Feline Leishmaniosis

Edited November, 2016

The Leishmaniosis in cats guidelines were first published in the J Feline Med Surg 2013, 15: 638-642 by Maria Grazia Pennisi et al. The present guidelines were updated by Maria Grazia Pennisi.

 

 

Synopsis

 

Leishmania infection is less known in cats than in dogs and humans; felids were traditionally considered as resistant, and canids as the main reservoir. Only sporadic feline disease cases have been reported worldwide, mainly caused by L. infantum. Epidemiological investigations have confirmed, however, that feline infections are not rare and that disease occurrence might be underestimated in endemic areas.

 

Cats are infected by the same Leishmania species that infect dogs and humans in tropical and subtropical areas worldwide. Sand fly vectors take blood meals from cats and are competent vectors for L. infantum, as shown experimentally.

 

Skin lesions (ulcerative, crusty, nodular or scaly dermatitis) are the most frequent clinical manifestation and sometimes the only finding at physical examination. Lymph node enlargement, weight loss, ocular involvement (nodular blepharitis, uveitis, panophthalmitis), decreased appetite, chronic gingivo-stomatitis, lethargy are the most frequent non-cutaneous findings, alone or in combination.

 

Direct confirmation can be obtained by cytology, histology, isolation or PCR from the skin, lymph nodes, blood or any affected tissue. Serology using validated immunofluorescence test, ELISA, direct agglutination or Western blot have been used to assess infection frequencies or to support the diagnosis in affected cats.

 

The information available for treatment is based only on case reports. Despite clinical improvements following long term oral administration of allopurinol (10-20 mg/kg q12h or q24h), the infection is not cleared, and recurrence of clinical signs may occur after the cessation of therapy, similar to dogs (EBM grade IV). Meglumine antimoniate (5-50 mg/kg or 375 mg/cat SID SC/IM under different protocols and as well in association with allopurinol) was less frequently used and led to good clinical responses, but a long term follow-up is lacking (EBM grade IV).

 

Preventative tools (ectoparasiticides effective against sandflies and vaccines) are licensed for dogs only.

 

Agent

 

After malaria and lymphatic filariasis, leishmaniasis is the third most important vector-borne disease in people; it is caused by several Leishmania species, most of zoonotic concern (Solano-Gallego et al., 2009). In veterinary medicine, canine leishmaniosis caused by L. infantum is of primary interest, because dogs are the main reservoir of the parasite for humans, and management of the canine disease may be challenging (Baneth et al., 2008).

 

Cats are naturally infected by the same Leishmania species that affect dogs and humans in tropical and subtropical areas worldwide: L. infantum in the Mediterranean basin, Iran and Brazil; L. mexicana in Texas, USA; L. braziliensis in Brazil and French Guiana; L. amazonensis in Brazil; L. venezuelensis in Venezuela (Bonfante-Garrido et al., 2001; Schubach et al., 2004; de Souza et al., 2005; Hatam et al., 2009; Trainor et al., 2010; Vides et al., 2011; Rougeron et al., 2011; Pennisi et al., 2015).

 

The susceptibility of cats has been confirmed by experimental studies (Kirkpatrick et al., 1984; Simoes-Mattos et al., 2005).

Fig. 1. Life cycle of Leishmania donovani. Wikipedia, public domain.

Fig. 1. Life cycle of Leishmania donovani. Wikipedia, public domain.

 

Life cycle and transmission

 

Leishmania spp. are protozoan parasites, the natural history of which involves two hosts: the phlebotomine sand fly and a vertebrate (Fig. 1). The vector harbours flagellated extracellular promastigote forms and transmits them to a vertebrate host; there, the parasite changes into the amastigote form that is able to survive and replicate in intracellular vacuoles within macrophages. Haematophagous female sand flies transmit the promastigotes or may take up amastigotes from an infected vertebrate host.

 

There is no evidence that ticks and fleas are involved in natural Leishmania transmission (Baneth et al., 2008; Solano-Gallego et al., 2009). The risk for transmission in the absence of sand flies is negligible, but transplacental infection occurs as a rare event in both dogs and humans (Baneth et al., 2008; Solano-Gallego et al., 2009). Venereal transmission is a potential way of infection (da Silva et al., 2009). Other types of direct transmission have been suggested to explain the spread of the infection among kennel dogs in the USA, in the absence of sand fly vectors (Baneth et al., 2008; Solano-Gallego et al., 2009). The risk of transmission by blood transfusion is important for humans and dogs in endemic areas (Baneth et al., 2008; Solano-Gallego et al., 2009; Kaplan et al., 2009).

 

Many studies have demonstrated that sand flies take blood meals from cats and they  have been found infected by L. infantum  after feeding on naturally infected cats (Maroli et al., 2006; da Silva et al., 2010).

