Leishmania spp, intracellular protozoan parasites, are the causative agents of a spectrum of clinical diseases in humans and animals, collectively called ‘leishmaniosis’. Leishmania are endemic in more than 98 countries, mainly in the Mediterranean region, Africa, Southern Asia, and Latin America, affecting more than 1 million people per year and causing significant public health risks. Canine leishmaniosis (CanL) is caused by Leishmania infantum; the only Leishmania spp. reported in both Old (Africa, Asia, Europe) and New (the Americas) Worlds and can cause fatal disease in humans and dogs. In cats five Leishmania spp. have been identified. These include Leishmania amazonensis, Leishmania braziliensis, Leishmania mexicana, and Leishmania venezuelensis in the New World, and L. infantum in both the New and Old Worlds.
Epidemiology
The prevalence of CanL in endemic regions (Albania, Croatia, Cyprus, Greece, France, Italy, Malta, Portugal, and Spain) and its expansion towards new, non-endemic locations has increased in recent years, presumably because of the increased mobility of dogs, tourism (domestic and international) and climatic changes. Likewise, the past few years has witnessed the emergence of an increasing number of Leishmania infections in cats from endemic areas in Italy, France, Spain, and Portugal. Also, four cases have been diagnosed in Switzerland in cats that had travelled to or been imported from Spain. The prevalence of leishmaniosis is predicted to continue to grow, creating more opportunities for the establishment of new endemic Leishmania foci in central and northern Europe (Pennisi, 2015).
In the UK, about 693 cases of CanL have been reported (Nash, 1993; Manser, 2004). Another study reported 257 clinical cases of CanL entering the UK between 2005 and 2007 (Shaw et al, 2009). Hence, there is a potentially significant reservoir of infected animals in the UK, which could increase because of the importation of infected dogs especially with the relaxation of the pet travel scheme (PETS) on the movement of dogs and cats across Europe, which with the lack of local preventive measures may allow competent vectors of leishmaniosis to become established in the UK. Hence, surveillance schemes that aim to link clinical, epidemiological, ecological, and laboratory data of Leishmania infection in dogs and cats together with monitoring of sandfly distribution patterns especially in the climatically most favourable regions could help reveal the scale of this disease at both local and national level.
Biology and transmission
The transmission of Leishmania is often described as being via bites of infectious phlebotomine sandflies (Figure 1) belonging to the genera Phlebotomus (Old World) or Lutzomyia (New World). Other, less frequent, forms of non-vectorial transmission between dogs can occur via transfused blood products from infected donors, and transplacental and venereal transmission. Dogs are the primary reservoir for L. infantum, due to their high susceptibility to the infection and their ability to transmit the parasite to the sandflies.
The life cycle of Leishmania is indirect (i.e. requires a vector host and a mammalian host) and alternates between two developmental forms (Figure 2). In the mammalian host, Leishmania spp. occurs as amastigotes (~2–5 μm in diameter) preferentially within phagocytic cells in the skin, bone marrow, and visceral organs. In the gut of sandflies, Leishmania spp. occur as flagellated promastigotes (~15–30 μm in length). The acquisition of L. infantum infection occurs when a feeding sandfly deposits promastigotes into the dermis of the mammalian host (Figure 3). Following a local multiplication in dendritic cells and macrophages in the skin, the parasites disseminate to various body organs via the lymphatic system and blood.
Clinical presentation
The signs associated with Leishmania infection in dogs include lymphadenomegaly, alopecia, dermatitis, lameness, anorexia, weight loss, conjunctivitis, epistaxis, and anaemia. Atypical manifestations include mucosal lesions, osteolytic and osteoproliferative lesions, chronic colitis, splenomegaly and hepatomegaly. Leishmania has been detected in apparently health dogs, leading to the theory that the manifestation of leishmaniosis may depend on host genetic factors. Indeed, some breeds of dogs (e.g. the Ibizan hound) rarely develop the clinical illness, probably mediated by a protective cellular immunity. In contrast, other dog breeds, including Boxer, Cocker spaniel, German shepherd, and Rottweiler, are more susceptible to the disease. In cats the most frequent clinical manifestations reported are skin (nodules, ulcerations or exfoliative dermatitis), mucocutaneous lesions, chronic gingivostomatitis or mucosal nodules, and enlarged lymph nodes. Uveitis and other ocular lesions have also been reported. Other non-specific signs include weight loss, dehydration, and lethargy, pale mucous membranes, hepatomegaly, cachexia, fever, vomiting, and diarrhoea.
