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Sample records for early experimental leishmaniasis

  1. Immunity and immunosuppression in experimental visceral leishmaniasis

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    Goto H.

    2004-01-01

    Full Text Available Leishmaniasis is a disease caused by protozoa of the genus Leishmania, and visceral leishmaniasis is a form in which the inner organs are affected. Since knowledge about immunity in experimental visceral leishmaniasis is poor, we present here a review on immunity and immunosuppression in experimental visceral leishmaniasis in mouse and hamster models. We show the complexity of the mechanisms involved and differences when compared with the cutaneous form of leishmaniasis. Resistance in visceral leishmaniasis involves both CD4+ and CD8+ T cells, and interleukin (IL-2, interferon (IFN- gamma, and IL-12, the latter in a mechanism independent of IFN- gamma and linked to transforming growth factor (TGF-ß production. Susceptibility involves IL-10 but not IL-4, and B cells. In immune animals, upon re-infection, the elements involved in resistance are different, i.e., CD8+ T cells and IL-2. Since one of the immunopathological consequences of active visceral leishmaniasis in humans is suppression of T-cell responses, many studies have been conducted using experimental models. Immunosuppression is mainly Leishmania antigen specific, and T cells, Th2 cells and adherent antigen-presenting cells have been shown to be involved. Interactions of the co-stimulatory molecule family B7-CTLA-4 leading to increased level of TGF-ß as well as apoptosis of CD4+ T cells and inhibition of macrophage apoptosis by Leishmania infection are other components participating in immunosuppression. A better understanding of this complex immune response and the mechanisms of immunosuppression in experimental visceral leishmaniasis will contribute to the study of human disease and to vaccine development.

  2. Concomitant early mucosal and cutaneous leishmaniasis in Brazil.

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    Boaventura, Viviane S; Cafe, Virginia; Costa, Jackson; Oliveira, Fabiano; Bafica, Andre; Rosato, Andrea; de Freitas, Luiz A R; Brodskyn, Claudia; Barral-Netto, Manoel; Barral, Aldina

    2006-08-01

    Mucosal leishmaniasis (ML) is often clinically silent until reaching a highly advanced state. In this prospective study, 6 of 220 patients with early cutaneous leishmaniasis were diagnosed with mucosal involvement by otorhinolaryngological examination (a rate similar to the reported rate of late ML). Detection of early ML may represent an important strategy in preventing severe mucosal destruction in human leishmaniasis.

  3. Canine leishmaniasis: epidemiological risk and the experimental model.

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    Moreno, Javier; Alvar, Jorge

    2002-09-01

    Increasing risk factors are making zoonotic visceral leishmaniasis a growing public health concern in many countries. Domestic dogs constitute the main reservoir of Leishmania infantum and Leishmania chagasi, and play a key role in the transmission to humans. New reagents and tools allow the detailed investigation of canine leishmaniasis, permitting the monitoring of the immunological status of dogs in both natural and experimental infections. Such studies are essential to determine the basis of the canine protective immune response and to establish a laboratory model, a significant aspect for the development of vaccines against canine leishmaniasis.

  4. Leishmaniasis

    DEFF Research Database (Denmark)

    Kemp, M; Theander, T G

    2000-01-01

    Leishmania parasites are obligate intracellular protozoa, that produce clinical pictures, ranging from localised, self-healing ulcers to systemic, lethal diseases. The diseases caused by the parasites can be divided into cutaneous, mucocutaneous, and visceral leishmaniasis. Recovery from the infe......Leishmania parasites are obligate intracellular protozoa, that produce clinical pictures, ranging from localised, self-healing ulcers to systemic, lethal diseases. The diseases caused by the parasites can be divided into cutaneous, mucocutaneous, and visceral leishmaniasis. Recovery from...... the infection often leaves lifelong immunity. Leishmaniasis may occur in individuals who have been to the Mediterranean countries, the countries on the Horn of Africa, the Arabian Peninsula, parts of Asia, and South and Central America. Co-infection of Leishmania parasites and HIV is a special problem....... Leishmaniasis can be treated with pentavalent compounds of antimony, but other drugs, including amphotericin B, are also affective. Udgivelsesdato: 2000-Nov-13...

  5. Leishmaniasis.

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    Herwaldt, B L

    1999-10-02

    In 1903, Leishman and Donovan separately described the protozoan now called Leishmania donovani in splenic tissue from patients in India with the life-threatening disease now called visceral leishmaniasis. Almost a century later, many features of leishmaniasis and its major syndromes (ie, visceral, cutaneous, and mucosal) have remained the same; but also much has changed. As before, epidemics of this sandfly-borne disease occur periodically in India and elsewhere; but leishmaniasis has also emerged in new regions and settings, for example, as an AIDS-associated opportunistic infection. Diagnosis still typically relies on classic microbiological methods, but molecular-based approaches are being tested. Pentavalent antimony compounds have been the mainstay of antileishmanial therapy for half a century, but lipid formulations of amphotericin B (though expensive and administered parenterally) represent a major advance for treating visceral leishmaniasis. A pressing need is for the technological advances in the understanding of the immune response to leishmania and the pathogenesis of leishmaniasis to be translated into field-applicable and affordable methods for diagnosis, treatment, and prevention of this disease.

  6. Therapeutic enhancement of protective immunity during experimental leishmaniasis.

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    Senad Divanovic

    2011-09-01

    Full Text Available Leishmaniasis remains a significant cause of morbidity and mortality in the tropics. Available therapies are problematic due to toxicity, treatment duration and emerging drug resistance. Mouse models of leishmaniasis have demonstrated that disease outcome depends critically on the balance between effector and regulatory CD4(+ T cell responses, something mirrored in descriptive studies of human disease. Recombinant IL-2/diphtheria toxin fusion protein (rIL-2/DTx, a drug that is FDA-approved for the treatment of cutaneous T cell lymphoma, has been reported to deplete regulatory CD4(+ T cells.We investigated the potential efficacy of rIL-2/DTx as adjunctive therapy for experimental infection with Leishmania major. Treatment with rIL-2/DTx suppressed lesional regulatory T cell numbers and was associated with significantly increased antigen-specific IFN-γ production, enhanced lesion resolution and decreased parasite burden. Combined administration of rIL-2/DTx and sodium stibogluconate had additive biological and therapeutic effects, allowing for reduced duration or dose of sodium stibogluconate therapy.These data suggest that pharmacological suppression of immune counterregulation using a commercially available drug originally developed for cancer therapy may have practical therapeutic utility in leishmaniasis. Rational reinvestigation of the efficacy of drugs approved for other indications in experimental models of neglected tropical diseases has promise in providing new candidates to the drug discovery pipeline.

  7. Therapeutic effect of ursolic acid in experimental visceral leishmaniasis

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    Jéssica A. Jesus

    2017-04-01

    Full Text Available Leishmaniasis is an important neglected tropical disease, affecting more than 12 million people worldwide. The available treatments are not well tolerated and present diverse side effects in patients, justifying the search for new therapeutic compounds. In the present study, the therapeutic potential and toxicity of ursolic acid (UA, isolated from the leaves of Baccharis uncinella C. DC. (Asteraceae, were evaluated in experimental visceral leishmaniasis. To evaluate the therapeutic potential of UA, hamsters infected with L. (L. infantum were treated daily during 15 days with 1.0 or 2.0 mg UA/kg body weight, or with 5.0 mg amphotericin B/kg body weight by intraperitoneal route. Fifteen days after the last dose, the parasitism of the spleen and liver was stimated and the main histopathological alterations were recorded. The proliferation of splenic mononuclear cells was evaluated and IFN-γ, IL-4, and IL-10 gene expressions were analyzed in spleen fragments. The toxicity of UA and amphotericin B were evaluated in healthy golden hamsters by histological analysis and biochemical parameters. Animals treated with UA had less parasites in the spleen and liver when compared with the infected control group, and they also showed preservation of white and red pulps, which correlate with a high rate of proliferation of splenic mononuclear cells, IFN-γ mRNA and iNOS production. Moreover, animals treated with UA did not present alterations in the levels of AST, ALT, creatinine and urea. Taken together, these findings indicate that UA is an interesting natural compound that should be considered for the development of prototype drugs against visceral leishmaniasis.

  8. Experimental models in vaccine research: malaria and leishmaniasis.

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    Teixeira, C; Gomes, R

    2013-02-01

    Animal models have a long history of being useful tools, not only to test and select vaccines, but also to help understand the elaborate details of the immune response that follows infection. Different models have been extensively used to investigate putative immunological correlates of protection against parasitic diseases that are important to reach a successful vaccine. The greatest challenge has been the improvement and adaptation of these models to reflect the reality of human disease and the screening of vaccine candidates capable of overcoming the challenge of natural transmission. This review will discuss the advantages and challenges of using experimental animal models for vaccine development and how the knowledge achieved can be extrapolated to human disease by looking into two important parasitic diseases: malaria and leishmaniasis.

  9. Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis

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    Cunha-Júnior, Edézio Ferreira; Martins, Thiago Martino; Canto-Cavalheiro, Marilene Marcuzzo; Marques, Paulo Roberto; Portari, Elyzabeth Avvad; Coelho, Marsen Garcia Pinto; Netto, Chaquip Daher; Costa, Paulo Roberto Ribeiro; Sabino, Katia Costa de Carvalho

    2016-01-01

    Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and anti-leukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg/kg of body weight/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. An in vivo toxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis. PMID:27067332

  10. Testing Experimental Compounds against Leishmaniasis in Laboratory Animal Model Systems.

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    1983-09-01

    buoyant density analysis, monoclonal antibody typ- ing, and infectivity for sandflies . 2. In Vivo Screening a. Visceral Leishmaniasis Six groups of 6...the case in "pian bois" where vectors are anthoprophilic and multiple lesions (>0) abound (37). Whether environmental temperature has any effect upon...buoyant density, iso-enzymes, reaction with monoclonal antibody and development in sandflies (#3). Each of these was grown in 250 ml BA flasks overlaid

  11. The efficacy of hydro alcoholic extract of Seidlitzia rosmarinus on experimental zoonotic cutaneous leishmaniasis lesions in murine model

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    Maryam Ahmadi

    2014-11-01

    Full Text Available Objective: Leishmaniasis is one of the most important parasitic infectious diseases in the world. Since last century, many efforts have been made to control and treat the disease, but appropriate vaccines, pesticides and medicines are not available or even eligible. The purpose of this study was to evaluate the effect of hydro-alcoholic extract of Seidlitzia rosmarinus on the lesions of experimental Cutaneous Leishmaniasis (CL in Balb/c mice. Materials and Methods: The population study was 60 Ballb/c mice which divided to 6 groups, all infected with Leishmania major [MRHO/75/IR]. Soon after the ulcer started to appear in the early stage, a dose of provided herbal extract with 5, 10 and 15% concentration applied on each lesion. The surface area of the lesions measured during an interval of 10 days. Direct Giemsa stained smears prepared two and four weeks after treatment. Results: Increasing the mean size of the lesions was statistically significant compared to those in control group (p>0.001. Visceral Leishmaniasis (VL developed in all of the mice including the control group that received Eucerine alone. Survival rate in group receiving 15% S. rosmarinus extracts showed significantly higher  compared to mice in control group (p

  12. INFLUENCE OF MICROBIOTA IN EXPERIMENTAL CUTANEOUS LEISHMANIASIS IN SWISS MICE

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    OLIVEIRA Marcia Rosa de

    1999-01-01

    Full Text Available Infection of Swiss/NIH mice with Leishmania major was compared with infection in isogenic resistant C57BL/6 and susceptible BALB/c mice. Swiss/NIH mice showed self-controlled lesions in the injected foot pad. The production of high levels of interferon-g (IFN-g and low levels of interleukin-4 (IL-4 by cells from these animals suggests that they mount a Th1-type immune response. The importance of the indigenous microbiota on the development of murine leishmaniasis was investigated by infecting germfree Swiss/NIH in the hind footpad with L. major and conventionalizing after 3 weeks of infection. Lesions from conventionalized Swiss/NIH mice were significantly larger than conventional mice. Histopathological analysis of lesions from conventionalized animals showed abscesses of variable shapes and sizes and high numbers of parasitized macrophages. In the lesions from conventional mice, besides the absence of abscess formation, parasites were rarely observed. On the other hand, cells from conventional and conventionalized mice produced similar Th1-type response characterized by high levels of IFN-g and low levels of IL-4. In this study, we demonstrated that Swiss/NIH mice are resistant to L. major infection and that the absence of the normal microbiota at the beginning of infection significantly influenced the lesion size and the inflammatory response at the site of infection.

  13. Compartment-specific remodeling of splenic micro-architecture during experimental visceral leishmaniasis.

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    Yurdakul, Pinar; Dalton, Jane; Beattie, Lynette; Brown, Najmeeyah; Erguven, Sibel; Maroof, Asher; Kaye, Paul M

    2011-07-01

    Progressive splenomegaly is a hallmark of visceral leishmaniasis in humans, canids, and rodents. In experimental murine visceral leishmaniasis, splenomegaly is accompanied by pronounced changes in microarchitecture, including expansion of the red pulp vascular system, neovascularization of the white pulp, and remodeling of the stromal cell populations that define the B-cell and T-cell compartments. Here, we show that Ly6C/G(+) (Gr-1(+)) cells, including neutrophils and inflammatory monocytes, accumulate in the splenic red pulp during infection. Cell depletion using monoclonal antibody against either Ly6C/G(+) (Gr-1; RB6) or Ly6G(+) (1A8) cells increased parasite burden. In contrast, depletion of Ly6C/G(+) cells, but not Ly6G(+) cells, halted the progressive remodeling of Meca-32(+) and CD31(+) red pulp vasculature. Strikingly, neither treatment affected white pulp neovascularization or the remodeling of the fibroblastic reticular cell and follicular dendritic cell networks. These findings demonstrate a previously unrecognized compartment-dependent selectivity to the process of splenic vascular remodeling during experimental murine visceral leishmaniasis, attributable to Ly6C(+) inflammatory monocytes.

  14. Early clinical manifestations associated with death from visceral leishmaniasis.

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    Valdelaine Etelvina Miranda de Araújo

    Full Text Available BACKGROUND: In Brazil, lethality from visceral leishmaniasis (VL is high and few studies have addressed prognostic factors. This historical cohort study was designed to investigate the prognostic factors for death from VL in Belo Horizonte (Brazil. METHODOLOGY: The analysis was based on data of the Reportable Disease Information System-SINAN (Brazilian Ministry of Health relating to the clinical manifestations of the disease. During the study period (2002-2009, the SINAN changed platform from a Windows to a Net-version that differed with respect to some of the parameters collected. Multivariate logistic regression models were performed to identify variables associated with death from VL, and these were included in prognostic score. PRINCIPAL FINDINGS: Model 1 (period 2002-2009; 111 deaths from VL and 777 cured patients included the variables present in both SINAN versions, whereas Model 2 (period 2007-2009; 49 deaths from VL and 327 cured patients included variables common to both SINAN versions plus the additional variables included in the Net version. In Model 1, the variables significantly associated with a greater risk of death from VL were weakness (OR 2.9; 95%CI 1.3-6.4, Leishmania-HIV co-infection (OR 2.4; 95%CI 1.2-4.8 and age ≥60 years (OR 2.5; 95%CI 1.5-4.3. In Model 2, the variables were bleeding (OR 3.5; 95%CI 1.2-10.3, other associated infections (OR 3.2; 95%CI 1.3-7.8, jaundice (OR 10.1; 95%CI 3.7-27.2 and age ≥60 years (OR 3.1; 95%CI 1.4-7.1. The prognosis score was developed using the variables associated with death from VL of the latest version of the SINAN (Model 2. The predictive performance of which was evaluated by sensitivity (71.4%, specificity (73.7%, positive and negative predictive values (28.9% and 94.5% and area under the receiver operating characteristic curve (75.6%. CONCLUSIONS: Knowledge regarding the factors associated with death from VL may improve clinical management of patients and contribute to lower

  15. Immunogenicity of the P-8 amastigote antigen in the experimental model of canine visceral leishmaniasis

    OpenAIRE

    Carrillo, E.; S. Ahmed; Goldsmith-Pestana, K.; Nieto, J; Y Osorio; Travi,B; Moreno, J; McMahon-Pratt, D

    2006-01-01

    The P-8 proteoglycolipid complex (P-8 PGLC), an amastigote antigen of L. pifanoi, has been demonstrated to induce protection in mouse models, as well as to induce Tc1/Th1-like cellular responses in American cutaneous leishmaniasis patients. Because the immunization with P-8 PGLC in the murine model does not appear to be genetically restricted, we have studied the reactivity of the P-8 PGLC in L. infantum infected dogs. In this study, it is shown that PBMC from experimentally infected dogs (as...

  16. Immunogenicity of the P-8 amastigote antigen in the experimental model of canine visceral leishmaniasis.

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    Carrillo, E; Ahmed, S; Goldsmith-Pestana, K; Nieto, J; Osorio, Y; Travi, B; Moreno, J; McMahon-Pratt, D

    2007-02-09

    The P-8 proteoglycolipid complex (P-8 PGLC), an amastigote antigen of Leishmania pifanoi, has been demonstrated to induce protection in mouse models, as well as to induce Tc1/Th1-like cellular responses in American cutaneous leishmaniasis patients. Because the immunization with P-8 PGLC in the murine model does not appear to be genetically restricted, we have studied the reactivity of the P-8 PGLC in Leishmania infantum infected dogs. In this study, it is shown that PBMC from experimentally infected dogs (asymptomatic, oligosymptomatic) significantly proliferated in response to soluble leishmanial antigen (SLA) or the P-8 PGLC. Further, quantification of the gene expression induced by the stimulation with P-8 in asymptomatically infected dogs showed an up-regulation of IFN-gamma and TNF-alpha, which were three to 4-fold higher than that induced by soluble Leishmania antigen (SLA). While no measurable induction of IL-10 was observed, low levels of IL-4 mRNA were observed in response to both P-8 and SLA antigens. Thus, our studies establish that P-8 is recognized by infected canines and elicits a potentially curative/protective Th1-like immune response. The identification of Leishmania antigens that elicit appropriate immune responses across different host species (humans, canine) and disease manifestations (cutaneous or visceral) could be an advantage in generating a general vaccine for leishmaniasis.

  17. Comparative evaluation of two vaccine candidates against experimental leishmaniasis due to Leishmania major infection in four inbred mouse strains.

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    Benhnini, Fouad; Chenik, Mehdi; Laouini, Dhafer; Louzir, Hechmi; Cazenave, Pierre André; Dellagi, Koussay

    2009-11-01

    Experimental leishmaniasis in BALB/c and C57BL/6 mice are the most investigated murine models that were used for the preclinical evaluation of Leishmania vaccine candidates. We have previously described two new inbred mouse strains named PWK and MAI issued from feral founders that also support the development of experimental leishmaniasis due to L. major. In this study, we sought to determine whether different mouse inbred strains generate concordant or discordant results when used to evaluate the potential of Leishmania proteins to protect against experimental leishmaniasis. To this end, two Leishmania proteins, namely, LACK (for Leishmania homolog of receptor for activated C kinase) and LmPDI (for L. major protein disulfide isomerase) were compared for their capacity to protect against experimental leishmaniasis in PWK, MAI, BALB/c, and C57BL/6 inbred mouse strains. Our data show that the capacity of Leishmania proteins to confer protection depends on the mouse strain used, stressing the important role played by the genetic background in shaping the immune response against the pathogen. These results may have important implications for the preclinical evaluation of candidate Leishmania vaccines: rather than using a single mouse strain, a panel of different inbred strains of various genetic backgrounds should be tested in parallel. The antigen that confers protection in the larger range of inbred strains may have better chances to be also protective in outbred human populations and should be selected for clinical trials.

  18. Comparative Evaluation of Two Vaccine Candidates against Experimental Leishmaniasis Due to Leishmania major Infection in Four Inbred Mouse Strains▿

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    Benhnini, Fouad; Chenik, Mehdi; Laouini, Dhafer; Louzir, Hechmi; Cazenave, Pierre André; Dellagi, Koussay

    2009-01-01

    Experimental leishmaniasis in BALB/c and C57BL/6 mice are the most investigated murine models that were used for the preclinical evaluation of Leishmania vaccine candidates. We have previously described two new inbred mouse strains named PWK and MAI issued from feral founders that also support the development of experimental leishmaniasis due to L. major. In this study, we sought to determine whether different mouse inbred strains generate concordant or discordant results when used to evaluate the potential of Leishmania proteins to protect against experimental leishmaniasis. To this end, two Leishmania proteins, namely, LACK (for Leishmania homolog of receptor for activated C kinase) and LmPDI (for L. major protein disulfide isomerase) were compared for their capacity to protect against experimental leishmaniasis in PWK, MAI, BALB/c, and C57BL/6 inbred mouse strains. Our data show that the capacity of Leishmania proteins to confer protection depends on the mouse strain used, stressing the important role played by the genetic background in shaping the immune response against the pathogen. These results may have important implications for the preclinical evaluation of candidate Leishmania vaccines: rather than using a single mouse strain, a panel of different inbred strains of various genetic backgrounds should be tested in parallel. The antigen that confers protection in the larger range of inbred strains may have better chances to be also protective in outbred human populations and should be selected for clinical trials. PMID:19726616

  19. Vaccine candidates for leishmaniasis: a review.

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    Nagill, Rajeev; Kaur, Sukhbir

    2011-10-01

    Leishmaniasis is a diverse group of clinical syndromes caused by protozoan parasites of the genus Leishmania. The clinical manifestation of the disease varies from self-limiting cutaneous lesions to progressive visceral disease. It is estimated that 350 million people are at risk in 88 countries, with a global incidence of 1-1.5 million cases of cutaneous and 500,000 cases of visceral leishmaniasis. The key control measures mainly rely on early case detection and chemotherapy which has been hampered by the toxicity of drugs, side-effects and by the emergence of drug resistance in parasites. Control of reservoir host and vector is difficult due to operational difficulties and frequent relapses in the host. Therefore, the development of effective and affordable vaccine against leishmaniasis is highly desirable. Although considerable progress has been made over the last decade in understanding immune mechanisms underlying potential candidate antigens, including killed, live attenuated parasites, crude parasites, pure or recombinant Leishmania proteins or DNA encoding leishmanial proteins, as well as immunomodulators from sand fly saliva, very few candidate vaccines have progressed beyond the experimental stage. As such there is no vaccine against any form of human leishmaniasis. In recent years, however, much interest has been stimulated towards vaccination against leishmaniasis focused mainly on cutaneous leishmaniasis with fewer attempts against visceral leishmaniasis.

  20. Experimental challenge models for canine leishmaniasis in hamsters and dogs, optimization and application in vaccine research

    NARCIS (Netherlands)

    Poot, Jacqueline

    2006-01-01

    In dogs, leishmaniasis caused by the protozoan parasite Leishmania infantum is a serious and potentially fatal disease. This parasite can also cause zoonotic visceral leishmaniasis in children and immunocompromised adults. A vaccine for dogs would not only be of great value in veterinary medicine bu

  1. Experimental Infection of Dogs with Leishmania and Saliva as a Model to Study Canine Visceral Leishmaniasis

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    Costa, Dirceu Joaquim; Carvalho, Rayssa M. de Araujo; Abbehusen, Melissa; Teixeira, Clarissa; Pitombo, Maiana; Trigo, Joelma; Nascimento, Flávia; Amorim, Lucilene; Abreu-Silva, Ana Lucia; do Socorro Pires Cruz, Maria; Miranda, José Carlos; Fukutani, Kyoshi; de Oliveira, Camila I.; Barral, Aldina; Barral-Netto, Manoel; Brodskyn, Cláudia

    2013-01-01

    Background Canine Visceral Leishmaniasis (CVL) is a zoonotic disease caused by Leishmania infantum, transmitted by the bite of Lutzomyia longipalpis sand flies. Dogs are the main domestic reservoir of the parasite. The establishment of an experimental model that partially reproduces natural infection in dogs is very important to test vaccine candidates, mainly regarding those that use salivary proteins from the vector and new therapeutical approaches. Methodology/Principal Findings In this report, we describe an experimental infection in dogs, using intradermal injection of Leishmania infantum plus salivary gland homogenate (SGH) of Lutzomyia longipalpis. Thirty-five dogs were infected with 1×107 parasites combined with five pairs of Lutzomyia longipalpis salivary glands and followed for 450 days after infection and clinical, immunological and parasitological parameters were evaluated. Two hundred and ten days after infection we observed that 31,4% of dogs did not display detectable levels of anti-Leishmania antibodies but all presented different numbers of parasites in the lymph nodes. Animals with a positive xenodiagnosis had at least 3,35×105 parasites in their lymph nodes. An increase of IFN-γ and IL-10 levels was detected during infection. Twenty two percent of dogs developed symptoms of CVL during infection. Conclusion The infection model described here shows some degree of similarity when compared with naturally infected dogs opening new perspectives for the study of CVL using an experimental model that employs the combination of parasites and sand fly saliva both present during natural transmission. PMID:23577121

  2. Leishmaniasis Disease

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    ... The CDC Cancel Submit Search The CDC Parasites - Leishmaniasis Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Leishmaniasis General Information Leishmaniasis FAQs Epidemiology & Risk Factors Biology ...

  3. Therapeutic vaccination with recombinant adenovirus reduces splenic parasite burden in experimental visceral leishmaniasis.

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    Maroof, Asher; Brown, Najmeeyah; Smith, Barbara; Hodgkinson, Michael R; Maxwell, Alice; Losch, Florian O; Fritz, Ulrike; Walden, Peter; Lacey, Charles N J; Smith, Deborah F; Aebischer, Toni; Kaye, Paul M

    2012-03-01

    Therapeutic vaccines, when used alone or in combination therapy with antileishmanial drugs, may have an important place in the control of a variety of forms of human leishmaniasis. Here, we describe the development of an adenovirus-based vaccine (Ad5-KH) comprising a synthetic haspb gene linked to a kmp11 gene via a viral 2A sequence. In nonvaccinated Leishmania donovani-infected BALB/c mice, HASPB- and KMP11-specific CD8(+) T cell responses were undetectable, although IgG1 and IgG2a antibodies were evident. After therapeutic vaccination, antibody responses were boosted, and IFNγ(+)CD8(+) T cell responses, particularly to HASPB, became apparent. A single vaccination with Ad5-KH inhibited splenic parasite growth by ∼66%, a level of efficacy comparable to that observed in early stage testing of clinically approved antileishmanial drugs in this model. These studies indicate the usefulness of adenoviral vectors to deliver leishmanial antigens in a potent and host protective manner to animals with existing L. donovani infection.

  4. Therapy of Venezuelan patients with severe mucocutaneous or early lesions of diffuse cutaneous leishmaniasis with a vaccine containing pasteurized Leishmania promastigotes and bacillus Calmette-Guerin: preliminary report

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    Jacinto Convit

    2004-02-01

    Full Text Available Severe mucocutaneous (MCL and diffuse (DCL forms of American cutaneous leishmaniasis (ACL are infrequent in Venezuela. Chemotherapy produces only transitory remission in DCL, and occasional treatment failures are observed in MCL. We have evaluated therapy with an experimental vaccine in patients with severe leishmaniasis. Four patients with MCL and 3 with early DCL were treated with monthly intradermal injections of a vaccine containing promastigotes of Leishmania (Viannia braziliensis killed by pasteurization and viable Bacillus Calmette- Guerin. Clinical and immunological responses were evaluated. Integrity of protein constituents in extracts of pasteurized promastigotes was evaluated by gel electrophoresis. Complete remission of lesions occurred after 5-9 injections in patients with MCL or 7-10 injections in patients with early DCL. DCL patients developed positive skin reactions, average size 18.7 mm. All have been free of active lesions for at least 10 months. Adverse effects of the vaccine were limited to local reactivity to BCG at the injection sites and fever in 2 patients. Extracts of pasteurized and fresh promastigotes did not reveal differences in the integrity of protein components detectable by gel electrophoresis. Immunotherapy with this modified vaccine offers an effective, safe option for the treatment of patients who do not respond to immunotherapy with vaccine containing autoclaved parasites or to chemotherapy .

  5. Efficacy of Desmodium gangeticum extract and its fractions against experimental visceral leishmaniasis.

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    Singh, Nasib; Mishra, Pushpesh Kumar; Kapil, Aruna; Arya, Kamal Ram; Maurya, Rakesh; Dube, Anuradha

    2005-04-08

    Crude ethanolic extract of Indian medicinal plant, Desmodium gangeticum (A001) and its three fractions-hexane (F002), n-butanol (F003) and aqueous (F004) were evaluated chemoprophylactically and chemotherapeutically against experimental visceral leishmaniasis in hamsters. Ethanolic extract showed 41.2+/-5.3% inhibition of parasite multiplication when administered at a dose of 250 mg/kgx2 on day -7 and +7 of Leishmania donovani challenge. Its n-butanol fraction exhibited better efficacy than the ethanolic extract to the tune of 66.7+/-6.1% inhibition when administered at similar dose schedule. But the other two fractions failed to exert any action prophylactically. F003 also imparted significant (P<0.001) non-specific resistance to peritoneal macrophages against Leishmania infection. F003 also showed moderate antileishmanial activity when tested against established infection of Leishmania donovani in hamsters but the rest three fractions failed to show any significant inhibition of parasite multiplication. These findings revealed that this plant has potential prophylactic and therapeutic efficacy against Leishmania infection and warrants detailed investigations on its possible immunopotentiatory actions.

  6. New administration model of trans-chalcone biodegradable polymers for the treatment of experimental leishmaniasis.

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    Piñero, Jose; Temporal, Rosane M; Silva-Gonçalves, Antonio J; Jiménez, I A; Bazzocchi, Isabel L; Oliva, Alexis; Perera, Antonio; Leon, Leonor L; Valladares, Basilio

    2006-04-01

    The present study was designed to investigate a new administration model and the antileishmanial activity of a semi-synthetic chalcone, benzylideneacetophenone (trans-chalcone). The antileishmanial activity of this product was first tested in vitro against promastigotes of L. braziliensis, L. tropica, L. infantum and L. amazonensis. An in vivo experiment was carried out using subcutaneous administration of trans-chalcone and implants of synthetic biodegradable polymers, polylactic acid (PLA) and polylactic/glycolic acid (PLGA). This compound showed potent inhibitory effects on the growth of all Leishmania strains examinated. Subcutaneous administration of trans-chalcone at a single dose of 4 mg/kg of body weight reduced lesion development in mice infected with L. amazonensis. A similar inhibition of the lesion growth in mice treated with trans-chalcone and pentamidine was observed. PLA and PGLA implants of trans-chalcone at 4 mg/kg were administered to mice infected with L. amazonensis. PLGA implants induced a highest reduction in the lesion size (31.25%) than PLA implants (10.75%). Treatment in vitro with trans-chalcone at IC50, completely inhibited the pathogenicity of this parasite in vivo. The development of this model provides a new practical technique for delivering drugs and can be useful for experimental leishmaniasis treatment.

  7. Experimental infection of dogs with Leishmania and saliva as a model to study Canine Visceral Leishmaniasis.

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    Dirceu Joaquim Costa

    Full Text Available BACKGROUND: Canine Visceral Leishmaniasis (CVL is a zoonotic disease caused by Leishmania infantum, transmitted by the bite of Lutzomyia longipalpis sand flies. Dogs are the main domestic reservoir of the parasite. The establishment of an experimental model that partially reproduces natural infection in dogs is very important to test vaccine candidates, mainly regarding those that use salivary proteins from the vector and new therapeutical approaches. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we describe an experimental infection in dogs, using intradermal injection of Leishmania infantum plus salivary gland homogenate (SGH of Lutzomyia longipalpis. Thirty-five dogs were infected with 1×10(7 parasites combined with five pairs of Lutzomyia longipalpis salivary glands and followed for 450 days after infection and clinical, immunological and parasitological parameters were evaluated. Two hundred and ten days after infection we observed that 31,4% of dogs did not display detectable levels of anti-Leishmania antibodies but all presented different numbers of parasites in the lymph nodes. Animals with a positive xenodiagnosis had at least 3,35×10(5 parasites in their lymph nodes. An increase of IFN-γ and IL-10 levels was detected during infection. Twenty two percent of dogs developed symptoms of CVL during infection. CONCLUSION: The infection model described here shows some degree of similarity when compared with naturally infected dogs opening new perspectives for the study of CVL using an experimental model that employs the combination of parasites and sand fly saliva both present during natural transmission.

  8. B cell: T cell interactions occur within hepatic granulomas during experimental visceral leishmaniasis.

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    John W J Moore

    Full Text Available Hepatic resistance to Leishmania donovani infection in mice is associated with the development of granulomas, in which a variety of lymphoid and non-lymphoid populations accumulate. Although previous studies have identified B cells in hepatic granulomas and functional studies in B cell-deficient mice have suggested a role for B cells in the control of experimental visceral leishmaniasis, little is known about the behaviour of B cells in the granuloma microenvironment. Here, we first compared the hepatic B cell population in infected mice, where ≈60% of B cells are located within granulomas, with that of naïve mice. In infected mice, there was a small increase in mIgM(lomIgD(+ mature B2 cells, but no enrichment of B cells with regulatory phenotype or function compared to the naïve hepatic B cell population, as assessed by CD1d and CD5 expression and by IL-10 production. Using 2-photon microscopy to quantify the entire intra-granuloma B cell population, in conjunction with the adoptive transfer of polyclonal and HEL-specific BCR-transgenic B cells isolated from L. donovani-infected mice, we demonstrated that B cells accumulate in granulomas over time in an antigen-independent manner. Intra-vital dynamic imaging was used to demonstrate that within the polyclonal B cell population obtained from L. donovani-infected mice, the frequency of B cells that made multiple long contacts with endogenous T cells was greater than that observed using HEL-specific B cells obtained from the same inflammatory environment. These data indicate, therefore, that a subset of this polyclonal B cell population is capable of making cognate interactions with T cells within this unique environment, and provide the first insights into the dynamics of B cells within an inflammatory site.

  9. Efecto de la temperatura de la piel en la leishmaniasis cutanea experimental

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    Rodrigo Zeledón

    1971-06-01

    Full Text Available The literature on the thermosensitive properties of strains or species of Leishmania and of other miercorganisms is revised. Cutaneous or mucocutaneous strains that infect animais in the coldest areas of the skin or mucosa in general can not grow in tissue culture at 37°C or higher temperatures and their respiratory metabolism decreases at these temperatures. These facts suggest a thermosensitive event in some important metabolism phase of the organisme. The strains or species that are able to produce visceral leishmaniasis were probably originated from cutaneous strains after genetioally determined physiological adaptation, to warmer temperatures. These strains can not only visceralize in animais and man but will also grow in tissue culture at 36-37°C and the respiratory metabolism will be higher at such temperatures. There are reasons to believe that intermediate strains, i. e., with properties of both groupsí do exist. A thermosensitive physiological event is a more general phenomenon and examples of it can also be found in the fields of virology, bacteriology and mycology. It has practical applications since some of the diseases produced by these agents can be cured by treatments with heat or artificial fever. Experiments along these line were performed on hamsters with a Costa Rican strain of L. braziliensis as an experimental model. Even after intraperitoneal inoculation lesions appear in the nose, ears, paws and tail with a subcutaneous temperature bellow 33°C at 22-24°C. Healing of the lesión is accomplished by increasing room temperature. A good lesión is produced in the rump of the animal if the area is depilated (comercial cream depilatory previously and the naked skin cooled artificially. Elevated temperature, or the growing back of the hair will tend to diminish or cure the lesion.

  10. Interleukin-10 and Transforming Growth Factor-β in Early and Late Lesions of Patients with Leishmania major induced Cutaneous Leishmaniasis

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    A Khamesipour

    2012-06-01

    Full Text Available Background: Cutaneous leishmaniasis is a neglected parasitic disease, which imposes massive human distress and financial costs to the endemic countries. Better understanding of host immune response to the parasite leads to helpful strategies for disease control. Interleukin (IL-10 and transforming growth factor (TGF-β are important immune regulatory cytokines, which appear to develop non-healing forms of leishmaniasis. However, there is little information about the function of IL-10 and TGF-β in old world cutaneous leismaniasis. The aim of this study was to analyze the role of IL-10 and TGF-β in human cutaneous leishmaniasis due to Leishmania major infection.Methods: Biopsies were obtained from lesions of twenty proven cases of L. major induced cutaneous leishmaniasis. IL-10 and TGF-β positive cells were detected by immunofluorescence staining of frozen sections and compared between two groups of patients with early and late lesions.Results: The mean percentage of IL-10 positive cells were significantly (P= 0.035 higher in late lesions (0.51±0.24 than early ones (0.15±0.07. Similar results were obtained for TGF-β with mean percentages of 0.16±0.05 and 0.53±0.28 in early and late lesions respectively (P= 0.008.Conclusion: IL-10 and TGF-β are present in lesions of L. major induced cutaneous leishmaniasis and contribute to the pathogenesis of long lasting disease forms.

  11. Interleukin-10 and Transforming Growth Factor-β in Early and Late Lesions of Patients with Leishmania major Induced Cutane­ous Leishmaniasis

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    A Khamesipour

    2012-09-01

    Full Text Available Background: Cutaneous leishmaniasis is a neglected parasitic disease, which imposes massive human distress and financial costs to the endemic countries. Better understanding of host immune response to the parasite leads to helpful strategies for disease control. Interleukin (IL-10 and transforming growth factor (TGF-β are important immune regulatory cytokines, which appear to develop non-healing forms of leishmaniasis. However, there is little information about the function of IL-10 and TGF-β in old world cutaneous leismaniasis. The aim of this study was to analyze the role of IL-10 and TGF-β in human cutaneous leishmaniasis due to Leishmania major infection. Methods: Biopsies were obtained from lesions of twenty proven cases of L. major induced cutaneous leishmaniasis. IL-10 and TGF-β positive cells were detected by immunofluorescence staining of frozen sections and compared between two groups of patients with early and late lesions. Results: The mean percentage of IL-10 positive cells were significantly (P= 0.035 higher in late lesions (0.51±0.24 than early ones (0.15±0.07. Similar results were obtained for TGF-β with mean percentages of 0.16±0.05 and 0.53±0.28 in early and late lesions respectively (P= 0.008. Conclusion: IL-10 and TGF-β are present in lesions of L. major induced cutaneous leishmaniasis and contribute to the pathogenesis of long lasting disease forms.

  12. Synthetic sex pheromone attracts the leishmaniasis vector Lutzomyia longipalpis to experimental chicken sheds treated with insecticide

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    Brazil Reginaldo P

    2010-03-01

    Full Text Available Abstract Background Current strategies for controlling American visceral leishmaniasis (AVL have been unable to prevent the spread of the disease across Brazil. With no effective vaccine and culling of infected dogs an unpopular and unsuccessful alternative, new tools are urgently needed to manage populations of the sand fly vector, Lutzomyia longipalpis Lutz and Neiva (Diptera: Psychodidae. Here, we test two potential strategies for improving L. longipalpis control using the synthetic sand fly pheromone (±-9-methylgermacrene-B: the first in conjunction with spraying of animal houses with insecticide, the second using coloured sticky traps. Results Addition of synthetic pheromone resulted in greater numbers of male and female sand flies being caught and killed at experimental chicken sheds sprayed with insecticide, compared to pheromone-less controls. Furthermore, a ten-fold increase in the amount of sex pheromone released from test sheds increased the number of females attracted and subsequently killed. Treating sheds with insecticide alone resulted in a significant decrease in numbers of males attracted to sheds (compared to pre-spraying levels, and a near significant decrease in numbers of females. However, this effect was reversed through addition of synthetic pheromone at the time of insecticide spraying, leading to an increase in number of flies attracted post-treatment. In field trials of commercially available different coloured sticky traps, yellow traps caught more males than blue traps when placed in chicken sheds. In addition, yellow traps fitted with 10 pheromone lures caught significantly more males than pheromone-less controls. However, while female sand flies showed a preference for both blue and yellow pheromone traps sticky traps over white traps in the laboratory, neither colour caught significant numbers of females in chicken sheds, either with or without pheromone. Conclusions We conclude that synthetic pheromone could

  13. Infecções experimentaes na Leishmaniose visceral americana Experimental infections in american visceral leishmaniasis

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    Aristides Marques da Cunha

    1938-01-01

    sôro-agglutinação, conforme mostramos em trabalho anterior, não permite a separação das especies do genero Leishmania, pois todas ellas, quando recentemente isoladas, possuem identica constituição antigenica, que se modifica depois, pela conservação longo tempo em cultura. É esse facto, que deu logar ás conclusões contradictorias a que chegaram os autores que se ocuparam do assumpto bem como os primeiros resultados que obtivemos. Deante de todos esses factos, nos julgamos autorizados a concluir como já fizemos anteriormente, que o agente da Leishmaniose visceral americana é identico á Leishmania infantum. Ao terminar, queremos deixar consignados nossos agradecimentos ao Dr. E. chagas, por ter posto a nossa disposição as culturas de Leishmania por elle isoladas, tornando possivel deste modo, a execução do presente trabalho.With cultures isolated from cases of american visceral leishmaniasis we succeeded in obtaining experimental infections in hamsters (Cricetus cricetus, rhesus monkeys (Macaca mullata and dogs. Hamsters were infected with strains obtained from man and dogs, the intraperitoneal way having been always employed. When cultures recently isolated are used, infection is obtained practically in 100% of the animals inoculated. The first negative results obtained by us may be explained by the use of cultures isolated some time before (about 7 months 0 and which had lost already their virulence. In some cases external lesions are observed represented by alterations of the skin and swelling of the paws. The skin lesions are observed on the ventral surface and consist in depilation, erythema and exudation. The skin thus affected shows to be extremely friable, rupturing at the movements of the animal when hold. On post-mortem examination, besides the lesions pointed out, the animals present enlargement of the spleen. The parasites are very numerous in the spleen, liver, bone marrow, etc. The changed skin shows considerable hypertrophy of the

  14. Indigenous microbiota and Leishmaniasis.

    Science.gov (United States)

    Lopes, M E M; Carneiro, M B H; Dos Santos, L M; Vieira, L Q

    2016-01-01

    Animals are colonized by their indigenous microbiota from the early days of life. The estimated number of associated bacterial cells in humans is around of 10(14) per individual, most of them in the gut. Several studies have investigated the microbiota-host relationship, and the use of germfree animals has been an important tool in these studies. These animals, when infected with a pathogen, have shown to be sometimes more resistant and other times more susceptible than conventional animals. Leishmaniasis is a worldwide public health problem and presents a spectrum of clinical manifestations. However, very few studies have addressed the role of the indigenous microbiota on the outcome of this disease. In this review, we will highlight and discuss the data available on the ways by which the microbiota can influence the outcome of the disease in murine experimental models of cutaneous infection with Leishmania.

  15. CCR7 facilitates the pro-inflammatory function of dendritic cells in experimental leishmaniasis.

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    Kling, J C; Darby, J; Körner, H

    2014-04-01

    Cutaneous leishmaniasis, caused by the parasite Leishmania major, results in lesions at the site of infection, which are self-healing in resistant hosts. However, in the absence of the chemokine receptor CCR7, mice are unable to heal the lesion and develop chronic disease. These B6.CCR7(-/-) mice display an increased number of Th2 cells and immunosuppressive cytokine levels, as well as more regulatory T cells. As CCR7 is expressed on activated dendritic cells (DCs), and these cells require CCR7 to migrate to the draining lymph node, we expected decreased migration of DCs into the lymph node in the absence of CCR7 during cutaneous leishmaniasis. Consequently, in an attempt to initiate a self-healing response, we adoptively transferred CCR7(+) (B6.WT) DCs into the site of infection of B6.CCR7(-/-) mice. Surprisingly, instead of healing the lesion, B6.CCR7(-/-) mice inoculated with B6.WT DCs developed augmented lesions and showed increased immunosuppression compared to control B6.CCR7(-/-) mice transferred with B6.CCR7(-/-) DCs or B6.WT mice with B6.WT DCs. Finally, B6.WT mice injected with B6.CCR7(-/-) DCs also presented delayed healing of the lesion. These results indicate that CCR7 must be expressed on DCs, as well as peripheral cells, to allow an efficient immune response to L. major.

  16. Immunogenicity of HSP-70, KMP-11 and PFR-2 leishmanial antigens in the experimental model of canine visceral leishmaniasis.

    Science.gov (United States)

    Carrillo, Eugenia; Crusat, Martín; Nieto, Javier; Chicharro, Carmen; Thomas, Maria del Carmen; Martínez, Enrique; Valladares, Basilio; Cañavate, Carmen; Requena, Jose María; López, Manuel Carlos; Alvar, Jorge; Moreno, Javier

    2008-03-28

    Zoonotic visceral leishmaniasis (ZVL) is a parasitic disease caused by Leishmania infantum/L. chagasi that is emerging as an important medical and veterinary problem. Dogs are the domestic reservoir for this parasite and, therefore, the main target for controlling the transmission to humans. In the present work, we have evaluated the immunogenicity of the Leishmania infantum heat shock protein (HSP)-70, paraflagellar rod protein (PFR)-2 and kinetoplastida membrane protein (KMP)-11 recombinant proteins in dogs experimentally infected with the parasite. We have shown that peripheral blood mononuclear cells (PBMC) from experimentally infected dogs proliferated in response to these recombinant antigens and against the soluble leishmanial antigen (SLA). We have also quantified the mRNA expression level of the cytokines induced in PBMC upon stimulation with the HSP-70, PFR-2 and KMP-11 proteins. These recombinant proteins induced an up-regulation of IFN-gamma. HSP-70 and PFR-2 also produced an increase of the TNF-alpha transcripts abundance. No measurable induction of IL-10 was observed and low levels of IL-4 mRNA were produced in response to the three mentioned recombinant antigens. Serum levels of specific antibodies against HSP-70, PFR-2 and KMP-11 recombinant proteins were also determined in these animals. Our study showed that HSP-70, KMP-11 and PFR-2 proteins are recognized by infected canines. Furthermore, these antigens produce a Th1-type immune response, suggesting that they may be involved in protection. The identification as vaccine candidates of Leishmania antigens that elicit appropriate immune responses in the canine model is a key step in the rational approach to generate a vaccine for canine visceral leishmaniasis.

  17. Preliminary study towards a novel experimental model to study localized cutaneous leishmaniasis caused bY Leishmania (Leishmania mexicana

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    Erika Ivett Sosa-Bibiano

    2012-06-01

    Full Text Available There is not an experimental model of localized cutaneous leishmaniasis (LCL caused by Leishmania (Leishmania mexicana. The aim of the present study was to characterize the clinical and histological features of Peromyscus yucatanicus experimentally infected with L. (L. mexicana. A total of 54 P. yucatanicus (groups of 18 were inoculated with 1x10(6 promastigotes of L. (L. mexicana in the base of the tail. They were euthanized at three and six months post experimental infection. The control group was inoculated with RPMI-1640. The predominant clinical sign observed was a single ulcerated lesion in 27.77% (5/18 and in 11.11% (2/18 P. yucatanicus at three and six months respectively. The histological pattern described as chronic granulomatous inflammation with or without necrosis was found in 7/7 (100% biopsies of euthanized P. yucatanicus at three (n = 5 and six (n = 2 months, respectively. These results resembled clinical and histological features caused by L. (L. mexicana in humans, and support the possibility to employ P. yucatanicus as a novel experimental model to study LCL caused by this parasite.

  18. Action of pentoxifylline on experimental cutaneous leishmaniasis due to Leishmania (Leishmania amazonensis

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    Thiago de Sá Oliveira

    2000-08-01

    Full Text Available In the animal model of leishmaniasis caused by Leishmania (Leishmania amazonensis there is a complex mechanism of the host-parasite interaction. The present study was performed to interfere with the inflammatory reaction to the parasites, through immune modulation. Female C5BL/6 isogenic mice were used, some of which were inoculated on the right ear and others on the right footpad with 3.10(6 stationary phase promastigotes of the MHOM/BR/PH8 strain of L. (L. amazonensis, and were allocated in three groups: the first received pentoxifylline 8mg/kg every 12 h, since the first day; the second one received the same dose since the 40th day of infection and a control group that did not receive any treatment. All the ears excised were analyzed to determine the variation in weight between both ears and for histopathological analyses. A quantification of the parasites was done using the limiting dilution assay. A significant reduction of the number of parasites, was observed among the animals treated which had an accordingly significant reduction on the weight of the ears. Pentoxifylline reduced the macrophages propensity to vacuolation and induced a more effective destruction of the parasites by these cells. Moreover, the group that began the treatment later did not show the same effectiveness.

  19. VCAM-1 and VLA-4 modulate dendritic cell IL-12p40 production in experimental visceral leishmaniasis.

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    Amanda C Stanley

    Full Text Available Vascular cell adhesion molecule-1 (VCAM-1 interacts with its major ligand very late antigen-4 (VLA-4 to mediate cell adhesion and transendothelial migration of leukocytes. We report an important role for VCAM-1/VLA-4 interactions in the generation of immune responses during experimental visceral leishmaniasis caused by Leishmania donovani. Our studies demonstrate that these molecules play no direct role in the recruitment of leukocytes to the infected liver, but instead contribute to IL-12p40-production by splenic CD8(+ dendritic cells (DC. Blockade of VCAM-1/VLA-4 interactions using whole antibody or anti-VCAM-1 Fab' fragments reduced IL-12p40 mRNA accumulation by splenic DC 5 hours after L. donovani infection. This was associated with reduced anti-parasitic CD4(+ T cell activation in the spleen and lowered hepatic IFNgamma, TNF and nitric oxide production by 14 days post infection. Importantly, these effects were associated with enhanced parasite growth in the liver in studies with either anti-VCAM-1 or anti-VLA-4 antibodies. These data indicate a role for VCAM-1 and VLA-4 in DC activation during infectious disease.

  20. Immunization with H1, HASPB1 and MML Leishmania proteins in a vaccine trial against experimental canine leishmaniasis

    Science.gov (United States)

    Moreno, J.; Nieto, J.; Masina, S.; Cañavate, C.; Cruz, I.; Chicharro, C.; Carrillo, E.; Napp, S.; Reymond, C.; Kaye, P.M.; Smith, D.F.; Fasel, N.; Alvar, J.

    2007-01-01

    The protective capabilities of three Leishmania recombinant proteins – histone 1 (H1) and hydrophilic acylated surface protein B1 (HASPB1) immunized singly, or together as a protein cocktail vaccine with Montanide™, and the polyprotein MML immunized with MPL®-SE adjuvant – were assessed in beagle dogs. Clinical examination of the dogs was carried out periodically under blinded conditions and the condition of the dogs defined as asymptomatic or symptomatic. At the end of the trial, we were able to confirm that following infection with L. infantum promastigotes, five out of eight dogs immunized with H1 Montanide™, and four out of eight dogs immunized with either the combination of HASPB1 with Montanide™ or the combination of H1 + HASPB1 with Montanide™, remained free of clinical signs, compared with two out of seven dogs immunized with the polyprotein MML and adjuvant MPL®-SE, and two out of eight dogs in the control group. The results demonstrate that HASPB1 and H1 antigens in combination with Montanide™ were able to induce partial protection against canine leishmaniasis, even under extreme experimental challenge conditions. PMID:17576026

  1. Laryngeal Leishmaniasis

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    Moraes, Bruno Teixeira de

    2012-01-01

    Full Text Available Introduction: Leishmaniasis is classified into three clinical presentations: visceral, coetaneous and mucocutaneous. The latter is usually secondary to hematogenous spread after months or years of skin infection and can manifest as infiltrative lesions, ulcerated or vegetating in nose, pharynx, larynx and mouth, associated or not with ganglionics infarction. Laryngeal involvement is part of the differential diagnosis of lesions in this topography as nonspecific chronic laryngitis, granulomatosis and even tumors of the upper aerodigestive tract presenting atypical evolution. Sometimes it is difficult for the correct diagnosis of Leishmaniasis, with description of cases in the literature were conducted improperly. Objective: The objective of this study is to report a case of laryngeal Leishmaniasis addressing the difficulty of diagnosis, complications and treatment applied. Case Report: A patient with pain throat, dysphagia, odynophagia, dysphonia and weight loss, with no improvement with symptomatic medication. At telelaringoscopy, infiltrative lesion showed nodular supraglottis. He underwent a tracheotomy for airway obstruction and biopsy with immunohistochemical study for a definitive diagnosis of laryngeal Leishmaniasis. The patient was referred to the infectious diseases that initiated treatment with N-methylglucamine antimoniate with satisfactory response to therapy. Final Comments: Faced with a clinical suspicion of granulomatous diseases, it is essential to follow protocol laboratory evaluation associated with histological injury, to get a precise definition etiological without prolonging the time of diagnosis. Medical treatment for mucosal Leishmaniasis, recommended by the World Health Organization, was adequate in the case of laryngeal disorders, with complete resolution of symptoms.

  2. Diagnosis of Leishmaniasis

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    ... The CDC Cancel Submit Search The CDC Parasites - Leishmaniasis Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Leishmaniasis General Information Leishmaniasis FAQs Epidemiology & Risk Factors Biology ...

  3. Leishmaniasis FAQs

    Science.gov (United States)

    ... U.S. civilian travelers have been acquired in common tourist destinations in Latin America, such as in Costa Rica. U.S. military personnel have become infected in various countries, such as Iraq and Afghanistan Back To Top Is leishmaniasis found in the United States? Not ...

  4. The role of natural killer cells in the early period of infection in murine cutaneous leishmaniasis

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    M.D. Laurenti

    1999-03-01

    Full Text Available In order to study the role of natural killer (NK cells during the early period of Leishmania infection, BALB/c mice were selectively and permanently depleted of NK cells by injection with 90Sr and subsequently infected with Leishmania (Leishmania amazonensis (HSJD-1 strain. 90Sr is known to selectively deplete NK cells, leaving an intact T- and B-cell compartment and preserving the ability to produce both interferon alpha and IL-2. This method of depletion has advantages when compared with depletion using anti-NK cell monoclonal antibodies because the effect is permanent and neither activates complement nor provokes massive cell death. In the present study, after one month of treatment with 90Sr, the depletion of NK cells was shown by a more than ten-fold reduction in the cytotoxic activity of these cells: 2 x 106 spleen cells from NK-depleted animals were required to reach the same specific lysis of target cells effected by 0.15 x 106 spleen cells from normal control animals. The histopathology of the skin lesion at 7 days after Leishmania infection showed more parasites in the NK cell-depleted group. This observation further strengthens a direct role of NK cells during the early period of Leishmania infection.

  5. [Cutaneous leishmaniasis].

    Science.gov (United States)

    Enk, C D; Gardlo, K; Hochberg, M; Ingber, A; Ruzicka, T

    2003-06-01

    Leishmaniasis is a vector-borne disease caused by an obligate intracellular protozoa, Leishmania, which resides in macrophages. The parasite is transmitted by an infected female sandfly. The incidence of cutaneous leishmaniasis approaches 2 million new cases per year with 90% of the cases occurring in the "Old World", while the "New World" accounts for the rest. Infection may be restricted to the skin with development of characteristic ulcers, or may affect the mucous membranes in its mucocutaneous form. The clinical diagnosis is verified by the presence of amastigotes in slit-skin smears. Therapeutic modalities include systemic treatments such as the pentavalent antimony compound sodium stibogluconate, liposomal formulations of amphotericin B, oral ketoconazole or itraconazole, as well as topical paromomycin sulphate, local heat, freezing with liquid nitrogen, or photodynamic therapy. An effective vaccine is not available.

  6. The Effect of Ursolic Acid on Leishmania (Leishmania) amazonensis Is Related to Programed Cell Death and Presents Therapeutic Potential in Experimental Cutaneous Leishmaniasis

    Science.gov (United States)

    Yamamoto, Eduardo S.; Campos, Bruno L. S.; Jesus, Jéssica A.; Laurenti, Márcia D.; Ribeiro, Susan P.; Kallás, Esper G.; Rafael-Fernandes, Mariana; Santos-Gomes, Gabriela; Silva, Marcelo S.; Sessa, Deborah P.; Lago, João H. G.; Levy, Débora; Passero, Luiz F. D.

    2015-01-01

    Among neglected tropical diseases, leishmaniasis is one of the most important ones, affecting more than 12 million people worldwide. The available treatments are not well tolerated, and present diverse side effects, justifying the search for new therapeutic compounds. In the present study, the activity of ursolic acid (UA) and oleanolic acid (OA) were assayed in experimental cutaneous leishmaniasis (in vitro and in vivo). Promastigote forms of L. amazonensis were incubated with OA and UA for 24h, and effective concentration 50% (EC50) was estimated. Ultraestructural alterations in Leishmania amazonensis promastigotes after UA treatment were evaluated by transmission electron microscopy, and the possible mode of action was assayed through Annexin V and propidium iodide staining, caspase 3/7 activity, DNA fragmentation and transmembrane mitochondrial potential. The UA potential was evaluated in intracellular amastigotes, and its therapeutic potential was evaluated in L. amazonensis infected BALB/c mice. UA eliminated L. amazonensis promastigotes with an EC50 of 6.4 μg/mL, comparable with miltefosine, while OA presented only a marginal effect on promastigote forms at 100 μg/mL. The possible mechanism by which promastigotes were eliminated by UA was programmed cell death, independent of caspase 3/7, but it was highly dependent on mitochondria activity. UA was not toxic for peritoneal macrophages from BALB/c mice, and it was able to eliminate intracellular amastigotes, associated with nitric oxide (NO) production. OA did not eliminate amastigotes nor trigger NO. L. amazonensis infected BALB/c mice submitted to UA treatment presented lesser lesion size and parasitism compared to control. This study showed, for the first time, that UA eliminate promastigote forms through a mechanism associated with programed cell death, and importantly, was effective in vivo. Therefore, UA can be considered an interesting candidate for future tests as a prototype drug for the treatment

  7. Early modern experimentation on live animals.

    Science.gov (United States)

    Bertoloni Meli, Domenico

    2013-01-01

    Starting from the works by Aselli (De lactibus sive lacteis venis, 1627) on the milky veins and Harvey (1628, translated in 1993) on the motion of the heart and the circulation of the blood, the practice of vivisection witnessed a resurgence in the early modern period. I discuss some of the most notable cases in the century spanning from Aselli's work to the investigations of fluid pressure in plants and animals by Stephen Hales (Vegetable Staticks, 1727). Key figures in my study include Johannes Walaeus, Jean Pecquet, Marcello Malpighi, Reinier de Graaf, Richard Lower, Anton Nuck, and Anton de Heide. Although vivisection dates from antiquity, early modern experimenters expanded the range of practices and epistemic motivations associated with it, displaying considerable technical skills and methodological awareness about the problems associated with the animals being alive and the issue of generalizing results to humans. Many practitioners expressed great discomfort at the suffering of the animals; however, many remained convinced that their investigations were not only indispensable from an epistemic standpoint but also had potential medical applications. Early modern vivisection experiments were both extensive and sophisticated and cannot be ignored in the literature of early modern experimentation or of experimentation on living organisms across time.

  8. Nitric oxide and Brazilian propolis combined accelerates tissue repair by modulating cell migration, cytokine production and collagen deposition in experimental leishmaniasis.

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    Milena Menegazzo Miranda

    Full Text Available The fact that drugs currently used in the treatment of Leishmania are highly toxic and associated with acquired resistance has promoted the search for new therapies for treating American tegumentary leishmaniasis (ATL. In this study, BALB/c mice were injected in the hind paw with Leishmania (Leishmania amazonensis and subsequently treated with a combination of nitric oxide (NO donor (cis-[Ru(bpy 2imN(NO](PF63 (Ru-NO, given by intraperitoneal injection, and oral Brazilian propolis for 30 days. Ru-NO reached the center of the lesion and increased the NO level in the injured hind paw without lesion exacerbation. Histological and immunological parameters of chronic inflammation showed that this combined treatment increased the efficacy of macrophages, determined by the decrease in the number of parasitized cells, leading to reduced expression of proinflammatory and tissue damage markers. In addition, these drugs in combination fostered wound healing, enhanced the number of fibroblasts, pro-healing cytokines and induced collagen synthesis at the lesion site. Overall, our findings suggest that the combination of the NO donor Ru-NO and Brazilian propolis alleviates experimental ATL lesions, highlighting a new therapeutic option that can be considered for further in vivo investigations as a candidate for the treatment of cutaneous leishmaniasis.

  9. Nitric Oxide and Brazilian Propolis Combined Accelerates Tissue Repair by Modulating Cell Migration, Cytokine Production and Collagen Deposition in Experimental Leishmaniasis

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    Miranda, Milena Menegazzo; Panis, Carolina; Cataneo, Allan Henrique Depieri; da Silva, Suelen Santos; Kawakami, Natalia Yoshie; Lopes, Luiz Gonzaga de França; Morey, Alexandre Tadachi; Yamauchi, Lucy Megumi; Andrade, Célia Guadalupe Tardelli de Jesus; Cecchini, Rubens; da Silva, Jean Jerley Nogueira; Sforcin, José Maurício; Conchon-Costa, Ivete; Pavanelli, Wander Rogério

    2015-01-01

    The fact that drugs currently used in the treatment of Leishmania are highly toxic and associated with acquired resistance has promoted the search for new therapies for treating American tegumentary leishmaniasis (ATL). In this study, BALB/c mice were injected in the hind paw with Leishmania (Leishmania) amazonensis and subsequently treated with a combination of nitric oxide (NO) donor (cis-[Ru(bpy) 2imN(NO)](PF6)3) (Ru-NO), given by intraperitoneal injection, and oral Brazilian propolis for 30 days. Ru-NO reached the center of the lesion and increased the NO level in the injured hind paw without lesion exacerbation. Histological and immunological parameters of chronic inflammation showed that this combined treatment increased the efficacy of macrophages, determined by the decrease in the number of parasitized cells, leading to reduced expression of proinflammatory and tissue damage markers. In addition, these drugs in combination fostered wound healing, enhanced the number of fibroblasts, pro-healing cytokines and induced collagen synthesis at the lesion site. Overall, our findings suggest that the combination of the NO donor Ru-NO and Brazilian propolis alleviates experimental ATL lesions, highlighting a new therapeutic option that can be considered for further in vivo investigations as a candidate for the treatment of cutaneous leishmaniasis. PMID:25973801

  10. Vaccines for canine leishmaniasis

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    Clarisa B. Palatnik-De-Sousa

    2012-04-01

    Full Text Available Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global-warming, co-infection with immunosuppressive diseases and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL in the Americas, the Middle East, Central Asia, China and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost-effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine visceral leishmaniasis. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans

  11. Protection against experimental visceral leishmaniasis by immunostimulation with herbal drugs derived from Withania somnifera and Asparagus racemosus.

