First report on clinical feline heartworm (Dirofilaria immitis) infection in Romania

Heartworm disease (HWD) is a severe and potentially fatal cardio-pulmonary disease caused by the mosquito-borne filariod Dirofilaria immitis, primarily infecting dogs, but also other carnivores, including domestic and wild felids. Adult worms are located in the pulmonary arteries and occasionally in the right heart. The dog is considered the main reservoir, although D. immitis can also affect cats and other mammal species, and in rare cases, humans (McCall et al., 2008). HWD is endemic in Mediterranean countries but currently an increase in the geographical range and its spreading towards central and eastern European areas are reported (Genchi et al., 2011).

Cats are also susceptible to heartworm infection, although they are considered more resistant to infection than are dogs. There are some indications based on which the cat is considered an imperfect or not ideal host for heartworms, such as: low adult worm burden (1 – 6 worms) (Dillon et al., 2007), their short life span (2 – 3 years) (Genchi et al., 2008), lack or short duration of microfilaremia, and a prolonged pre-patent period (8 months) (Dillon et al., 2007; Atkins et al., 2008). Therefore, most cats seem to tolerate heartworm infection for prolonged period without or only with transient clinical signs (González-Miguel et al., 2010).

Moreover, clinical signs associated with HWD in cats are usually nonspecific, comprising predominantly respiratory sings (intermittent coughing, dyspnea, tachypnea, ataxia) but also gastrointestinal disorders (e.g. vomiting, diarrhea, weight loss, anorexia), as well as the frequent asymptomatic course of feline dirofilariosis in which the sudden death of the animal is sometimes the only clinical sign shown (Dillon, 1984; McCall et al., 1994; Lee & Atkins 2010). Some spontaneously self-cure as a result of natural death of parasites in infected cats without showing clinical signs or a suddenly acute respiratory syndrome may arise without warning (Atkins et al., 2000; McCall et al., 2008). All these facts make the diagnosis of HWD in cats more difficult and underestimated (Lee & Atkins 2010).

Dirofilariosis is usually diagnosed by detection of the circulating microfilariae in the peripheral blood, immunological tests (ESDA, 2017) and molecular approaches (Liu et al., 2005; Nuchprayoon et al., 2006). Because of the specific features that characterize HWD in cats, reflected by the relatively low adult worm burden, low intensity and transitory microfilaraemia, low circulating anti-genemia, the diagnostic approach to feline heartworm infection must incorporate a combination of testing methods (Lee and Atkins, 2010). Of these, heartworm serology (antigen test, antibody test), thoracic radiography and echocardiography are considered the most useful tools of clinical confirmation (Atkins et al., 2000; ESDA, 2017).

Though microfilaraemia is seldom present in infected cats, because patency is short, and performing a modified Knott test for detecting circulating microfilariae is rarely successful, when present, microfilaraemia is considered a definitive diagnosis (ESDA, 2017). However, serological tests are typically the initial screening tool for feline dirofilariosis and have been used for large-scale studies (Kramer & Genchi, 2002) and also to assess clinical infections (Atkins et al., 2000). Currently, commercially available antigen tests, that target a protein in the reproductive tract of adult females, are considered highly specific and sensitive (100 % and 98.9 %, respectively) methods for infection screening or for confirming a clinical suspicion (Genchi et al., 2018). However, sensitivity can be lower in case of low burden or single worm/sex infection (ESDA, 2017). Antibody tests are able to detect infection by both male and female worms and are the only tests that can be positive as early as 2 months post infection (Morchon et al., 2004) but do not confirm a current infection or the presence of adult worms (Snyder et al., 2000).

In cats with either immature or adult heartworms, significant parenchymal and airway disease is manifested radiographically and histologically (Atkins et al., 2000; Dillon et al., 2007). Therefore, additionally, and independent of serologic test results, thoracic radiography may provide strong evidence of feline HWD and is valuable for assessing the severity of disease and its monitoring (ESDA, 2017). Also, echocardiography is a useful adjunctive test in cats with clinical suspicion of HWD and, in almost all cases, is the only definitive way to diagnose infection antemortem (Atkins et al., 2008 ).

During the last years, several different Polymerase-Chain-Reaction (PCR)-based protocols have been developed for single species or simultaneous detection of different Dirofilaria species in cats using nested and multiplex PCR and PCR-RFLP (Restriction Fragment Length Polymorphism), respectively assays, as useful diagnostic tools to detect the D. immitis low infection in feline HWD (Liu et al., 2005; Nuchprayoon et al., 2006).

The clinical importance of HWD in cats has increased in recent years, especially in heartworm endemic areas, mainly do to increased awareness of this disease, as even a small number of worms are potentially life-threatening (McCall et al., 1994).