 

 

Epidemiology

 

Leishmaniosis caused by L. infantum is an emerging disease globally (Baneth et al., 2008; Solano-Gallego et al., 2009). Using molecular diagnostic techniques on dogs in endemic areas, it was shown that the prevalence of the infection is much higher than that of the disease (Lombardo et al., 2012). The same is true for people: in some endemic areas, latent infections approach 30% of the population, based on a positive leishmanin skin test (Kaplan et al., 2009). Feline leishmaniosis is sporadically reported worldwide, usually from the same areas where the disease occurs in dogs or humans (Pennisi et al., 2015). Cases have been seen in Switzerland, in cats imported from Spain; increased pet movement throughout Europe will lead to more disease also in non-endemic areas (Rüfenacht et al., 2005).

 

Epidemiological studies have been performed during the last 15 years in endemic areas using serological (immunofluorescence, ELISA, Western blot, direct agglutination) and/or parasitological methods (cytology, immunohistochemistry, PCR); the rates of infection vary widely, which may be due to the methodology used, the geographic area, and population under study. Positive blood PCR rates range between 0.43 and 61% of the population tested, and antibody prevalence between 3 and 59% (Pennisi et al., 2015).

 

 

Pathogenesis

 

Disease development is influenced by immunological factors, which are linked to the complex genetic background of the hosts, as demonstrated by studies in laboratory animals, dogs and humans (Baneth et al., 2008). In people, L. infantum can induce anything between a local skin lesion and a severe visceral disease. The latter form is the typical presentation in immune-incompetent patients (Kaplan et al., 2009). In dogs, leishmaniosis is a multisystemic disease with a wide spectrum of severity that reflects the balance between the protective cell-mediated, and the non-protective humoral immune response. In both humans and dogs there is a dynamic range from subclinical infection to self-limiting mild and non-self-limiting severe disease (Baneth et al., 2008; Solano-Gallego et al., 2009).

 

In all host species, macrophages play a central role in the control of the infection. Cytokines such as IFN-γ, IL-2 and TNF-α, secreted by activated T cells, stimulate macrophages to intracellular killing of Leishmania amastigotes. The presence of Leishmania-infected macrophages is usually associated with a granulomatous inflammatory reaction (Baneth et al., 2008). Lymphoid hyperplasia is also common. A massive antibody response is associated with severe disease and responsible for immune complex deposition in the kidney, with glomerulonephritis and subsequent renal failure (Baneth et al., 2008; Solano-Gallego et al., 2009).

 

Histopathology of feline skin lesions mainly shows a diffuse granulomatous dermatitis with macrophages containing many Leishmania parasites, or a granulomatous perifolliculitis and lichenoid tissue reaction/interface dermatitis, with a lower parasite load (Navarro et al., 2010; Puleio et al., 2011). Granulomatous inflammation has also been seen in the liver and kidney (Puleio et al., 2011).

 

Epidemiological studies have shown that Leishmania infection of cats is more common than the associated disease; cats may remain PCR and antibody positive for a long time (Pennisi et al., 2015). Cats may be more resistant than dogs to developing disease.

 

Clinical signs

 

Canine leishmaniosis is usually chronic and progressive, with an incubation period lasting for months or even years. Any tissue or organ may be involved, but skin lesions are most suggestive, and renal disease is most important prognostically (Solano-Gallego et al., 2009).

 

Fig. 2. Leishmania infantum associated ulcerative dermatitis in a cat (courtesy Maria Grazia Pennisi)

Fig. 2. Leishmania infantum associated ulcerative dermatitis in a cat (courtesy Maria Grazia Pennisi)

 

Feline leishmaniosis caused by L. infantum has been documented mainly in the last twenty years in Europe or Brazil (Pennisi et al., 2015). Cases have been reported in cats of all ages, almost all domestic shorthair, with no gender predilection, but quite often a retroviral infection is also detected. Some cats suffer from other concurrent disease as squamous cell carcinoma, or had been treated with immunesuppressive drugs before developing clinical manifestation caused by L. infantum.

Skin lesions are the most frequent clinical manifestation, which sometimes are the only finding at physical examination. Ulcerative, crusty, nodular or scaly dermatitis is found mainly on the head and neck (Fig. 2, 3), less often on the trunk and legs. Pruritus is usually absent; alopecia or a poor coat condition are reported. Conversely some cats do not show any skin lesions and lymph node enlargement, ocular involvement (nodular blepharitis, uveitis, panophthalmitis), chronic gingivo-stomatitis, decreased appetite, weight loss and lethargy are the most frequent non-cutaneous findings. Dehydration, pale mucous membranes, vomiting, hepatomegaly, fever, jaundice, polyuria/polydipsia, spleen enlargement, nasal discharge, recurrent abortion, dyspnoea are also found, though less often.

