Summary

Despite a widespread focus on the diagnosis, treatment and prevention of Angiostrongylus vasorum in the veterinary literature lungworm infections in dogs and cats remain somewhat of an enigma to many vets in general practice. While several species of lungworm are clinically relevant, A. Vasorum is common and can be highly pathogenic. Furthermore, there is now convincing evidence of geographic spread within the wildlife reservoir and in the incidence of clinical cases in our canine patients. Diagnostic tests for the accurate identification of infected animals are now much more readily available. Well informed clinicians are therefore much better equipped to deal with the challenges that this group of parasites presents. The aim of this webinar is to review the lifecycle, epidemiology, pathogenesis, diagnosis, treatment and prevention of Angiostrongylus vasorum in particular, but also to consider the other helminth parasites of the canine and feline respiratory systems.

Canine Lungworms

Angiostrongylus vasorum

Epidemiology

Recent post mortem examination surveys in foxes agree with suggestions from practice surveys and case reports that there is strong evidence for the northward spread of A vasorum in the UK.

While the parasite is now undoubtedly established in parts of Scotland and northern England, its prevalence remains higher in long-standing endemic foci in the south. Consequently, geography remains a risk factor for infection in dogs.

Foxes act as a reservoir and climate change and increased rainfall are likely to favour parasite development and transmission, so it seems likely that the parasite will continue to become more common and widely distributed.

Increased awareness should ensure that angiostrongylosis, which can present in unusual ways and remains challenging to diagnose in some cases, does not escape recognition as it likely has been in the past.

More options are now available for preventive worming as well as treatment. Hopefully this should help to curtail further spread in future.

Life cycle

Adult parasites are located in the right side of the heart and the pulmonary arterial circulation, and, being small in size, are often found in the small arteries in the periphery of the lungs, as well as the heart chambers.

Eggs contain larvae that hatch and cross into the alveoli and are carried to the pharynx and swallowed, to pass out in the faeces. These stage 1 larvae (L1) develop within slug and snail intermediate hosts to the infective, third larval stage (L3). Development from L1 to L3 takes several weeks, with the exact time depending on temperature.

The development from L1 to L3 is a critical phase of the life cycle. Without a mollusc intermediate host development of L3 larvae cannot take place.

Slugs and snails are infected by ingesting dog or fox faeces, although penetration of the tegument might also occur. Dogs are infected by ingesting infected molluscs containing mature L3.

Experimental studies have shown that L3 can sometimes leave the intermediate host and persist for several days in lab conditions. There is no categorical evidence that this occurs in the natural environment, but it remains possible that dogs could be infected from the environment directly, for example, by drinking surface water or eating vegetation contaminated with L3.

Frogs can act as both paratenic and intermediate hosts for A vasorum and it is possible that other vertebrates act as natural paratenic hosts for the parasite, although the main route of infection for dogs is still likely to be ingestion of infected slugs and snails, either intentionally or accidentally.

Clinical presentation

The majority of cases tend to be in young dogs (less than 24 months of age).

Breeds such as cavalier King Charles spaniels and Staffordshire bull terriers have been reported to be overrepresented in some studies.

However, dogs of all ages and breeds are known to be at risk of infection and disease is often diagnosed in older dogs.

Dogs infected with A vasorum can present with a wide variety of clinical signs, some of which can be severe and life threatening in nature.

A vasorum is the most pathogenic lungworm in the UK.

Mortality varies among studies, with an estimated rate of 2 to 13 per cent in those seen in specialist referral facilities) despite appropriate treatment and intervention.

Mortality in the wider population and in dogs seen in first-opinion practice is unknown.

Most common clinical presentation: cardiorespiratory, including coughing (presumably due to the presence of parasite eggs and larvae in the lungs, and associated inflammation) and respiratory distress.

Cardiorespiratory clinical signs can be seen in combination with bleeding disorders and/or neurological signs.

In some cases, bleeding disorders and neurological signs can be seen in the absence of obvious cardiorespiratory clinical signs.

A vasorum infection should be a differential in any bleeding patient or those with a wide variety of neurological presentations.

Dogs presenting with coagulopathy generally have a poorer prognosis than those without.

Pulmonary hypertension is also described, which may lead to echocardiographic changes (such as right atrial and ventricular dilatation, atrial septal deviation, a dilated pulmonary trunk and tricuspid and pulmonary insufficiency.