Diagnosis
Clinical signs are only observed in a proportion of infected animals, which can lead to the sign-free infected dogs or cats being misdiagnosed and left untreated, increasing the reservoir/carrier of infection for sandflies. For this reason, and because Leishmania infection shares clinical and pathological features with other diseases, confirmation of infection using laboratory testing methods is needed. Indeed, a number of approaches to laboratory diagnosis are available:
Treatment
Meglumine antimoniate and allopurinol are the main drugs used for treatment and control of leishmaniosis in dogs. The same anti-leishmanial drugs, allopurinol and meglumine antimoniate, are also used to treat infected cats. Problems associated with these drugs are cost, side effects, length and duration of treatment, and, recently, the development of drug resistance (Yasur-Landau et al, 2016). Following treatment, most animals experience clinical remission, but complete eradication of the parasite is usually not achieved and relapse may occur. Although these drugs are generally well tolerated careful monitoring of the health status of animals under treatment via analysis of renal and liver functions especially during allopurinol therapy is warranted due to the potential occurrence of acute kidney injury.
Vaccination and other preventive measures
Vaccines to combat Leishmania in dogs have been developed and tested, and one efficacious vaccine, CaniLeish® (Virbac), is now available to consumers in Europe. Vaccination can induce a strong protective cellular anti-Leishmania immune response within 3–4 weeks of administration (Palatnik-de-Sousa, 2012). This vaccine can significantly reduce the number of actively infected dogs (Martin et al, 2014; Oliva et al, 2014). However, vaccination does not prevent from contact with the vector. Hence, a history of vaccination does not eliminate the need to consider the use of vector control measures, such as long-acting synthetic pyrethroid insecticides available as spray, spot-on or collar formulations, to prevent the sandflies from taking a blood meal and thus reducing the risk of transmission of leishmaniosis. Concerns remain regarding the toxicity of most pyrethroids, permethrin and deltamethrin, to cats. Thus, the development of a safe and efficacious commercial vaccine for the prophylaxis of leishmaniosis in cats remains a priority.
‘One Health’ paradigm
Even though some progress has been made towards treating and controlling leishmaniosis in dogs and cats this disease still imposes an increasing threat to animals and humans in Europe. Part of the challenge is due to the complexity of this disease. The impact and occurrence of leishmaniosis can be influenced by environmental and ecological changes, which enhance the propagation and spread of sandfly vectors, the presence of reservoir animals, increased travelling of people and pets especially to endemic areas, the lack of complete cure of the disease, and human susceptibility to infection. These dynamic interactions between animal, human, the vector, the parasite, and the environment indicate that such a complex issue cannot be dealt with by one discipline or one solution, emphasising the need for coordinated strategies to implement the One Health approach’ by engaging various sectors of the society, including animal health, public health, medicine, environmental science, economics, and policy stakeholders for the effective surveillance and control of this disease. The One Health approach can be a promising tool to mitigate the risk of emergence and spread of leishmaniosis through improved diagnosis surveillance, prevention and control activities (Palatnik-de-Sousa and Day, 2011; Vilas et al, 2014). This holistic, integrated approach requires cooperation in surveillance, including identification of hotspots and predicting the risk of the disease emerging into new localities and the risk of parasite spread through travel and trade. Currently, reliable disease surveillance data is lacking and control measures implemented by various countries are not consistent.
Conclusion
Despite the availability of treatment and prophylactic measures, clinical infections with Leishmania will likely remain both common and serious in animals and humans. Not only have there been waves of increasing leishmaniosis spread via infected animals to non-endemic European countries where a competent sandfly vector exists, but the prevalence of clinical disease also continues to change. There is no doubt that there will continue to be an evolving landscape in the interactions between the Leishmania parasites and the vertebrate host as well as invertebrate sandfly vector in the decades to come. Therefore, veterinary nurses should keep abreast of the latest advances in the epidemiology, diagnosis, treatment and prevention of leishmaniosis, and remain aware of the increasing opportunities of dealing with clinical cases in the future. Every effort should be made to prevent any further dissemination of leishmaniosis to non-endemic regions. Dogs or cats imported from endemic areas should be tested for Leishmania infection by sensitive diagnostic methods before their exportation and positive animals may not be allowed to enter non-endemic countries (Solano-Gallego et al, 2009). Because Leishmania infections are known to have a long incubation period, owners should be advised to re-test their imported pets for leishmaniosis for at least 2 years after importation or in case of a clinical suspicion (Paltrinieri et al, 2010). Because there is no test that is 100% sensitive additional measures aimed at reducing the risk of infection in dogs and cats from endemic areas (e.g. using repellents) are needed for animals that will be imported into non-endemic areas (Mattin et al, 2013). Vaccination of all dogs travelling to endemic regions can also be recommended. More information about this disease is available at http://www.leishvet.info and http://www.esccap.org.