Elusive Angiostrongylus vasorum infections
© Di Cesare et al. 2015
Received: 23 July 2015
Accepted: 17 August 2015
Published: 27 August 2015
The parasitic nematode Angiostrongylus vasorum causes severe clinical signs in dogs. The disease is often challenging because infected animals are often presented with clinical signs overlapping those of other diseases.
The present article describes six angiostrongylosis cases (Cases 1-6) that represent key examples of how canine angiostrongylosis may be extremely confounding. The six animals presented clinical signs compatible with canine angiostrongylosis but they were subjected to clinical examinations for other diseases (e.g. dirofilariosis or immune-mediated disorders) before achieving a correct diagnosis.
In Case 1 clinical, radiographic and ultrasound examinations' results resembled a lung neoplasia. Case 2 was a dog with a mixed infection caused by A. vasorum and Dirofilaria immitis. Case 3 was a critically ill dog presented in emergency for an acute onset of dyspnoea caused by lungworm infection. The dog died a few hours after presentation despite support and etiologic therapy. Case 4 was a dog presented for chronic hemorrhages and ecchymoses caused by thrombocytopenia of unknown origin, thought to have an inherited, immune-mediated or infective cause. Case 5 was referred for neurological signs due to a suspected discospondylitis. Case 6 was erroneously diagnosed infected only with D. immitis although the dog was infected only with A. vasorum. A timely administration of an anthelmintic (mostly moxidectin) showed to be effective in treating the infection in those dogs (i.e. Cases 1,2, 4 and 5) that did not suffer with severe lung haemorrhages yet.
Dogs 1-5 were referred in two regions of Italy that are considered non-endemic for A. vasorum. These findings indicate that veterinarians should include angiostrongylosis in the differential diagnosis of cardio-respiratory distress also in non-endemic regions and should perform appropriate diagnostics in the presence of compatible signs even if the clinical picture is atypical.
Angiostrongylus vasorum (Nematoda, Metastrongyloidea) is a molluscan-borne parasitic nematode affecting the heart and pulmonary arteries of dogs and wild canids [1–3]. This nematode is present in well-known endemic foci of Europe (i.e. France, UK and Denmark) but it has been recently found in dogs living in regions previously considered free of infection [3–6], e.g. central and southern regions of Italy [7, 8]. At present, there is a clear indication for a geographic expansion of A. vasorum in countries of Europe. In infected dogs clinical signs range from a subclinical infection to severe, acute or hyperacute respiratory and cardiac distresses, coagulopathies, gastrointestinal and neurological disorders, with possible fatal outcomes [2, 5, 7, 9, 10]. The diagnosis is difficult because clinical, laboratory, and diagnostic imaging findings are not specific and subclinical or atypical pictures may occur [9, 11, 12]. A suspicion can be confirmed with the detection of L1s via the Baermann’s test  or of circulating antigens with a rapid kit .
However, many veterinarians are not vigilant about dog angiostrongylosis and these methods are not applied in several canine practices. It is important that the guard against this parasite is kept high in both endemic and previously free regions. The present article describes six unexpected cases of dog angiostrongylosis in Italy and discusses the importance of appropriate diagnostic approaches even in territories that are not considered endemic.
Before starting with any treatment, the dog was subjected to a routine copromicroscopic examination that showed the presence of A. vasorum larvae in the faeces. Then, the animal was treated with Advocate® before initiating the treatment for cardiopulmonary filariosis. In the month after treatment with moxidectin the clinical signs gradually disappeared and, the Baermann examination was negative for A. vasorum. The echocardiography showed the persistence of filariid echoes in the right pulmonary artery without signs of pulmonary hypertension. After a few days, to avoid any risk of thromboembolisms, the dog underwent surgical removal of about ten heartworms and recovered completely.
Results and discussion
Although these dogs showed clinical signs compatible with angiostrongylosis, other differential diagnoses were chosen at first attempt. Therefore, it is indicated that dogs presenting a clinical picture compatible with angiostrongylosis should always be examined with appropriate diagnostic methods before excluding the infection even when other diseases are more plausible.
The clinical signs presented by the here examined dogs were due to the typical pathogenic mechanisms caused by A. vasorum, i.e. inflammation triggered by parasite eggs and larval stages in the lungs, and by damage caused by adult worms in the pulmonary vessels. In particular, infected dogs suffer from obstructed thrombotic endarteritis and fibrosis, and additionally, the parasite induces alterations of metabolic pathways (e.g. chronic Disseminated Intravascular Coagulation, DIC) [1–3, 5, 7–10]. In Case 1, clinical signs and Rx features were suggestive of a lung disease, including A. vasorum. However, veterinarians were misled to make another diagnosis by cytological examination and the absence of reports of this nematode in northern regions of Italy. In fact, the cytological findings of lesions were typical of lung haemangiosarcoma, that usually does not release neoplastic cells but only peri-tumoral tissue reaction .