In one retrospective study pulmonary hypertension was noted in 14.6% of cases. Patients with moderate to severe pulmonary hypertension had a significantly shorter survival time than patients without evidence of pulmonary hypertension.

Rare clinical presentations are also described in the literature, such as ocular larval migrans, gastric dilation (most likely secondary to aerophagia), exsanguination secondary to ruptured femoral artery (in an experimentally infected dog) and parasitic dermatitis.

Some dogs may be asymptomatic despite active infection and consequently these patients can present with bleeding problems during routine/elective surgery

Diagnosis

Baermann technique

Baermann faecal examination is often referred to as the gold standard diagnostic test for A vasorum. Baermann faecal examination relies upon adequate larval shedding and accurate identification based on the parasite’s distinct morphological features, especially a notable kink and spine at the end of the tail.

Despite its place as a gold standard, the sensitivity of faecal Baermann is low due to the inability to detect larvae before completion of the prepatent period and intermittent parasite shedding.

Pooling three faecal samples can increase the sensitivity, but further limitations include the time taken to yield results (up to eight hours) and the practicalities of acquiring three samples of faeces from an ill dog.

The Baermann technique remains the gold standard test because the specificity of the test remains high. Furthermore, it is a multivalent test in that it can recover larvae of multiple species of lungworm.

As a result of the test’s inherent downsides the Baermann technique seems to have been superseded by the Angiodetect (IDEXX) ‘bedside’ blood test in most cases in the general practice setting. However, it should also be remembered that the efficacies of all other available definitive diagnostic tests have been tested against Baermann faecal examination as the gold standard test.

Faecal smear

Direct faecal smears are a simple test to perform at the ‘bedside’ and can provide rapid results, but the sensitivity is inferior to the Baermann technique.

To prepare a faecal smear, a small amount of faeces is mixed in a drop of water on a microscope slide, and the slide tilted such that the drop hangs down away from the larger debris. A coverslip should then be placed on the drop and the slide examined at low and then medium power.

Except in faeces grossly contaminated with grass and soil, the presence of numerous larvae indicates probable lungworm infection and justifies treatment.

Bedside Blood Testing

The SNAP Angiodetect (IDEXX) test detects circulating parasite antigen in blood, is easy to use and the results are obtained in less than 15 minutes.

The reported sensitivity of this test is 84.6 per cent in dogs testing positive by the Baermann technique and its specificity is 100 per cent, with no cross-reactivity to other tested parasites, including lungworms (Schnyder and others 2014).

In practical terms, a positive result is very reliable, but a negative result in a case highly suspicious for disease should be followed up with an alternative diagnostic test or retested at a later date, without delaying appropriate prompt treatment.

Other General Laboratory Findings

General laboratory and diagnostic imaging findings can provide supportive evidence for a diagnosis of A vasorum infection and also enable directed therapy and give parameters that can be monitored over time.

Angiostrongylus infection is commonly associated with an eosinophilia (found in approximately 50 per cent of reported cases) and hyperglobulinaemia (with a 2-globulin peak) (found in approximately 75 per cent of reported cases) on routine blood testing.

Prolonged coagulation times and a reduction in platelet numbers is usually attributable to a chronic disseminated intravascular coagulation (DIC), but other causes of coagulopathy are postulated and include a secondary immune-mediated thrombocytopenia (IMTP), acquired von Willebrand’s factor deficiency and a decrease in clotting factors V and VIII.

The pathophysiological mechanism of IMTP secondary to A vasorum infection is thought to involve the development of antiplatelet antibodies triggered by the parasite. However, the exact pathophysiological mechanism for the other coagulation derangements is not fully understood: it may be that a protein is secreted or released by the parasite (either the adult or the larvae), which then triggers a coagulopathy, but at present there are no studies confirming this. It is also possible that DIC is linked to endothelial disruption by the migrating larvae and adult parasites.

An overview of the coagulation parameter changes seen in DIC is shown below.

