Heartworm disease in the cat

The frequency of infestation by D. immitis in the cat is related to that in the dog living in the same area, but the prevalence is usually lower. Given that cats are two to four times less attractive to mosquitoes than are dogs and that 25% of cats are naturally resistant to infestation by D. immitis, the prevalence in the cat is about 10% that found in dogs [3](data verified in the field by Venco et al., 2010). The dog constitutes a reservoir for the parasite, while the cat can be considered a host of little epidemiological interest. In fact, it is a susceptible, but not ideal host for D. immitis, which rarely reaches reproduction in this species (microfilariaemia is mostly absent or transient) and has a shorter lifespan (2-3 years) in cats than in dogs (5-6 years). The low number of infesting larvae that reach maturation, the behavioural features of the cat which render the animal less exposed to the action of the intermediate host and the different association between the diptera vectors and this species of animal mean that naturally occurring infestations in the cat are caused by a small number of parasites (on average from 1 to 6).

CLINICAL ASPECTS

Despite the foregoing, the clinical relevance of heartworm infection (cardiopulmonary filariasis) is substantial because, given the cat’s small body size, even infestation by a few parasites can be considered severe in terms of the ratio between the biomass of the parasite and that of the host and, therefore, capable of threatening the survival of the infested animal. The small volumes of the right heart chambers and the pulmonary arterial circulation and the limited collateral circulation in the cat mean that even only a few parasites can cause sudden and severe cardiopulmonary failure which can lead to the death of the infested subject before appropriate treatment can be instituted. In cats the inflammatory reaction is particularly marked and is accompanied by a strongly reactive antibody immune response: this is shown by the high number of eosinophils in the lung parenchyma and the tracheal aspirate of infested cats and the positive response to an intradermal reaction test. The traumatic effect of the parasites on the endothelium of the vessels causes villous endoarteritis, cellular infiltration (of white blood cells) in the tunica intima and severe hypertrophy of the muscle layer, in particular of the caudal pulmonary arteries, caused by the release of  platelet factors and macrophages.

The clinical course of the disease in the cat is very different from that in the dog. The different individual reactivity of the infested host translates into heterogeneous clinical pictures which are ambiguous, not easily identified and do not resemble those found in dogs. It is difficult to schematise a disease as complex as heartworm, but there are completely asymptomatic subjects and paucisymptomatic ones and the signs may be acute, hyperacute or chronic (Table 1).

Table 1. Clinical manifestations of heartworm disease in cats (Drawn from Genchi et al., 1995).

In most cases the onset of an acute clinical picture coincides with the arrival of L₄ in the pulmonary arterial circulation or with the death of adult parasites and consequent phenomena of pulmonary thromboembolism.

The acute-hyperacute forms are manifested mainly by violent respiratory, gastrointestinal, cardiovascular and neurological signs. Sudden death, with no premonitory signs, is common. Among the acute forms, a special place is held by the “vena cava syndrome”, which in the cat is manifested by the same signs as those in the dog (dyspnoea, haemoglobinuria, heart murmur) but with an even faster course.

The chronic forms, which are less common, are mostly associated with respiratory and/or gastrointestinal signs which cause severe wasting to the point of cachexia. The rich literature on heartworm in the cat does not highlight problems of right heart failure, which are so common in the dog. As far as concerns lesions of the arterial walls, in comparisons of experimentally infested cats and dogs, cats seem to tolerate the presence of parasites better, since they do not develop severe pulmonary hypertension or, at any rate, levels of hypertension such as to expose the right ventricle to unsupportable pressure overloads. Furthermore, taking into consideration that the infestations are less severe (caused by few parasites) and of shorter duration than in the dog (the parasite’s life in the cat is, in fact, shorter) it can be understood that lesions of the intimal layer of the vessels, although severe, are not able to cause an increase in pulmonary resistances. Last, but not least, it should be considered that physical activity, which is one of the most important factors causing a worsening of pulmonary hypertension, is normally limited in the cat. For these reasons, right heart failure, which is so common in dogs, is found less frequently in cats.

DIAGNOSIS

The notable differences in the pathogenic mechanisms, immune response to the parasite and the clinical course of the disease in the feline host compared to the canine one have a series of consequences, also from a diagnostic point of view. The diagnostic tests used in routine clinical practice for the diagnosis of heartworm infection in the dog are difficult to apply in the cat.

Tests to detect circulating antigen, considered the gold standard in dogs because of their sensitivity and specificity, while having a high specificity do not have a high sensitivity in the cat. In fact, the antigens detected are released exclusively by the adult female parasite and in greater quantities during reproduction or death (spontaneous or drug-induced). Since infestations by only male parasites or immature larvae are common, but can, in any case cause severe clinical signs when they reach the pulmonary circulation, it is clear that an antigen-based test can lead to an underestimate of the number of truly infected animals, with a series of false negatives. Nevertheless, it is important to underline the diagnostic utility and importance of this test when the parasite load includes even a single female parasite.

Another clinically available procedure is the antibody test, which detects the immune response mediated by immunoglobulins produced by the host starting from about 8 weeks after the transmission of the infesting larvae by the vector. The immune response in cats infested by D. immitis is particularly marked (especially in the early stages of the infestation) and is efficiently stimulated by parasites of both sexes, therefore making it possible to detect infestations by only male parasites. However, the antibody response develops following contact with the infesting form of the nematode and is not necessarily related to the development of adult parasites. The tests used to detect circulating antibodies can, therefore, lead to an overestimate of the number of infested subjects, with a series of false positive results, and a diagnosis of heartworm infection based only on a positive antibody test may be misleading and unreliable. On the other hand, some studies aimed at confirming or excluding the presence of heartworms by post-mortem examinations carried out on animals that had previously undergone an antibody test showed that there was also a possibility of false negative results: this would suggest that the antibody reaction decreases with the maturation of the microfilariae, making it more difficult to detect with serological tests. Furthermore, it seems that cats with heartworm which do not have clinical signs have a higher probability of having a negative antibody test.

