Gad Baneth

Canine leishmaniosis - new concepts and insights on an expanding zoonosis: part one

Recent research has provided new insights on the epidemiology, pathology and immunology of canine leishmaniosis (CanL) and its genetic basis. The prevalence of infection in endemic areas is considerably higher than that of apparent clinical illness. In addition, infection spreads rapidly among dogs in the presence of optimal conditions for transmission. Infection involves a variety of granulomatous and harmful immune-mediated responses, and susceptibility to the disease is influenced by a complex genetic basis. These concepts will be instrumental for devising control programs. This review, the first in a series of two articles on CanL, presents an updated view on progress in elucidating the epidemiology and pathogenesis of this challenging disease, and the second part focuses on advances in diagnosis, treatment and prevention.

Directions for the diagnosis, clinical staging, treatment and prevention of canine leishmaniosis

Canine leishmaniosis (CanL) due to Leishmania infantum is a life threatening zoonotic disease with a wide distribution in four continents and importance also in non-endemic regions. The purpose of this report is to present a consensus of opinions on the diagnosis, treatment, prognosis and prevention of CanL in order to standardize the management of this infection. CanL is a disease in which infection does not equal clinical illness due to the high prevalence of subclinical infection among endemic canine populations. The most useful diagnostic approaches include serology by quantitative techniques and PCR. High antibody levels are associated with severe parasitism and disease and are diagnostic of clinical leishmaniosis. However, the presence of lower antibody levels is not necessarily indicative of disease and further work-up is necessary to confirm CanL by other diagnostic methods such as cytology, histopathology and PCR. We propose a system of four clinical stages, based on clinical signs, clinicopathological abnormalities and serological status. Suitable therapy and expected prognosis are presented for each of the stages. The combination of meglumine antimoniate and allopurinol constitutes the first line pharmaceutical protocol. However, although most dogs recover clinically after therapy, complete elimination of the parasite is usually not achieved and infected dogs may eventually relapse. Follow-up of treated dogs with blood counts, serum biochemistry, urinalysis, serology and PCR is essential for prevention of relapses. Protection against sand fly bites by topical insecticides is effective in reducing infection, and recent development of vaccines has indicated that prevention by vaccination is feasible.

LeishVet guidelines for the practical management of canine leishmaniosis.

The LeishVet group has formed recommendations designed primarily to help the veterinary clinician in the management of canine leishmaniosis. The complexity of this zoonotic infection and the wide range of its clinical manifestations, from inapparent infection to severe disease, make the management of canine leishmaniosis challenging. The recommendations were constructed by combining a comprehensive review of evidence-based studies, extensive clinical experience and critical consensus opinion discussions. The guidelines presented here in a short version with graphical topic displays suggest standardized and rational approaches to the diagnosis, treatment, follow-up, control and prevention of canine leishmaniosis. A staging system that divides the disease into four stages is aimed at assisting the clinician in determining the appropriate therapy, forecasting prognosis, and implementing follow-up steps required for the management of the leishmaniosis patient.

Canine hepatozoonosis: two disease syndromes caused by separate Hepatozoon spp.

Hepatozoonosis is caused by apicomplexan haemoparasites of the genus Hepatozoon, which are closely related to Plasmodium spp. and piroplasms. Recent research revealed that two tick-borne Hepatozoon spp. infect dogs and cause distinct syndromes. Comparisons of these related species illustrates that whereas Hepatozoon canis appears to be well adapted to its canine host, Hepatozoon americanum, an emerging pathogen producing severe and frequently fatal myositis, is highly virulent and might have recently crossed the species barrier from a wild host.

Babesiosis in dogs and cats--expanding parasitological and clinical spectra.

Canine babesiosis caused by different Babesia species is a protozoal tick-borne disease with worldwide distribution and global significance. Historically, Babesia infection in dogs was identified based on the morphologic appearance of the parasite in the erythrocyte. All large forms of Babesia were designated Babesia canis, whereas all small forms of Babesia were considered to be Babesia gibsoni. However, the development of molecular methods has demonstrated that other Babesia species such as Babesia conradae, Babesia microti like piroplasm, Theileria spp. and a yet unnamed large form Babesia spp. infect dogs and cause distinct diseases. Babesia rossi, B. canis and Babesia vogeli previously considered as subspecies are identical morphologically but differ in the severity of clinical manifestations which they induce, their tick vectors, genetic characteristics, and geographic distributions, and are therefore currently considered separate species. The geographic distribution of the causative agent and thus the occurrence of babesiosis are largely dependent on the habitat of relevant tick vector species, with the exception of B. gibsoni where evidence for dog to dog transmission indicates that infection can be transmitted among fighting dog breeds independently of the limitations of vector tick infestation. Knowledge of the prevalence and clinicopathological aspects of Babesia species infecting dogs around the world is of epidemiologic and medical interest. Babesiosis in domestic cats is less common and has mostly been reported from South Africa where infection is mainly due to Babesia felis, a small Babesia that causes anemia and icterus. In addition, Babesia cati was reported from India and sporadic cases of B. canis infection in domestic cats have been reported in Europe, B. canis presentii in Israel and B. vogeli in Thailand. Babesiosis caused by large Babesia spp. is commonly treated with imidocarb dipropionate with good clinical response while small Babesia spp. are more resistant to anti-babesial therapy. Clinical and parasitological cure are often not achieved in the treatment of small Babesia species infections and clinical relapses are frequent. The spectrum of Babesia pathogens that infect dogs and cats is gradually being elucidated with the aid of molecular techniques and meticulous clinical investigation. Accurate detection and species recognition are important for the selection of the correct therapy and prediction of the course of disease.