Coagulation parameter Expected result with decompensated DIC

Prothrombin time (PT) Increase or normal

Activated partial thromboplastin time Increase (often before the PT)

Fibrinogen Mild decrease (consumptive)

Fibrin degradation products Increase (positive test result)

D-dimers Increase (positive test result)

Platelets Mild decrease (consumptive)

It should be borne in mind that an angiostrongylus triggered coagulopathy can present with no obvious changes to coagulation parameters in very rare cases Very rarely, cases of coagulopathy in angiostrongylosis may have no obvious changes to coagulation parameters.

Anaemia has been reported in approximately one third of all cases and is usually regenerative in nature and therefore accounted for by blood loss. Hypercalcaemia (thought to be secondary to granuloma formation) and low serum levels of fructosamine have also been reported, though inconsistently.

Diagnostic Imaging

Diagnostic imaging modalities are useful to raise the clinical index of suspicion of disease or support a diagnosis. Thoracic radiographic findings typically include an initial diffuse bronchial thickening and interstitial pattern with focal (often peripheral) alveolar infiltrates. As the patent period develops, a patchy alveolar pattern predominates.

Treatment

Drug Examples of trade name Preparation Licensed

Species

UseLegal

categoryTreat Prevent

Moxidectin/ imidacloprid

Advocate (Bayer) Endectrid (MiPet) Spot on D + C

Angiostrongylus vasorum Crenosoma vulpis

Dirofilaria immitis Dirofilaria repens A vasorum Spirocerca lupi

POM-V

Prinovox (Virbac) Spot on D + C D immitis A vasorum C vulpis

D immitis D repens A vasorum S lupi POM-V

Afoxolaner and milbemycin oxime

NexGard Spectra (Merial/ Boehringer Ingelheim)

Chewable tablet D A vasorum D

immitis POM-V

Fenbendazole

Granofen (Virbac)Panacur (MSD Animal Health) Wormazole (Norbrook)

Granules D + C

Oslerus (Filaroides) osleri Cats infected with Aelurostrongylus abstrusus

NFA-VPS

Milbemycin oxime/ praziquantel

Milbemax (Elanco Animal Health)

Chewable tablet D + C C vulpisA vasorum

Thelazia callipaeda D immitis POM-V

Milpro (Virbac) Flavoured tablet

Dogs and cats

C vulpisA vasorum D immitis POM-V

Milbactor (Ceva) Milquantel (MSD Animal Health)

Tablet Dogs and cats

C vulpisA vasorum T callipaeda

A vasorum D immitis POM-V

POM-V Prescription-only medicine – veterinarian, NFA-VPS Non-food animal – veterinarian, pharmacist, suitably qualified person

In the UK there are two products currently licensed to treat A vasorum infection: imidacloprid/moxidectin in combination and milbemycin oxime. However, fenbendazole is also widely used, despite the lack of a licensed indication for the treatment of A vasorum. The reason for this is unknown but it may be due to a lower perceived risk of anaphylaxis from rapid worm kill, although this would also be the case with the licensed products.

Based on the veterinary cascade, veterinarians should prescribe imidacloprid/moxidectin or milbemycin oxime before using fenbendazole.

Supportive care

Given the variety of clinical presentations in cases of angiostrongylosis, there is often a requirement for supportive care and a blood transfusion is indicated for some patients with bleeding disorders.

As anaphylaxis following rapid worm kill is rare using modern anthelmintics, high doses of immunosuppressive corticosteroids are not indicated unless the clinician confirms (or strongly suspects) that immune-mediated disease has been triggered by the parasite.

Oxygen supplementation and anti-inflammatory doses of corticosteroids are, however, often indicated for patients with significant respiratory signs, although there is a weak evidence base for the use of steroids even in this situation.

Prevention

Imidacloprid/moxidectin and milbemycin oxime are both licensed preventive drugs when applied on a monthly basis. For this reason, these products have been included in the routine worming regimen of many practices’ pet healthcare plans.

However, the actual compliance rates for monthly dosing of these products is unknown and is likely to decline with time. Some anecdotal reports suggest that long-term compliance rates could be as low as 30 – 40%. Consequently, lungworm infection should not be categorically ruled out based on assumed monthly compliance rates of 100%. Even one missed dose is known to significantly increase the risk of a new infection.

It is also recommended that owners are encouraged to adhere to best practice as follows:

Keep dogs up to date with a full worming regimen and consider the above prophylactic anthelmintics.

