Current Projects

Since pathogenesis of dermal leishmaniasis is mediated by the immune and inflammatory responses, resolution of disease and control of infection are intimately linked to the host response. Consequently, antileishmanial drugs alone are often insufficient to clinically resolve disease even in immunocompetent individuals, and furthermore, do not eliminate infection. Although immune mechanisms underlying the outcome of infection differ among Leishmania species, non-healing phenotypes of infection by different species can be converted to healing phenotypes and vice versa by intervention of the host immune response. In experimental models, a wide range of interventions (including deletion of T cell populations, neutralization or genetic depletion of cytokines that drive T cell differentiation, down regulate macrophage activation, or modulate T regulatory cell function) invert susceptibility and resistance. Importantly, these interventions have broadly targeted immune function rather than responses to specific parasite antigens. The feasibility of translating this experience with murine models to human leishmaniasis is supported by the clinical resolution of cutaneous and mucosal disease unresponsive to chemotherapy alone, by co-adjuvant immunotherapy. However, neither the immunological basis of the healing response enabled by these interventions, the mechanisms involved nor the generalizability of any immunotherapeutic intervention (to different species of Leishmania or for the spectrum of clinical outcomes) has been determined. Local as well as systemic and combined therapies have recently been recommended as alternatives for New World cutaneous leishmaniasis by the WHO Expert Committee on Leishmaniasis. Risk/benefit considerations of the toxicity of current systemic treatment regimens, persistence of infection following treatment, and evidence of the effectiveness of various local therapies compelled the amplification of therapeutic options to include local and combined strategies. Such strategies may be optimized through innovative delivery of antileishmanial drugs and immunomodulators via nanoparticle technology. This project seeks to identify the immunologic bases of healing of cutaneous leishmaniasis caused by Leishmania Viannia species, and to discern the mechanisms of immunomodulation that together with chemotherapy, improve clinical outcome, reduce parasite burden and persistence, and preserve the effective life of antileishmanial drugs.

Leishmaniasis is a sand fly-borne parasitic infection endemic to tropical and subtropical regions. Sand flies that carry these pathogens can infect humans. One of the ways to prevent infection is to practice good pest management techniques. In order to identify and eradicate infected sand fly populations, pest control personnel need a simple, field-usable test kit that can detect the sand flies carrying (and capable of transmitting) Leishmania species. Lateral flow test strips (LFTS) format is attractive because all the reagents required for testing are incorporated on the test strip itself. The sensitivity of these test strips, however, is only moderate and usually a single pathogen is measured using these test strips. We have addressed these challenges by incorporating multiple quantum dots as part of a Lateral flow test strips. This approach has allowed the ability to multiplex the assays and also to achieve very high sensitivity (quantum dots emit bright light when illuminated with long UV light). Intelligent Optical System (IOS) has also developed proprietary protein stabilization technologies that currently can retain activity at 50°C for two months. This chemistry with further optimization may allow for enhanced stability in the future extending to 2 years. Thus the benefits of a LFTS are retained and the previous limitations can be mitigated. This project is a collaborative effort to develop a novel LFTS assay format for a simple, field-usable rapid test kit for simultaneous analysis of multiple Leishmania species.