Due to a sharp rise in its incidence, leishmaniasis is considered a priority re-emerging disease in Colombia and the world. The World Health Organization (WHO) has declared, and recently reiterated, leishmaniasis´s categorization as a neglected disease, in other words, one that is closely linked to poverty and for which there is little economic interest in investing in drug and control strategy development.

Our research on leishmaniasis is directed towards understanding and mitigating the factors that determine the development of disease and therapeutic failure (immune response, virulence, and drug resistance). Our research is multidisciplinary, integrating basic fields – molecular and cellular biology, immunology and biochemistry – with epidemiologic and applied clinical research. We work in continuous collaboration with public health authorities and diverse national and international institutions. A particular interest of the thematic area is to identify therapeutic alternatives that are more effective, safe and easier to administer than those currently in use, especially for the pediatric population which has demonstrated suboptimal therapeutic response to the first-line drug.

The trajectory and quality of leishmaniasis research in CIDEIM has granted us acknowledgement as a WHO Collaborating Center since 1992, and a Reference Center for the identification of Leishmania species.

Strategic objectives

• To establish the role of humans in the transmission and dissemination of leishmaniasis.
• To identify the factors in the host-parasite interaction which lead to pathogenesis or self-resolution of the disease.
• To provide critical evidence for the design of effective community-level control strategies.
• To identify alternative therapies and therapeutic regimens that are safer and whose delivery can be adjusted to specific populations and individuals.

Research

• Pharmacology of anti-Leishmania compounds and alternative therapies:
  • Molecular Pharmacology: Delivery, accumulation and metabolism of drugs in human macrophages and their implication for therapeutic response.
  • Pharmacokinetics: Understanding the intracellular and plasma pharmacokinetics of miltefosine in children and adults, and its implications in the emergence of pharmaco-resistance.
  • Immunomodulation: Evaluation of immunomodulator compounds as coadjuvants in the treatment of cutaneous leishmaniasis.
• Drug resistance and tolerance in Leishmania:
  • Identification of molecular mechanisms associated with the development of primary and secondary resistance.
  • Evaluation of drug susceptibility levels in clinical samples of Leishmania Viannia and its relation to therapeutic response.
• Asymptomatic infection:
  • Presence and viability of Leishmania in extralesional healthy tissue, and its role in transmission, persistence of the parasite and susceptibility to drugs.
• Host-parasite interactions:
  • The role of inflammatory mediators and cellular receptors (chemokines, cytokines and receptors) in the pathogenicity and clinical outcome in American cutaneous leishmaniasis.
  • The role of regulator T-cells in clinical manifestation and therapeutic outcome of cutaneous leishmaniasis.

Current Services

• Medical care and diagnostic procedures, including direct examination (swab), sample aspirate culture, histopathological biopsy, and application of the Montenegro Test.
• Typification (identification) of Leishmania species through izoenzyme electrophoretic mobility and indirect immunofluorescence using monoclonal antibodies.

Achievements

The interdisciplinary research approach has yielded fundamental knowledge regarding cutaneous leishmaniasis and innovative tools for its diagnosis and treatment. Contributions to this knowledge base include an understanding of the natural history of American cutaneous leishmaniasis, the epidemiological importance of persistence of the disease and its recurrence in humans; having demonstrated that acquisition by the parasite of resistance to antimonials and its contribution to therapeutic failure; having shown decreased efficacy and increased velocity of elimination of antimonials among children; providing support for the efficacy of oral miltefosine in children; offering evidence for the anthroponotic transmission of American cutaneous leishmaniasis; and the identification of vectors and wild reservoirs. This knowledge is essential to the definition of prevention and control measures that can be adapted to the realities of cutaneous leishmaniasis in Colombia, as well as to determining appropriate treatment strategies.

Contact

Nancy Gore Saravia, PhD
Scientific Director, CIDEIM
Leader Leishmaniasis Thematic Area
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