Zoonotic Cutaneous Leishmaniasis (ZCL) is a disease highly prevalent in North Africa and Middle East that is caused by Leishmania major. The TMRC program has three main goals :1-Describe the natural history of L. major infection as expressed in an endemic area especially with regard to asymptomatic infection .disease severity and risk of disease recurrence;2-Analyse the respective roles of factors specific of the vector(sand fly saliva ),or the parasite(intraspecies polymorphism) or the host immune response(innate or adaptative), in the clinical expression of ZCL with special emphasis on the identification of immune correlates of protection against primoinfection, disease occurrence or recurrence;3-Reinforce the application of Good Epidemiological Clinical and Laboratory Practices at all levels of programme implementation. In order to reach these goals, we shall conduct a large clinical prospective survey in a region endemic for ZCL. All enrolled individuals will be extensively investigated, clinically and immunologically, in order to accurately define their clinical history with regard to leishmania infection (including LST reactivity) as well as their in vitro immune responses to vector saliva components and parasite antigens at baseline Then an active detection of all ZCL cases, that will emerge among the cohort members will be conducted during the two following years .Leishmania isolates that could be grown from active lesions will be extensively investigated at the functional level in order to identify intraspecies diversity due to differential expression of virulence factors. The study will draw a picture of the natural history of L major infection in the region. In addition the clinical, immunological and parasitological informations generated by the program will be integrated into a multiparametric analysis. This will permit to identify immune correlates of protection that take into consideration the eventual effects of intraspecies functional polymorphism of L major and reservoir diversity. These data are of crucial importance for the development and evaluation of effective vaccines or antileishmanial drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center (P50)
Project #
5P50AI074178-05
Application #
8127871
Study Section
Special Emphasis Panel (ZAI1-GSM-M (J1))
Program Officer
Rao, Malla R
Project Start
2007-08-15
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2013-07-31
Support Year
5
Fiscal Year
2011
Total Cost
$442,091
Indirect Cost
Name
Institute Pasteur de Tunis
Department
Type
DUNS #
499250553
City
Tunis
State
Country
Tunisia
Zip Code
1002
Ghouila, Amel; Guerfali, Fatma Z; Atri, Chiraz et al. (2017) Comparative genomics of Tunisian Leishmania major isolates causing human cutaneous leishmaniasis with contrasting clinical severity. Infect Genet Evol 50:110-120
Kammoun-Rebai, Wafa; Naouar, Ikbel; Libri, Valentina et al. (2016) Protein biomarkers discriminate Leishmania major-infected and non-infected individuals in areas endemic for cutaneous leishmaniasis. BMC Infect Dis 16:138
Naouar, Ikbel; Boussoffara, Thouraya; Chenik, Mehdi et al. (2016) Prediction of T Cell Epitopes from Leishmania major Potentially Excreted/Secreted Proteins Inducing Granzyme B Production. PLoS One 11:e0147076
Marzouki, Soumaya; Kammoun-Rebai, Wafa; Bettaieb, Jihene et al. (2015) Validation of Recombinant Salivary Protein PpSP32 as a Suitable Marker of Human Exposure to Phlebotomus papatasi, the Vector of Leishmania major in Tunisia. PLoS Negl Trop Dis 9:e0003991
Harrabi, Myriam; Bettaieb, Jihène; Ghawar, Wissem et al. (2015) Spatio-temporal Genetic Structuring of Leishmania major in Tunisia by Microsatellite Analysis. PLoS Negl Trop Dis 9:e0004017
Kharrat, Nadia; Aissa, Imen; Sghaier, Manel et al. (2014) Lipophilization of ascorbic acid: a monolayer study and biological and antileishmanial activities. J Agric Food Chem 62:9118-27
Ghawar, Wissem; Attia, Hanène; Bettaieb, Jihene et al. (2014) Genotype profile of Leishmania major strains isolated from tunisian rodent reservoir hosts revealed by multilocus microsatellite typing. PLoS One 9:e107043
Naouar, Ikbel; Boussoffara, Thouraya; Ben Ahmed, Melika et al. (2014) Involvement of different CD4(+) T cell subsets producing granzyme B in the immune response to Leishmania major antigens. Mediators Inflamm 2014:636039
Bettaieb, Jihene; Toumi, Amine; Chlif, Sadok et al. (2014) Prevalence and determinants of Leishmania major infection in emerging and old foci in Tunisia. Parasit Vectors 7:386
Lemaire, Julien; Mkannez, Ghada; Guerfali, Fatma Z et al. (2013) MicroRNA expression profile in human macrophages in response to Leishmania major infection. PLoS Negl Trop Dis 7:e2478

Showing the most recent 10 out of 18 publications