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    Kaur, Sukhbir; Chauhan, Kalpana; Sachdeva, Heena

    2014-10-01

    Visceral leishmaniasis (VL) is a vector-borne parasitic disease targeting tissue macrophages. It is among the most neglected infectious diseases. As available therapeutics for treatment of this disease have many side effects, there is a need for safer alternatives. One of the immunopathological consequences of active visceral leishmaniasis is suppression of protective T-helper (Th)-1 cells and induction of disease-promoting Th-2 cells, and thus the treatment of VL relies on immunomodulation. In the current study, herbal drugs derived as whole-plant extracts of Asparagus racemosus and Withania somnifera were used to treat Leishmania donovani-infected BALB/c mice. Keeping the scenario of immunosuppression during VL in mind, the potential of these drugs in the restoration of murine Th-1-type protective immune responses was evaluated. To investigate the propensity of these drugs to treat VL, liver parasite load, delayed-type hypersensitivity responses and parasite-specific immunoglobulin levels were studied. Various biochemical and haematological tests were also carried out. A positive-control group used the standard drug treatment of sodium stibogluconate. Treatment of infected mice with A. racemosus and W. somnifera in combination at the higher dose of 200 mg (kg body weight)(-1) not only resulted in a successful reduction in parasite load but also generated protective Th1-type immune responses with normalization of biochemical and haematological parameters, suggesting their potential as potent anti-leishmanial agents.

  12. The experimental chemotherapy of leishmaniasis. II. The activity in tissue culture of some antiparasitic and antimicrobial compounds in clinical use.

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    Mattock, N M; Peters, W

    1975-09-01

    A variety of compounds used in the treatment of parasitic or bacterial infections in man, including leishmaniasis itself, were examined for their activity against three lines of Leishmania in tissue culture. The organisms used were L. mexicana mexicana, L. tropical major and L. donovani; they were grown in dog sarcoma and hamster peritoneal exudate cell lines. Leishmanicidal activity was observed in a number of compounds currently in clinical use for the treatment of one or other form of leishmaniasis. Cycloguanil, nifurtimox, amphotericin B and monomycin were effective but pentamidine showed poor activity. In each case marked differences were observed in the level of response in the different parasite lines. Organic antimonials were most active when anmastigotes were exposed to them prior to entry of the parasites into host cells. This suggests that such compounds may exert an effect on amastigotes during their brief extracellular transit from one host cell to another in vivo. A number of antimalarials showed good to moderate leishmanicidal action, particularly against L. mexicana and L.t. major. Several schistosomicidal agents also possessed leishmanicidal properties. The commonly used broad spectrum antibiotics showed little if any activity. In discusssion a comparison is drawn between data published on the action of some of these drugs against L.t. major in mice and our observations with the same strain and L. mexicana in tissue culture. A remarkably good agreement is found for most of the compounds examined. General agreement is also noted between these data and reports of clinical trials although it is not possible to draw too many conclusions because of the failure in most clinical studies to make an accurate identification of the causative Leishmania. It is concluded that, although the tissue culture model is not to be considered as ideal and can probably be improved, data obtained by its use do bear relevance to the action compounds in vivo, and the model

  13. Isolated lingual leishmaniasis

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    Habibzadeh F

    2005-01-01

    Full Text Available Cutaneous leishmaniasis is endemic in Fars Province, southern Iran. However, mucosal leishmaniasis is extremely uncommon. Herein, we report a patient with isolated lingual leishmaniasis in an immunocompetent 40-year-old man. The lesion was totally excised. The patient was cured completely and is doing well after four years of follow-up, with no medical treatment

  14. A comparative evaluation of efficacy of chemotherapy, immunotherapy and immunochemotherapy in visceral leishmaniasis-an experimental study.

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    Joshi, Jyoti; Malla, Nancy; Kaur, Sukhbir

    2014-08-01

    Visceral leishmaniasis (VL) represents the second most challenging infectious disease worldwide, leading to nearly 500,000 new cases and 60,000 deaths annually. Ninety per cent of VL cases occur in five countries namely Bangladesh, India, Nepal, Sudan and Brazil. No licensed vaccine is available till date against any form of leishmaniasis. High toxicity and increasing resistance to the current chemotherapeutic regimens have further complicated the situation in VL endemic regions of the world. To combat this situation, immunochemotherapy can provide a solution. In the present study, an attempt has been made to assess the in vivo antileishmanial efficacy of chemotherapy, immunotherapy and immunochemotherapy with the use of a first generation antigen Killed Leishmania donovani (KLD) along with a standard drug sodium stibogluconate (SSG) and a newly tested antileishmanial cisplatin. Inbred BALB/c mice were infected with 10(7) promastigotes/0.1 ml of Leishmania donovani. A month after infection, these animals were given specific immunotherapy (KLD/KLD+MPL-A) or chemotherapy (SSG/cisplatin) or immunochemotherapy (SSG+KLD/SSG+KLD+MPL-A/cisplatin+KLD/cisplatin+KLD+MPL-A). Animals were sacrificed on 1, 15 and 30(th) day post treatment. The efficacy of these combinations was assessed in terms of parasite load and by immunological investigations. Infected mice and normal mice served as controls. Results showed that combination of drug and KLD significantly reduced the parasite burden, enhanced the DTH (Delayed Type Hypersensitivity) responses, showed increased levels of IgG2a and decreased levels of IgG1 as compared to mice given chemotherapy or immunotherapy alone. Further maximum protection was provided by SSG+KLD+MPL-A and it was most effective as depicted by 98.5% reduction in parasite load, a potent increase in IFN-γ levels and a significant decrease in IL-10 and IL-4 levels thus skewing the immune response towards Th1 type. Hence, immunochemotherapy is more effective

  15. Holochilus brasiliensis nanus Thomas, 1897: sugestão de modelo experimental para filariose, leishmaniose e esquistossomose Holochilus brasiliensis nanus Thomas, 1897: as an experimental model for filariasis, leishmaniasis and schistosomiasis

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    Othon de Carvalho Bastos

    1984-12-01

    Full Text Available Roedores silvestres, classificados como Holochilus brasiliensis nanus Thomas,1897, foram capturados na cidade de São Bento, pertencente à Região da Baixada, do Estado do Maranhão, Brasil, naturalmente infectados com formas adultas de filaria, na cavidade peritoneal, e microfilárias sangüíneas, assim como, com esquistossoma mansoni (vermes adultos e granulomas peri-ovulares hepáticos; intestinais; pulmonares; esplênicos e pancreáticos. Animais nascidos em Biotério, descendentes de Holochilus da Região da Baixada, foram infectados experimentalmente com Leishmania m. amazonensis e Schistosoma mansoni. Em observações semanais, foram encontradas lesões teciduais, semelhantes às que se desenvolvem em hamsters infectados com Leishmania, e hipergamaglobulinemia. Nos esquistossomóticos, foram constatadas hipergamaglobulinemia e reações granulomatosas similares às encontradas nos animais infectados naturalmente. Foram observadas, também, lesões hepática graves, semelhantes às encontradas na esquistossomose humana. Estes achados sugerem a utilização do Holochilus b. nanus como modelo experimental destas três doenças tropicais.Wild rodents classified as Holochilus brasiliensis nanus THOMAS, 1897, were captured in Lowland Region of State of Maranhão-Brazil. Natural infection by schistosome and filaria was detected in the most of these animals. Rodents born in the Animal House of the University of Maranhão were experimentally infected with Leishmania mexicana amazonensis or Schistosoma mansoni. Pathological aspects of leishmaniasis in these animals were found similar to that found in hamsters infected with Leishmania. Severe hepatic lesions were found in the animals infected with schistosome similar to that seen in human infection. These findings suggest the utilization of this animal as an experimental model of filariasis, leishmaniasis and schistosomiasis.

  16. Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis

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    Shahbazi, Mehdi; Zahedifard, Farnaz; Taheri, Tahereh; Taslimi, Yasaman; Jamshidi, Shahram; Shirian, Sadegh; Mahdavi, Niousha; Hassankhani, Mehdi; Daneshbod, Yahya; Zarkesh-Esfahani, Sayyed Hamid; Papadopoulou, Barbara; Rafati, Sima

    2015-01-01

    Canine Visceral Leishmaniasis (CVL) is a major veterinary and public health problem caused by Leishmania infantum (L. infantum) in many endemic countries. It is a severe chronic disease with generalized parasite spread to the reticuloendothelial system, such as spleen, liver and bone marrow and is often fatal when left untreated. Control of VL in dogs would dramatically decrease infection pressure of L. infantum for humans, since dogs are the main domestic reservoir. In the past decade, various subunits and DNA antigens have been identified as potential vaccine candidates in experimental animal models, but none has been approved for human use so far. In this study, we vaccinated outbreed dogs with a prime-boost regimen based on recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinase genes (CPA and CPB without its unusual C-terminal extension (CPB-CTE) and evaluated its immunogenicity and protective immunity against L. infantum infectious challenge. We showed that vaccinated animals produced significantly higher levels of IgG2, but not IgG1, and also IFN-γ and TNF-α, but low IL-10 levels, before and after challenge as compared to control animals. Protection in dogs was also correlated with a strong DTH response and low parasite burden in the vaccinated group. Altogether, immunization with recombinant L. tarentolae A2-CPA-CPB-CTE was proven to be immunogenic and induced partial protection in dogs, hence representing a promising live vaccine candidate against CVL. PMID:26197085

  17. Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis.

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    Mehdi Shahbazi

    Full Text Available Canine Visceral Leishmaniasis (CVL is a major veterinary and public health problem caused by Leishmania infantum (L. infantum in many endemic countries. It is a severe chronic disease with generalized parasite spread to the reticuloendothelial system, such as spleen, liver and bone marrow and is often fatal when left untreated. Control of VL in dogs would dramatically decrease infection pressure of L. infantum for humans, since dogs are the main domestic reservoir. In the past decade, various subunits and DNA antigens have been identified as potential vaccine candidates in experimental animal models, but none has been approved for human use so far. In this study, we vaccinated outbreed dogs with a prime-boost regimen based on recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinase genes (CPA and CPB without its unusual C-terminal extension (CPB-CTE and evaluated its immunogenicity and protective immunity against L. infantum infectious challenge. We showed that vaccinated animals produced significantly higher levels of IgG2, but not IgG1, and also IFN-γ and TNF-α, but low IL-10 levels, before and after challenge as compared to control animals. Protection in dogs was also correlated with a strong DTH response and low parasite burden in the vaccinated group. Altogether, immunization with recombinant L. tarentolae A2-CPA-CPB-CTE was proven to be immunogenic and induced partial protection in dogs, hence representing a promising live vaccine candidate against CVL.

  18. Antileishmanial activity of essential oil from Chenopodium ambrosioides and its main components against experimental cutaneous leishmaniasis in BALB/c mice.

    Science.gov (United States)

    Monzote, L; Pastor, J; Scull, R; Gille, L

    2014-01-01

    Chenopodium ambrosioides have been used during centuries by native people to treat parasitic diseases. To compare the in vivo anti-leishmanial activity of the essential oil (EO) from C. ambrosioides and its major components (ascaridole, carvacrol and caryophyllene oxide). Anti-leishmanial effect was evaluated in BALB/c mice infected with Leishmania amazonensis and treated with the EO, main compounds and artificial mix of pure components by intralesional route at 30 mg/kg every 4 days during 14 days. Diseases progression and parasite burden in infected tissues were determined. EO prevented lesion development compared (p<0.05) with untreated animals and treated with vehicle. In addition, the efficacy of EO was also statistically superior (p<0.05) compared with the glucantime-treated animals. No potential effects were observed with pure components treatment. Mix of pure compounds cause death of animals after 3 days of treatment. Our results demonstrate the superiority of EO against experimental cutaneous leishmaniasis caused by L. amazonensis. Copyright © 2014 Elsevier GmbH. All rights reserved.

  19. SLA-PGN-primed dendritic cell-based vaccination induces Th17-mediated protective immunity against experimental visceral leishmaniasis: a crucial role of PKCβ.

    Science.gov (United States)

    Jawed, Junaid Jibran; Majumder, Saikat; Bandyopadhyay, Syamdas; Biswas, Satabdi; Parveen, Shabina; Majumdar, Subrata

    2016-07-01

    Emergence of drug resistance during visceral leishmaniasis (VL) is a major obstacle imposed during successful therapy. An effective vaccine strategy against this disease is therefore necessary. Our present study exploited the SLA (soluble leishmanial antigen) and PGN (peptidoglycan) stimulated bone marrow-derived dendritic cells (DCs) as a suitable vaccine candidate during experimental VL. SLA-PGN-stimulated DCs showed a significant decrease in hepatic and splenic parasite burden, which were associated with increased production of nitric oxide and pro-inflammatory cytokines such as IL-12, IFN-γ and IL-17. Elevated level of IL-17 was accompanied with the generation of more Th17 cells. Further studies on DC provided the evidence that these SLA-PGN-stimulated DCs played an important role in providing necessary cytokines such as IL-6, IL-23 and TGF-β for the generation of Th17 cells. Interestingly, inhibition of protein kinase C-β (PKCβ) in DCs led to decreased production of Th17 polarizing cytokines, causing reduction of the Th17 population size. Altogether, our finding highlighted the important role of DC-based PKCβ in regulation of the function and generation of Th17 cells. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis.

    Science.gov (United States)

    Shahbazi, Mehdi; Zahedifard, Farnaz; Taheri, Tahereh; Taslimi, Yasaman; Jamshidi, Shahram; Shirian, Sadegh; Mahdavi, Niousha; Hassankhani, Mehdi; Daneshbod, Yahya; Zarkesh-Esfahani, Sayyed Hamid; Papadopoulou, Barbara; Rafati, Sima

    2015-01-01

    Canine Visceral Leishmaniasis (CVL) is a major veterinary and public health problem caused by Leishmania infantum (L. infantum) in many endemic countries. It is a severe chronic disease with generalized parasite spread to the reticuloendothelial system, such as spleen, liver and bone marrow and is often fatal when left untreated. Control of VL in dogs would dramatically decrease infection pressure of L. infantum for humans, since dogs are the main domestic reservoir. In the past decade, various subunits and DNA antigens have been identified as potential vaccine candidates in experimental animal models, but none has been approved for human use so far. In this study, we vaccinated outbreed dogs with a prime-boost regimen based on recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinase genes (CPA and CPB without its unusual C-terminal extension (CPB-CTE) and evaluated its immunogenicity and protective immunity against L. infantum infectious challenge. We showed that vaccinated animals produced significantly higher levels of IgG2, but not IgG1, and also IFN-γ and TNF-α, but low IL-10 levels, before and after challenge as compared to control animals. Protection in dogs was also correlated with a strong DTH response and low parasite burden in the vaccinated group. Altogether, immunization with recombinant L. tarentolae A2-CPA-CPB-CTE was proven to be immunogenic and induced partial protection in dogs, hence representing a promising live vaccine candidate against CVL.

  1. Vaccines for Canine Leishmaniasis

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    Faeze Foroughi-Parvar

    2014-01-01

    Full Text Available Leishmania infantum is the obligatory intracellular parasite of mammalian macrophages and causes zoonotic visceral leishmaniasis (ZVL. The presence of infected dogs as the main reservoir host of ZVL is regarded as the most important potential risk for human infection. Thus the prevention of canine visceral leishmaniasis (CVL is essential to stop the current increase of the Mediterranean visceral leishmaniasis. Recently considerable advances in achieving protective immunization of dogs and several important attempts for achieving an effective vaccine against CVL lead to attracting the scientists trust in its important role for eradication of ZVL. This paper highlights the recent advances in vaccination against canine visceral leishmaniasis from 2007 until now.

  2. Laryngeal leishmaniasis in Malta.

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    Fsadni, C; Fsadni, P; Piscopo, T; Mallia Azzopardi, C

    2007-02-01

    The localization of Leishmania spp. in the larynx is rare especially when not associated with immunosuppression or with visceral or cutaneous leishmaniasis. We present a case of isolated laryngeal leishmaniasis, the first of its kind documented in Malta and infrequently reported from the Mediterranean basin.

  3. A current perspective on leishmaniasis

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    Angela Clem

    2010-01-01

    Full Text Available There are many challenges facing the successful control and eradication of cutaneous and visceral leishmaniasis. Leishmaniasis is still endemic in many poverty stricken and war torn areas. Through the use of an extensive literature review, this article examined the global disease burden of cutaneous and visceral leishmaniasis. Surveillance and control measures for leishmaniasis being used by the World Health Organization were also discussed in this article. Finally, potential new treatments and possible vaccines for leishmaniasis were reviewed in this article.

  4. A Current Perspective on Leishmaniasis

    Science.gov (United States)

    Clem, Angela

    2010-01-01

    There are many challenges facing the successful control and eradication of cutaneous and visceral leishmaniasis. Leishmaniasis is still endemic in many poverty stricken and war torn areas. Through the use of an extensive literature review, this article examined the global disease burden of cutaneous and visceral leishmaniasis. Surveillance and control measures for leishmaniasis being used by the World Health Organization were also discussed in this article. Finally, potential new treatments and possible vaccines for leishmaniasis were reviewed in this article. PMID:20606967

  5. 2,3,7,8-tetrachlorodibenzo-p-dioxin slows the progression of experimental cutaneous Leishmaniasis in susceptible BALB/c and SCID mice.

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    Gregory K DeKrey

    Full Text Available In a model of experimental cutaneous leishmaniasis, pre-exposure of Leishmania major-resistant mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, an aryl hydrocarbon receptor agonist, causes suppression of the protective anti-parasite T helper 1 response while paradoxically also reducing parasite burdens in those animals. In this study, we examined if TCDD exposure could also reduce parasite burdens in L. major-susceptible BALB/c mice. In the highest dose group (160 µg/Kg, TCDD treatment caused a significant reduction of parasite burdens by 10-fold after three weeks while also causing a significant lymphoid atrophy indicating suppression of the non-protective T helper 2 response. A dose-dependent delay of foot lesion progression was also observed such that lesion size in the highest dose group was less than half that of controls after 35 days of infection. Importantly, although TCDD exposure initially reduced disease severity and prolonged the course of disease by as much as three fold in some animals, this effect was transitory and TCDD did not induce resistance to L. major infection. Because TCDD exposure reduced L. major burdens in both resistant and susceptible mice, we hypothesized that TCDD reduces L. major burdens in mice by a mechanism that does not involve adaptive immunity. To test this, severe combined immunodeficient (SCID mice were used. In mice infected with a moderate number of L. major (10,000, TCDD treatment caused a time- and dose-dependent decrease of parasite burdens by nearly 100-fold after six weeks in the highest dose group (200 µg/Kg. A significant and dose-dependent delay of foot lesion progression was also observed in these animals. These results indicate that TCDD exposure can reduce the severity of leishmanial disease in mice independent of adaptive immunity.

  6. Chromone linked nitrone derivative induces the expression of iNOS2 and Th1 cytokines but reduces the Th2 response in experimental visceral leishmaniasis.

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    Mallick, Suvadip; Halder, Subhadra; Dutta, Aritri; Dey, Somaditya; Paul, Kausik; Maiti, Sourav; Bandyopadhyay, Chandrakanta; Saha, Bhaskar; Pal, Chiranjib

    2013-04-01

    In our previous work we have shown that the novel synthetic chromone derivative could effectively inhibit the Leishmania donovani replication in vitro and in vivo with less cytotoxicity on murine splenocytes. The aim of the present study is to explore the possible mechanism of anti-leishmanial effect of C-(6-methyl-4-oxo-4H-1-benzopyran-3-yl)-N-(p-tolyl) nitrone (designated as NP1) in vitro and in vivo in experimental visceral leishmaniasis caused by L. donovani. The cytotoxic effect of this derivative was studied in murine peritoneal macrophages by MTT method. NP1 at a dose of 17.06 μM showed 50% inhibition on L. donovani promastigotes but found less cytotoxic to the RAW 264.7 cells. Even the higher concentration of IC50 (up to four fold) did not exert much cytotoxic effect on RAW 264.7. Interestingly, NP1 at lower concentration (8.53 μM) could inhibit 50% of intracellular amastigotes in murine peritoneal macrophages. L. donovani is known to exert its pathogenic effects mainly by the suppression of NO generation and subversion of the cellular inflammatory responses in the macrophages. NP1 was found to induce a potent host-protective immune response by enhancing NO generation and iNOS2 expression at mRNA level and by up-regulating proinflammatory cytokines such as IL-12 and IFN-γ and limiting the expression of IL-10 in vivo. The NO dependent killing was further confirmed in iNOS(-/-) mice compared to wild type. In agreement with the fact, induced synthesis of IL-12 and IFN-γ and associated down-regulation of IL-10 by the treatment of NP1 clearly indicated the possibility of novel strategy of drug development against Leishmania infection. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Therapeutic immunization with radio-attenuated Leishmania parasites through i.m. route revealed protection against the experimental murine visceral leishmaniasis.

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    Datta, Sanchita; Manna, Madhumita; Khanra, Supriya; Ghosh, Moumita; Bhar, Radhaballav; Chakraborty, Anindita; Roy, Syamal

    2012-07-01

    After our promising results from prophylactic and therapeutic study (i.p. route) with the radio-attenuated Leishmania donovani parasites against experimental murine visceral leishmaniasis, we prompted to check their therapeutic efficacy through i.m route. BALB/c mice were infected with highly virulent L. donovani parasites. After 75 days, mice were treated with gamma (γ)-irradiated parasites. A second therapeutic immunization was given after 15 days of first immunization. The protection against kala-azar was estimated with the reduction of Leishman-Donovan unit from spleen and liver that scored up to 80% and 93%, respectively, while a twofold increase in nitric oxide (NO) and reactive oxygen species (ROS) productions has been observed in the immunized groups of animals. These groups of mice also showed disease regression by skewing Th2 cytokines (IL-10) towards Th1 cytokine (IFN-γ) bias along with the increased generation of NO and ROS, while the infected control group of mice without such treatment surrendered to the disease. Establishment of Th1 ambience in the treated groups has also been supported from the measured antileishmanial antibody IgG subsets (IgG2a and IgG1) with higher anti-soluble Leishmania antigen-specific IgG2a titer. As seen in our previous studies, doses of attenuation by γ-radiation should be taken into serious consideration. Attenuation of parasites at 50 Gy of absorbed dose of gamma rays has not worked well. Thus, therapeutic use of L. donovani parasites radio-attenuated at particular doses can be exploited as a promising vaccine agent. Absence of any adjuvant may increase its acceptability as vaccine candidate further.

  8. Unusual Presentation of Cutaneous Leishmaniasis: Ocular Leishmaniasis

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    Masoud Doroodgar

    2017-01-01

    Full Text Available The leishmaniases are parasitic diseases that are transmitted to humans by infected female sandflies. Cutaneous leishmaniasis (CL is one of 3 main forms of the disease. CL is the most common form of the disease and is endemic in many urban and rural parts of Iran and usually caused by two species of Leishmania: L. major and L. tropica. We report a case of unusual leishmaniasis with 25 lesions on exposed parts of the body and right eyelid involvement (ocular leishmaniasis. The patient was a 75-year-old male farmer referred to health care center in Aran va Bidgol city. The disease was diagnosed by direct smear, culture, and PCR from the lesions. PCR was positive for Leishmania major.

  9. Unusual Presentation of Cutaneous Leishmaniasis: Ocular Leishmaniasis

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    Doroodgar, Masoud; Doroodgar, Moein

    2017-01-01

    The leishmaniases are parasitic diseases that are transmitted to humans by infected female sandflies. Cutaneous leishmaniasis (CL) is one of 3 main forms of the disease. CL is the most common form of the disease and is endemic in many urban and rural parts of Iran and usually caused by two species of Leishmania: L. major and L. tropica. We report a case of unusual leishmaniasis with 25 lesions on exposed parts of the body and right eyelid involvement (ocular leishmaniasis). The patient was a 75-year-old male farmer referred to health care center in Aran va Bidgol city. The disease was diagnosed by direct smear, culture, and PCR from the lesions. PCR was positive for Leishmania major. PMID:28210511

  10. Qualitative differences in the early immune response to live and killed Leishmania major: Implications for vaccination strategies against Leishmaniasis.

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    Okwor, Ifeoma; Liu, Dong; Uzonna, Jude

    2009-04-28

    Recovery from natural or deliberate infection with Leishmania major leads to the development of lifelong immunity against rechallenge infections. In contrast, vaccination with killed parasites or defined leishmanial antigens generally induces only short-term protection. The reasons for this difference are currently not known but may be related to differences in the quality of the early immune responses to live and killed parasites. Here, we report that live and killed L. major parasites elicit comparable early inflammatory response as evidenced by influx and/or proliferation of cells in the draining lymph nodes (dLNs). In contrast, the early cytokine responses were qualitatively different. Cells from mice inoculated with killed parasites produced significantly more antigen-specific IL-4 and less IFN-gamma than those from mice injected with live parasites. Inclusion of CpG ODN into killed parasite preparations changed the early response to killed parasites from IL-4 to a predominantly IFN-gamma response, resulting in better protection following secondary high dose virulent L. major challenge. Interestingly, CpG-mediated enhancement of killed parasites-induced protection was short-lived and waned after 12 weeks. Taken together, these results suggest that the nature of primary immunity induced by killed and live parasites are qualitatively different and that these differences may account for the differential protection seen in mice following vaccination with live and killed parasites. They further suggest that modulating the early response with an appropriate adjuvant could enhance efficacy of killed parasite vaccines.

  11. Dermatologic and otorhinolaryngologic manifestations in leishmaniasis

    Directory of Open Access Journals (Sweden)

    Mota, Luiz Alberto Alves

    2011-07-01

    Full Text Available Introduction: Leishmaniasis is an extremely important parasitic disease as regards epidemiology, and, in such a disease, man is an occasional host to the Leishmania protozoon. Some of the major clinical, visceral and integumentary features are the mucocutaneous ways that can harm face and upper airways and even cause deforming lesions, leading to a functional impairment. Objective: Review the main dermatologic and otorhinolaryngologic manifestations in leishmaniasis. Methods: It was based on the Virtual Health Library (BVS, by entering the following keywords: Leishmaniasis, mucocutaneous leishmaniasis, nasal mucosa, and nose. References dated from 1999 to 2008 have been regarded. Final Comments: It is about a zoonosis, in which the human being is an occasional host attacked by Lutzomya or Phlebotomus insects that are, in turn, infected by the Leishmania parasite, and the early diagnosis of a leishmania-related lesion is essential, especially when a nasopharyngeal impairment is evident, with a view to preventing deformities or functional harms. The evaluation of cutaneous and/or mucosa lesions and the accurate definition of leishmaniasis diagnosis given by either dermatologists or otorhinolaryngologists enables the proper treatment to be implemented and the subsequent reduction in the disease dissemination.

  12. Vaccines for visceral leishmaniasis: A review.

    Science.gov (United States)

    Jain, Keerti; Jain, N K

    2015-07-01

    Visceral leishmaniasis, which is also known as Kala-Azar, is one of the most severely neglected tropical diseases recognized by the World Health Organization (WHO). The threat of this debilitating disease continues due to unavailability of promising drug therapy or human vaccine. An extensive research is undergoing to develop a promising vaccine to prevent this devastating disease. In this review we compiled the findings of recent research with a view to facilitate knowledge on experimental vaccinology for visceral leishmaniasis. Various killed or attenuated parasite based first generation vaccines, second generation vaccines based on antigenic protein or recombinant protein, and third generation vaccines derived from antigen-encoding DNA plasmids including heterologous prime-boost Leishmania vaccine have been examined for control and prevention of visceral leishmaniasis. Vaccines based on recombinant protein and antigen-encoding DNA plasmids have given promising results and few vaccines including Leishmune®, Leishtec, and CaniLeish® have been licensed for canine visceral leishmaniasis. A systematic investigation of these vaccine candidates can lead to development of promising vaccine for human visceral leishmaniasis, most probably in the near future.

  13. Leishmaniasis vaccines: past, present and future.

    Science.gov (United States)

    Modabber, Farrokh

    2010-11-01

    No vaccine exists against any form of leishmaniasis. Because recovery from infection is usually accompanied by a strong immunity and because it is possible to protect experimental animals against live challenge, hope for the development of a vaccine for humans has been high. However, leishmaniasis is a disease of the poor and the market for a vaccine is very limited. Until a few years ago, with minimal resources, only a pragmatic approach was possible for testing the first-generation vaccines (i.e. killed whole parasites). Recently, funding has become available for developing defined second-generation vaccines, including recombinant proteins and DNA constructs. With new adjuvants also being developed there is new hope, and several new vaccines are in development against leishmaniasis.

  14. Chemotherapy of Leishmaniasis.

    Science.gov (United States)

    1978-12-01

    NOTES 1S. KEY WORDS (Continue on reverse side linscoeawy and identiIIy by block number) LEISHMANIA LEISHMANIASIS CHEMOTHERAPY ANTILEISHMANIAL PENTOSTAM...number of compounds was supplied by WRAIR for testing on four strains of Leishmania in December 1977. Preliminary data were supplied to WRAIR by the...j_ = L. tropica major (Strain LV39 from USSR) and the New World cutaneous leishmaniasis by L. mexicana amazonensis (Strain LV78 from Brazil). The test

  15. Immunogenicity and Efficacy of Live L. tarentolae Expressing KMP11-NTGP96-GFP Fusion as a Vaccine Candidate against Experimental Visceral Leishmaniasis Caused by L. infantum

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    Vahid NASIRI

    2016-10-01

    Full Text Available Background: The aim of present study was to evaluate the protective efficacy of live recombinant L. tarentolae expressing KMP11-NTGP96-GFP fusion as candidates for live engineered recombinant vaccine against visceral leishmaniasis in BALB/c mice.Methods: KMP-11 and NT-GP96 genes cloned into the pJET1.2/blunt cloning vector and then into pEGFP-N1 expression vector. The KMP-11, NT-GP96 and GFP fused in pEGFP-N1 and subcloned into Leishmanian pLEXSY-neo vector. Finally this construct was transferred to L. tarentolae by electroporation. Tranfection was confirmed by SDS-PAGE, WESTERN blot, flowcytometry and RT-PCR. Protective efficacy of this construct was evaluated as a vaccine candidate against visceral leishmaniasis. Parasite burden, humoral and cellular immune responses were assessed before and at 4 weeks after challenge.Results: KMP- NT-Gp96-GFP Fusion was cloned successfully into pLEXSY -neo vector and this construct successfully transferred to L. tarentolae. Finding indicated that immunization with L. tarentolae tarentolae-KMP11-NTGP96-GFP provides significant protection against visceral leishmaniasis and was able to induce an increased expression of IFN-γ and IgG2a. Following challenge, a reduced parasite load in the spleen of the KMP11-NTGP96-GFP immunized group was detected.Conclusion: The present study is the first to use a combination of a Leishmania antigen with an immunologic antigen in live recombinant L. tarentolae and results suggest that L. tarentolae-KMP11-NTGP96-GFP could be considered as a potential tool in vaccination against visceral leishmaniasis and this vaccination strategy could provide a potent rout for future vaccine development. 

  16. The history of leishmaniasis.

    Science.gov (United States)

    Steverding, Dietmar

    2017-02-15

    In this review article the history of leishmaniasis is discussed regarding the origin of the genus Leishmania in the Mesozoic era and its subsequent geographical distribution, initial evidence of the disease in ancient times, first accounts of the infection in the Middle Ages, and the discovery of Leishmania parasites as causative agents of leishmaniasis in modern times. With respect to the origin and dispersal of Leishmania parasites, the three currently debated hypotheses (Palaearctic, Neotropical and supercontinental origin, respectively) are presented. Ancient documents and paleoparasitological data indicate that leishmaniasis was already widespread in antiquity. Identification of Leishmania parasites as etiological agents and sand flies as the transmission vectors of leishmaniasis started at the beginning of the 20(th) century and the discovery of new Leishmania and sand fly species continued well into the 21(st) century. Lately, the Syrian civil war and refugee crises have shown that leishmaniasis epidemics can happen any time in conflict areas and neighbouring regions where the disease was previously endemic.

  17. Leishmaniasis in the knee area

    Institute of Scientific and Technical Information of China (English)

    Bava Amadeo Javier; Rossi Maria Laura; Seley Celeste; Troncoso Alcides

    2010-01-01

    Leishmaniasis is a parasitic infection caused by species leishmaniae, which can produce two types of manifestations: visceral and cutaneous. In south America cutaneous leishmaniasis is more common than visceral leishmaniasis. A case of primary cutaneous leishmaniasis from Bolivia is presented for its rarity. The patient of our case showed an ulcerated lesion of the knee. Montenegro's intradermal test was positive. Giemsa-stained touch preparation of the skin biopsy revealed amastigotes inside macrophages, consistent with leishmaniasis. The patient was treated with meglumine antimoniate intramuscular (20 mg of Sb+/kg/day) three weeks, with complete cicatrization of the lesion.

  18. Cutaneous leishmaniasis: immune responses in protection and pathogenesis.

    Science.gov (United States)

    Scott, Phillip; Novais, Fernanda O

    2016-09-01

    Cutaneous leishmaniasis is a major public health problem and causes a range of diseases from self-healing infections to chronic disfiguring disease. Currently, there is no vaccine for leishmaniasis, and drug therapy is often ineffective. Since the discovery of CD4(+) T helper 1 (TH1) cells and TH2 cells 30 years ago, studies of cutaneous leishmaniasis in mice have answered basic immunological questions concerning the development and maintenance of CD4(+) T cell subsets. However, new strategies for controlling the human disease have not been forthcoming. Nevertheless, advances in our knowledge of the cells that participate in protection against Leishmania infection and the cells that mediate increased pathology have highlighted new approaches for vaccine development and immunotherapy. In this Review, we discuss the early events associated with infection, the CD4(+) T cells that mediate protective immunity and the pathological role that CD8(+) T cells can have in cutaneous leishmaniasis.

  19. Diagnosis of Cutaneous Leishmaniasis by Multiplex PCR

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    M Heiat

    2010-07-01

    Full Text Available Introduction: Annually, more than 14 million people are reported to be infected with Leishmaniasis all over the world. In Iran, this disease is seen in the form of cutaneous and visceral leishmaniasis, of which the cutaneous form is more wide spread. In recent years, cutaneous leishmaniaisis is diagnosed by PCR utilizing specific primers in order to amplify different parasite genes including ribosomal RNA genes, kinetoplast DNA or tandem repeating sequences. The aim of this research was to detect early stage cutaneous leishmaniasis using Multiplex-PCR technique. Methods: In this study, 67 samples were prepared from patients with cutaneous leishmaniasis. DNA was extracted with phenolchloroform. Each specimen was analyzed using two different pairs of PCR primers. The sensitivity of each PCR was optimized on pure Leishmania DNA prior to use for diagnosis. Two standard parasites L. major and L. tropica were used as positive control. Results: DNA amplification fragments were two 115 bp and 683 bp for AB and UL primers, respectively. The sensitivity of two primers was not equal for detection of L. major and L. tropica. The sensivity of PCR with AB primer was 35 cells, while that for UL primer was 40 cells. Conclusion: The results of this study indicate that PCR is a sensitive diagnostic assay for cutaneous leishmaniasis and could be employed as the new standard for routine diagnosis when species identification is not required. However, the ability to identify species is especially important in prognosis of the disease and in deciding appropriate therapy, especially in regions where more than one type of species and disease are seen by clinicians.

  20. A novel recombinant Leishmania donovani p45, a partial coding region of methionine aminopeptidase, generates protective immunity by inducing a Th1 stimulatory response against experimental visceral leishmaniasis.

    Science.gov (United States)

    Gupta, Reema; Kushawaha, Pramod K; Tripathi, Chandra Dev Pati; Sundar, Shyam; Dube, Anuradha

    2012-05-01

    The development of a vaccine against visceral leishmaniasis (VL) conferring long-lasting immunity remains a challenge. Identification and proteomic characterization of parasite proteins led to the detection of p45, a member of the methionine aminopeptidase family. To our knowledge the present study is the first known report that describes the molecular and immunological characterization of p45. Recombinant Leishmania donovani p45 (rLdp45) induced cellular responses in cured hamsters and generated Th1-type cytokines from peripheral blood mononuclear cells of cured/endemic VL patients. Immunization with rLdp45 exerted considerable prophylactic efficacy (∼85%) supported by an increase in mRNA expression of iNOS, IFN-γ, TNF-α and IL-12 and decrease in TGF-β and IL-4, indicating its potential as a vaccine candidate against VL.

  1. Immucillins ImmA and ImmH Are Effective and Non-toxic in the Treatment of Experimental Visceral Leishmaniasis.

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    Elisangela Oliveira Freitas

    2015-12-01

    Full Text Available Immucillins ImmA (IA, ImmH (IH and SerMe-ImmH (SMIH are synthetic deazapurine nucleoside analogues that inhibit Leishmania (L. infantum chagasi and Leishmania (L. amazonensis multiplication in vitro without macrophage toxicity. Immucillins are compared to the Glucantime standard drug in the chemotherapy of Leishmania (L. infantum chagasi infection in mice and hamsters. These agents are tested for toxicity and immune system response.BALB/c mice were infected with 107 amastigotes, treated with IA, IH, SMIH or Glucantime (2.5mg/kg/day and monitored for clinical variables, parasite load, antibody levels and splenocyte IFN-γ, TNF-α, and IL-10 expression. Cytokines and CD4+, CD8+ and CD19+ lymphocyte frequencies were assessed in uninfected controls and in response to immucillins. Urea, creatinine, GOT and GPT levels were monitored in sera. Anti-Leishmania-specific IgG1 antibodies (anti-NH36 increased in untreated animals. IgG2a response, high levels of IFN-γ, TNF-α and lower levels of IL-10 were detected in mice treated with the immucillins and Glucantime. Immucillins permitted normal weight gain, prevented hepato-splenomegaly and cleared the parasite infection (85-89% without renal and hepatic toxicity. Immucillins promoted 35% lower secretion of IFN-γ in uninfected controls than in infected mice. IA and IH increased the CD4+ T and CD19+ B cell frequencies. SMIH increased only the proportion of CD-19 B cells. IA and IH also cured infected hamsters with lower toxicity than Glucantime.Immucillins IA, IH and SMIH were effective in treating leishmaniasis in mice. In hamsters, IA and IH were also effective. The highest therapeutic efficacy was obtained with IA, possibly due to its induction of a TH1 immune response. Low immucillin doses were required and showed no toxicity. Our results disclose the potential use of IA and IH in the therapy of visceral leishmaniasis.

  2. A new experimental hybrid of cabbage suitable for early production

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    Červenski Janko

    2012-01-01

    Full Text Available The paper analyzes experimental hybrids of early cabbage developed at the Institute of Field and Vegetable Crops in the previous period. The hybrids were tested together for two years and then one (H17 was chosen and submitted to the Variety Commission of the Republic of Serbia. In 2011, the experimental hybrid H17 was officially released as an early cabbage hybrid and registered under the name of NS Mendo F1. The hybrid had been developed by crossing two early lines, one of which was sterile. It is characterized by a short growing season - 65 days from transplanting to harvest. The head weight ranges from 2.5 to 3.5 kg depending on the cultural practice applied. The head is light green in color, sweet-tasting, and suitable for fresh consumption. The hybrid’s traits that contributed significantly to the formation of the first principal component were in fact those that the breeders attach most importance to in their breeding programs. These are the traits that directly influence the market value of a new hybrid and make a given hybrid recognizable on the market. Most notable among such traits are head weight and the weight of the useful part of the head.[Projekat Ministarstva nauke Republike Srbije, br. TR 31030

  3. Interferon Gamma in Leishmaniasis

    OpenAIRE

    2013-01-01

    Leishmaniasis is a complex disease that is caused by parasites of the Leishmania genus. Leishmania are further classified into several complexes, each of which can engage in distinct interactions with mammalian hosts resulting in differing disease presentations. It is therefore not unexpected that host immune responses to Leishmania are variable. The induction of interferon gamma (IFN-γ) and response to it in these infections has received considerable attention. In this review, we summarize o...

  4. Chemotherapy of Cutaneous Leishmaniasis

    Science.gov (United States)

    2012-10-01

    Leishmaniasis It has been around for centuries and remains a serious problem in areas such as Iraq, Afghanistan, Iran, Saudi Arabia, Yemen , Peru and Brazil...Vibro cholerae 01 in San Pedro Sula, Honduras. Lancet. 349: 924, 1997. Torok, D.S., Ziffer, H., Meshnick, S.R., Pan, X.Q., Ager, A. Synthesis and...Dubon, M. Makler, V. Vorndam, W. Klaskala, M. Baum and A. Ager. Simultaneous outbreak of malaria and dengue in Honduras. International Conference on

  5. Feline leishmaniasis: a review

    OpenAIRE

    Soares, Carla Sofia Alves

    2014-01-01

    Abstract According to the World Health Organization (WHO), Leishmaniasis’ endemic areas have spread and the prevalence of the disease has increased, as well as the number of reported cases. Europe is one of the most affected continents concerning the risk of re-emergency of this zoonosis. Feline Leishmaniasis (FeL) was for the first time described in Algeria, 1912. The significance of the cat as a reservoir of Leishmania and not simply an alternative host seems to be gaining...

  6. Current scenario of drug development for leishmaniasis.

    Science.gov (United States)

    Croft, Simon L; Seifert, Karin; Yardley, Vanessa

    2006-03-01

    Although three new drugs or drug formulations, liposomal amphotericin B (AmBisome), miltefosine and paromomycin should be available for the treatment of visceral leishmaniasis (VL) within the next year, they all suffer from limitations of either cost, specific toxicities or parenteral administration. As part of research to identify better treatments for VL and cutaneous leishmaniasis (CL), alternative and potentially cheaper formulations of amphotericin B, alklyphosphocholines other than miltefosine and improved formulations of paromomycin for CL have been identified. Other drugs or compounds that have demonstrated activity in experimental rodent models of infection include licochalcone derivatives, quinoline derivatives, bisphosphonates and a maesabalide; further chemistry based upon these leads is warranted. The process for discovery and development of new antileishmanials would also benefit from improved models, for example, transfected parasites, and non invasive methods of measuring parasite load in rodent models of infection.

  7. Estudios sobre leishmaniasis tegumentaria en el Perú. I. Infección experimental de perros con cepas de leishmanias procedentes de casos de Uta

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    Arístides Herrer

    1951-01-01

    Full Text Available Se han inoculado varias series de perros con cepas de leishmanias procedentes de la forma clínica de la leishmaniasis tegumentaria conocida en el Perú con el nombre de uta, usando con tal objeto material tomado directamente de las lesiones utosas así como también cultivos del parásito. Los principales resultados obtenidos en tales inoculaciones son los siguientes: 1. Ha sido imposible infectar al perro con cultivos mantenidos solamente in vitro por espacio de cinco a ocho años, no obstante de haberse ensayado en tres series distintas de inoculaciones. 2. Se ha conseguido infecciones experimentales en el 87 por ciento de los perros que fueron inoculados con cultivos de reciente aislamiento. Aunque las inoculaciones fueran hechas bajo las mismas circunstancias en el dorso del hocico y la cara interna de una de las orejas, la infección se ha obtenido principalmente en el hocico. 3. También se ha logrado infectar perros inoculándoles material tomado directamente de las lesiones leishmaniásicas, ya sea de casos de uta o de lesiones producidas experimentalmente en otros perros.

  8. Immunization with the DNA-encoding N-terminal domain of proteophosphoglycan of Leishmania donovani generates Th1-type immunoprotective response against experimental visceral leishmaniasis.

    Science.gov (United States)

    Samant, Mukesh; Gupta, Reema; Kumari, Shraddha; Misra, Pragya; Khare, Prashant; Kushawaha, Pramod Kumar; Sahasrabuddhe, Amogh Anant; Dube, Anuradha

    2009-07-01

    Leishmania produce several types of mucin-like glycoproteins called proteophosphoglycans (PPGs) which exist as secretory as well as surface-bound forms in both promastigotes and amastigotes. The structure and function of PPGs have been reported to be species and stage specific as in the case of Leishmania major and Leishmania mexicana; there has been no such information available for Leishmania donovani. We have recently demonstrated that PPG is differentially expressed in sodium stibogluconate-sensitive and -resistant clinical isolates of L. donovani. To further elucidate the structure and function of the ppg gene of L. donovani, a partial sequence of its N-terminal domain of 1.6 kb containing the majority of antigenic determinants, was successfully cloned and expressed in prokaryotic as well as mammalian cells. We further evaluated the DNA-encoding N-terminal domain of the ppg gene as a vaccine in golden hamsters (Mesocricetus auratus) against the L. donovani challenge. The prophylactic efficacy to the tune of approximately 80% was observed in vaccinated hamsters and all of them could survive beyond 6 mo after challenge. The efficacy was supported by a surge in inducible NO synthase, IFN-gamma, TNF-alpha, and IL-12 mRNA levels along with extreme down-regulation of TGF-beta, IL-4, and IL-10. A rise in the level of Leishmania-specific IgG2 was also observed which was indicative of enhanced cellular immune response. The results suggest the N-terminal domain of L. donovani ppg as a potential DNA vaccine against visceral leishmaniasis.

  9. Association of liposome-encapsulated trivalent antimonial with ascorbic acid: an effective and safe strategy in the treatment of experimental visceral leishmaniasis.

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    Renata A O Castro

    Full Text Available BACKGROUND: Visceral leishmaniasis (VL is a chronic debilitating disease endemic in tropical and subtropical areas, caused by protozoan parasites of the genus Leishmania. Annually, it is estimated the occurrence of 0.2 to 0.4 million new cases of the disease worldwide. Considering the lack of an effective vaccine the afflicted population must rely on both, an accurate diagnosis and successful treatment to combat the disease. Here we propose to evaluate the efficacy of trivalent antimonial encapsulated in conventional liposomes, in association with ascorbic acid, by monitoring its toxicity and efficacy in BALB/c mice infected with Leishmania infantum. METHODOLOGY/PRINCIPAL FINDINGS: Infected mice were subjected to single-dose treatments consisting in the administration of either free or liposome-encapsulated trivalent antimony (SbIII, in association or not with ascorbic acid. Parasite burden was assessed in the liver, spleen and bone marrow using the serial limiting dilution technique. After treatment, tissue alterations were examined by histopathology of liver, heart and kidney and confirmed by serum levels of classic biomarkers. The phenotypic profile of splenocytes was also investigated by flow cytometry. Treatment with liposome-encapsulated SbIII significantly reduced the parasite burden in the liver, spleen and bone marrow. Co-administration of ascorbic acid, with either free SbIII or its liposomal form, did not interfere with its leishmanicidal activity and promoted reduced toxicity particularly to the kidney and liver tissues. CONCLUSIONS/SIGNIFICANCE: Among the evaluated posological regimens treatment of L. infantum-infected mice with liposomal SbIII, in association with ascorbic acid, represented the best alternative as judged by its high leishmanicidal activity and absence of detectable toxic effects. Of particular importance, reduction of parasite burden in the bone marrow attested to the ability of SbIII-carrying liposomes to

  10. Fostering Early Math Comprehension: Experimental Evidence from Paraguay

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    Emma Naslund-Hadley

    2014-11-01

    Full Text Available Research indicates that preschool children need to learn pre-math skills to build a foundation for primary- and secondary-level mathematics. This paper presents the results from the early stages of a pilot mathematics program implemented in Cordillera, Paraguay. In a context of significant gaps in teacher preparation and pedagogy, the program uses interactive audio segments that cover the entire preschool math curriculum. Since Paraguayan classrooms tend to be bilingual, the audio and written materials use a combination of Spanish and Guaraní. Based on an experimental evaluation since the program’s implementation, we document positive and significant improvements of 0.16 standard deviations in standardized test scores. The program helped narrow learning gaps between low- and high-performing students, and between students with trained teachers and those whose teachers lack formal training in early childhood education. Moreover, the program improved learning equally among both Guaraní- and Spanish-speaking students. But not all learning gaps narrowed as a result of the program. Although girls improved significantly, boys improved much more, ultimately increasing the gender gap. To close this gender gap, the program has been modified to encourage girls’ increased participation in the classroom and general interest in math

  11. A review of Leishmaniasis in Eastern Africa

    Institute of Scientific and Technical Information of China (English)

    Peter K. Ngure; Albert Kimutai; Zipporah W. Ng'ang'a; Geoffrey Rukunga; Willy K. Tonui

    2009-01-01

    The review presents the epidemiology of leishmaniasis in the Eastern Africa region. We searched PUB MED and MEDLINE with several key words-namely,"leishmaniasis";"cutaneous"," diffuse cutaneous"," mucosal", and "visceral leishmaniasis";"kala azar" and "post kala azar dermal leishmaniasis"-for recont clinical and basic science articles related to leishmaniasis in countries in the Eastern Africa region. Poverty, wars, conflicts and migration have significantly aggravated leishmaniases in Eastern Africa. Of particular concern is the increasing incidence of Leishmania-HIV co-infection in Ethiopia where 20--40% of the persons affected by visceral leishmaniasis are HIV-co-infected. Sudan has the highest prevalence rate of post kala-azar dermal leishmaniasis(PKDL) in the world, a skin complication of visceral leishmaniasis(VL) that mainly afflicts children below age ten. In view of its spread to previously non-endemic areas and an increase in imported cases, leishmaniasis in Eastern Africa should be considered a health emergency.

  12. Development of novel prime-boost strategies based on a tri-gene fusion recombinant L. tarentolae vaccine against experimental murine visceral leishmaniasis.

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    Noushin Saljoughian

    Full Text Available Visceral leishmaniasis (VL is a vector-borne disease affecting humans and domestic animals that constitutes a serious public health problem in many countries. Although many antigens have been examined so far as protein- or DNA-based vaccines, none of them conferred complete long-term protection. The use of the lizard non-pathogenic to humans Leishmania (L. tarentolae species as a live vaccine vector to deliver specific Leishmania antigens is a recent approach that needs to be explored further. In this study, we evaluated the effectiveness of live vaccination in protecting BALB/c mice against L. infantum infection using prime-boost regimens, namely Live/Live and DNA/Live. As a live vaccine, we used recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinases (CPA and CPB without its unusual C-terminal extension (CPB(-CTE as a tri-fusion gene. For DNA priming, the tri-fusion gene was encoded in pcDNA formulated with cationic solid lipid nanoparticles (cSLN acting as an adjuvant. At different time points post-challenge, parasite burden and histopathological changes as well as humoral and cellular immune responses were assessed. Our results showed that immunization with both prime-boost A2-CPA-CPB(-CTE-recombinant L. tarentolae protects BALB/c mice against L. infantum challenge. This protective immunity is associated with a Th1-type immune response due to high levels of IFN-γ production prior and after challenge and with lower levels of IL-10 production after challenge, leading to a significantly higher IFN-γ/IL-10 ratio compared to the control groups. Moreover, this immunization elicited high IgG1 and IgG2a humoral immune responses. Protection in mice was also correlated with a high nitric oxide production and low parasite burden. Altogether, these results indicate the promise of the A2-CPA-CPB(-CTE-recombinant L. tarentolae as a safe live vaccine candidate against VL.

  13. Transcriptional Profiling in Experimental Visceral Leishmaniasis Reveals a Broad Splenic Inflammatory Environment that Conditions Macrophages toward a Disease-Promoting Phenotype

    Science.gov (United States)

    Spratt, Heidi; Travi, Bruno L.; Luxon, Bruce A.

    2017-01-01

    Visceral Leishmaniasis (VL), caused by the intracellular protozoan Leishmania donovani, is characterized by relentlessly increasing visceral parasite replication, cachexia, massive splenomegaly, pancytopenia and ultimately death. Progressive disease is considered to be due to impaired effector T cell function and/or failure of macrophages to be activated to kill the intracellular parasite. In previous studies, we used the Syrian hamster (Mesocricetus auratus) as a model because it mimics the progressive nature of active human VL. We demonstrated previously that mixed expression of macrophage-activating (IFN-γ) and regulatory (IL-4, IL-10, IL-21) cytokines, parasite-induced expression of macrophage arginase 1 (Arg1), and decreased production of nitric oxide are key immunopathologic factors. Here we examined global changes in gene expression to define the splenic environment and phenotype of splenic macrophages during progressive VL. We used RNA sequencing coupled with de novo transcriptome assembly, because the Syrian hamster does not have a fully sequenced and annotated reference genome. Differentially expressed transcripts identified a highly inflammatory spleen environment with abundant expression of type I and type II interferon response genes. However, high IFN-γ expression was ineffective in directing exclusive M1 macrophage polarization, suppressing M2-associated gene expression, and restraining parasite replication and disease. While many IFN-inducible transcripts were upregulated in the infected spleen, fewer were induced in splenic macrophages in VL. Paradoxically, IFN-γ enhanced parasite growth and induced the counter-regulatory molecules Arg1, Ido1 and Irg1 in splenic macrophages. This was mediated, at least in part, through IFN-γ-induced activation of STAT3 and expression of IL-10, which suggests that splenic macrophages in VL are conditioned to respond to macrophage activation signals with a counter-regulatory response that is ineffective and even

  14. Cutaneous Leishmaniasis with HIV.

    Science.gov (United States)

    Talat, Humaira; Attarwala, Sharmeen; Saleem, Mubasshir

    2014-05-01

    Cutaneous Leishmaniasis (CL) is a vector borne disease caused by various species of the Leishmania parasite. CL is endemic in the province of Balochistan in Pakistan. In certain instances a Human Immunodeficiency Virus (HIV)-related immunocompromised is associated with atypical clinical presentation and occurrence of reactivated lesions of CL. Such presentations respond poorly to the standard treatment and frequent relapses are noted. We are reporting three cases of localized and disseminated CL due to Leishmania tropica which responded to meglumine antimoniate. Due to the fact that CL is endemic in Balochistan, we did not consider HIV infection as a causative organism. It was their presentation with history of weight loss and fever that prompted Enzyme-linked Immunosorbent Assay (ELISA) tests for HIV, which turned out to be positive. CL is becoming visible as an opportunistic infection associated with HIV/AIDS and may even be the first symptom in HIV positive patients in an endemic area.

  15. [Visceral leishmaniasis: new drugs].

    Science.gov (United States)

    Minodier, P; Robert, S; Retornaz, K; Garnier, J M

    2003-12-01

    The standard treatment of visceral leishmaniasis is pentavalent antimony (meglumine antimoniate or sodium stibogluconate), but toxicity is frequent with this drug. Moreover, antimony unresponsiveness is increasing, both in immunocompetent and in immunosuppressed patients. Amphotericin B is a polyene macrolide antibiotic that binds to sterols in cell membranes. It is the most active antileishmanial agent in use. Its infusion-related and renal toxicity may be reduced by lipid-based delivery. Liposomal amphotericin B (Ambisome) seems to be less toxic than other amphotericin B lipid formulations (Amphocil, Amphotec). Optimal drug regimens of Ambisome vary from one geographical area to another. In the Mediterranean Basin, a total dose of 18 to 24 mg/kg is safe and effective. Shortening the duration of treatment without decreasing the total dose (i.e., 10 mg/kg/day for 2 days) seems promising to reduce the global cost of the therapy.

  16. Development and pharmacokinetic of antimony encapsulated in liposomes of phosphatidylserine using radioisotopes in experimental leishmaniasis; Desenvolvimento e farmacocinetica de antimonio encapsulado em lipossomas de fosfatidilserina utilizando radioisotopos em leishmaniose experimental

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    Borborema, Samanta Etel Treiger

    2010-07-01

    Leishmaniasis are a complex of parasitic diseases caused by intra macrophage protozoa of the genus Leishmania, and is fatal if left untreated. Pentavalent antimonials, though toxic and their mechanism of action being unclear, remain the first-line drugs for treatment. Effective therapy could be achieved by delivering antileishmanial drugs to these sites of infection. Liposomes are phospholipid vesicles that promote improvement in the efficacy and action of drugs in target cell. Liposomes are taken up by the cells of mononuclear phagocytic system (MPS). The purpose of this study was to develop a preparation of meglumine antimonate encapsulated in liposomes of phosphatidylserine and to study its pharmacokinetic in healthy mice to establish its metabolism and distribution. Quantitative analysis of antimony from liposomes demonstrated that Neutron Activation Analysis was the most sensitive technique with almost 100 % of accuracy. All liposome formulations presented a mean diameter size of 150 nm. The determination of IC{sub 50} in infected macrophage showed that liposome formulations were between 10 - 63 fold more effective than the free drug, indicating higher selectivity index. By fluorescence microscopy, an increased uptake of fluorescent-liposomes was seen in infected macrophages during short times of incubation compared with non-infected macrophages. Biodistribution studies showed that meglumine antimonate irradiated encapsulated in liposomes of phosphatidylserine promoted a targeting of antimony for MPS tissues and maintained high doses in organs for a prolonged period. In conclusion, these data suggest that meglumine antimonate encapsulated in liposomes showed higher effectiveness than the non-liposomal drug against Leishmania infection. The development of liposome formulations should be a new alternative for the chemotherapy of infection diseases, especially Leishmaniasis, as they are used to sustain and target pharmaceuticals to the local of infection. (author)

  17. Epidemiology of visceral leishmaniasis

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    Ready PD

    2014-05-01

    Full Text Available Paul D ReadyDisease Control Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UKAbstract: Leishmania species are the causative agents of leishmaniasis, a neglected tropical disease. These parasitic protozoans are usually transmitted between vertebrate hosts by the bite of blood sucking female phlebotomine sand flies. This review focuses on the two parasites causing most human visceral leishmaniasis (VL, which leads to substantial health problems or death for up to 400,000 people per year. Except for travel cases, Leishmania donovani infections are restricted to the (sub-tropics of Asia and Africa, where transmission is mostly anthroponotic, while Leishmania infantum occurs in the drier parts of Latin America as well as in the Mediterranean climate regions of the Old World, with the domestic dog serving as the main reservoir host. The prevalence of VL caused by L. infantum has been declining where living standards have improved. In contrast, infections of L. donovani continue to cause VL epidemics in rural areas on the Indian subcontinent and in East Africa. The current review compares and contrasts these continental differences and suggests priorities for basic and applied research that might improve VL control. Transmission cycles, pathogenesis, diagnosis, treatment and prognosis, prevention (including vector control, surveillance, transmission modeling, and international control efforts are all reviewed. Most case detection is passive, and so routine surveillance does not usually permit accurate assessments of any changes in the incidence of VL. Also, it is not usually possible to estimate the human inoculation rate of parasites by the sand fly vectors because of the limitations of survey methods. Consequently, transmission modeling rarely passes beyond the proof of principle stage, and yet it is required to help develop risk factor analysis for control programs. Anthroponotic VL

  18. Visceral leishmaniasis: an update of laboratory diagnosis

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    Zineb Tlamcani

    2016-07-01

    Full Text Available Visceral leishmaniasis, is an infection due to obligate intracellular protozoa of the genus Leishmania. There exist two varieties of visceral leishmaniasis, that vary in their transmission aspects: zoonotic visceral leishmaniasis and anthroponotic visceral leishmaniasis. Their clinical features are comparable with sevral differences. Laboratory diagnosis of visceral leishmaniasis consists of microscopic observation of parasite, culture from appropriate samples, detection of antigen, serological tests, and identification of parasite DNA. In this review, we will discuss the different techniques of diagnosis and the interet of the recent methods such as rapid diagnostic test and direct agglutination test.

  19. Many faces of cutaneous leishmaniasis

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    Bari Arfan Ul

    2008-01-01

    Full Text Available Background: Cutaneous leishmaniasis (CL is known for its clinical diversity and increasing numbers of new and rare variants of the disease are being reported these days. Aim: The aim of this descriptive study was to look for and report the atypical presentations of this common disease occurring in Pakistan. Methods: The study was carried out in three hospitals (MH, Rawalpindi; PAF Hospital, Sargodha; and CMH, Muzaffarabad from 2002 to 2006. Military and civilian patients of all ages, both males and females, belonging to central and north Punjab province and Kashmir were included in the study. Clinical as well as parasitological features of cutaneous leishmaniasis were studied. The unusual lesions were photographed and categorized accordingly using simple descriptive statistics. Results: Out of 718 patients of cutaneous leishmaniasis, 41 (5.7% had unusual presentations. The commonest among unusual morphologies was lupoid leishmaniasis 14 (34.1%, followed by sporotrichoid 5 (12.1%, paronychial 3 (7.3%, lid leishmaniasis 2 (4.9%, psoriasiform 2 (4.9%, mycetoma-like 2 (4.9%, erysipeloid 2 (4.9%, chancriform 2 (4.9%, whitlow 1 (2.4%, scar leishmaniasis 1 (2.4%, DLE-like 1 (2.4%, ′squamous cell carcinoma′-like 1 (2.4%, zosteriform 1 (2.4%, eczematous 1 (2.4%, verrucous 1 (2.4%, palmar/plantar 1 (2.4% and mucocutaneous 1 (2.4%. Conclusion: In Pakistan, an endemic country for CL, the possibility of CL should be kept in mind while diagnosing common dermatological diseases like erysipelas, chronic eczema, herpes zoster, paronychia; and uncommon disorders like lupus vulgaris, squamous cell carcinoma, sporotrichosis, mycetoma and other deep mycoses.

