Vet Times The website for the veterinary profession https://www.vettimes.co.uk Advances in feline leishmaniosis Author : Hany Elsheikha Categories : Companion animal, Feline, Vets Date : February 15, 2016 ABSTRACT Leishmaniosis is a serious vector-borne disease in southern Europe, but is spreading northwards, driven by climate changes and the increased travel of pets across the continent. Dogs are the main reservoir, but cats and other potential vertebrate reservoirs have been also reported. Feline infection has started to become common in endemic areas, but prevalence is generally still lower than in dogs. Sandflies are the sole known vector, but non-vectorial transmission has been reported. Clinical disease affects only a proportion of infected animals and the susceptibility to the disease is mainly influenced by genetic predisposition and immune response, as well as factors as yet unknown. A number of diagnostic tools can be used to ascertain the presence of Leishmania parasites in cats. Some antileishmanial drugs used in dogs are also used to treat infected cats. No vaccine yet exists, thus chemotherapy should be augmented by the implementation of measures to combat the sandfly vector of the disease. More knowledge of the epidemiology and pathogenesis of the leishmaniosis in cats is needed to assess its impact on the feline health and to provide a basis from which development of better interventional strategies may be created. In this article, the author will discuss the recent advances concerning the epidemiology, diagnosis and management of feline leishmaniosis. Some progress has been made towards treating and controlling leishmaniosis; however, this disease continues to impose a growing threat to animals and humans in Europe. 1 / 8
Part of the challenge is due to the environmental and ecological changes that support the propagation and spread of sandfly vectors; increase of reservoir animal populations; increased travelling of people and pets especially to endemic areas; the lack of complete cure of the disease; the lack of accesses to necessary health control of stray and sheltered animals in some endemic areas; and human susceptibility to infection. All of these challenges emphasise the need for coordinated strategies engaging various sectors of society, including public health, medicine, animal health, environmental science, economics and policy stakeholders. Feline leishmaniosis Five Leishmania species have been identified in cats: Leishmania mexicana, Leishmania venezuelensis, Leishmania braziliensis and Leishmania amazonensis in the New World, and Leishmania infantum in both the New and Old Worlds. L infantum is the only species isolated from cats in Europe. 2 / 8
Figure 1. Life cycle of Leishmania infantum. Cats or dogs act as the definitive host and become infected when bitten by a sandfly. (a) Promastigotes are inoculated into the dermis and (b) colonise the resident macrophages. Within macrophages, they develop to amastigotes and proliferate within phagolysosome (c). After the rupture of macrophages, the released amastigotes infect new macrophages (d). If the host fails to control the infection in the skin, amastigotes disseminate via regional lymphatics and the blood to infect the entire reticuloendothelial system. (e) Amastigotes ingested by a female sandfly during feeding transform back into promastigotes, which replicate within the sandfly to complete the life cycle. Image: Designed by Hany Elsheikha and Hind Mamdowh. Even though the mode of transmission to cats has not been confirmed, it is expected to occur via bites of infectious phlebotomine sandflies (Figure 1) as for other vertebrate species. Blood meal analysis has confirmed the natural vector sandflies can feed on cats and xenodiagnosis a technique in which laboratory-reared (uninfected) arthropod vector sandflies are fed on a suspected cat or dog and subsequently examined, in an effort to recover the Leishmania parasite substantiated the sandflies Phlebotomus perniciosus in the Old World and Lutzomyia longipalpis in the New World can be infected with L infantum after feeding on naturally infected cats (Johnson et al, 1993; Maroli et al, 2007). This points out the potential role cats can play in the transmission cycle of L infantum. Hence, it is reasonable to anticipate cats are likely to be infected by the same Leishmania species found in other vertebrate hosts in the same geographic region and feline Leishmania infection can be relatively common in areas where canine leishmaniosis is endemic. However, the prevalence of Leishmania infection in dogs is still higher than in cats, even from the same locations or geographic regions (Millán et al, 2011; Miró et al, 2014). Leishmaniosis in cats is a historically overlooked disease or neglected probably because most of the attention was directed to dogs. Even though the disease has more economic and public health impact in dogs, feline leishmaniosis should not be ignored because of the susceptibility of cats to infection and their risk of developing a severe chronic disease. Epidemiology The past decade has witnessed the emergence of an increasing number of infections in cats from endemic areas in Italy, France, Spain and Portugal. Four cases were also diagnosed in Switzerland in cats that had travelled to, or been imported from, Spain. The altitude, outdoor lifestyle, rural habitat, seasonality, male gender, age (2 to 15 years) and 3 / 8
