HISTORICAL DATA

Greece has the "privilege" to be one of the Mediterranean regions where both human and canine leishmaniosis is of great interest among the scientific community, as the disease was diagnosed early in the last century. It must be mentioned that as early as 1835 there were reports of the disease in man with various names, of which the most well known was the Greek term "ponos " (means pain) as it appeared in publications of that period (e.g., is ponos Kala-azar?)

The identification of the pathogenic agent in India (1903) along with continuous efforts by the Pasteur researchers of that period resulted in disease detection for the first time in dogs in North Africa and Greece. Thus, there was a parallel research for leishmaniosis as well as sand fly vectors. It has become clear that dogs are the main reservoir of the parasite Leishmania sp. with the species of the genus Phlebotomus being the intermediate vector.

CURRENT STATUS

It is well known, nowadays, that canine leishmaniosis (CL) in the Mediterranean countries is caused by Leishmania infantum. The vast majority of the parasite strains has been identified as MON-1 type by enzymatic assays.

Further investigation provided evidence that there is relative polymorphism in respect of the parasite genome, although the later cannot be related yet to its pathogenic action.

Different species of Phlebotomus,are proven or probable vectors of canine leishmaniosis in eastern and western Mediterranean Basin and variations also exist in different regions of this area. In the New World (South and Central America) Leishmania chagasi is the causative agent of CL which is considered identical to Leishmania infantum, although vectors of the former are species of sand flies of the genus Lutzomyia.

Both species of Leishmania are considered causative agents of Human Visceral Leishmaniosis (HVL).

Canine leishmaniosis is endemic in all countries bordering the Mediterranean Sea, regardless the sanitary conditions and economic development of the country.

Epidemiological surveys, based on various methods, have demonstrated a seroprevalence range between 1 and 50% in canine population living in endemic countries for leishmaniosis. Although there is decreased credibility in respect of the methods used in the above surveys, associated with various parameters such as sampling procedures, specificity and interpretation of the method, there is no doubt that CL is endemic in the Mediterranean Basin with its frequency declining from coastal to continental regions, as climate variations influence the distribution and density of sand fly vector.

It must be said at this point, that any intervention undertaken in respect of disease control in canine population should be associated with relative intervention as far as the sand flies are concerned.

Despite the fact that CL is zoonotic disease, considerable difference exists between epidemiological data regarding HVL and CL with the former occurring as sporadic cases only as opposed to the later.

In particular, in some provinces in Greece just one case of HVL is usually diagnosed every 5-10 years while in others the frequency is even lower.

At the same time, the clinical case load of CL per small animal practice is estimated to account 10 to 50 cases per year. One possible explanation for this could be a host specificity of sand fly vectors of Leishmania infantum.

CLINICAL PICTURE AND DIAGNOSIS OF CL

The clinical picture of CL has been well studied. It concerns a chronic infection with a variety of systemic manifestations, many of which can be considered pathognomonic for a series of the other specific pathological conditions.

In endemic areas, many veterinary practitioners usually consider that canine leishmaniosis has to be ruled out before any further diagnostic investigation is attempted, in many canine patients regardless the history and clinical data.

This kind of approach has some negative aspects, as in many cases the diagnosis of CL is based simply on a positive serology test for leishmania.

Seropositiveness or even the detection of few parasites (amastigotes) in direct smears from lymph node aspiration does not mean active disease.

The clinical signs of CL in decreasing frequency are as follows:

Skin lesions, peripheral lymphadenopathy, conjunctivitis, myositis, pale mucus membranes, fever, splenomegaly, epistaxis, rhinitis, uveitis and hepatomegaly.