  20. Vaccines and vaccination strategies against human cutaneous leishmaniasis.

    Science.gov (United States)

    Okwor, Ifeoma; Uzonna, Jude

    2009-05-01

    One might think that the development of a vaccine against cutaneous leishmaniasis would be relatively straightforward because the type of immune response required for protection is known and natural immunity occurs following recovery from primary infection. However, there is as yet no effective vaccine against the disease in humans. Although vaccination in murine studies has yielded promising results, these vaccines have failed miserably when tested in primates or humans. The reasons behind these failures are unknown and remain a major hurdle for vaccine design and development against cutaneous leishmaniasis. In contrast, recovery from natural, deliberate or experimental infections results in development of long-lasting immunity to re-infection. This so called infection-induced resistance is the strongest anti-Leishmania immunity known. Here, we briefly review the different approaches to vaccination against cutaneous leishmaniasis and argue that vaccines composed of genetically modified (attenuated) parasites, which induce immunity akin to infection-induced resistance, may provide best protection against cutaneous leishmaniasis in humans.

  1. Current treatment of visceral leishmaniasis (Kala-azar: an overview

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    Premshanker S. Singh

    2014-06-01

    Full Text Available Visceral Leishmaniasis (VL is also popularly known as kala-azar which was first reported in early forties and since then it continues to affect millions of people. The ranges of common drugs available for the treatment of visceral leishmaniasis are limited. It mainly includes pentavalent antimonials e.g. stibogluconate (SbV, amphotericin B deoxycholate (AB, lipid formulations of amphotericin B (L-AB, miltefosine (MF and paromomycin (PM - all of which have limitations in terms of toxicity, variable efficacy, price and inconvenient treatment schedules. Most are parenteral except MF which is administered orally. Due to the parasite and #8217;s drug resistance, the most widely used (SbV of these drugs is now of little use in northern Bihar, India, which alone accounts for 50% of the worlds burden of visceral leishmaniasis. In areas of resistance to SbV, AB is highly effective. The formulation of AB in liposomes (L-AB has been a major advancement in the treatment of visceral leishmaniasis. However, despite a significant reduction in price, this treatment remains very expensive for endemic countries like India. Combination short course therapy has been reported by many researchers who found that it is equally effective as conventional monotherapy with added benefits of less side effects, better compliance and less resistance. The aim of this article is to review the current aspects of the treatment for leishmaniasis, giving an overview of current agents clinically used to new agents and modalities of treatment under development. [Int J Res Med Sci 2014; 2(3.000: 810-817

  2. Ancient Leishmaniasis in a highland desert of Northern Chile.

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    Maria Antonietta Costa

    Full Text Available BACKGROUND: Leishmaniasis is an infectious disease endemic today in many areas of South America. METHODOLOGY: We discovered morphologic and molecular evidence of ancient infections in 4 female skulls in the archaeological cemetery of Coyo Oriente, in the desert of San Pedro de Atacama, Northern Chile. The boney facial lesions visible in the skulls could have been caused by a number of chronic infections including chronic Leishmaniasis. This diagnosis was confirmed using PCR-sequenced analyses of bone fragments from the skulls of the affected individuals.Leishmaniasis is not normally found in the high-altitude desert of Northern Chile; where the harsh climate does not allow the parasite to complete its life cycle. The presence of Leishmaniasis in ancient skulls from the region implies infection by the protozoan in an endemic area-likely, in our subjects, to have been the lowlands of North-Eastern Argentina or in Southern Bolivia. CONCLUSIONS: We propose that the presence of the disease in ancient times in the high altitude desert of San Pedro de Atacama is the result of an exogamic system of patrilocal marriages, where women from different cultures followed their husbands to their ancestral homes, allowing immigrant women, infected early in life, to be incorporated in the Atacama desert society before they became disfigured by the disease. The present globalization of goods and services and the extraordinary facile movement of people across borders and continents have lead to a resurgence of infectious diseases and re-emergence of infections such as Leishmaniasis. We show here that such factors were already present millennia ago, shaping demographic trends and the epidemiology of infections just as they do today.

  3. Systemic hypertension in dogs with leishmaniasis: prevalence and clinical consequences.

    Science.gov (United States)

    Cortadellas, Oscar; del Palacio, María Josefa Fernández; Bayón, Alejandro; Albert, Angel; Talavera, Jesús

    2006-01-01

    A prospective study was performed (November 1998 to December 2003) to determine the prevalence of systemic hypertension (SH) in dogs with glomerular disease secondary to leishmaniasis. One hundred and five dogs with leishmaniasis were screened and staged for the presence of renal disease (RD) and SH. For the purpose of the study, RD was defined as serum creatinine concentration > or = 1.4 mg/dL, a urine protein/creatinine ratio > or = 0.5, or both. SH was defined as a systolic blood pressure (SBP) > or =180 mm Hg or an SBP between 150 and 179 mm Hg in the presence of clinical manifestations of SH. Fifty-two (49.5%) of the dogs had some degree of RD, and 32 (61.5%) of these dogs were diagnosed with SH. Moreover, SH also was diagnosed in 3 dogs without RD. Left ventricular hypertrophy (LVH), estimated by echocardiography, was the most frequently observed systemic consequence of hypertension, being present in 32 (91.4%) of the hypertensive dogs. Echocardiographic abnormalities were not detected in any of the 33 dogs with leishmaniasis without RD, which were used as controls. Ocular consequences of SH were observed in only 2 (5.7%) of the dogs with hypertension. We conclude that SH is prevalent in dogs with RD secondary to leishmaniasis, not only in the more severe stages but also in the early course of the illness before azotemia becomes apparent. Canine leishmaniasis may be a useful natural model to study SH secondary to glomerular disease.

  4. Cutaneous leishmaniasis in Dutch military

    NARCIS (Netherlands)

    van Thiel, P.P.A.M.

    2010-01-01

    Leishmaniasis is een tropische ziekte veroorzaakt door een parasiet die wordt overgebracht door de zandvlieg. Pieter-Paul van Thiel beschrijft de besmetting van militairen tijdens drie missies in Afghanistan, en jungletrainingen in Suriname en Belize. Bij een missie in Noord-Afghanistan in 2005 raak

  5. Experimental Evidence on the Effects of Early Meetings and Activation

    DEFF Research Database (Denmark)

    Pedersen, Jonas Maibom; Rosholm, Michael; Svarer, Michael

    We analyze the effects of four randomized experiments involving intensive active labour market policy, conducted in Denmark in 2008. The interventions consisted of early and frequent meetings and activation programmes. The effects are remarkable; frequent meetings between newly unemployed workers...... reveals that meetings yield the largest net benefits....

  6. Mathematical Modelling and Experimental Analysis of Early Age Concrete

    DEFF Research Database (Denmark)

    Hauggaard-Nielsen, Anders Boe

    1997-01-01

    The report deals with mathematical models for concrete at early age. In the hardening process chemical reactions take place and the concrete skeleton is created. The processes changes the moisture content and produces heat. The associated temperature rise gives expansion of the material which may...

  7. Fostering Early Math Comprehension: Experimental Evidence from Paraguay

    Science.gov (United States)

    Naslund-Hadley, Emma; Parker, Susan W.; Hernandez-Agramonte, Juan Manuel

    2014-01-01

    Research indicates that preschool children need to learn pre-math skills to build a foundation for primary- and secondary-level mathematics. This paper presents the results from the early stages of a pilot mathematics program implemented in Cordillera, Paraguay. In a context of significant gaps in teacher preparation and pedagogy, the program uses…

  8. Experimental Evidence from an Early Childhood Parenting Intervention in Nicaragua

    Science.gov (United States)

    Macours, Karen; Premand, Patrick; Schady, Norbert; Vakis, Renos

    2015-01-01

    Despite the strong argument for investing in young children and the many types of interventions and delivery mechanisms that have been developed, knowledge on Early Childhood Development (ECD) programs' effectiveness in low-income settings remains thin. Yet a growing number of programs in developing countries contain interventions seeking to…

  9. Non invasive diagnostic tools for visceral leishmaniasis: a comparison of the immunoserological tests DAT, rK26 and rK39

    NARCIS (Netherlands)

    Teran-Angel, G.; Rodriguez, V.; de Silva, R.; Zerpa, O.; Schallig, H.; Ulrich, M.; Cabrera, M.

    2010-01-01

    Introduction. Human visceral leishmaniasis is a serious public health problem in endemic countries because of its high potential lethality, particularly in children. Rapid diagnosis is essential to early treatment and control of visceral leishmaniasis. Objective. The aim was to compare three serodia

  10. Voice disorders in mucosal leishmaniasis.

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    Ana Cristina Nunes Ruas

    Full Text Available INTRODUCTION: Leishmaniasis is considered as one of the six most important infectious diseases because of its high detection coefficient and ability to produce deformities. In most cases, mucosal leishmaniasis (ML occurs as a consequence of cutaneous leishmaniasis. If left untreated, mucosal lesions can leave sequelae, interfering in the swallowing, breathing, voice and speech processes and requiring rehabilitation. OBJECTIVE: To describe the anatomical characteristics and voice quality of ML patients. MATERIALS AND METHODS: A descriptive transversal study was conducted in a cohort of ML patients treated at the Laboratory for Leishmaniasis Surveillance of the Evandro Chagas National Institute of Infectious Diseases-Fiocruz, between 2010 and 2013. The patients were submitted to otorhinolaryngologic clinical examination by endoscopy of the upper airways and digestive tract and to speech-language assessment through directed anamnesis, auditory perception, phonation times and vocal acoustic analysis. The variables of interest were epidemiologic (sex and age and clinic (lesion location, associated symptoms and voice quality. RESULTS: 26 patients under ML treatment and monitored by speech therapists were studied. 21 (81% were male and five (19% female, with ages ranging from 15 to 78 years (54.5+15.0 years. The lesions were distributed in the following structures 88.5% nasal, 38.5% oral, 34.6% pharyngeal and 19.2% laryngeal, with some patients presenting lesions in more than one anatomic site. The main complaint was nasal obstruction (73.1%, followed by dysphonia (38.5%, odynophagia (30.8% and dysphagia (26.9%. 23 patients (84.6% presented voice quality perturbations. Dysphonia was significantly associated to lesions in the larynx, pharynx and oral cavity. CONCLUSION: We observed that vocal quality perturbations are frequent in patients with mucosal leishmaniasis, even without laryngeal lesions; they are probably associated to disorders of some

  11. The experimental chemotherapy of leishmaniasis, VI. The development of rodent models for cutaneous infection with L. major and L. mexicana amazonensis.

    Science.gov (United States)

    Trotter, E R; Peters, W; Robinson, B L

    1980-06-01

    infections, but precautions must be taken to ensure its absorption by experimental animals.

  12. The Early Endocrine Stress Response in Experimental Subarachnoid Hemorrhage.

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    Christoffer Nyberg

    Full Text Available In patients with severe illness, such as aneurysmal subarachnoid hemorrhage (SAH, a physiologic stress response is triggered. This includes activation of the hypothalamic-pituitary-adrenal (HPA axis and the sympathetic nervous system. The aim of this study was to investigate the very early responses of these systems.A porcine animal model of aneurysmal SAH was used. In this model, blood is injected slowly to the basal cisterns above the anterior skull base until the cerebral perfusion pressure is 0 mm Hg. Sampling was done from blood and urine at -10, +15, +75 and +135 minutes from time of induction of SAH. Analyses of adrenocorticotropic hormone (ACTH, cortisol, aldosterone, catecholamines and chromogranin-A were performed.Plasma ACTH, serum cortisol and plasma aldosterone increased in the samples following induction of SAH, and started to decline after 75 minutes. Urine cortisol also increased after SAH. Urine catecholamines and their metabolites were found to increase after SAH. Many samples were however below detection level, not allowing for statistical analysis. Plasma chromogranin-A peaked at 15 minutes after SAH, and thereafter decreased.The endocrine stress response after aneurysmal SAH was found to start within 15 minutes in the HPA axis with early peak values of ACTH, cortisol and aldosterone. The fact that the concentrations of the HPA axis hormones decreased 135 minutes after SAH may suggest that a similar pattern exists in SAH patients, thus making it difficult to catch these early peak values. There were also indications of early activation of the sympathetic nervous system, but the small number of valid samples made interpretation difficult.

  13. Early Results in Capella's Prior Learning Assessment Experimental Site Initiative

    Science.gov (United States)

    Klein, Jillian

    2017-01-01

    In July 2014, the U.S. Department of Education announced a new round of experimental sites focusing on competency-based education. Capella University was selected to participate in three of the Department of Education's competency-based education (CBE) experiments and began by implementing the prior learning assessment experiment, which allows…

  14. Treatment of visceral leishmaniasis

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    E M Moore

    2010-01-01

    Full Text Available The available treatment options for visceral leishmaniasis (VL have problems relating to efficacy, adverse effects and cost, making treatment a complex issue. We review the evidence relating to the different methods of treatment in relation to - efficacy and toxicity of the drugs in different areas of the world; ability to monitor side effects, length of treatment; ability of patients to pay for and stay safe during treatment, ability of the healthcare services to give intramuscular, intravenous or oral therapy; the sex and child-bearing potential of the patient and the immune status of the patient. The high mortality of untreated/ poorly treated VL infection makes the decisions paramount, but a unified and coordinated response by each area is likely to be more effective and informative to future policies than an ad hoc response. For patients in resource-rich countries, liposomal amphotericin B appears to be the optimal treatment. In South Asia, miltefosine is being used; the combination of single dose liposomal amphotericin B and short course miltefosine looks encouraging but has the problem of potential reproductive toxicities in females. In Africa, the evidence to switch from SSG is not yet compelling. The need to monitor and plan for evolving drug failure, secondary to leishmania parasite resistance, is paramount. With a few drugs the options may be limited; however, we await key ongoing trials in both Africa and India to explore the effects of combination treatment. If safe and reliable combinations are revealed by the ongoing studies, it is far from clear as to whether this will avoid leishmania parasite resistance. The development of new drugs to add to the armamentarium is paramount. Lessons can be learnt from the management of diseases such as tuberculosis and malaria in terms of planning the switch to combination treatment. As important as establishing the best choice for specific antileishmanial agent is ensuring treatment centers

  15. Aspectos ecológicos da leishmaniose tegumentar americana: 1. estudo experimental da freqüência de flebotomineos a ecótopos artificiais com referência especial a Psychodopygus intermedius Ecological aspects of American cutaneous leishmaniasis: 1. experimental study of the frequency of phlebotomine sandflies in artificial biotope with special reference to Psychodopygus intermedius

    Directory of Open Access Journals (Sweden)

    Almério de Castro Gomes

    1980-12-01

    Full Text Available A utilização de galinheiro como modelo experimental na observação do comportamento de Psychodopygus intermedius, desenvolvida na região do Vale do Ribeira, Estado de São Paulo, Brasil, revelou uma estreita associação entre o flebotomíneo e biótopo artificial estudado. Sua maior densidade à margem da mata sugeriu a hipótese de estar adaptado ao efeito marginal. As investigações em ambiente florestal e extraflorestal demonstraram sua nítida preferência pelo último. Diversos aspectos discutidos explicam parcialmente a ocorrência de leishmaniose tegumentar nesse Estado.The use of chicken roosts as experimental models for observing the behavior of Psychodopygus intermedius in the Ribeira River Valley region of the State of S. Paulo (Brazil, showed that there is a close association between the biotope studied and the phlebotomine sandfly. Its greater frequency along the edge of woods suggested the hypothesis of its adaptation to the edge effect. Investigation of forest and extraforest environments showed the fly's clear preference for the latter. Several of the aspects discussed in the paper partially explain the occurrence of cutaneous leishmaniasis in S. Paulo State.

  16. Visceral Leishmaniasis In A Native Kashmiri Boy

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    Deepti Mahajan, M.L. Bhat

    2009-07-01

    Full Text Available Leishmaniasis, though widely prevalent in South Asia, is not seen in the Kashmir valley where the coldclimatic conditions create a hostile environment for the growth of the parasite or its vector, the sandfly.However, a few cases of cutaneous leishmaniasis have been documented from the hot and arid Uri belt ofKashmir. We present a case of visceral leishmaniasis in a boy hailing from Uri, a rarity in this region.

  17. Diagnóstico molecular para Leishmaniasis

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    Ysabel Montoya

    1997-01-01

    Full Text Available El potencial diagnóstico de epitopes inmunodominantes seleccionados fue ensayado satisfactoriamente a fin de obtener una prueba serodiagnóstica alternativa para la Leishmaniasis Tegumentaria Americana. Dos proteínas recombinantes prometedoras de L. (v. peruviana referidas como T-26-U2/T26-U4 fueron reconocidas por sueros individuales de pacientes con Leishmaniasis Tegumentaria Americana usando Western Blot. La sensibilidad de la prueba fue de 86% con sueros permanentes con Leishmaniasis peruana.

  18. Reactive Oxygen Species and Nitric Oxide in Cutaneous Leishmaniasis

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    Maria Fátima Horta

    2012-01-01

    Full Text Available Cutaneous leishmaniasis affects millions of people around the world. Several species of Leishmania infect mouse strains, and murine models closely reproduce the cutaneous lesions caused by the parasite in humans. Mouse models have enabled studies on the pathogenesis and effector mechanisms of host resistance to infection. Here, we review the role of nitric oxide (NO, reactive oxygen species (ROS, and peroxynitrite (ONOO− in the control of parasites by macrophages, which are both the host cells and the effector cells. We also discuss the role of neutrophil-derived oxygen and nitrogen reactive species during infection with Leishmania. We emphasize the role of these cells in the outcome of leishmaniasis early after infection, before the adaptive Th-cell immune response.

  19. Optimized subunit vaccine protects against experimental leishmaniasis.

    Science.gov (United States)

    Bertholet, Sylvie; Goto, Yasuyuki; Carter, Lauren; Bhatia, Ajay; Howard, Randall F; Carter, Darrick; Coler, Rhea N; Vedvick, Thomas S; Reed, Steven G

    2009-11-23

    Development of a protective subunit vaccine against Leishmania spp. depends on antigens and adjuvants that induce appropriate immune responses. We evaluated a second generation polyprotein antigen (Leish-110f) in different adjuvant formulations for immunogenicity and protective efficacy against Leishmania spp. challenges. Vaccine-induced protection was associated with antibody and T cell responses to Leish-110f. CD4 T cells were the source of IFN-gamma, TNF, and IL-2 double- and triple-positive populations. This study establishes the immunogenicity and protective efficacy of the improved Leish-110f subunit vaccine antigen adjuvanted with natural (MPL-SE) or synthetic (EM005) Toll-like receptor 4 agonists.

  20. Treatment strategies for mucocutaneous leishmaniasis

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    Emilio Palumbo

    2010-01-01

    Full Text Available Mucocutaneous is an infection caused by a single celled parasite transmitted by sand fly bites. There are about 20 species of Leishmania that may cause mucocutaneous leishmaniasis. Some Leishmania species are closely linked to humans and are therefore found in cities (L. tropica whereas some others are more traditionally associated with animal species and therefore considered zoonoses (L. major. The evidence for optimal treatment of mucocutaneous leishmaniasis is patchy. Although the cutaneous form of the disease is often self-limiting, it does result in significant scarring and can spread to more invasive, mucocutaneous disease. Therefore, treatment may be considered to prevent these complications. Drugs for systemic and topical treatment are presented and discussed with regard to their application, use and adverse effects.

  1. Early protective effects of Iloprost after experimental spinal cord injury.

    Science.gov (United States)

    Attar, A; Tuna, H; Sargon, M F; Yüceer, N; Türker, R K; Egemen, N

    1998-06-01

    This investigation was undertaken to study the early protective effects of Iloprost, a stable analogue of prostacyclin, after spinal cord injury in rabbit. Sixteen adult male rabbits (New Zealand Albino) were injured by application of epidural aneurysm clip. Eight rabbits received an intravenous (i.v.) infusion of 30 micrograms kg-1 Iloprost, and eight rabbits received an infusion of saline (SF). Treatment with Iloprost started immediately after spinal cord injury and continued for one hour. Evoked potentials were recorded for each rabbit at one, 15, and 60 minutes after the spinal cord injury. Twenty-four hours later, all the rabbits were deeply anesthetized and spinal cords were removed for histopathological examinations. There was no meaningful statistical difference between cortical somatosensorial evoked potentials (CSEP) of the saline and Iloprost group. However, light and electron microscopic studies showed that the Iloprost treated group had moderate protection of myelin and axons; and limited edema. These results suggest that intravenous Iloprost treatment after spinal cord injury has a highly protective effect without any side effects.

  2. Oral manifestations in the American tegumentary leishmaniasis.

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    Daniel Cesar Silva da Costa

    Full Text Available American tegumentary leishmaniasis (ATL can affect the skin or mucosa (mucocutaneous leishmaniasis - MCL including the oral cavity. MCL oral lesions are often confused with other oral diseases, delaying diagnosis and specific treatment, and increasing the likelihood of sequelae. Thus, increasing the knowledge of the evolution of ATL oral lesions can facilitate its early diagnosis improving the prognosis of healing.Evaluate the frequency of ATL oral lesion and describe its clinical, laboratory and therapeutic peculiarities.A descriptive transversal study was carried out, using data from medical records of 206 patients with MCL examined at the outpatient clinics-IPEC-Fiocruz between 1989 and 2013. Proportions were calculated for the categorical variables and the association among them was assessed by the Pearson's chi-square test. Measures of central tendency and dispersion were used for the continuous variables and their differences were assessed by both parametric (t test and non parametric (Mann-Whitney tests. P-values <0.05 were considered as significant.The most affected site was the nose, followed by the mouth, pharynx and larynx. Seventy eight (37.9% have oral lesions and the disease presented a lower median of the evolution time than in other mucous sites as well as an increased time to heal. The presence of oral lesion was associated with: the presence of lesions in the other three mucosal sites; a smaller median of the leishmanin skin test values; a longer healing time of the mucosal lesions; a higher recurrence frequency; and a smaller frequency of treatment finishing and healing. When the oral lesion was isolated, it was associated with an age 20 years lower than when the oral lesion was associated with other mucosal sites.Considering the worst therapy results associated with the presence of oral lesions, we suggest that lesions in this location represent a factor of worse prognosis for MCL.

  3. [Visceral leishmaniasis. Pediatric case report].

    Science.gov (United States)

    Gomila H, Andrés; Vanzo, Carolina; Garnero, Analía; Peruzzo, Luisina; Badalotti, Mónica

    2017-08-01

    La leishmaniasis es una enfermedad causada por parásitos obligados intracelulares pertenecientes al género Leishmania y que reconoce tres formas clínicas principales: cutánea, visceral y mucocutánea. Es una patología del grupo de las "enfermedades desatendidas". Es la única enfermedad tropical transmitida a través de vectores que se ha mantenido endémica por décadas en el sur de Europa. La leishmaniasis visceral representa la forma más grave. Se caracteriza por fiebre, pérdida de peso, anemia y hepatoesplenomegalia. Su período de incubación oscila entre 2 semanas y 18 meses. La leishmaniasis se considera una enfermedad reemergente a nivel mundial. Algunos de los factores que favorecen esta situación son los cambios en las condiciones climáticas, migraciones y urbanizaciones deficitarias en saneamiento ambiental. Se presenta el caso de un niño europeo que estaba vacacionando en Córdoba y fue derivado a nuestro Hospital por fiebre y pancitopenia, lo que generó un abordaje multidisciplinario con resolución clínica favorable. Sociedad Argentina de Pediatría.

  4. Compartmentalized Immune Response in Leishmaniasis: Changing Patterns throughout the Disease.

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    Alhelí Rodríguez-Cortés

    Full Text Available Visceral leishmaniasis (VL is characterized by loss of T-cell responsiveness and absence of Leishmania-specific IFN-γ production by peripheral blood mononuclear cells. However, the expressions of IFN-γ and TNF-α are up-regulated in the tissues and plasma of VL patients. There is a paucity of information regarding the cytokine profile expressed by different target tissues in the same individual and the changes it undergoes throughout the course of infection. In this work we evaluated IFN-γ, TNF-α, IL-10, and TGF-β mRNA expression using real-time RT-PCR in 5 target tissues at 6 months and 16 months post-infection (PI in a canine experimental model which mimics many aspects of human VL. The spleen and liver of Leishmania infantum experimentally-infected dogs elicited a pro- and anti- inflammatory response and high parasite density at 6 and 16 months PI. The popliteal lymph node, however, showed an up-regulation of IFN-γ cytokin at commencement of the study and was at the chronic phase when the IL-10 and TGF-β expression appeared. In spite of skin parasite invasion, local cytokine response was absent at 6 months PI. Parasite growth and onset of clinical disease both correlated with dermal up-regulation of all the studied cytokines. Our VL model suggests that central target organs, such as the spleen and liver, present a mixed cytokine immune response early on infection. In contrast, an anti-inflammatory/regulatory immune response in peripheral tissues is activated in the later chronic-patent stages of the disease.

  5. Compartmentalized Immune Response in Leishmaniasis: Changing Patterns throughout the Disease

    Science.gov (United States)

    Carrillo, Eugenia; Martorell, Susanna; Todolí, Felicitat; Martínez-Flórez, Alba; Urniza, Alicia; Moreno, Javier

    2016-01-01

    Visceral leishmaniasis (VL) is characterized by loss of T-cell responsiveness and absence of Leishmania-specific IFN-γ production by peripheral blood mononuclear cells. However, the expressions of IFN-γ and TNF-α are up-regulated in the tissues and plasma of VL patients. There is a paucity of information regarding the cytokine profile expressed by different target tissues in the same individual and the changes it undergoes throughout the course of infection. In this work we evaluated IFN-γ, TNF-α, IL-10, and TGF-β mRNA expression using real-time RT-PCR in 5 target tissues at 6 months and 16 months post-infection (PI) in a canine experimental model which mimics many aspects of human VL. The spleen and liver of Leishmania infantum experimentally-infected dogs elicited a pro- and anti- inflammatory response and high parasite density at 6 and 16 months PI. The popliteal lymph node, however, showed an up-regulation of IFN-γ cytokin at commencement of the study and was at the chronic phase when the IL-10 and TGF-β expression appeared. In spite of skin parasite invasion, local cytokine response was absent at 6 months PI. Parasite growth and onset of clinical disease both correlated with dermal up-regulation of all the studied cytokines. Our VL model suggests that central target organs, such as the spleen and liver, present a mixed cytokine immune response early on infection. In contrast, an anti-inflammatory/regulatory immune response in peripheral tissues is activated in the later chronic-patent stages of the disease. PMID:27171409

  6. Leishmaniasis cutis:report of two cases

    Institute of Scientific and Technical Information of China (English)

    XU Ke-jian; LIU Yue-hua; FANG Kai

    2005-01-01

    @@ Leishmaniasis cutis is a chronic dermatosis resulting from infestation by Leishmania of the skin.The diagnosis could not be established until a biopsy specimen revealed Leishman-Donovan(LD)bodies.We report two cases of leishmaniasis cutis diagnosed and treated recently in our department.

  7. Oral mucosal involvement in visceral leishmaniasis

    Institute of Scientific and Technical Information of China (English)

    Sunny Garg; Richik Tripathi; Kamlakar Tripathi

    2013-01-01

    Leishmaniasis affects both the visceral and cutaneous tissues in body.OralMucosal involvement in leishmaniasis is rare and is often overlooked.We present a case17 year old boy from the north east region ofBihar who has a history of visceral leishmaniasis one year back, came to the department of oral surgery for treatment of persistent oral ulcers.Oral examination did not give any diagnostic information while systemic examination revealed enlarged spleen and low grade fever.Patient was screened for leishmaniasis by rK39 based immunochromatographic strip test which came to be positive.Biopsy of the ulcer as well as splenic and bone marrow aspirate confirmed the presence of leishmaniasis.Patient was administeredAmphotericinB for20 days following which significant clinical and haematological improvement followed.

  8. Two cases of primary endonasal leishmaniasis in Sardinia (Italy).

    Science.gov (United States)

    Pau, Monica; Atzori, Laura; Aste, Natalia; Aste, Nicola

    2009-06-15

    Leishmaniasis is an endemic protozoan infection in Sardinia, one of the major islands of the Mediterranean Basin. We report two cases of endonasal primary Leishmaniasis, which is a very rare event in adult men who are immunocompetent, born in, and residents of Sardinia. The diagnosis was confirmed by the presence of intra and extracellular Leishmania amastigotes in the histological smear. Isoenzymatic characterization identified Leishmania infantum zymodeme MON-111 in both cases. Laboratory and instrumental investigations excluded visceral involvement. Treatment with meglumine antimoniate (Glucantim) intralesional administration, 1 ml weekly for 4-5 weeks, led to complete resolution. The unusual location is likely a reflection an uncommon site of inoculation of the protozoa, transmitted by flying vectors. The patients were a shepherd and a farmer, respectively, both professions at high risk of infection because of their habits of sleeping outdoors under trees or in country cottages during spring and summer and exposed to sand fly bites. Although mucosal involvement and infection by Leishmania infantum, a potential cause of visceral leishmaniasis, the Sardinian patients experienced a benign disease course considering muco-cutaneous forms described in the New World. Differential diagnosis and early detection are necessary in order to start effective treatment and prevent more serious complications.

  9. [Importance of drug carriers in the treatment of visceral leishmaniasis].

    Science.gov (United States)

    Fusai, T; Durand, R; Boulard, Y; Paul, M; Bories, C; Rivollet, D; Houin, R; Deniau, M

    1995-01-01

    Visceral leishmaniasis is caused by hemoflagellate protozoa which are obligatory parasites of the mononuclear phagocyte system. Leishmaniasis causes high morbidity and mortality worldwide. The treatment of choice remains pentavalent antimonials, but high toxicity and failures have been reported. An alternative to conventional treatment is delivery anti-leishmania agents using colloidal carrier systems. Carriers improve drug activity against intracellular disease involving the mononuclear phagocyte system. The principle of drug delivery by carrier systems has been applied successfully for anticancer drugs. Recently complete remission of polyresistant visceral leishmaniasis was obtained by injection of liposomal amphotericin B. At present, no colloidal drug carrier for antimony derivatives is available, but pentamidine can be linked experimentally to methacrylate polymer nano-particles. Drug-loaded nanoparticles have been shown to be effective against amastigote leishmania both in vitro and in vivo. Another colloidal system of major interest for drug delivery, the liposome has already been loaded with amphotericin B and used for human therapy. The concept of particulate drug carriers opens the way for new chemotherapeutic approaches in the field of parasitology.

  10. Cutaneous Leishmaniasis with Unusual Presentation

    Directory of Open Access Journals (Sweden)

    N Bagherani

    2009-05-01

    Full Text Available "nThis case report states a 25-year-old woman, residing in the city of Dezfool, Khuzestan Province, south of Iran with the diagnosis of cutaneous leishmaniasis in June 2008. Her skin lesion had de­veloped from 8 months earlier as a nodule on her left arm, 1×3 cm in diameter. Because of sever­ity of the lesion, we prescribed meglumine antimoniate intralesionally with giving up her breast feeding. After 6 months follow-up, no recurrence was seen.

  11. Leishmaniasis in the genital area

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    CABELLO Ismery

    2002-01-01

    Full Text Available Two patients from the gold mines of Bolivar State, Venezuela, presenting cutaneous leishmaniasis in the genital region, an unusual location, are described. The first patient showed an ulcerated lesion of the glans penis. Leishmanin skin test was positive. A biopsy specimen revealed a granulomatous infiltrate containing Leishmania parasites. In the second patient, Leishmanin skin test was positive, HIV and VDRL were negative. Leishmania parasites were present in a biopsy of an ulcerated lesion in the scrotum, with an indurated base, infiltrative borders with an yellowish exudate. Patients were treated with meglumine antimoniate and the lesions healed.

  12. The organization of health services and visceral leishmaniasis: an integrated intervention to improve diagnosis and treatment.

    Science.gov (United States)

    Luz, Zélia M P; Carneiro, Mariângela; Schall, Virgínia; Rabello, Ana

    2009-05-01

    The objective of this study, carried out in municipalities located in a metropolitan region of Brazil, was to promote the early diagnosis and prompt treatment of visceral leishmaniasis. In the intervention model a health professional underwent training that covered all procedures involved in assisting patients with suspected visceral leishmaniasis. The professionals then returned to their municipalities where they implemented a workplan with the following aims: (a) at least one physician able to diagnose and treat patients; (b) training of professionals for the laboratorial diagnosis of visceral leishmaniasis; (c) delivery of information on visceral leishmaniasis to the health workers. The implementation process was evaluated by follow-up meetings. Attendance of health professionals at the meetings, implementation of the workplan, and the visceral leishmaniasis case fatality rate before (1998-1999) and after (2001-2002) implementation of the model were used in the analysis. Among the 36 municipalities in the region, 22 were enrolled. Eight (36.3%) guaranteed at least 50% attendance in the meetings, and 14 (63.6%) had less than 50% attendance with no activities implemented. The fatality rate decreased in the municipalities that implemented the activities.

  13. Recent advances in leishmaniasis treatment.

    Science.gov (United States)

    Tiuman, Tatiana S; Santos, Adriana O; Ueda-Nakamura, Tânia; Filho, Benedito P Dias; Nakamura, Celso V

    2011-08-01

    About 1.5 million new cases of cutaneous leishmaniasis and 500,000 new cases of visceral leishmaniasis occur each year around the world. For over half a century, the clinical forms of the disease have been treated almost exclusively with pentavalent antimonial compounds. In this review, we describe the arsenal available for treating Leishmania infections, as well as recent advances from research on plants and synthetic compounds as source drugs for treating the disease. We also review some new drug-delivery systems for the development of novel chemotherapeutics. We observe that the pharmaceutical industry should employ its modern technologies, which could lead to better use of plants and their extracts, as well as to the development of synthetic and semi-synthetic compounds. New studies have highlighted some biopharmaceutical technologies in the design of the delivery strategy, such as nanoparticles, liposomes, cochleates, and non-specific lipid transfer proteins. These observations serve as a basis to indicate novel routes for the development and design of effective anti-Leishmania drugs.

  14. Leishmaniasis in dogs: Case study

    Directory of Open Access Journals (Sweden)

    Aleksić Jelena

    2009-01-01

    Full Text Available The paper presents a case of leishmaniasis in a 2.5-month-old dog imported from France. The clinical examination established a generally poor state of health, expressed cachexia, atrophy of the temporal musculature, weakness of movement, as well as abnormally long and brittle nails. There was also hyperkeratosis of the nose tip and paws. A histological examination of biopsy sections of the altered skin parts showed inflammatory changes in the area of the dermis, together with infiltration of macrophages and a smaller number of lymphocytes, plasmocytes and neutrophil granulocytes in the area around the sebaceous glands and hair follicles. The determined changes correspond to superficial dermatitis. Edema followed by partial degeneration of connective-tissue fibers is observed in connective tissue. A smaller number of intracellular parasitic forms was established in mononuclear cells. A smaller number of oval amastigotes with round dark red nucleis were observed in sections stained using the Gimza method in the cytoplasm of macrophages located in the dermis, but also extracellularly. It was concluded that the dog was diseased with leishmaniasis on the grounds of the clinical picture and the microscopic findings.

  15. Visceral leishmaniasis in a rheumatoid arthritis patient receiving methotrexate.

    Science.gov (United States)

    Reina, Delia; Cerdà, Dacia; Güell, Elena; Martínez Montauti, Joaquín; Pineda, Antonio; Corominas, Hèctor

    2016-08-11

    Patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs are susceptible to severe infections such as leishmaniasis. As L. infantum is endemic in the Mediterranean region, it is necessary to rule this infectious process out in any RA patient presenting with fever and pancytopenia. An early diagnosis based on a high suspicion can prevent a fatal outcome. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  16. Early loss of oligodendrocytes in human and experimental neuromyelitis optica lesions.

    Science.gov (United States)

    Wrzos, Claudia; Winkler, Anne; Metz, Imke; Kayser, Dieter M; Thal, Dietmar R; Wegner, Christiane; Brück, Wolfgang; Nessler, Stefan; Bennett, Jeffrey L; Stadelmann, Christine

    2014-04-01

    Neuromyelitis optica (NMO) is a chronic, mostly relapsing inflammatory demyelinating disease of the CNS characterized by serum anti-aquaporin 4 (AQP4) antibodies in the majority of patients. Anti-AQP4 antibodies derived from NMO patients target and deplete astrocytes in experimental models when co-injected with complement. However, the time course and mechanisms of oligodendrocyte loss and demyelination and the fate of oligodendrocyte precursor cells (OPC) have not been examined in detail. Also, no studies regarding astrocyte repopulation of experimental NMO lesions have been reported. We utilized two rat models using either systemic transfer or focal intracerebral injection of recombinant human anti-AQP4 antibodies to generate NMO-like lesions. Time-course experiments were performed to examine oligodendroglial and astroglial damage and repair. In addition, oligodendrocyte pathology was studied in early human NMO lesions. Apart from early complement-mediated astrocyte destruction, we observed a prominent, very early loss of oligodendrocytes and oligodendrocyte precursor cells (OPCs) as well as a delayed loss of myelin. Astrocyte repopulation of focal NMO lesions was already substantial after 1 week. Olig2-positive OPCs reappeared before NogoA-positive, mature oligodendrocytes. Thus, using two experimental models that closely mimic the human disease, our study demonstrates that oligodendrocyte and OPC loss is an extremely early feature in the formation of human and experimental NMO lesions and leads to subsequent, delayed demyelination, highlighting an important difference in the pathogenesis of MS and NMO.

  17. [Feline leishmaniasis: what's the epidemiological role of the cat?].

    Science.gov (United States)

    Mancianti, F

    2004-06-01

    . Visceral leishmaniasis is not common in cats: this form shows visceral involvement: liver and spleen are interested, with lymph nodes and kidney. The cat probably has to considerate to play an active role in the disease, in contrast to goats, calves and horses who could act as accidental reservoirs of leishmania, while sheep appears to be not susceptible to experimental infection. In endemic foci for kala-azar in Sudan cows, goats and donkeys had a high prevalence of specific antibodies. Recently in Europe sporadic cases of equine leishmaniasis have been reported: L. infantum was the causative agent. Equine leishmaniasis appears as a self-healing skin-dwelling disease, with a massive accumulation of parasites. The animals do not often show detectable specific antibodies and recover without any chemotherapy. Untreated affected cats can frequently die and we also observed lymph nodes and blood involvement indicating a spread of leishmania in feline hosts. The epidemiological role of the cat has never been clarified due also to lack of xenodiagnosis trials. This species is believed to have a high degree of natural resistance, as observed following experimental infection. Some of the affected cats were FIV and/or FeLV positive and these viroses such as stress may induce an impaired cellular immune response, even if leishmania infected cat was not submitted to CD4+, CD8+ lymphocyte counts nor other immunological test. However the resistance of the cat to leishmania infection probably depends on genetic factors, not strictly related to cell mediated immunity, taking into account the high seroprevalence of FIV infections (30%) in our country versus the number of clinical cases.

  18. Cardioprotective effects of early and late aerobic exercise training in experimental pulmonary arterial hypertension.

    Science.gov (United States)

    Moreira-Gonçalves, Daniel; Ferreira, Rita; Fonseca, Hélder; Padrão, Ana Isabel; Moreno, Nuno; Silva, Ana Filipa; Vasques-Nóvoa, Francisco; Gonçalves, Nádia; Vieira, Sara; Santos, Mário; Amado, Francisco; Duarte, José Alberto; Leite-Moreira, Adelino F; Henriques-Coelho, Tiago

    2015-11-01

    Clinical studies suggest that aerobic exercise can exert beneficial effects in pulmonary arterial hypertension (PAH), but the underlying mechanisms are largely unknown. We compared the impact of early or late aerobic exercise training on right ventricular function, remodeling and survival in experimental PAH. Male Wistar rats were submitted to normal cage activity (SED), exercise training in early (EarlyEX) and in late stage (LateEX) of PAH induced by monocrotaline (MCT, 60 mg/kg). Both exercise interventions resulted in improved cardiac function despite persistent right pressure-overload, increased exercise tolerance and survival, with greater benefits in EarlyEX+MCT. This was accompanied by improvements in the markers of cardiac remodeling (SERCA2a), neurohumoral activation (lower endothelin-1, brain natriuretic peptide and preserved vascular endothelial growth factor mRNA), metabolism and mitochondrial oxidative stress in both exercise interventions. EarlyEX+MCT provided additional improvements in fibrosis, tumor necrosis factor-alpha/interleukin-10 and brain natriuretic peptide mRNA, and beta/alpha myosin heavy chain protein expression. The present study demonstrates important cardioprotective effects of aerobic exercise in experimental PAH, with greater benefits obtained when exercise training is initiated at an early stage of the disease.

  19. Experimental early-stage coalification of a peat sample and a peatified wood sample from Indonesia

    Science.gov (United States)

    Orem, W.H.; Neuzil, S.G.; Lerch, H.E.; Cecil, C.B.

    1996-01-01

    Experimental coalification of a peat sample and a buried wood sample from domed peat deposits in Indonesia was carried out to examine chemical structural changes in organic matter during early-stage coalification. The experiment (125 C, 408 atm lithostatic pressure, and 177 atm fluid pressure for 75 days) was designed to maintain both lithostatic and fluid pressure on the sample, but allow by-products that may retard coalification to escape. We refer to this design as a geologically open system. Changes in the elemental composition, and 13C NMR and FTIR spectra of the peat and wood after experimental coalification suggest preferential thermal decomposition of O-containing aliphatic organic compounds (probably cellulose) during early-stage coalification. The elemental compositions and 13C NMR spectra of the experimentally coalified peat and wood were generally similar to those of Miocene coal and coalified wood samples from Indonesia. Yields of lignin phenols in the peat and wood samples decreased following experimental coalification; the wood sample exhibited a larger change. Lignin phenol yields from the experimentally coalified peat and wood were comparable to yields of lignin phenols from Miocene Indonesian lignite and coalified wood. Changes in syringyl/vanillyl and p-hydroxy/vanillyl ratios suggest direct demethoxylation as a secondary process to demethylation of methoxyl groups during early coalification, and changes in lignin phenol yields and acid/aldehyde ratios point to a coupling between demethoxylation processes and reactions in the alkyl side chain bonds of the ??-carbon in lignin phenols.

  20. Cutaneous leishmaniasis: diagnostic pitfall. Case report

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    Asmae EL Hatimi

    2014-01-01

    Full Text Available Introduction: Cutaneous Leishmaniasis is a parasitic infection encountered in our daily dermatologic practice. Case report: We present a case of 57 year-old man of Moroccan origin, with erythematous squamous and indurated plaque on the abdomen, treated as sarcoidosis with corticosteroids with no improvement. Discussion: Cutaneous Leishmaniasis is endemic in 88 countries. Aside from its classical presentation it can manifest in multiple different ways. In our case, the diagnostic of Erysipeloide Leishmaniasis was corrected on the basis of the skin smear and the histopathological examination. Our observation is particular in its clinical presentation and location. To our knowledge it is the first Moroccan case. Conclusion: Even in endemic countries it is worth reporting unusual forms and locations of Cutaneous Leishmaniasis in order to avoid inappropriate diagnosis and management.

  1. Development of Vaccines against Visceral Leishmaniasis

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    Krystal J. Evans

    2012-01-01

    Full Text Available Leishmaniasis is a neglected disease resulting in a global morbidity of 2,090 thousand Disability-Adjusted Life Years and a mortality rate of approximately 60,000 per year. Among the three clinical forms of leishmaniasis (cutaneous, mucosal, and visceral, visceral leishmaniasis (VL accounts for the majority of mortality, as if left untreated VL is almost always fatal. Caused by infection with Leishmania donovani or L. infantum, VL represents a serious public health problem in endemic regions and is rapidly emerging as an opportunistic infection in HIV patients. To date, no vaccine exists for VL or any other form of leishmaniasis. In endemic areas, the majority of those infected do not develop clinical symptoms and past infection leads to robust immunity against reinfection. Thus the development of vaccine for Leishmania is a realistic public health goal, and this paper summarizes advances in vaccination strategies against VL.

  2. Pediatric visceral leishmaniasis in northwest of Iran.

    Science.gov (United States)

    Abdinia, Babak; Oliaei-Motlagh, Mohammad; Teimouri-Dereshki, Amir

    2016-11-01

    Leishmaniasis is one of the major health problems in Iran. Although the incidence of visceral leishmaniasis (VL) is reported almost everywhere, the northwestern Iran is one of the major endemic regions.To do this study, clinical, laboratory as well as disease characteristics of children admitted to Children Cure and Health Hospital, Tabriz University of Medical Sciences, were examined as the reference hospital for the treatment of VL in northwestern Iran.In this study, 156 children hospitalized in a pediatric hospital from 2000 to 2015 for VL were included. Gender, age, anemia, thrombocytopenia, increase in the erythrocyte sedimentation rate (ESR), alanine transaminase (SGPT), and aspartate transaminase (SGOT), major clinical manifestations such as fever, splenomegaly, hepatomegaly, treatment type, and the disease were studied.Among 156 patients examined in this study, 88 (56.41%) and 68 (43.59%) participants were male and female, respectively. The minimum and maximum ages of the infection were 4.5 months and 6 years, respectively. The mean age of the infected children was 17.94 months. Fever (94.24%) and splenomegaly (86.53%) were the most common symptoms of this disease among children. In addition, 49 (31.41%), 64 (41.02%), 18 (11.53%), 33 (21.15%), and 40 (25.64%) participants had leukopenia, hemoglobin count below 8, ESR above 100, ESR above 60, and platelets below 100,000, respectively. Moreover, 39 (25%) and 17 (10.89%) patients had high aspartate transaminase (AST) and alanine transaminase (ALT). Also, 96.2% of the participants responded to the treatment with glucantime. The rate of mortality in this study was 3.2%.Clinically, almost all children had fever and splenomegaly at the onset of the disease. In addition, hepatic involvement was observed in all cases of mortality, cases with a lack of initial response, and those in need of auxiliary medication. Hepatic involvement appears to be related to the prognosis of the disease. In our study, bone marrow

  3. Ulcerative penile Leishmaniasis in a child

    Directory of Open Access Journals (Sweden)

    Yavuz Yesilova

    2014-01-01

    Full Text Available Penile ulcers may be caused by several different agents. Rarely, cutaneous leishmaniasis may also be accompanied by penile ulcers. We report a five-year-old boy with who had an ulcer on the glans penis. Smears from the ulcer demonstrated amastigotes, biopsy showed histopathological features of leishmaniasis and Leishmania was grown in culture. Treatment with meglumine antimoniate injections led to improvement.

  4. Case study for a vaccine against leishmaniasis.

    Science.gov (United States)

    Alvar, Jorge; Croft, Simon L; Kaye, Paul; Khamesipour, Ali; Sundar, Shyam; Reed, Steven G

    2013-04-18

    Leishmaniasis in many ways offers a unique vaccine case study. Two reasons for this are that leishmaniasis is a disease complex caused by several different species of parasite that are highly related, thus raising the possibility of developing a single vaccine to protect against multiple diseases. Another reason is the demonstration that a leishmaniasis vaccine may be used therapeutically as well as prophylactically. Although there is no registered human leishmaniasis vaccine today, immunization approaches using live or killed organisms, as well as defined vaccine candidates, have demonstrated at least some degree of efficacy in humans to prevent and to treat some forms of leishmaniasis, and there is a vigorous pipeline of candidates in development. Current approaches include using individual or combined antigens of the parasite or of salivary gland extract of the parasites' insect vector, administered with or without formulation in adjuvant. Animal data obtained with several vaccine candidates are promising and some have been or will be entered into clinical testing in the near future. There is sufficient scientific and epidemiological justification to continue to invest in the development of vaccines against leishmaniasis.

  5. Epidemiology of human leishmaniasis in Greece, 1981-2011.

    Science.gov (United States)

    Gkolfinopoulou, K; Bitsolas, N; Patrinos, S; Veneti, L; Marka, A; Dougas, G; Pervanidou, D; Detsis, M; Triantafillou, E; Georgakopoulou, T; Billinis, C; Kremastinou, J; Hadjichristodoulou, C

    2013-07-18

    Leishmaniasis is endemic and mandatorily notifiable in Greece. Epidemiological surveillance data for leishmaniasis in Greece between 1981 and 2011 are presented. In 1998, the notification system began distinguishing between visceral and cutaneous leishmaniasis. The mean annual incidence of reported leishmaniasis cases between 1998 and 2011 was 0.36 per 100,000 population. Of a total 563 leishmaniasis cases reported after 1998, 523 (93%) were visceral leishmaniasis cases. Incidence of reported visceral leishmaniasis cases fluctuated during this period, generally decreasing after 2007, with a small re-increase in 2011. The mean annual incidence rate of reported visceral leishmaniasis cases was significantly higher in less than four year-olds (p islands. Between 1998 and 2011, Attica concentrated almost half of the reported visceral leishmaniasis cases, with incidence rates in western Attica and western Athens above 12.00 per 100,000 population. Compared to visceral leishmaniasis, cutaneous leishmaniasis had a rather sporadic distribution, with many prefectures appearing free of cases. From 2004, the notification also included risk factors and of 287 cases with known immune status, 44 (15%) were immunocompromised. Moreover having a dog at home was reported by 209 of 312 leishmaniasis cases (67%), whereas 229 of 307 cases (75%) reported the presence of stray dogs near their residence. Linking clinical surveillance data with laboratory data and improving collaboration with the veterinary public health sector are some of the future challenges for leishmaniasis surveillance in Greece.

  6. Therapeutic trial in experimental tegumentary leishmaniasis caused by Leishmania (Leishmania amazonensis. A comparative study between mefloquine and aminosidine Ensaio terapêutico na leishmaniose tegumentar experimental causada por Leishmania (Leishmania amazonensis. Um estudo comparativo entre mefloquina e aminosidine

    Directory of Open Access Journals (Sweden)

    Letícia Oba Galvão

    2000-08-01

    Full Text Available One hundred and eighty-two male inbred C57/BL/6 mice were infected with 3 x 106 Leishmania (Leishmania amazonensis promastigotes of the MHOM/BR/PH8 strain by means of a subcutaneous injection in the right ear. The animals were separated in three groups: 1 oral mefloquine hydrochloride treatment (16mg/kg/day/10 days, 2 intramuscular aminosidine (Paromomycin® treatment (20mg/kg/20 days and 3 control. Twenty six mice of each treated group were sacrificed, one at the end of treatment (nine weeks after inoculation, and one six weeks later (fifteen weeks after inoculation. Control Group animals were sacrificed at weeks six, nine and fifteen after inoculation. There was no significant difference between Group 1 (mefloquine and Group 3 (control subjects. Group 2 animals (aminosidine presented the smallest differences of all, both at the end of the treatment and six weeks later. The histopato-logical parameters have shown the following findings: a there was no significant difference between the mefloquine treated group and the control group; the group treated with aminosidine showed fewer of vacuolated macrophages than the control group, at week 9 (end of treatment. b both at the end of treatment and six weeks later, evaluation of tissue necrosis and tissue fibrosis revealed no differences between the treated groups. It was found that six weeks after the end of treatment, mice in the control group presented significantly more severe degrees of fibrosis than mice in the other groups. It can be concluded that mefloquine showed limited therapeutic effect in this experimental model, whereas aminosidine had a significant effect. Nevertheless, neither of them resulted in cure of the lesions.Foram utilizados 182 camundongos machos, isogênicos, da linhagem C57BL/6 inoculados na orelha direita com 3,0 x 10(6 formas promastigotas da cepa MHOM/BR/PH8 de Leishmania (Leishmania amazonensis. Os animais foram separados em três grupos: 1 52 animais tratados com

  7. Occupationally Acquired American Cutaneous Leishmaniasis

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    Maria Edileuza Felinto de Brito

    2012-01-01

    Full Text Available We report two occupationally acquired cases of American cutaneous leishmaniasis (ACL: one accidental laboratory autoinoculation by contaminated needlestick while handling an ACL lesion sample, and one acquired during field studies on bird biology. Polymerase chain reaction (PCR assays of patient lesions were positive for Leishmania, subgenus Viannia. One isolate was obtained by culture (from patient 2 biopsy samples and characterized as Leishmania (Viannia naiffi through an indirect immunofluorescence assay (IFA with species-specific monoclonal antibodies (mAbs and by multilocus enzyme electrophoresis (MLEE. Patients were successfully treated with N-methyl-glucamine. These two cases highlight the potential risks of laboratory and field work and the need to comply with strict biosafety procedures in daily routines. The swab collection method, coupled with PCR detection, has greatly improved ACL laboratory diagnosis.

  8. Occupationally Acquired American Cutaneous Leishmaniasis

    Science.gov (United States)

    Felinto de Brito, Maria Edileuza; Andrade, Maria Sandra; de Almeida, Éricka Lima; Medeiros, Ângela Cristina Rapela; Werkhäuser, Roberto Pereira; de Araújo, Ana Isabele Freitas; Brandão-Filho, Sinval Pinto; Paiva de Almeida, Alzira Maria; Gomes Rodrigues, Eduardo Henrique

    2012-01-01

    We report two occupationally acquired cases of American cutaneous leishmaniasis (ACL): one accidental laboratory autoinoculation by contaminated needlestick while handling an ACL lesion sample, and one acquired during field studies on bird biology. Polymerase chain reaction (PCR) assays of patient lesions were positive for Leishmania, subgenus Viannia. One isolate was obtained by culture (from patient 2 biopsy samples) and characterized as Leishmania (Viannia) naiffi through an indirect immunofluorescence assay (IFA) with species-specific monoclonal antibodies (mAbs) and by multilocus enzyme electrophoresis (MLEE). Patients were successfully treated with N-methyl-glucamine. These two cases highlight the potential risks of laboratory and field work and the need to comply with strict biosafety procedures in daily routines. The swab collection method, coupled with PCR detection, has greatly improved ACL laboratory diagnosis. PMID:23227369

  9. Leishmaniasis: vaccine candidates and perspectives.

    Science.gov (United States)

    Singh, Bhawana; Sundar, Shyam

    2012-06-06

    Leishmania is a protozoan parasite and a causative agent of the various clinical forms of leishmaniasis. High cost, resistance and toxic side effects of traditional drugs entail identification and development of therapeutic alternatives. The sound understanding of parasite biology is key for identifying novel drug targets, that can induce the cell mediated immunity (mainly CD4+ and CD8+ IFN-gamma mediated responses) polarized towards a Th1 response. These aspects are important in designing a new vaccine along with the consideration of the candidates with respect to their ability to raise memory response in order to improve the vaccine performance. This review is an effort to identify molecules according to their homology with the host and their ability to be used as potent vaccine candidates.

  10. Treatment Approaches for Cutaneous Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Sema Aytekin

    2009-06-01

    Full Text Available Cutaneous leishmaniasis (CL is a widespread tropical infection caused by numerous different species of Leishmania protozoa. In our country, CL is due frequently to L. major and L. tropica. Its clinical presentation is extremely diverse. Treatment of CL aims to prevent mucosal invasion, to accelerate the healing of skin lesions, and avoid disfiguring scar. Local and physical treatment modalities including topical paromomycin, cryotherapy, localized controlled heat, carbon dioxide laser therapy, or pentavalant antimonals can be effective against. Intralesional antimonals are still the drug of choice may patients. WHO recommends an injection of drug under edges of the lesions and the entire lesion until the surface has blanched. Parenteral antimonials are useful for large, persistent or recurrent lesions. Combinations with other drugs such as allopurinol, pentoxifylline must be used for antimony unresponsive lesions.

  11. Pharmacokinetic of antimony in mice with cutaneous Leishmaniasis

    Energy Technology Data Exchange (ETDEWEB)

    Borborema, Samanta E.T.; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil). Lab. de Biologia Molecular]. E-mails: samanta@usp.br; nnascime@ipen.br; Andrade Junior, Heitor F. de [Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil). Lab. de Biologia Molecular; Instituto de Medicina Tropical de Sao Paulo, Sao Paulo, SP (Brazil); E-mail: hfandrad@usp.br; Osso Junior, Joao A. [Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil). Centro de Radiofarmacia]. E-mail: jaosso@ipen.br

    2007-07-01

    Cutaneous Leishmaniasis (CL) remains a major world health problem, with about 1.5 million new cases each year. Caused by protozoa Leishmania, in South America, this infection can vary from a chronic skin ulcer, to an erosive mucosal disease and severe facial disfigurement. Pentavalent antimony (Sb{sup +5}) as sodium stibogluconate (Pentostam) or meglumine antimoniate (Glucantime) are main drugs for treating most forms of human leishmaniasis. For six decades, despite the recent developments, the effective therapy to cutaneous leishmaniasis has been based on long parenteral courses of such drugs, even though these are fairly costly, toxic and inconvenient to use, without adequate knowledge on their pharmacokinetics or mechanism of action. Pharmacokinetics studies could be based on bioactive traceable drugs, usually with radioactive isotopes, but antimony radioisotopes are unavailable commercially. Neutron irradiation is a powerful tool in the analysis of mineral content of samples, for antimony, there are at least two main isotopes that could be formed after neutron irradiation in nuclear reactor. The aim of the present study was to construct antimony salts with those radioisotopes to obtain tracers to compare the pharmacokinetic and the tissue distribution of neutron irradiated meglumine antimoniate in healthy and cutaneous leishmaniasis experimentally infected mice. Meglumine antimoniate, (Glucantime, Aventis, S.P, Brazil), was neutron irradiated inside the IEA-R1 nuclear reactor (IPEN/CNEN-SP), producing two radioisotopes {sup 122}Sb and {sup 124}Sb. Its biodistribution was verified in BALB/c mice experimentally infected with Leishmania (Leishmania) Amazonensis, which received a single intraperitoneal dose of the drug. At different times after injection, the tissues and blood were excised and activity measured in a NaI (Tl) scintillation counter. Compared with the healthy mice, experimentally infected mice had significantly lower maximum concentration of antimony

  12. Immunotherapy and Immunochemotherapy in Visceral Leishmaniasis: Promising Treatments for this Neglected Disease

    Science.gov (United States)

    Roatt, Bruno Mendes; Aguiar-Soares, Rodrigo Dian de Oliveira; Coura-Vital, Wendel; Ker, Henrique Gama; Moreira, Nádia das Dores; Vitoriano-Souza, Juliana; Giunchetti, Rodolfo Cordeiro; Carneiro, Cláudia Martins; Reis, Alexandre Barbosa

    2014-01-01

    Leishmaniasis has several clinical forms: self-healing or chronic cutaneous leishmaniasis or post-kala-azar dermal leishmaniasis; mucosal leishmaniasis; visceral leishmaniasis (VL), which is fatal if left untreated. The epidemiology and clinical features of VL vary greatly due to the interaction of multiple factors including parasite strains, vectors, host genetics, and the environment. Human immunodeficiency virus infection augments the severity of VL increasing the risk of developing active disease by 100–2320 times. An effective vaccine for humans is not yet available. Resistance to chemotherapy is a growing problem in many regions, and the costs associated with drug identification and development, make commercial production for leishmaniasis, unattractive. The toxicity of currently drugs, their long treatment course, and limited efficacy are significant concerns. For cutaneous disease, many studies have shown promising results with immunotherapy/immunochemotherapy, aimed to modulate and activate the immune response to obtain a therapeutic cure. Nowadays, the focus of many groups centers on treating canine VL by using vaccines and immunomodulators with or without chemotherapy. In human disease, the use of cytokines like interferon-γ associated with pentavalent antimonials demonstrated promising results in patients that did not respond to conventional treatment. In mice, immunomodulation based on monoclonal antibodies to remove endogenous immunosuppressive cytokines (interleukin-10) or block their receptors, antigen-pulsed syngeneic dendritic cells, or biological products like Pam3Cys (TLR ligand) has already been shown as a prospective treatment of the disease. This review addresses VL treatment, particularly immunotherapy and/or immunochemotherapy as an alternative to conventional drug treatment in experimental models, canine VL, and human disease. PMID:24982655

  13. Immunotherapy and immunochemotherapy in visceral leishmaniasis: promising treatments for this neglected disease

    Directory of Open Access Journals (Sweden)

    Bruno Mendes Roatt

    2014-06-01

    Full Text Available Leishmaniasis has several clinical forms: self-healing or chronic cutaneous leishmaniasis or post-kala-azar dermal leishmaniasis; mucosal leishmaniasis; and visceral leishmaniasis, which is fatal if left untreated. The epidemiology and clinical features of VL vary greatly due to the interaction of multiple factors including parasite strains, vectors, host genetics, and the environment. HIV infection, augments the severity of VL increasing the risk of developing active disease by 100 to 2320 times. An effective vaccine for humans is not yet available. Resistance to chemotherapy is a growing problem in many regions, and the costs associated with drug identification and development, make commercial production for leishmaniasis, unattractive. The toxicity of currently drugs, their long treatment course, and limited efficacy are significant concerns. For cutaneous disease, many studies have shown promising results with immunotherapy/immunochemotherapy, aimed to modulate and activate the immune response to obtain a therapeutic cure. Nowadays, the focus of many groups centers on treating canine VL by using vaccines and immunomodulators with or without chemotherapy. In human disease, the use of cytokines like Interferon-γ associated with pentavalent antimonials demonstrated promising results in patients that did not respond to conventional treatment. In mice, immunomodulation based on monoclonal antibodies to remove endogenous immunosuppressive cytokines (interleukin-10 or block their receptors, antigen-pulsed syngeneic dendritic cells, or biological products like Pam3Cys (TLR ligand has already been shown as a prospective treatment of the disease. This review addresses VL treatment, particularly immunotherapy and/or immunochemotherapy as an alternative to conventional drug treatment in experimental models, canine VL, and human disease.