The simultaneous presence of A. vasorum and D. immitis in Case 2 represented an intriguing case study as it provided a difficult diagnostic challenge. In fact A. vasorum was not suspected because history (i.e. the dog lived in a D. immitis-hyper-endemic region of northern Italy) and clinical findings were consistent with a diagnosis of cardiopulmonary filariosis. However, this dog had a subclinical occult dirofilariosis and the respiratory distress was due only to A. vasorum. Indeed, the similar localization of A. vasorum and D. immitis may cause overlapping clinical signs but A. vasorum is more prone than D. immitis to cause acute life-threatening diseases. Therefore, in this case an early diagnosis of angiostrongylosis was crucial to prevent the onset of a severe disease and death. Unfortunately, this was not the case of Case 6. In fact the detection of A. vasorum L1s coincided with a sudden worsening of the clinical condition of the dog. As moxidectin has a very high efficacy in treating dog angiostrongylosis [2, 3], the dog died from a severe lung hemorrhage that likely started hours before the administration of the anthelmintic. Interestingly, potential cross-reactions with A. vasorum in commercially available test kits for the diagnosis of filariosis were recently described for experimentally A. vasorum-infected dogs  but not for the Snap Test here used. This is the first evidence for a false positive reaction of the IDEXX 4Dx Plus® Test for D. immitis in a dog naturally infected with A. vasorum. Further studies are necessary to understand if this is an occasional finding due to the limit of specificity of the test (99.3% ); or more frequent cross-reactions may occur in clinical settings. On the other hand, it should be noted that the test was run using a sample of whole blood that could interfere with the reading phase of the test, thus causing difficulties in the interpretation of the result.
The critical presentation of Case 3 is not common for A.vasorum infection and the cause of the severe respiratory distress of the dog was not thought to be of parasitic origin until characteristic diagnostic imaging lesions put A. vasorum in the possible differential diagnoses. In this case a direct fecal smear proved useful in rapid detection of the lungworm considering the emergency situation of the dog. This copromicroscopical technique could be very helpful in emergencies, nevertheless a more sensitive and easy to perform test is now available for rapid detection of A.vasorum antigens on blood (IDEXX Angio DetectTM).
The hemostatic disorder of Case 4 was initially thought to be due to a poisoning but the finding of a severe thrombocytopenia led to a suspicion of inherited abnormal production of platelet or infective or haemoprotozoan diseases. Diagnostic imaging abnormalities observed in the thorax were compatible with hemorrhagic lesions and could fit easily the hemostatic disorder, thus masking the lungworms infection. Angiostrongylosis was not considered initially because this region of Italy is not considered endemic for A. vasorum and also because the clinicopathological picture of immune-mediated thrombocytopenia secondary to angiostrongylosis without evidence of intravascular coagulation is infrequent .
The atypical neurologic presentation of the dog n. 5 misled the clinicians to a discospondylitis or myelitis suspicion but a subsequent CT, performed to evaluate the spinal cord, revealed the coexistence of lung lesions compatible with A. vasorum.
At present, dog angiostrongylosis is emerging in several areas due to biological and epizootiological drivers, e.g. global warming and changes in dynamics of intermediate hosts and fox populations [3, 4]. At the same time, D. immitis, which is hyper-endemic in Northern Italy, is spreading southward in Italy [7, 18] and also in European regions where also A. vasorum is expanding at the same time [3, 19]. Under a practical standpoint, the presence of clinical signs that could be present in both infections, should alert veterinarians to perform appropriate diagnostic techniques for both parasitoses. Angiostrongylosis should be further investigated also in dogs living in regions where the parasite is expected with null or low prevalence or even when more frequent diseases are suspected. The present report indicates that veterinarians are prone to exclude some diseases based on each local epizootiological situation. In fact, in Italy, dog angiostrongylosis is endemic in central and southern regions of Italy, while its occurrence in dogs living in the North is negligible and confined in certain areas [8, 20]. A prompt diagnosis of dog angiostrongylosis is crucial because, albeit the parasite may be life-threatening, the anthelmintic treatment is simple, straightforward and most often successful. In particular, a single application of moxidectin spot-on presents a high efficacy, i.e. similar to that observed in dogs treated with fenbendazole daily at 25 mg/kg for 20 days  and overlapping the efficacy achieved using milbemycin oxime (0.5 mg/kg) given orally once a week for 4 weeks . Also, additional treatments (one or two, 15 days apart) with moxidectin are able to stop the larval shedding in dogs which are still infected after the first treatment, along with clinical and radiological improvements [8, 21, 23]. The cases here presented confirmed the efficacy of moxidectin spot-on and fenbendazole in treating A. vasorum. The death of dog n. 6 despite the administration of moxidectin was caused by the severity of the lung lesions and the pulmonary hemorrhages that in all likelihood started before the administration of the parasiticide. Under a practical point of view, it should be noted that easy-to-apply spot-on products are a suitable choice for the treatment of canine parasitoses when the alternative is represented by oral products requiring multiple dosing. In fact, the administration of oral formulations can be problematical in indocile, feral or moribund animals.
Considering that the current epizootiological changes will favor a spread of A. vasorum in previously free areas and an overlapping distribution of this nematode with that of D. immitis, a simultaneous use of highly specific diagnostic tools is crucial in both epizootiological surveys and clinical cases where these heartworms may occur and dogs present compatible clinical signs. Recently, an in-clinic rapid kit (IDEXX Angio Detect™ Test) has been marketed to achieve a fast and reliable diagnosis of the infection in veterinary practices . The use of this kit, along with the Baermann’s test, would allow a fast and reliable diagnosis of dog angiostrongylosis and a timely anthelmintic treatment. The use of this rapid kit in routine screening of animals living in endemic areas is crucial especially for the occurrence of asymptomatic infected dogs .
The Authors are grateful to Roland Schaper and Bayer Animal Health (Leverkusen, Germany), for supporting the publication of this article.
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