Leishmaniosis

Edited November 2, 2015

 

 

The Leishmaniosis in cats guidelines that the present article is updating were published in J Feline Med Surg 2013; 15: 638-642 by Maria Grazia Pennisi et al.

 

 

 

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.

 

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.3, 25 (EBM grade IV) Meglumine antimoniate (5-50 mg/kg or 375 mg/cat SID SC/IM under different protocols) was used for therapy in 4 cases and led to good clinical responses, but a long term follow-up is lacking.2 (EBM grade IV)

 

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.1 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.2

 

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.3-10

 

The susceptibility of cats has been confirmed by experimental studies.11,12

 

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

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

 

Life cycle and transmission

 

Leishmanias 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.1,2 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.1,2 Venereal transmission is a potential way of infection.13 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.1,2 The risk of transmission by blood transfusion is important for humans and dogs in endemic areas. 1,2,14

 

Many studies have demonstrated that sand flies take blood meals from cats; experimentally, sand flies have been found competent vectors for L. infantum in cats.15,16

 

 

Epidemiology

 

Leishmaniosis caused by L. infantum is an emerging disease globally.1,2 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.17 The same is true for people: in some endemic areas, latent infections approach 30% of the population, based on a positive leishmanin skin test.14 Leishmaniosis is sporadically reported worldwide, usually from the same areas where the disease occurs in dogs or humans.3 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.18

 

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%.3

 

 

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.2 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.14 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.1,2

 

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.2 Lymphoid hyperplasia is also common. A massive antibody response is responsible for immune complex deposition in the kidney, with glomerulonephritis and subsequent renal failure.1,2

 

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.19,20 Granulomatous inflammation has also been seen in the liver and kidney.20

 

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.3 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.1

 

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.3 Cases have been reported in cats of all ages, almost all domestic shorthair, with no gender predilection. 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. Lymph node enlargement, weight loss, ocular involvement (nodular blepharitis, uveitis, panophthalmitis), decreased appetite, chronic gingivo-stomatitis, 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; in a few cases followed up until death or euthanasia, glomerular disease and chronic renal failure have been seen to develop.21

 

Data from complete blood counts and serum protein electrophoresis are available but the results may have been influenced by concurrent disease as well as retroviral infection. Various haematological abnormalities have been described in three cats suffering from pancytopenia; in one of them, a retrovirus-negative patient with myelofibrosis, 4% of the circulating neutrophils contained Leishmania parasites.22 Hyperglobulinaemia and gammopathy are found in most investigated cases.3

 

 

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 gamma-interferon, IL2 and TNF-alpha is associated with anti-leishmania activation of macrophages. A combination of high antibody levels and a reduced cellular, mixed Th1 and Th2 response is found in dogs developing the disease.1,2

 

All 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.3,23

 

Infection experiments with L. braziliensis have shown that the development of skin lesions precedes antibody appearance, and seroconversion occurs when the lesions are healing.12

 

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. 23-25

 

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.3 Immunohistochemistry has been used on skin biopsies.19,20

 

Serological tests for leishmaniosis are not commercially available. Recently immunofluorescence testing has been validated for usage on feline samples.23

 

 

Treatment

 

The available information is mostly based on single case reports, not always with an appropriate follow-up (EBM grade IV).3 Long-term administration of allopurinol (10-20 mg/kg SID or BID) is usually clinical 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.3,26 Meglumine antimoniate (5-50 mg/kg or 375 mg/cat SID SC/IM under different protocols) was used for therapy in 4 cases giving good clinical responses.3 Surgical excision of nodules done in two cats was followed by recurrence.18,27

 

 

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.1

 

 

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.28

 

 

References

 