  14. Experimental DC extraction of the thermal resistance of bipolar transistors taking into account the Early effect

    Science.gov (United States)

    d'Alessandro, Vincenzo

    2017-01-01

    This paper presents three methods to experimentally extract the thermal resistance of bipolar transistors taking into account the Early effect. The approaches are improved variants of recently-proposed techniques relying on common-base DC measurements. The accuracy is numerically verified by making use of a compact model calibrated on I-V characteristics of state-of-the-art SOG BJTs and SiGe:C HBTs.

  15. Leishmaniasis

    Science.gov (United States)

    ... culture Montenegro skin test (not approved in the United States) Skin biopsy and culture Other tests that may be done include: Complete blood count Serologic testing Serum albumin Serum immunoglobulin levels ...

  16. Leishmaniasis

    Science.gov (United States)

    ... be uncomfortable to sleep under such a closely woven bed net when it is hot. Treatment of ... College of the American Osteopathic Association. The AOCD now oversees 32 dermatology residency programs that are currently ...

  17. Leishmaniasis

    Science.gov (United States)

    ... Respond to Pre-Award Requests Manage Your Award Negotiation & Initial Award After Award ... New Trial Launched in West Africa to Evaluate Three Vaccination Strategies , April 6, 2017 Monoclonal Antibody Cures Marburg Infection ...

  18. Leishmaniasis

    Science.gov (United States)

    1993-01-01

    particle. Nevertheless, compared to amphotericin B deoxycholate, all three new formulations of lipidassociated amphotericin B do seem to be more...in Table 3. This table indicates that for both new formulations of amphotericin B, the site of increased tissue deposition is primarily the liver...1983. 54. Wlebe, V. J. and D’Gregorlo, M. W., Liposome encapsulated amphotericin B: a prom- ising new treatment for disseminated fungal infections

  19. Impact of leishmaniasis on public health

    Directory of Open Access Journals (Sweden)

    L. B Camargo

    2006-01-01

    Full Text Available Leishmaniasis is a parasitic zoonosis caused by protozoans of the genus Leishmania transmitted by insects known as phlebotomines, which are found in wild or urban environments. It affects domestic and wild animals and transmission to man happens by accident. The disease occurs in tropical and sub-tropical areas, mainly in Asia, Europe, Africa, and the Americas. There are two forms that affect man: American cutaneous leishmaniasis (ACL and American visceral leishmaniasis (AVL. The latter is caused by three species of Leishmania: Leishmania (Leishmania donovani, Leishmania (Leishmania infantum, and Leishmania (Leishmania chagasi, which are grouped in the Leishmania (Leishmania donovani complex. Wild reservoir hosts of L. chagasi known so far are foxes and marsupials. In domestic environment, dogs are the most important reservoir hosts and sources of infection to the vectors Lutzomyia longipalpis. Leishmaniasis is difficult to control, causing epidemic outbreaks, thus being an important public health problem. Due to lesions caused by the mucocutaneous type and the severity of those caused by the visceral type in humans, visceral leishmaniasis is one of the main public health concerns. This paper is part of the monograph presented at the end of the residency program in the field of Zoonosis and Public Health at the School of Veterinary Sciences and Animal Husbandry, São Paulo State University, UNESP, Botucatu, São Paulo State, Brazil, in 2005.

  20. Characterization of glycolytic enzymes--rAldolase and rEnolase of Leishmania donovani, identified as Th1 stimulatory proteins, for their immunogenicity and immunoprophylactic efficacies against experimental visceral leishmaniasis.

    Science.gov (United States)

    Gupta, Reema; Kumar, Vikash; Kushawaha, Pramod Kumar; Tripathi, Chandradev Pati; Joshi, Sumit; Sahasrabuddhe, Amogh Anant; Mitra, Kalyan; Sundar, Shyam; Siddiqi, Mohammad Imran; Dube, Anuradha

    2014-01-01

    Th1 immune responses play an important role in controlling Visceral Leishmaniasis (VL) hence, Leishmania proteins stimulating T-cell responses in host, are thought to be good vaccine targets. Search of such antigens eliciting cellular responses in Peripheral blood mononuclear cells (PBMCs) from cured/exposed/Leishmania patients and hamsters led to the identification of two enzymes of glycolytic pathway in the soluble lysate of a clinical isolate of Leishmania donovani--Enolase (LdEno) and aldolase (LdAld) as potential Th1 stimulatory proteins. The present study deals with the molecular and immunological characterizations of LdEno and LdAld. The successfully cloned and purified recombinant proteins displayed strong ability to proliferate lymphocytes of cured hamsters' along with significant nitric-oxide production and generation of Th1-type cytokines (IFN-γ and IL-12) from stimulated PBMCs of cured/endemic VL patients. Assessment of their prophylactic potentials revealed ∼ 90% decrease in parasitic burden in rLdEno vaccinated hamsters against Leishmania challenge, strongly supported by an increase in mRNA expression levels of iNOS, IFN-γ, TNF-α and IL-12 transcripts along with extreme down-regulation of TGF-β, IL-4 and IL-10. However, animals vaccinated with rLdAld showed comparatively lesser prophylactic efficacy (∼ 65%) with inferior immunological response. Further, with a possible implication in vaccine design against VL, identification of potential T-cell epitopes of both the proteins was done using computational approach. Additionally, in-silico 3-D modelling of the proteins was done in order to explore the possibility of exploiting them as potential drug targets. The comparative molecular and immunological characterizations strongly suggest rLdEno as potential vaccine candidate against VL and supports the notion of its being effective T-cell stimulatory protein.

  1. Molecular Epidemiology for Vector Research on Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Hirotomo Kato

    2010-03-01

    Full Text Available Leishmaniasis is a protozoan disease caused by the genus Leishmania transmitted by female phlebotomine sand flies. Surveillance of the prevalence of Leishmania and responsive vector species in endemic and surrounding areas is important for predicting the risk and expansion of the disease. Molecular biological methods are now widely applied to epidemiological studies of infectious diseases including leishmaniasis. These techniques are used to detect natural infections of sand fly vectors with Leishmania protozoa and are becoming powerful tools due to their sensitivity and specificity. Recently, genetic analyses have been performed on sand fly species and genotyping using PCR-RFLP has been applied to the sand fly taxonomy. In addition, a molecular mass screening method has been established that enables both sand fly species and natural leishmanial infections to be identified simultaneously in hundreds of sand flies with limited effort. This paper reviews recent advances in the study of sand flies, vectors of leishmaniasis, using molecular biological approaches.

  2. [Experimental studies on the early treatment of soft tissue explosion injury by vacuum-assisted closure].

    Science.gov (United States)

    Song, Peng; Xue, Yun; Ge, Bao-feng; Chen, Ke-ming; Zhao, Dong-hua; Han, Gui-qiu; Wang, Yong

    2011-07-01

    To investigate the effect on early treatment with vacuum-assisted closure(VAC) to wound healing of acute explosion injury in pigs, and provide a new way for early treatment of battle wounds. Eight healthy 3-month Landrace pigs of both sexes with the body mass of (50 +/- 5) kg were selected in the study. Sixteen battle wounds were made by explosion of same type detonator (pattern number: 660929F48840-55, included DDNP 0.3 g, RDX 0.7 g) in hibateral skin of buttock of 8 pigs, which were divided into experimental group and control group (pair wounds of left and right). The raw sufaces were thorough debrided at 3 h after exposure, according to the characteristics of treatment on the battlefield, experimental group was treated with VAC under the pressure of (-50 +/- 5) Kpa after debridement and sterilization and control group was treated with routine dry sterile gauze draping. Results of bacteriology (bacterial counts and the proportion of G+ bacteria) and pathology (HE stain and Masson stain) were detected at every wound before and after treatment. At the 3 days after treatment,the bacterial number in the experimental group was [(7.82 +/- 0.55) x 10(4) ] CFU/g, in control group was [(1.07 +/- 0.14) x 10(6)] CFU/g. There was significant difference between two groups. The proportion of G+ bacteria in experimental group was significantly increased. The raw surface in experimental group was clean with affluent and neoformative granulation tissue, blood vessels and collagen, necrotic tissue decreased obviously by pathological observation. VAC could reduce the quantity of bacteria, improve the proportion of G+ bacteria, and promote the formation of granulation tissue and the healing of wound. The VAC for the treatment of battle wounds has a positive effect.

  3. Selective dentate gyrus disruption causes memory impairment at the early stage of experimental multiple sclerosis.

    Science.gov (United States)

    Planche, Vincent; Panatier, Aude; Hiba, Bassem; Ducourneau, Eva-Gunnel; Raffard, Gerard; Dubourdieu, Nadège; Maitre, Marlène; Lesté-Lasserre, Thierry; Brochet, Bruno; Dousset, Vincent; Desmedt, Aline; Oliet, Stéphane H; Tourdias, Thomas

    2017-02-01

    Memory impairment is an early and disabling manifestation of multiple sclerosis whose anatomical and biological substrates are still poorly understood. We thus investigated whether memory impairment encountered at the early stage of the disease could be explained by a differential vulnerability of particular hippocampal subfields. By using experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, we identified that early memory impairment was associated with selective alteration of the dentate gyrus as pinpointed in vivo with diffusion-tensor-imaging (DTI). Neuromorphometric analyses and electrophysiological recordings confirmed dendritic degeneration, alteration in glutamatergic synaptic transmission and impaired long-term synaptic potentiation selectively in the dentate gyrus, but not in CA1, together with a more severe pattern of microglial activation in this subfield. Systemic injections of the microglial inhibitor minocycline prevented DTI, morphological, electrophysiological and behavioral impairments in EAE-mice. Furthermore, daily infusions of minocycline specifically within the dentate gyrus were sufficient to prevent memory impairment in EAE-mice while infusions of minocycline within CA1 were inefficient. We conclude that early memory impairment in EAE is due to a selective disruption of the dentate gyrus associated with microglia activation. These results open new pathophysiological, imaging, and therapeutic perspectives for memory impairment in multiple sclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Protective effects of bendazac lysine on early experimental diabetic nephropathy in rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-xing YIN; Yin-di ZHANG; Jian-ping SHEN; Hai-wei WU; Xiang ZHU; Li-min LI; Jun QIU; Shao-jun JIANG; Xiao-gang ZHENG

    2005-01-01

    Aim: To investigate the preventive and protective effects of bendazac lysine(BDL) on experimental early diabetic nephropathy (DN) rats. Methods: After an early DN model was induced by streptozotocin, rats were administered BDL at doses of 100, 200, and 400 mg/kg for 8 weeks. Blood glucose, microalbuminuria,kidney index, total antioxidative capacity, laminin, advanced glycation end products (AGE), aldose reductase (AR) activity, and the relative quantity of transforming growth factor β1 (TGF-β1) mRNA were measured by different methods.The ultrastructural morphology was observed by transmission electron microscope. Results: The physical behaviors of early DN rats were hypopraxia,cachexia, and polyuria, while those treated with high doses of BDL were vibrant and vigorous. For BDL-treated DN rats, when compared with vehicle-treated DN rats, the blood glucose level and the intensity of oxidative stress were ameliorated.Also, the microalbuminuria level, AGE either in serum or in renal, and AR activity were significantly reduced. Furthermore, the expression of TGF-β1 mRNA in the kidney cortex was declined and the thickness of glomerular base membrane was decreased significantly. The ultrastructure of glomerulus and mesangial matrix of BDL-treated DN rats were ameliorated. Conclusion: BDL has protective effects on several pharmacological targets in the progress of DN and is a potential drug for the prevention of early DN.

  5. Ceruloplasmin gene-deficient mice with experimental autoimmune encephalomyelitis show attenuated early disease evolution.

    Science.gov (United States)

    Gresle, Melissa M; Schulz, Katrin; Jonas, Anna; Perreau, Victoria M; Cipriani, Tania; Baxter, Alan G; Miranda-Hernandez, Socorro; Field, Judith; Jokubaitis, Vilija G; Cherny, Robert; Volitakis, Irene; David, Samuel; Kilpatrick, Trevor J; Butzkueven, Helmut

    2014-06-01

    We conducted a microarray study to identify genes that are differentially regulated in the spinal cords of mice with the inflammatory disease experimental autoimmune encephalomyelitis (EAE) relative to healthy mice. In total 181 genes with at least a two-fold increase in expression were identified, and most of these genes were associated with immune function. Unexpectedly, ceruloplasmin (Cp), a ferroxidase that converts toxic ferrous iron to its nontoxic ferric form and also promotes the efflux of iron from astrocytes in the CNS, was shown to be highly upregulated (13.2-fold increase) in EAE spinal cord. Expression of Cp protein is known to be increased in several neurological conditions, but the role of Cp regulation in CNS autoimmune disease is not known. To investigate this, we induced EAE in Cp gene knockout, heterozygous, and wild-type mice. Cp knockout mice were found to have slower disease evolution than wild-type mice (EAE days 13-17; P = 0.05). Interestingly, Cp knockout mice also exhibited a significant increase in the number of astrocytes with reactive morphology in early EAE compared with wild-type mice at the same stage of disease. CNS iron levels were not increased with EAE in these mice. Based on these observations, we propose that an increase in Cp expression could contribute to tissue damage in early EAE. In addition, endogenous CP either directly or indirectly inhibits astrocyte reactivity during early disease, which could also worsen early disease evolution.

  6. Early weight development of goats experimentally infected with Mycobacterium avium subsp. paratuberculosis.

    Directory of Open Access Journals (Sweden)

    Alyssa N Malone

    Full Text Available Johne's disease is an infectious chronic inflammatory bowel disease in ruminants. The key factor for the management of this disease is an early positive diagnosis. Unfortunately, most diagnostics detect animals with Johne's disease in the clinical stage with positive serology and/or positive fecal cultures. However, for effective management of the disease within herds, it is important to detect infected animals as early as possible. This might only be possible with the help of parameters not specific for Johne's disease but that give an early indication for chronic infections such as weight development. Here we report our findings on the development of total body weight and weight gain during the first six months of goats experimentally infected to induce Johne's disease. Twenty dairy goat kids age 2 to 5 days were included in this study. Goats were divided into two groups: a negative control group and a positive infected group. The weight was obtained weekly throughout the study. Goats of the positive group were infected at the age of seven weeks. We detected significant changes in weight gain and total body weight as early as one week after infection. Differences are significant throughout the six month time period. Weight as a non-specific parameter should be used to monitor infection especially in studies on Johne's disease using the goat model. Our study suggests that goats with Johne's disease have a reduced weight gain and reduced weight when compared with healthy goats of the same age.

  7. Intraretinal hemorrhage associated with visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Ricardo Evangelista Marrocos de Aragão

    2015-12-01

    Full Text Available ABSTRACT Visceral Leishmaniasis, also know as Kala-azar, is a parasitic tropical disease caused by protozoa of the genus Leishmania donovani. It is an endemic disease in many countries. It affects approximately 1,5 million people every year, and when associated with mal-nutrition and co-infection it may be fatal. Fever, hepatosplenomegaly, and pancytopenia is its typical clinical picture. Ocular manifestations of Kalaazar are relatively rare and can affect either anterior or posterior segment of the eye. We report a patient with kala-azar presenting intraretinal hemorrhages that regress completely after the successful treatment for visceral leishmaniasis.

  8. T-cell response in human leishmaniasis

    DEFF Research Database (Denmark)

    Kharazmi, A; Kemp, K; Ismail, A

    1999-01-01

    In the present communication we provide evidence for the existence of a Th1/Th2 dichotomy in the T-cell response to Leishmania antigens in human leishmaniasis. Our data suggest that the pattern of IL-4 and IFN-gamma response is polarised in these patients. Lymphocytes from individuals recovered......+. Furthermore, IL-10 plays an important role in the development of post kala azar dermal leishmaniasis (PKDL) from VL. The balance between the parasitic-specific T-cell response plays an important regulatory role in determining the outcome of Leishmania infections in humans....

  9. Leishmaniasis visceral: senderos que confluyen, se bifurcan

    OpenAIRE

    Oscar Daniel Salomón; Andrea Verónica Mastrángelo; María Soledad Santini; Silvina Ruvinsky; Tomás Orduna; Angel Sinagra; Concepción Luna; Adelina Riarte; Natalia Casas; Paola Amiotti

    2012-01-01

    La leishmaniasis visceral urbana es una zoonosis emergente en Argentina. En América es producida por Leishmania infantum, con el perro como reservorio principal e insectos flebotomíneos como vectores. En este artículo se presenta el conocimiento acumulado a partir de su emergencia y dispersión en el país, por los referentes del Programa Nacional de Leishmaniasis, en el diagnóstico clínico y de laboratorio, tratamiento, biología de vectores, manejo de reservorio, y el conflicto generado con la...

  10. Feline leishmaniasis in Jerusalem: serological investigation.

    Science.gov (United States)

    Nasereddin, Abedelmajeed; Salant, Harold; Abdeen, Ziad

    2008-12-20

    Visceral leishmaniasis caused by Leishmania infantum is an endemic zoonosis, present in the Mediterranean area and well recognized in Israel and Palestine for human and dog disease. A serological study using an ELISA technique was performed on 104 cats living in the Jerusalem area. Seroprevalence was 6.7% (7/104). Significant correlation between seropositive cat results and altitude > 2500 ft was observed (p = 0.02). This is the first serological survey of feline leishmaniasis (FL) in the Middle East. To prove cat involvement as a secondary host, more investigations are still needed. The study concludes that cat involvement in Leishmania host studies should not be ignored.

  11. EXPERIMENTAL MEASUREMENTS OF THE DEVELOPMENT OF SOCIAL INTELLIGENCE DURING PERSONALITY FORMATION IN EARLY ADOLESCENCE

    Directory of Open Access Journals (Sweden)

    Inga PLATON

    2017-05-01

    Full Text Available This article describes the results of experimental-formative study regarding the social intelligence development during early adolescence, which was performed to understand the human behavior in terms of adaptability and functionality, in the context of contemporary. Within the formative experiment, we intend to develop the level of social intelligence that determines the appropriateness understanding of the ability of behavioral and communicative knowledge in the process of formation and establishment of adolescent personality, which will consequently facilitate adolescents’ adaptation to the new conditions and requirements of interrelation and efficient operation during its maturity.

  12. Effect of Reinforcement on Early-Age Concrete Temperature Stress: Preliminary Experimental Investigation and Analytical Simulation

    Directory of Open Access Journals (Sweden)

    Jianda Xin

    2015-01-01

    Full Text Available For concrete under short-term loading, effect of reinforcement on concrete crack resistance capability is usually negligible; however, recent research results show that extension of this viewpoint to concrete under long-term loading (temperature variation may be unsuitable. In order to investigate this phenomenon, this paper presents the experimental and analytical results of early-age reinforced concrete temperature stress development under uniaxial restraint. The experiments were carried out on a temperature stress testing machine (TSTM. Experimental results show that the coupling of reinforcement and concrete creep behavior influenced the concrete temperature stress development, and nearly 16% of concrete stress was reduced in the current research. Moreover, the cracking time of reinforced concrete was also delayed. Finally, based on the principle of superposition, analytical simulations of effect of reinforcement on concrete temperature stress have been performed.

  13. Leishmaniasis in Yemen: a clinicoepidemiological study of leishmaniasis in central Yemen.

    Science.gov (United States)

    Al-Kamel, Mohamed A

    2016-08-01

    Leishmaniasis is a serious public health problem in Yemen. This study was designed to identify clinical and epidemiological features of leishmaniasis in Yemen. The study was conducted at the Regional Leishmaniasis Control Center in central Yemen. Data sourced from the medical records of 152 patients with confirmed active leishmaniasis, managed during April-August 2013, were analyzed. A total of 94.1% of patients were rural residents. Al Bayda was the most endemic governorate (59.9%). Children represented the group at highest risk (57.2%), followed by adult females (32.9%); together these groups accounted for 90.1% of all patients. Mucocutaneous leishmaniasis was the most prevalent form (49.3%), followed by cutaneous leishmaniasis (47.4%), and visceral leishmaniasis (3.3%). The wet ulcer was the most common type of lesion (49.7%) and the single lesion (69.4%) represented the most common presentation. All patients were ignorant of the nature of the disease, and 55.9% had a history of using "popular" treatments. Cutaneous, mucocutaneous, and visceral leishmaniases have significant endemicity in Yemen, especially in central areas. Al Bayda is the governorate with the highest endemicity, and rural children and women represent the populations at highest risk. Mucocutaneous leishmaniasis seems to be the most prevalent form and a single wet ulcer is the most common presentation. Infected refugees may represent new foci for imported Leishmania species. Ecology, geography, climate change, cultural gender- and age-specific duties, urban night activities, and use of popular treatments are among proven risk factors. © 2015 The International Society of Dermatology.

  14. Early cyclosporin A treatment retards axonal degeneration in an experimental peripheral nerve injection injury model

    Institute of Scientific and Technical Information of China (English)

    Ibrahim Erkutlu; Mehmet Alptekin; Sirma Geyik; Abidin Murat Geyik; Inan Gezgin; Abdulvahap Gk

    2015-01-01

    Injury to peripheral nerves during injections of therapeutic agents such as penicillin G potas-sium is common in developing countries. It has been shown that cyclosporin A, a powerful immunosuppressive agent, can retard Wallerian degeneration after peripheral nerve crush injury. However, few studies are reported on the effects of cyclosporin A on peripheral nerve drug in-jection injury. This study aimed to assess the time-dependent efifcacy of cyclosporine-A as an immunosuppressant therapy in an experimental rat nerve injection injury model established by penicillin G potassium injection. The rats were randomly divided into three groups based on the length of time after nerve injury induced by cyclosporine-A administration (30 minutes, 8 or 24 hours). The compound muscle action potentials were recorded pre-injury, early post-injury (within 1 hour) and 4 weeks after injury and compared statistically. Tissue samples were taken from each animal for histological analysis. Compared to the control group, a significant im-provement of the compound muscle action potential amplitude value was observed only when cyclosporine-A was administered within 30 minutes of the injection injury (P < 0.05); at 8 or 24 hours after cyclosporine-A administration, compound muscle action potential amplitude was not changed compared with the control group. Thus, early immunosuppressant drug therapy may be a good alternative neuroprotective therapy option in experimental nerve injection injury induced by penicillin G potassium injection.

  15. Modeling Mycobacterium tuberculosis early granuloma formation in experimental human lung tissue

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    Venkata Ramanarao Parasa

    2014-02-01

    Full Text Available The widely used animal models for tuberculosis (TB display fundamental differences from human TB. Therefore, a validated model that recapitulates human lung TB is attractive for TB research. Here, we describe a unique method for establishment of TB infection in an experimental human lung tissue model. The model is based on cell lines derived from human lungs and primary macrophages from peripheral blood, and displays characteristics of human lung tissue, including evenly integrated macrophages throughout the epithelium, production of extracellular matrix, stratified epithelia and mucus secretion. Establishment of experimental infection in the model tissue with Mycobacterium tuberculosis, the bacterium that causes TB, resulted in clustering of macrophages at the site of infection, reminiscent of early TB granuloma formation. We quantitated the extent of granuloma formation induced by different strains of mycobacteria and validated our model against findings in other TB models. We found that early granuloma formation is dependent on ESAT-6, which is secreted via the type VII secretion machinery of virulent mycobacteria. Our model, which can facilitate the discovery of the interactions between mycobacteria and host cells in a physiological environment, is the first lung tissue model described for TB.

  16. Glutamine Randomized Studies in Early Life: The Unsolved Riddle of Experimental and Clinical Studies

    Directory of Open Access Journals (Sweden)

    Efrossini Briassouli

    2012-01-01

    Full Text Available Glutamine may have benefits during immaturity or critical illness in early life but its effects on outcome end hardpoints are controversial. Our aim was to review randomized studies on glutamine supplementation in pups, infants, and children examining whether glutamine affects outcome. Experimental work has proposed various mechanisms of glutamine action but none of the randomized studies in early life showed any effect on mortality and only a few showed some effect on inflammatory response, organ function, and a trend for infection control. Although apparently safe in animal models (pups, premature infants, and critically ill children, glutamine supplementation does not reduce mortality or late onset sepsis, and its routine use cannot be recommended in these sensitive populations. Large prospectively stratified trials are needed to better define the crucial interrelations of “glutamine-heat shock proteins-stress response” in critical illness and to identify the specific subgroups of premature neonates and critically ill infants or children who may have a greater need for glutamine and who may eventually benefit from its supplementation. The methodological problems noted in the reviewed randomized experimental and clinical trials should be seriously considered in any future well-designed large blinded randomized controlled trial involving glutamine supplementation in critical illness.

  17. Glutamine randomized studies in early life: the unsolved riddle of experimental and clinical studies.

    Science.gov (United States)

    Briassouli, Efrossini; Briassoulis, George

    2012-01-01

    Glutamine may have benefits during immaturity or critical illness in early life but its effects on outcome end hardpoints are controversial. Our aim was to review randomized studies on glutamine supplementation in pups, infants, and children examining whether glutamine affects outcome. Experimental work has proposed various mechanisms of glutamine action but none of the randomized studies in early life showed any effect on mortality and only a few showed some effect on inflammatory response, organ function, and a trend for infection control. Although apparently safe in animal models (pups), premature infants, and critically ill children, glutamine supplementation does not reduce mortality or late onset sepsis, and its routine use cannot be recommended in these sensitive populations. Large prospectively stratified trials are needed to better define the crucial interrelations of "glutamine-heat shock proteins-stress response" in critical illness and to identify the specific subgroups of premature neonates and critically ill infants or children who may have a greater need for glutamine and who may eventually benefit from its supplementation. The methodological problems noted in the reviewed randomized experimental and clinical trials should be seriously considered in any future well-designed large blinded randomized controlled trial involving glutamine supplementation in critical illness.

  18. Early cyclosporin A treatment retards axonal degeneration in an experimental peripheral nerve injection injury model

    Directory of Open Access Journals (Sweden)

    Ibrahim Erkutlu

    2015-01-01

    Full Text Available Injury to peripheral nerves during injections of therapeutic agents such as penicillin G potassium is common in developing countries. It has been shown that cyclosporin A, a powerful immunosuppressive agent, can retard Wallerian degeneration after peripheral nerve crush injury. However, few studies are reported on the effects of cyclosporin A on peripheral nerve drug injection injury. This study aimed to assess the time-dependent efficacy of cyclosporine-A as an immunosuppressant therapy in an experimental rat nerve injection injury model established by penicillin G potassium injection. The rats were randomly divided into three groups based on the length of time after nerve injury induced by penicillin G potassium administration (30 minutes, 8 or 24 hours. The compound muscle action potentials were recorded pre-injury, early post-injury (within 1 hour and 4 weeks after injury and compared statistically. Tissue samples were taken from each animal for histological analysis. Compared to the control group, a significant improvement of the compound muscle action potential amplitude value was observed only when cyclosporine-A was administered within 30 minutes of the injection injury (P < 0.05; at 8 or 24 hours after cyclosporine-A administration, compound muscle action potential amplitude was not changed compared with the control group. Thus, early immunosuppressant drug therapy may be a good alternative neuroprotective therapy option in experimental nerve injection injury induced by penicillin G potassium injection.

  19. Sexual and vertical transmission of visceral leishmaniasis.

    Science.gov (United States)

    Turchetti, Andreia P; Souza, Tayse D; Paixão, Tatiane A; Santos, Renato L

    2014-04-15

    Visceral leishmaniasis (VL) is an important zoonosis caused by Leishmania infantum, which has in the domestic dog its principal vertebrate host. VL is usually transmitted by phlebotomine sand flies, however atypical routes of transmission have been described. In this review we discuss the the role of sexual and vertical transmissions, and their role in the maintenance of VL in canine populations.

  20. Leishmaniasis visceral: senderos que confluyen, se bifurcan

    Directory of Open Access Journals (Sweden)

    Oscar Daniel Salomón

    2012-01-01

    Full Text Available La leishmaniasis visceral urbana es una zoonosis emergente en Argentina. En América es producida por Leishmania infantum, con el perro como reservorio principal e insectos flebotomíneos como vectores. En este artículo se presenta el conocimiento acumulado a partir de su emergencia y dispersión en el país, por los referentes del Programa Nacional de Leishmaniasis, en el diagnóstico clínico y de laboratorio, tratamiento, biología de vectores, manejo de reservorio, y el conflicto generado con las acciones recomendadas en relación con los perros infectados. La detección temprana y el tratamiento precoz, con estrategias descentralizadas y horizontales, contribuirán a disminuir la morbimortalidad asociada a la leishmaniasis visceral. El control de su transmisión y dispersión requiere de un manejo ambiental integral y la tenencia responsable de perros. Se discuten los intereses y discursos en conflicto generados por la leishmaniasis visceral en el marco de la relación humano-perro, proponiendo la búsqueda de un discurso consensuado de riesgo.

  1. Social and Economic Burden of Human Leishmaniasis.

    Science.gov (United States)

    Okwor, Ifeoma; Uzonna, Jude

    2016-03-01

    Leishmaniasis continues to pose a major public health problem worldwide. With new epidemics occurring in endemic areas and the spread of the disease to previously free areas because of migration, tourism, and military activities, there is a great need for the development of an effective vaccine. Leishmaniasis is a disease of the poor, occurring mostly in remote rural villages with poor housing and little or no access to modern health-care facilities. In endemic areas, diagnosis of any form of leishmaniasis puts a huge financial strain on an already meagre financial resource at both the individual and community levels. Most often families need to sell their assets (land and livestock) or take loans from informal financial outfits with heavy interest rates to pay for the diagnosis and treatment of leishmaniasis. Here, we discuss the disease with special emphasis on its socioeconomic impact on the affected individual and community. In addition, we highlight the reasons why continued research aimed at developing an effective Leishmania vaccine is necessary.

  2. [Visceral leishmaniasis: not only a tropical disease].

    NARCIS (Netherlands)

    Cuperus, F.J.C.; Oosterwijk, P.R.; Vos, A.; Remijn, J.A.; Dobbenburgh, A. van; Bisseling, T.M.

    2013-01-01

    We report 2 cases of visceral leishmaniasis in Dutch patients after a stay in Greece and the former Yugoslavia, respectively. Patient A, a 69-year-old woman, was referred to our department with abdominal pain. Additional examinations were suggestive of chronic liver disease. After a liver biopsy, wh

  3. Mefloquine in the treatment of cutaneous leishmaniasis

    Directory of Open Access Journals (Sweden)

    Correia Dalmo

    1999-01-01

    Full Text Available Three cases of cutaneous leishmaniasis were treated orally with a mefloquine dose of 4.2mg/kg/day for six days in the Teaching Hospital of the Faculdade de Medicina do Triângulo Mineiro, Uberaba, MG, Brazil. Three weeks later a new series was repeated. No patient was cured.

  4. Hemophagocytic lymphohistiocytosis in children with visceral leishmaniasis.

    Science.gov (United States)

    Blázquez-Gamero, Daniel; Domínguez-Pinilla, Nerea; Chicharro, Carmen; Negreira, Sagrario; Galán, Pilar; Pérez-Gorricho, Beatriz; Calvo, Cristina; Prieto, Luis; De la Parte, María; Otheo, Enrique; Vivanco, Jose Luis; Ruiz-Contreras, Jesús

    2015-06-01

    Acquired hemophagocytic lymphohistiocitosis (HLH) syndrome can be a complication of visceral leishmaniasis (VL). A multicenter prospective study was conducted to determine the frequency of HLH syndrome in children with VL. Twenty-four children with VL were identified, and 10 (41%) developed HLH syndrome. VL should be ruled out in all children with HLH criteria living in or coming from endemic areas.

  5. [Visceral leishmaniasis: not only a tropical disease].

    NARCIS (Netherlands)

    Cuperus, F.J.C.; Oosterwijk, P.R.; Vos, A.; Remijn, J.A.; Dobbenburgh, A. van; Bisseling, T.M.

    2013-01-01

    We report 2 cases of visceral leishmaniasis in Dutch patients after a stay in Greece and the former Yugoslavia, respectively. Patient A, a 69-year-old woman, was referred to our department with abdominal pain. Additional examinations were suggestive of chronic liver disease. After a liver biopsy,

  6. Intra-abdominal hypertension--an experimental study of early effects on intra-abdominal metabolism.

    Science.gov (United States)

    Skoog, Per; Hörer, Tal; Nilsson, Kristofer F; Agren, Göran; Norgren, Lars; Jansson, Kjell

    2015-01-01

    The main aim of this experimental study was to investigate the early effects of intra-abdominal hypertension (IAH) on intra-abdominal metabolism and intestinal mucosal blood flow to evaluate whether metabolites can serve as markers for organ dysfunction during IAH. A swine model was used, and the animals were anesthetized and ventilated. Fifteen animals were subjected to IAH of 30 mm Hg for 4 hr by carbon dioxide insufflation. Seven animals served as controls. Hemodynamic data, arterial blood samples, and urine output were analyzed. Intraluminal laser Doppler flowmetry measured intestinal mucosal blood flow. Glucose, glycerol, lactate, and pyruvate concentrations and lactate-to-pyruvate (l/p) ratio were measured intraperitoneally and intramurally in the small intestine and rectum using microdialysis. IAH lowered the abdominal perfusion pressure by 12-18 mm Hg, reduced the intestinal mucosal blood flow by 45-63%, and decreased urine output by 50-80%. In the intervention group, glycerol concentrations increased at all locations, pyruvate concentrations decreased, and the l/p ratio increased intraperitoneally and intramurally in the small intestine. Control animals remained metabolically stable. Glucose and lactate concentrations were only slightly affected or unchanged in both the groups. IAH reduces intestinal blood flow and urinary output and causes early metabolic changes, indicating a discrete shift toward anaerobic metabolism. Intraperitoneal microdialysis may be useful in the early detection of impaired organ dysfunction with metabolic consequences in IAH and abdominal compartment syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. [Visceral leishmaniasis in an HIV positive patient].

    Science.gov (United States)

    Rossiere-Echazarreta, Natalia Lorena; Rodríguez-Campos, Esther Alicia; Morales-Esponda, Mario; Domínguez-Moreno, Rogelio; Cruz-Ortiz, Margarita; Rodríguez-Guzmán, Leoncio Miguel

    2013-01-01

    Introducción: la leishmaniasis visceral o kala azar es la presentación clínica más grave. En México, es una enfermedad rara por lo que su diagnóstico es tardío y generalmente culmina en la muerte del paciente. Se describe a un paciente VIH positivo que desarrolló leishmaniasis visceral. El objetivo es explicar sus características fisiopatológicas y de su tratamiento. Caso clínico: hombre de 45 años de edad, quien ingresó al hospital por cuadro crónico de diarrea sanguinolenta, distensión abdominal, dolor tipo cólico, pérdida de peso y fiebre. A la exploración física se identificó paciente febril con dolor en fosa iliaca derecha y hepatoesplenomegalia. La prueba ELISA para VIH resultó positiva y el ultrasonido hizo evidente una tumoración en ciego, por lo que se realizó biopsia. El informe histopatológico indicó que se trataba de leishmaniasis. Conclusiones: en los pacientes con leishmaniasis e infección por VIH existe pobre respuesta al tratamiento y la mortalidad es alta, causada por la menor respuesta inmune del huésped. En la literatura especializada se sugiere el tratamiento establecido para la infección por VIH combinado con miltefosine y anfotericina B liposomal para la leishmaniasis.

  8. Comparison of the efficacy and pharmacology of formulations of amphotericin B used in treatment of leishmaniasis.

    OpenAIRE

    Barratt, Gillian; Legrand, Philippe

    2005-01-01

    International audience; PURPOSE OF REVIEW: Several lipid-based formulations of the antifungal and antiparasitic drug amphotericin B are now available on the market. The purpose of this review is to assess their efficacy against leishmaniasis in both experimental and clinical settings, and to point out new developments in the formulation of this antibiotic. RECENT FINDINGS: The development of resistance to pentavalent antimony compounds has shifted the emphasis to amphotericin B for the treatm...

  9. Liposomal amphotericin B as a treatment for human leishmaniasis

    OpenAIRE

    Balasegaram, Manica; Ritmeijer, Koert; Lima, Maria Angeles; Burza, Sakib; Ortiz Genovese, Gemma; Milani, Barbara; Gaspani, Sara; Potet, Julien; Chappuis, François

    2012-01-01

    Abstract INTRODUCTION: Leishmaniasis is a parasitic disease transmitted by phlebotomine sandflies. Between 700,000 and 1.2 million cases of cutaneous leishmaniasis and between 200,000 and 400,000 cases of visceral leishmaniasis (VL), which is fatal if left untreated, occur annually worldwide. Liposomal amphotericin B (LAMB), alone or in combination with other drugs, has been extensively studied as VL treatment, but data on routine field use are limited, and several challenges to patients' acc...

  10. Lacrimal excretory system sequelae in patients treated for leishmaniasis

    OpenAIRE

    Hoyama,Erika; Schellini,Silvana Artioli; Stolf,Hamilton Ometo; Nakajima,Vitor

    2006-01-01

    Leishmaniasis infection may involve destruction of nasal tissues resulting in lacrimal drainage system alteration. PURPOSE: To evaluate the frequency of lacrimal excretory system sequelae in patients treated for leishmaniasis. METHODS: Forty-five leishmaniasis-treated patients (90 nasolacrimal ducts) were submitted to lacrimal excretory system evaluation. All were evaluated by Jones I test and when it was abnormal, dacryocystography and nasal endoscopy were performed. This situation occurred ...

  11. Music and the emergence of experimental science in early modern Europe

    Directory of Open Access Journals (Sweden)

    Penelope Gouk

    2012-04-01

    Full Text Available The seventeenth century witnessed major advances in physics and experimental science. This paper argues that while the role of new visual technologies (e.g. the microscope has been well studied, less attention has been paid to acoustic technologies in early modern natural philosophy. In particular, I attend to the relationship between making music, a specific form of organised sound mediated through instruments, and the production of new scientific knowledge. On the one hand, this relationship developed in the context of acoustics, a new discipline first mapped out by Francis Bacon. On the other hand, music’s relationship to natural philosophy was also more fundamental, since harmony was understood as an organising principle of the universe, the laws of musical strings providing a model for other forms of vibrative motion. I also show the importance of musical training for Galileo’s experiments and the significance of harmony for Isaac Newton and Robert Hooke.

  12. The role of tone sensation and musical stimuli in early experimental psychology.

    Science.gov (United States)

    Klempe, Sven Hroar

    2011-01-01

    In this article, the role of music in early experimental psychology is examined. Initially, the research of Wilhelm Wundt is considered, as tone sensation and musical elements appear as dominant factors in much of his work. It is hypothesized that this approach was motivated by an understanding of psychology that dates back to Christian Wolff 's focus on sensation in his empirical psychology of 1732. Wolff, however, had built his systematization of psychology on Gottfried Wilhelm von Leibniz, who combined perception with mathematics,and referred to music as the area in which sensation is united with numerical exactitude. Immanuel Kant refused to accept empirical psychology as a science, whereas Johann Friedrich Herbart reintroduced the scientific basis of empirical psychology by, among other things, referring to music.

  13. Drug resistance in Indian visceral leishmaniasis.

    Science.gov (United States)

    Sundar, S

    2001-11-01

    Throughout the world, pentavalent antimonial compounds (Sb(v)) have been the mainstay of antileishmanial therapy for more than 50 years. Sb(v) has been highly effective in the treatment of Indian visceral leishmaniasis (VL: kala-azar) at a low dose (10 mg/kg) for short durations (6-10 days). But in the early 1980s reports of its ineffectiveness emerged, and the dose of Sb(v) was eventually raised to 20 mg/kg for 30-40 days. This regimen cures most patients with VL except in India, where the proportion of patients unresponsive to Sb(v) has steadily increased. In hyperendemic districts of north Bihar, 50-65% patients fail treatment with Sb(v). Important reasons are rampant use of subtherapeutic doses, incomplete duration of treatment and substandard drugs. In vitro experiments have established emergence of Sb(v) resistant strains of Leishmania donovani, as isolates from unresponsive patients require 3-5 times more Sb(v) to reach similarly effectiveness against the parasite as in Sb(v) responders. Anthroponotic transmission in India has been an important factor in rapid increase in the Sb(v) refractoriness. Pentamidine was the first drug to be used and cured 99% of these refractory patients, but over time even with double the amount of initial doses, it cures only 69-78% patients now and its use has largely been abandoned in India. Despite several disadvantages, amphotericin B is the only drug available for use in these areas and should be used as first-line drug instead of Sb(v). The new oral antileishmanial drug miltefosine is likely to be the first-line drug in future. Unfortunately, development of newer antileishmanial drugs is rare; two promising drugs, aminosidine and sitamaquine, may be developed for use in the treatment of VL. Lipid associated amphotericin B has an excellent safety and efficacy profile, but remains out of reach for most patients because of its high cost.

  14. Bone marrow leishmaniasis: a review of situation in Thailand.

    Science.gov (United States)

    Wiwanitkit, Viroj

    2011-10-01

    Leishmaniasis is an important tropical vector-borne disease. This infection can be seen in tropical area and it is considered to be one of the most important vector-borne infections at present. The general situation of the leishmaniasis in Thailand is hereby reviewed. Although Thailand is a tropical country, the leishmaniasis is not endemic but sporadic. The imported cases are documented in some literatures. The serious form of leishmaniasis, the visceral leishmaniasis is also detectable in Thailand. Also, the author performed an in depth literature review of the reports of bone marrow leishmaniasis, a specific kind of visceral leishmaniasis, in Thailand in order to summarize the characteristics of this infection among Thai patients. According to this review, there have been at least 5 reports in the literature of 6 cases of bone marrow leishmaniasis in the Thai population, of which no case was lethal. Concerning the clinical manifestations, all except had prolonged fever with unknown origin. From physical examination, all had hepatosplenomegaly. The striking findings were active hemophagocytosis with increased proliferation of lymphoidplasma cell line in the bone marrow and amastigotes of Leishmania donovani was demonstrated. Considering the treatment, pantavalent antimony compound was used and the excellent improvement and complete recovery. Finally, the author also discussed on the importance of leishmaniasis in Thailand relating to the present globalization and good traveling system.

  15. Visceral leishmaniasis diagnosed in a patient with MALT lymphoma

    DEFF Research Database (Denmark)

    Kaae, Jeanette; Nørgaard, Peter; Himmelstrup, B

    2007-01-01

    We report a case of visceral leishmaniasis in a 66-year-old female with a history of MALT lymphoma in the gastrointestinal tract. The patient presented with major hemorrhage per rectum and perforation of the small intestine. Due to unexplained decreasing platelets, lymphoma bone marrow involvement...... was suspected and bone marrow examination was performed. Surprisingly, Leishman-Donovan bodies were detected. The low platelet count, caused by the combination of MALT lymphoma and visceral leishmaniasis, appears to have aggravated the symptoms of the intestinal lymphoma. Leishmaniasis should be suspected even...... among asymptomatic patients with immune compromising illnesses and a travel history to areas where leishmaniasis is endemic....

  16. A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Sebastian Weckbach

    2012-01-01

    Full Text Available Background. The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response. Methods. Male Wistar rats (250 g, 6–10/group were anesthetized and exposed to chest trauma (ChT, closed head injury (CHI, or Tib/Fib fracture including a soft tissue trauma (Fx + STT or to the following combination of injuries: (1 ChT; (2 ChT + Fx + STT; (3 ChT + CHI; (4 CHI; (5 polytrauma (PT = ChT + CHI + Fx + STT. Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of “key” inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL fluid samples. Results. Polytraumatized (PT rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. Conclusion. This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma.

  17. PPARα augments heart function and cardiac fatty acid oxidation in early experimental polymicrobial sepsis.

    Science.gov (United States)

    Standage, Stephen W; Bennion, Brock G; Knowles, Taft O; Ledee, Dolena R; Portman, Michael A; McGuire, John K; Liles, W Conrad; Olson, Aaron K

    2017-02-01

    Children with sepsis and multisystem organ failure have downregulated leukocyte gene expression of peroxisome proliferator-activated receptor-α (PPARα), a nuclear hormone receptor transcription factor that regulates inflammation and lipid metabolism. Mouse models of sepsis have likewise demonstrated that the absence of PPARα is associated with decreased survival and organ injury, specifically of the heart. Using a clinically relevant mouse model of early sepsis, we found that heart function increases in wild-type (WT) mice over the first 24 h of sepsis, but that mice lacking PPARα (Ppara(-/-)) cannot sustain the elevated heart function necessary to compensate for sepsis pathophysiology. Left ventricular shortening fraction, measured 24 h after initiation of sepsis by echocardiography, was higher in WT mice than in Ppara(-/-) mice. Ex vivo working heart studies demonstrated greater developed pressure, contractility, and aortic outflow in WT compared with Ppara(-/-) mice. Furthermore, cardiac fatty acid oxidation was increased in WT but not in Ppara(-/-) mice. Regulatory pathways controlling pyruvate incorporation into the citric acid cycle were inhibited by sepsis in both genotypes, but the regulatory state of enzymes controlling fatty acid oxidation appeared to be permissive in WT mice only. Mitochondrial ultrastructure was not altered in either genotype indicating that severe mitochondrial dysfunction is unlikely at this stage of sepsis. These data suggest that PPARα expression supports the hyperdynamic cardiac response early in the course of sepsis and that increased fatty acid oxidation may prevent morbidity and mortality. In contrast to previous studies in septic shock using experimental mouse models, we are the first to demonstrate that heart function increases early in sepsis with an associated augmentation of cardiac fatty acid oxidation. Absence of peroxisome proliferator-activated receptor-α (PPARα) results in reduced cardiac performance and fatty

  18. Presentation of two cases with periocular cutaneous leishmaniasis leading to ptosis

    Directory of Open Access Journals (Sweden)

    Enver Turan

    2013-03-01

    Full Text Available Leishmaniasis is a parasitic disease caused by flagellate protozoan of the genus Leishmania that are transmitted to humans through sand fly bites. The disease is a major health problem in our country as in many regions in the world. Although the disease is more often seen in children, it could affect any age group. The lesions usually occur on the exposed areas of the body such as face, neck, hands, arms and lower legs. Also, it could be seen in other areas of the body such as scalp, trunk, eyelids and, penis. Eyelid involvement is not common because, the eyelid is moving and so female phlebotomine sandfly probably could not freely touch down. We present two cases diagnosed cutaneous leishmaniasis on the basis of clinical and laboratory findings and we want to take attention if palpebral lesions are not treated early, they can lead to the dysfunction of palpebrae along with the cosmetic problems.

  19. Management of visceral leishmaniasis with therapeutic vaccines

    Directory of Open Access Journals (Sweden)

    Rawat K

    2016-09-01

    Full Text Available Keerti Rawat,1 Narendra K Yadav,1 Sumit Joshi,1 Sneha Ratnapriya,1 Amogh A Sahasrabuddhe,2 Anuradha Dube1 1Division of Parasitology, 2Division of Molecular and Structural Biology, Council of Scientific and Industrial Research-Central Drug Research Institute, Lucknow, India Abstract: Visceral leishmaniasis (VL, a phlebotomine-borne neglected tropical disease, is caused by parasites of the Leishmania donovani complex. While L. donovani infection is restricted to the Indian subcontinent and East Africa, where transmission is anthroponotic, Leishmania infantum occurs in Europe, North Africa, and parts of Latin America, where it is zoonotic in nature with dogs as reservoir hosts. Though the incidence of VL caused by L. infantum has been on the decline, L. donovani continues to cause epidemics periodically. By and large, a small proportion of L. donovani infection manifests as clinical disease but majority of the infected individuals remain asymptomatic and contribute to the perpetuation of the VL transmission cycle via the sand fly vector. This is one of the major stumbling blocks to World Health Organization initiatives to eliminate this deadly disease by 2020. These parasites reside within the host macrophages and impair the immune system of the infected individual, which ultimately results in marked immunosuppression. In the absence of any safe and effective vector control measure, attempts have been made to design therapeutic vaccine(s that can exclusively target infected macrophages. So far, two vaccines – a glycoprotein complex from L. donovani promastigote, fucose–mannose ligand with saponin, commercialized as Leishmune®, as well as a polyprotein vaccine formulation, Leish-111f + monophosphoryl lipid A plus squalene emulsion in combination with glucantime, have been successfully evaluated for their immunotherapeutic potential against canine VL. However, encouraging results obtained from several experimental trials so far against human VL

  20. Epistaxis in visceral leishmaniasis with hematological correlation.

    Science.gov (United States)

    Sigdel, B; Bhandary, S; Rijal, S

    2012-01-01

    Objective. To study the prevalence of epistaxis in visceral leismaniasis and its correlation with hematological profile. Methods. Out of 80 diagnosed cases of visceral leishmaniasis, 19 patients with epistaxis were included in the study. Diagnosis was made by Rk-39 from peripheral smear and LD bodies from bone marrow. Before starting anti-kala-azar treatment, nasal examination findings and hematological profile were noted. Study Design. Prospective cross-sectional hospital-based study. Results. Epistaxis was found in the age group of 7-66 years. Epistaxis was observed in 19 (23.8%) cases. One patient died because of epistaxis and neck hematoma. Conclusion. Epistaxis is a common ENT finding in endemic area of visceral leishmaniasis like our case.

  1. Epistaxis in Visceral Leishmaniasis with Hematological Correlation

    Directory of Open Access Journals (Sweden)

    B. Sigdel

    2012-01-01

    Full Text Available Objective. To study the prevalence of epistaxis in visceral leismaniasis and its correlation with hematological profile. Methods. Out of 80 diagnosed cases of visceral leishmaniasis, 19 patients with epistaxis were included in the study. Diagnosis was made by Rk-39 from peripheral smear and LD bodies from bone marrow. Before starting anti-kala-azar treatment, nasal examination findings and hematological profile were noted. Study Design. Prospective cross-sectional hospital-based study. Results. Epistaxis was found in the age group of 7–66 years. Epistaxis was observed in 19 (23.8% cases. One patient died because of epistaxis and neck hematoma. Conclusion. Epistaxis is a common ENT finding in endemic area of visceral leishmaniasis like our case.

  2. Intraretinal hemorrhage associated with visceral leishmaniasis

    OpenAIRE

    Ricardo Evangelista Marrocos de Aragão; Barreira,Ieda Maria A.; Leidiane Alexandre Pereira; Arrais,Barbara Lorena A.; Francisco Holanda Oliveira Neto; Everton Fernandes Vieira de Almeida; André Jucá Machado

    2015-01-01

    ABSTRACT Visceral Leishmaniasis, also know as Kala-azar, is a parasitic tropical disease caused by protozoa of the genus Leishmania donovani. It is an endemic disease in many countries. It affects approximately 1,5 million people every year, and when associated with mal-nutrition and co-infection it may be fatal. Fever, hepatosplenomegaly, and pancytopenia is its typical clinical picture. Ocular manifestations of Kalaazar are relatively rare and can affect either anterior or posterior segment...

  3. Epistaxis in Visceral Leishmaniasis with Hematological Correlation

    OpenAIRE

    Sigdel, B.; Bhandary, S.; Rijal, S

    2012-01-01

    Objective. To study the prevalence of epistaxis in visceral leismaniasis and its correlation with hematological profile. Methods. Out of 80 diagnosed cases of visceral leishmaniasis, 19 patients with epistaxis were included in the study. Diagnosis was made by Rk-39 from peripheral smear and LD bodies from bone marrow. Before starting anti-kala-azar treatment, nasal examination findings and hematological profile were noted. Study Design. Prospective cross-sectional hospital-based study. Result...

  4. Development of Cutaneous Leishmaniasis after Leishmania Skin Test

    Science.gov (United States)

    Machado, Paulo R.; Carvalho, Augusto M.; Machado, Gustavo U.; Dantas, Marina L.; Arruda, Sérgio

    2011-01-01

    Thirty-year-old female with a previous history of a cutaneous ulcer suspicious of leishmaniasis 20 years ago presented with a new complaint of a depressed papular lesion 8 × 7 mm in the right lower extremity. The lesion was of 10-day duration. Because early cutaneous leishmaniasis (CL) lesions may have a non-ulcerated appearance, a Leishmania skin test (LST) was performed on the forearm with a strong positive result (38 × 32 mm). After 8 days, the lesion in the leg, which was diagnosed as folliculitis, completely healed. However, a typical CL ulcer (26 × 24 mm) developed at the LST site. Histopathology of the new lesion did not identifiy parasites, but the findings were consistent with a diagnosis of CL. Further analysis identified amastigotes by immunohistochemical stain. Mononuclear cells harvested from the patient were stimulated with Leishmania antigen and showed high levels of production of both tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ): 2,943 pg/mL and 2,313 pg/mL, respectively. After 40 days of treatment with antimony and pentoxifylline, the ulcer resolved. The development of CL at the LST site suggests a strong Th1 immune response, and it is an in vivo documentation of the role of the host immune response in the pathology of CL. It teaches us that LST should be cautiously, if at all, used in patients with self-healing CL ulcers. PMID:22162702

  5. Development of cutaneous leishmaniasis after leishmania skin test.

    Science.gov (United States)

    Machado, Paulo R; Carvalho, Augusto M; Machado, Gustavo U; Dantas, Marina L; Arruda, Sérgio

    2011-01-01

    Thirty-year-old female with a previous history of a cutaneous ulcer suspicious of leishmaniasis 20 years ago presented with a new complaint of a depressed papular lesion 8 × 7 mm in the right lower extremity. The lesion was of 10-day duration. Because early cutaneous leishmaniasis (CL) lesions may have a non-ulcerated appearance, a Leishmania skin test (LST) was performed on the forearm with a strong positive result (38 × 32 mm). After 8 days, the lesion in the leg, which was diagnosed as folliculitis, completely healed. However, a typical CL ulcer (26 × 24 mm) developed at the LST site. Histopathology of the new lesion did not identifiy parasites, but the findings were consistent with a diagnosis of CL. Further analysis identified amastigotes by immunohistochemical stain. Mononuclear cells harvested from the patient were stimulated with Leishmania antigen and showed high levels of production of both tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ): 2,943 pg/mL and 2,313 pg/mL, respectively. After 40 days of treatment with antimony and pentoxifylline, the ulcer resolved. The development of CL at the LST site suggests a strong Th1 immune response, and it is an in vivo documentation of the role of the host immune response in the pathology of CL. It teaches us that LST should be cautiously, if at all, used in patients with self-healing CL ulcers.

  6. Cutaneous Leishmaniasis – Dermoscopic Findings And Cryotherapy

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    Dobrev Hristo P.

    2015-03-01

    Full Text Available We present a 60-year-old male patient who, three months after a holiday in Southern Greece, found a small ‘pimple’ on his back, which gradually got as big as a small walnut, the central part becoming ulcerated and scabby. Dermatological examination found an erythematous-to-livid nodular lesion on the right shoulder; it was 16 mm in diameter with central ulceration, covered with brownish crust which discharged pus-like secretion upon pressure. Microscope examination of Romanowsky-Giemsa stained lesion material detected amastigote forms of Leishmania tropica. The culture investigation and serological tests for leishmaniasis were negative. Dermoscopy of the lesion found the following features: erythema, hyperkeratosis, central ulceration covered with brownish crust, “yellow tears-like” structures and “white starburst-like” patterns, and various vascular structures (including dotted vessels, comma-shaped vessels, hairpin- and glomerular-like vessels. The patient was diagnosed with cutaneous leishmaniasis and underwent four cryotherapy sessions every other week with excellent therapeutic results - complete resolution of infiltrate with subsequent gentle hypopigmented scarring. In conclusion, dermoscopy is an easily accessible non-invasive method which can be useful for the diagnosis of cutaneous leishmaniasis. Cryotherapy is the treatment of choice for single skin lesions.

  7. American visceral Leishmaniasis: a case report

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    H. Langoni

    2005-09-01

    Full Text Available Visceral leishmaniasis is a zoonotic disease caused by parasites of the Leishmania genus. Dog is the major source of infection to man, especially in urban areas. The authors report a case of visceral leishmaniasis in a pit bull female dog from Bocaina, São Paulo, Brazil. The animal presented clinical signs compatible with leishmaniasis, including skin lesions in the body and partial damage of the external ears. The indirect fluorescent antibody test (IFAT demonstrated a titer of 1280, and promastigote forms of Leishmania sp were isolated by the culture of bone marrow puncture. Cytological analysis of the lymph node and smear of the bone marrow puncture revealed macrophages containing amastigote forms of Leishmania sp in their inner region. The test of Polymerase Chain Reaction (PCR utilized the primers LINR4 and LIN19, which amplify 720 base pairs, specific for Leishmania sp. The authors discuss the importance of techniques for a quick and precise diagnosis to this serious zoonosis with great impact in animal and public health.

  8. Recent advances in the diagnosis of leishmaniasis.

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    Singh S

    2003-01-01

    Full Text Available Leishmaniasis is a parasitic disease caused by a haemoflagellate Leishmania. There are more than 21 species causing human infection. The infection is transmitted to humans through the bites of female sandflies belonging to 30 species. The disease manifests mainly in 3 forms: the visceral, the cutaneous and the mucocutaneous leishmaniasis. The diagnosis of visceral form is conventionally made by the demonstration of amastigotes of the parasite in the aspirated fluid from the bone marrow, the spleen, and rarely from the lymph nodes, or the liver. The parasite demonstration and isolation rates are rather poor from cutaneous and mucocutaneous lesions due to low parasite load and high rate of culture contamination. Recently several recombinant proteins have been developed to accomplish accurate diagnosis. Recombinant kinesin protein of 39 kDa called rK 39 is the most promising of these molecules. The antigen used in various test formats has been proved highly sensitive and specific for visceral leishmaniasis. It is useful in the diagnosis of HIV-Leishmania co-infection and as a prognostic marker. Molecular techniques targeting various genes of the parasite have also been reported, the PCR being the most common molecular technique successfully used for diagnosis and for differentiation of species.

  9. Genetically modified organisms and visceral leishmaniasis.

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    Chhajer, Rudra; Ali, Nahid

    2014-01-01

    Vaccination is the most effective method of preventing infectious diseases. Since the eradication of small pox in 1976, many other potentially life compromising if not threatening diseases have been dealt with subsequently. This event was a major leap not only in the scientific world already burdened with many diseases but also in the mindset of the common man who became more receptive to novel treatment options. Among the many protozoan diseases, the leishmaniases have emerged as one of the largest parasite killers of the world, second only to malaria. There are three types of leishmaniasis namely cutaneous (CL), mucocutaneous (ML), and visceral (VL), caused by a group of more than 20 species of Leishmania parasites. Visceral leishmaniasis, also known as kala-azar is the most severe form and almost fatal if untreated. Since the first attempts at leishmanization, we have killed parasite vaccines, subunit protein, or DNA vaccines, and now we have live recombinant carrier vaccines and live attenuated parasite vaccines under various stages of development. Although some research has shown promising results, many more potential genes need to be evaluated as live attenuated vaccine candidates. This mini-review attempts to summarize the success and failures of genetically modified organisms used in vaccination against some of major parasitic diseases for their application in leishmaniasis.

  10. Canine cutaneous leishmaniasis by Leishmania (Viannia braziliensis in an agricultural settlement, endemic area for leishmaniasis

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    A.F. Brilhante

    2016-08-01

    Full Text Available ABSTRACT Cutaneous leishmaniasis has several species of Leishmania as agents, and a wide variety of wild and domestic animals as hosts and different species of phlebotomines as vectors. A case of cutaneous leishmaniasis in a dog coming from an agricultural settlement is described. This is the first report of parasitism in a dog by Le. (Viannia braziliensis in Mato Grosso do Sul State. Attention is called to the importance of including this protozoonosis in the differential diagnosis of dermopathies in dogs as also the need to assess the importance of the domestic dog as a possible reservoir of Le. braziliensis.

  11. In Vivo Changes in Lamina Cribrosa Microarchitecture and Optic Nerve Head Structure in Early Experimental Glaucoma.

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    Kevin M Ivers

    Full Text Available The lamina cribrosa likely plays an important role in retinal ganglion cell axon injury in glaucoma. We sought to (1 better understand optic nerve head (ONH structure and anterior lamina cribrosa surface (ALCS microarchitecture between fellow eyes of living, normal non-human primates and (2 characterize the time-course of in vivo structural changes in the ONH, ALCS microarchitecture, and retinal nerve fiber layer thickness (RNFLT in non-human primate eyes with early experimental glaucoma (EG. Spectral domain optical coherence tomography (SDOCT images of the ONH were acquired cross-sectionally in six bilaterally normal rhesus monkeys, and before and approximately every two weeks after inducing unilateral EG in seven rhesus monkeys. ONH parameters and RNFLT were quantified from segmented SDOCT images. Mean ALCS pore area, elongation and nearest neighbor distance (NND were quantified globally, in sectors and regionally from adaptive optics scanning laser ophthalmoscope images. In bilaterally normal monkeys, ONH parameters were similar between fellow eyes with few inter-eye differences in ALCS pore parameters. In EG monkeys, an increase in mean ALCS Depth (ALCSD was the first structural change measured in 6 of 7 EG eyes. A decrease in mean minimum rim width (MRW simultaneously accompanied this early change in 4 of 6 EG eyes and was the first structural change in the 7th EG eye. Mean ALCS pore parameters were among the first or second changes measured in 4 EG eyes. Mean ALCS pore area and NND increased in superotemporal and temporal sectors and in central and peripheral regions at the first time-point of change in ALCS pore geometry. RNFLT and/or mean ALCS radius of curvature were typically the last parameters to initially change. Survival analyses found mean ALCSD was the only parameter to significantly show an initial change prior to the first measured loss in RNFLT across EG eyes.

