Angiostrongylus vasorum, commonly known as the French heartworm, is a metastrongylid nematode that causes canine cardiopulmonary angiostrongylosis. The parasite, in its adult stage, localises to the right ventricle and pulmonary artery of the definitive host (dog, fox and occasionally wolf, coyote and ferret) causing clinical pictures of variable severity, but often fatal. The biological life cycle of this parasite is indirect and includes intermediate hosts, which are gastropod molluscs.
In the past, infection by A. vasorum was considered restricted to well-identified and isolated geographical areas (e.g. North America, south-east France, the United Kingdom and Denmark). However, recent reports of the infection from other countries, Italy included, show that the range of A. vasorum is expanding. Given the broadening spread of angiostrongylosis and the clinical severity of this infection in the dog, interest in this parasite is increasing considerably.
THE PARASITE
Angiostrongylus vasorum is a slender, small nematode (the males are 14-18 mm long, while the females are about 25 mm long). One particular morphological characteristic of the females is the position of their white-coloured ovaries, which are wrapped round the red-coloured intestine. In the definitive host the adult A. vasorum live in the right heart, in the pulmonary artery and in its branches, although, occasionally, the adults can be found in the pericardium, bladder, liver, femoral artery and anterior chamber of the eye. The females lay embyronated eggs in the sites of choice; once these eggs reach the pulmonary capillaries, they hatch, releasing first stage larvae (L1). These larvae penetrate the walls of vessels and alveoli and migrate actively up the respiratory tree to reach the pharynx; once they have reached this site, the L1 are swallowed and, after having transited through the gastrointestinal tract of the host, are eliminated to the exterior in the faeces. The biological cycle of the parasite continues with the development of L1 in the intermediate hosts, which are numerous species of gastropod molluscs (e.g. Arion spp., Arianta spp., Limax spp., Cepaea spp., Deroceras spp.).
The L1, after having been ingested by the gastropod, moult twice to reach the third larval stage (L3), which is infestant, in about 2 weeks. The life cycle of the parasite continues with the ingestion of the L3-containing mollusc by the definitive host. It has been hypothesised that various paratenic hosts, such as some species of amphibians (e.g., Rana temporaria), may be involved in the cycle or that the L3 leave the mollusc and remain free in the external environment in the gastropod’s mucus, while awaiting to continue their life cycle. The dog is infected by eating the larvae present in the gastropod or, through the alternative, yet to be demonstrated, routes. After ingestion by the dog, the L3 reach the lymph nodes of the gastrointestinal tract, moult and then, through the lymphohaematic circulation, home to the heart and pulmonary artery where they undergo sexual maturation. After mating the females begin to lay eggs; the pre-patent period usually lasts about 40-60 days, but can range from 1 to 6 months. The adult parasites can survive for many years.
The presence and distribution of A. vasorum are influenced by many factors, the most important including the biology of the intermediate hosts and the receptivity of the definitive hosts. In the last few decades there has been an increase in the spread of vector-transmitted diseases[1], including angiostrongylosis whose area of distribution has been found to have enlarged. Changes in mollusc phenology, induced by various factors such as global warming, seem to play a key role in determining this phenomenon. The age of the host and its access to the external environment and, therefore, its possibility of coming into contact with the intermediate hosts, are the most important definitive host-related factors for the transmission of the parasitosis. The animal’s temperament also plays an important role in the epidemiology of angiostrongylosis. Young animals, generally more predisposed to playing and catching prey, are those more frequently affected. Furthermore, young dogs are more receptive to the disease, since they are immunologically more sensitive to contact with the parasite.
PATHOGENIC ROLE AND SIGNS
The clinical signs occurring in angiostrongylosis are very variable and range from a few, mild signs to extremely severe cardio-respiratory signs and clotting disorders that can cause the host’s death within a short time. The clinical manifestations are more severe in young animals, in immunocompromised or immunodeficient hosts and, in general, when the parasite load is high. Repeated infections, even when caused by a small number of parasites, can also lead to the death of the definitive host.
The most common respiratory signs are cough, dyspnoea and tachypnoea and are caused by the bronchopneumonia induced by the parasite in the pulmonary vessels. The presence of adult parasites in the pulmonary artery, with consequent vascular thrombosis and muscle hypertrophy, can lead to the development of pulmonary hypertension with or without right ventricular failure (cor pulmonale). The clinical signs of the compromised cardiac function include intolerance of physical activity, ascites, pale mucosae, heart murmurs and syncope.
Clotting disorders can also develop, such as petecchiae and ecchymoses of the conjunctiva and sclera, epistaxis, haemoptysis, post-operative haematomas, gastrointestinal tract bleeding, haematuria and anaemia. The underlying mechanisms of these clotting defects have not been completely clarified but could involve the development of chronic disseminated intravascular coagulation. Infected animals have thrombocytopenia, depletion of clotting factors (factors V and VII) and a prolonged prothrombin time. Cases of immune-mediated thrombocytopenia have also been reported.
Other possible signs are neurological ones, caused by bleeding in the central nervous system or by intracranial or subdural emboli of parasites: sensorial depression, ataxia[2], convulsions, vestibular symptoms[3], paralysis[2]and acute lumbar pain. Ocular symptoms, such as uveitis[4],and gastrointestinal symptoms, such as vomiting[5], diarrhoea, anorexia and weight loss, can also occur.