Despite the limitations of these diagnostic procedures they are of considerable utility and can be used in combination to achieve a higher level of diagnostic precision.

The evaluation of microfilariaemia (Knott’s test) is of little use and can, indeed, lead to deceptive results because, as already discussed, the cat rarely has microfiliariae in the blood stream and if it does, this is often a transient state. Thus, although this is a very specific test (the morphological identification of microfilariae of D.immitis is a definitive demonstration of infestation), it has a very low sensitivity.

One important instrument for diagnostic and clinical purposes is the chest X-ray, which can provide information to support a putative diagnosis by showing changes in the pulmonary arteries and lung parenchyma (dilatation of the caudal pulmonary arteries, interstitial lung pattern, foci of radio-opaque parenchyma) and, on the basis of the same alterations, enable an evaluation of the severity of the infestation. Radiographic changes can be seen in experimentally infested animals already 6 months after inoculation with larvae. Changes to the cardiac silhouette are rare. The presence of areas of radio-opaque parenchyma with enlargement of one (more frequently the right) or both of the caudal pulmonary arteries is strongly suggestive of heartworm infection in the cat. It should, however, by remembered that in some cases the radiographic picture can appear normal even in the presence of infestation or changes may be present only transiently creating the risk of a mistaken diagnosis. Natural infestations caused by a single parasite may not produce any radiographically detectable alterations. Such infestations are not uncommon given the above-described epidemiological and pathogenic features of the disease in the cat, but are in any case potentially severe for the affected subject. For this reason it is essential that the clinician, considering the advantages and limitations of each diagnostic instrument, exploits all the procedures available in order to obtain reliable results and, therefore, greater diagnostic certainty.

Echocardiography (Fig. 1) is an important instrument and, with a high-frequency probe, allows an expert to obtain a certain diagnosis if the worms are located in sites that can be investigated with ultrasound. These sites include the right heart chambers, the distal part of the venous vessels emptying into these chambers (cranial and caudal venae cavae), the common branch of the pulmonary arteries, a long segment of the right caudal lobar pulmonary artery and a short part of the left one, because of the interference caused by the air-filled lung parenchyma. It is essential to investigate all these sites, even though the worms most frequently localise in the common branch and the right lobar branch. Since these nematodes have an echogenic cuticle, they are easily seen by ultrasonography as hyperechoic, double-walled structures floating freely in the vessel lumen or in the right heart chambers. It should also be added that adult parasites are large in comparison with the pulmonary arteries of the cat, making the parasites easy to detect.

Finally, a post-mortem by a pathologist is indicated in suspected cases in which the animal dies before a diagnosis can be made or in cases in which despite the negative results of the diagnostic procedures performed it is not possible to exclude that the animal did actually have a heartworm infection. Besides the classical sites of localisation of the nematode (right heart chambers, pulmonary arterial circulation and venae cavae) it is worth investigating other sites of the body in order to exclude the presence of parasites in ectopic sites (systemic arterial circulation, body cavities and, if there are neurological signs, the brain and spinal cord). It is also worth remembering that some subjects may develop severe signs and die if pre-adult parasites, which are small and may evade observation, reach the pulmonary arterial circulation.

The difficulties in making a diagnosis of heartworm in the cat, both because of the very heterogeneous clinical pictures and the lack of a single diagnostic test which combines sufficient sensitivity and specificity, hampers estimation of the prevalence of this disease in cats in areas in which the infestation is endemic.

TREATMENT

Besides the problems described with diagnosing this disease, the treatment of heartworm is also associated with a series of problems. The medical therapy that kills the adult worms used in dogs (melarsomine dihydrochloride) cannot be prescribed for cats because of the high risk of it causing contemporaneous death of the parasites and also because of the low therapeutic index of this substance in the feline species.

Although infestations in the cat are often caused by few parasites, it must not be forgotten that, given the small volumes of the right heart chambers and the pulmonary arterial circulation, even a few parasites can cause sudden and severe cardiopulmonary failure and such infestations should, therefore, be considered extremely serious and potentially fatal.

For the same reasons, another alternative used in dogs, i.e., monthly doses of ivermectin for a prolonged period (for at least 2 years) is excluded, although studies are underway on its use (or that of moxidectin) in cats in association with the administration of doxycycline (for an anti-symbiont effect on Wolbachia spp.)

Surgical treatment in the cat, unlike in the dog, is considered extremely dangerous because, given the small size of the jugular vein in the cat, it is not always possible to remove the parasites from the heart chambers without damaging them. Accidental dissection of the adult worms often leads to the release of substances into the circulation which cause shock and subsequent death of the host animal.

For these reasons, the only treatment advised in cats with heartworm disease is supportive therapy with corticosteroids, in order to control the signs until the life cycle of the adult parasite is completed spontaneously and the infested subject is cured by itself.

PROPHYLAXIS

In the light of all the above the importance of providing the owner correct information is clear: it must be explained that the only effective management is prophylaxis. In cats, as in dogs, the prevention of heartworm involves the use of macrocyclic lactones: ivermectin, selamectin, milbemycin oxime and moxidectin, administered monthly per os or using spot-on formulations, guarantee effective protection from transmission of the parasite.

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