  12. Vaccines for leishmaniasis in the fore coming 25 years.

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    Palatnik-de-Sousa, Clarisa B

    2008-03-25

    Human vaccination against leishmaniasis using live Leishmania was used in Middle East and Russia (1941-1980). First-generation vaccines, composed by killed parasites induce low efficacies (54%) and were tested in humans and dogs Phase III trials in Asia and South America since 1940. Second-generation vaccines using live genetically modified parasites, or bacteria or viruses containing Leishmania genes, recombinant or native fractions are known since the 1990s. Due to the loss of PAMPs, the use of adjuvants increased vaccine efficacies of the purified antigens to 82%, in Phase III dog trials. Recombinant second-generation vaccines and third-generation DNA vaccines showed average values of parasite load reduction of 68% and 59% in laboratory animal models, respectively, but their success in field trials had not yet been reported. This review is focused on vaccine candidates that show any efficacy against leishmaniasis and that are already in different phase trials. A lot of interest though was generated in recent years, by the studies going on in experimental models. The promising candidates may find a place in the forth coming years. Among them most probably are the multiple-gene DNA vaccines that are stable and do not require cold-chain transportation. In the mean time, second-generation vaccines with native antigens and effective adjuvants are likely to be licensed and used in Public Health control programs in the fore coming 25 years. To date, only three vaccines have been licensed for use: one live vaccine for humans in Uzbekistan, one killed vaccine for human immunotherapy in Brazil and a second-generation vaccine for dog prophylaxis in Brazil.

  13. Effect of a xenograft on early bone formation in extraction sockets: an experimental study in dog.

    Science.gov (United States)

    Araújo, M; Linder, E; Lindhe, J

    2009-01-01

    The aim of this study was to study the effect on early bone formation resulting from the placement of a xenograft in the fresh extraction socket in dogs. Five beagle dogs were used. The distal roots of the third and fourth mandibular premolars were removed. In one quadrant, a graft consisting of Bio-Oss Collagen was placed in the fresh extraction wound, while the corresponding premolar sites in the contra-lateral jaw quadrant were left non-grafted. After 2 weeks of healing, the dogs were perfused with a fixative, the mandibles removed, the experimental sites dissected, demineralized, sectioned in the mesio-distal plane and stained in hematoxyline-eosine. The central portion of the non-grafted sockets was occupied by a provisional matrix comprised of densely packed connective tissue fibers and mesenchymal cells. Apical and lateral to the provisional matrix, newly formed woven bone was found to occupy most of the sockets. In the apical part of the grafted sockets, no particles of the xenograft could be observed but newly formed bone was present in this portion of the experimental site. In addition, limited numbers of woven bone trabeculae occurred along the lateral socket walls. The central and marginal segments of the grafted sockets, however, were occupied by a non-mineralized connective tissue that enclosed Bio-Oss particles that frequently were coated by multinucleated cells. The placement of Bio-Oss Collagen in the fresh extraction wound obviously delayed socket healing. Thus, after 2 weeks of tissue repair, only minute amounts of newly formed bone occurred in the apical and lateral borders of the grafted sockets, while large amounts of woven bone had formed in most parts of the non-grafted sites.

  14. CpG Type A Induction of an Early Protective Environment in Experimental Multiple Sclerosis

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    James Crooks

    2017-01-01

    Full Text Available Experimental autoimmune encephalomyelitis (EAE is an inflammatory, demyelinating disease of the CNS that mimics human multiple sclerosis (MS, and it is thought to be driven by Th1 and Th17 myelin-reactive cells. Although adaptive immunity is clearly pivotal in the pathogenesis of EAE, with an essential role of CD4+ T cells, little is known of early, innate responses in this experimental setting. CpG-rich oligodeoxynucleotides (ODNs, typically found in microbial genomes, are potent activators of TLR9 in plasmacytoid dendritic cells (pDCs. In this study, we compared the effects of two types of CpG, namely, type A and type B, on EAE. We found that treatment with CpG type A ODN (CpG-A, known to induce high amounts of IFN-α in pDCs, significantly reduced disease severity in EAE, relative to controls (12.63±1.86 versus 23.49±1.46, resp.; p=0.001. Treatment also delayed onset of neurological deficits and reduced spinal cord demyelination, while increasing the percentage of splenic regulatory (Foxp3+ CD4+ T cells. CpG-A likewise reduced the levels of IL-17 and IFN-γ in the CNS. Mechanistic insight into those events showed that CpG-A promoted a regulatory phenotype in pDCs. Moreover, adoptive transfer of pDCs isolated from CpG-A-treated mice inhibited CNS inflammation and induced disease remission in acute-phase EAE. Our data thus identify a link between TLR9 activation by specific ligands and the induction of tolerance via innate immunity mechanisms.

  15. Effects of child development accounts on early social-emotional development: an experimental test.

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    Huang, Jin; Sherraden, Michael; Kim, Youngmi; Clancy, Margaret

    2014-03-01

    This study, based on Oklahoma's statewide Child Development Accounts (CDAs) program, presents findings from the first experimental test of the hypothesis that creating lifelong savings accounts for children at birth promotes their long-term well-being. To examine the effects of CDAs, an innovative social policy to encourage lifelong saving and asset building for long-term development, on parent-reported social-emotional development in early childhood. A statewide randomized experiment of CDAs was conducted in 2008, drawing a probability sample of 7328 children from all infants born in two 3-month periods in Oklahoma (April 1 through June 30 and August 1 through October 31, 2007). After agreeing to participate in the experiment, caregivers of 2704 infants completed a baseline survey and were randomly assigned to treatment (n = 1358) and control groups (n = 1346). Approximately 84% of participants completed a follow-up survey in the spring of 2011. The intervention offered CDAs, built on the existing Oklahoma 529 college-savings plan, to treatment participants. It also provided additional financial incentives and information. The primary outcome-child social-emotional development-is measured by scores from a 17-item version of the Ages and Stages Questionnaire: Social-Emotional. Caregivers completed it in the 3-year follow-up survey. Lower scores indicate better functioning. The CDAs have positive effects on social-emotional development for children at approximately age 4 years. The nonweighted treatment-control difference is -1.56 (90% CI, -2.87 to -0.22; P = .06), but the weighted difference is nonsignificant. The effects appear to be greater for disadvantaged subsamples, such as low-income households (weighted mean difference, -2.21; 90% CI, -4.01 to -0.42; P = .04). As a complement to other early education and health interventions, CDAs may improve social-emotional development in early childhood. Their effects may be explained as a mediating

  16. Arsenic-induced phosphate limitation under experimental Early Proterozoic oceanic conditions

    Science.gov (United States)

    Chi Fru, Ernest; Hemmingsson, Christoffer; Holm, Mikaela; Chiu, Beverly; Iñiguez, Enrique

    2016-01-01

    Comparison of phosphorus concentrations associated with modern hydrothermal Fe(III)(oxyhydr)oxides and ancient Fe(III) oxide-rich iron formations, is used to estimate bioavailable Precambrian marine phosphorus (P) concentrations. This led to the proposition of a low dissolved P budget of ˜10-25% of present-day levels, before ˜1.9 billion years ago. Estimates incorporating ancient marine Si levels ≥ 0.67 mM instead suggested global dissolved P levels greater than today. Here we unite current experimental models that have considered NaCl solutions containing elevated dissolved Fe(II), Si, Ca2+ and Mg2+ ions in the incorporation of P in Precambrian marine Fe(III)(oxyhydr)oxides, in addition to arsenic as a hydrothermal proxy. We show that the coprecipitation of dissolved P and Fe(III)(oxyhydr)oxides from arsenic-rich marine waters produces an average P distribution coefficient of ˜0.072 (± 0.01) μM-1. This is comparable to the ˜ 0.07 μM-1 predicted for Fe(III)(oxyhydr)oxides in modern arsenic-rich, submarine hydrothermal settings, from which the lower Early Proterozoic dissolved marine P concentrations were predicted. As/P molar ratios below modern seawater ratios removed the negative feedback effect high Si impose on P scavenging by Fe(III)(oxyhydr)oxides. The binding of As(III) to Fe(III)(oxyhydr)oxides exhibits a lower competitive influence on P fixation. As(V) that likely became prominent in the surficially oxidized Early Proterozoic oceans induced dissolved P limitation because of preferential P sequestration at the expense of dissolved As(V) enrichment. The control of As on P scavenging by the precipitating Fe(III)(oxyhydr)oxides is strong regardless of common seawater cations (Mg2+ and Ca2+). The data suggest that the application of Si and Fe(III)(oxyhydr)oxides as an ancient seawater P proxy should consider chemical variability between depositional basins, taking into account the rather strong role hydrothermal arsenic has on the distribution of P in

  17. Bayesian geostatistical modeling of leishmaniasis incidence in Brazil.

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    Dimitrios-Alexios Karagiannis-Voules

    Full Text Available BACKGROUND: Leishmaniasis is endemic in 98 countries with an estimated 350 million people at risk and approximately 2 million cases annually. Brazil is one of the most severely affected countries. METHODOLOGY: We applied Bayesian geostatistical negative binomial models to analyze reported incidence data of cutaneous and visceral leishmaniasis in Brazil covering a 10-year period (2001-2010. Particular emphasis was placed on spatial and temporal patterns. The models were fitted using integrated nested Laplace approximations to perform fast approximate Bayesian inference. Bayesian variable selection was employed to determine the most important climatic, environmental, and socioeconomic predictors of cutaneous and visceral leishmaniasis. PRINCIPAL FINDINGS: For both types of leishmaniasis, precipitation and socioeconomic proxies were identified as important risk factors. The predicted number of cases in 2010 were 30,189 (standard deviation [SD]: 7,676 for cutaneous leishmaniasis and 4,889 (SD: 288 for visceral leishmaniasis. Our risk maps predicted the highest numbers of infected people in the states of Minas Gerais and Pará for visceral and cutaneous leishmaniasis, respectively. CONCLUSIONS/SIGNIFICANCE: Our spatially explicit, high-resolution incidence maps identified priority areas where leishmaniasis control efforts should be targeted with the ultimate goal to reduce disease incidence.

  18. [Landscape-epidemiological zoning of Turkmenistan by leishmaniasis].

    Science.gov (United States)

    Ponirovskiĭ, E N; Darchenkova, N N

    2008-01-01

    Based on the long-term (1961-1992) study of the parasitic systems of zoonotic cutaneous and visceral leishmaniasis in the context of a landscape, the authors made an epidemiological regional and typological zoning of Turkmenistan. Regional zoning identified 13 districts by zoonotic cutanenous leishmaniasis and 6 districts by visceral leishmaniasis. While typologically zoning according to the human hazard ofzoonotic cutaneous leishmaniasis, the authors divided the landscapes of Turkmenistan into 5 groups: hyperendemic; mesoendemic; hypoendemic; enzootic by cutaneous leishmaniasis, but not dangerous to man; nonenzootic by cutaneous leishmaniasis and not dangerous to man. While typologically zoning with respect with visceral leishmaniasis, the authors divided them into 4 groups: epidemically hazardous landscapes of sandy deserts and semisavanna low-mountain of South-Eastern Turkmenistan; epidemically hazardous landscapes of foothills, low-mountains, and middle mountains of Kopetdag; epidemiologically potentially dangerous landscapes of the piedmont plain of Kopetdag and the valley of the Murgab river; nonenzootic landscapes in terms of visceral leishmaniasis, and those not dangerous to man.

  19. Cutaneous leishmaniasis with lymphadenopathy due to Leishmania donovani

    NARCIS (Netherlands)

    W.R. Faber; J. Wonders; A.J. Jensema; E. Chocholova; P.A. Kager

    2009-01-01

    Summary We describe a case of cutaneous leishmaniasis with lymphadenopathy due to Leishmania donovani, which was successfully treated with oral miltefosine. Given the increased prevalence of travelling, patients presenting with lymph-node enlargement should have leishmaniasis included in the differe

  20. Systematic Review of Biomarkers To Monitor Therapeutic Response in Leishmaniasis

    NARCIS (Netherlands)

    Kip, Anke E; Balasegaram, Manica; Beijnen, Jos H; Schellens, Jan H M; de Vries, Peter J; Dorlo, Thomas P C

    2015-01-01

    Recently, there has been a renewed interest in the development of new drugs for the treatment of leishmaniasis. This has spurred the need for pharmacodynamic markers to monitor and compare therapies specifically for visceral leishmaniasis, in which the primary recrudescence of parasites is a particu

  1. Localised Leishmaniasis of Oral Mucosa: Report of an Unusual Clinicopathological Entity

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    Deepak Passi

    2014-01-01

    Full Text Available The term leishmaniasis comprises of a group of diseases caused by different species of a protozoan called Leishmania. There are three main clinical forms of leishmaniasis: visceral leishmaniasis, cutaneous leishmaniasis, and mucocutaneous leishmaniasis. Exclusive involvement of the mucosa is very rare. We present a case of mucosal leishmaniasis located in the oral cavity. The only manifestation of leishmaniasis disease in the described case was the appearance of an oral lesion. Treatment was provided in the form of antimoniates (oral miltefosine and systemic sodium stibogluconate. A review of literature is made on the subject.

  2. Experimental infection with Toxocara cati in pigs: migratory pattern and pathological response in early phase.

    Science.gov (United States)

    Sommerfelt, Irma Estela; Duchene, Adriana; Daprato, Betina; Lopez, Clara María; Cardillo, Natalia; Franco, Aníbal Juan

    2014-01-01

    Experimental inoculations of approximately 100,000 infective Toxocara cati larval eggs were done in twelve pigs. The T. cati eggs used for inoculation were collected from cat's feces. Another group of three pigs served as an uninfected control. Groups of infected pigs were euthanized at seven, 14, 21, and 28 days post-inoculation (dpi). Tissue samples were taken for digestion and histopathology changes in early phase. The number of larvae recovered from the lungs peaked at seven and 14 dpi and were also present at 21, and 28 dpi. Larvae of T. cati were present in the lymph nodes of the small and large intestine at seven, 14, and 28 dpi and at seven, 14, 21, and 28 dpi respectively. In other studied tissues, no larvae or less than one larva per gram was detected. The pathological response observed in the liver and lungs at seven and 14 dpi, showed white spots on the liver surface and areas of consolidation were observed in the lungs. The lungs showed an inflammatory reaction with larvae in center at 28 dpi. In the liver we observed periportal and perilobular hepatitis. The lymph nodes of the intestines displayed eosinophil lymphadenitis with reactive centers containing parasitic forms in some of them. The granulomatous reaction was not observed in any tissues. The role of the other examined tissues had less significance. The relevance of this parasite as an etiological agent that leads to disease in paratenic hosts is evident.

  3. EXPERIMENTAL INFECTION WITH Toxocara cati IN PIGS: MIGRATORY PATTERN AND PATHOLOGICAL RESPONSE IN EARLY PHASE

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    Irma Estela Sommerfelt

    2014-07-01

    Full Text Available Experimental inoculations of approximately 100,000 infective Toxocara cati larval eggs were done in twelve pigs. The T. cati eggs used for inoculation were collected from cat's feces. Another group of three pigs served as an uninfected control. Groups of infected pigs were euthanized at seven, 14, 21, and 28 days post-inoculation (dpi. Tissue samples were taken for digestion and histopathology changes in early phase. The number of larvae recovered from the lungs peaked at seven and 14 dpi and were also present at 21, and 28 dpi. Larvae of T. cati were present in the lymph nodes of the small and large intestine at seven, 14, and 28 dpi and at seven, 14, 21, and 28 dpi respectively. In other studied tissues, no larvae or less than one larva per gram was detected. The pathological response observed in the liver and lungs at seven and 14 dpi, showed white spots on the liver surface and areas of consolidation were observed in the lungs. The lungs showed an inflammatory reaction with larvae in center at 28 dpi. In the liver we observed periportal and perilobular hepatitis. The lymph nodes of the intestines displayed eosinophil lymphadenitis with reactive centers containing parasitic forms in some of them. The granulomatous reaction was not observed in any tissues. The role of the other examined tissues had less significance. The relevance of this parasite as an etiological agent that leads to disease in paratenic hosts is evident.

  4. Cathepsin L is crucial for the development of early experimental diabetic nephropathy.

    Science.gov (United States)

    Garsen, Marjolein; Rops, Angelique L W M M; Dijkman, Henry; Willemsen, Brigith; van Kuppevelt, Toin H; Russel, Frans G; Rabelink, Ton J; Berden, Jo H M; Reinheckel, Thomas; van der Vlag, Johan

    2016-11-01

    Proteinuria is one of the first clinical signs of diabetic nephropathy and an independent predictor for the progression to renal failure. Cathepsin L, a lysosomal cysteine protease, can be involved in the development of proteinuria by degradation of proteins that are important for normal podocyte architecture, such as the CD2-associated protein, synaptopodin, and dynamin. Cathepsin L also activates heparanase, a heparan sulfate endoglycosidase previously shown to be crucial for the development of diabetic nephropathy. Here, we evaluated the exact mode of action of cathepsin L in the development of proteinuria in streptozotocin-induced diabetes. Cathepsin L-deficient mice, in contrast to their wild-type littermates, failed to develop albuminuria, mesangial matrix expansion, tubulointerstitial fibrosis, and renal macrophage influx and showed a normal renal function. In wild-type mice the early development of albuminuria correlated with the activation of heparanase and loss of heparan sulfate expression, whereas loss of synaptopodin expression and podocyte damage occurred at a later stage. Thus, cathepsin L is causally involved in the pathogenesis of experimental diabetic nephropathy. Most likely, cathepsin L-dependent heparanase activation is crucial for the development of albuminuria and renal damage. Copyright © 2016 International Society of Nephrology. All rights reserved.

  5. Early and Persistent Dendritic Hypertrophy in the Basolateral Amygdala following Experimental Diffuse Traumatic Brain Injury.

    Science.gov (United States)

    Hoffman, Ann N; Paode, Pooja R; May, Hazel G; Ortiz, J Bryce; Kemmou, Salma; Lifshitz, Jonathan; Conrad, Cheryl D; Currier Thomas, Theresa

    2017-01-01

    In the pathophysiology of traumatic brain injury (TBI), the amygdala remains understudied, despite involvement in processing emotional and stressful stimuli associated with anxiety disorders, such as post-traumatic stress disorder (PTSD). Because the basolateral amygdala (BLA) integrates inputs from sensory and other limbic structures coordinating emotional learning and memory, injury-induced changes in circuitry may contribute to psychiatric sequelae of TBI. This study quantified temporal changes in dendritic complexity of BLA neurons after experimental diffuse TBI, modeled by midline fluid percussion injury. At post-injury days (PIDs) 1, 7, and 28, brain tissue from sham and brain-injured adult, male rats was processed for Golgi, glial fibrillary acidic protein (GFAP), or silver stain and analyzed to quantify BLA dendritic branch intersections, activated astrocytes, and regional neuropathology, respectively. Compared to sham, brain-injured rats at all PIDs showed enhanced dendritic branch intersections in both pyramidal and stellate BLA neuronal types, as evidenced by Sholl analysis. GFAP staining in the BLA was significantly increased at PID1 and 7 in comparison to sham. However, the BLA was relatively spared from neuropathology, demonstrated by an absence of argyrophilic accumulation over time, in contrast to other brain regions. These data suggest an early and persistent enhancement of dendritic complexity within the BLA after a single diffuse TBI. Increased dendritic complexity would alter information processing into and through the amygdala, contributing to emotional symptoms post-TBI, including PTSD.

  6. The Early Characterization of Irradiation Effects in Stainless Steels at the Experimental Breeder Reactor-II

    Energy Technology Data Exchange (ETDEWEB)

    D. L. Porter

    2008-01-01

    The new Global Nuclear Energy Partnership (GNEP) program is revitalizing interest in materials development for fast spectrum reactors. With this comes the need for new, high-performance materials that are resistant to property changes caused by radiation damage. In the 1970s there was an effort to monitor the irradiation effects on stainless steels used in fast reactor cores, largely because there were a number of ‘surprises’ where materials subjected to a high flux of fast neutrons incurred dimensional and property changes that had not been expected. In the U.S., this applied to the Experimental Breeder Reactor-II. Void swelling and irradiation-induced creep caused dimensional changes in the reactor components that shortened their useful lifetime and impacted reactor operations by creating fuel handling difficulties and reactivity anomalies. The surveillance programs and early experiments studied the simplest of austenitic stainless steels, such as Types 304 and 304L stainless steel, and led to some basic understanding of the links between these irradiation effects and microchemical changes within the steel caused by operational variables such as temperature, neutron flux and neutron fluence. Some of the observations helped to define later alloy development programs designed to produce alloys that were much more resistant to the effects of neutron irradiation.

  7. [Management of cutaneous leishmaniasis in adults and children].

    Science.gov (United States)

    Minodier, P; Noël, G; Blanc, P; Uters, M; Retornaz, K; Garnier, J M

    2005-11-01

    Cutaneous leishmaniasis can present a variety of clinical features and courses. The causative Leishmania species is an important prognostic factor in immunocompetent patients. Local treatment modalities including topical paromomycin, cryotherapy, localized controlled heat, carbon dioxide laser therapy, or intralesional meglumine antimoniate can be effective against Leishmania major or Leishmania tropica. Oral fluconazole may be a second-line treatment. Parenteral antimonials are useful for persistent or recurrent Old World leishmaniasis. For New World leishmaniasis, parenteral antimonials represent the first-line treatment in all forms except those caused by Leishmania guyanensis in which pentamidine is preferable. Liposomal amphotericin B appears to be effective for treatment of cutaneous leishmaniasis but further study will be needed. Results using oral Miltefosine are promising against Indian kala-azar (Leishmania donovani) but disappointing against South American leishmaniasis.

  8. Potential Challenges of Controlling Leishmaniasis in Sri Lanka at a Disease Outbreak

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    Tharaka Wijerathna

    2017-01-01

    Full Text Available The present works reviewed the existing information on leishmaniasis in Sri Lanka and in other countries, focusing on challenges of controlling leishmaniasis in the country, in an outbreak. Evidence from recent studies suggests that there is a possibility of a leishmaniasis outbreak in Sri Lanka in the near future. Difficulty of early diagnosis due to lack of awareness and unavailability or inadequacy of sensitive tests are two of the main challenges for effective case management. Furthermore, the absence of a proper drug for treatment and lack of knowledge about vector biology, distribution, taxonomy and bionomics, and reservoir hosts make the problem serious. The evident potential for visceralization in the cutaneous variant of L. donovani in Sri Lanka may also complicate the issue. Lack of knowledge among local communities also reduces the effectiveness of vector and reservoir host control programs. Immediate actions need to be taken in order to increase scientific knowledge about the disease and a higher effectiveness of the patient management and control programs must be achieved through increased awareness about the disease among general public and active participation of local community in control activities.

  9. Use of hematological parameters in evaluation of treatment efficacy in cutaneous leishmaniasis

    Directory of Open Access Journals (Sweden)

    Bilal Sula

    2015-12-01

    Full Text Available Objective: In the present study we investigated the role of hematological parameters, including neutrophil/lymphocyte ratio and platelet/lymphocyte ratio, mean platelet volume and platelet distribution width in the evaluation of treatment efficacy in adult patients diagnosed with cutaneous leishmaniasis. Methods: The study group included 45 adult patients diagnosed with cutaneous leishmaniasis and treated as inpatients in the dermatology clinic between 2011 and 2014. A group of 45 healthy adults served as a control group. Results: Pre- and post-treatment white blood cell count, neutrophils, and lymphocytes were significantly reduced among the patient group relative to the control group. Platelet distribution width, red cell distribution width, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were significantly elevated among the patients compared to the healthy subjects. Pre-treatment white blood cell, lymphocyte and platelet counts were significantly elevated compared to post-treatment counts among the patient cohort. Treatment was associated with reduced eosinophil count, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio relative to pre-treatment status. Conclusion: Routine hematological testing results such as platelet/lymphocyte ratio, white blood cell count, neutrophil count, red cell distribution width, platelet distribution width, and mean platelet volume may be clinically significant markers of the inflammatory state useful in the evaluation of early treatment efficacy among patients with cutaneous leishmaniasis. J Microbiol Infect Dis 2015;5(4: 167-172

  10. [Retrospective eco-epidemiology as a tool for the surveillance of leishmaniasis in Misiones, Argentina, 1920-2014].

    Science.gov (United States)

    Salomón, Oscar Daniel; Mastrángelo, Andrea Verónica; Santini, María Soledad; Liotta, Domingo Javier; Yadón, Zaida Estela

    2016-08-01

    A retrospective analytical method is presented, based on theoretical eco-epidemiology, applied on a subnational spatial scale. This method was used here to describe scenarios for the transmission of leishmaniasis in the Argentine province of Misiones- bordering Brazil and Paraguay-and formed the basis for recommendations for surveillance and control appropriate to the subnational scale. An exhaustive search of the literature on leishmaniasis in the province was carried out. Three scenarios for the transmission of cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) were found, corresponding to three periods: from 1920 to 1997, during which the transmission of CL distributed over time and space was confirmed; 1998 to 2005, during which there were focal outbreaks of CL; and 2006 to 2014, during which outbreaks were also reported and the geographical dispersion of VL was documented. To describe the risk scenarios and the anthropic processes that produce them, the results were summarized and integrated into the social, historical, and bio-ecological context of each period. Surveillance and control recommendations are based on the territory studied. They include establishing active surveillance to monitor possible rising trends in parasitic and vector circulation, conducting studies of any focal outbreak in order to confirm indigenous transmission and severity. Also, it should be a legal requirement for persons responsible for projects that alter the environment to adopt additional control measures, such as studies assessing transmission risk, risk mitigation, early detection, and timely case management.

  11. Open Experimentation on Phenomena of Chemical Reactions via the Learning Company Approach in Early Secondary Chemistry Education

    Science.gov (United States)

    Beck, Katharina; Witteck, Torsten; Eilks, Ingo

    2010-01-01

    Presented is a case study on the implementation of open and inquiry-type experimentation in early German secondary chemistry education. The teaching strategy discussed follows the learning company approach. Originally adopted from vocational education, the learning company method is used to redirect lab-oriented classroom practice towards a more…

  12. An Experimental Test of Parenting Practices as a Mediator of Early Childhood Physical Aggression

    Science.gov (United States)

    Brotman, Laurie Miller; O'Neal, Colleen R.; Huang, Keng-Yen; Gouley, Kathleen Kiely; Rosenfelt, Amanda; Shrout, Patrick E.

    2009-01-01

    Background: Parenting practices predict early childhood physical aggression. Preventive interventions that alter parenting practices and aggression during early childhood provide the opportunity to test causal models of early childhood psychopathology. Although there have been several informative preventive intervention studies that test mediation…

  13. Infectivity of seropositive dogs, showing different clinical forms of leishmaniasis, to Lutzomyia longipalpis phlebotomine sand flies.

    Science.gov (United States)

    Michalsky, Erika Monteiro; Rocha, Marília Fonseca; da Rocha Lima, Ana Cristina Vianna Mariano; França-Silva, João Carlos; Pires, Marize Quinhone; Oliveira, Fernanda Santos; Pacheco, Raquel Silva; dos Santos, Sara Lopes; Barata, Ricardo Andrade; Romanha, Alvaro José; Fortes-Dias, Consuelo Latorre; Dias, Edelberto Santos

    2007-06-20

    Visceral leishmaniasis (VL) is a growing zoonosis with an increasing number of new cases and a rapid geographical spreading of the disease. In the present study, a canine survey was carried out in the city of Montes Claros (320,000 inhabitants), an endemic area of American visceral leishmaniasis in the state of Minas Gerais, Brazil. A total number of 4795 dogs were examined by serology, which showed a rate of seropositivity of 5%. Isoenzymatic analysis confirmed Leishmania infantum chagasi as the local aetiological agent of CVL. Canine tissues were assayed for the presence of Leishmania parasite DNA using different techniques. The infectivity of asymptomatic, oligosymptomatic and symptomatic seropositive dogs was tested by xenodiagnosis using laboratory reared Lutzomyia longipalpis. Rates of infection of 5.4%, 5.1% and 28.4% were found for the phlebotomine sand flies that fed in asymptomatic, oligosymptomatic and symptomatic dogs, respectively. Our results indicate that, under experimental conditions, symptomatic dogs are about four times more infective to VL vectors than oligosymptomatic or asymptomatic animals. The lower infectivity rates of dogs displaying any of the last two clinical forms of leishmaniasis, however, must be taken into account in the epidemiology of CVL.

  14. Ecological interactions of visceral leishmaniasis in the state of Bahia, Brazil

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    Italo A Sherlock

    1996-12-01

    Full Text Available The laboratory and field observations summarized in this paper on visceral leishmaniasis ecology in the State of Bahia, Brazil are based on the author's observations over the past 35 years in a number of state's foci, public health records and literature citations. The disease is endemic with epidemic outbreaks occurring every ten years and its geographical distribution is expanding rapidly in the last years. Leishmania chagasi is the main ethiologic agent of the visceral leishmaniasis but Le. amazonensis s. lato was the only leishmania isolated by other authors from some visceral leishmaniasis human cases in the state. Lutzomyia longipalpis (with one or two spots on tergites III and IV and two sized different populations was epidemiologically incriminated as the main vector. It was found naturally infected with promastigotes, and it was infected with four species of leishmanias in the laboratory. Although the experimental transmission of Le. amazonensis by the bite of Lu. longipalpis to hamsters was performed, the author was not successful in transmitting Le. chagasi in the same way. The dog is the most important domestic source for infection of the vector, however it is not a primary reservoir. The opossum Didelphis albiventris was found naturally infected with Le. chagasi but its role as reservoir is unknown. Foxes and rodents were not found infected with leishmanias in Bahia.

  15. Prophylactic immunization against experimental leishmaniasis. III. Protection against fatal Leishmania tropica infection induced by irradiated promastigotes involves Lyt-1/sup +/2/sup -/ T cells that do not mediate cutaneous DTH

    Energy Technology Data Exchange (ETDEWEB)

    Liew, F.Y.; Howard, J.G.; Hale, C.

    1984-01-01

    Protective immunity against fatal L. tropica infection in genetically vulnerable BALB/c mice can be induced by prophylactic immunization with irradiated promastigotes even when heat-killed. Such immunity is adoptively transferable transiently into intact or durably into sub-lethally irradiated (200 or 550 rad) syngeneic recipients by splenic T but not B cells. The effector T cells are of the Lyt-1/sup +/2/sup -/ phenotype, devoid of demonstrable cytotoxic activity. The immune splenic T cell population expresses specific helper activity for antibody synthesis. A causal role for helper T cells in this capacity, however, seems unlikely, because it was shown that antibody does not determine the protective immunity against L. tropica. The immunized donors show no detectable cutaneous DTH or its early memory recall in response to live or killed promastigotes or a soluble L. tropica antigen preparation. Spleen, lymph node, and peritoneal exudate cells from protectively immunized donors similarly fail to transfer DTH locally or systemically. These cells also lack demonstrable suppressive activity against the expression or induction of DTH to L. tropica. Thus, protection against L. tropica induced by prophylactic i.v. immunization with irradiated promastigotes appears to be conferred by Lyt-1/sup +/2/sup -/ T cells that are distinguishable from T cells mediating either both DTH and T help, or cytotoxicity.

  16. Experimental Study and Early Clinical Application Of a Sutureless Aortic Bioprosthesis

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    Walter J. Gomes

    2015-10-01

    Full Text Available ABSTRACT INTRODUCTION: The conventional aortic valve replacement is the treatment of choice for symptomatic severe aortic stenosis. Transcatheter technique is a viable alternative with promising results for inoperable patients. Sutureless bioprostheses have shown benefits in high-risk patients, such as reduction of aortic clamping and cardiopulmonary bypass, decreasing risks and adverse effects. OBJECTIVE: The objective of this study was to experimentally evaluate the implantation of a novel balloon-expandable aortic valve with sutureless bioprosthesis in sheep and report the early clinical application. METHODS: The bioprosthesis is made of a metal frame and bovine pericardium leaflets, encapsulated in a catheter. The animals underwent left thoracotomy and the cardiopulmonary bypass was established. The sutureless bioprosthesis was deployed to the aortic valve, with 1/3 of the structure on the left ventricular face. Cardiopulmonary bypass, aortic clamping and deployment times were recorded. Echocardiograms were performed before, during and after the surgery. The bioprosthesis was initially implanted in an 85 year-old patient with aortic stenosis and high risk for conventional surgery, EuroSCORE 40 and multiple comorbidities. RESULTS: The sutureless bioprosthesis was rapidly deployed (50-170 seconds; average=95 seconds. The aortic clamping time ranged from 6-10 minutes, average of 7 minutes; the mean cardiopulmonary bypass time was 71 minutes. Bioprostheses were properly positioned without perivalvar leak. In the first operated patient the aortic clamp time was 39 minutes and the patient had good postoperative course. CONCLUSION: The deployment of the sutureless bioprosthesis was safe and effective, thereby representing a new alternative to conventional surgery or transcatheter in moderate- to high-risk patients with severe aortic stenosis.

  17. Early transient mild hypothermia attenuates neurological deficits and brain damage after experimental subarachnoid hemorrhage in rats.

    Science.gov (United States)

    Lilla, Nadine; Rinne, Christoph; Weiland, Judith; Linsenmann, Thomas; Ernestus, Ralf-Ingo; Westermaier, Thomas

    2017-09-23

    Metabolic exhaustion in ischemic tissue is the basis for a detrimental cascade of cell damage. In the acute stage of subarachnoid hemorrhage (SAH), a sequence of global and focal ischemia occurs, threatening brain tissue to undergo ischemic damage. This study was conducted to investigate whether early therapy with moderate hypothermia can offer neuroprotection after experimental SAH. 20 male Sprague-Dawley rats were subjected to SAH and treated by active cooling (34° C) or served as controls by continuous maintenance of normothermia (37.0° C). Mean arterial blood pressure (MABP), intracranial pressure (ICP) and local cerebral blood flow (CBF) over both hemispheres were continuously measured. Neurological assessment was performed 24 hours later. Hippocampal damage was assessed by hematoxylin and eosin and Caspase-3 staining. By a slight increase of MABP in the cooling phase and a significant reduction of ICP, hypothermia improved cerebral perfusion pressure (CPP) in the first 60 minutes after SAH. Accordingly, a trend to increased CBF was observed during this period. The rate of injured neurons was significantly reduced in hypothermia-treated animals compared to normothermic controls. The results of this series cannot finally answer whether this form of treatment permanently attenuates or only delays ischemic damage. In the latter case, slowing down metabolic exhaustion by hypothermia may still be a valuable treatment during this state of ischemic brain damage and prolong the therapeutic window for possible causal treatments of the acute perfusion deficit. Therefore, it may be useful as a first-tier therapy in suspected SAH. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Histological and ultrastructural changes induced by selenium in early experimental gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Yan-Ping Su; Jun-Min Tang; Yan Tang; Hui-Ying Gao

    2005-01-01

    AIM: To investigate the effect and significance of selenium in early experimental gastric carcinogenesis.METHODS: Weaning male Wistar rats were divided randomly into normal control group, experiment control group, low selenium (2 mg/L) group and high selenium (4 mg/L) group. Wistar rat gastric carcinogenesis was induced by N-methyl-N-nitro-N-nitroso guanidine (MNNG) (20 mg/kg) gavage daily for 10 d. Na2SeO3 was given by piped drinking 1 wk prior to MNNG gavage. The rats were killed at the 43rd wk. The surface characteristics of gastric mucosa were observed with naked eyes. Histopathologic changes of rat gastric mucosa were observed by HE staining and AB-PAS methods. The changes of cellular ultrastructure were observed under transmission electron microscope. Statistical analysis was carried out by SPSS.RESULTS: The incidence rate of gastric mucosa erosion,hemorrhage and intestinal metaplasia was 0, 45.5%,66.7%, and 92.9%, respectively (92.9% vs45.5%, P<0.05)in the normal control group, experiment control group,low selenium group, and high selenium group. Leiomyoma formed in the process of inducement of rat gastric carcinoma. Dietary Na2SeO3 (2 and 4 mg/L) slightly increased the incidence rate of leiomyoma (0, 23%, 46.6%, and 46.6%). gastric mucosa did not change in the course of rat gastric carcinogenesis. Dietary Na2SeO3 by pipe drinking could expand the intracellular secretory canaliculus of parietal cells and increase the number of endocrine cells and lysosomes.CONCLUSION: Dietary Na2SeO3 by pipe drinking aggravates gastric erosion, hemorrhage and promotes intestinal metaplasia of gastric mucosa. The mechanism may be related with the function of parietal cells.

  19. Early events following experimental infection with Peste-Des-Petits ruminants virus suggest immune cell targeting.

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    Robert A Pope

    Full Text Available Peste-des-petits ruminants virus (PPRV is a viral pathogen that causes a devastating plague of small ruminants. PPRV is an economically significant disease that continues to be a major obstacle to the development of sustainable agriculture across the developing world. The current understanding of PPRV pathogenesis has been heavily assumed from the closely related rinderpest virus (RPV and other morbillivirus infections alongside data derived from field outbreaks. There have been few studies reported that have focused on the pathogenesis of PPRV and very little is known about the processes underlying the early stages of infection. In the present study, 15 goats were challenged by the intranasal route with a virulent PPRV isolate, Côte d'Ivoire '89 (CI/89 and sacrificed at strategically defined time-points post infection to enable pre- and post-mortem sampling. This approach enabled precise monitoring of the progress and distribution of virus throughout the infection from the time of challenge, through peak viraemia and into a period of convalescence. Observations were then related to findings of previous field studies and experimental models of PPRV to develop a clinical scoring system for PPRV. Importantly, histopathological investigations demonstrated that the initial site for virus replication is not within the epithelial cells of the respiratory mucosa, as has been previously reported, but is within the tonsillar tissue and lymph nodes draining the site of inoculation. We propose that virus is taken up by immune cells within the respiratory mucosa which then transport virus to lymphoid tissues where primary virus replication occurs, and from where virus enters circulation. Based on these findings we propose a novel clinical scoring methodology for PPRV pathogenesis and suggest a fundamental shift away from the conventional model of PPRV pathogenesis.

  20. Early events following experimental infection with Peste-Des-Petits ruminants virus suggest immune cell targeting.

    Science.gov (United States)

    Pope, Robert A; Parida, Satya; Bailey, Dalan; Brownlie, Joe; Barrett, Thomas; Banyard, Ashley C

    2013-01-01

    Peste-des-petits ruminants virus (PPRV) is a viral pathogen that causes a devastating plague of small ruminants. PPRV is an economically significant disease that continues to be a major obstacle to the development of sustainable agriculture across the developing world. The current understanding of PPRV pathogenesis has been heavily assumed from the closely related rinderpest virus (RPV) and other morbillivirus infections alongside data derived from field outbreaks. There have been few studies reported that have focused on the pathogenesis of PPRV and very little is known about the processes underlying the early stages of infection. In the present study, 15 goats were challenged by the intranasal route with a virulent PPRV isolate, Côte d'Ivoire '89 (CI/89) and sacrificed at strategically defined time-points post infection to enable pre- and post-mortem sampling. This approach enabled precise monitoring of the progress and distribution of virus throughout the infection from the time of challenge, through peak viraemia and into a period of convalescence. Observations were then related to findings of previous field studies and experimental models of PPRV to develop a clinical scoring system for PPRV. Importantly, histopathological investigations demonstrated that the initial site for virus replication is not within the epithelial cells of the respiratory mucosa, as has been previously reported, but is within the tonsillar tissue and lymph nodes draining the site of inoculation. We propose that virus is taken up by immune cells within the respiratory mucosa which then transport virus to lymphoid tissues where primary virus replication occurs, and from where virus enters circulation. Based on these findings we propose a novel clinical scoring methodology for PPRV pathogenesis and suggest a fundamental shift away from the conventional model of PPRV pathogenesis.

  1. Early Events following Experimental Infection with Peste-Des-Petits Ruminants Virus Suggest Immune Cell Targeting

    Science.gov (United States)

    Pope, Robert A.; Parida, Satya; Bailey, Dalan; Brownlie, Joe; Barrett, Thomas; Banyard, Ashley C.

    2013-01-01

    Peste-des-petits ruminants virus (PPRV) is a viral pathogen that causes a devastating plague of small ruminants. PPRV is an economically significant disease that continues to be a major obstacle to the development of sustainable agriculture across the developing world. The current understanding of PPRV pathogenesis has been heavily assumed from the closely related rinderpest virus (RPV) and other morbillivirus infections alongside data derived from field outbreaks. There have been few studies reported that have focused on the pathogenesis of PPRV and very little is known about the processes underlying the early stages of infection. In the present study, 15 goats were challenged by the intranasal route with a virulent PPRV isolate, Côte d’Ivoire ’89 (CI/89) and sacrificed at strategically defined time-points post infection to enable pre- and post-mortem sampling. This approach enabled precise monitoring of the progress and distribution of virus throughout the infection from the time of challenge, through peak viraemia and into a period of convalescence. Observations were then related to findings of previous field studies and experimental models of PPRV to develop a clinical scoring system for PPRV. Importantly, histopathological investigations demonstrated that the initial site for virus replication is not within the epithelial cells of the respiratory mucosa, as has been previously reported, but is within the tonsillar tissue and lymph nodes draining the site of inoculation. We propose that virus is taken up by immune cells within the respiratory mucosa which then transport virus to lymphoid tissues where primary virus replication occurs, and from where virus enters circulation. Based on these findings we propose a novel clinical scoring methodology for PPRV pathogenesis and suggest a fundamental shift away from the conventional model of PPRV pathogenesis. PMID:23418464

  2. Distinguishing malaria and influenza: early clinical features in controlled human experimental infection studies.

    Science.gov (United States)

    Lillie, Patrick J; Duncan, Christopher J A; Sheehy, Susanne H; Meyer, Joel; O'Hara, Geraldine A; Gilbert, Sarah C; Hill, Adrian V S

    2012-07-01

    During the H1N1 influenza pandemic (pH1N1/09) diagnostic algorithms were developed to guide antiviral provision. However febrile illnesses are notoriously difficult to distinguish clinically. Recent evidence highlights the importance of incorporating travel history into diagnostic algorithms to prevent the catastrophic misdiagnosis of life-threatening infections such as malaria. We applied retrospectively the UK pH1N1/09 case definition to a unique cohort of healthy adult volunteers exposed to Plasmodium falciparum malaria or influenza to assess the predictive value of this case definition, and to explore the distinguishing clinical features of early phase infection with these pathogens under experimental conditions. For influenza exposure the positive predictive value of the pH1N1/09 case definition was only 0.38 (95% CI: 0.06-0.60), with a negative predictive value of 0.27 (95% CI: 0.02-0.51). Interestingly, 8/11 symptomatic malaria-infected adults would have been inappropriately classified with influenza by the pH1N1/09 case definition, while 5/8 symptomatic influenza-exposed volunteers would have been classified without influenza (P = 0.18 Fisher's exact). Cough (P = 0.005) and nasal symptoms (P = 0.001) were the only clinical features that distinguished influenza-exposed from malaria-exposed volunteers. An open mind regarding the clinical cause of undifferentiated febrile illness, particularly in the absence of upper respiratory tract symptoms, remains important even during influenza pandemic settings. These data support incorporating travel history into pandemic algorithms.

  3. Generation of growth arrested Leishmania amastigotes: a tool to develop live attenuated vaccine candidates against visceral leishmaniasis.

    Science.gov (United States)

    Selvapandiyan, Angamuthu; Dey, Ranadhir; Gannavaram, Sreenivas; Solanki, Sumit; Salotra, Poonam; Nakhasi, Hira L

    2014-06-30

    Visceral leishmaniasis (VL) is fatal if not treated and is prevalent widely in the tropical and sub-tropical regions of world. VL is caused by the protozoan parasite Leishmania donovani or Leishmania infantum. Although several second generation vaccines have been licensed to protect dogs against VL, there are no effective vaccines against human VL [1]. Since people cured of leishmaniasis develop lifelong protection, development of live attenuated Leishmania parasites as vaccines, which can have controlled infection, may be a close surrogate to leishmanization. This can be achieved by deletion of genes involved in the regulation of growth and/or virulence of the parasite. Such mutant parasites generally do not revert to virulence in animal models even under conditions of induced immune suppression due to complete deletion of the essential gene(s). In the Leishmania life cycle, the intracellular amastigote form is the virulent form and causes disease in the mammalian hosts. We developed centrin gene deleted L. donovani parasites that displayed attenuated growth only in the amastigote stage and were found safe and efficacious against virulent challenge in the experimental animal models. Thus, targeting genes differentially expressed in the amastigote stage would potentially attenuate only the amastigote stage and hence controlled infectivity may be effective in developing immunity. This review lays out the strategies for attenuation of the growth of the amastigote form of Leishmania for use as live vaccine against leishmaniasis, with a focus on visceral leishmaniasis.

  4. Arylimidamide-Azole Combinations against Leishmaniasis

    Science.gov (United States)

    2016-09-01

    for Cutaneous Leishmaniasis. Am J Trop Hyg 88(2), pp. 216-221, 2013. 2. Khraiwesh, Mozna, Leed, Susan, Roncal, Norma , Johnson, Jacob, Sciotti, Richard...L. donovoni IC50 (nM) L. guyanensis IC50 (nM) L. panamensis IC50 (nM) L. tropica IC50 (nM) L. mexicana IC50 (nM) DB2336 180 80...using an amastigote-macrophage assay against L. major, L. infantum, L. guyanensis, L. panamensis, L. tropica, and L. mexicana . All 3 compounds were

  5. Immune regulation during chronic visceral leishmaniasis.

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    Rebecca J Faleiro

    2014-07-01

    Full Text Available Visceral leishmaniasis is a chronic parasitic disease associated with severe immune dysfunction. Treatment options are limited to relatively toxic drugs, and there is no vaccine for humans available. Hence, there is an urgent need to better understand immune responses following infection with Leishmania species by studying animal models of disease and clinical samples from patients. Here, we review recent discoveries in these areas and highlight shortcomings in our knowledge that need to be addressed if better treatment options are to be developed and effective vaccines designed.

  6. Immune regulation during chronic visceral leishmaniasis.

    Science.gov (United States)

    Faleiro, Rebecca J; Kumar, Rajiv; Hafner, Louise M; Engwerda, Christian R

    2014-07-01

    Visceral leishmaniasis is a chronic parasitic disease associated with severe immune dysfunction. Treatment options are limited to relatively toxic drugs, and there is no vaccine for humans available. Hence, there is an urgent need to better understand immune responses following infection with Leishmania species by studying animal models of disease and clinical samples from patients. Here, we review recent discoveries in these areas and highlight shortcomings in our knowledge that need to be addressed if better treatment options are to be developed and effective vaccines designed.

  7. Prevalence of Cutaneous Leishmaniasis in Ramshir, Iran; an Epidemiological Study

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    Vazirianzadeh B.* PhD,

    2014-08-01

    Full Text Available Aims Cutaneous leishmaniasis is a prevalent parasitological disease with diverse clinical manifestations in Iran. Therefore, the present retrospective study carried out to describe the demographic features of cutaneous leishmaniasis in Ramshir, Iran. Materials & Methods This descriptive study was performed on 136 cutaneous leishmaniasis patients whose data were recorded in the Ramshir health center during 2006-9. Demographic information of patients including age, sex, habitat and sites of lesions, month and years of incidence were recorded. The data were analyzed by SPSS 16 software. Findings Totally 79 patients (58.1% resided in urban areas and the born to 9 years (49.3% was recognized as the most infected age group. Hands (41.2% had the highest rates of cutaneous leishmaniasis lesions followed by face (36.0% and foot (22.8%. The maximum number of cutaneous leishmaniasis lesions was reported in March. Conclusion As cutaneous leishmaniasis in Ramshir seemed to be an endemic rural type, the appropriate preventing measures regarding to the rural cutaneous leishmaniasis should be considered to decrease incidence of the disease in the region.

  8. Animal reservoirs for visceral leishmaniasis in densely populated urban areas.

    Science.gov (United States)

    Diniz, Soraia A; Silva, Fabiana L; Carvalho Neta, Alcina C; Bueno, Regina; Guerra, Rita M S N C; Abreu-Silva, Ana L; Santos, Renato L

    2008-02-01

    Leishmaniasis is a zoonotic disease of major public health and veterinary importance, affecting 88 countries with up to 2 million cases per year. This review emphasizes the animal reservoirs and spreading of visceral leishmaniasis (VL) in urban areas, particularly in two Brazilian metropolitan areas, namely São Luis and Belo Horizonte, where the disease has become endemic in the past few years. Urbanization of visceral leishmaniasis in Brazil during the last decades has created favorable epidemiological conditions for maintenance of the disease, with dense human populations sharing a tropical environment with abundant populations of the mammalian reservoir and the invertebrate vector, facilitating transmission of the disease.

  9. Causes of pediatric visceral leishmaniasis in southeastern iran.

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    Ali Hosseininasab

    2014-12-01

    Full Text Available Leishmania infantum is the most frequent cause of visceral leishmaniasis and L. tropica has been rarely linked to the disease in Iran. In this study, bone marrow aspirates were collected from 10 child patients, suspected with visceral leishmaniasis referred to the Pediatric Wards of Kerman Medical Hospitals, Kerman, Iran during 2002-2011. Leishmania species were identified by using nested PCR in all slides. The PCR samples from nine patients indicated L. infantum as principal causative agent of visceral leishmaniasis and one L.tropica as a minor species.

  10. Early

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    Kamel Abd Elaziz Mohamed

    2014-04-01

    Conclusion: Early PDT is recommended for patients who require prolonged tracheal intubation in the ICU as outcomes like the duration of mechanical ventilation length of ICU stay and hospital stay were significantly shorter in early tracheostomy.

  11. Genetically Modified Organisms and Visceral Leishmaniasis

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    NAHID eALI

    2014-05-01

    Full Text Available Vaccination is the most effective method of preventing infectious diseases. Since the eradication of small pox in 1976, many other potentially life compromising if not threatening diseases have been dealt with subsequently. This event was a major leap not only in the scientific world already burdened with many diseases but also in the mindset of the common man who became more receptive to novel treatment options. Among the many protozoan diseases, the leishmaniases have emerged as one of the largest parasite killers of the world, second only to malaria. There are three types of leishmaniases namely cutaneous (CL, mucocutaneous (ML and visceral (VL, caused by a group of more than 20 species of Leishmania parasites. Visceral leishmaniasis, also known as kala-azar is the most severe form and almost fatal if untreated. Since the first attempts at leishmanization, we have killed parasite vaccines, subunit protein or DNA vaccines, and now we have live recombinant carrier vaccines and live attenuated parasite vaccines under various stages of development. Although some research has shown promising results, many more potential genes need to be evaluated as live attenuated vaccine candidates. This mini-review attempts to summarize the success and failures of genetically modified organisms used in vaccination against some of major parasitic diseases for their application in leishmaniasis.

  12. Natural Products: Insights into Leishmaniasis Inflammatory Response

    Science.gov (United States)

    Rodrigues, Igor A.; Mazotto, Ana Maria; Cardoso, Verônica; Alves, Renan L.; Amaral, Ana Claudia F.; Silva, Jefferson Rocha de Andrade; Pinheiro, Anderson S.; Vermelho, Alane B.

    2015-01-01

    Leishmaniasis is a vector-borne disease that affects several populations worldwide, against which there are no vaccines available and the chemotherapy is highly toxic. Depending on the species causing the infection, the disease is characterized by commitment of tissues, including the skin, mucous membranes, and internal organs. Despite the relevance of host inflammatory mediators on parasite burden control, Leishmania and host immune cells interaction may generate an exacerbated proinflammatory response that plays an important role in the development of leishmaniasis clinical manifestations. Plant-derived natural products have been recognized as bioactive agents with several properties, including anti-protozoal and anti-inflammatory activities. The present review focuses on the antileishmanial activity of plant-derived natural products that are able to modulate the inflammatory response in vitro and in vivo. The capability of crude extracts and some isolated substances in promoting an anti-inflammatory response during Leishmania infection may be used as part of an effective strategy to fight the disease. PMID:26538837

  13. ANIMAL MODELS FOR THE STUDY OF LEISHMANIASIS IMMUNOLOGY

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    Elsy Nalleli Loria-Cervera

    2014-01-01

    Full Text Available Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail are being infected, and different numbers (“low” 1×102 and “high” 1×106 of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease.

  14. A canine leishmaniasis pilot survey in an emerging focus of visceral leishmaniasis: Posadas (Misiones, Argentina

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    Deschutter Jorge

    2010-12-01

    Full Text Available Abstract Background An increasing number of reports are calling our attention to the worldwide spread of leishmaniasis. The urbanization of zoonotic visceral leishmaniasis (VL has been observed in different South American countries, due to changes in demographic and ecological factors. In May 2006, VL was detected for the first time in the city of Posadas (Misiones, Argentina. This event encouraged us to conduct a clinical and parasitological pilot survey on domestic dogs from Posadas to identify their potential role as reservoirs for the disease. Methods One hundred and ten dogs from the city of Posadas were included in the study. They were selected based on convenience and availability. All dogs underwent clinical examination. Symptomatology related to canine leishmaniasis was recorded, and peripheral blood and lymph node aspirates were collected. Anti-Leishmania antibodies were detected using rK39-immunocromatographic tests and IFAT. Parasite detection was based on peripheral blood and lymph node aspirate PCR targeting the SSUrRNA gene. Molecular typing was addressed by DNA sequence analysis of the PCR products obtained by SSUrRNA and ITS-1 PCR. Results According to clinical examination, 69.1% (76/110 of the dogs presented symptoms compatible with canine leishmaniasis. Serological analyses were positive for 43.6% (48/110 of the dogs and parasite DNA was detected in 47.3% (52/110. A total of 63 dogs (57.3% were positive by serology and/or PCR. Molecular typing identified Leishmania infantum (syn. Leishmania chagasi as the causative agent. Conclusions This work confirms recent findings which revealed the presence of Lutzomyia longipalpis, the vector of L. infantum in this area of South America. This new VL focus could be well established, and further work is needed to ascertain its magnitude and to prevent further human VL cases.

  15. Post-kala-azar dermal leishmaniasis associated with AIDS

    Directory of Open Access Journals (Sweden)

    Bittencourt Achiléa

    2003-01-01

    Full Text Available Post-kala-azar dermal leishmaniasis (PKDL is rarely reported in South America. In spite of the fact that there are many reports about the association of visceral leishmaniasis and AIDS, PKDL is very uncommon in HIV-positive patients, and so far only four cases have been documented in the literature. We present another case with unusual clinicopathological aspects. The patient, a 28-year-old male, from Salvador, Bahia (an endemic area presented with clinical manifestations of visceral leishmaniasis three years after the diagnosis of AIDS. During treatment for visceral leishmaniasis he developed disseminated miliary papules. Microscopically, the skin biopsy showed a "saw-tooth" pattern with a lichenoid mononuclear infiltrate simulating lichen planus. The histopathological diagnosis was achieved through the finding of amastigotes. The authors discuss the clinicopathological aspects of this case based on a review of the specific literature.

  16. Post-kala-azar dermal leishmaniasis associated with AIDS

    Directory of Open Access Journals (Sweden)

    Bittencourt Achiléa

    2002-01-01

    Full Text Available Post-kala-azar dermal leishmaniasis (PKDL is rarely reported in South America. In spite of the fact that there are many reports about the association of visceral leishmaniasis and AIDS, PKDL is very uncommon in HIV-positive patients, and so far only four cases have been documented in the literature. We present another case with unusual clinicopathological aspects. The patient, a 28-year-old male, from Salvador, Bahia (an endemic area presented with clinical manifestations of visceral leishmaniasis three years after the diagnosis of AIDS. During treatment for visceral leishmaniasis he developed disseminated miliary papules. Microscopically, the skin biopsy showed a "saw-tooth" pattern with a lichenoid mononuclear infiltrate simulating lichen planus. The histopathological diagnosis was achieved through the finding of amastigotes. The authors discuss the clinicopathological aspects of this case based on a review of the specific literature.

  17. First generation leishmaniasis vaccines: a review of field efficacy trials.

    Science.gov (United States)

    Noazin, Sassan; Modabber, Farrokh; Khamesipour, Ali; Smith, Peter G; Moulton, Lawrence H; Nasseri, Kiumarss; Sharifi, Iraj; Khalil, Eltahir A G; Bernal, Ivan Dario Velez; Antunes, Carlos M F; Kieny, Marie Paule; Tanner, Marcel

    2008-12-09

    First generation candidate vaccines against leishmaniasis, prepared using inactivated whole parasites as their main ingredient, were considered as promising because of their relative ease of production and low cost. These vaccines have been the subject of many investigations over several decades and are the only leishmaniasis vaccine candidates which have undergone phase 3 clinical trial evaluation. Although the studies demonstrated the safety of the vaccines and several studies showed reasonable immunogenicity and some indication of protection, an efficacious prophylactic vaccine is yet to be identified. Despite this overall failure, these trials contributed significantly to increasing knowledge on human leishmaniasis immunology. To provide a collective view, this review discusses the methods and findings of field efficacy trials of first generation leishmaniasis vaccine clinical trials conducted in the Old and New Worlds.

  18. Cutaneous leishmaniasis in germfree, gnotobiotic, and conventional mice

    Directory of Open Access Journals (Sweden)

    Enio Cardillo Vieira

    1987-12-01

    Full Text Available Cutaneous leishmaniasis was much more severe in conventional than in gnotobiotic mice as revealed by macro and microscopic examination. An inoculum of Leishmania mexicana amazonensis was used.

  19. Breaking the Cycle of Deprivation: An Experimental Evaluation of an Early Childhood Intervention

    OpenAIRE

    Doyle, O.

    2012-01-01

    Barrington Lecture read before the Society, 18 April 2012 Deprivation early in life has multiple long term consequences for both the individual and society. An increasing body of evidence finds that targeted, early interventions aimed at at-risk children and their families can reduce socioeconomic inequalities in children?s skills and capabilities. This paper describes a randomised control trial (RCT) evaluation of a five-year preventative programme which aims to improve the school readine...

  20. FLI1 polymorphism affects susceptibility to cutaneous leishmaniasis in Brazil

    OpenAIRE

    Castellucci, L; Jamieson, SE; Miller, EN; de Almeida, LF; J. Oliveira; Magalhães, A.; Guimarães, LH; LESSA, M.; E. Lago; Jesus,AR de; Carvalho, EM; Blackwell, JM

    2011-01-01

    Mapping murine genes controlling cutaneous leishmaniasis (CL) identified Fli1 as a candidate influencing resistance to L. major and enhanced wound healing. We examine FLI1 as a gene controlling CL and mucosal leishmaniasis (ML) caused by L. braziliensis in humans. Intron 1 single nucleotide polymorphisms tagging promoter and enhancer elements were analysed in 168 nuclear families (250 CL; 87 ML cases) and replicated in 157 families (402 CL; 39 ML cases). Robust case-pseudocontrol logistic reg...

  1. RENAL HISTOPATHOLOGICAL FINDINGS IN DOGS WITH VISCERAL LEISHMANIASIS

    OpenAIRE

    Rosangela Silva Rigo; Cristiano Marcelo Espínola Carvalho; Michael Robin Honer; Gisele Braziliano de Andrade; Iandara Shetter Silva; Leonardo Rigo; Helen Rezende Figueiredo; Wanessa Teixeira Gomes Barreto

    2013-01-01

    Visceral leishmaniasis affects various organs including the kidneys; which can lead to renal failure and death. In order to verify this renal involvement, material was evaluated from 100 dogs naturally infected and with serological diagnosis of canine visceral leishmaniasis (CVL). Inflammatory changes were present in 25.3% of the tubules, in 67.0% of interstitium and in 52.0% of glomeruli. There was no significant difference (p > 0.05) between the presence of glomerulonephritis in symptomatic...

  2. Ancient Leishmaniasis in a Highland Desert of Northern Chile

    OpenAIRE

    Maria Antonietta Costa; Carney Matheson; Lucia Iachetta; Agustín Llagostera; Otto Appenzeller

    2009-01-01

    BACKGROUND: Leishmaniasis is an infectious disease endemic today in many areas of South America. METHODOLOGY: We discovered morphologic and molecular evidence of ancient infections in 4 female skulls in the archaeological cemetery of Coyo Oriente, in the desert of San Pedro de Atacama, Northern Chile. The boney facial lesions visible in the skulls could have been caused by a number of chronic infections including chronic Leishmaniasis. This diagnosis was confirmed using PCR-sequenced analyses...

  3. Epidemiological surveillance of Leishmaniasis in Montenegro, 1992-2013

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    Medenica Sanja

    2015-01-01

    Full Text Available Introduction. The diseases caused by Leishmania are spread worldwide and represent a significant public health problem. Objective. The aim of this study was to present the results of epidemiological surveillance of leishmaniasis in humans in Montenegro in the period from 1992 to 2013. Methods. The study was planned and realized as a descriptive epidemiological study. The sample included patients of leishmaniasis in Montenegro in the period from 1992 to 2013. The health and demographic data were collected from medical records. The disease was microbiologically proven in the patients. For statistical analysis the χ2-test was used, which examined the significance of the incidence rate. Results. During this period, 66 cases of leishmaniasis were identified (40 men and 26 women aged 0 to 62 (mean 15.61±16.76 years. A visceral form of the disease was diagnosed in 65 (98% patients, and one patient was diagnosed with cutaneous leishmaniasis. The average incidence rate for the abovementioned period is 0.48 per 100,000 inhabitants. The highest average incidence rate was identified in patients up to seven years of age (3.50 per 100,000 inhabitants. The highest average incidence rates of leishmaniasis were identified in the coastal region of Montenegro, while seasonal distribution indicates that the disease occurs throughout the year with predominance in late spring and summer. Conclusion. The research has shown that Montenegro is among the countries with low incidence of leishmaniasis. Nevertheless, because of leishmaniasis re-emergence in the entire Mediterranean Basin, a comprehensive research of ecological and epidemiological characteristics of leishmaniasis, including better monitoring and notification system, is required.