DIAGNOSIS
It is extremely difficult to make a clinical diagnosis of angiostrongylosis given that the signs and symptoms are non-specific. It is, however, possible, to make a suspected diagnosis on the basis of the reported clinical picture, the history, radiological and ultrasound findings and results of biochemical and haematological investigations. The radiological changes occurring during angiostrongylosis vary depending on the period of the infection and are related to the severity of the lesions induced by the nematode in the cardiopulmonary system. The initial findings include mild opacity of the pulmonary parenchyma with interstitial and/or alveolar focal lesions. The alveolar lesions tend to be more evident after the pre-patent period and areas of pulmonary consolidation, due to haemorrhages induced by the migration of larvae, may be seen. The most severe alterations usually appear between 9 and 21 weeks post-infection and consist of increased interstitial opacity, enlargement of the cardiac shadow, dilatation of the pulmonary artery and, occasionally, pneumothorax. Despite the fact that the distribution of the alveolar changes in A. vasorum infection is always multifocal and/or peripheral, none of the above described radiological signs can be considered pathognomonic.
Although ultrasound studies can evaluate the degree of cardiac compromise, they do not enable a definitive diagnosis to be made. The main possible findings (tricuspid and pulmonary valve insufficiency, sometimes combined with regurgitation, eccentric and concentric ventricular hypertrophy, and dilatation of the pulmonary artery) are, in fact, all non-specific and only allow a diagnosis of pulmonary hypertension and cor pulmonale to be made, and, possibly, help to evaluate the severity of the parasitosis.
Blood and biochemistry tests can reveal the presence of changes compatible with clotting disorders: depletion of factors V and VII and a prolonged prothrombin time, as well as thrombocytopenia and anaemia.
The only possibility of making a certain diagnosis is to show that the parasite in present in the infected dog. The larvae of A. vasorum can be isolated by bronchoalveolar or tracheal lavage, but the techniques involved are very laborious and require skilled staff.
Copromicroscopic examination of the faeces is the simplest method for isolating and identifying the parasite. It is, however, necessary to realise that, independently of the presence of the nematode and the appearance of clinical symptoms, L1 cannot be found in the faeces in the pre-patent period. Subsequently, the larvae are eliminated intermittently and false negative results can, therefore, occur even during the course of patent, clinically evident angiostrongylosis. In order to minimise the possibility of false negative results, copromicroscopic examination of the faeces should be carried out on samples collected for 3 consecutive days or on alternate days over the period of 1 week. Faecal flotation using saturated solutions of sucrose, sodium chloride or zinc sulphate, with a specific gravity of 1200-1350, can sometimes reveal the presence of A. vasorum, but these solutions usually dehydrate the L1, preventing their identification and in some cases can cause their precipitation.
Baermann’s method is the gold standard technique for diagnosing angiostrongylosis in that it enables live larvae to be isolated (Fig. 1). Exploiting this technique it is therefore possible to morphometrically and morphologically identify the L1, thus giving a definite diagnosis. This technique does, however, require about 24-36 hours and the morphological identification of the larvae must be carried out by an expert since the L1 of A. vasorum must be distinguished from other canine parasites (e.g., Crenosoma vulpis, Filaroides spp.) and free-living nematodes. The L1 of A. vasorum are 310-400 µm long (Fig. 2) and have a curved S-shaped extremity with a dorsal spine (Fig. 3).
Molecular biology methods have recently been developed that enable parasite DNA to be detected in both the blood and faeces of infected dogs, and enzyme-linked immunosorbent assays (ELISA) can show the presence of circulating antigens of A. vasorum. However, although these approaches are sensitive and specific, they are not currently used in routine clinical practice.
TREATMENT
Although angiostrongylosis may produce only few symptoms, anti-parasitic treatment is always recommended, even in the least severe cases, given the potential danger of the disease to dogs.
Drugs used to treat this parasitic infection include macrocyclic lactones and benzimidazoles. For example milbemycin oxime is effective when administered at a dose of 0.5 mg/kg per os once a week for 4 consecutive weeks. There has been a recent comparison of the efficacy and safety of fenbendazole, administered at a dose of 25 mg/kg per os for 20 consecutive days, and a single dose of moxidectin 2.5% in combination with imidacloprid 10% in a spot-on formulation. The two compounds were safe and effective and the single dose of moxidectin was equally effective as repeated doses of fenbendazole.
Furthermore, there is experimental evidence that the spot-on formulation containing moxidectin 2.5% combined with imidacloprid 10% can prevent infections. Indeed, a single monthly administration of this formulation could eliminate developing larvae after an infestation, thus preventing the larvae from becoming adult and the parasitosis from becoming patent and, therefore, limiting pulmonary damage and clinical symptoms. Prophylactic treatment is advisable in endemic areas, given the pathogenic relevance of A. vasorum.
Suggested reading
- Ferdushy F., Hassan M.T., 2010. Angiostrongylus vasorum: the “French Heartworm”. Parasitology Research, 107:765-771.
- Morgan E.R., Shaw S.E., Brennan S.F., De Waal T.D., Jones B.R., Mulcahy G., 2005. Angiostrongylus vasorum: a real heartbreaker. Trends in Parasitology, 21:49–51.
- Morgan E.R., Shaw S.E., 2010. Angiostrongylus vasorum infection in dogs: continuing spread and developments in diagnosis and treatment. Journal of Small Animal Practice, 2010 Oct 21.
- Traversa D., Guglielmini C., 2008. Feline aelurostrongylosis and canine angiostrongylosis: a challenging diagnosis for two emerging verminous pneumonia infections.Veterinary Parasitology 157:163-174.
- Traversa D., Di Cesare A., Conboy G., 2010. Canine and feline cardiopulmonary parasitic nematodes in Europe: emerging and underestimated. Parasites & Vectors, 3:62.