Article

Leishmaniasis: Prevention, Parasite Detection and Treatment

Laboratory of Molecular and Cellular Immunology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic.
Current Medicinal Chemistry (Impact Factor: 3.85). 02/2012; 19(10):1443-74. DOI: 10.2174/092986712799828300
Source: PubMed

ABSTRACT

Leishmaniasis remains a public health problem worldwide, affecting approximately 12 million people in 88 countries; 50 000 die of it each year. The disease is caused by Leishmania, obligate intracellular vector-borne parasites. In spite of its huge health impact on the populations in vast areas, leishmaniasis is one of the most neglected diseases. No safe and effective vaccine currently exists against any form of human leishmaniasis. The spectrum and efficacy of available antileishmanial drugs are also limited. First part of this review discusses the approaches used for the vaccination against leishmaniasis that are based on the pathogen and includes virulent or attenuated parasites, parasites of related nonpathogenic species, whole killed parasites, parasites' subunits, DNA vaccines, and vaccines based on the saliva or saliva components of transmitting phlebotomine vector. Second part describes parasite detection and quantification using microscopy assays, cell cultures, immunodetection, and DNA-based methods, and shows a progress in the development and application of these techniques. In the third part, first-line and alternative drugs used to treat leishmaniasis are characterized, and pre-clinical research of a range of natural and synthetic compounds studied for the leishmanicidal activity is described. The review also suggests that the application of novel strategies based on advances in genetics, genomics, advanced delivery systems, and high throughput screenings for leishmanicidal compounds would lead to improvement of prevention and treatment of this disease.

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    • "Leishmania is a genus of obligate intracellular protozoa that parasitizes humans and whose infection is revealed in wide spectrum of clinical manifestations generally known as leishmaniasis. The parasite survives inside of macrophages using a strategy that involve apoptosis of some parasites after the mosquito bite (Kobets et al. 2012, Naderer and McConville 2011). Disease exacerbation has been found to occur upon the injection of a mixture of live and apoptotic parasites, whereas parasites have been found to not establish a successful infection after the depletion "

