Obiettivo Leishmania major, the cause of human zoonotic cutaneous leishmaniasis (ZCL) is widely distributed in arid regions of Africa and Asia. Sand flies support the circulation of L.major within foci, and host-parasite associations are typical for certain endemic areas. Different species of rodent are the reservoir for human infection in different endemic areas. Differences in epidemiology and human clinical manifestation, including duration of lesions, have been recorded in foci with different rodent host species-parasite combinations.The aim of this project is to expose intra-specific variation in the species L. major and use it to comprehend rodent host species-L. major parasite specificities and the molecular epidemiology of ZCL, using populations of L. major from Uzbekistan and Israel. Variation in human clinical symptoms occurs in both regions, and varying success of immunization (leishmanization) was reported from Uzbekistan. Whether this is owing to variation of parasites' virulence and/or hosts' immune response is still not clear. Psammomys obesus and Rhombomys opimus serve as reservoir hosts of L. major in Middle East and Central Asia, respectively, and own preliminary data indicate clear host-parasite specificity in both regions. Previous biochemical, serological, immunological studies and also own molecular data suggest genetic differences among strains of L. major from the two regions, however, none of these studies included statistically significant numbers of strains.In this study, old well-characterised, and newly isolated strains from Israel and Uzbekistan will be characterised by determining variations of micro satellite repeats and single nucleotide polymorphisms in nuclear and kinetoplast DNA markers. The results will be compared to those of well-established fingerprinting methods (schizodeme analysis, PPIP-PCR) and to excreted factor (EF)/ lipophosphoglycan (LPG) antigenic variation. Genetic heterogeneity of the strains will be correlated with geographical origins of strains, type of rodent host, type of clinical condition seen in human cases and degrees of virulence as measured in experimental animal models and determined from different clinical symptoms observed in leishmanization 'vaccines'. The same techniques will be applied to compare virulent and attenuated lines of organisms from the same strain(s) of L. major genetically. A modified differential display technique that allows reverse transcription and amplification of complete mRNA molecules, which is specific for Leishmania, will be employed to identify genetic determinants associated with virulence and attenuation in L. major. Confirmed differentially expressed determinants will be sequenced and compared to published sequences.Variation in the immune response of human natural cases, human 'vaccines', and animal hosts will be measured by screening cytokine profiles by ELISA-based techniques, and antibody production patterns by 2D protein electrophoresis. To test for parasite-rodent host specificity the two different rodent species will be infected with their locale and foreign strains of L. major. PCR approaches will be used to search for parasites in different body sites and attempts will be made to re-isolate them. The immune response in the rodents will be investigated using the methods mentioned above.A better understanding of genetic basis of leishmanial infectivity and virulence will help to develop a more rational approach for selecting candidate strains of L. major for immunization by leishmanization, and in selecting international and regional reference strains.Co-operation will involve the training of young scientists of NIS teams in newer molecular techniques. Programma(i) IC-INTAS - International Association for the promotion of cooperation with scientists from the independent states of the former Soviet Union (INTAS), 1993- Argomento(i) 4 - Life Sciences OPEN - OPEN Call Invito a presentare proposte Data not available Meccanismo di finanziamento Data not available Coordinatore Humbold Universität zu Berlin Contributo UE Nessun dato Indirizzo Dorotheenstr. 96 10098 Berlin Germania Mostra sulla mappa Costo totale Nessun dato Partecipanti (4) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto Hebrew University of Jerusalem Israele Contributo UE Nessun dato Indirizzo 91120 Jerusalem Mostra sulla mappa Costo totale Nessun dato Isaev Institute of Medical Parasitology Uzbekistan Contributo UE Nessun dato Indirizzo ul. Isaeva 38 703005 Samarkand Mostra sulla mappa Costo totale Nessun dato M.V. Lomonosov Moscow State University Russia Contributo UE Nessun dato Indirizzo 119899 Moscow Mostra sulla mappa Costo totale Nessun dato Sechenov Moscow Medical Academy Russia Contributo UE Nessun dato Indirizzo B. Pirogovskaya 3/6 119830 Moscow Mostra sulla mappa Costo totale Nessun dato