Dispose of faeces daily. Consider reducing the access of foxes to gardens and reduce contact with slugs. Avoid off-lead walks after dark in damp weather and in habitats frequented by foxes.

Crenosoma vulpis

Life cycle and epidemiology

C vulpis causes respiratory disease that can be severe but without the bleeding disorders recognised in angiostrongylosis cases. This species resides as adults in the upper respiratory tract of the infected animal.

Its life cycle is similar to that of A vasorum, with larvae shed in the faeces and infecting slug and snail intermediate hosts, where they develop into the infective stage and are ingested by dogs. Again, foxes act as a reservoir of infection.

C vulpis is widespread throughout the UK and there is no evidence of recent geographical spread or increased prevalence.

Diagnosis

Dogs can harbour asymptomatic infection.

When clinical signs occur, they are respiratory in nature (a productive cough often accompanied by retching that will become chronic if not appropriately treated; in some cases, there is a purulent nasal discharge), which is secondary to an inflammatory response to the adult worms within the bronchial tree.

Findings on thoracic radiographs are varied and non- specific. They may include diffuse bronchial patterns with alveolar infiltrates and nodular densities.

Examination using bronchoscopy can demonstrate erythema and inflammation with a mucopurulent discharge. Eosinophils usually predominate on the cytological examination of BAL fluid, although their absence does not rule out the disease.

A definitive diagnosis is made by finding L1 or adults/ late larval stages in BAL fluid or on faecal examination.

Recovery of L1 from faeces is possible using the Baermann migration-sedimentation method, which can be conducted in any practice laboratory. However, C vulpis L1 are typically not as numerous or as vigorous as those of A vasorum and this method is likely to under diagnose C vulpis infection, especially when there are co-infections.

The larvae can be distinguished from those of A vasorum by their smoothly tapering tails, without the kink of A vasorum, although this requires some specialist experience and many laboratories do not specify the species or erroneously identify all larvae as A vasorum.

First stage larvae of Crenosoma vulpis (left) and Angiostrongylus vasorum (right) found in faeces of a dog isolated by the Baermann method.

The practical consequences of confusing the two species are generally limited as licensed anthelmintics are generally effective against both species.

Treatment

In the UK, two products are currently licensed to treat C vulpis infection: imidacloprid/moxidectin and milbemycin oxime but, as for A vasorum, fenbendazole is also used, despite not being licensed for treatment.

Supportive therapy is less likely to be required, compared to treatment for A vasorum.

Generally, the prognosis is good, although some treatment failures and disease relapses have been reported.

Filaroides (previously Oslerus) osleri

Life cycle and epidemiology

Unlike A vasorum and C vulpis, Filaroides osleri has a direct life cycle and L1 are thought to be mainly transmitted from a bitch to its pups in the sputum. This is a globally distributed parasitic disease that can occur as individual cases or as an outbreak in dogs that are housed together; for example, in kennels. It is usually a disease of young dogs (often those less than two years of age) and, although it can occur in older animals, it rarely causes clinical signs. The adult worms inhabit nodules at the base of the trachea.

Diagnosis

Dogs usually present with chronic respiratory signs: mild to severe inspiratory sounds or wheezing, dyspnoea and/or coughing, which is often harsh in nature and accompanied by retching. As such, these dogs may be misdiagnosed as having infectious tracheobronchitis or ‘kennel cough’.

A definitive diagnosis is made by finding larvae on faecal Baermann or zinc sulfate flotation examination. Larvae and eggs may also be seen in the sputum or tracheal wash fluid. Radiographs may demonstrate tracheal thickening with ill-defined soft tissue densities within the trachea; a tracheoscopy is very useful to visualise these nodules.

Treatment

Fenbendazole is the licensed preparation for treatment of F osleri. Efficacy is demonstrated by the absence of clinical signs, a negative faecal analysis and resolution of nodules on repeat tracheoscopy/bronchoscopy, although it can take several weeks for any nodules to resolve fully. If F osleri causes problems in kennels, monitoring of infection and regular anthelmintic treatment ought to reduce worm burdens and control the disease.

Filaroides hirthi

Filaroides hirthi appears to be widely distributed globally but is relatively uncommon and is rarely diagnosed clinically.

It can be present in the adult form in plaques or nodules in the lung parenchyma, and L1 in the sputum may be passed to pups; outbreaks of disease have been recorded in breeding kennels.