 

Fig. 3. Leishmania infantum associated hemorrhagic nodule in a cat (courtesy Maria Grazia Pennisi)

Fig. 3. Leishmania infantum associated hemorrhagic nodule in a cat (courtesy Maria Grazia Pennisi)

 

Information on clinico-pathological abnormalities is scarce, however non regenerative anemia, hyperglobulinemia and proteinuria are most frequently reported. In a few cases followed up until death or euthanasia, glomerular disease and chronic renal failure have been seen to develop (Pennisi et al., 2004).

 

Clinical and clinico-pathological abnormalities can obviously be influenced also by concurrent diseases as well as retroviral infection.

 

 

Immunity

 

Leishmania immunity is complex. In the dog, a susceptible species, protective immunity against L. infantum is CD4 T cell mediated, and the release of IFN-γ, IL-2 and TNF-α is associated with anti-leishmania activation of macrophages. A combination of high antibody levels and a reduced cell-mediated response are found in dogs developing the disease (Baneth et al., 2008; Solano-Gallego et al., 2009).

 

Sick cats possess specific antibodies, and hyperglobulinemia is often found. As reported for dogs, Leishmania PCR-positive healthy cats may be seronegative for anti-Leishmania antibodies (Pennisi et al., 2012, 2015).

 

Infection experiments with L. braziliensis have shown that the development of skin lesions precedes antibody appearance, and seroconversion occurs when the lesions are healing (Simoes-Mattos et al., 2005).

 

An association between FIV and L. infantum infections was found in endemic areas. Most cats developing clinical signs are suspected to have an impaired immune system because of concurrent FIV infections, FIV plus FeLV infections, cancer (squamous cell carcinoma), diabetes mellitus, autoimmune disease (pemphigus foliaceus), treatment with corticosteroid or other immune suppressive drugs (Pennisi et al., 2000, 2012; Sobrinho et al., 2012).

 

Fig. 4. Lymph node smear from a cat: Leishmania amastigotes in a macrophage (MG-G stain; x64 objective). Photomicrograph courtesy Maria Grazia Pennisi)

Fig. 4. Lymph node smear from a cat: Leishmania amastigotes in a macrophage (MG-G stain; x64 objective). Photomicrograph courtesy Maria Grazia Pennisi)

 

Diagnosis

 

The diagnosis can be accomplished by parasitological (cytology, histology, PCR, isolation) and serological methods (immunofluorescence test, ELISA, direct agglutination, Western blot). In most feline cases where cytology, isolation and PCR were performed, they confirmed the diagnosis obtained using lymph node, skin, bone marrow or blood samples (Fig. 4). Ocular disease caused by L. infantum was diagnosed by histology after enucleation of the affected eye. Upon post mortem examination, parasitological evidence of infection was obtained also from samples of the spleen, liver, kidney, pancreas, and gastro-intestinal organs (Pennisi et al., 2015). Immunohistochemistry has been used on skin biopsies (Navarro et al., 2010; Puleio et al., 2011).

 

Serological tests for leishmaniosis are not commercially available. Recently immunofluorescence testing has been validated for usage on feline samples (Pennisi et al., 2012).

 

 

Treatment

 

The available information is mostly based on single case reports or case series, not always with an appropriate follow-up (EBM grade IV) (Pennisi et al., 2015). Long-term administration of allopurinol (10-20 mg/kg SID or BID) is usually clinically effective, even in FIV-positive cats; however, the infection is not cleared and clinical signs may recur after stopping therapy, as is the case in dogs (Pocholle et al., 2012; Pennisi et al., 2015). Meglumine antimoniate (5-50 mg/kg or 375 mg/cat SID SC/IM under different protocols and as well in association with allopurinol) was less frequently used for therapy  giving good clinical responses (Pennisi et al., 2015; Basso et al., 2016). Surgical excision of nodules done in two cats was followed by recurrence (Costa Durao et al., 1994; Rüfenacht et al., 2005).

 

Prevention

 

Information is not available for the prevention of feline leishmaniosis. In dogs the disease is prevented by means of application of repellent agents against sand flies and, more recently, also by vaccination (Solano-Gallego et al., 2009).

 

 

Zoonotic risk

 

Leishmania species reported in cats are of zoonotic concern but no information is available on the risk associated for owners of infected cats. Vectorial transmission is considered the main way of transmission for L. infantum and dogs are considered the main peridomestic reservoir. In any case, only one study performed in Iran found that owners of infected dogs have a higher risk for leishmaniosis caused by L. infantum (Gavgani et al., 2002).

 

 

References

 

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