  4. Epidemiology of visceral leishmaniasis in Georgia.

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    Giorgi Babuadze

    2014-03-01

    Full Text Available This study investigated the transmission and prevalence of Leishmania parasite infection of humans in two foci of Visceral Leishmaniasis (VL in Georgia, the well known focus in Tbilisi in the East, and in Kutaisi, a new focus in the West of the country. The seroprevalence of canine leishmaniasis was investigated in order to understand the zoonotic transmission. Blood samples of 1575 dogs (stray and pet and 77 wild canids were tested for VL by Kalazar Detect rK39 rapid diagnostic tests. Three districts were investigated in Tbilisi and one in Kutaisi. The highest proportions of seropositive pet dogs were present in District #2 (28.1%, 82/292 and District #1 (26.9%, 24/89 in Tbilisi, compared to 17.3% (26/150 of pet dogs in Kutaisi. The percentage of seropositive stray dogs was also twice as high in Tbilisi (16.1%, n = 670 than in Kutaisi (8%, n = 50; only 2/58 wild animals screened were seropositive (2. 6%. A total of 873 Phlebotomine sand flies were collected, with 5 different species identified in Tbilisi and 3 species in Kutaisi; 2.3% of the females were positive for Leishmania parasites. The Leishmanin Skin Test (LST was performed on 981 human subjects in VL foci in urban areas in Tbilisi and Kutaisi. A particularly high prevalence of LST positives was observed in Tbilisi District #1 (22.2%, 37.5% and 19.5% for ages 5-9, 15-24 and 25-59, respectively; lower prevalence was observed in Kutaisi (0%, 3.2% and 5.2%, respectively; P<0.05. This study shows that Tbilisi is an active focus for leishmaniasis and that the infection prevalence is very high in dogs and in humans. Although exposure is as yet not as high in Kutaisi, this is a new VL focus. The overall situation in the country is alarming and new control measures are urgently needed.

  5. Miltefosine for Old World cutaneous leishmaniasis: An experimental ...

    African Journals Online (AJOL)

    Maha M. Eissa

    2012-06-21

    Jun 21, 2012 ... a Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt ..... Table 1 Effect of miltefosine on the mean footpad thickness of infected ..... ferase in Madin-Darby canine kidney cells.

  6. Testing Experimental Compounds against American Cutaneous and Mucocutaneous Leishmaniasis

    Science.gov (United States)

    1982-06-01

    neither of thiese imida - zoles shows promise for further development. They will not be tested further. C. Combination Chemotherapy Three types of...From 1980 - 1982, five 8-aminoquinolines, two imida - zoles, and the antimalarial primaquine phosphate were tested for efficacy as antileishmanial agents

  7. Testing Experimental Compounds against Leishmaniasis in Laboratory Animal Model Systems

    Science.gov (United States)

    1988-04-01

    available in recombinant form (eg. rIFN-gamma, rGM-CSF), and have been previously evaluated in the treatment of humans (88,98,135). The mode of action...diseases and useful for molecular 0 biological studies. DNA viruses have been found in Amoeba (30), double stranded RNA viruses have been found in Giardia ...viruses have been found in Amoeba (1), double stranded RNA viruses have been found in Giardia (2) and Trichomonas (3) and circular DNAs have been

  8. Status of vaccine research and development of vaccines for leishmaniasis.

    Science.gov (United States)

    Gillespie, Portia M; Beaumier, Coreen M; Strych, Ulrich; Hayward, Tara; Hotez, Peter J; Bottazzi, Maria Elena

    2016-06-03

    A number of leishmaniasis vaccine candidates are at various stages of pre-clinical and clinical development. Leishmaniasis is a vector-borne neglected tropical disease (NTD) caused by a protozoan parasite of the genus Leishmania and transmitted to humans by the bite of a sand fly. Visceral leishmaniasis (VL, kala-azar) is a high mortality NTD found mostly in South Asia and East Africa, while cutaneous leishmaniasis (CL) is a disfiguring NTD highly endemic in the Middle East, Central Asia, North Africa, and the Americas. Estimates attribute 50,000 annual deaths and 3.3 million disability-adjusted life years to leishmaniasis. There are only a few approved drug treatments, no prophylactic drug and no vaccine. Ideally, an effective vaccine against leishmaniasis will elicit long-lasting immunity and protect broadly against VL and CL. Vaccines such as Leish-F1, F2 and F3, developed at IDRI and designed based on selected Leishmania antigen epitopes, have been in clinical trials. Other groups, including the Sabin Vaccine Institute in collaboration with the National Institutes of Health are investigating recombinant Leishmania antigens in combination with selected sand fly salivary gland antigens in order to augment host immunity. To date, both VL and CL vaccines have been shown to be cost-effective in economic modeling studies.

  9. [Therapy of leishmaniasis in France: consensus on proposed guidelines].

    Science.gov (United States)

    Buffet, Pierre A; Rosenthal, Éric; Gangneux, Jean-Pierre; Lightburne, Edward; Couppié, Pierre; Morizot, Gloria; Lachaud, Laurence; Marty, Pierre; Dedet, Jean-Pierre

    2011-02-01

    Because it relies on potentially toxic, difficult-to-handle, or expensive compounds the therapy of leishmaniasis is still a complex issue in 2010, especially for visceral leishmaniasis in immuno-suppressed subjects, or in patients with cutaneous and mucosal involvement. This induces a wide diversity of observed therapeutic practices, some being sub-optimal. The Société de Pathologie Exotique organised a meeting dedicated to the therapy of leishmaniasis in France that led to the first consensus on therapeutic guidelines. Liposomal amphotericin B is the first-line option for visceral leishmaniasis both in immunocompetent, and immunosuppressed patients (cumulated doses of 20 mg/kg and 30-40 mg/kg, respectively). Secondary prophylaxis with either liposomal amphotericin B, pentamidine or meglumine antimoniate is proposed to patients with heavy immunosuppression until immunity has been restored for at least 6 months. While the efficacy of new topical formulations of paromomycin is being tested, patients with Old World cutaneous leishmaniasis may be left untreated, or be administered a combination of superficial cryotherapy plus intralesional antimony, or even--in complex situations--receive systemic therapy. The efficacy of a short course of pentamidine (L. guyanensis/L. panamensis) and a 20-day schedule of meglumine antimoniate (L. braziliensis) is solidly established. However, in well-defined situations, local therapy of New World cutaneous leishmaniasis is now considered acceptable.

  10. Importance of cats in zoonotic leishmaniasis in Portugal.

    Science.gov (United States)

    Maia, Carla; Nunes, Mónica; Campino, Lenea

    2008-08-01

    Leishmaniasis, caused by Leishmania infantum, is an endemic zoonosis in the Mediterranean basin. Dogs are considered the major host for these parasites, as well as the main reservoir for human visceral infection. In recent years, asymptomatic infection or clinical disease caused by L. infantum in cats has been reported in several countries where zoonotic leishmaniasis is present. The aim of the present study was to perform a leishmaniasis survey in cats from an endemic focus. Twenty-three adult stray cats were surveyed by clinical examination, and peripheral blood samples for serological and molecular analysis were collected. In 7 of the 23 cats (30.4%) Leishmania DNA was detected in blood. A low level of fluorescent antibodies was detected in four serum samples. All the animals were asymptomatic. Taking into account the high rate of asymptomatic feline leishmaniasis in this survey, it can be suggested that cats may act as a habitual reservoir host of L. infantum infection in endemic areas. Furthermore, it will be important in the future to add this parasitosis to the differential diagnosis of feline infections from leishmaniasis foci in cats. Feline leishmaniasis diagnosis should be accessed by molecular tools.

  11. Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Want MY

    2017-03-01

    Full Text Available Muzamil Y Want,1 Mohammad Islammudin,1 Garima Chouhan,1 Hani A Ozbak,2 Hassan A Hemeg,2 Asoke P Chattopadhyay,3 Farhat Afrin2 1Parasite Immunology Laboratory, Department of Biotechnology, Jamia Hamdard, Hamdard University, New Delhi, India; 2Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Taibah University, Medina, Saudi Arabia; 3Department of Chemistry, University of Kalyani, Kalyani, India Abstract: Visceral leishmaniasis (VL is a fatal, vector-borne disease caused by the intracellular protozoa of the genus Leishmania. Most of the therapeutics for VL are toxic, expensive, or ineffective. Sesquiterpenes are a new class of drugs with proven antimicrobial and antiviral activities. Artemisinin is a sesquiterpene lactone with potent antileishmanial activity, but with limited access to infected cells, being a highly lipophilic molecule. Association of artemisinin with liposome is a desirable strategy to circumvent the problem of poor accessibility, thereby improving its efficacy, as demonstrated in a murine model of experimental VL. Nanoliposomal artemisinin (NLA was prepared by thin-film hydration method and optimized using Box–Behnken design with a mean particle diameter of 83±16 nm, polydispersity index of 0.2±0.03, zeta potential of -27.4±5.7 mV, and drug loading of 33.2%±2.1%. Morphological study of these nanoliposomes by microscopy showed a smooth and spherical surface. The mechanism of release of artemisinin from the liposomes followed the Higuchi model in vitro. NLA was free from concomitant signs of toxicity, both ex vivo in murine macrophages and in vivo in healthy BALB/c mice. NLA significantly denigrated the intracellular infection of Leishmania donovani amastigotes and the number of infected macrophages ex vivo with an IC50 of 6.0±1.4 µg/mL and 5.1±0.9 µg/mL, respectively. Following treatment in a murine model of VL, NLA demonstrated superior efficacy compared to artemisinin with a

  12. Is an early retirement offer good for your health? Quasi-experimental evidence from the army.

    Science.gov (United States)

    Hallberg, Daniel; Johansson, Per; Josephson, Malin

    2015-12-01

    This paper studies empirically the consequences on health of an early retirement offer. To this end we use a targeted retirement offer to military officers 55 years of age or older. Before the offer was implemented, the normal retirement age in the Swedish defense was 60 years of age. Estimating the effect of the offer on individuals' health within the age range 56-70, we find support for a reduction in both mortality and in inpatient care as a consequence of the early retirement offer. Increasing the mandatory retirement age may thus not only have positive government income effects but also negative effects on increasing government health care expenditures.

  13. Hyponatremia in visceral leishmaniasis Hiponatremia no calazar

    OpenAIRE

    Frederico A. Lima Verde; Francisco A.A. Lima Verde; Francisco José V. Veronese; Augusto S. Neto; Galdino Fuc; Emir M. Lima Verde

    2010-01-01

    There are few reports linking hyponatremia and visceral leishmaniasis (kala-azar). This is a study of 55 consecutive kala-azar patients and 20 normal individuals as a control group. Hyponatremia and serum hypo-osmolality were detected in 100% of kala-azar patients. High first morning urine osmolality (750.0 ± 52.0 vs. 894.5 ± 30.0mOsm/kg H2O, p < 0.05), and high 24-hour urine osmolality (426.0 ± 167.0 vs. 514.6 ± 132.0 mOsm/kg H2O, p < 0.05) demonstrated persistent antidiuretic hormone secret...

  14. Proteome Profiling of Human Cutaneous Leishmaniasis Lesion

    Science.gov (United States)

    da Silva Santos, Claire; Attarha, Sanaz; Saini, Ravi Kanth; Boaventura, Viviane; Costa, Jackson; Khouri, Ricardo; Barral-Netto, Manoel; Brodskyn, Cláudia Ida; Souchelnytskyi, Serhiy

    2015-01-01

    In this study, we used proteomics and biological network analysis to evaluate the potential biological processes and components present in the identified proteins of biopsies from cutaneous leishmaniasis (CL) patients infected by Leishmania braziliensis in comparison with normal skin. We identified 59 proteins differently expressed in samples from infected and normal skin. Biological network analysis employing identified proteins showed the presence of networks that may be involved in the cell death mediated by cytotoxic T lymphocytes. After immunohistochemical analyses, the expression of caspase-9, caspase-3, and granzyme B was validated in the tissue and positively correlated with the lesion size in CL patients. In conclusion, this work identified differentially expressed proteins in the inflammatory site of CL, revealed enhanced expression of caspase-9, and highlighted mechanisms associated with the progression of tissue damage observed in lesions. PMID:25207817

  15. NEWER DRUGS FOR VISCERAL LEISHMANIASIS: A REVIEW

    Directory of Open Access Journals (Sweden)

    Krishna Pandey

    2014-01-01

    Full Text Available Visceral Leishmaniasis (VL is one of the most neglected tropical diseases worldwide. The diagnosis and treatment of this disease is quite complex. Sodium Antimony Gluconate (SAG which used to be a very effective treatment has now developed resistance and is potentially a cardio-toxic drug. Pentamidine has now been discarded because of adverse effect of diabetes mellitus. Amphotericin-B is an effective drug but can cause nephrotoxicity. Miltefosine is a new oral effective drug which has recently been introduced in the kala-azar elimination program in the Indian subcontinent. Paromomycin is an injectable aminoglycoside which is quite cheap but can cause ototoxicity and nephrotoxicity. Sitamaquine, an oral antimalarial drug is still in phase-II trial stage. Combination Therapy is been tried with good results. Single dose Ambisome (liposomal Amphotericin-B though costly is a very good alternative.

  16. Pancytopenia in a cat with visceral leishmaniasis.

    Science.gov (United States)

    Marcos, Ricardo; Santos, Marta; Malhão, Fernanda; Pereira, Rui; Fernandes, Ana Cristina; Montenegro, Luís; Roccabianca, Paola

    2009-06-01

    A 4-year-old, domestic shorthair, female spayed cat was presented for decreased appetite and depression. Severe pancytopenia with erythrocyte autoagglutination was found. The cat was seronegative for feline immunodeficiency and leukemia viruses. Immune-mediated hemolytic anemia was suspected but no response to treatment with a blood transfusion, enrofloxacin, and prednisone was observed. Blood and bone marrow smears obtained 11 days later contained Leishmania amastigotes in the cytoplasm of neutrophils and macrophages, respectively. Serologic and PCR testing of peripheral blood confirmed infection with Leishmania infantum. Despite treatment, the cat worsened clinically and was euthanized. At necropsy, visceral dissemination of the parasite was confirmed. The findings in this case indicate that visceral leishmaniasis should be considered as a differential diagnoses in cats with pancytopenia in areas endemic for Leishmania. In addition, amastigotes may be observed in peripheral blood neutrophils.

  17. Theory of mind and neurocognition in early psychosis: a quasi-experimental study.

    Science.gov (United States)

    Langdon, Robyn; Connors, Michael H; Still, Megan; Ward, Philip B; Catts, Stanley

    2014-12-04

    People with chronic psychosis often display theory of mind impairments that are not fully accounted for by other, more general neurocognitive deficits. In these patients, both theory of mind and neurocognitive deficits contribute to poor functioning, independently of psychotic symptoms. In young people with recent-onset psychosis, however, it is unclear the extent to which theory of mind impairment is independent of neurocognitive deficits. The primary aim of this study was to examine the evidence for specific theory of mind impairments in early psychosis. A secondary aim was to explore the relations between theory of mind, neurocognition, symptom severity, and functional outcomes. Twenty-three patients who were within two years of their first psychotic episode and 19 healthy controls completed theory of mind and neurocognitive batteries. Social functioning, quality of life, and symptom severity were also assessed in patients. Patients demonstrated deficits in tasks assessing theory of mind and neurocognition relative to controls. Patients' deficits in theory of mind were evident even after adjusting for their deficits in neurocognition. Neither theory of mind nor neurocognition predicted social functioning or quality of life in this early psychosis sample. Severity of negative symptoms, however, was a significant predictor of both outcomes. While a specific theory of mind impairment was evident in this early psychosis sample, severity of negative symptoms emerged as the best predictor of poor functional outcome. Further early psychosis research is needed to examine the longitudinal progression of theory of mind impairments - independent of neurocognitive deficits - and their impact on psychosocial function.

  18. LeishMan recommendations for treatment of cutaneous and mucosal leishmaniasis in travelers, 2014

    NARCIS (Netherlands)

    Blum, Johannes; Buffet, Pierre; Visser, Leo; Harms, Gundel; Bailey, Mark S; Caumes, Eric; Clerinx, Jan; van Thiel, Pieter P A M; Morizot, Gloria; Hatz, Christoph; Dorlo, Thomas P C; Lockwood, Diana N J

    2014-01-01

    BACKGROUND: Treatment of cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) in travelers is still controversial. Over the last decade, national and international consortia have published recommendations for treating CL in travelers. These guidelines harmonize many issues, but there are some

  19. Localized Leishmaniasis of the oral mucosa. A report of three cases.

    Science.gov (United States)

    García de Marcos, José Antonio; Dean Ferrer, Alicia; Alamillos Granados, Francisco; Ruiz Masera, Juan José; Cortés Rodríguez, Begoña; Vidal Jiménez, Alfredo; García Lainez, Ana; Lozano Rodríguez-Mancheno, Aquiles

    2007-08-01

    The term leishmaniasis comprises a group of diseases caused by different species of a protozoon called Leishmania. Leishmaniasis is found worldwide, and is considered to be endemic in 88 countries. There are three main clinical forms of leishmaniasis: visceral leishmaniasis, cutaneous leishmaniasis and mucocutaneous leishmaniasis. Exclusive involvement of the mucosa is very rare. We present a series of three cases of mucosal leishmaniasis located in the oral cavity. The fact that all three cases were recorded in Spain (an area where L. infantum is endemic), suggests that the latter was the causal agent. The only manifestation of leishmaniasis disease in the described cases was the appearance of an oral lesion. Treatment was provided in the form of meglumine antimoniate in two patients, with a favorable response. One of the patients left the hospital after diagnosis, without receiving treatment, and the subsequent course is not known. A review is made of the literature on the subject.

  20. Early Detection of Junctional Adhesion Molecule-1 (JAM-1 in the Circulation after Experimental and Clinical Polytrauma

    Directory of Open Access Journals (Sweden)

    Stephanie Denk

    2015-01-01

    Full Text Available Severe tissue trauma-induced systemic inflammation is often accompanied by evident or occult blood-organ barrier dysfunctions, frequently leading to multiple organ dysfunction. However, it is unknown whether specific barrier molecules are shed into the circulation early after trauma as potential indicators of an initial barrier dysfunction. The release of the barrier molecule junctional adhesion molecule-1 (JAM-1 was investigated in plasma of C57BL/6 mice 2 h after experimental mono- and polytrauma as well as in polytrauma patients (ISS ≥ 18 during a 10-day period. Correlation analyses were performed to indicate a linkage between JAM-1 plasma concentrations and organ failure. JAM-1 was systemically detected after experimental trauma in mice with blunt chest trauma as a driving force. Accordingly, JAM-1 was reduced in lung tissue after pulmonary contusion and JAM-1 plasma levels significantly correlated with increased protein levels in the bronchoalveolar lavage as a sign for alveolocapillary barrier dysfunction. Furthermore, JAM-1 was markedly released into the plasma of polytrauma patients as early as 4 h after the trauma insult and significantly correlated with severity of disease and organ dysfunction (APACHE II and SOFA score. The data support an early injury- and time-dependent appearance of the barrier molecule JAM-1 in the circulation indicative of a commencing trauma-induced barrier dysfunction.

  1. Scientific biography, cognitive deficits, and laboratory practice. James McKeen Cattell and early American experimental psychology, 1880-1904.

    Science.gov (United States)

    Sokal, Michael M

    2010-09-01

    Despite widespread interest in individual life histories, few biographies of scientists make use of insights derived from psychology, another discipline that studies people, their thoughts, and their actions. This essay argues that recent theoretical work in psychology and tools developed for clinical psychological practice can help biographical historians of science create and present fuller portraits of their subjects' characters and temperaments and more nuanced analyses of how these traits helped shape their subjects' scientific work. To illustrate this thesis, the essay examines the early career of James McKeen Cattell--an influential late nineteenth- and early twentieth-century experimental psychologist--through a lens offered by psychology and argues that Cattell's actual laboratory practices derived from an "accommodation" to a long-standing "cognitive deficit." These practices in turn enabled Cattell to achieve more precise experimental results than could any of his contemporaries; and their students readily adopted them, along with their behavioral implications. The essay concludes that, in some ways, American psychology's early twentieth-century move toward a behavioral understanding of psychological phenomena can be traced to Cattell's personal cognitive deficit. It closes by reviewing several "remaining general questions" that this thesis suggests.

  2. Early Detection of Junctional Adhesion Molecule-1 (JAM-1) in the Circulation after Experimental and Clinical Polytrauma.

    Science.gov (United States)

    Denk, Stephanie; Wiegner, Rebecca; Hönes, Felix M; Messerer, David A C; Radermacher, Peter; Weiss, Manfred; Kalbitz, Miriam; Ehrnthaller, Christian; Braumüller, Sonja; McCook, Oscar; Gebhard, Florian; Weckbach, Sebastian; Huber-Lang, Markus

    2015-01-01

    Severe tissue trauma-induced systemic inflammation is often accompanied by evident or occult blood-organ barrier dysfunctions, frequently leading to multiple organ dysfunction. However, it is unknown whether specific barrier molecules are shed into the circulation early after trauma as potential indicators of an initial barrier dysfunction. The release of the barrier molecule junctional adhesion molecule-1 (JAM-1) was investigated in plasma of C57BL/6 mice 2 h after experimental mono- and polytrauma as well as in polytrauma patients (ISS ≥ 18) during a 10-day period. Correlation analyses were performed to indicate a linkage between JAM-1 plasma concentrations and organ failure. JAM-1 was systemically detected after experimental trauma in mice with blunt chest trauma as a driving force. Accordingly, JAM-1 was reduced in lung tissue after pulmonary contusion and JAM-1 plasma levels significantly correlated with increased protein levels in the bronchoalveolar lavage as a sign for alveolocapillary barrier dysfunction. Furthermore, JAM-1 was markedly released into the plasma of polytrauma patients as early as 4 h after the trauma insult and significantly correlated with severity of disease and organ dysfunction (APACHE II and SOFA score). The data support an early injury- and time-dependent appearance of the barrier molecule JAM-1 in the circulation indicative of a commencing trauma-induced barrier dysfunction.

  3. No delayed behavioral and phenotypic responses to experimental early-life lead exposure in great tits (Parus major).

    Science.gov (United States)

    Ruuskanen, Suvi; Eeva, Tapio; Kotitalo, Päivi; Stauffer, Janina; Rainio, Miia

    2015-02-01

    Early-life exposure to pollutants, such as lead, may have long-lasting consequences on health, behavior, and cognition. However, experiments on delayed effects of specific pollutants are very rare in wild animals. We experimentally exposed wild nestling great tits (Parus major) to dietary lead (high, low, or control group) in levels relevant to exposure levels of wild populations in Europe and studied delayed effects on phenotypic and behavioral traits in captivity. We also included a group of birds from a vicinity of a copper smelter, exposed to a mixture of toxic metals and altered food supply during development. This experimental setup allowed us to compare the strength of direct (exposure to lead per se) and indirect (pollution-related changes in diet) effects of pollutants. Our experimental lead treatment significantly increased lead levels in bone and feces compared with controls. However, we found no carry-over effect of early-life dietary lead on morphology, plumage coloration, or heat shock proteins. Treatment did not affect activity, exploration, neophobia, or success in learning and spatial memory task. We conclude that with the exposure levels and relatively short exposure period used, delayed effects on the measured traits were not found. However, it is important to further study other types of behavioral traits and ultimately fitness effects.

  4. Leishmaniasis, an emerging imported infection: report of 20 cases from Australia.

    Science.gov (United States)

    Stark, Damien; van Hal, Sebastian; Lee, Rogan; Marriott, Deborah; Harkness, John

    2008-01-01

    Leishmaniasis is a protozoan infection rarely reported in Australia. However, with the advent of increased international tourism and migration of refugees from endemic regions, leishmaniasis has emerged as an increasingly imported infection. We report 20 cases (17 cutaneous, 2 visceral, and 1 post-kala-azar dermal leishmaniasis). These data highlight the range of species causing leishmaniasis imported in Australia and demonstrate the importance of species identification in determining proper treatment.

  5. First Report on Ambisome-Associated Allergic Reaction in Two Sudanese Leishmaniasis Patients

    OpenAIRE

    Mukhtar, Maowia; Aboud, Mona; Kheir, Musa; Bakhiet, Sahar; Abdullah, Nazik; Ali, Ahmed; Hassan, Nadia; Elamin, Elwaleed; Elagib, Atif

    2011-01-01

    Post kala-azar dermal leishmaniasis (PKDL) and mucosal leishmaniasis (ML) are serious clinical forms of leishmaniasis caused by Leishmania donovani parasites in Sudan. Although pentavalent antimonys are used as the first line of treatment of all clinical forms of leishmaniasis, persistent PKDL and ML patients are treated with liposomal amphotericin B (Ambisome) as a second-line drug. In this work, we report the development of allergic reactions by a PKDL and a ML Sudanese patient to Ambisome....

  6. Biomarkers of safety and immune protection for genetically modified live attenuated Leishmania vaccines against visceral leishmaniasis-Discovery and implications

    Directory of Open Access Journals (Sweden)

    Sreenivas eGannavaram

    2014-05-01

    Full Text Available Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, sub-unit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in L. donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen1-/- in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated

  7. Loss of vascular early response gene reduces edema formation after experimental stroke

    Directory of Open Access Journals (Sweden)

    Liu Fudong

    2012-06-01

    Full Text Available Abstract Vascular Early Response Gene (Verge is an immediate early gene (IEG that is up-regulated in endothelial cells in response to a number of stressors, including ischemic stroke. Endothelial cell lines that stably express Verge show enhanced permeability. Increased Verge expression has also been associated with blood brain barrier breakdown. In this study we investigated the role of Verge in ischemic injury induced by middle cerebral artery occlusion (MCAO in both Verge knockout (KO and wild type (WT mice. Verge KO mice had significantly less cerebral edema formation after MCAO compared to WT mice. However, stroke outcome (infarct size and neurological deficit scores evaluated at either 24 or 72 hours after stroke showed no differences between the two genotypes. Verge deletion leads to decreased edema formation after ischemia; however acute stroke outcomes were unchanged.

  8. Brazilian propolis promotes immunomodulation on human cells from American Tegumentar Leishmaniasis patients and healthy donors infected with L. braziliensis.

    Science.gov (United States)

    Dos Santos Thomazelli, Ana Paula Fortes; Tomiotto-Pellissier, Fernanda; da Silva, Suelen Santos; Panis, Carolina; Orsini, Tatiane Marcusso; Cataneo, Allan Henrique Depieri; Miranda-Sapla, Milena Menegazzo; Custódio, Luiz Antonio; Tatakihara, Vera Lúcia Hideko; Bordignon, Juliano; Silveira, Guilherme Ferreira; Sforcin, José Maurício; Pavanelli, Wander Rogério; Conchon-Costa, Ivete

    2017-01-01

    American Tegumentar Leishmaniasis (ATL) is an infectious disease caused by Leishmania parasites with ineffective treatment. The properties of propolis have been studied in different experimental studies, however, few works have investigated the effects of propolis on human-derived peripheral blood mononuclear cells (PBMC) in leishmaniasis models. Thus, we investigate the immunomodulatory effects of propolis treatment on PBMC from ATL patients and on PBMC from healthy donors infected with Leishmania braziliensis. Our data demonstrate that propolis pretreatment shows immunomodulatory effects on both healthy donors and ATL patients adherent cells, increasing IL-4 and IL-17 and decreasing IL-10, in either the presence or absence of the L. braziliensis infection, demonstrating that propolis contributes with the decrease of the inflammation and could also contribute with parasite control. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Potential early predictors for outcomes of experimental hemorrhagic shock induced by uncontrolled internal bleeding in rats.

    Directory of Open Access Journals (Sweden)

    Zaid A Abassi

    Full Text Available Uncontrolled hemorrhage, resulting from traumatic injuries, continues to be the leading cause of death in civilian and military environments. Hemorrhagic deaths usually occur within the first 6 hours of admission to hospital; therefore, early prehospital identification of patients who are at risk for developing shock may improve survival. The aims of the current study were: 1. To establish and characterize a unique model of uncontrolled internal hemorrhage induced by massive renal injury (MRI, of different degrees (20-35% unilateral nephrectomy in rats, 2. To identify early biomarkers those best predict the outcome of severe internal hemorrhage. For this purpose, male Sprague Dawley rats were anesthetized and cannulas were inserted into the trachea and carotid artery. After abdominal laparotomy, the lower pole of the kidney was excised. During 120 minutes, hematocrit, pO2, pCO2, base excess, potassium, lactate and glucose were measured from blood samples, and mean arterial pressure (MAP was measured through arterial tracing. After 120 minutes, blood loss was determined. Statistical prediction models of mortality and amount of blood loss were performed. In this model, the lowest blood loss and mortality rate were observed in the group with 20% nephrectomy. Escalation of the extent of nephrectomy to 25% and 30% significantly increased blood loss and mortality rate. Two phases of hemodynamic and biochemical response to MRI were noticed: the primary phase, occurring during the first 15 minutes after injury, and the secondary phase, beginning 30 minutes after the induction of bleeding. A Significant correlation between early blood loss and mean arterial pressure (MAP decrements and survival were noted. Our data also indicate that prediction of outcome was attainable in the very early stages of blood loss, over the first 15 minutes after the injury, and that blood loss and MAP were the strongest predictors of mortality.

  10. Experimental study on ultrasonic pulse velocity evaluation of the microstructure of cementitious material at early age

    NARCIS (Netherlands)

    Guang Ye; Van Breugel, K.; Fraaij, A.L.A.

    2001-01-01

    This paper describes an ultrasonic experimental set-up to monitor the development of the microstructure of fresh concrete at different temperatures (isothermal curing at 10, 20, 30 and 50 °C) and water/cement ratios (0.40, 0.45 and 0.55). The Ultrasonic Pulse Velocity (UPV) is used as an indication

  11. Experimental study on ultrasonic pulse velocity evaluation of the microstructure of cementitious material at early age

    NARCIS (Netherlands)

    Guang Ye; Van Breugel, K.; Fraaij, A.L.A.

    2001-01-01

    This paper describes an ultrasonic experimental set-up to monitor the development of the microstructure of fresh concrete at different temperatures (isothermal curing at 10, 20, 30 and 50 °C) and water/cement ratios (0.40, 0.45 and 0.55). The Ultrasonic Pulse Velocity (UPV) is used as an indication

  12. Experimental evaluation of early patterns of colonisation of space on rocky shores and seawalls.

    Science.gov (United States)

    Bulleri, Fabio

    2005-09-01

    The introduction of artificial structures in coastal areas can cause fragmentation and loss of natural habitats. Previous studies found that variation in colonisation of space at mid-shore levels could account for differences in mature assemblages between seawalls and vertical surfaces on adjacent rocky shores in Sydney Harbour (Australia). This study tests the model that the nature of the substratum is responsible for different patterns of early colonisation between vertical ledges of rocky shores and seawalls. According to this model, patterns in early colonisation would differ between cleared areas created on vertical surfaces on rocky shores and seawalls, but not between standard surfaces (panels) installed on each structure. Early colonisation of space differed between seawalls and rocky shores, regardless of the type of substratum (clearings versus panels). Differences in relative abundances between structures were evident on both types of substrata for some taxa, while they varied between substrata for others. No taxa, however, showed consistent differences between structures in only the clearings. In addition, the abundance of some taxa differed between panels on the different structures, suggesting that the effects of the substratum were modulated by factors operating differentially between rocky shores and seawalls.

  13. Sandfly fauna of endemic leishmaniasis foci in Anzoátegui State, Venezuela.

    Science.gov (United States)

    González, R; Jorquera, A; De Sousa, L; Ledezma, E; Devera, R

    2002-01-01

    A census of the sandfly fauna was undertaken in 1993-98 in 5 endemic leishmaniasis foci situated at different altitudes in Anzoátegui State, Venezuela. From the 17 species of Lutzomyia identified, we believe that Lu. ovallesi, Lu. panamensis and Lu. gomezi are the probable vectors of cutaneous leishmaniasis, while Lu. evansi might transmit visceral leishmaniasis.

  14. Intracellular replication-deficient Leishmania donovani induces long lasting protective immunity against visceral leishmaniasis.

    Science.gov (United States)

    Selvapandiyan, Angamuthu; Dey, Ranadhir; Nylen, Susanne; Duncan, Robert; Sacks, David; Nakhasi, Hira L

    2009-08-01

    No vaccine is currently available for visceral leishmaniasis (VL) caused by Leishmania donovani. This study addresses whether a live attenuated centrin gene-deleted L. donovani (LdCen1(-/-)) parasite can persist and be both safe and protective in animals. LdCen1(-/-) has a defect in amastigote replication both in vitro and ex vivo in human macrophages. Safety was shown by the lack of parasites in spleen and liver in susceptible BALB/c mice, immune compromised SCID mice, and human VL model hamsters 10 wk after infection. Mice immunized with LdCen1(-/-) showed early clearance of virulent parasite challenge not seen in mice immunized with heat killed parasites. Upon virulent challenge, the immunized mice displayed in the CD4(+) T cell population a significant increase of single and multiple cytokine (IFN-gamma, IL-2, and TNF) producing cells and IFN-gamma/IL10 ratio. Immunized mice also showed increased IgG2a immunoglobulins and NO production in macrophages. These features indicated a protective Th1-type immune response. The Th1 response correlated with a significantly reduced parasite burden in the spleen and no parasites in the liver compared with naive mice 10 wk post challenge. Protection was observed, when challenged even after 16 wk post immunization, signifying a sustained immunity. Protection by immunization with attenuated parasites was also seen in hamsters. Immunization with LdCen1(-/-) also cross-protected mice against infection with L. braziliensis that causes mucocutaneous leishmaniasis. Results indicate that LdCen1(-/-) can be a safe and effective vaccine candidate against VL as well as mucocutaneous leishmaniasis causing parasites.

  15. Early laboratories c.1600 - c.1800 and the location of experimental science.

    Science.gov (United States)

    Crosland, Maurice

    2005-04-01

    Surprisingly little attention has been given hitherto to the definition of the laboratory. A space has to be specially adapted to deserve that title. It would be easy to assume that the two leading experimental sciences, physics and chemistry, have historically depended in a similar way on access to a laboratory. But while chemistry, through its alchemical ancestry with batteries of stills, had many fully fledged laboratories by the seventeenth century, physics was discovering the value of mathematics. Even experimental physics was content to make use of almost any indoor space, if not outdoors, ignoring the possible value of a laboratory. The development of the physics laboratory had to wait until the nineteenth century.

  16. Experimental evidence and early translational steps using bone marrow derived stem cells after human stroke.

    Science.gov (United States)

    Kasahara, Yukiko; Ihara, Masafumi; Taguchi, Akihiko

    2013-01-01

    Neurogenesis is principally restricted to the subventricular zone of the lateral ventricle wall and the subgranular zone of the hippocampal dentate gyrus in physiological situations. However, neuronal stem cells are known to be mobilized into the post- and peristroke area and we have demonstrated that appropriate support of these stem cells, achieved by therapeutic angiogenesis, enhances neuroregeneration followed by neuronal functional recovery in an experimental stroke model. We also found that neural stem cells are mobilized in patients after stroke, as well as in animal models. Based on these observations, we have started cell-based therapy using autologous bone marrow-derived stem/progenitor cells in patients after stroke. This review summarizes the findings of recent experimental and clinical studies that have focused on neurogenesis in the injured brain after cerebral infarction. We also refer to the challenges for future cell-based therapy, including regeneration of the aged brain. Copyright © 2013 S. Karger AG, Basel.

  17. Early changes in [{sup 18}F]FLT uptake after chemotherapy: an experimental study

    Energy Technology Data Exchange (ETDEWEB)

    Dittmann, Helmut; Dohmen, Bernhard Matthias; Bartusek, Gabi; Pritzkow, Maren; Bares, Roland [Department of Nuclear Medicine, Eberhard-Karls-University, Roentgenweg 13, 72076 Tuebingen (Germany); Kehlbach, Rainer [Department of Diagnostic Radiology, Eberhard-Karls-University, Tuebingen (Germany); Sarbia, Mario [Institute of Pathology, Heinrich-Heine-University, Duesseldorf (Germany)

    2002-11-01

    This study evaluated the use of 3'-deoxy-3'-[{sup 18}F]fluorothymidine ([{sup 18}F]FLT) for monitoring of the early effects of anticancer chemotherapy on tumour cell proliferation. Cells derived from human oesophageal squamous cell carcinoma (OSC-1) were grown for 2 days and incubated with cisplatin (CDDP), 5-fluorouracil (5-FU), methotrexate (MTX) or gemcitabine (GEM) for 4 h. Cultures were incubated with drug doses (CDDP: 0.67, 6.7, 67 {mu}M; 5-FU 15.4, 154, 1,540 {mu}M; MTX: 4.4, 44, 440 {mu}M; GEM: 0.0067, 0.067, 0.67 {mu}M) corresponding to approximately 10%-95% proliferation inhibition (MTX: 10%-75%). Treatment was stopped and cells were allowed to recover for 4, 24 or 72 h. [{sup 18}F]FLT was added for 10-180 min. Control cultures were incubated with [{sup 18}F]fluorodeoxyglucose (FDG). Cell counts, viability, clonogenic activity and cell cycle distribution estimated by flow cytometry were used to evaluate the cytotoxic effects of chemotherapy. Strikingly, FLT uptake per 10{sup 5} viable cells was increased seven- to tenfold 24 h after treatment with 5-FU or MTX irrespective of dose. Thus, total FLT uptake per tissue culture exceeded that of controls despite a considerable decrease in overall cell counts due to cytostasis up to 72 h after treatment. 5-FU-treated cells showed accumulation in early S phase (overall S phase: 88% vs 42%). GEM treatment resulted in a more moderate increase in total FLT accumulation, to a maximum of fivefold at the dose close to the IC{sub 50}. In contrast, FLT accumulation was significantly reduced at cytostatic concentrations of CDDP and was still decreasing in a dose-related manner at 72 h despite considerable S phase arrest. With 5-FU or CDDP, the uptake of FDG did not differ significantly from control values 24 h after treatment. These findings demonstrate that tumour cell uptake of FLT - in contrast to that of FDG - reveals specific changes depending on the cytostatic drug used for treatment. The antimetabolites 5

  18. The development of undernourished children: an experimental study on early feeding

    OpenAIRE

    Pollitt, Ernesto; Durnin, John; Aitchison, Tom; Husaini, Mahdi; Jahari, Abas; Schürch, Beat

    2013-01-01

    The study was a randomized clinical tria! involving two cohorts (12 and 18 months) of nutritionally at risk Jndonesian children and three types of supplementary feeding: high energy and micronutrients; skimmed milk and micronutrients; and skimmed milk. The hypothesis of the study was that high energy and micronutrient supplements given early to children could delay on physical growing and mental development. The results showed that a combined energy and micronutrient supplement given for ayea...

  19. [Diffuse cutaneous leishmaniasis (DCL) and visceral leishmaniasis (VL) concurrent with cancer: Presentation of a case].

    Science.gov (United States)

    Blum-Domínguez, Selene Del C; Martínez-Vázquez, Alejandro; Núñez-Oreza, Luis A; Martínez-Hernández, Fernando; Villalobos, Guiehdani; Tamay-Segovia, Paulino

    2017-01-01

    Male of 52 year old with chronic alcoholism and ulcerated lesion on the face and disseminated nodular skin lesions, underwent to biopsy of ulcer edges where was observed a concomitant epidermoid malignancy with Leishmania (L.). Besides others, biopsies of nodule in the periumbilical region, lymph node and bone marrow were assayed, and all biopsies had abundant amastigotes. The amplified Polymerase Chain Reaction (PCR) products from nodule were sequenced and the alignment analysis demonstrated homology with L. mexicana confirming the infection by this parasite. This is considered the first case of visceral and diffuse cutaneous leishmaniasis concurrent with epidermoid cancer in the state of Campeche.

  20. The case of diagnosis of imported cutaneous leishmaniasis in Zaporozhye

    Directory of Open Access Journals (Sweden)

    V. G. Savelyev

    2014-08-01

    Full Text Available Aim. Article presents the current data on the clinical and epidemiological issue of leishmaniasis. Methods and results. Leishmaniasis is endemic disease in 88 countries, mainly in tropical and subtropical climates. Probability of importation of American cutaneous leishmaniasis in our country is practically zero, but, given the rarity of this disease, we present own clinical observation of imported cutaneous leishmaniasis in Zaporozhye. At the beginning of the third millennium has greatly increased the urgency of tropical parasitic diseases, including leishmaniasis. According to WHO, the world's 14 million people are infected each year there is about 2 million new cases and about 350 million live in areas at risk. Leishmaniasis - a group of vector-borne protozoal disease in humans and animals characterized by lesions of the internal organs (visceral leishmaniasis or the skin and mucous membranes (cutaneous leishmaniasis, which is the vector mosquitoes. We present their own clinical observations of American cutaneous leishmaniasis imported. Patient S., 41 years was hospitalized in Zaporozhye Regional Clinical Hospital infectious on 07.17.2013, with suspected cutaneous leishmaniasis. From the history of the disease is known that for the first time in February 2013 the patient have got relative to blade area redness and bump that appeared above the skin, and had a magnitude of 2,3 mm brownish-red. To the doctor the patient has not addressed. After 1,5-2 months bump grew and he began to stand out ichor, which dries and formed a crust on top of the hump. Further small ulcers that did not bring discomfort and pain to the patient appeared. However, every month ulcer increased. In July, after vacation at sea, rose weeping sores and perifocal inflammation appeared. Ulcer size reached 2 cm in diameter. The patient first applied to the dermatologist at the beginning of July 2013. Dermatologist excluded secondary syphilis and tuberculosis skin and sent to an

  1. Leishmaniasis, conflict, and political terror: A spatio-temporal analysis.

    Science.gov (United States)

    Berry, Isha; Berrang-Ford, Lea

    2016-10-01

    Leishmaniasis has been estimated to cause the ninth largest burden amongst global infectious diseases. Occurrence of the disease has been anecdotally associated with periods of conflict, leading to its referral as a disease of 'guerrilla warfare.' Despite this, there have been few studies that quantitatively investigate the extent to which leishmaniasis coincides with conflict or political terror. This study employed a longitudinal approach to empirically test for an association between cutaneous and visceral leishmaniasis incidence with occurrence of conflict and political terror at the national level, annually for 15 years (1995-2010). Leishmaniasis incidence data were collected for 54 countries, and combined with UCDP/PRIO Armed Conflict and Amnesty International political terror datasets. Mixed effects negative binomial regression models clustered at the country-level were constructed to evaluate the incidence rate ratios against the predictors, while controlling for wealth. Additionally, to understand how and why conflict-terror may be associated with leishmaniasis incidence, we conducted a historical analysis. We identify and discuss posited causal mechanisms in the literature, and critically assessed pathways by which leishmaniasis might occur in places and times of conflict-terror. There was a significant dose-response relationship for disease incidence based on increasing levels of conflict and terror. Country-years experiencing very high levels of conflict-terror were associated with a 2.38 times higher [95% CI: 1.40-4.05] and 6.02 times higher [95% CI: 2.39-15.15] incidence of cutaneous and visceral leishmaniasis, respectively. Historical analysis indicated that conflict and terror contribute to-or coincide with-leishmaniasis incidence through processes of population displacement and health system deterioration. This research highlights the potentially increased risks for cutaneous and visceral leishmaniasis incidence in areas of high conflict

  2. Fortified Extract of Red Berry, Ginkgo biloba, and White Willow Bark in Experimental Early Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Claudio Bucolo

    2013-01-01

    Full Text Available Diabetic retinopathy is a complex condition where inflammation and oxidative stress represent crucial pathways in the pathogenesis of the disease. Aim of the study was to investigate the effects of a fortified extract of red berries, Ginkgo biloba and white willow bark containing carnosine and α-lipoic acid in early retinal and plasma changes of streptozotocin-induced diabetic rats. Diabetes was induced by a single streptozotocin injection in Sprague Dawley rats. Diabetics and nondiabetic (control rats were treated daily with the fortified extract for the ten days. Retina samples were collected and analyzed for their TNF-α and VEGF content. Moreover, plasma oxidative stress was evaluated by thiobarbituric acid reacting substances (TBARS. Increased TNF-α and VEGF levels were observed in the retina of diabetic rats. Treatment with the fortified extract significantly lowered retinal cytokine levels and suppressed diabetes-related lipid peroxidation. These data demonstrate that the fortified extract attenuates the degree of retinal inflammation and plasma lipid peroxidation preserving the retina in early diabetic rats.

  3. Early Childhood Professional Development: An Experimental Study of Adult Teaching Practices Derived from Adult Learning Theory

    Science.gov (United States)

    Weber-Mayrer, Melissa M.

    Research that describes how adults acquire and use new information, collectively called adult learning theory, has potentially important implications for facilitating such adult learning experiences as educator professional development. The purpose of this study was to examine whether integrating adult teaching practices derived from adult learning theories into early childhood educators professional development would result in better gains in educator engagement in professional development, phonological awareness abilities, phonological awareness knowledge, and language and literacy beliefs. The impact on educator engagement and educator proximal knowledge was analyzed using one way ANOVA. The impact on educator phonological awareness abilities, phonological awareness general knowledge, and beliefs was analyzed using a 3 X (2 X S) mixed analyses of variance to examine the pretest to posttest change between educators participating the three conditions. Results revealed significant findings for increased engagement in professional learning and gains in educators general knowledge. This study is a first step in understanding effective adult teaching practices that may or may not contribute to better educator outcomes and promoting more effective professional learning experiences for early childhood educators.

  4. Preparing beginning reading teachers: An experimental comparison of initial early literacy field experiences.

    Science.gov (United States)

    Al Otaiba, Stephanie; Lake, Vickie E; Greulich, Luana; Folsom, Jessica S; Guidry, Lisa

    2012-01-01

    This randomized-control trial examined the learning of preservice teachers taking an initial Early Literacy course in an early childhood education program and of the kindergarten or first grade students they tutored in their field experience. Preservice teachers were randomly assigned to one of two tutoring programs: Book Buddies and Tutor Assisted Intensive Learning Strategies (TAILS), which provided identical meaning-focused instruction (shared book reading), but differed in the presentation of code-focused skills. TAILS used explicit, scripted lessons, and the Book Buddies required that code-focused instruction take place during shared book reading. Our research goal was to understand which tutoring program would be most effective in improving knowledge about reading, lead to broad and deep language and preparedness of the novice preservice teachers, and yield the most successful student reading outcomes. Findings indicate that all pre-service teachers demonstrated similar gains in knowledge, but preservice teachers in the TAILS program demonstrated broader and deeper application of knowledge and higher self-ratings of preparedness to teach reading. Students in both conditions made similar comprehension gains, but students tutored with TAILS showed significantly stronger decoding gains.

  5. Laparoscopy for the management of early-stage endometrial cancer: from experimental to standard of care.

    Science.gov (United States)

    Acholonu, Uchenna C; Chang-Jackson, Shao-Chun R; Radjabi, A Reza; Nezhat, Farr R

    2012-01-01

    We performed a search of PUBMED and MEDLINE for articles concerning surgical management of early stage endometrial cancer from 1950 to 2011. From the articles collected we extracted data such as estimated blood loss, operating room time, complications, conversion to laparotomy, and length of hospital stay. Forty-seven relevant sources were analyzed. The patients in the laparoscopy group had less blood loss, fewer complications, longer operating room times, and a shorter length of stay. Lymph node count was similar in both groups. Although obesity is not a contraindication to laparoscopy, it does lead to a higher conversion rate. Route of surgical treatment had no impact on recurrence or survival. Robotic surgery has significant advantages over laparotomy, but advantages over laparoscopy are not as distinct. Laparoscopic hysterectomy offers several advantages over laparotomy. These advantages relate to improvements in patient care with comparable clinical outcome. After careful analysis we believe laparoscopy should be the standard of care for surgical management of early stage endometrial cancer. Copyright © 2012 AAGL. Published by Elsevier Inc. All rights reserved.

  6. [The impact of climate change on leishmaniasis in Brazil].

    Science.gov (United States)

    Mendes, Chrystian Soares; Coelho, Alexandre Bragança; Féres, José Gustavo; Souza, Elvanio Costa de; Cunha, Dênis Antônio da

    2016-01-01

    This paper sought to assess how climate change will affect the proliferation of leishmaniasis in Brazil in three time frames: 2010-2039, 2040-2079 and 2080-2100, and with two climate change scenarios. The relation of temperature, precipitation and the number of hospital admissions due to leishmaniasis was estimated and projections were made using these results. Results show that precipitation has a strong relation with leishmaniasis incidence and projections show that by the end of the twenty-first century there will be a 15% growth in the annual number of hospital admissions due to leishmaniasis in Brazil, compared to the base scenario (1992-2002). In regional terms, projections indicate growth in every region, with the exception of the Mid-West. The highest relative growth will be in the South of the country, while the highest increase in absolute terms will be observed in the Northeast region. In general, the incidence of leishmaniasis will grow in Brazil due to climate change.

  7. Misdiagnosis and Mistreatment of Post-Kala-Azar Dermal Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Ahmed Mohamed El Hassan

    2013-01-01

    Full Text Available Post-kala-azar dermal leishmaniasis (PKDL is a known complication of visceral leishmaniasis (VL caused by L. donovani. It is rare in VL caused by L. infantum and L. chagasi. In Sudan, it occurs with a frequency of 58% among successfully treated VL patients. In the majority of cases, PKDL can be diagnosed on the basis of clinical appearance, distribution of the lesions, and past history of treated VL. The ideal diagnostic method is to demonstrate the parasite in smears, by culture or PCR. Diagnosis is particularly difficult in patients who develop PKDL in the absence of previous history of visceral leishmaniasis. We describe a case of cutaneous leishmaniasis misdiagnosed as PKDL and 3 cases of PKDL who were either misdiagnosed or mistreated as other dermatoses. This caused exacerbation of their disease leading to high parasite loads in the lesions and dissemination to internal organs in one of the patients, who was also diabetic. The latter patient had L. major infection. A fourth patient with papulonodular lesions on the face and arms of 17-year duration and who was misdiagnosed as having PKDL is also described. He turned out to have cutaneous leishmaniasis due to L. major. Fortunately, he was not treated with steroids. He was cured with intravenous sodium stibogluconate.

  8. Visceral leishmaniasis in a renal transplant recipient treated with allopurinol

    Directory of Open Access Journals (Sweden)

    Harzallah Kais

    2010-01-01

    Full Text Available Leishmaniasis is an infection caused by a protozoan parasite belonging to the genus Leishmania and transmitted by the Phlebotomus sandfly. We report a case of visceral leishmaniasis in a 49-year-old male renal transplant recipient, a resident of the western part of Tunisia, which is an endemic zone for the disease. Just before and after the transplantation, the patient resided in Tunis, which is non-endemic for leishmaniasis. Visceral leishmaniasis occurred eight years after renal transplantation, and the clinical picture was characterized by fever and pancytopenia. Leish-maniae were detected by bone marrow aspiration. Pentavalent antimonal was used for 28 days and was substituted by allopurinol (20 mg/kg per day. One year after the infection, the patient remains totally asymptomatic. Our report suggests that visceral leishmaniasis may complicate the clinical course of organ transplantation and can be fatal, particularly when untreated. Relapses may occur after completion of the apparently effective treatment. Allopurinol could be a solution to avoid these relapses.

  9. Documenting Differences between Early Stone Age Flake Production Systems: An Experimental Model and Archaeological Verification.

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    Presnyakova, Darya; Archer, Will; Braun, David R; Flear, Wesley

    2015-01-01

    This study investigates morphological differences between flakes produced via "core and flake" technologies and those resulting from bifacial shaping strategies. We investigate systematic variation between two technological groups of flakes using experimentally produced assemblages, and then apply the experimental model to the Cutting 10 Mid -Pleistocene archaeological collection from Elandsfontein, South Africa. We argue that a specific set of independent variables--and their interactions--including external platform angle, platform depth, measures of thickness variance and flake curvature should distinguish between these two technological groups. The role of these variables in technological group separation was further investigated using the Generalized Linear Model as well as Linear Discriminant Analysis. The Discriminant model was used to classify archaeological flakes from the Cutting 10 locality in terms of their probability of association, within either experimentally developed technological group. The results indicate that the selected independent variables play a central role in separating core and flake from bifacial technologies. Thickness evenness and curvature had the greatest effect sizes in both the Generalized Linear and Discriminant models. Interestingly the interaction between thickness evenness and platform depth was significant and played an important role in influencing technological group membership. The identified interaction emphasizes the complexity in attempting to distinguish flake production strategies based on flake morphological attributes. The results of the discriminant function analysis demonstrate that the majority of flakes at the Cutting 10 locality were not associated with the production of the numerous Large Cutting Tools found at the site, which corresponds with previous suggestions regarding technological behaviors reflected in this assemblage.

  10. Leishmanization revisited: immunization with a naturally attenuated cutaneous Leishmania donovani isolate from Sri Lanka protects against visceral leishmaniasis.

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    McCall, Laura-Isobel; Zhang, Wen-Wei; Ranasinghe, Shanlindra; Matlashewski, Greg

    2013-02-27

    Leishmaniasis is a neglected tropical disease caused by Leishmania protozoa and associated with three main clinical presentations: cutaneous, mucocutaneous and visceral leishmaniasis. Visceral leishmaniasis is the second most lethal parasitic disease after malaria and there is so far no human vaccine. Leishmania donovani is a causative agent of visceral leishmaniasis in South East Asia and Eastern Africa. However, in Sri Lanka, L. donovani causes mainly cutaneous leishmaniasis, while visceral leishmaniasis is rare. We investigate here the possibility that the cutaneous form of L. donovani can provide immunological protection against the visceral form of the disease, as a potential explanation for why visceral leishmaniasis is rare in Sri Lanka. Subcutaneous immunization with a cutaneous clinical isolate from Sri Lanka was significantly protective against visceral leishmaniasis in BALB/c mice. Protection was associated with a mixed Th1/Th2 response. These results provide a possible rationale for the scarcity of visceral leishmaniasis in Sri Lanka and could guide leishmaniasis vaccine development efforts.

  11. Experimental investigation of the early interaction between cyanobacterial soil crusts and vascular plants

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    Klemens Zaplata, Markus; Veste, Maik; Pohle, Ina; Schümberg, Sabine; Abreu Schonert, Iballa; Hinz, Christoph

    2016-04-01

    While there are hints that biological soil crusts (BSCs) can constitute physical barriers for the emergence of vascular plants, a conceptual approach for the quantitative evaluation of these effects is still missing. Here we present an experimental design to test the emergence of seedlings in situ with (i) capping natural intact, (ii) destroyed and (iii) removed BSC. The selected field site is directly adjacent to the constructed Hühnerwasser catchment (Lusatia, Germany). This site exists since the end of 2008 and consists of loamy sand. Serving as proxy for seedling thrust, we inserted pre-germinated seeds of three confamiliar plant species with different seed masses (members of the Fabaceae family: Lotus corniculatus L., Ornithopus sativus Brot., and Glycine max (L.) Merr.). In each treatment as well as in the control group planting depths were 10 mm. We took care that experimental plots had identical crust thickness, slightly less than 4 mm, serving as proxy for mechanical resistance. A plot became established as follows: Firstly, the pristine crusted surface was vertically cut. To the windward side the BSC remained intact (i: "with BSC" stripe). To the downwind side soil material was temporarily excavated for laterally inserting the seeds beneath the surface of the first stripe. Then at the thereby disturbed second stripe pulverised BSC material became filled as a top layer (ii: "BSC mix" stripe). From the next stripe the BSC was removed (iii: "no BSC" stripe). Thus each plot had each experimental group in spatial contiguity (within 50 cm × 50 cm). The overall 50 plots were distributed across an area of 40 m × 12 m. When individuals of a species either emerged at all stripes, "× × ×", or at no stripe of a plot, "- - -", there was no reason to suppose any effect of a crust. The "- × ×" emergence pattern (depicting the appearance of seedlings in both stripes possessing manipulated surfaces) points towards hindrance more clearly than "- × -" or "- -

  12. Epidemiology of Imported Leishmaniasis in Italy: Implications for a European Endemic Country.

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    Trentina Di Muccio

    Full Text Available In the past decade, the number of imported leishmaniasis cases has increased in countries of Western Europe. The trend is associated with increasing travels, ecotourism activity, military operations and immigration. While in endemic countries leishmaniasis is usually well diagnosed, accurate patient history and parasite identification are necessary to distinguish between autochthonous and imported cases. This is particularly important, as new Leishmania species/genotypes may be introduced and transmitted by local phlebotomine vectors without appropriate surveillance, with unpredictable consequences. We report on the surveillance of imported leishmaniasis performed by the Leishmania Identification Reference Centre of Rome from 1986 through 2012, involving health care centres from 16/20 Italian regions. Suspected imported cases were analyzed and conclusions were based on clinical, epidemiological and diagnostic findings. Over the years, different parasite identification methods were employed, including MultiLocus Enzyme Electrophoresis and molecular techniques combining disease diagnosis (SSU rDNA nested-PCR and Leishmania typing (nuclear repetitive sequence and ITS-1 PCR-RFLPs. A total of 105 imported cases were recorded (annual range: 0-20 of which 36 were visceral (VL (16 HIV-coinfections and 69 cutaneous (CL cases; 85 cases (52 CL were from the Old World and 20 (17 CL from the New World. Eight Leishmania species were identified, of which 7 were exotic to Italy. VL importation until 1995 was associated with the spread of Mediterranean Leishmania-HIV co-infections in early 1990s. Following the introduction of HAART treatment, such cases became occasional in Italians but relatively frequent among immigrants. In contrast, a steady increase of CL cases was observed from different areas of the Old and New Worlds, that in recent years included mainly immigrants 'visiting friends and relatives' and Italian tourists. This positive trend likely depends

  13. Early Childhood Student Teachers’ Observation and Experimentation of Creative Practices as a Design Processes

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    Janaina Minelli de Oliveira

    2015-07-01

    Full Text Available In this paper, we address the guidance of student teachers in initial training in schools as an invaluable opportunity to raise creative learning awareness. The objective of this present research is to develop guidance strategies for guiding the identification of creative practices and for analyzing that moment as a “way of knowing”. We analyze how to mentor future teachers so they feel willing to promote student engagement and creative thinking through their own practices. We adopted a case study approach guided by multimodal principles. We found that triangulation of individual interviews, focus group discussions and a diary of class observation was a useful strategy in the guidance of student teachers in initial training in schools. Results show these strategies allowed them to become more accepting of unpredicted or undesired results, as they approached their sessions’ designs as forms of experimentation. We argue it is essential to guide future educators in the critical analysis of the “standard classroom”, helping them design creative alternatives through collaborative experimentation.

  14. Early supra- and subgingival plaque formation in experimental gingivitis in smokers and never-smokers.

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    Branco, Paula; Weidlich, Patricia; Oppermann, Rui Vicente; Rösing, Cassiano Kuchenbecker

    2015-01-01

    To evaluate supragingival and subgingival plaque formation on the dentogingival area in smokers and never smokers using the experimental gingivitis model and a plaque scoring system that considers the presence of an area free of plaque between plaque and the gingival sulcus called the plaque free zone (PFZ). Male volunteers, 9 current smokers and 10 never-smokers, refrained from oral hygiene procedures in the maxillary incisors and canines (test teeth) for 25 days. Under conditions of clinically healthy gingiva (phase 1) and gingival inflammation (phase 2), the supragingival plaque formation pattern was observed for 4 days in the dentogingival area. Gingival crevicular fluid was also measured. Plaque was dyed with fucsine and its presence was recorded by a calibrated examiner based on a 3-criteria scoring system: 0 - absence of stained plaque; 1 - presence of stained plaque and supragingival PFZ; 2 - presence of stained plaque and absence of PFZ, indicating that subgingival plaque formation has taken place. In both phases, smokers presented a significantly lower relative frequency of sites with subgingival plaque compared to never-smokers (P < 0.001). Mean gingival crevicular fluid was significantly higher in the presence of gingival inflammation for both groups (P = 0.001), whereas smokers demonstrated a significantly lower frequency of gingival bleeding than did non-smokers (23.6% vs 66.1%; P < 0.001). Smokers presented significantly lower percentages of sites with subgingival plaque in all experimental periods and presented less gingival inflammation as shown by GBI and gingival crevicular fluid quantification.

  15. Risk factors for death in children with visceral leishmaniasis.

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    Márcia Jaqueline Alves de Queiroz Sampaio

    Full Text Available BACKGROUND: Despite the major public health importance of visceral leishmaniasis (VL in Latin America, well-designed studies to inform diagnosis, treatment and control interventions are scarce. Few observational studies address prognostic assessment in patients with VL. This study aimed to identify risk factors for death in children aged less than 15 years admitted for VL treatment in a referral center in northeast Brazil. METHODOLOGY/PRINCIPAL FINDINGS: In a retrospective cohort, we reviewed 546 records of patients younger than 15 years admitted with the diagnosis of VL at the Instituto de Medicina Integral Professor Fernando Figueira between May 1996 and June 2006. Age ranged from 4 months to 13.7 years, and 275 (50% were male. There were 57 deaths, with a case-fatality rate of 10%. In multivariate logistic regression, the independent predictors of risk of dying from VL were (adjusted OR, 95% CI: mucosal bleeding (4.1, 1.3-13.4, jaundice (4.4, 1.7-11.2, dyspnea (2.8, 1.2-6.1, suspected or confirmed bacterial infections (2.7, 1.2-6.1, neutrophil count <500/mm³ (3.1, 1.4-6.9 and platelet count <50,000/mm³ (11.7, 5.4-25.1. A prognostic score was proposed and had satisfactory sensitivity (88.7% and specificity (78.5%. CONCLUSIONS/SIGNIFICANCE: Prognostic and severity markers can be useful to inform clinical decisions such as whether a child with VL can be safely treated in the local healthcare facility or would potentially benefit from transfer to referral centers where advanced life support facilities are available. High risk patients may benefit from interventions such as early use of extended-spectrum antibiotics or transfusion of blood products. These baseline risk-based supportive interventions should be assessed in clinical trials.

