To identify parasite characters linked with variability in clinical response to infection with parasites of the Leishmania braziliensis complex in Peru and Bolivia:
* To collect and analyse comparable clinical and epidemiological data from three endemic areas in the Amazon basin of Peru and Bolivia in order to discriminate factors underlying clinical variability in infection and disease.
* To strengthen the argument that there is apparently a consistent association between parasite genetic variation, virulence and clinical variability.
* To initiate experimental studies on biological parameters that might be involved in Leishmania virulence, by using isolates with well defined genotypes obtained from representative clinical categories.
* Comparable epidemiological, ecological and clinical data in the three study sites of Peru and Bolivia (Andean valleys, Amazonian foothills, Amazonian lowlands).
* Collection of parasites from isolates and in biopsies, characterized genomically and genetically according to clinical grading.
* In vivo and in vitro models for biological characterization of parasite virulence.
* Discrimination of factors underlying clinical variability in infection and disease.
* Documenting whether there is a correlation between parasite genetic variability and clinical variability. If there is a correlation, validation of (i) corresponding risk factors for patient's care, and of (ii) corresponding probes and primers for parasite identification in field biopsies.
* Genetic structure of parasite populations in the three study sites.
* To collect comparable epidemiological and ecological data in the two previous STD3 (LEISHBOLPE 3) study areas (Pilcopata, Amazonian foothills, Peru; Isiboro Secure, Amazonian Iowlands, Bolivia) in reference to the methodology already developed for Huanuco Valley (Peru).
* To quantify clinical variability of both cutaneous and mucosal stages of infection and disease by data collection with the same standardised gradings in the 3 study areas (Pilcopata, Isiboro Secure, Huanuco).
* To undertake epidemiometric statistical analysis of field data for discriminating factors underlying clinical variability in infection and disease.
* To collect both biopsy samples and parasite isolates from lesions of patients documented above, for activities described below.
* To pursue genomic and genetic characterization of parasites according to clinical grading.
* To qualify the predictive value of candidate genetic markers associated with specific clinical and phenotypic patterns by:
* Analysis of the genetic structure of parasite populations under study.
* Characterization of identified marker chromosomes and corresponding nucleotide sequences.
Validating the operational value of corresponding probes and primers on the collection of biopsy samples (cryobanked) if time and tools permit.
* Complete molecular characterization of isolates collected by the previous project LEISHBOLPE 3 until isolates considered herein (LEISHBOLPE 4) become available.
* Developing biological in vitro and in vivo characterization of a limited set of parasites, preferably cloned, representative of the genetic and clinical categories identified above.
* Assessing Leishmania survival inside the macrophage as a measurement of parasite virulence.
* To process the data for global analysis of correlations between genetic and clinical variability.
Contract number ERBIC18CT960123
Funding SchemeCSC - Cost-sharing contracts
WC1E 7HT London