the management of heartworm infections in cats.''' Guerrero, J.; The North American Veterinary Conference, Gainesville, USA, Small animal and exotics. Proceedings of the North American Veterinary Conference, Orlando, Florida, USA, 16-20 January 2010, 2010, pp 1173-1176, 1 ref.]
 
  
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[http://www.cabi.org/cabdirect/FullTextPDF/2008/20083097550.pdf '''Epidemiology and prevention of ''Dirofilaria'' infections in dogs and cats.''' Genchi, C.; Guerrero, J.; McCall, J. W.; Venco, L.; Veterinary Parasitology and Parasitic Diseases, Naples, Italy, Mappe Parassitologiche, 2007, 8, pp 145-161, many ref.]
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1) Pre-treatment evaluation
  
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[http://www.cabi.org/cabdirect/FullTextPDF/2006/20063226177.pdf ''' Heartworm of dog - its aetiopathogenesis, diagnosis, treatment and prevention.''' Kundu, P.; Intas Pharmaceuticals Ltd, Ahmedabad, India, Intas Polivet, 2006, 7, 1, pp 106-110, 16 ref.]
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2) Adulticide: 4-6weeks restricted exercise
  
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[http://www.cabi.org/cabdirect/FullTextPDF/2005/20053201370.pdf ''' The utility of echocardiography in the diagnosis of feline heartworm disease: a review of published reports.''' Defrancesco, T. C.; Atkins, C. E.; Seward, R. L.; Knight, D. H.; American Heartworm Society, Batavia, USA, Recent advances in heartworm disease: Symposium '98, Tampa, Florida, USA, 1-3 May, 1998, 1998, pp 103-106, 20 ref.]
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3) Microfilaricide: 3weeks after adulticide
  
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|Vetstream = [https://www.vetstream.com/canis/search?s=nematode Nematodes]
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4) Initiation of monthly preventative treatments
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}}
 
  
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5) Check for microfilariae after 2weeks
  
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{{Chapter}}
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6) Check for adults (ELISA) 4-6months after adulticide, and before start of each subsequent mosquito season.
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{{Mansonchapter
 
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|chapterlink = http://www.mansonpublishing.co.uk/book-images/9781840760576_sample.pdf
 
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|chaptername = Cardiopulmonary Dirofilariasis
 
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|book = Arthropod-borne Infectious Diseases of the Dog and Cat
 
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|author = Susan E. Shaw, Michael J. Day
 
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|isbn = 9781840760576
 
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}}
 
  
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==Prognosis==
 
==Links==
 
==Links==
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*[http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/11300.htm The Merck Veterinary Manual - Heartworm Disease]
 
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*[http://www.dogheartworm.org/ dogheartworm.org]
 
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*[http://www.defra.gov.uk/foodfarm/farmanimal/diseases/vetsurveillance/dactari/ DEFRA - Dog and Cat Travel and Risk Information]
 
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==References==
 
==References==
  
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#Merck & Co (2008) '''The Merck Veterinary Manual (Eighth Edition)''', ''Merial''.
 
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#Ferasin, L (2004) Disease risks for the travelling pet: Heartworm disease, ''In Practice'', '''26(6)''', 350-357.
 
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#Tilley, L P and Smith, F W K (2004) '''The 5-minute Veterinary Consult (Fourth Edition)''',''Blackwell''.
 
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#Venco, L (2007) Heartworm (Dirofilaria immitis) disease in dogs. ''Dirofilaria immitis and D. repens in dog and cat and human infections'', 117-125.
 
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#Venco, L (2007) Heartworm (Dirofilaria immitis) disease in cats. ''Dirofilaria immitis and D. repens in dog and cat and human infections'', 126-132.
 
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#Ridyard, A (2005) Heartworm and lungworm in dogs and cats in the UK, ''In Practice'', '''27(3)''', 147-153.
 
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{{review}}
 
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==Webinars==
 
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<rss max="10" highlight="none">https://www.thewebinarvet.com/parasitology/webinars/feed</rss>
 
  
 
[[Category:Filarioidea]]
 
[[Category:Filarioidea]]
 
[[Category:Dog_Nematodes]]
 
[[Category:Dog_Nematodes]]
 
[[Category:Cat_Nematodes]]
 
[[Category:Cat_Nematodes]]
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[[Category:Zoonoses]]
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[[Category:To_Do_-_Parasites]]
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[[Category:Cardiovascular Diseases - Dog]]
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[[Category:Cardiovascular Diseases - Cat]]
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[[Category:Respiratory Parasitic Infections]]
 
[[Category:Respiratory Parasitic Infections]]
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[[Category:To_Do_-_Lizzie]]
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[[Category:Expert_Review]]
 
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[[Category:Cardiology Section]]
 

Revision as of 18:07, 25 August 2010


 This article is still under construction.



Description

Dirofilaria immitus - Courtesy of the Laboratory of Parasitology, University of Pennsylvania School of Veterinary Medicine
Dirofilariasis. Courtesy of T. Scase
Dirofilariasis. Courtesy of T. Scase

Dirofilaria is a filarial worm. Female worms measure up to 30cm in length and males up to 15cm. The worms have a life-span of 5-7 years. Up to 250 worms may establish in the heart and pulmonary arteries of dogs and cats. Dirofilaria worms 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.

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.


Feline Heartworm Disease

  • A canine parasite - see under Dog Nematodes for life-cycle etc.
  • Cats are abnormal hosts, and so D. immitis is not very infective for cats.
  • Nevertheless, feline infection is common (up to 25%) in some heavily endemic areas.
  • But only small numbers of adult worms (1-3) establish.
  • The prepatent period is longer (approximately 8months) than in the dog.
  • Few, if any, microfilariae are produced (<20% of cases positive).
  • The life-span of the worm is shorter (2-3years).
  • However: one dead adult → acute pulmonary crisis (thromboembolism).
  • Lung pathology similar to dog, but little heart pathology.
  • Coughing starts 4-6months post-infection.
  • Antibody-detection ELISA used for diagnosis, but false positives occur (antigen ELISA cannot be used as antigen rarely expressed in cats).
  • There is no licensed adulticidal therapy, and treatment may be fatal for the cat as well as the worm.
  • Ivermectin or selamectin can be used for prevention.

Signalment

Diagnosis

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.

Clinical Signs

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)

Diagnostic Imaging

Laboratory Tests

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.

Treatment

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.

Prognosis

Links

References

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