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      Leishmaniasis Vaccine: Where are We Today?

      meeting-report
      Journal of Global Infectious Diseases
      Medknow Publications
      Immune response, Leishmania, Vaccine

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          Abstract

          Leishmaniasis is a disease that ranges in severity from skin lesions to serious disfigurement and fatal systemic infection. WHO has classified the disease as emerging and uncontrolled and estimates that the infection results in two million new cases a year. There are 12 million people currently infected worldwide, and leishmaniasis threatens 350 million people in 88 countries. Current treatment is based on chemotherapy, which relies on a handful of drugs with serious limitations such as high cost, toxicity, difficult route of administration and lack of efficacy in endemic areas. Vaccination remains the best hope for control of all forms of the disease, and the development of a safe, effective and affordable antileishmanial vaccine is a critical global public-health priority. Extensive evidence from studies in animal models indicates that solid protection can be achieved by immunization with defined subunit vaccines or live-attenuated strains of Leishmania. However, to date, no such vaccine is available despite substantial efforts by many laboratories. The major impediment in vaccine design is the translation of data from animal models to human disease, and the transition from the laboratory to the field. Furthermore, a thorough understanding of protective immune responses and generation and maintenance of the immunological memory, the most important and least-studied aspect of antiparasitic vaccine development, during Leishmania infection is needed. This review focuses on recent findings in antileishmania vaccine field and highlights current difficulties facing vaccine development and implementation.

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          Most cited references80

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          Effects of environmental change on emerging parasitic diseases.

          Ecological disturbances exert an influence on the emergence and proliferation of malaria and zoonotic parasitic diseases, including, Leishmaniasis, cryptosporidiosis, giardiasis, trypanosomiasis, schistosomiasis, filariasis, onchocerciasis, and loiasis. Each environmental change, whether occurring as a natural phenomenon or through human intervention, changes the ecological balance and context within which disease hosts or vectors and parasites breed, develop, and transmit disease. Each species occupies a particular ecological niche and vector species sub-populations are distinct behaviourally and genetically as they adapt to man-made environments. Most zoonotic parasites display three distinct life cycles: sylvatic, zoonotic, and anthroponotic. In adapting to changed environmental conditions, including reduced non-human population and increased human population, some vectors display conversion from a primarily zoophyllic to primarily anthrophyllic orientation. Deforestation and ensuing changes in landuse, human settlement, commercial development, road construction, water control systems (dams, canals, irrigation systems, reservoirs), and climate, singly, and in combination have been accompanied by global increases in morbidity and mortality from emergent parasitic disease. The replacement of forests with crop farming, ranching, and raising small animals can create supportive habitats for parasites and their host vectors. When the land use of deforested areas changes, the pattern of human settlement is altered and habitat fragmentation may provide opportunities for exchange and transmission of parasites to the heretofore uninfected humans. Construction of water control projects can lead to shifts in such vector populations as snails and mosquitoes and their parasites. Construction of roads in previously inaccessible forested areas can lead to erosion, and stagnant ponds by blocking the flow of streams when the water rises during the rainy season. The combined effects of environmentally detrimental changes in local land use and alterations in global climate disrupt the natural ecosystem and can increase the risk of transmission of parasitic diseases to the human population.
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            The regulation of immunity to Leishmania major.

            Experimental infection with the intracellular protozoan Leishmania major constitutes a particularly versatile model for assessing the role of CD4+ subset development in the host response to infectious disease. The association of Th1 development with control of infection, and of Th2 cell development with progressive disease, has been well established. The capacity to manipulate the outcome, using distinct immunologic interventions, in both genetically resistant and susceptible mice has identified key effector cytokines that must be present during the time of initial priming of T cells in order to affect the CD4 switch phenotype. Roles for interferon-gamma (IFN-gamma), interleukin 12 (IL-12), and IL-4 in Th1 and Th2 maturation have been demonstrated, although additional undefined signals are required. Study of the genetically susceptible BALB/c mouse has shown failure to downmodulate IL-4 production in response to infection, a response that is critically associated with the failure to develop appropriate Th1 responses. Use of the murine L. major model continues to elucidate new methods for vaccine development and suggests a promising system for identification of genes that determine susceptibility to infection.
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              The role of nitric oxide in innate immunity.

              Type 2 nitric oxide synthase (iNOS or NOS2) was originally described as an enzyme that is expressed in activated macrophages, generates nitric oxide (NO) from the amino acid L-arginine, and thereby contributes to the control of replication or killing of intracellular microbial pathogens. Since interferon (IFN)-gamma is the key cytokine for the induction of NOS2 in macrophages and the prototypic product of type 1 T-helper cells, high-level expression of NOS2 has been regarded to be mostly restricted to the adaptive phase of the immune response. In this review, we summarize data that demonstrate a prominent role of NOS2/NO also during innate immunity. During the early phase of infection with the intracellular pathogen Leishmania major, focally expressed NOS2/NO not only exerts antimicrobial activities but also controls the function of natural killer cells and the expression of cytokines such as IFN-gamma or transforming growth factor-beta. Some of these effects result from the function of NOS2/NO as an indispensable co-factor for the activation of Tyk2 kinase and, thus, for interleukin-12 and IFN-alpha/beta signaling in natural killer cells.
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                Author and article information

                Journal
                J Glob Infect Dis
                JGID
                Journal of Global Infectious Diseases
                Medknow Publications (India )
                0974-777X
                0974-8245
                May-Aug 2010
                : 2
                : 2
                : 177-185
                Affiliations
                Infection and Immunity Division, Walter+Eliza Hall Institute of Medical Research, Melbourne, Australia
                Author notes
                Address for correspondence: Dr. Lukasz Kedzierski, E-mail: kedzierski@ 123456wehi.edu.au
                Article
                JGID-02-177
                10.4103/0974-777X.62881
                2889658
                20606974
                f46f200b-5770-4cb5-bf9c-e33f15534474
                © Journal of Global Infectious Diseases

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Symposium - Lieshmaniasis

                Infectious disease & Microbiology
                leishmania,vaccine,immune response
                Infectious disease & Microbiology
                leishmania, vaccine, immune response

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