Some dogs may remain healthy while infected, while others can develop severe disease or even die. Severe disease is more likely in young, small-breed or immunosuppressed dogs. Clinical signs, if they occur, are often respiratory in nature, that is, coughing or dyspnoea.

Treatment

Albendazole given orally at 25 mg/kg twice a day has been successful at clearing infection, whereas fenbendazole has been reported to be unsuccessful in historical cases.

Eucoleus species

Eucoleus species (previously Capillaria species) infect the upper respiratory tract of dogs and other species: Eucoleus aerophilus occurs in the trachea and Eucoleus boehmi in the nasal passages. Little information is available on current epidemiology or the implications or management of infection in dogs.

Eucoleus aerophilus can infect cats, causing respiratory signs including increased breath sounds, sneezing, wheezing and a dry cough. This species has long been considered mild to non-pathogenic, but case reports suggest that this view might be complacent. Wildlife surveys (eg, in foxes) indicate a wide distribution across the UK.

Toxocara canis

Toxocara canis undergoes hepatotracheal migration after larvated eggs have been ingested, and transplacentally transmitted larvae accumulate in the lungs until birth. In both situations, respiratory signs can ensue and are most severe in pups soon after birth, when larvae in the lungs mobilise synchronously and can cause pulmonary damage, which is evident as coughing, dyspnoea and sometimes nasal discharge. Respiratory signs are only present in very heavy infections. Larvae transmitted to the pup via milk do not migrate via the lungs.

As dogs get older, hepatotracheal migration occurs less frequently following oral infection, with larvae arresting in the somatic tissues instead.

Prevention of pulmonary toxocarosis in pups should focus on effective treatment of migrating larvae in bitches and early routine treatment of pups, starting from two weeks of age. There is no effective way of removing the reservoir of somatically arrested larvae completely.

Feline lungworms

Aelurostrongylus abstrusus

Life cycle and epidemiology

Adult Aelurostrongylus (Ae) abstrusus worms are found in the lung parenchyma and bronchioles, within nodules. The life cycle is generally similar to that of C vulpis in dogs, with L1 larvae shed in the faeces and developing in slug and snail intermediate hosts.

Cats are infected by ingestion of the mollusc or an infected paratenic host, which can include rodents and birds; such hosts are likely to be more important for the transmission of lungworms in cats than in dogs.

There is very little data on how common or clinically important Ae abtrusus is likely to be in the UK.

Diagnosis

Cats infected with Ae abstrusus may be asymptomatic or present with mild to severe respiratory disease, which is caused by an inflammatory response to the presence of the parasite. Features can include coughing, wheezing, sneezing, nasal discharge, dyspnoea and tachypnoea.

Anorexia is present in some cases and, occasionally, pulmonary hypertension can lead to death. Nevertheless, most cases are of mild to moderate severity. Findings on thoracic radiography are variable. Combinations of alveolar, bronchial and interstitial patterns are reported. Young cats (often less than one year of age) tend to have an alveolar pattern. Miliary interstitial densities and vascular pathology are also reported. Sternal lymphadenopathy was detected in 43 per cent of cases in one study.

Ae abstrusus is therefore a differential diagnosis in any case of intrathoracic lymphadenomegaly, together with neoplasia, other infectious disease such as tuberculosis, granulomatous disease, and so on.

A definitive diagnosis is made when L1 are found in either faeces or BAL fluid, although, as with all of the above parasites, their absence does not necessarily rule out disease.

Treatment

Early diagnosis and treatment greatly improves the prognosis of cats with lungworm. Fenbendazole is currently the only licensed preparation for the treatment of Ae abstrusus in the UK.

Prednisolone (at an anti-inflammatory dose) is thought to be beneficial at alleviating some of the clinical signs during treatment with parasiticides.

Prevention

There are currently no licensed products to prevent Ae abstrusus in the UK.

Preventing hunting is likely to lower the risk of cats acquiring Ae abstrusus.

Other feline lungworms

E aerophilus has a wide host range and can infect cats, causing respiratory signs including increased breath sounds, sneezing, wheezing and a dry cough. This species has long been considered mild to non-pathogenic, but case reports suggest that this view might be complacent.

Wildlife surveys (eg, in foxes) indicate a wide distribution across the UK.