The leishmaniases are a spectrum of human diseases found in over 88 countries world-wide caused by protozoan parasites belonging to the genus Leishmania. Both cutaneous leishmaniasis (CL), caused by Leishmania major and L. tropica, and visceral (VL) leishmanasis, caused by L. infantum, are endemic to Israel. The latter disease is fatal if not rapidly diagnosed and treated. In many areas of the Mediterranean Region where it is strongly associated with AIDS VL is an emerging disease. In Israel it is a zoonotic disease with dogs and wild canids acting as the reservoir hosts. Together with Dr. Gad Baneth of the Kuvin Centre we are carrying out epidemiological work in central Israel on a new focus for VL with several studies underway to identify risk factors for disease in dogs and humans. Longitudinal studies on the immunology of canine VL before and after drug treatment are in progress using experimental models and naturally infected animals. This information will be vital to understanding disease spread and in developing new therapies for this fatal disease. New molecular diagnostic tests for leishmaniasis and other zoonotic diseases are also under development. These assays are used for patient diagnosis, both CL and VL, and studies on emerging CL foci in Israel. Routine identification of Leishmania species causing disease is carried out in our laboratory using an internal transcribed 1 spacer region of the rRNA gene (ITS1) - polymerase chain reaction (PCR). In addition serological and classical parasitological assays for leishmaniasis are also performed.
Other research carried out in my laboratory has focused on the role of leishmanial protein kinases (PK) specifically, cAMP-dependent protein kinase (PKA) and casein kinases (CK), in parasite virulence and survival. These PK enable the parasite to sense and respond to the external environment, as well as modify host soluble and cellular proteins. It was shown that some PKs are constitutively released by the parasite, while others are shed only in the presence of potential substrates for these enzymes. The genes for PKA catalytic and regulatory subunits; and casein kinase 1 (CK1) and CK2 isoforms were cloned and characterized. In addition, we have begun to screen PK inhibitors as potential new drugs for treatment of these diseases using fluorescent assays.
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Ehrenfreund-Kleinmam, T., Domb, A.J., Jaffe, C.L., Nasereddin, A ., Leshem, B. and Golenser, J. (2005). Effect of Amphotericin B Derivatives on Leishmania and Immune Functions. J. Parasitol. 91:158-163.
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Nasereddin, A., Ereqat, S., Azmi, K., Baneth, G., Jaffe, C.L. and Abdeen, Z. (2005). Serological survey with PCR validation for canine visceral leishmaniasis in Northern Palestine. J. Parasitol. In press.
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