    Full-text · Dataset · Jan 2015
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    • "Vaccines against leishmaniasis were classified into three main categories namely first generation vaccines, second generation vaccines and third generation ones (Zand and Narasu, 2013). First generation vaccines include a procedure known as leishmanization (Handman, 2001), vaccination with killed parasites (Kobets et al., 2012) and vaccination with live attenuated parasites (Evans and Kedzierski, 2012). Second generation vaccines include vaccination with defined proteins (Spitzer et al., 1999) and vaccination with parasite subunits (Griffiths and Khader, 2014). "
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    ABSTRACT: Leishmaniasis is a significant worldwide health problem for which no vaccine exists. Recent trend in vaccine design has been shifted to epitope-based vaccines that are more specific, safe and easy to produce. Indeed, as far as we knew, the B cell epitope technique for vaccine development has not been used for preparation of Leishmania vaccine till now. Hence, the aim of the present work was to evaluate a new vaccine using different antigenic B cell epitopes. To achieve this aim, eighty albino mice were used. They were classified into 3 main groups; group I (10 mice) (non-infected, non-vaccinated), group II (10 mice) (infected, non-vaccinated) and group III (60 mice) (infected, vaccinated). Group III was subclassified into 6 subgroups named "a "to" f ", each subgroup was formed of 10 mice. They were vaccinated by epitopes: 239-247 DGMEGSCSG, 6-14 SWGANHYDG, 163-171 SYETGSSTL, 190-198 NDGDGEEEE, 359-367 KQKKDEGNQ and477-485 ASGSADGDE, respectively. Serum IgG OD values were evaluated using ELISA. Histopathological examination of spleen and skin tissues was performed using hematoxylin and eosin staining. Immunohistochemical staining of spleen tissue was accomplished for measuring CD4+ and CD8+T cells counts. The most considerable findings were the detection of higher serum IgG OD values in subgroups IIIa & IIIb than in group II with the presence of high statistical significant difference. No mice related to subgroups IIIa or IIIb showed hyaline changes of spleen (with the presence of statistical significant difference when compared to group II), ulcer in skin or atrophic epidermis (with the presence of high statistical significant difference when compared to group II). CD4+T cells count was significantly higher in all subgroups of group III than group II while the CD8+T cells count was significantly higher in group II than all subgroups of group III. In conclusion, the currently used new B cell epitope-based vaccine proved beneficial in protection against leishmaniasis. Epitopes 239-247 DGMEGSCSG and 6-14 SWGANHYDG gave the best prophylactic yield as evidenced by detection of high serum IgG OD values together with the best resolution of histopathological changes in spleen and skin tissues when compared to the non-vaccinated infected group. It seems that CD4+T cells expressed in spleen tissue in this study were related to Th-1 subset which proved protective against leishmaniasis. It is advised to apply these two promising epitopes in vaccine design against leishmaniasis in clinical trials. [Nadia S. El-Nahas, Gehan S. Sadek, Amal M. Husein, Amany A. Rady, Salwa F. Oshiba and Reham M. Barakat. Immunological, histopathological and immunohistochemical responses to a new B cell epitope-based vaccine against leishmaniasis in experimental mice. J Am Sci 2015;11(7):1-15]. (ISSN: 1545-1003).
    Full-text · Article · Jan 2015
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    • "Leishmania is a genus of obligate intracellular protozoa that parasitizes humans and whose infection is revealed in wide spectrum of clinical manifestations generally known as leishmaniasis. The parasite survives inside of macrophages using a strategy that involve apoptosis of some parasites after the mosquito bite (Kobets et al. 2012, Naderer and McConville 2011). Disease exacerbation has been found to occur upon the injection of a mixture of live and apoptotic parasites, whereas parasites have been found to not establish a successful infection after the depletion "
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    ABSTRACT: Background and objectives: Endonuclease G (EndoG) is an enzyme that specifically cleaves double stranded DNA at the dG and dC positions and has been shown to participate in chromatin degradation during apoptosis in Leishmania. The main goal of this work was to purify and crystallize EndoG in preparation for future structural studies that will permit a detailed understanding of the function of this enzyme. Materials and methods: EndoG protein was purified using Ni-affinity chromatography under denaturing conditions, then refolded in vitro and crystallized by the hanging-drop vapor diffusion method. Results and conclusion: The endonuclease G protein from Leishmania (viannia) panamensis was overexpressed, refolded, purified and demonstrated to be enzymatically active. Here, we reports the first successful crystallization of the EndoG protein in this group of protozoan parasites. The protein was crystallized by the hanging-drop vapor diffusion method. High quality EndoG crystals were obtained that perhaps will permit determination of the three-dimensional structure of EndoG using X-ray diffraction. Resumen Antecedentes y objetivos: La endonucleasa G (EndoG) es una enzima que escinde específicamente en las posiciones dG y dC del ADN de cadena doble y se ha demostrado que participa en la degradación de la cromatina durante el proceso de apoptosis en Leishmania. El objetivo principal de este trabajo fue la purificación y cristalización de EndoG como preámbulo para los estudios estructurales futuros que permitan entender detalladamente el funcionamiento de esta enzima. Materiales y métodos: La proteína EndoG fue purificada en condiciones desnaturalizantes usando cromatografía de Ni, luego fue renaturalizada in vitro y cristalizada por el método de difusión de vapor por gota colgante. Resultados y conclusión: La proteína EndoG de Leishmania (viannia) panamensis fue sobreexpresada, renaturalizada, purificada y demostró estar enzimáticamente activa. Aquí, se registra la primera cristalización exitosa de la proteína EndoG de este grupo de parásitos protozoarios. La proteína fue cristalizada por el método de difusión de vapor por gota colgante. Se obtuvieron cristales de alta calidad de EndoG que posiblemente nos permitirán determinar la estructura tridimensional de EndoG usando difracción de rayos-X.
    Full-text · Article · Jan 2015
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