In the last decade the dynamics of canine HWD in Romania has been changed from sporadic to emerging (Ionita et al., 2012) and currently an alarming increased prevalence is reported, with endemic foci in South-Eastern areas (Mircean et al., 2012; Girdan et al., 2015; Pana et al., 2018). However, to our knowledge, there are no reports about feline heartworm disease in Romania. Here we describe a clinical case of natural heartworm infection in a cat in Southern Romania.

All applicable national and institutional guidelines for the care and use of animals were followed.

Over the recent decades feline dirofilariosis, caused by D. immitis heartworm, has gained the attention of the scientific community which recognized significant differences between feline and the classical, better known, canine heartworm disease, in all aspects: host response, patho-physiology, and clinical presentation (Lee & Atkins 2010; ESDA, 2017). Therefore, a conscious awareness of clinicians of its existence is critical.

Here we describe the first survey carried out on the clinical evolution and radiographic and echocardiographic features of a naturally heartworm-infected cat in Southeastern Romania. To the authors’ knowledge, no epidemiological surveys were carried out to investigate the exposure of cats to D. immitis infection in Romania.

In contrast to heartworm infection in dogs, the prevalence of feline heartworm infection is less well defined because definitive ante-mortem diagnosis is difficult to achieve. Additionally, according to the current opinion, most feline HW infections are asymptomatic, which support the idea that the true prevalence of HW infection in cats in HW-endemic areas is underestimated (Venco et al., 2008). However, it is generally estimated to be 5 % to 20 % that of the canine population in a particular area (Hermesmeyer et al., 2000). This estimation is supported by recent field surveys, such as epidemiological surveys in Italian endemic areas and the metropolitan area of Barcelona (Spain), that reported a prevalence of feline HW infection of approximately 10 % and 10.4 %, respectively of that of dogs in the same area (Venco et al., 2011; Montoya-Alonso et al., 2014).

For Romania, recently, several studies have been reported on existing endemic foci for canine HWD in Southeastern Romania, the infection rate values varying from 13.4 % to 23.0 % (Ionita et al., 2012; Girdan et al., 2015; Anghel et. al., 2016; Pană et al., 2018). The infected cat in the present study originated from such heartworm-endemic area in Southeastern Romania, Moreover, the cat was living with dogs of which 20.8 % were confirmed to be heartworm infected. These demonstrate that cats from that area are at high risk for HW infection and it is very likely that many clinicians are not aware about the real risks of cats for HWD. Further epidemiological surveys will elucidate the current status of feline dirofilariosis in Romania.

Moreover, it is suggested that cats that are living in the urban areas are also at risk to be infected with heartworm. Building construction and human activity increase the density of potential hosts and develop suitable environments for the proliferation of mosquitoe populations due to an increase in the provision of water sources and vegetation (Harrus & Baneth, 2005; Petrίc et al., 2014).

The outdoor lifestyle of the infected cats in the present study appears as a risk factor for HW infection. It is states that outdoor lifestyle increases cat’s exposure to mosquito vectors in HW-endemic areas (Genchi et al., 2008). However, different studies showed that cats living strictly indoors are not fully protect against HW infection, as between 19 % and 27 % of confirmed HW-infected cats were indoor only (Atkins et al., 2000).

The observed patho-physiology and clinical picture including history of vomiting, intermittent coughing, and increased respiratory efforts, are of the most common clinical signs heartworm-infection associated in cats (Venco et al., 2015). The echocardiography has proved the clinical suspicion of heartworm disease in the cat with positive serology (Ab test), but the Ag test for circulating D. immitis microfilariae was negative. These findings clearly support the recommendation that multiple test diagnosis must be used for clinical confirmation of HWD in cats, some of which may need to be repeated, especially in endemic areas characterized by high index of suspicion (ESDA, 2017).

Recent evidence-based knowledge acquired from various field studies on the detrimental effects of the both larval and adult stages of D. immitis that can potentially have of any exposed cat, clearly demonstrate that prevention against infection in cats is the best approach to feline heartworm disease (Venco et al., 2015). For this, there are several highly effective heartworm preventive products commercially available, all from the macrocyclic lactone group. Therefore, a monthly feline heartworm chemoprophylaxis with either ivermectin (24 μg/kg) or milbemycin oxime (2.0 mg/kg) orally, or topical selamectin (6 – 12 mg/kg), moxidectin (1.0 mg/ kg), or eprinomectin (0.48 mg/kg) is recommended at least during of the heartworm transmission season (Lee & Atkins, 2010; ESDA, 2017).

The present study shows that cats are at risk for D. immitis infection in heartworm-endemic areas in Romania. Additionally, this study highlights the urgent need for increased awareness among veterinary practitioners of the existence of feline heartworm disease and for adequate prophylactic measures to be applied.