concurrent infection with immunosuppressive viral diseases are risk factors that may predispose cats to contracting L infantum infection. Figure 2. A map showing the geographic distribution of Phlebotomus perniciosus sandfly species in Europe at regional administrative level (Nomenclature of Territorial Units for Statistics level three). The map is based on published historical data and confirmed data provided by experts from the respective countries as part of the VBORNET project. Image: http://ecdc.europa.eu/en/healthtopics/vectors/vector-maps/pages/vbornet_maps_sandflies.aspx Due to a number of determinants, not limited to the different levels of endemicity, characteristics of the population under study or differences in diagnostic methodologies, there is discordance between data reported based on seroprevalence (0% to 68.5%) or molecular detection of infection (0% to 60.7%) in endemic regions of Europe (Pennisi et al, 2015). The epidemiology of feline leishmaniosis is predicted to continue to evolve due to climate change, creating opportunities for the establishment of new endemic L infantum foci in central and northern Europe. Hence, robust surveillance of Leishmania infection in vertebrate hosts and monitoring of sandfly distribution patterns especially in the climatically most favourable regions of Europe is crucial (Figure 2). Clinical presentation The most frequent clinical manifestations reported in feline leishmaniosis are skin (nodules, ulcerations or exfoliative dermatitis) or mucocutaneous lesions, chronic gingivostomatitis or mucosal nodules, and lymph node enlargement (solitary or multicentric). Cats can exhibit dermatological lesions alone, or a combination of skin lesions and systemic signs. In a few cases, some cats do not have any skin detectable lesions on clinical presentation. 4 / 8
Uveitis and other ocular lesions have also been reported in affected cats. Non-specific signs such as weight loss, dehydration and lethargy, pale mucous membranes, hepatomegaly, cachexia, fever, vomiting, diarrhoea, chronic nasal discharge, splenomegaly, polyuria/polydipsia, dyspnoea, wheezing, abortion, fever, jaundice, malabsorption or pancytopenia and hypothermia have been reported. Diagnosis Due to the polymorphic clinical nature of the disease and its insidious progressive course, as well as the discordance between results obtained by serological and molecular techniques (Millán et al, 2011), leishmaniosis could persist for a long time before cats are brought to a veterinarian, so accurate diagnosis can be delayed especially in non-endemic areas. Figure 3. The intracellular, non-motile tissue stage of Leishmania amastigote. Note the presence of multiple amastigotes (white arrows) released from the cytoplasm of a macrophage (a special type of white blood cell). Abbreviation N: nucleus of the macrophage. Image: Najoua Haouas. It should be noted most diagnostic techniques for Leishmania infection used in dogs are also employed in cats. Diagnosis is generally made by serologic (immunofluorescence antibody test), cytologic, immunohistochemistry (IHC), culture or PCR methods. Specific diagnosis of leishmaniosis can be achieved via the use of a simple, quick and cheap parasitological test for the demonstration of amastigotes in Giemsa-stained smears from aspirates of lymph node or bone marrow (Figure 3). 5 / 8
The diagnosis should not be excluded based on negative or low positive serology especially if the cat exhibits clinical signs compatible with feline leishmaniosis and additional diagnostic confirmatory methods (cytology, histology with IHC, PCR and culture) should be employed on affected tissues (for example, skin, lymph nodes, oral tissue or nasal discharge) and also blood, buffy coat and bone marrow samples. Infected cats can exhibit hypergammaglobulinaemia and normocytic normochromic anaemia. Differential diagnoses for cutaneous lesions in cats include squamous cell carcinoma, cutaneous vasculitis and dermatophytosis. Treatment and prevention No scientific evidence on best treatment for feline leishmaniosis is available. However, oral therapy with allopurinol (10mg/kg twice a day or 20mg/kg once a day) and subcutaneous injections of meglumine antimoniate have been administered in a few cases. These drugs are generally well tolerated, but careful health status monitoring of animals under treatment via analysis of renal and liver functions especially during allopurinol therapy is warranted. This is due to potential acute kidney injury occurrence, indicated by increased