  16. Geographical distribution of cutaneous leishmaniasis and sand flies in Pakistan.

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    Shakila, Ashraf; Bilqees, Fatima Mujib; Salim, Azra; Moinuddin, Moinuddin

    2006-01-01

    Cutaneous leishmaniasis is found in all the four provinces of Pakistan; these are NWFP, Balochistan, Sindh and Punjab. In Balochistan the areas from where the patients came are Uthal, Quetta and Ormara. The highest number of patients came from Quetta and least from Ormara. The patients included in this study were from the Mangopir and Chakewara, areas of Karachi. The infection is endemic in this country and the recent epidemics in the Dadu District and Nawabshah indicate its importance in the locality. The sand fly vector is found in all four provinces of Pakistan that are listed here. It is quite obvious that presence of leishmaniasis indicates the presence of sand flies and cutaneous leishmaniasis is more common.

  17. Maiden Visit of Visceral Leishmaniasis to Malwa Region

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    Shirish S Nandedkar, Kamal Malukani, Amit Varma

    2013-01-01

    Full Text Available Visceral Leishmaniasis is a well known public health problem in eastern parts of India. So far the cases have not been reported from Malwa plateu of Madhya Pradesh, to the best of our knowledge and available literature. We report here two cases of Visceral Leishmaniasis first time from the Malwa region. Both the cases are from the migratory population of Bihar. The diseases like Leishmaniasis which were previously restricted to endemic areas of the country are spreading to non endemic areas along with the large migratory population, which is seen with the development of the country.. The cases are reported to inform the National health authorities to take proper steps to curb the spread of the disease to non -endemic areas and to emphasize the need of vector surveys in these areas.

  18. Tuberous sclerosis with visceral leishmaniasis: a case report

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    Pandey Krishna

    2009-09-01

    Full Text Available Abstract Introduction Visceral leishmaniasis, a tropical infectious disease, is a major public health problem in India. Tuberous sclerosis, a congenital neuro-ectodermosis, is an uncommon disease which requires life long treatment. Case presentation A 15-year-old Indian patient, presented to the outpatient department of our institute with a high-grade fever for two months, splenomegaly and a history of generalized tonic-clonic convulsions since childhood. The clinical and laboratory findings suggested visceral leishmaniasis with tuberous sclerosis. The patient was treated with miltefosine and antiepileptics. Conclusion The patient responded well and in a follow up six months after presentation, she was found free of visceral leishmaniasis and seizures. Diagnosis and treatment of this rare combination of diseases is difficult.

  19. Clinical and epidemiological aspects of feline leishmaniasis in Brazil

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    Luiz da Silveira Neto

    2015-06-01

    Full Text Available Tegumentary and visceral leishmaniasis are severe and unfortunately common parasitic diseases in Brazil. Among domestic animals, dogs are considered the main urban reservoir of the protozoan parasites, however, there is evidence that infected cats can also contribute towards the disease pool. The number of cats diagnosed with leishmaniasis has greatly increased in the last few years, highlighting the importance of thorough investigations on the role of the cat in the epidemiological cycle of the disease and in public health related issues. The main clinical manifestations of leishmaniasis suffered by cats, even when infected with Leishmania chagasi, a viscerotropic species, are skin abnormalities, which can be confounded with multiple other diseases. Indirect ELISA should be used as a screening test in epidemiological investigations for being a sensitive technique, followed by more specific laboratory tests. The standardization and validation of rapid, economical and reproducible diagnostic methods, to be employed in epidemiological surveillance, are still required

  20. An experimental public: heterogeneous groups defining embodiment in the early twenty-first century.

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    Laki, Julia

    2014-01-01

    In this paper, I take a look at certain forms of contemporary art as practices that allow meanings within biomedical science and medical practice to emerge in novel ways. I claim that conceptual art and biological art are two unique spaces within which the understanding of embodiment and disease comes to be shaped actively and reflexively, sometimes on the very level of the materiality of the body, sometimes through the articulation and representation of medical images and technologies. I link these developments to Paul Rabinow's notion of biosociality and argue that the molecularization and geneticization of the medical gaze, conjoined with certain social and cultural shifts, results in the formation of an experimental public of artists, scientists and lay people, all invested in actively shaping the conceptualization of bodies and diseases. This will take me to a consideration of the intertwining of art and medicine beyond the domain of the visual.

  1. Post-operative levamisole may compromise early healing of experimental intestinal anastomoses.

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    de Waard, J. W.; Wobbes, T.; de Man, B. M.; van der Linden, C. J.; Hendriks, T.

    1995-01-01

    There exists growing interest in immediate post-operative local adjuvant therapy after resection of intestinal malignancies. It is therefore necessary to assess it potential effect on the healing of intestinal anastomoses. Five groups (n = 20) of rats underwent resection and anastomosis of both ileum and colon: a control group and four experimental groups receiving intraperitoneal 5-fluorouracil (5-FU), 5-FU plus leucovorin, 5-FU plus levamisole or levamisole alone, on the day of surgery and the next 2 days. Animals were killed 3 or 7 days after operation. Another three groups (n = 6) of animals were used to compare anastomotic collagen synthetic capacity in control rats or rats receiving 5-FU or 5-FU plus levamisole. On the third post-operative day, the average anastomotic bursting pressure in the 5-FU/levamisole group was reduced by 36% as compared with the control group, both in ileum (P = 0.02) and in colon (P = 0.01). Values in the other groups were similar to those in the control group. Anastomotic breaking strength was significantly (P < 0.025) lowered in the ileum from the levamisole group at both days 3 and 7. Anastomotic collagen synthetic capacity was strongly reduced in the 5-FU and 5-FU/levamisole groups. However, there was no significant difference between the control group and the four experimental groups with regard to anastomotic hydroxyproline concentration and content, either 3 or 7 days after operation. Thus, limited use of levamisole, alone or in combination with intraperitoneal 5-FU, may compromise intestinal healing. PMID:7640232

  2. Mucocutaneous Leishmaniasis/HIV Coinfection Presented as a Diffuse Desquamative Rash

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    Guilherme Almeida Rosa da Silva

    2014-01-01

    Full Text Available Leishmaniasis is an infectious disease that is endemic in tropical areas and in the Mediterranean. This condition spreads to 98 countries in four continents, surpassing 12 million infected individuals, with 350 million people at risk of infection. This disease is characterized by a wide spectrum of clinical syndromes, caused by protozoa of the genus Leishmania, with various animal reservoirs, such as rodents, dogs, wolves, foxes, and even humans. Transmission occurs through a vector, a sandfly of the genus Lutzomyia. There are three main clinical forms of leishmaniasis: visceral leishmaniasis, cutaneous leishmaniasis, and mucocutaneous leishmaniasis. The wide spectrum of nonvisceral forms includes: localized cutaneous leishmaniasis, a papular lesion that progresses to ulceration with granular base and a large framed board; diffuse cutaneous leishmaniasis; mucocutaneous leishmaniasis, which can cause disfiguring and mutilating injuries of the nasal cavity, pharynx, and larynx. Leishmaniasis/HIV coinfection is considered an emerging problem in several countries, including Brazil, where, despite the growing number of cases, a problem of late diagnosis occurs. Clinically, the cases of leishmaniasis associated with HIV infection may demonstrate unusual aspects, such as extensive and destructive lesions. This study aims to report a case of mucocutaneous leishmaniasis/HIV coinfection with atypical presentation of diffuse desquamative eruption and nasopharyngeal involvement.

  3. Changes of inflammation-associated cytokine expressions during early phase of experimental endotoxic shock in macaques

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hui Ji; Ke-Yi Sun; Yan-Hong Feng; Guo-Qing Yin

    2004-01-01

    AIM: To study changes of inflammation-associated cytokine expressions during early phase of endotoxic shock in macague.METHODS: Experiments were performed in Macaque mulatta treated with LPS 2.8 mg/kg in shock model group or with normal saline in control group. Blood samples were collected before, or 60 min, or 120 min after LPS injection,respectively. Liver and spleen tissues were obtained at 120 min after LPS injection. The plasma levels of TNF-α,IL-1 β, IL-10 and IL-12P40 were determined by doubleantibody sandwich ELISA with antibodies against human cytokines. The mRNA levels of TNF-α, IL-1 β, and IL-18 in peripheral blood mononuclear cells (PBMCs), liver and spleen were examined by real-time fluorescence semi-quantitative RT-PCR with the primers based on human genes.RESULTS: Mean systemic arterial pressure (MAP), systemic vascular resistance index (SVRI) and left ventricular work index (LVWI) of macaques were significant declined in shock model group on average 60 min after LPS injection. The plasma levels of TNF-α and IL-10 were significantly increased 60 min after LPS injection and then decreased.The plasma levels of IL-1 β and IL-12P40 were significantly increased at 120 min after LPS injection. The mRNA levels of TNF-α and IL-1 β were significantly increased 60 min after LPS stimulation in PBMCs and 120 min after LPS stimulation in livers. The mRNA level of IL-18 was significantly increased 120 min after LPS stimulation in PBMCs and livers. But in spleen, only TNF-α mRNA level in LPS group was significantly higher 120 min after LPS stimulation, compared with that in control group.CONCLUSION: An endotoxic shock model of Macaque mulatta was successfully established. Both antibodies for ELISA and PCR primers based on human cytokine assays were successfully applied to detect macaque cytokines. In the model, inflammatory cytokines, such as TNF-α, IL-1 β,IL-12 and IL-18 as well as anti-inflammation cytokine IL-10,were released at very early phase of

  4. Animal reservoirs of visceral leishmaniasis in India.

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    Singh, Niti; Mishra, Jyotsna; Singh, Ram; Singh, Sarman

    2013-02-01

    Visceral leishmaniasis (VL) is a disease that has both zoonotic and anthroponotic etiologies. In India, VL is endemic, considered to be anthroponotic, and caused by Leishmania donovani . Anthroponotic diseases are maintained by transmission from human to human and to a lesser extent from human to animals. Serum samples from 1,220 animals from 7 human VL endemic districts of Bihar, India, were tested for antibodies to a recombinant kinetoplast antigen (rK39 antigen) present in amastigotes of visceralizing Leishmania species, i.e., L. donovani complex. Additionally, PCR was used to examine samples positive by rK39 antigen serology. Antibodies to rK39 indicative of VL were detected in 33 of 1,220 animals. Thirty-one of 867 goats (Capra hircus), 1 of 161 cattle (Bos indicus), and 1 of 54 wild rats (Rattus sp.) were positive by rK39 serology. None of 106 chickens (Gallus domesticus), 26 sheep (Ovis aries), 3 water buffaloes (Bubalus bubalus), or 3 dogs (Canis familiaris) was positive by rK39 serology. Leishmania donovani DNA was detected by PCR in 20 rK39 positive blood samples from goats and 1 sample from a cow. The present study indicates that goats are potential animal reservoirs of human VL in India.

  5. Cutaneous Leishmaniasis in North Africa: a review

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    2014-01-01

    Full Text Available In North African countries, cutaneous leishmaniasis transmission has been increasing since the 1980s, with a significant increase in the incidence of cases and a spread of the geographical distribution. The disease currently represents a major public health problem with a productivity gap and an impediment for development, which results in dramatic socioeconomic and psycho-sanitary impacts. The incidence is more than thousands of cases every year in Algeria, Libya, Morocco, and Tunisia. In Egypt, only a few dozen cases per year are reported, mainly in the Sinai Peninsula. Three Leishmania species, associated with distinct eco-epidemiological and clinical patterns, are involved, namely Leishmania infantum, L. major, and L. tropica. However, L. major is by far the most frequent in Algeria, Libya, and Tunisia, with more than 90% of the registered cases. It is mainly encountered in rural areas under semi-arid, arid and Saharan climates. Leishmania tropica is more prevalent in Morocco, reaching 30–40% of isolates in some districts. Much data is still missing concerning the risk factors of the infection and the lesion development, as well as vector and reservoir ecology and behavior. The knowledge of such parameters, following multidisciplinary and integrated approaches, is crucial for better management and control of the disease, that also faces a lack of resources and efficient control measures.

  6. Visceral leishmaniasis in adults with nephropathy

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    H Kaaroud El Jeri

    2017-01-01

    Full Text Available The aim of this study is to evaluate the features of visceral leishmaniasis (VL in adults with nephropathy, who were not infected with the human immunodeficiency virus. This is a retrospective study of 14 adults hospitalized between 2000 and 2014, with VL and renal involvement. Clinical, biological, and therapeutic data were collected from the patients′ medical files. Eleven women and three men, most of whom were from the North of the country, with a mean age of 40.5 years were studied. Lupus was present in five cases, the Sicca syndrome in three cases, diabetes in one case, renal failure on dialysis in two cases, and there were three renal transplant recipients. Major clinical symptoms were fever and weakness in all cases. Enlargement of the spleen was present in eight cases and hepatomegaly in six cases. Biologic inflammatory syndrome and anemia were present in all cases, and pancytopenia was present in seven cases. Renal insufficiency was noted in all cases. Diagnosis of VL was confirmed by bone marrow examination or serology. Treatment consisted of antimoniate in 10 cases and amphotericin B in four cases. Seven deaths were recorded. Clinical symptoms of VL are atypical in patients with nephropathy and therefore, the diagnosis should be suspected in such patients because VL is still endemic in our country.

  7. Distribution of Human Leishmaniasis (VL and Its Associated Risk Factors, in Metemma, Ethiopia

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    Yibeltal Terefe

    2015-01-01

    Full Text Available Background. Leishmaniasis is a parasitic disease caused by obligate intracellular protozoans of the genus Leishmania. Objective. To assess the distribution of human leishmaniasis and assess community knowledge, attitude, and practice with regard to assumed risk factors and control options used by the society. Methods. Retrospective study from November 2013 to May 2014 was used. Six-year data from Metemma hospital record was reviewed and 89 people were interviewed. Results. The rates were 29% (n = 374/1270 and 26% (n = 328/1270 in 2005 E.C and 2003 E.C, respectively. 94% (1194/1270 of the affected individuals were in the age exceeding 15 years. At the same time, the rates in males and female were 97% (n = 1226/1270 and 3% (n = 44/1270, respectively. According to 88.8% (n = 79/89 of the respondents, transmission occurs through bite of sandflies, while 98.9% (n = 88/89 of the respondent’s indicated that waste disposal in an open space was one of the risk factors for disease occurrence. Regarding the control measures, respondents replied that 73% (n = 65/89 of them use impregnated bed net and others use cleaning and proper waste disposal. Conclusion. The current finding indicated that the disease was common in the study area; as a result, proper use of impregnated bed net, early diagnosis and treatment, and reduction of different risk factors were essential.

  8. Interest in paromomycin for the treatment of visceral leishmaniasis (kala-azar

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    Wiwanitkit V

    2012-06-01

    Full Text Available Viroj Wiwanitkit1–31Wiwanitkit House, Bang Khae, Bangkok, Thailand; 2Hainan Medical University, Haikou, Hainan, People's Republic of China; 3Joseph Ayo Babalola University, Ikeji-Arakeji, Osun State, NigeriaAbstract: Leishmaniasis is an important vector-borne disease, and it is classified as one of the most important tropical fly-borne infections. This disease can cause two types of clinical manifestations: cutaneous forms and visceral forms. Visceral leishmaniasis, which is also called kala-azar, is a very serious infection that can be fatal. The management of visceral leishmaniasis requires informed diagnostic and therapeutic approaches. Continuous research and development regarding the treatment of visceral leishmaniasis had led to many improvements. Paromomycin is a relatively new antibiotic drug that has been used for the treatment of visceral leishmaniasis for several years. This article reviews and discusses the use of paromomycin for visceral leishmaniasis therapy.Keywords: visceral, leishmaniasis, paromomycin

  9. Local suppression of T cell responses by arginase-induced L-arginine depletion in nonhealing leishmaniasis.

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    Manuel Modolell

    Full Text Available The balance between T helper (Th 1 and Th2 cell responses is a major determinant of the outcome of experimental leishmaniasis, but polarized Th1 or Th2 responses are not sufficient to account for healing or nonhealing. Here we show that high arginase activity, a hallmark of nonhealing disease, is primarily expressed locally at the site of pathology. The high arginase activity causes local depletion of L-arginine, which impairs the capacity of T cells in the lesion to proliferate and to produce interferon-gamma, while T cells in the local draining lymph nodes respond normally. Healing, induced by chemotherapy, resulted in control of arginase activity and reversal of local immunosuppression. Moreover, competitive inhibition of arginase as well as supplementation with L-arginine restored T cell effector functions and reduced pathology and parasite growth at the site of lesions. These results demonstrate that in nonhealing leishmaniasis, arginase-induced L-arginine depletion results in impaired T cell responses. Our results identify a novel mechanism in leishmaniasis that contributes to the failure to heal persistent lesions and suggest new approaches to therapy.

  10. Possibilities and challenges for developing a successful vaccine for leishmaniasis.

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    Srivastava, Saumya; Shankar, Prem; Mishra, Jyotsna; Singh, Sarman

    2016-05-12

    Leishmaniasis is a vector-borne disease caused by different species of protozoan parasites of the genus Leishmania. It is a major health problem yet neglected tropical diseases, with approximately 350 million people worldwide at risk and more than 1.5 million infections occurring each year. Leishmaniasis has different clinical manifestations, including visceral (VL or kala-azar), cutaneous (CL), mucocutaneous (MCL), diffuse cutaneous (DCL) and post kala-azar dermal leishmaniasis (PKDL). Currently, the only mean to treat and control leishmaniasis is by rational medications and vector control. However, the number of available drugs is limited and even these are either exorbitantly priced, have toxic side effects or prove ineffective due to the emergence of resistant strains. On the other hand, the vector control methods are not so efficient. Therefore, there is an urgent need for developing a safe, effective, and affordable vaccine for the prevention of leishmaniasis. Although in recent years a large body of researchers has concentrated their efforts on this issue, yet only three vaccine candidates have gone for clinical trial, until date. These are: (i) killed vaccine in Brazil for human immunotherapy; (ii) live attenuated vaccine for humans in Uzbekistan; and (iii) second-generation vaccine for dog prophylaxis in Brazil. Nevertheless, there are at least half a dozen vaccine candidates in the pipeline. One can expect that, in the near future, the understanding of the whole genome of Leishmania spp. will expand the vaccine discovery and strategies that may provide novel vaccines. The present review focuses on the development and the status of various vaccines and potential vaccine candidates against leishmaniasis.

  11. Role of Mitochondrial Calcium Uniporter in Early Brain Injury After Experimental Subarachnoid Hemorrhage.

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    Yan, Huiying; Zhang, Dingding; Hao, Shuangying; Li, Kuanyu; Hang, Chun-Hua

    2015-12-01

    Previous studies have shown that mitochondrial Ca(2+) is undertaken by mitochondrial calcium uniporter (MCU), and its accumulation is associated with the development of many diseases. However, little was known about the role of MCU in early brain injury (EBI) after subarachnoid hemorrhage (SAH). MCU can be opened by spermine under a physiological condition and inhibited by ruthenium red (RR). Herein, we investigated the effects of RR and spermine to reveal the role of MCU in SAH animal model. The data obtained with biochemical and histological assays showed that mitochondrial Ca(2+) concentration was significantly increased in the temporal cortex of rats 1, 2, and 3 days after SAH, consistent with constant high levels of cellular Ca(2+) concentration. In agreement with the observation in the acute phase, SAH rats showed an obvious increase of reactive oxygen species (ROS) level and decrease of ATP production. Blockage of MCU prevented Ca(2+) accumulation, abated the level of oxidative stress, and improved the energy supply. Translocation of cytochrome c, increased cleaved caspase-3, and a large amount of apoptotic cells after SAH were reversed by RR administration. Surprisingly, exogenous spermine did not increase cellular Ca(2+) concentration, but lessened the Ca(2+) accumulation after SAH to benefit the rats. Taken together, our results demonstrated that blockage of MCU or prevention of Ca(2+) accumulation after SAH is essential in EBI after SAH. These findings suggest that MCU is considered to be a therapeutic target for patients suffering from SAH.

  12. Dutch law and ethics concerning the experimental treatment of early psychosis.

    Science.gov (United States)

    van Leeuwen, E

    2001-08-01

    Moral and social attitudes towards medical treatment and research rapidly changed during the last four decades of the Twentieth Century. In the Netherlands these changes are reflected in three laws adopted in the 1990s. The Law on Medical Treatment Agreement (Wet Geneeskundige BehandelOvereenkomst, WGBO, 1992) reflects the respect for autonomy and the protection of patient's rights. The Law on Special Admission to Psychiatric Hospitals (Bijzondere Opneming Psychiatrische Ziekenhuizen, BOPZ, 1994) reflects the idea that psychiatric subjects should be entitled to execute their civil rights as long as no danger exists to themselves or others, while the Law on Medical Research (Wet Medisch Onderzoek, WMO 1999), reflects the present moral opinions on bio-medical research. From these laws objections can be derived against the development of treatment and experiments on early psychosis. It will be argued here that these laws can also be taken to stimulate this kind of research. The difference between the two options is related to preconceived moral opinions towards psychosis and schizophrenia.

  13. High levels of plasma IL-10 and expression of IL-10 by keratinocytes during visceral leishmaniasis predict subsequent development of post-kala-azar dermal leishmaniasis

    DEFF Research Database (Denmark)

    Gasim, S; Elhassan, A M; Khalil, E A

    1998-01-01

    Some patients develop post-kala-azar dermal leishmaniasis (PKDL) after they have been treated for the systemic infection kala-azar (visceral leishmaniasis). It has been an enigma why the parasites cause skin symptoms after the patients have been successfully treated for the systemic disease. We...... report here that PKDL development can be predicted before treatment of visceral leishmaniasis, and that IL-10 is involved in the pathogenesis. Before treatment of visceral leishmaniasis, Leishmania parasites were present in skin which appeared normal on all patients. However, IL-10 was detected...

  14. Trace elements in sera from patients with visceral leishmaniasis

    Energy Technology Data Exchange (ETDEWEB)

    Mukhopadhyay, R.; Bhattacharya, A. [Department of Zoology, Calcutta University, Calcutta (India); Chakraborty, A.; Sudarshan, M.; Jal, P.K.; Chintalapudi, S.N. [Inter University Consortium for DAE Facilities, Calcutta Centre 3/LB-8, Bidhan Nagar, Calcutta (India); Dutta, R.K. [Schonland Research Centre for Nuclear Sciences, University of Witwatersrand, Johannesburg (South Africa)

    2000-07-01

    Trace elements are known to have pivotal role in human health and disease. Present investigation employed PIXE analysis to probe into the elemental profile of patients suffering from visceral Leishmaniasis. Remarkable alternations were observed in concentration of elements like Cl, K, Ca, Mn, Fe, Cu, Zn. The pattern of enhancement of elemental concentration corresponds to the progression of the disease. Additionally, our present data reflect probable correlation between alteration in trace elemental status and other pathological syndromes associated with Leishmaniasis. The possibility of considering trace elements as a diagnostic marker for a better understanding of the disease is discussed. (author)

  15. Leishmaniasis: a review [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Edoardo Torres-Guerrero

    2017-05-01

    Full Text Available Leishmaniasis is caused by an intracellular parasite transmitted to humans by the bite of a sand fly. It is endemic in Asia, Africa, the Americas, and the Mediterranean region. Worldwide, 1.5 to 2 million new cases occur each year, 350 million are at risk of acquiring the disease, and leishmaniasis causes 70,000 deaths per year. Clinical features depend on the species of Leishmania involved and the immune response of the host. Manifestations range from the localized cutaneous to the visceral form with potentially fatal outcomes. Many drugs are used in its treatment, but the only effective treatment is achieved with current pentavalent antimonials.

  16. Combined Immune Therapy for the Treatment of Visceral Leishmaniasis

    Science.gov (United States)

    Bunn, Patrick T.; Singh, Neetu; Chauhan, Shashi Bhushan; Sheel, Meru; Amante, Fiona H.; Montes de Oca, Marcela; Edwards, Chelsea L.; Ng, Susanna S.; Best, Shannon E.; Haque, Ashraful; Beattie, Lynette; Hafner, Louise M.; Sacks, David; Nylen, Susanne; Sundar, Shyam; Engwerda, Christian R.

    2016-01-01

    Chronic disease caused by infections, cancer or autoimmunity can result in profound immune suppression. Immunoregulatory networks are established to prevent tissue damage caused by inflammation. Although these immune checkpoints preserve tissue function, they allow pathogens and tumors to persist, and even expand. Immune checkpoint blockade has recently been successfully employed to treat cancer. This strategy modulates immunoregulatory mechanisms to allow host immune cells to kill or control tumors. However, the utility of this approach for controlling established infections has not been extensively investigated. Here, we examined the potential of modulating glucocorticoid-induced TNF receptor-related protein (GITR) on T cells to improve anti-parasitic immunity in blood and spleen tissue from visceral leishmaniasis (VL) patients infected with Leishmania donovani. We found little effect on parasite growth or parasite-specific IFNγ production. However, this treatment reversed the improved anti-parasitic immunity achieved by IL-10 signaling blockade. Further investigations using an experimental VL model caused by infection of C57BL/6 mice with L. donovani revealed that this negative effect was prominent in the liver, dependent on parasite burden and associated with an accumulation of Th1 cells expressing high levels of KLRG-1. Nevertheless, combined anti-IL-10 and anti-GITR mAb treatment could improve anti-parasitic immunity when used with sub-optimal doses of anti-parasitic drug. However, additional studies with VL patient samples indicated that targeting GITR had no overall benefit over IL-10 signaling blockade alone at improving anti-parasitic immune responses, even with drug treatment cover. These findings identify several important factors that influence the effectiveness of immune modulation, including parasite burden, target tissue and the use of anti-parasitic drug. Critically, these results also highlight potential negative effects of combining different

  17. Combined Immune Therapy for the Treatment of Visceral Leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Rebecca J Faleiro

    2016-02-01

    Full Text Available Chronic disease caused by infections, cancer or autoimmunity can result in profound immune suppression. Immunoregulatory networks are established to prevent tissue damage caused by inflammation. Although these immune checkpoints preserve tissue function, they allow pathogens and tumors to persist, and even expand. Immune checkpoint blockade has recently been successfully employed to treat cancer. This strategy modulates immunoregulatory mechanisms to allow host immune cells to kill or control tumors. However, the utility of this approach for controlling established infections has not been extensively investigated. Here, we examined the potential of modulating glucocorticoid-induced TNF receptor-related protein (GITR on T cells to improve anti-parasitic immunity in blood and spleen tissue from visceral leishmaniasis (VL patients infected with Leishmania donovani. We found little effect on parasite growth or parasite-specific IFNγ production. However, this treatment reversed the improved anti-parasitic immunity achieved by IL-10 signaling blockade. Further investigations using an experimental VL model caused by infection of C57BL/6 mice with L. donovani revealed that this negative effect was prominent in the liver, dependent on parasite burden and associated with an accumulation of Th1 cells expressing high levels of KLRG-1. Nevertheless, combined anti-IL-10 and anti-GITR mAb treatment could improve anti-parasitic immunity when used with sub-optimal doses of anti-parasitic drug. However, additional studies with VL patient samples indicated that targeting GITR had no overall benefit over IL-10 signaling blockade alone at improving anti-parasitic immune responses, even with drug treatment cover. These findings identify several important factors that influence the effectiveness of immune modulation, including parasite burden, target tissue and the use of anti-parasitic drug. Critically, these results also highlight potential negative effects of

  18. Experimental studies on pathogenesis of the brain radiation injury in early stage

    Energy Technology Data Exchange (ETDEWEB)

    Ye Tian [Suzhou Medical Coll., Jiangsu (China). 2nd Affiliated Hospital; Shiyao Bao; Weibo Yin; Chunfeng Liu; Zhilin Zhang

    2000-05-01

    To investigate the pathogenesis of the brain radiation injury in the early stage, a series of experiments were performed as below. The SD rats halfbrain were irradiated by the single dose of 10, 20, and 30 Gy of 4 MeV electron, all those experiments were performed in 1 day to 3 months after radiation. The neurological symptoms, the weight and the skin response inside the field of all the rats were evaluated sequentially. The measurement of regional cerebral blood flow (rCBF) using hydrogen gas generated by electrolysis, the calculation of the brain water content percentage with wet-dry weight formula. The DNA contents and the quantities of bcl-2 protein were analyzed by flow cytometry. The brain histological sections were scanned to assess the present or absence of white matter necrosis in the region of hippocampus, and then the hippocampus region was observed for the morphological changes of the blood vessel, neuroglial, and the neurons. Some of the data were analyzed by the Student t test. Intra-portal alopecia was observed in all rats which received 30 Gy and some rats which received 20 Gy, the abnormal neurological signs were not found in all the rats, but the tend of weight increase was less pronounced in 1-3 months in the irradiated rats than those unirradiated. By comparison the unirradiated hemisphere, the rCBF of the contralateral brain decreased in most of the rats. In 20 Gy and 30 Gy groups, rCBF decreased areas expand gradually along with the prolong of observation time, from the nucleus caudate putamen, to the frontal cortex and then the hippocampus, the rCBF of whole the irradiated hemibrain was reduced significantly at 3 month after radiation. The water content of the irradiated halfbrain increased progressively, it means the brain edema exists in the meantime. By comparison the unirradiation halfbrain, the apoptosis of the hippocampus cells in the irradiated brain increased, and the expression of bcl-2 protein decreased at the meantime, and those

  19. Early prediction of functional outcome using dynamic contrast enhanced magnetic resonance imaging in experimental stroke.

    Science.gov (United States)

    Huang, Wei-Yuan; Wu, Gang; Li, Jian-Jun; Geng, Dao-Ying; Tan, Wen-Li; Yu, Xiang-Rong

    2016-09-01

    Early prediction of functional outcome in cerebral ischemia stroke using MRI remains a challenge. The aim of this study was to evaluate the predictive value of dynamic contrast-enhanced (DCE) MRI in terms of functional outcome of ischemia stroke. Right middle cerebral artery occlusion (MCAO) was performed in male SD rats (n=50), followed by withdrawal of the occluding filament after 3 (n = 10), 4 (n = 10), 5 (n = 10), 6 (n = 10) or 7 (n = 10) h to establish ischemia and reperfusion stroke. DCE and conventional MRI were performed in each animal 60 ± 15 min before and after reperfusion. The outcome was assessed by the modified Neurological Severity Scores (mNSS) (before reperfusion and at 72 h after reperfusion) and the infarct volume. Comparisons of functional prognosis and DCE parameters (K(trans), Ve and Kep) were performed using binary logistic regression and operating characteristic (ROC) analysis. DCE parameters results indicated that blood brain barrier (BBB) permeability increased with prolonged reperfusion timing. Using binary logistic regression analysis on stroke characteristics (reperfusion timing, infarct volume) and BBB permeability parameters (drK(trans)subcortex, drK(trans)cortex, drVesubcortex, drVecortex, drKepsubcortex and drKepcortex) as covariates , the results demonstrated that reperfusion timing, infarct volume, drK(trans)subcortex and drKepsubcortex were independent factors that were associated with prognosis (OR=0.01, OR=0.23, OR=245.23, OR=1.29). ROC analysis indicated that a drK(trans)subcortex threshold of 0.88 with a sensitivity of 95.7% and a specificity of 85.2% and a drKepsubcortex threshold of -0.25 with a sensitivity of 69.6% and a specificity of 70.4% for differentiation between favourable and unfavourable prognosis. Quantitative DCE-MRI can be used to predict the functional outcomes of cerebral ischemia injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Design, rationale and feasibility of a multidimensional experimental protocol to study early life stress

    Directory of Open Access Journals (Sweden)

    M. Dillwyn Bartholomeusz

    2017-09-01

    Full Text Available There is a rapidly accumulating body of evidence regarding the influential role of early life stress (ELS upon medical and psychiatric conditions. While self-report instruments, with their intrinsic limitations of recall, remain the primary means of detecting ELS in humans, biological measures are generally limited to a single biological system. This paper describes the design, rationale and feasibility of a study to simultaneously measure neuroendocrine, immune and autonomic nervous system (ANS responses to psychological and physiological stressors in relation to ELS. Five healthy university students were recruited by advertisement. Exclusion criteria included chronic medical conditions, psychotic disorders, needle phobia, inability to tolerate pain, and those using anti-inflammatory medications. They were clinically interviewed and physiological recordings made over a two-hour period pre, during and post two acute stressors: the cold pressor test and recalling a distressing memory. The Childhood Trauma Questionnaire and the Parental Bonding Index were utilised to measure ELS. Other psychological measures of mood and personality were also administered. Measurements of heart rate, blood pressure, respiratory rate, skin conductance, skin blood flow and temporal plasma samples were successfully obtained before, during and after acute stress. Participants reported the extensive psychological and multisystem physiological data collection and stress provocations were tolerable. Most (4/5 participants indicated a willingness to return to repeat the protocol, indicating acceptability. Our protocol is viable and safe in young physically healthy adults and allows us to assess simultaneously neuroendocrine, immune and autonomic nervous system responses to stressors in persons assessed for ELS.

  1. Quantitative assessment of early experimental diabetes in rats using dynamic contrast-enhanced computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Murase, Kenya [Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871 (Japan)], E-mail: murase@sahs.med.osaka-u.ac.jp; Kitamura, Akihiro; Tachibana, Atsushi; Kusakabe, Yoshinori; Matsuura, Risa; Miyazaki, Shohei [Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871 (Japan)

    2010-04-15

    Purpose: To quantitatively assess the time course of changes of the renal volume and function in the early phase of streptozotocin (STZ)-induced diabetes in rats using dynamic contrast-enhanced computed tomography (DCE-CT). Methods: The DCE-CT studies were performed in 24 male Sprague-Dawley rats (n = 6 for control and n = 18 for STZ-treated group) on days 0, 4, 7, 11, and 14 using a multi-detector row CT. The rats of an STZ-treated group were given intraperitoneally 65 mg/kg body weight of STZ on day 0, and were divided into two groups based on the blood glucose concentration on day 4 being less than 300 mg/dL [STZ-treated group (L), n = 8] or greater than 300 mg/dL [STZ-treated group (G), n = 10]. The contrast clearance per unit renal volume (K{sub 1}) was estimated from the DCE-CT data using the Patlak model. The renal volume (V{sub CT}) was calculated by manually delineating the kidney on the contrast-enhanced CT image. The contrast clearance of the entire kidney (K) was obtained by K{sub 1} x V{sub CT}. Results: V{sub CT} in the STZ-treated group was significantly enlarged on day 4 compared to that on day 0 and continued until day 14. Although there were no significant changes in the time course of K{sub 1} in all groups, K in the STZ-treated groups (L) and (G) significantly increased on days 7 and 4, respectively, and continued until day 14, suggesting that hyperfiltration occurs in parallel with renal volume enlargement. Conclusion: The present method appears useful for quantitatively evaluating the time course of STZ-induced diabetes in rats, because it allows repeated and simultaneous evaluation of renal morphology and function.

  2. Modeling the early evolution of massive OB stars with an experimental wind routine

    CERN Document Server

    Keszthelyi, Zsolt; Wade, Gregg

    2016-01-01

    Stellar evolution models of massive stars are very sensitive to the adopted mass-loss scheme. The magnitude and evolution of mass-loss rates significantly affect the main sequence evolution, and the properties of post-main sequence objects, including their rotational velocities. Driven by potential discrepancies between theoretically predicted and observationally derived mass-loss rates in the OB star range, we particularly aim to investigate the response to mass-loss rates that are lower than currently adopted, in parallel with the mass-loss behavior at the "first" bi-stability jump. We perform 1D hydrodynamical model calculations of single $20 - 60 \\, M_{\\odot}$ Galactic ($Z = 0.014$) stars where the effects of stellar winds are already significant during the main sequence phase. We develop an experimental wind routine to examine the behavior and response of the models under the influence of different mass-loss rates. This observationally guided, simple and flexible wind routine is not a new mass-loss descr...

  3. Evidence for an early wet Moon from experimental crystallization of the lunar magma ocean

    Science.gov (United States)

    Lin, Yanhao; Tronche, Elodie J.; Steenstra, Edgar S.; van Westrenen, Wim

    2017-01-01

    The Moon is thought to have been covered initially by a deep magma ocean, its gradual solidification leading to the formation of the plagioclase-rich highland crust. We performed a high-pressure, high-temperature experimental study of lunar mineralogical and geochemical evolution during magma ocean solidification that yields constraints on the presence of water in the earliest lunar interior. In the experiments, a deep layer containing both olivine and pyroxene is formed in the first ~50% of crystallization, β-quartz forms towards the end of crystallization, and the last per cent of magma remaining is extremely iron rich. In dry experiments, plagioclase appears after 68 vol.% solidification and yields a floatation crust with a thickness of ~68 km, far above the observed average of 34-43 km based on lunar gravity. The volume of plagioclase formed during crystallization is significantly less in water-bearing experiments. Using the relationship between magma water content and the resulting crustal thickness in the experiments, and considering uncertainties in initial lunar magma ocean depth, we estimate that the Moon may have contained at least 270 to 1,650 ppm water at the time of magma ocean crystallization, suggesting the Earth-Moon system was water-rich from the start.

  4. New, exciting developments in experimental therapies in the early 21st century.

    Science.gov (United States)

    Los, Marek

    2009-12-25

    The volume is dedicated to novel anticancer strategies. Our aim was to identify and cover novel, emerging anticancer approaches that will form the backbone of future, more efficient anticancer therapies. Beside classical "small molecule" pharmacologic approaches, or radiotherapy, the review introduces cancer stem cell, their markers involved in metastasizing, it covers various immunotherapeutic experimental treatment, inclusive anticancer cellular vaccines, as well as computational strategies aimed at modeling of cancer therapy or at least the intermolecular interactions between drug and the cellular target. Large portion of the volume is dedicated to various targeted anticancer approaches that involve either novel targets within cancer cells (i.e. endoplasmic reticulum and protein folding, or cell-cell adherence), or novel molecules like TRAIL and another human cytokine mda-7/IL-24, Brevinin-2R, viral proteins R4orf4, NS1, and apoptin, HAMLET, onconase, and other molecules. Significant part of the review is also dedicated towards targeting of receptor-initiated and intracellular kinase cascades that are often upregulated in various malignancies. We hope that the variety of topics highlighted in this volume will foster cross-discipline collaborations, so necessary for the development of novel therapeutics.

  5. Decreased effect of glucantime in cutaneous leishmaniasis complicated with secondary bacterial infection

    Directory of Open Access Journals (Sweden)

    G Sadeghian

    2011-01-01

    Full Text Available Background: Glucantime is regarded as the first-line treatment of cutaneous leishmaniasis (CL; however, failure to treatment is a problem in many cases. Aim: The aim was to evaluate the therapeutic effect of glucantime in CL complicated with secondary bacterial infection compared to uncomplicated lesions. Methods: This experimental study was performed in Skin Diseases and Leishmaniasis Research Center, Isfahan, Iran. A total of 161 patients enrolled in the study had CL confirmed by positive smear of lesions. All the patients were treated with systemic glucantime for 3 weeks and followed for 2 months. Response to treatment was defined as loss of infiltration, reepithelization, and negative smear. Depending on the results of bacterial cultures, the lesions were divided into two groups and the efficacy of glucantime was compared. Results: A total of 123 patients (76.4% were negative, and 38 patients (23.6% were positive for secondary bacterial infection. In groups with negative bacterial culture response to treatment was 65% (80 patients and in the other positive group, it was 31.6% (12 patients, with a difference (χ2 = 13.77, P < 0.01. Conclusion: Therapeutic effect of glucantime showed a decrease in CL lesions with secondary bacterial infection. Therefore, in the cases of unresponsiveness to treatment, the lesions should be evaluated for bacterial infection, before repeating the treatment.

  6. Leishmaniavirus-Dependent Metastatic Leishmaniasis Is Prevented by Blocking IL-17A

    Science.gov (United States)

    Hartley, Mary-Anne; Bourreau, Eliane; Rossi, Matteo; Castiglioni, Patrik; Eren, Remzi Onur; Prevel, Florence; Couppié, Pierre; Hickerson, Suzanne M.; Launois, Pascal; Beverley, Stephen M.; Ronet, Catherine

    2016-01-01

    Cutaneous leishmaniasis has various outcomes, ranging from self-healing reddened papules to extensive open ulcerations that metastasise to secondary sites and are often resistant to standard therapies. In the case of L. guyanensis (L.g), about 5–10% of all infections result in metastatic complications. We recently showed that a cytoplasmic virus within L.g parasites (LRV1) is able to act as a potent innate immunogen, worsening disease outcome in a murine model. In this study, we investigated the immunophenotype of human patients infected by L.g and found a significant association between the inflammatory cytokine IL-17A, the presence of LRV1 and disease chronicity. Further, IL-17A was inversely correlated to the protective cytokine IFN-γ. These findings were experimentally corroborated in our murine model, where IL-17A produced in LRV1+ L.g infection contributed to parasite virulence and dissemination in the absence of IFN-γ. Additionally, IL-17A inhibition in mice using digoxin or SR1001, showed therapeutic promise in limiting parasite virulence. Thus, this murine model of LRV1-dependent infectious metastasis validated markers of disease chronicity in humans and elucidated the immunologic mechanism for the dissemination of Leishmania parasites to secondary sites. Moreover, it confirms the prognostic value of LRV1 and IL-17A detection to prevent metastatic leishmaniasis in human patients. PMID:27658195

  7. Topical Simvastatin as Host-Directed Therapy against Severity of Cutaneous Leishmaniasis in Mice

    Science.gov (United States)

    Parihar, Suraj P.; Hartley, Mary-Anne; Hurdayal, Ramona; Guler, Reto; Brombacher, Frank

    2016-01-01

    We recently demonstrated that statins mediate protection against intracellular pathogens, Mycobacterium tuberculosis and Listeria monocytogenes in mice. Here, we investigated the immunomodulatory potential of simvastatin as a topical or systemic host-directed drug therapy in controlling inflammatory responses in an experimental mouse model of cutaneous leishmaniasis caused by Leishmania major (LV39). In an ear infection model, topical application of simvastatin directly on established lesions significantly reduced severity of the disease reflected by ear lesion size and ulceration. The host protective effect was further accompanied by decreased parasite burden in the ear and draining lymph nodes in both BALB/c and C57BL/6 mice. Pre-treatment of these mice on a low-fat cholesterol diet and systemic simvastatin also reduced footpad swelling, as well as parasite burdens and ulceration/necrosis in the more robust footpad infection model, demonstrating the prophylactic potential of simvastatin for cutaneous leishmaniasis. Mechanistically, following L. major infection, simvastatin-treated primary macrophages responded with significantly reduced cholesterol levels and increased production of hydrogen peroxide. Furthermore, simvastatin-treated macrophages displayed enhanced phagosome maturation, as revealed by increased LAMP-3 expression in fluorescent microscopy and Western blot analysis. These findings demonstrate that simvastatin treatment enhances host protection against L. major by increasing macrophage phagosome maturation and killing effector functions. PMID:27632901

  8. Cross-protective efficacy from a immunogen firstly identified in Leishmania infantum against tegumentary leishmaniasis.

    Science.gov (United States)

    Martins, V T; Lage, D P; Duarte, M C; Costa, L E; Chávez-Fumagalli, M A; Roatt, B M; Menezes-Souza, D; Tavares, C A P; Coelho, E A F

    2016-02-01

    Experimental vaccine candidates have been evaluated to prevent leishmaniasis, but no commercial vaccine has been proved to be effective against more than one parasite species. LiHyT is a Leishmania-specific protein that was firstly identified as protective against Leishmania infantum. In this study, LiHyT was evaluated as a vaccine to against two Leishmania species causing tegumentary leishmaniasis (TL): Leishmania major and Leishmania braziliensis. BALB/c mice were immunized with rLiHyT plus saponin and lately challenged with promastigotes of the two parasite species. The immune response generated was evaluated before and 10 weeks after infection, as well as the parasite burden at this time after infection. The vaccination induced a Th1 response, which was characterized by the production of IFN-γ, IL-12 and GM-CSF, as well as by high levels of IgG2a antibodies, after in vitro stimulation using both the protein and parasite extracts. After challenge, vaccinated mice showed significant reductions in their infected footpads, as well as in the parasite burden in the tissue and organs evaluated, when compared to the control groups. The anti-Leishmania Th1 response was maintained after infection, being the IFN-γ production based mainly on CD4(+) T cells. We described one conserved Leishmania-specific protein that could compose a pan-Leishmania vaccine.

  9. Vaccination with Leishmania histone H1-pulsed dendritic cells confers protection in murine visceral leishmaniasis.

    Science.gov (United States)

    Agallou, Maria; Smirlis, Despina; Soteriadou, Ketty P; Karagouni, Evdokia

    2012-07-20

    Visceral leishmaniasis is the most severe form of leishmaniases affecting millions of people worldwide often resulting in death despite optimal therapy. Thus, there is an urgent need for the development of effective anti-infective vaccine(s). In the present study, we evaluated the prophylactic value of bone marrow-derived dendritic cells (BM-DCs) pulsed with the Leishmania (L.) infantum histone H1. We developed fully mature BM-DCs characterized by enhanced capacity of IL-12 production after ex vivo pulsing with GST-LeishH1. Intravenous administration of these BM-DCs in naive BALB/c mice resulted in antigen-specific spleenocyte proliferation and IgG1 isotype antibody production and conferred protection against experimental challenge with L. infantum independently of CpG oligonucleotides (ODNs) co-administration. Protection was associated with a pronounced enhancement of parasite-specific IFNγ-producing cells and reduction of cells producing IL-10, whereas IL-4 production was comparable in protected and non-protected mice. The polarization of immune responses to Th1 type was further confirmed by the elevation of parasite-specific IgG2a/IgG1 ratio in protected mice. The above data indicate the immunostimulatory capacity of Leishmania histone H1 and further support its exploitation as a candidate protein for vaccine development against leishmaniasis.

  10. [Impacts of early metoprolol intervention on connexin 43 and phosphorylated connexin 43 expression in rabbits with experimental myocardial infarction].

    Science.gov (United States)

    Zhou, M; Lu, Q; Jiang, J Q; Chen, Z N; Gong, Z G; Li, Z G; Fu, W W; Ding, S F

    2017-04-24

    early treatment group than in routine treatment group. (4)The p-Cx43/Cx43 ratio of protein was significantly lower in myocardial infarction group than in sham group (0.165±0.011 vs. 0.363±0.046, Pmyocardial infarction group (both Pmyocardial Cx43 in rabbits with experimental myocardial infarction.

  11. Early outcome and blood-brain barrier integrity after co-administered thrombolysis and hyperbaric oxygenation in experimental stroke

    Directory of Open Access Journals (Sweden)

    Michalski Dominik

    2011-06-01

    Full Text Available Abstract Background After promising results in experimental stroke, normobaric (NBO or hyperbaric oxygenation (HBO have recently been discussed as co-medication with tissue plasminogen activator (tPA for improving outcome. This study assessed the interactions of hyperoxia and tPA, focusing on survival, early functional outcome and blood-brain barrier (BBB integrity following experimental stroke. Methods Rats (n = 109 underwent embolic middle cerebral artery occlusion or sham surgery. Animals were assigned to: Control, NBO (60-minute pure oxygen, HBO (60-minute pure oxygen at 2.4 absolute atmospheres, tPA, or HBO+tPA. Functional impairment was assessed at 4 and 24 hours using Menzies score, followed by intravenous application of FITC-albumin as a BBB permeability marker, which was allowed to circulate for 1 hour. Further, blood sampling was performed at 5 and 25 hours for MMP-2, MMP-9, TIMP-1 and TIMP-2 concentration. Results Mortality rates did not differ significantly between groups, whereas functional improvement was found for NBO, tPA and HBO+tPA. NBO and HBO tended to stabilize BBB and to reduce MMP-2. tPA tended to increase BBB permeability with corresponding MMP and TIMP elevation. Co-administered HBO failed to attenuate these early deleterious effects, independent of functional improvement. Conclusions The long-term consequences of simultaneously applied tPA and both NBO and HBO need to be addressed by further studies to identify therapeutic potencies in acute stroke, and to avoid unfavorable courses following combined treatment.

  12. Global change ecotoxicology: Identification of early life history bottlenecks in marine invertebrates, variable species responses and variable experimental approaches.

    Science.gov (United States)

    Byrne, M

    2012-05-01

    Climate change is a threat to marine biota because increased atmospheric CO₂ is causing ocean warming, acidification, hypercapnia and decreased carbonate saturation. These stressors have toxic effects on invertebrate development. The persistence and success of populations requires all ontogenetic stages be completed successfully and, due to their sensitivity to environmental stressors, developmental stages may be a population bottleneck in a changing ocean. Global change ecotoxicology is being used to identify the marine invertebrate developmental stages vulnerable to climate change. This overview of research, and the methodologies used, shows that most studies focus on acidification, with few studies on ocean warming, despite a long history of research on developmental thermotolerance. The interactive effects of stressors are poorly studied. Experimental approaches differ among studies. Fertilization in many species exhibits a broad tolerance to warming and/or acidification, although different methodologies confound inter-study comparisons. Early development is susceptible to warming and most calcifying larvae are sensitive to acidification/increased pCO₂. In multistressor studies moderate warming diminishes the negative impact of acidification on calcification in some species. Development of non-calcifying larvae appears resilient to near-future ocean change. Although differences in species sensitivities to ocean change stressors undoubtedly reflect different tolerance levels, inconsistent handling of gametes, embryos and larvae probably influences different research outcomes. Due to the integrative 'developmental domino effect', life history responses will be influenced by the ontogenetic stage at which experimental incubations are initiated. Exposure to climate change stressors from early development (fertilization where possible) in multistressor experiments is needed to identify ontogenetic sensitivities and this will be facilitated by more consistent

  13. Treatment of Cutaneous Leishmaniasis in Murine Model by Hydro Alcoholic Essence of Artemisia sieberi

    Directory of Open Access Journals (Sweden)

    A Doroodgar

    2008-12-01

    Full Text Available Background: Considering the prevalence of leishmaniasis in Iran and many side effects associated with pentavalent antimony compounds use in its treatment, this study was designed to evaluate the effect of Artemisia sieberi essence on the experimental ulcers of cutaneous leishmaniasis on BALB/c mice."nMethods: This experimental research was performed to determine the effect of various concentrations of  Artemisia essence in BALB/c mice previously infected with active Leishmania major promastigote. A total of 50 infected BALB/c mice were randomly divided into 5 groups. Three groups (30 mice were used in the experimental condi­tions and the others were assigned as the control groups. The experimental groups received 1%, 3% and 5% of Ar­temisia, respectively. One of the control groups received ethanol 80% and the other received no treatment. The drug was administered by dropping the liquid on the top lesions, three times daily for maximum of 30 d. Every 10 days the ulcers diameter were measured and sampled for amastigote in all groups. Ulcers diameter changes were deter­mined by statistical tests."nResults: After 30 days, diameter of CL lesions increased in 1%, 3% and 5% Artemisia concentrations and the control groups. Ulcers got bigger with the more concentration. Treatments could not reduce the diameter or caused small lesions. In addition, the mice direct smears in microscopic studies were positive."nConclusion: To find the effective concentration and the mechanism of the effectiveness of the drug, further investi­gations with less concentrates of A. sieberi essence are recommended.

  14. TGF-β1 expression in wound healing is acutely affected by experimental malnutrition and early enteral feeding.

    Science.gov (United States)

    Alves, Claudia Cristina; Torrinhas, Raquel Susana; Giorgi, Ricardo; Brentani, Maria Mitzi; Logullo, Angela Flavia; Waitzberg, Dan Linetzky

    2014-10-01

    Malnutrition is associated with the delay or failure of healing. We assessed the effect of experimental malnutrition and early enteral feeding with standard diet or diet supplemented with arginine and antioxidants on the levels of mRNA encoding growth factors in acute, open wound healing. Standardised cutaneous dorsal wounds and gastrostomies for enteral feeding were created in malnourished (M, n = 27) and eutrophic control (E, n = 30) Lewis male adult rats. Both M and E rats received isocaloric and isonitrogenous regimens with oral chow and saline (C), standard (S) or supplemented (A) enteral diets. On post-trauma day 7, mRNA levels of growth factor genes were analysed in wound granulation tissue by reverse transcription polymerase chain reaction (RT-PCR). M(C) rats had significantly lower transforming growth factor β(TGF-β1 ) mRNA levels than E(C) rats (2·58 ± 0·83 versus 3·53 ± 0·57, P malnutrition decreased local mRNA levels of TGF-β1 genes, which was minimised by early enteral feeding with standard or supplemented diets.

  15. Laboratory diagnosis of human visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Hercules Sakkas

    2016-01-01

    Full Text Available Visceral leishmaniasis (VL, caused by the Leishmania donovani complex, is a vector-borne systemic disease, with a worldwide distribution causing high morbidity and mortality in the developing world. VL patients may be asymptomatic or they may present symptoms and findings of a systemic infection. The positive predictive value of clinical diagnosis in patients with typical symptoms is usually high, but more often, the signs and symptoms are inconclusive and mistaken with other co-endemic diseases. The fact that HIV co-infections often produce atypical presentations and the heterogeneity of Leishmania species, which is common in many endemic regions, also complicate the diagnosis. Despite that, some of the parasitological methods are still considered to be the reference standard for VL diagnosis due to their specificity. The development of serological and molecular tests has further enhanced the diagnostic approach of VL. Recombinant antigens have improved the performance of serodiagnostic tests, with DAT and the rK39 antigen based immunochromatographic test being the most appropriate methods for the serological diagnosis of VL. Molecular techniques, despite the fact that their implementation is often difficult and infeasible, have become increasingly relevant due to remarkable sensitivity and specificity, and to the variability of tested samples. Quantitative polymerase chain reaction (qPCR has been shown to be superior than conventional PCR for the differentiation between active VL and asymptomatic infections, such as for the detection of VL-HIV coinfection. This review summarizes the available methods with their applications in the diagnosis of VL, and focuses on the recent developments in VL diagnostics.

  16. Human visceral leishmaniasis: a picture from Italy.

    Science.gov (United States)

    Abdalmaula, Giuma Harun; Barbadoro, Pamela; Marigliano, Anna; Illuminati, Diego; Di Stanislao, Francesco; D'Errico, Marcello Mario; Prospero, Emilia

    2013-12-01

    The aim of our study was to describe the distribution of Visceral Leishmaniasis (VL) in Italy, focusing on HIV-infected patients, to estimate the burden of the disease and the public health actions that should be undertaken. A review of official notifications and hospitalization data has been performed. From 2006 to 2008, a total of 289 cases of VL were notified; the overall notification rate was 1.63/1,000,000 (95% CI 1.45-1.83). In total, 1192 VL-associated hospitalizations were detected, with a hospitalization rate of 6.71/1,000,000 (95% CI 6.34-7.10). For the age group "≤ 24 years", a statistically significant increase was detected (p<0.05). A total of 68.9% (n = 821) of hospitalizations were detected in HIV-positive patients. The geographic distribution of rates revealed a significant increase in the north-eastern area of the country. Our study confirms that the epidemiological pattern of VL is changing and that, in Italy, control measures and preventive strategies should be based on not only the official notification system but also hospital data. This would lead to the identification of areas of parasite spread and to the creation of awareness campaigns geared toward general practitioners in the affected areas. Easy case detection would allow for timely public health actions and strategies for the implementation of more effective interventions for reservoir control. Copyright © 2013 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  17. Leishmaniasis in the middle East: incidence and epidemiology.

    Directory of Open Access Journals (Sweden)

    Nasir Salam

    2014-10-01

    Full Text Available Leishmaniasis is a major health problem worldwide, with several countries reporting cases of leishmaniasis resulting in loss of human life or a lifelong stigma because of bodily scars. The Middle East is endemic for cutaneous leishmaniasis, with countries like Syria reporting very high incidence of the disease. Despite several countries establishing national control programs for containing the sandfly vector and treatment of infection, the disease continues to spread. In addition to the endemicity of the region for leishmaniasis, the Middle East has seen a great deal of human migration either for earning of livelihood or due to political upheaval in the region. These factors contribute to the spread and proliferation of the causative species Leishmania and its sandfly host. This review discusses the current epidemiological scenario in Iraq, Syria, Saudi Arabia, and Jordan, emphasizing the number of cases reported, vector species, Leishmania species, and treatment available. The data is primarily from WHO reports for each country and current and old literature.

  18. [Visceral leishmaniasis and pregnancy in renal transplanted patient: case report].

    Science.gov (United States)

    Silva, Jaqueline de Almeida; Araújo, Ivan de Melo; Pavanetti, Luiz Carlos; Okamoto, Liene Shigaki; Dias, Mônica

    2015-01-01

    Visceral leishmaniasis (VL) is a severe and potentially fatal disease caused by different Leishmania species, Leishmania chagasi prevailing in Brazil. Main symptoms include fever, malaise, anorexia, weight loss and abdominal enlargement with typically occurring hepatosplenomegaly Currently, VL is considered an opportunistic infection in immunocompromised hosts, including solid organ transplanted patients. The present study reports a case of VL associated to pregnancy after renal transplantation.

  19. Clinical pharmacology in leishmaniasis: treatment optimization of a neglected disease

    NARCIS (Netherlands)

    Dorlo, T.P.C.

    2013-01-01

    This thesis presents various novel applications of clinical pharmacokinetics and pharmacodynamics in the treatment of leishmaniasis, by which diverse clinically relevant issues, mainly related to the efficacy and safety of miltefosine, could be elucidated. Throughout this thesis, the added value of

  20. [Epidemic outbreak of tegumentary leishmaniasis in Puerto Esperanza, Misiones, 1998].

    Science.gov (United States)

    Salomón, O D; Sosa Estani, S; Monzani, A S; Studer, C

    2001-01-01

    The province of Misiones reported 205 leishmaniasis cases during 1998, 98% of them from the locality of Puerto Esperanza. The reports of Puerto Esperanza Hospital (January to September 1998) for leishmaniasis were analysed (n: 129). The mainly reported lesion was the single cutaneous ulcer (97.2%), localized in the inferior limbs (72.5%), without any mucosa involvement. The results are consistent with the knowledge from other Argentinean leishmaniasis foci due to Leishmania (V.) braziliensis. The difference in incidence among sexes was not significant, leishmaniasis was reported in all age groups, and it was susceptible to the conventional treatment. The main focus was located in Km 1 neighbourhood, the transmission peak was during April 1998. The Montenegro skin test among general population (n: 205) did not show reactivity among asymptomatic people. The prevalent Phlebotominae species were Lutzomyia intermedia (79.7%) and Lu. whitmani (10.9%), among the 577 individuals belonging to 8 species collected. The Phlebotominae were abundant in peridomestic habitats of Km 1 neighbourhood, close to human dwellings, in places associated with residual primary forest and secondary vegetation. The results are discussed in the frame of surveillance and possible control strategies.

  1. Epidemiological study on acute cutaneous leishmaniasis in Morocco

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    Kholoud Kahime

    2016-01-01

    Conclusions: ZCL and ACL are still major health problems in Morocco. We highlight the spatiotemporal change of cutaneous leishmaniasis incidence through the country during the last ten years and we underline the correlation between ZCL incidence and the percentage of rural population in Morocco.

  2. [Cutaneous leishmaniasis in France: towards the end of injectable therapy?].

    Science.gov (United States)

    Buffet, P A; Morizot, G

    2003-01-01

    Today no drug likely to be efficient on the majority of human-infecting species, well tolerated, and easy to administer is available for the treatment of human cutaneous leishmaniasis. But recent progress has been made. Efficient against visceral leishmaniasis, orally administered miltefosine may supplant pentavalent antimonials for the treatment of cutaneous leishmaniasis acquired in the New World. Right now, the reference treatment is still parenteral pentavalent antimonials 20 mg Sbv/kg/d for a duration that may probably be reduced from 20 to 10 days. The benefit/risk ratio of pentamidine still compares well with that of pentavalent antimonials for the treatment of lesions due to species belonging to the L. panamensis/L. guyanensis/L. shawi group. Pentamidine, which is easier to handle than antimonials, remains the reference treatment for cases from areas where these species predominate. Oral fluconazole is an improvement, readily available for cases from L. major foci. If its efficacy is confirmed in other foci and against other species, mechanisms will have to be implemented to make this therapeutic improvement affordable to poor patients in endemic countries. The development of an efficient and well tolerated topical treatment is still warranted. A new formulation of aminosidine is currently under evaluation. One can hope that the treatment of cutaneous leishmaniasis will soon become simpler, both for patients and doctors. For the benefits of this simplification to be rapidly affordable to all patients, the pharmaceutical and clinical research outlay must be maintained.

  3. What about Th1/Th2 in cutaneous leishmaniasis vaccine discovery?

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    Campos-Neto A.

    2005-01-01

    Full Text Available The T helper cell type 1 (Th1 response is essential to resist leishmaniasis, whereas the Th2 response favors the disease. However, many leishmanial antigens, which stimulate a Th1 immune response during the disease or even after the disease is cured, have been shown to have no protective action. Paradoxically, antigens associated with an early Th2 response have been found to be highly protective if the Th1 response to them is generated before infection. Therefore, finding disease-associated Th2 antigens and inducing a Th1 immune response to them using defined vaccination protocols is an interesting unorthodox alternative approach to the discovery of a leishmania vaccine.

