Colombia is a country of over 46 million inhabitants. Insect vector borne diseases, including leishmaniasis, constitute a significant public health concern and disease burden in Colombia and neighboring countries. The cutaneous form of leishmaniasis accounts for 99% of the leishmaniasis cases in Colombia.
Cutaneous leishmaniasis can vary in presentation from simple resolving lesions to chronic and recurrent disease. Passive case detection and treatment constitute the principal, often the sole measure of control for cutaneous leishmaniasis (CL) in Central and South America yet first line therapies (pentavalent antimonials, pentamidine and miltefosine) are poorly tolerated and often ineffective (overall non response is of the order of 24% based on a recent meta analysis).
Further, children respond poorly to the standard treatment (pentavalent antimonial drugs) due to a more rapid elimination of the drug and consequent lower exposure to antimony in comparison to adults. While males (between 15 and 44 years of age) are generally the most affected group (59.8%), emerging statistical information from endemic/epidemic areas of transmission of leishmaniasis indicate a changing epidemiologic situation in which 25-30% of cases are children, including infants under 1 year of age. High incidence in children implicates intra- and/or peri-domestic transmission of what was previously a predominantly sylvatic disease.
The variation in pathogenicity of Leishmania infection (subclinical to chronic) underscore the role of yet undefined host determinants in the human response to treatment. Increasing evidence indicates that infection persists and can be reactivated following clinical resolution of lesions (with or without treatment). Immunotherapeutic approaches to the treatment of dermal leishmaniasis have substantiated the feasibility of favorably activating the host response to achieve clinical cure. The host immune response contributes to the pathogenesis of leishmaniasis and is also a determinant of the therapeutic response. Because leishmaniasis is an immunologically mediated disease; control of pathology and hence disease requires an understanding of inflammation and immune processes. A better understanding of the pathogenic mechanisms of lesion development and the asymptomatic persistence of infection is needed to mobilize the host response to eliminate the parasite and to promote healing.
Vector/Host-Parasite Interface of Leishmaniasis in Colombia (Parent Grant and Supplement Grant)
The goal of the training grant is to build research capacity to identify strategies and devise means to interrupt the cycle of transmission and pathogenesis of leishmaniasis through intervention of the invertebrate and vertebrate host pathogen interactions. To achieve this goal, the training program will implement research capacity in the molecular analysis of the interaction between Leishmania and both the sandfly vector and the mammalian host. The program builds upon the existing research capacity and ongoing projects of the developing country institution in clinical, epidemiological and biological aspects of cutaneous and visceral leishmaniasis and other transmissible diseases, prior collaboration with Yale faculty, and the critical mass of faculty and infrastructure for the conduct of molecular analyses of kinetoplastid parasites and host responses available at Yale University.
Colombian scientists receive training at Yale through the conduct of mentored research, auditing of postgraduate courses and short courses on research skills, such as biosafety, responsible conduct of research, and scientific writing. Workshops will be offered each year at CIDEIM with the participation of Yale Faculty (on site and teleconferencing) to build and multiply research skills and introduce national investigators to concepts and principles of molecular analysis (bioinformatics and data mining, functional genomics, expression analysis). Predoctoral trainees will be selected among postgraduate students from Colombian universities who conduct thesis research in CIDEIM. Students will be recent graduates of human or veterinary medicine and basic science who have qualified for scholarship support within the framework of COLCIENCIAS' Young Investigator program. Post-doctoral training and scientific exchange for periods of up to 4 months will be available to research staff of CIDEIM whose research is relevant to the vector or host-Leishmania interaction. During year 5 of the program, formal postgraduate courses on the molecular genetic analyses of host (mammalian/vector)-parasite interactions will be offered to national and regional students by CIDEIM. A further aim of this application is to build institutional capacity in CIDEIM to develop and use virtual e-learning methodologies to develop virtual training programs focused on health research management skills and access to information. Overall, the training conducted will prepare investigators in new areas of research, implement training by teleconferencing, and assure the capacity to offer formal courses for Colombian and regional post-graduate students. All of these will contribute to the sustainability of research capacity.
Vector/Host-Parasite Interface of Leishmaniasis in Colombia (supplement)
The overall objective of our Fogarty Training Program is to increase research capacity to identify and evaluate strategies to interrupt the transmission and pathogenesis of leishmaniasis and other vector-borne diseases endemic in Colombia (Dengue and Malaria). With the aim of building long-term sustainable capacity to address national and regional research needs, the parent grant has enabled Yale and CIDEIM to develop and deliver a series of live learning post-graduate courses on topics relevant to vector-borne prevention, treatment and control that are not sufficiently covered in traditional graduate and post-graduate academic curricula. At the same time, there is a critical need for strengthening core research skills which can be applied to the development, planning, implementation, evaluation and subsequent writing of research on any infectious disease or public health issue. The general aim of this application is to build institutional capacity in CIDEIM to develop and use virtual e-learning methodologies to develop virtual training programs focused on health research management skills and access to information. More specifically, this application is to: (1) develop an appropriate, user-friendly, interactive online version of the "Effective Project Planning and Evaluation for Health Research" (EPPE) training program; (2) develop an online training program in Access to Scientific Literature; (3) transfer an existing Biostatistics course taught at CIDEIM to a fully online format; (4) offer these new virtual courses through the CIDEIM website and explore other avenues to make these courses widely available to health students, researchers and practitioners.