  1. Solano-Gallego L, Koutinas A, Miró G, Cardoso L, Pennisi MG, Ferrer L et al. Directions for the diagnosis, clinical staging, treatment and prevention of canine leishmaniosis. Vet Parasitol 2009; 165:1-18.
  2. 2 Baneth G, Koutinas AF, Solano-Gallego L, Bourdeau P, Ferrer L. Canine leishmaniosis – New concepts and insights on an expanding zoonosis: part one. Trends Parasitol 2008; 24:324-330.
  3. 3 Pennisi MG. La leishmaniosi felina dalla A alla Z. In: Leishmaniosi canina: recenti acquisizioni su epidemiologia, implicazioni cliniche, diagnosi, terapia e prevenzione. Cremona: Edizioni Veterinarie, 2010, pp. 59-64
  4. 4 Hatam GR, Adnani SJ, Asgari Q, Fallah E, Motazedian MH et al. First report of natural infection in cats with Leishmania infantum in Iran. Vector Borne Zoonotic Dis 2009; 10: 313-316
  5. Vides JP, Schwardt TF, Sobrinho LS, Marinho M, Laurenti MD, Biondo AW et al. Leishmania chagasi infection in cats with dermatologic lesions from an endemic area of visceral leishmaniosis in Brazil. Vet Parasitol 2011; 178:22-8.
  6. Trainor KE, Porter BF, Logan KS, Hoffman RJ, Snowden KF. Eight cases of feline cutaneous leishmaniasis in Texas. Vet Pathol 2010; 47:1076-81.
  7. 7 Schubach TM, Figueredo FB, Pereira SA, Madeira MF, Santos IB, Andrade MV. American cutaneous leishmaniasis in two cats from Rio de Janeiro, Brazil: first report of natural infection with Leishmania (Viannia) braziliensis. Transaction of the Royal Society of Tropical medicine and Hygiene 2004; 98: 165-167
  8. Rougeron V, Catzeflis F, Hide M, De Meeûs T, Bañuls AL. First clinical case of cutaneous leishmaniasis due to Leishmania (Viannia) braziliensis in a domestic cat from French Guiana. Vet Parasitol 2011;181:325-8.
  9. 9 de Souza AI, Barros EM, Ishikawa E, Iiha IM, Marin GR, Nunes VL. Feline leishamniasis due to Leishmania (Leishmania) amazonensis in Mato Grosso do Sul State, Brazil. Vet Parasitol 2005; 128:41-45.
  10. 10 Bonfante-Garrido R, Melendez E, Barroeta S. Cutaneous leishmaniasis in Barquisimeto, Lara State, Venezuela. Abstract book of Worldeish 2; 2001 May20-24; Hersonissos, Crete (Greece). p 21
  11. 11 Kirkpatrick CE, Farrell JP, Goldschmit MH. Leishmania chagasi and donovani: experimental infection in domestic cats. Exp Parasitol 1984 ; 58:125-131.
  12. 12 Simoes-Mattos L, Mattos MR, Teixeira MJ, Oliveira-Lima JW, Bevilacqua CM, Prata-Junior RC et al. The susceptibility of domestic cats (Felis catus) to experimental infection with Leishmania braziliensis. Vet Parasitol 2005; 127: 199-208
  13. 13 da Silva SM, Ribeiro VM, Ribeiro RR, Tafuri WL, Melo MN, Michalick MS. First report of vertical transmission of Leishmania (Leishmania) infantum in a naturally infected bitch from Brazil. Vet Parasitol 2009; 166:159-62.
  14. 14 Kaplan JE, Benson C, Holmes KH, Brooks JT, Pau A, Masur H; Centers for Disease Control and Prevention (CDC); National Institute of Health; HIV Medicine Association of the Infectious Diseases Society of America. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institute of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 2009; 58: 1-207.
  15. 15 Maroli M, Pennisi MG, Gramiccia M, Di Muccio T, Khouri C, Lo Giudice S et al. First report of experimental Leishmania infection in Phlebotomus perniciosus fed on a cat with natural acquired leishmaniosis in Italy. Parassitologia 2006; 48: 332
  16. 16 da Silva SM, Rabelo PF, Gontijo Nde F, Ribeiro RR, Melo MN, Ribeiro VM et al. , Michalick MS. First report of infection of Lutzomyia longipalpis by Leishmania (Leishmania) infantum from a naturally infected cat of Brazil. Vet Parasitol 2010; 174:150-4.
  17. 17 Lombardo G, Pennisi MG, Lupo T, Migliazzo A, Caprì A, Solano-Gallego L. Detection of Leishmania infantum DNA by real-time PCR in canine oral and conjunctival swabs and comparison with other diagnostic techniques. Vet Parasitol 2012; 184:10-17.
  18. 18 Rüfenacht S, Sager H, Mueller N, Schaerer V, Heier A, Welle MM et al. Two cases of feline leishamniasis in Switzerland. Vet Rec 2005; 156: 542-545.
  19. 19 Navarro JA, Sanchez J, Peňafiel-Verdù, Buendìa AJ, Altimira J, Vilafranca M. Histopathological lesions in 15 cats with leishmaniosis. J Comp Pathol 2010; 143:297-302.
  20. 20 Puleio R, Tamburello A, Lupo T, Migliazzo A, Loria GR, Pennisi MG. Aspetti istopatologici, immunoistochimici e molecolari in quattro casi di leishmaniosi felina. Proceedings of the 8th National Congress of the Italian Society of Veterinary Pathologists (AIPVet); 2011 Jun 15-17; Padova, Italia. p 87
  21. 21 Pennisi MG, Venza M., Reale S, Vitale F, Lo Giudice S. Case report of leishmaniasis in four cats. Vet Res Comm2004; 28: 363-366
  22. 22 Marcos R, Santos M, Malhão F, Pereira R, Fernandes AC, Montenegro L et al. Pancytopenia in a cat with visceral leishmaniasis. Vet Clin Pathol 2009; 38: 201-205.
  23. 23 Pennisi MG, Lupo T, Malara D, Masucci M, Migliazzo A, Lombardo G. Serological and molecular prevalence of Leishmania infantum infection in cats from Southern Italy [abstract]. J Feline Med Surg 2012; 14:656-657
  24. 24 Pennisi MG., Maxia L, Vitale F, Masucci M, Borruto G, Caracappa S. Studio dell’infezione da Leishmania mediante PCR in gatti che vivono in zona endemic. Proceedings of the 54th National Congresso of Società Italiana delle Scienze Veterinarie. 2000 Sept 28-30; Riva del Garda, Trento (Italia). Messina: Grafiche Scuderi, 2000, pp. 215-216.
  25. 25 Sobrinho LS, Rossi CN, Vides JP, Braga ET, Gomes AA, de Lima VM et al. Coinfection of Leishmania chagasi with Toxoplasma gondii, Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) in cats from an endemic area of zoonotic visceral leishmaniasis. Vet Parasitol 2012; 187:302-6.
  26. 26 Pocholle E, Reyes-Gomez E, Giacomo A, Delaunay P, Hasseine L, Marty P. Un cas de leishmaniose féline disséminée dans le sud de la France. Le chat (Felis catus), réservoir potential de Leishmania infantum. Parasite 2012; 19: 77-80
  27. 27 Costa Durao JF, Reselo E, Peleteiro MC, Correia JJ, Simoes G. Primeiro caso de leishmaniose em gato domestico (Felis catus) detectado em Portugal (Concelho de Sesimbra). Nota Preliminar. Revista Portuguesa de Ciencias Veterinarias 1994; 89:140-144.
  28. 28 Gavgani AS, Mohite H, Edrissian GH, Mohebali M, Davies CR. Domestic dog ownership in Iran is a risk factor for human infection with Leishmania infantum. Am J Trop Med Hyg 2002; 67:511-515.

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