Desjeux P. Leishmaniasis: current situation and new perspectives
Department of Control, Prevention and Elimination (CDS/CPE), Cluster of Communicable Diseases, World Health Organization (WHO), Avenue Appia, 1211 Geneva 27, Switzerland.Comparative Immunology Microbiology and Infectious Diseases (Impact Factor: 2.02). 10/2004; 27(5):305-18. DOI: 10.1016/j.cimid.2004.03.004
Leishmaniasis represents a complex of diseases with an important clinical and epidemiological diversity. Visceral leishmaniasis (VL) is of higher priority than cutaneous leishmaniasis (CL) as it is a fatal disease in the absence of treatment. Anthroponotic VL foci are of special concern as they are at the origin of frequent and deathly epidemics (e.g. Sudan). Leishmaniasis burden remains important: 88 countries, 350 million people at risk, 500,000 new cases of VL per year, 1-1.5 million for CL and DALYs: 2.4 millions. Most of the burden is concentrated on few countries which allows clear geographic priorities. Leishmaniasis is still an important public health problem due to not only environmental risk factors such as massive migrations, urbanisation, deforestation, new irrigation schemes, but also to individual risk factors: HIV, malnutrition, genetic, etc em leader Leishmaniasis is part of those diseases which still requires improved control tools. Consequently WHO/TDR research for leishmaniasis has been more and more focusing on the development of new tools such as diagnostic tests, drugs and vaccines. The ongoing effort has already produced significant results. The newly available control tools should allow a scaling up of control activities in priority areas. In anthroponotic foci, the feasibility of getting a strong impact on mortality, morbidity and transmission, is high.
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- "Visceral Leishmaniasis (VL) is the severest form, caused by an intracellular pathogen Leishmania donovani and is fatal if left untreated . VL still remains a global health burden with 400,000 new cases and 40,000 deaths reported annually  . VL accounts for more than 2 million disabilityadjusted life years (DALYs) lost  and approx. "
ABSTRACT: Visceral Leishmaniasis (VL), caused by Leishmania donovani is endemic in Indian sub-continent. Mannose-Binding Lectin (MBL) is a complement lectin protein that binds to the surface of Leishmania promastigotes and results in activation of the complement lectin cascade. We utilized samples of 218 VL patients and 215 healthy controls from Indian population. MBL2 functional variants were genotyped and the circulating MBL serum levels were measured. MBL serum levels were elevated in patients compared to the healthy controls (adjusted P = 0.007). The MBL2 promoter variants -78C/T and +4P/Q were significantly associated with relative protection to VL (-78C/T, OR=0.7, 95% CI = 0.5-0.96, adjusted P = 0.026 and +4P/Q, OR=0.66, 95% CI = 0.48-0.9, adjusted P = 0.012). MBL2*LYQA haplotypes occurred frequently among controls (OR=0.69, 95% CI = 0.5-0.97, adjusted P = 0.034). MBL recognizes Leishmania and plays a relative role in establishing L. donovani infection and subsequent disease progression. In conclusion, MBL2 functional variants were associated with VL. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.Parasitology International 08/2015; 64(6). DOI:10.1016/j.parint.2015.08.003 · 1.86 Impact Factor
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- "The infection can range from self-limited cutaneous to the more severe diffuse cutaneous and visceral forms. Leishmaniasis represents an important public health issue in different parts of the world, requiring that measures be put in place to control the spread of the disease worldwide (Grimaldi and Tesh, 1993; Desjeux, 2004; Dujardin, 2006). "
ABSTRACT: Visceral leishmaniasis represents an important public health issue in different parts of the world, requiring that measures be put in place to control the spread of the disease worldwide. The canine leishmaniasis diagnosis is not easy based on clinical signs, since dogs may not develop the infection with recognizable signs. Thus, the laboratorial diagnosis is essential to ascertain the incidence and prevalence of canine leishmaniasis especially in areas with major control efforts. Although, the diagnosis can be performed by the use of different approaches, the molecular methods such as PCR have become an indispensable tool for leishmaniases diagnosis. A TaqMan assay for real-time PCR (Linj31-qPCR) was developed to determine the parasite occurrence in clinical cases of leishmaniasis. The assay targets a L. (L.) infantum hypothetical protein region. The specificity of the assay was verified by using Leishmania World Health Organization reference strains including parasites belonging to subgenus L. (Leishmania), subgenus L. (Viannia), other Leishmania species and Trypanosoma cruzi. The sensitivity was verified by using isolates of L. (L.) amazonensis and L. (L.) infantum. The usefulness of the assay for diagnosis was ascertained by testing 277 samples from dogs in regions endemic for visceral and/or cutaneous leishmaniasis and from regions in which leishmaniasis was not endemic in São Paulo State, Brazil. Diagnosis of canine visceral leishmaniasis (CVL) was determined on these animals by conventional PCR and three serological tests. The dog samples were divided into four groups. I, dogs with CVL (n=101); II, dogs with other diseases and without CVL (n=97); III, dogs with American cutaneous leishmaniasis (n=7), and, IV, dogs without CVL (n=72) from areas where leishmaniasis was not endemic as control group. Results indicated that Linj31-qPCR was able to identify parasites belonging to subgenus L. (Leishmania) with no cross-amplification with other parasite subgenera. The Linj31-qPCR detected Leishmania parasites DNA in 98% of samples from Group I. In conclusion this methodology can be used as routine diagnostic tools to detect parasites from subgenus Leishmania. Copyright © 2015. Published by Elsevier Inc.Experimental Parasitology 08/2015; 157. DOI:10.1016/j.exppara.2015.08.014 · 1.64 Impact Factor
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- "Leishmaniasis is a parasitic illness caused by haemoflagellate protozoans belonging to the genus Leishmania. Leishmania donovani is the most common agent causing VL . VL manifests as fever, hepatosplenomegaly and pancytopenia. "
ABSTRACT: As part of Drugs for Neglected Diseases initiative's lead optimization program for the development of new chemical entities to treat visceral leishmaniasis (VL), a series of aminothiazoles were synthesized and screened for in vitro efficacy, solubility and microsomal stability. The primary aim of identifying a lead structure with sub-micromolar activity was achieved. Out of 43 compounds synthesized, 16 compounds showed in vitro activity at less than 1 μM against VL. Compound 32 showed excellent antileishmanial potency (IC50 = 3 nM) and had all the acceptable properties except for metabolic instability. Blocking the metabolic soft spots in compound 32, where the 4-methoxy pyridine substituent was replaced by 5-ethoxy group, led to compound 36 (IC50 = 280 nM) with improved stability. To understand the disposition of 36, in vivo pharmacokinetic study was conducted in a mouse model. Compound 36 showed high clearance (91 mL/min/kg); short half-life (0.48 h) after intravenous administration (1 mg/kg) and exposure (AUC0-24) following oral administration was 362 ng h/mL with absolute bioavailability of 8%. To summarize, 43 analogs were synthesized out of which 15 compounds showed very potent sub-nanomolar efficacy in in vitro systems but the liability of metabolic instability seemed to be the major challenge for this chemical class and remains to be addressed. Copyright © 2015 Elsevier Masson SAS. All rights reserved.European Journal of Medicinal Chemistry 08/2015; 102:582-593. DOI:10.1016/j.ejmech.2015.08.013 · 3.45 Impact Factor
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