On the basis of clinical and laboratory findings of dogs in respect of Leishmania namely clinical symptoms, hematological, and/or biochemical alterations, parasite detection, antileishmanial antibody titers by IFA test, culture, PCR, cytokine determination and leishmanin skin test and in an attempt to classify the various disease entities in association with management of these animals, the following groups of leishmania infected dogs have been described:

1.  Asymptomatic resistant dogs

2.  Asymptomatic dogs (Preclinical)

3.  Dogs with minimal signs of Leishmaniosis (aliposymptomatic dogs? Chromic forms of Leishmaniosis?) and

4.  Dogs suffering from different forms of clinical leishmaniosis (symptomatic dogs)

The above mentioned classification seems to reflect the relation between dogs and parasite in endemic areas. However, a group of dogs that, according to the above criteria, are considered ''normal '' or ''non-contacted'' should be added.

In order for someone to have an integrated picture of the relation between Leishmania and dogs, we consider that the following points are essential:

1.  According to the criteria in any particular study, there may be a possibility for long-term studies to lack detection of ''non-contacted'' dogs in endemic areas.

2.  A similar study needs to be done in man because it is possible to draw out relative results, which would fully differentiate the whole approach.

3.  The previously mentioned classification of dogs in respect of Leishmania infection can only be interpreted as a dynamic process during which an individual dog examined under standard criteria could fall into one or another category due to a variety of factors.
Among those factors some are endogenous such as the immune reaction of the animal (Th1 versus Th2 response) and the virulence of parasite strain involved, while other factors are exogenous such as living conditions, nutrition, re-infections, phlebotomus density and various co-infections with protozoa, rickettsiae and other pathogenic microorganisms along with the administration of leishmanicidal or leishmaniostatic drugs.

4.  Diagnosis of CL in practice includes, in great deal, animals suffering from various clinical syndromes because it is difficult for the clinician to obtain the specific data to meet the criteria mentioned earlier, mainly due to economic reasons.

Accordingly, the diagnosis of canine leishmaniosis is based on the clinical picture, qualitative serology assays (ELISA--Kits and IFA test) and microscopic search for the parasite in direct smears. However, it is well known that symptomatic animals comprise just the top of the ''iceberg'' from an epidemiological point of view.

TREATMENT AND PREVENTION

It should be noticed, that as far as the research, regarding leishmanicidal drugs, is concerned, unfortunately there are not significant results so far, as the drugs used for the treatment of Leishmaniosisremain almost the same over the last 60 years.

The drugs of choice against Leishmania sp. are antimonial compounds. The main drugs used currently for the treatment of canine leishmaniasis in various protocols are Antimonials, Allopurinol, Paromomycin (Aminosidine), Azoles, Pentamidine or Lomidine and Amphotericin B.

The answer to pseudo-dilemma if dogs with CL can be treated is yes, in the majority of cases. Even dogs with high BUN and creatinine levels can be delivered "healthy" to their owners, provided the owner has understood the problem and is prepared for the cost and duration of the treatment.

On the other hand, the answer to the question if the treated dogs can be classified in the group of non-contacted dogs, namely if these dogs are parasitologically sterile, is no in the majority of cases. However, treated dogs have a good quality of life and are capable of offering labor or company to their owners.

In conclusion, all CL can and must be treated, provided the owners of CL patients meet the necessary prerequisites. Otherwise the best option for the clinician is to suggest euthanasia.

The use of allopurinol alone per os for the treatment of CL is a mismanagement practice and should be avoided since despite the overall improvement of the general health condition, the dogs in most cases harbour high numbers of amastigotes both within the skin and other tissues (e.g., lymph nodes) and constitute a public health risk as well as a risk for other healthy dogs.

As far as the prevention is concerned, because there is no effective vaccine for canine leishmaniosis so far, this is restricted to avoidance of phlebotomus biting on dogs. Effective insect repellents and insecticides in various formulations are available in the market with promising results. Their use, no doubt, should be part of the treatment protocol, since many cases presented as relapses are actually re-infections. It is well known that CL leaves no immunity and on the other hand a treated dog usually returns to the same area where first was inoculated by sand flies.

It would be useful to seek solutions, regarding sand flies, by implementation of massive insecticide methods, although the later would challenge the ecological sensitivities of the public.