alanine aminotransferase and aspartate aminotransferase values. Owners should promptly report abnormal clinical signs to their vet. It is important to note the development of chronic renal failure has been reported in both treated and untreated cats, and glomerular disease should be investigated because of the frequent occurrence of hyperglobulinaemia and the consequent risk for immune complex-related renal disease (Pennisi et al, 2004). Specific preventive measures for leishmaniosis in cats are not available because prevention efforts have traditionally been focused on dogs, as they are the primary animal reservoirs for disease transmission in both humans and other vertebrates. Due to the lack of vaccine against feline leishmaniosis, preventive strategies have included the use of topical insecticides, chemical compounds with sandfly repellent activity, similar to those used for dogs. Unfortunately, most pyrethroids, such as permethrin and deltamethrin, cannot be used in cats due to their toxicity to this animal species. The launch of a collar containing an additional compound belonging to this chemical class, flumethrin, well tolerated in the cat might represent a valid preventive option for the individual reduction of risk for infection of cats in highly endemic settings, and for limiting the infectiousness of those already infected. The collar has been useful in reducing the incidence of L infantum infection in dogs. Cat owners should be advised to use preventive measures (insecticides with a repellent effect against sandflies) on cats during the full duration of travels to areas where leishmaniosis is endemic, to 6 / 8
reduce the risk of infection. Vets in non-endemic regions need to be aware of feline leishmaniosis, including its non-vectorial potential transmission modes, and should advise cat owners on preventive measures. Conclusions and future challenges Further insights into the pathogenesis of Leishmania through the use of basic science techniques are needed to advance our understanding of the disease and uncover potential avenues for therapeutic interventions. Standardisation of diagnostic techniques and the development of new, more sensitive methods in areas of high endemicity are needed to improve the pace and accuracy of diagnosis. Further studies to assess the optimal regimen and length of treatment would also assist in managing patients using the available tools. The development of a feline leishmaniosis vaccine would have a significant positive impact on feline health. But it is essential to understand the dynamics of protective T cell immune response and antileishmanial antibodies in cats to develop an effective and long-lasting vaccine, and one that does not have any deleterious effects associated with unregulated inflammation. The advent of high-throughput molecular technologies, such as next generation sequencing, can contribute to a further understanding of the taxonomy of Leishmania in cats and help the answering of questions surrounding the strains shared by, and circulating among, cats and other vertebrate species. Defining the structures of protozoan parasite populations in various (domestic and wild) hosts will have important implications for studies of the parasite transmission, immunogenicity and pathogenesis. Further research is needed to investigate the genetic diversity of sandflies and their associated Leishmania strains that may be shared with wild and domestic felids and canids. These studies could provide information on the dynamics of parasite infections among wild and domestic populations, as well as humans, and should enable the development of more effective control strategies. Competing interests The author declares he has no competing interests associated with this publication. Acknowledgements Because of space limitation, the author notes he was unable to comprehensively cite many worthy contributions to the field. 7 / 8
Powered by TCPDF (www.tcpdf.org) References Some drugs in this article are used under the cascade. Johnson RN, Ngumbi PM, Mwanyumba JP and Roberts CR (1993). Host feeding preference of Phlebotomus guggisbergi, a vector of Leishmania tropica in Kenya, Med Vet Entomol 7(3): 216-218. Maroli M, Pennisi MG, Di Muccio T et al (2007). Infection of sandflies by a cat naturally infected with Leishmania infantum, Vet Parasitol 145(3-4): 357-360. Millán J, Zanet S, Gomis M et al (2011). An investigation into alternative reservoirs of canine leishmaniasis on the endemic island of Mallorca (Spain), Trans Emerg Dis 58(4): 352-357. Miró G, Rupérez C, Checa R et al (2014). Current status of L infantum infection in stray cats in the Madrid region (Spain): implications for the recent outbreak of human leishmaniosis? Parasit Vect 7: 112. Pennisi MG (2015). Leishmaniosis of companion animals in Europe: an update, Vet Parasitol 208(1-2): 35-47. Pennisi MG, Venza M, Reale S et al (2004). Case report of feline leishmaniasis in four cats, Vet Res Comm 28(Suppl 1): 363-366. 8 / 8