Chemotherapy of canine leishmaniosis.

Visceral leishmaniosis is a widespread and potentially fatal disease of dogs and humans common in the Mediterranean region, the Middle East, and South America. Canine leishmaniosis is most frequently treated with the drugs meglumine antimoniate, allopurinol, amphotericin B, or a combination of meglumine antimoniate and allopurinol. Therapy with the currently used drugs often achieves temporary clinical improvement and changes in immunologic parameters with restoration of the ability to mount parasite-specific cell mediated responses and decrease in anti-leishmanial antibody titers. However, treatment usually does not prevent relapse of disease or eliminate parasite carriage. Due to the current lack of an ultimate and effective therapy for canine leishmaniosis, new drugs, delivery systems and treatment strategies are necessary to achieve a consistent parasitological cure in infected dogs.

Polymerase Chain Reaction Using Noninvasively Obtained Samples, for the Detection of Leishmania infantum DNA in Dogs

A polymerase chain reaction (PCR) procedure using noninvasively obtained samples, for the identification of Leishmania infantum in canine tissues, was evaluated and compared with serologic testing and culture. A total of 92% of naturally infected, symptomatic, seropositive dogs were found to be positive by use of DNA from conjunctival swabs. Spleen or lymph node aspirates were found to be positive by PCR in 86% and by culture in 74% of these dogs. The sensitivity and specificity of conjunctival PCR were 92% and 100%, respectively. Experimentally infected dogs were found to be positive by conjunctival PCR already at 45 days of infection (83%) and before seroconversion. PCR using noninvasively obtained conjunctival samples will be useful for epidemiological studies and for direct diagnosis of canine visceral leishmaniasis.

A new Hepatozoon species from dogs : Description of the causative agent of canine Hepatozoonosis in North America

A new species of Adeleina, Hepatozoon americanum, is described from the skeletal muscle, cardiac muscle, visceral organs, and blood of dogs (Canis familiaris) in the Southern United States. The organism was previously identified as Hepatozoon canis (James, 1905) Wenyon, 1926; however, differences in clinical signs, histopathological and serological findings, gamont size, and ultrastructure define the new species of Hepatozoon. Attempts to transmit the protozoan from infected dogs to nymphal Rhipicephalus sanguineus ticks, the definitive host of H. canis, were not successful.

Outbreak of Cutaneous Leishmaniasis in Northern Israel

This study describes a new focus of cutaneous leishmaniasis (CL) due to Leishmania tropica, in the Galilee region of northern Israel. Thirty-three cases from 4 villages (northern part) and from the city of Tiberias (southern part) have been clinically diagnosed since 1996. Parasites from 13 patients and from 6 sand flies were characterized by isoenzyme electrophoresis, 2 immunological methods, and 3 polymerase chain reaction (PCR)-based methods. Isolates from the northern part were antigenically similar to Leishmania major and were different from other L. tropica isolates, including those from the southern part of the focus. They belonged to a newly reported zymodeme and were separable from all known Israeli L. tropica isolates, by use of 2 different PCR-based methods. Five (5.2%) of 97 Phlebotomus (Adlerius) arabicus and 2 (1.2%) of 162 Phlebotomus (Paraphlebotomus) sergenti females from the northern part of the focus were found to be infected with L. tropica. Three of 29 hyraxes (Procavia capensis) were positive for Leishmania ribosomal DNA. Thus, the northern part of this emerging focus of CL in Israel is distinct from all known L. tropica foci. P. arabicus is the main vector, and it transmits parasites that are different from other L. tropica isolates, with respect to antigenic, molecular, and biochemical parameters.

Distinct transmission cycles of Leishmania tropica in 2 adjacent foci, Northern Israel.

TOC summary for table of contents: Infection with Leishmania tropica is emerging because of encroachment of rock hyraxes and transmission by multiple vector species.