  4. Serial study of the immune response of an individual with exacerbated simple cutaneous leishmaniasis.

    Science.gov (United States)

    Klaus, S N; Frankenburg, S; Gross, A; Jonas, F; Vardy, D

    1994-01-01

    The immunological responses of a patient with exacerbated cutaneous leishmaniasis, measured during the course of the disease, are described. Except for skin lesions the patient was healthy and showed no signs of immunosuppression. Three immunological parameters were measured: specific lymphocyte proliferation (LPA), monocyte effector activity (MEA), and antibody levels. LPA was positive early in the course of the disease, became negative as the lesions enlarged, and was positive again as the lesions healed 28 weeks after initiation of the study. In the MEA test, in which the mononuclear cells of the patient were incubated in the presence of Leishmania major promastigotes in a 3-day assay, the number of amastigotes per 100 monocytes remained constant until week 28 and then decreased significantly. Antibody levels remained elevated until week 28 and then decreased to background levels. The results indicate that the cell-mediated immune response parallels the course of the disease while circulating antibodies show an inverse relationship.

  5. The first canine visceral leishmaniasis outbreak in Campinas, State of São Paulo Southeastern Brazil

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    Andrea Paula Bruno von Zuben

    2014-06-01

    Full Text Available Introduction Early detection of American visceral leishmaniasis (AVL outbreak in animals is crucial for controlling this disease in non-endemic areas. Methods Epidemiological surveillance (2009-2012 was performed in Campinas, State of São Paulo, Brazil. Results In 2009, Leishmania chagasi was positively identified in four dogs. Entomological research and three serological studies (2010-2012 were undertaken as monitoring measures; these approaches revealed a moderate prevalence of Leishmania present in 4% of the canine population. Nyssomyia whitmani and Lutzomyia longipalpis were the predominant species identified. Conclusions Detection of an AVL outbreak in dogs in an area with an evolving natural landscape containing sand flies is crucial for control programs.

  6. Epidemiological changes in leishmaniasis in Spain according to hospitalization-based records, 1997-2011: raising awareness towards leishmaniasis in non-HIV patients.

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    Zaida Herrador

    2015-03-01

    Full Text Available In Spain, Leishmania infantum is endemic, human visceral and cutaneous leishmaniasis cases occurring both in the Peninsula, as well as in the Balearic Islands. We aimed to describe the clinical characteristics of leishmaniasis patients and the changes in the disease evolution after the introduction of antiretroviral therapy in 1997. In this descriptive study, we used Spanish Centralized Hospital Discharge Database for the hospitalized leishmaniasis cases between 1997 and 2011. We included in the analysis only the records having leishmaniasis as the first registered diagnosis and calculated the hospitalization rates. Disease trend was described taking into account the HIV status. Adjusted odds-ratio was used to estimate the association between clinical and socio-demographic factors and HIV co-infection. Of the total 8010 Leishmaniasis hospitalizations records, 3442 had leishmaniasis as first diagnosis; 2545/3442 (75.6% were males and 2240/3442 (65.1% aged between 14-65 years. Regarding disease forms, 2844/3442 (82.6% of hospitalizations were due to visceral leishmaniasis (VL, while 118/3442 (3.4% hospitalizations were cutaneous leishmaniasis (CL. Overall, 1737/2844 of VL (61.1% were HIV negatives. An overall increasing trend was observed for the records with leishmaniasis as first diagnosis (p=0.113. Non-HIV leishmaniasis increased during this time period (p=0.021 while leishmaniasis-HIV co-infection hospitalization revealed a slight descending trend (p=0.717. Leishmaniasis-HIV co-infection was significantly associated with male sex (aOR=1.6; 95% CI: 1.25-2.04, 16-64 years age group (aOR=17.4; 95%CI: 2.1-143.3, visceral leishmaniasis aOR=6.1 (95%CI: 3.27-11.28 and solid neoplasms 4.5 (95% CI: 1.65-12.04. The absence of HIV co-infection was associated with lymph/hematopoietic neoplasms (aOR=0.3; 95%CI:0.14-0.57, other immunodeficiency (aOR=0.04; 95% CI:0.01-0.32 and transplant (aOR=0.01; 95%CI:0.00-0.07. Our findings suggest a significant increase

  7. Hyponatremia in visceral leishmaniasis Hiponatremia no calazar

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    Frederico A. Lima Verde

    2010-10-01

    Full Text Available There are few reports linking hyponatremia and visceral leishmaniasis (kala-azar. This is a study of 55 consecutive kala-azar patients and 20 normal individuals as a control group. Hyponatremia and serum hypo-osmolality were detected in 100% of kala-azar patients. High first morning urine osmolality (750.0 ± 52.0 vs. 894.5 ± 30.0mOsm/kg H2O, p Existem poucos relatos relacionando hiponatremia com a leshmaniose visceral (calazar. Este é um estudo de 55 pacientes portadores de calazar e um grupo controle de 20 indivíduos normais. Hiponatremia e hipo-osmolalidade sérica foram detectados em 100% dos pacientes portadores de calazar. A presença de alta osmolalidade da primeira urina da manhã (750,0 ± 52,0 vs. 894,5 ± 30 mOsm/Kg H2O, p < 0,05 e da urina de 24h (426,0 ± 167,0 vs. 514,6 ± 132,0 mOsm/Kg H2O, p < 0,05, demonstraram a presença de persistente secreção de hormônio antidiurético. A concentração de sódio urinário foi elevada (82,3 ± 44,2 vs. 110,3 ± 34,7 mEq/L, p < 0,05. Hipouricemia ocorreu em 61,8% dos pacientes e aumento da fração de excreção urinária de ácido úrico foi detectada em 74,5% dos casos. Aumento da velocidade de filtração glomerular estava presente em 25,4% dos pacientes. Não havia evidência clínica de depleção de volume extracelular. Valores normais de ADH plasmático foram observados nos pacientes com calazar. Não foi detectada disfunção renal ou endócrina. É provável, que a maioria dos pacientes com calazar apresente uma síndrome de secreção inapropriada de hormônio antidiurético.

  8. Therapeutic efficacy of melatonin in reducing retinal damage in an experimental model of early type 2 diabetes in rats.

    Science.gov (United States)

    Salido, Ezequiel M; Bordone, Melina; De Laurentiis, Andrea; Chianelli, Mónica; Keller Sarmiento, María Inés; Dorfman, Damián; Rosenstein, Ruth E

    2013-03-01

    Diabetic retinopathy (DR) is a leading cause of acquired blindness in adults, mostly affected by type 2 diabetes mellitus (T2DM). We have developed an experimental model of early T2DM in adult rats which mimics some features of human T2DM at its initial stages and provokes significant retinal alterations. The aim of this work was to analyze the effect of melatonin on retinal changes induced by the moderate metabolic derangement. For this purpose, adult male Wistar rats received a control diet or 30% sucrose in the drinking water. Three weeks after this treatment, animals were injected with vehicle or streptozotocin (STZ, 25 mg/kg). One day or 3 wk after vehicle or STZ injection, animals were subcutaneously implanted with a pellet of melatonin. Fasting and postprandial glycemia, and glucose, and insulin tolerance tests were analyzed. At 12 wk of treatment, animals which received a sucrose-enriched diet and STZ showed significant differences in metabolic tests, as compared with control groups. Melatonin, which did not affect glucose metabolism in control or diabetic rats, prevented the decrease in the electroretinogram a-wave, b-wave, and oscillatory potential amplitude, and the increase in retinal lipid peroxidation, NOS activity, TNFα, Müller cells glial fibrillary acidic protein, and vascular endothelial growth factor levels. In addition, melatonin prevented the decrease in retinal catalase activity. These results indicate that melatonin protected the retina from the alterations observed in an experimental model of DR associated with type 2 diabetes.

  9. Intradermal Infection Model for Pathogenesis and Vaccine Studies of Murine Visceral Leishmaniasis

    OpenAIRE

    2003-01-01

    The levels of protection found in vaccine studies of murine visceral leishmaniasis are significantly lower than for cutaneous leishmaniasis; whether this is due to the high-challenge murine model employed and/or is a consequence of differences required in tissue-specific local immune responses is not understood. Consequently, an intradermal murine model of visceral leishmaniasis has been explored. Intradermal inoculation established a chronic infection in susceptible mice which was associated...

  10. Analysis of immune responses in dogs with canine visceral leishmaniasis before, and after, drug treatment.

    Science.gov (United States)

    Rhalem, A; Sahibi, H; Lasri, S; Jaffe, C L

    1999-10-01

    The incidence of canine visceral leishmaniasis (CVL) is increasing in the Mediterranean region. Many drugs have been tested for treatment of CVL, but little is known regarding their effect on test immune responses. In our study, three dogs naturally infected with Leishmania infantum and five dogs experimentally infected with the same strain, were treated with dimethasulfonate pentamidine (Lomidine) and the immune response evaluated before, and after, treatment. After the last injection, animals began to gain weight and the major clinical signs disappeared. Antibody titers gradually decreased to low levels, six months after treatment. At the same time, antigen specific lymphoproliferation reappeared in the sampled animals. This study shows that, after treatment, immune cellular responses to leishmanial antigens, involved in protection against Leishmania infection, were established.

  11. An experimental investigation of the early dynamic impact behaviour of textile armour systems: Decoupling material from system response

    Science.gov (United States)

    Cepus, Elvis

    This work focuses on the early impact response of textile armour systems. A relatively new data acquisition system, the Enhanced Laser Velocity Sensor (ELVS), was refined and used to generate a large database of results for a 5.57 mm diameter, 3 gram, non-deforming projectile impacting single-ply configurations of Ballistic Nylon, two weaves of Kevlar 129, and Zylon (PBO) over a range of velocities from 61 m/s to 248 m/s. In addition, one Kevlar 129 material was tested in configurations of 2, 3, 4, 8 and 16 plies over a range of strike velocities from 90 m/s to 481 m/s. ELVS results consisted of high-resolution timehistories of displacement, velocity and energy for each system tested. The strain wave velocity and ballistic performance of each system was also determined. Results taken from during the impact event were analysed up to just prior to the strain-wave rebounding from the boundary and returning to the impact point---effectively removing boundary influences. Regardless of system type, a constant rate of energy absorption within the pre-rebound timeframe was found to exist, which scales with the strike velocity to approximately the 8/3-power. Well-established single fibre theory was modified and applied to woven materials. It was assumed that three primary energy absorption mechanisms exist; elastic strain, in-plane kinetic and out-of-plane kinetic. This simple model yields the experimentally observed 8/3 exponent and parametrically predicts the difference between the different single-ply material systems, but underpredicts the observed behaviour by a factor of 2 and cannot address the performance reduction with increasing ply count. This combined experimental and analytical work confirms the long-held assumption that single fibre wave physics is applicable to multi-ply woven systems. More significantly, for the first time, it decouples material response from overall system response and provides the experimental tools and methodology required to analyse

  12. New Approaches on Leishmaniasis Treatment and Prevention: A Review of Recent Patents.

    Science.gov (United States)

    Barbosa, Juliana F; de Figueiredo, Sônia M; Monteiro, Fabricio M; Rocha-Silva, Fabiana; Gaciele-Melo, Cidiane; Coelho, Sabrina S C; Lyon, Sandra; Caligiorne, Rachel B

    2015-01-01

    Leishmaniasis is considered a neglected tropical disease having a worldwide distribution. The disease is caused by protozoa belonging to the genus Leishmania, being clinically divided into visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL). Domestic dogs are the main parasite reservoir and effectively participate in the protozoa transmission. The human leishmaniasis treatment is based on a selection of therapeutic compounds, but the available drugs are toxic, presenting adverse side effects. The decision to treat or not to treat seropositive dogs is under discussion in some countries, because treatment is even more toxic to animals and, also, can generate drug resistant strains. Therefore, very few treatment choices have reached the clinic for this disease and there is an urgent need of new chemotherapy for both humans and animals. This study presents a review of new patents related to treatment and prevention of Leishmania infections. Some of these patents are related to new vaccine formulations for combating leishmaniasis. Likewise, the inventions related to the cream formulations for the treatment of cutaneous leishmaniasis are very important, avoiding the side effects of drugs during the treatment. Furthermore, anti leishmaniasis products that are extracted from nature has increasingly been patented each year, demonstrating the importance of bioprospection studies to improve the armamentarium of anti leishmaniasis drugs.

  13. Molecular epidemiology of imported cases of leishmaniasis in Australia from 2008 to 2014.

    Directory of Open Access Journals (Sweden)

    Tamalee Roberts

    Full Text Available Leishmaniasis is a vector borne disease caused by protozoa of the genus Leishmania. Human leishmaniasis is not endemic in Australia though imported cases are regularly encountered. This study aimed to provide an update on the molecular epidemiology of imported leishmaniasis in Australia. Of a total of 206 biopsies and bone marrow specimens submitted to St Vincent's Hospital Sydney for leishmaniasis diagnosis by PCR, 55 were found to be positive for Leishmania DNA. All PCR products were subjected to restriction fragment length polymorphism analysis for identification of the causative species. Five Leishmania species/species complexes were identified with Leishmania tropica being the most common (30/55. Travel or prior residence in a Leishmania endemic region was the most common route of acquisition with ~47% of patients having lived in or travelled to Afghanistan. Cutaneous leishmaniasis was the most common manifestation (94% with only 3 cases of visceral leishmaniasis and no cases of mucocutaneous leishmaniasis encountered. This report indicates that imported leishmaniasis is becoming increasingly common in Australia due to an increase in global travel and immigration. As such, Australian clinicians must be made aware of this trend and consider leishmaniasis in patients with suspicious symptoms and a history of travel in endemic areas. This study also discusses the recent identification of a unique Leishmania species found in native kangaroos and a potential vector host which could create the opportunity for the establishment of a local transmission cycle within humans.

  14. First report on Ambisome-associated allergic reaction in two Sudanese leishmaniasis patients.

    Science.gov (United States)

    Mukhtar, Maowia; Aboud, Mona; Kheir, Musa; Bakhiet, Sahar; Abdullah, Nazik; Ali, Ahmed; Hassan, Nadia; Elamin, Elwaleed; Elagib, Atif

    2011-10-01

    Post kala-azar dermal leishmaniasis (PKDL) and mucosal leishmaniasis (ML) are serious clinical forms of leishmaniasis caused by Leishmania donovani parasites in Sudan. Although pentavalent antimonys are used as the first line of treatment of all clinical forms of leishmaniasis, persistent PKDL and ML patients are treated with liposomal amphotericin B (Ambisome) as a second-line drug. In this work, we report the development of allergic reactions by a PKDL and a ML Sudanese patient to Ambisome. The findings warrant future close supervision of patients to be treated with the drug.

  15. Early social deprivation and the social buffering of cortisol stress responses in late childhood: An experimental study.

    Science.gov (United States)

    Hostinar, Camelia E; Johnson, Anna E; Gunnar, Megan R

    2015-11-01

    The goal of the present study was to investigate the role of early social deprivation in shaping the effectiveness of parent support to alleviate hypothalamic-pituitary-adrenal (HPA)-axis-stress responses of children (ages 8.9-11, M = 9.83 years, SD = .55). The sample was equally divided between children who had been adopted internationally from orphanage care by age 5 (n = 40) and an age- and gender-matched group of nonadopted (NA) children (n = 40). On average, internationally adopted children were invited to the laboratory 7.6 years postadoption (SD = 1.45). We experimentally manipulated the provision of parent support during the 5-min speech preparation period before a modified Trier Social Stress Test (TSST) and examined its effect on levels of salivary cortisol secreted in response to this laboratory stressor. All participants were randomly assigned to receive support from their parent or a stranger. Analyses revealed a significant interaction of support condition and group such that parent support significantly dampened the cortisol-stress response in NA children compared with support from a stranger, whereas the cortisol response curves of postinstitutionalized (PI) children did not differ between the parent- and stranger-support conditions. Cortisol reactivity for PI children in both conditions was lower than that of NA children in the stranger-support condition. Social deprivation during the first few years of life may shape neurobehavioral development in ways that reduce selective responses to caregivers versus strangers.

  16. Early Social Deprivation and the Social Buffering of Cortisol Stress Responses in Late Childhood: An Experimental Study

    Science.gov (United States)

    Hostinar, Camelia E.; Johnson, Anna E.; Gunnar, Megan R.

    2015-01-01

    The goal of the present study was to investigate the role of early social deprivation in shaping the effectiveness of parent support to alleviate hypothalamic-pituitary-adrenal (HPA) axis stress responses of children (ages 8.9–11, M = 9.83 years, SD = .55). The sample was equally divided between children who had been adopted internationally from orphanage care by age 5 (N = 40) and an age- and gender-matched group of non-adopted children (N = 40). On average, internationally adopted children were invited to the laboratory 7.6 years post-adoption (SD = 1.45). We experimentally manipulated the provision of parent support during the 5-minute speech preparation period before a modified Trier Social Stress Test (TSST) and examined its effect on levels of salivary cortisol secreted in response to this laboratory stressor. All participants were randomly assigned to receive support from their parent or a stranger. Analyses revealed a significant interaction of support condition and group such that parent support significantly dampened the cortisol stress response in non-adopted children compared to support from a stranger, whereas the cortisol response curves of post-institutionalized children did not differ between the parent and stranger support conditions. Cortisol reactivity for PI children in both conditions was lower than that of non-adopted children in the stranger support condition. Social deprivation during the first few years of life may shape neurobehavioral development in ways that reduce selective responses to caregivers versus strangers. PMID:26322485

  17. Experimental evidence of genome-wide impact of ecological selection during early stages of speciation-with-gene-flow.

    Science.gov (United States)

    Egan, Scott P; Ragland, Gregory J; Assour, Lauren; Powell, Thomas H Q; Hood, Glen R; Emrich, Scott; Nosil, Patrik; Feder, Jeffrey L

    2015-08-01

    Theory predicts that speciation-with-gene-flow is more likely when the consequences of selection for population divergence transitions from mainly direct effects of selection acting on individual genes to a collective property of all selected genes in the genome. Thus, understanding the direct impacts of ecologically based selection, as well as the indirect effects due to correlations among loci, is critical to understanding speciation. Here, we measure the genome-wide impacts of host-associated selection between hawthorn and apple host races of Rhagoletis pomonella (Diptera: Tephritidae), a model for contemporary speciation-with-gene-flow. Allele frequency shifts of 32 455 SNPs induced in a selection experiment based on host phenology were genome wide and highly concordant with genetic divergence between co-occurring apple and hawthorn flies in nature. This striking genome-wide similarity between experimental and natural populations of R. pomonella underscores the importance of ecological selection at early stages of divergence and calls for further integration of studies of eco-evolutionary dynamics and genome divergence. © 2015 The Authors Ecology Letters published by John Wiley & Sons Ltd and CNRS.

  18. Nitrogen fixation on early Mars and other terrestrial planets: experimental demonstration of abiotic fixation reactions to nitrite and nitrate.

    Science.gov (United States)

    Summers, David P; Khare, Bishun

    2007-04-01

    Understanding the abiotic fixation of nitrogen is critical to understanding planetary evolution and the potential origin of life on terrestrial planets. Nitrogen, an essential biochemical element, is certainly necessary for life as we know it to arise. The loss of atmospheric nitrogen can result in an incapacity to sustain liquid water and impact planetary habitability and hydrological processes that shape the surface. However, our current understanding of how such fixation may occur is almost entirely theoretical. This work experimentally examines the chemistry, in both gas and aqueous phases, that would occur from the formation of NO and CO by the shock heating of a model carbon dioxide/nitrogen atmosphere such as is currently thought to exist on early terrestrial planets. The results show that two pathways exist for the abiotic fixation of nitrogen from the atmosphere into the crust: one via HNO and another via NO(2). Fixation via HNO, which requires liquid water, could represent fixation on a planet with liquid water (and hence would also be a source of nitrogen for the origin of life). The pathway via NO(2) does not require liquid water and shows that fixation could occur even when liquid water has been lost from a planet's surface (for example, continuing to remove nitrogen through NO(2) reaction with ice, adsorbed water, etc.).

  19. Leishmaniasis worldwide and global estimates of its incidence.

    Science.gov (United States)

    Alvar, Jorge; Vélez, Iván D; Bern, Caryn; Herrero, Mercé; Desjeux, Philippe; Cano, Jorge; Jannin, Jean; den Boer, Margriet

    2012-01-01

    As part of a World Health Organization-led effort to update the empirical evidence base for the leishmaniases, national experts provided leishmaniasis case data for the last 5 years and information regarding treatment and control in their respective countries and a comprehensive literature review was conducted covering publications on leishmaniasis in 98 countries and three territories (see 'Leishmaniasis Country Profiles Text S1, S2, S3, S4, S5, S6, S7, S8, S9, S10, S11, S12, S13, S14, S15, S16, S17, S18, S19, S20, S21, S22, S23, S24, S25, S26, S27, S28, S29, S30, S31, S32, S33, S34, S35, S36, S37, S38, S39, S40, S41, S42, S43, S44, S45, S46, S47, S48, S49, S50, S51, S52, S53, S54, S55, S56, S57, S58, S59, S60, S61, S62, S63, S64, S65, S66, S67, S68, S69, S70, S71, S72, S73, S74, S75, S76, S77, S78, S79, S80, S81, S82, S83, S84, S85, S86, S87, S88, S89, S90, S91, S92, S93, S94, S95, S96, S97, S98, S99, S100, S101'). Additional information was collated during meetings conducted at WHO regional level between 2007 and 2011. Two questionnaires regarding epidemiology and drug access were completed by experts and national program managers. Visceral and cutaneous leishmaniasis incidence ranges were estimated by country and epidemiological region based on reported incidence, underreporting rates if available, and the judgment of national and international experts. Based on these estimates, approximately 0.2 to 0.4 cases and 0.7 to 1.2 million VL and CL cases, respectively, occur each year. More than 90% of global VL cases occur in six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. Cutaneous leishmaniasis is more widely distributed, with about one-third of cases occurring in each of three epidemiological regions, the Americas, the Mediterranean basin, and western Asia from the Middle East to Central Asia. The ten countries with the highest estimated case counts, Afghanistan, Algeria, Colombia, Brazil, Iran, Syria, Ethiopia, North Sudan, Costa Rica

  20. Leishmaniasis worldwide and global estimates of its incidence.

    Directory of Open Access Journals (Sweden)

    Jorge Alvar

    Full Text Available As part of a World Health Organization-led effort to update the empirical evidence base for the leishmaniases, national experts provided leishmaniasis case data for the last 5 years and information regarding treatment and control in their respective countries and a comprehensive literature review was conducted covering publications on leishmaniasis in 98 countries and three territories (see 'Leishmaniasis Country Profiles Text S1, S2, S3, S4, S5, S6, S7, S8, S9, S10, S11, S12, S13, S14, S15, S16, S17, S18, S19, S20, S21, S22, S23, S24, S25, S26, S27, S28, S29, S30, S31, S32, S33, S34, S35, S36, S37, S38, S39, S40, S41, S42, S43, S44, S45, S46, S47, S48, S49, S50, S51, S52, S53, S54, S55, S56, S57, S58, S59, S60, S61, S62, S63, S64, S65, S66, S67, S68, S69, S70, S71, S72, S73, S74, S75, S76, S77, S78, S79, S80, S81, S82, S83, S84, S85, S86, S87, S88, S89, S90, S91, S92, S93, S94, S95, S96, S97, S98, S99, S100, S101'. Additional information was collated during meetings conducted at WHO regional level between 2007 and 2011. Two questionnaires regarding epidemiology and drug access were completed by experts and national program managers. Visceral and cutaneous leishmaniasis incidence ranges were estimated by country and epidemiological region based on reported incidence, underreporting rates if available, and the judgment of national and international experts. Based on these estimates, approximately 0.2 to 0.4 cases and 0.7 to 1.2 million VL and CL cases, respectively, occur each year. More than 90% of global VL cases occur in six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. Cutaneous leishmaniasis is more widely distributed, with about one-third of cases occurring in each of three epidemiological regions, the Americas, the Mediterranean basin, and western Asia from the Middle East to Central Asia. The ten countries with the highest estimated case counts, Afghanistan, Algeria, Colombia, Brazil, Iran, Syria, Ethiopia, North

  1. RENAL HISTOPATHOLOGICAL FINDINGS IN DOGS WITH VISCERAL LEISHMANIASIS

    Directory of Open Access Journals (Sweden)

    Rosangela Silva Rigo

    2013-04-01

    Full Text Available Visceral leishmaniasis affects various organs including the kidneys; which can lead to renal failure and death. In order to verify this renal involvement, material was evaluated from 100 dogs naturally infected and with serological diagnosis of canine visceral leishmaniasis (CVL. Inflammatory changes were present in 25.3% of the tubules, in 67.0% of interstitium and in 52.0% of glomeruli. There was no significant difference (p > 0.05 between the presence of glomerulonephritis in symptomatic and oligosymptomatic dogs. The membranous and membranoproliferative glomerulonephritis were the most frequent, both with 18.0% frequency, followed by focal segmental glomerulosclerosis with 14.0%. Changes such as cylindruria, tubular and fibrosis hypertrophy, periglomerular inflammatory infiltrate, and multifocal and diffuse peritubular inflammatory infiltrate were observed. The findings are consistent with those of other authors indicating that renal involvement is common in CVL and the standards of membranous and membranoploriferative glomerulonephritis, as well as the tubulointerstitial involvement, are frequent.

  2. Renal histopathological findings in dogs with visceral leishmaniasis.

    Science.gov (United States)

    Rigo, Rosangela Silva; Carvalho, Cristiano Marcelo Espínola; Honer, Michael Robin; Andrade, Gisele Braziliano de; Silva, Iandara Shetter; Rigo, Leonardo; Figueiredo, Helen Rezende; Barreto, Wanessa Teixeira Gomes

    2013-01-01

    Visceral leishmaniasis affects various organs including the kidneys; which can lead to renal failure and death. In order to verify this renal involvement, material was evaluated from 100 dogs naturally infected and with serological diagnosis of canine visceral leishmaniasis (CVL). Inflammatory changes were present in 25.3% of the tubules, in 67.0% of interstitium and in 52.0% of glomeruli. There was no significant difference (p > 0.05) between the presence of glomerulonephritis in symptomatic and oligosymptomatic dogs. The membranous and membranoproliferative glomerulonephritis were the most frequent, both with 18.0% frequency, followed by focal segmental glomerulosclerosis with 14.0%. Changes such as cylindruria, tubular and fibrosis hypertrophy, periglomerular inflammatory infiltrate, and multifocal and diffuse peritubular inflammatory infiltrate were observed. The findings are consistent with those of other authors indicating that renal involvement is common in CVL and the standards of membranous and membranoploriferative glomerulonephritis, as well as the tubulointerstitial involvement, are frequent.

  3. Asymptomatic infection with American cutaneous leishmaniasis: epidemiological and immunological studies

    Science.gov (United States)

    Andrade-Narvaez, Fernando J; Loría-Cervera, Elsy Nalleli; Sosa-Bibiano, Erika I; Van Wynsberghe, Nicole R

    2016-01-01

    American cutaneous leishmaniasis (ACL) is a major public health problem caused by vector-borne protozoan intracellular parasites from the genus Leishmania, subgenera Viannia and Leishmania. Asymptomatic infection is the most common outcome after Leishmania inoculation. There is incomplete knowledge of the biological processes explaining the absence of signs or symptoms in most cases while other cases present a variety of clinical findings. Most studies of asymptomatic infection have been conducted in areas of endemic visceral leishmaniasis. In contrast, asymptomatic ACL infection has been neglected. This review is focused on the following: (1) epidemiological studies supporting the existence of asymptomatic ACL infection and (2) immunological studies conducted to understand the mechanisms responsible for controlling the parasite and avoiding tissue damage. PMID:27759762

  4. Asymptomatic infection with American cutaneous leishmaniasis: epidemiological and immunological studies

    Directory of Open Access Journals (Sweden)

    Fernando J Andrade-Narvaez

    Full Text Available American cutaneous leishmaniasis (ACL is a major public health problem caused by vector-borne protozoan intracellular parasites from the genus Leishmania, subgenera Viannia and Leishmania. Asymptomatic infection is the most common outcome after Leishmania inoculation. There is incomplete knowledge of the biological processes explaining the absence of signs or symptoms in most cases while other cases present a variety of clinical findings. Most studies of asymptomatic infection have been conducted in areas of endemic visceral leishmaniasis. In contrast, asymptomatic ACL infection has been neglected. This review is focused on the following: (1 epidemiological studies supporting the existence of asymptomatic ACL infection and (2 immunological studies conducted to understand the mechanisms responsible for controlling the parasite and avoiding tissue damage.

  5. Leishmaniasis recidiva cutis of the lips mimicking granulomatous cheilitis

    Directory of Open Access Journals (Sweden)

    Özlem Ekiz

    2015-01-01

    Full Text Available Leishmaniasis recidiva cutis (LRC is an unusual form of acute cutaneous leishmaniasis. Herein, we present a case of LRC of the lips mimicking granulomatous cheilitis. An 8-year-old, Syrian child admitted with a swelling and disfigurement of his lips for 4 years. Abundant intra and extracellular Leishmania amastigotes were determined in the smear prepared from the lesion with Giemsa stain. Histopathology showed foamy histiocytes and leishmania parasites within the cytoplasm of macrophages in the epidermis and a dense dermal mixed type inflammatory cell infiltrate composed of lymphocytes, foamy histiocytes with multinucleated giant cells. On the basis of anamnestic data, the skin smears results, clinical and histopathologic findings, LRC was diagnosed. The patient was treated with meglumine antimoniate intramuscularly and fluconazole orally. Cryotherapy was applied to the residual papular lesions. The lesion improved markedly at the first month of the treatment.

  6. [American integumentary leishmaniasis associated with AIDS in Argentina].

    Science.gov (United States)

    Romero, Héctor D; Taranto, Néstor J; Malchiodi, Emilio L

    2004-01-01

    Migration of HIV infected individuals from cities to small towns and rural areas spreads AIDS among non urban population, superimposing HIV with other endemic or epidemic infections as parasitoses. This situation is a big challenge to public health because in most cases the association between these infections worsens both prognoses. We present here the first case in Argentina of AIDS associated to a mucocutaneous form of American tegumentary leishmaniasis. The patient was from Orán, an area where in the middle eighties, an epidemic outbreak took place. By now more than 2000 cases have been parasitologically confirmed in our Institute and the causing species were identified as Leishmania (V.) braziliensis and L. (L.) amasonensis. Considering the existence of co-infection of HIV and Leishmania, it is recommended that in patients from endemic areas with records of cutaneous or mucocutaneous ulcers, even healed, leishmaniasis must be investigated, among other diseases.

  7. [A case of feline leishmaniasis in the south of France].

    Science.gov (United States)

    Pocholle, E; Reyes-Gomez, E; Giacomo, A; Delaunay, P; Hasseine, L; Marty, P

    2012-02-01

    We report a case of disseminated feline leishmaniasis in a FIV-seropositive 14-year-old male cat (Felis catus) living in the Alpes-Maritimes (south of France). The cat presented with erythematous ulcerated papules on the head and withers, and with an ulcerated proliferative lesion on the left pinnae. The condition was diagnosed, along with a squamous cell carcinoma of the pinnae, after histopathological examination of the cutaneous lesions. Total remission of the cutaneous lesions was obtained after oral administration of 100 mg of allopurinol once a day for four months. Necropsic samples revealed that the parasite was still present in the organism after six months of treatment. This case discusses of the cat sensibility to the leishmaniasis pathology and of his potential ability of being a reservoir host.

  8. Leishmania infantum AS A CAUSATIVE AGENT OF CUTANEOUS LEISHMANIASIS IN THE STATE OF MATO GROSSO DO SUL, BRAZIL

    Science.gov (United States)

    CASTRO, Ludiele Souza; FRANÇA, Adriana de Oliveira; FERREIRA, Eduardo de Castro; HANS, Günther; HIGA, Minoru German; GONTIJO, Célia Maria Ferreira; PEREIRA, Agnes Antônia Sampaio; DORVAL, Maria Elizabeth Moraes C.

    2016-01-01

    Cutaneous leishmaniasis is caused by different species of theLeishmania genus. Leishmania(Leishmania) infantum, causing cutaneous leishmaniasis, has been described in patients living in areas where visceral leishmaniasis is endemic. In this study, it was possible to characterize this species in seven slides from cutaneous tissue imprints from patients with cutaneous leishmaniasis in the State of Mato Grosso do Sul, Brazil. PMID:27007566

  9. Early bone formation adjacent to rough and turned endosseous implant surfaces. An experimental study in the dog.

    Science.gov (United States)

    Abrahamsson, Ingemar; Berglundh, Tord; Linder, Elena; Lang, Niklaus P; Lindhe, Jan

    2004-08-01

    To validate a proposed model (Berglundh et al. 2003) and to evaluate the rate and degree of osseointegration at turned (T) and sand blasted and acid etched (SLA) implant surfaces during early phases of healing. The devices used for the study of early healing had a geometry that corresponded to that of a solid screw implant with either a SLA or a T surface configuration. A circumferential trough had been prepared within the thread region (intra-osseous portion) that established a geometrically well-defined wound chamber. Twenty Labrador dogs received totally 160 experimental devices to allow the evaluation of healing between 2 h and 12 weeks. Both ground and decalcified sections were prepared from mesial/distal and buccal/lingual device sites. Histometric and morphometric analyses of the ground sections and morphometric analysis of the tissue components in decalcified sections were performed. The ground sections provided an overview of the various phases of tissue formation, while the decalcified, thin sections enabled a more detailed study of events involved in bone tissue modeling and remodeling for both SLA and T surfaces. The initially empty wound chamber became occupied with a coagulum and a granulation tissue that was replaced by a provisional matrix. The process of bone formation started already during the first week. The newly formed bone present at the lateral border of the cut bony bed appeared to be continuous with the parent bone, but on the SLA surface woven bone was also found at a distance from the parent bone. Parallel-fibered and/or lamellar bone as well as bone marrow replaced this primary bone after 4 weeks. In the SLA chambers, more bone-to-device contact, more initial woven bone and earlier lamellar bone formation was found than in the T chambers. Osseointegration represents a dynamic process both during its establishment and its maintenance. While healing showed similar characteristics with resorptive and appositional events for both SLA and T

  10. Reactive Oxygen Species and Nitric Oxide in Cutaneous Leishmaniasis

    OpenAIRE

    Maria Fátima Horta; Bárbara Pinheiro Mendes; Eric Henrique Roma; Fátima Soares Motta Noronha; Juan Pereira Macêdo; Luciana Souza Oliveira; Myrian Morato Duarte; Leda Quercia Vieira

    2012-01-01

    Cutaneous leishmaniasis affects millions of people around the world. Several species of Leishmania infect mouse strains, and murine models closely reproduce the cutaneous lesions caused by the parasite in humans. Mouse models have enabled studies on the pathogenesis and effector mechanisms of host resistance to infection. Here, we review the role of nitric oxide (NO), reactive oxygen species (ROS), and peroxynitrite (ONOO−) in the control of parasites by macrophages, which are both the host c...

  11. One Health: The global challenge of epidemic and endemic leishmaniasis

    Directory of Open Access Journals (Sweden)

    Day Michael J

    2011-10-01

    Full Text Available Abstract 'One Health' proposes the unification of medical and veterinary sciences with the establishment of collaborative ventures in clinical care, surveillance and control of cross-species disease, education, and research into disease pathogenesis, diagnosis, therapy and vaccination. The concept encompasses the human population, domestic animals and wildlife, and the impact that environmental changes ('environmental health' such as global warming will have on these populations. Visceral leishmaniasis is a perfect example of a small companion animal disease for which prevention and control might abolish or decrease the suffering of canine and human patients, and which aligns well with the One Health approach. In this review we discuss how surveillance for leishmaniases is undertaken globally through the control of anthroponootic visceral leishmaniasis (AVL and zoonotic visceral leishmaniasis (ZVL. The ZVL epidemic has been managed to date by the culling of infected dogs, treatment of human cases and control of the sandfly vector by insecticidal treatment of human homes and the canine reservoir. Recently, preventive vaccination of dogs in Brazil has led to reduction in the incidence of the canine and human disease. Vaccination permits greater dog owner compliance with control measures than a culling programme. Another advance in disease control in Africa is provided by a surveillance programme that combines remote satellite sensing, ecological modelling, vector surveillance and geo-spatial mapping of the distribution of vectors and of the animal-to-animal or animal-to-human pathogen transmission. This coordinated programme generates advisory notices and alerts on emerging infectious disease outbreaks that may impede or avoid the spreading of visceral leishmaniasis to new areas of the planet as a consequence of global warming.

  12. Liposomal amphotericin B for the treatment of visceral leishmaniasis

    OpenAIRE

    Bern, C.; Adler-Moore, J.; Berenguer, J.; Boelaert, M; van den Boer, M.; Davidson, R N; Figueras, C; Gradoni, L.; Kafetzis, D. A.; Ritmeijer, E.; Rosenthal, E.; Royce, C; Russo, R; Sundar, S; Alvar, J.

    2006-01-01

    During the past decade, liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL). The World Health Organization convened a workshop to review current knowledge and to develop guidelines for liposomal amphotericin B use for VL. In Europe, liposomal amphotericin B is widely used to treat VL. In Africa and Asia, the VL disease burden is high and drug access is poor; liposomal amphotericin B is available only through preferential pricing for nonprofit ...

  13. Liposomal Amphotericin B and Leishmaniasis: Dose and Response

    OpenAIRE

    Shyam Sundar; Jaya Chakravarty

    2010-01-01

    Liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL). It is the treatment of choice for immunocompetent patients in the Mediterranean region and the preferred drug for HIV/VL co-infection. Although there is a regional variation in the susceptibility of the parasite a total dose of 20 mg/kg is effective in immunocompetent patients. Randomized clinical trials of liposomal amphotericin B in the treatment and secondary prophylaxis of HIV-VL coinfec...

  14. Development of Novel Therapeutics for Neglected Tropical Disease Leishmaniasis

    Science.gov (United States)

    2016-10-01

    developmental need of lead optimization in the context of drug potency and specificity. Solubility and stability, key parameters in the development of... research team from CIDEIM in Colombia has established a robust assay to estimate the susceptibility of Leishmania spp parasites to various drugs used in...AWARD NUMBER: W81XWH-14-2-0169 TITLE: Development of Novel Therapeutics for Neglected Tropical Disease Leishmaniasis PRINCIPAL INVESTIGATOR

  15. Membranoproliferative Glomerulonephritis due to Visceral Leishmaniasis in an HIV Patient

    OpenAIRE

    2015-01-01

    Patient: Male, 47 Final Diagnosis: Membranoproliferative glomerulonephritis Symptoms: Nephrotic syndrome Medication: — Clinical Procedure: Renal biopsy Specialty: Nephrology Objective: Rare disease Background: Visceral leishmaniasis is an important opportunistic disease in HIV-positive patients. The information available on the effects of such co-infection in the kidney is limited. We describe a patient with HIV/leishmania coinfection who developed nephrotic syndrome and membranoproliferative...

  16. Visceral leishmaniasis: immunology and prospects for a vaccine.

    Science.gov (United States)

    Kaye, P M; Aebischer, T

    2011-10-01

    Human visceral leishmaniasis (HVL) is the most severe clinical form of a spectrum of neglected tropical diseases caused by protozoan parasites of the genus Leishmania. Caused mainly by L. donovani and L. infantum/chagasi, HVL accounts for more than 50 000 deaths every year. Drug therapy is available but costly, and resistance against several drug classes has evolved. Here, we review our current understanding of the immunology of HVL and approaches to and the status of vaccine development against this disease.

  17. Epidemiological study on acute cutaneous leishmaniasis in Morocco

    Institute of Scientific and Technical Information of China (English)

    Kholoud Kahime; Samia Boussaa; Haddou Nhammi; Ali Boumezzough

    2016-01-01

    Objective: To describe and compare the epidemiological features of anthroponotic cutaneous leishmaniasis (ACL) caused by Leishmania tropica, and zoonotic cutaneous leishmaniasis (ZCL) due to Leishmania major in Morocco. Methods: We performed a retrospective study of ZCL and ACL cases reported during the last ten years in Morocco (2004–2013). Epidemiological data were analyzed by using Pearson's correlation method as well as Tukey test and digital maps were produced for incidence repartition calculated by using ArcMap GIS version 10. Results: A total of 41 656 cases of cutaneous leishmaniasis were notified between 2004 and 2013 in Morocco. The mean incidence was 139 cases/100 000 population/10 years and it was significantly higher in 2010. In the spatial context, ACL form was the most common in Morocco, while ZCL was the most important in terms of the number of reported cases. For both forms, the highest incidence occurred in females and children (0–14 years). When analyzed according to the number of cases in each province, Errachidia (8 728 cases) and Azilal (3 523 cases) were the most affected by ZCL and ACL, respectively, while the highest incidence was noted in Zagora (231 cases/100 000 pop-ulation/10 years) and in Chichaoua (97 cases/100 000 population/10 years), for ZCL and ACL, respectively. Maps of incidence repartition were performed to identify the risk area of ZCL and ACL. Conclusions: ZCL and ACL are still major health problems in Morocco. We highlight the spatiotemporal change of cutaneous leishmaniasis incidence through the country during the last ten years and we underline the correlation between ZCL incidence and the percentage of rural population in Morocco.

  18. Spitz Nevus on the Earlobe Mimicking Cutaneous Leishmaniasis

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    İbrahim Özmen

    2010-06-01

    Full Text Available Spitz nevus is a benign, usually acquired melanocytic tumor which is seen especially in children and adolescents. It usually appears as a pink or light-brown, smooth-surfaced, well-circumscribed and asymptomatic papulonodular lesion. A large group of dermatologic disorders should be considered in the differential diagnosis. Herein we present a case of Spitz nevus with a two month history of a nodular lesion on the earlobe which mimicks cutaneous leishmaniasis clinically.

  19. Visceral leishmaniasis in Malta—an 18 year paediatric, population based study

    Science.gov (United States)

    Grech, V.; Mizzi, J.; Mangion, M.; Vella, C.

    2000-01-01

    BACKGROUND—Visceral leishmaniasis (VL) is a chronic parasitic infection that infects approximately 400 000 individuals annually, with a predilection towards early childhood.
AIMS—To study the epidemiology of VL in childhood.
METHODS—VL is endemic in Malta, a small archipelago of islands in the centre of the Mediterranean with a total population approaching half a million. Notification of human cases of leishmaniasis is compulsory. Case records of all 81 paediatric patients with VL between 1980 and 1998 were analysed.
RESULTS—The annual incidence of VL declined for all cases of VL, and declined significantly for paediatric cases (p = 0.01). For 1994to 1998, the overall incidence of VL was 0.9 per 100 000 total population and the paediatric incidence was 2.5 per 100 000 population. Median age at presentation was 34 months. Common features at presentation were splenomegaly, hepatomegaly, fever, and pancytopenia with high lymphocyte and monocyte counts. The diagnostic sensitivity of isolated immunofluorescent antibody testing was equivalent to bone marrow aspiration (95%). Blood transfusions for anaemia were required in 93% of patients. Eleven per cent had intercurrent infections. All patients were cured, and were initially treated with intravenous sodium stibogluconate. Defervescence occurred after a median of six days of treatment, and patients continued to be treated on a day case basis. Nine relapsers were retreated with sodium stibogluconate, achieving a cure rate of 94%, but five patients required additional drug therapy. There were no permanent sequelae associated with VL or its treatment.
CONCLUSIONS—The decreased incidence is attributed to the eradication of stray dogs which are the disease reservoir.

 PMID:10799428

  20. American tegumentary leishmaniasis: correlations among immunological, histopathological and clinical parameters*

    Science.gov (United States)

    Martins, Ana Luiza Grizzo Peres; Barreto, Jaison Antonio; Lauris, José Roberto Pereira; Martins, Ana Claudia Grizzo Peres

    2014-01-01

    BACKGROUND American tegumentary leishmaniasis has an annual incidence of 1 to 1.5 million cases. In some cases, the patient's immune response can eliminate the parasite, and the lesion spontaneously resolves. However, when this does not occur, patients develop the disseminated form of the disease. OBJECTIVE To investigate the association between clinical, laboratory and pathological findings in cases of American tegumentary leishmaniasis. METHODS A retrospective study of the medical records of 47 patients with American cutaneous leishmaniasis. Clinical, laboratory and epidemiological data were collected, and semi-quantitative histopathological analyses were performed using the Spearman correlation coefficient (p Montenegro reaction, degree of granulomatous transformation and epithelioid cell count; duration of disease, Montenegro reaction and number of lymphocytes; epithelial hyperplasia and edema, hemorrhaging, and epithelial aggression; number of plasmocytes and number of parasites. The main negative correlations found were as follows: age and serology; time and parasite load; epithelial hyperplasia and degree of granulomatous transformation. CONCLUSION The long duration of the disease could be explained by the fact that lesions were relatively asymptomatic, and therefore ignored by patients with low literacy levels. Individuals may have simply waited for spontaneous healing, which proved to be dependent on the activation of hypersensitivity mechanisms. PMID:24626648

  1. Epidemiological Investigation of Canine Leishmaniasis in Southern Morocco

    Directory of Open Access Journals (Sweden)

    Samia Boussaa

    2014-01-01

    Full Text Available Dogs are the major reservoir of Leishmania infantum, the causative agent of human and canine visceral leishmaniasis in the Mediterranean basin. In Morocco, canine leishmaniasis (CanL is usually believed to be widespread mainly, if not only, in the northern regions and few data are available about the situation in southern parts of the country. Here, we report the results of a preliminary, clinical, and serological study carried out in 2004–2007, in four provinces of southern Morocco. Serological analyses were processed using two different Elisa techniques, a homemade Elisa test and IDVET commercial kit, and confirmed by two different western blot (WB tests, homemade and LDBIO commercial kits. We highlighted the presence of CanL infection in southern regions, known until then as free of the disease: 19.8% (48/243 of examined dogs displayed clinical signs compatible with CanL and the seroprevalence was particularly high, respectively, 81.8% and 87.8% by Elisa and western blot tests. Our current developed and validated homemade (Elisa and WB tools will be cost-effective and useful for next large-scale epidemiological studies on Moroccan leishmaniasis animal reservoir.

  2. Leishmaniasis recidivans in Ethiopia: cutaneous and mucocutaneous features.

    Science.gov (United States)

    Dassoni, Federica; Daba, Frehiwot; Naafs, Bernard; Morrone, Aldo

    2017-01-30

    Cutaneous leishmaniasis (CL) is endemic in Ethiopia. An unusual clinical form of this disease is leishmaniasis recidivans (LR), a prolonged, relapsing form of cutaneous leishmaniasis resembling tuberculosis of the skin that may persist for many years with a chronic and relapsing course. This rare variant has been shown to be caused by Leishmania tropica species in the Old World and by Leishmania braziliensis, Leishmania amazonensis, Leishmania panamensis, and Leishmania guyanensis in the New World, as reported in various studies. To our knowledge, there are no reports from Ethiopia, and mucocutaneous involvement of LR has not been described to date. This was a retrospective analysis of the patients seen at the Italian Dermatological Center in Mekelle on the Tigrean highlands over a three-year period (2008-2011). Seven patients with typical clinical features of LR were seen. Two of them presented with signs of mucosal involvement. To date, Leishmania aethiopica is shown to be the only species causing CL that is endemic in the Ethiopian highlands. Therefore, it had to be assumed that the lesions in these patients were caused by this species. The aims of this communication are to report, for the first time, the presence of LR, most likely due to Leishmania aethiopica, in Ethiopia, and to report mucosal involvement in this rare clinical form of CL.

  3. Treatment of canine Old World visceral leishmaniasis: a systematic review.

    Science.gov (United States)

    Noli, Chiara; Auxilia, Silvia T

    2005-08-01

    Canine visceral leishmaniasis is a systemic disease caused by Leishmania infantum. The aim of this systematic review was to identify and evaluate the evidence of efficacy of interventions for treatment or prevention of canine visceral leishmaniasis, and to propose recommendations for or against their use. Forty-seven articles describing clinical trials published between 1980 and 2004 fulfilled selection criteria. The evaluation of clinical trials provided good evidence for recommending the use of meglumine antimoniate at a minimum dosage of 100 mg kg(-1) daily for at least 3-4 weeks, combined with allopurinol in order to obtain a good clinical efficacy and a reduced relapse rate. The evaluation of the articles also provided fair evidence for recommending the use of pentamidine (4 mg kg(-1) twice weekly) and aminosidine (5 mg kg(-1) twice daily) for 3-4 weeks. There was insufficient evidence for recommending the use of allopurinol alone, amphotericin B, buparvaquone, ketoconazole, enrofloxacin, and the combinations of metronidazole with spiramicyn or metronidazole with enrofloxacin. Fair evidence against the use of aminosidine at high dosages (20-80 mg kg(-1) per day) was proposed due to its side effects. Evaluation of articles on repellent measures against sand fly vectors of leishmaniasis provided good evidence for recommending deltamethrin collars and fair evidence for recommending spot-on permethrin.

  4. Eight cases of feline cutaneous leishmaniasis in Texas.

    Science.gov (United States)

    Trainor, K E; Porter, B F; Logan, K S; Hoffman, R J; Snowden, K F

    2010-11-01

    Leishmaniasis is a zoonotic disease caused by intracellular Leishmania protozoa that are transmitted by sandflies. The disease occurs in 3 forms: cutaneous, mucocutaneous, and visceral. Cutaneous leishmaniasis has been reported in cats in Europe and South America and in 1 cat from Texas. Leishmania mexicana is endemic in Texas and has been reported to cause cutaneous lesions in humans. This article describes the pathology of 8 biopsy cases of feline cutaneous leishmaniasis presented to the Texas Veterinary Medical Diagnostic Laboratory over a 3.5-year period. The median age of the cats was 3 years; each was presented with nodular, ulcerative lesions on the pinnae and less commonly on the muzzle and periorbital skin. Histologically, the lesions were nodular to diffuse histiocytic dermatitis with numerous amastigotes (2-4 μm) within macrophages and occasionally within the interstitium. Organisms were often contained within round, clear, intracellular vacuoles. In areas of necrosis, organisms were also free within the interstitium. The overlying epidermis was hyperkeratotic, hyperplastic, and often ulcerated. The organisms were not argyrophilic (Gomori methenamine silver), reacted poorly with periodic acid-Schiff reagent, and were inconsistently basophilic with Giemsa. Although not readily visible histologically, kinetoplasts were evident in amastigotes in cytologic preparations. The lesions were similar to those described for cutaneous L. mexicana infection in humans. In 5 of the 8 cats, Leishmania mexicana DNA was amplified from paraffin-embedded tissue by polymerase chain reaction and sequenced.

  5. Systemic and local immune responses in sheep after Neospora caninum experimental infection at early, mid and late gestation.

    Science.gov (United States)

    Arranz-Solís, David; Benavides, Julio; Regidor-Cerrillo, Javier; Horcajo, Pilar; Castaño, Pablo; del Carmen Ferreras, María; Jiménez-Pelayo, Laura; Collantes-Fernández, Esther; Ferre, Ignacio; Hemphill, Andrew; Pérez, Valentín; Ortega-Mora, Luis Miguel

    2016-01-06

    Besides its importance in cattle, Neospora caninum may also pose a high risk as abortifacient for small ruminants. We have recently demonstrated that the outcome of experimental infection of pregnant sheep with 10(6) Nc-Spain7 tachyzoites is strongly dependent on the time of gestation. In the current study, we assessed peripheral and local immune response in those animals. Serological analysis revealed earlier and higher IFN-γ and IgG responses in ewes infected at early (G1) and mid (G2) gestation, when abortion occurred. IL-4 was not detected in sera from any sheep. Inflammatory infiltrates in the placenta mainly consisted of CD8+ and, to a lesser extent, CD4+ T cells and macrophages (CD163+). The infiltrate was more intense in sheep infected at mid-gestation. In the foetal mesenchyme, mostly free tachyzoites were found in animals infected at G1, while those infected in G2 displayed predominantly particulate antigen, and parasitophorous vacuoles were detected in sheep infected at G3. A similar pattern of placental cytokine mRNA expression was found in all groups, displaying a strengthened upregulation of IFN-γ and IL-4 and milder increases of TNF-α and IL-10, reminiscent of a mixed Th1 and Th2 response. IL-12 and IL-6 were only slightly upregulated in G2, and TGF-β was downregulated in G1 and G2, suggestive of limited T regulatory (Treg) cell activity. No significant expression of TLR2 or TLR4 could be detected. In summary, this study confirms the pivotal role of systemic and local immune responses at different times of gestation during N. caninum infection in sheep.

  6. Increasing access to institutional deliveries using demand and supply side incentives: early results from a quasi-experimental study

    Directory of Open Access Journals (Sweden)

    Serwadda David

    2011-03-01

    Full Text Available Abstract Background Geographical inaccessibility, lack of transport, and financial burdens are some of the demand side constraints to maternal health services in Uganda, while supply side problems include poor quality services related to unmotivated health workers and inadequate supplies. Most public health interventions in Uganda have addressed only selected supply side issues, and universities have focused their efforts on providing maternal services at tertiary hospitals. To demonstrate how reforms at Makerere University College of Health Sciences (MakCHS can lead to making systemic changes that can improve maternal health services, a demand and supply side strategy was developed by working with local communities and national stakeholders. Methods This quasi-experimental trial is conducted in two districts in Eastern Uganda. The supply side component includes health worker refresher training and additions of minimal drugs and supplies, whereas the demand side component involves vouchers given to pregnant women for motorcycle transport and the payment to service providers for antenatal, delivery, and postnatal care. The trial is ongoing, but early analysis from routine health information systems on the number of services used is presented. Results Motorcyclists in the community organized themselves to accept vouchers in exchange for transport for antenatal care, deliveries and postnatal care, and have become actively involved in ensuring that women obtain care. Increases in antenatal, delivery, and postnatal care were demonstrated, with the number of safe deliveries in the intervention area immediately jumping from Conclusions Transport and service vouchers appear to be a viable strategy for rapidly increasing maternal care. MakCHS can design strategies together with stakeholders using a learning-by-doing approach to take advantage of community resources.

  7. Early Stage HIV Management and Reduction of Stavudine-Induced Hepatotoxicity in Rats by Experimentally Developed Biodegradable Nanoparticles.

    Science.gov (United States)

    Ghosh, Saikat; Mondal, Laboni; Chakraborty, Samrat; Mukherjee, Biswajit

    2017-04-01

    The objectives of this research work were to develop optimized nanoparticulate formulations of poly (d,l-lactic-co-glycolic acid) (PLGA) (85:15) with an anti-AIDS drug stavudine and to evaluate their in-vitro uptake by the macrophages and hepatotoxicity in-vivo. Nanoparticles were prepared by nanoprecipitation method based on a factorial design with varying parameters such as the amounts of polymer and stabilizer used. Physicochemical characterizations such as drug-excipient interaction, surface morphology, particle size, and zeta potential measurements were carried out. The best formulation was selected and tagged with fluorescein isothiocyanate (FITC) for cellular uptake study of the formulation. In-vitro uptake of nanoparticles by macrophages was carried out. Formulation-induced hepatotoxicity was assessed by analyzing some serum hepatotoxic parameters and hepatic histology following 10-day treatment in comparison with the free drug. Nanoparticles exhibited smooth surface with particle size 84-238 nm, high entrapment efficiency (approx 85%), and negative surface charge. Formulations showed a sustained drug release pattern over the study period. In-vitro uptake study by macrophages exhibited a time-dependent profile. In-vivo studies on rats showed improvement in the serum parameters and maintenance of the integrity of the hepatic architecture indicating decreased hepatotoxicity with the formulations as compared to the free drug. The experimental results showed a positive outcome in the development of antiretroviral drug carrier exhibiting sustained drug release, macrophage-targeted delivery characteristics, and having reduced hepatoxicity. This could be beneficial for the management of early stage of HIV infection besides reducing the drug load for effective treatment, thereby offering an attractive option in AIDS therapy.

  8. High levels of C-reactive protein in the peripheral blood during visceral leishmaniasis predict subsequent development of post kala-azar dermal leishmaniasis

    DEFF Research Database (Denmark)

    Gasim, S; Theander, T G; ElHassan, A M

    2000-01-01

    Post kala-azar dermal leishmaniasis (PKDL) is a known sequel to visceral leishmaniasis in India and East Africa, and in Sudan about 50% of the kala-azar patients develop PKDL. In this study we followed kala-azar patients from diagnosis and up to 2 years after initiation of treatment. During...... and in keratinocytes during visceral leishmaniasis predict subsequent development of PKDL. The method however requires expensive equipment and reagents. The results of the present study indicate that kala-azar patients, who have a high risk of developing PKDL after treatment can be identified by measuring plasma CRP....

  9. Effect of Echinacea purpurea on Control of Leishmania major Induced Cutaneous Leishmaniasis in Mice

    Directory of Open Access Journals (Sweden)

    MS Sadati

    2011-04-01

    Full Text Available Introduction & Objective: Leishmaniasis is a disease caused by intracellular protozoa parasites of the genus Leishmania and is endemic in some areas of Iran. Echinacea purpurea is a native plant from North America which is one of the most important medical herbs known with immuno-stimulant properties. This study was performed to determine the effect of alcoholic extract of Echinacea purpurea on prophylaxis and treatment of Leishmania cutaneous lesions. Materials & Methods: In this experimental study which was conducted at Shiraz University of Medical Sciences in 2009, eighteen mice were divided into 3 groups. Group one received Echinacea purpurea extract (200 mg/ml in their water, for 2 weeks before parasite injection, while group two were first injected with parasite amastigotes, followed by administration of Echinacea purpurea extract for 2 weeks. Group three was the control group, which received parasites, but not the extract. The size of Leishmania lesions in the tail base, right and left foot were measured with vernier caliper. The lesion areas were calculated and the collected data were analyzed with SPSS software. Results: The mean of lesion size in each group of mice were compared and analyzed. No significant differences in the lesions size were found between the three mice groups. Therefore, Echinacea purpurea extract was not effective against Leishmania major based on the findings of this study. Conclusion: Our findings suggest that Echinacea extract is not effective in treatment or prophylaxis of leishmaniasis in mice. Yet, further studies are needed to determine the effects of other extracts of this plant.

  10. Searching for cutaneous leishmaniasis in tribals from Kerala, India

    Directory of Open Access Journals (Sweden)

    S M Simi

    2010-01-01

    Full Text Available Background : In India, indigenous cases of cutaneous leishmaniasis (CL are mainly confined to the northwestern region. But now, more and more case reports are coming in from other parts of India. In January 2009, a 26-year-old lady residing in a forest area in Thiruvananthapuram district of Kerala State presented with bluish red nodules on her upper extremities, of six months duration, which was clinically more in favor of cutaneous leishmaniasis. She had never gone out of the district of Thiruvananthapuram in her life. Aim : To investigate whether the patient hails from a new endemic focus of cutaneous leishmaniasis. Setting and Design : An epidemiological investigation in the form of a survey was carried out in March 2009 by a multidisciplinary team among 63 persons residing in the Mele Aamala and Aayiramkala forest tribal settlements in Kuttichal Panchayat of Thiruvananthapuram district. Material and Methods : History taking and clinical examination of 38 persons in the area with special consideration to skin lesions was undertaken. Microbiological and histopathological examination of the skin lesions was done. Breeding places of sand fly and possible reservoirs of Leishmania were also simultaneously investigated. Statistical analysis used : The data obtained was tabulated as frequency and percentage. Chi-square test was done to find out the statistical significance of differences in distributions. Results : Out of the 38 persons examined, active lesions were found in 12 persons and six had healed lesions. Tissue samples were obtained from seven out of the 12 suspected cases. Four of them showed Leishman Donovan (LD bodies in tissue smears. Out of the cultures taken from three patients, one showed promastigote forms in Novy McNeal Nicolle (NNN medium. Histopathological study was done in five patients and two patients had LD bodies, one had epithelioid cell granuloma and the other two had mixed infiltrate with predominantly macrophages. All

  11. Can Saffron (Crocus sativus) be effective in the treatment of leishmaniasis?

    Science.gov (United States)

    Bagherani, Nooshin

    2013-10-01

    Leishmaniasis is a parasitic disease caused by Leishmania, transmitted by the bite of some sandfly species. It is endemic in 88 countries throughout the world. Pentavalent antimonials are the standard therapy for leismaniasis. Saffron (crocus sativus) belongs to the iridaceae family. This paper will outline the benefits and challenges of repurposing saffron for treating leishmaniasis.

  12. Comparison of Proinflammatory Gene Expression in Lesions Caused by either Burn Injuries or Cutaneous Leishmaniasis

    OpenAIRE

    Akhzari; Rezvan; Zolhavarieh; Moafi

    2016-01-01

    Background Leishmaniasis is a worldwide disease prevalent in tropical and sub-tropical countries in the world. Characterization of inflammatory responses produced in cutaneous Leishmaniasis has not yet been completed. The current study aims to assess and compare pro-inflammatory cytokines between burning injuries and Leishmania infection. Methods the specific primers were designed for 10 proinflammatory genes including CCL4, CCL3,...

  13. Leishmaniasis isoleret til larynx som årsag til kronisk laryngitis

    DEFF Research Database (Denmark)

    Kaltoft, Mikkel; Munch-Petersen, Helga Richert; Møller, Henrik

    2010-01-01

    Mucosal leishmaniasis is uncommon outside Central and South America, where it is commonly caused by Leishmania (L.) braziliensis. We present a case of isolated laryngeal leishmaniasis detected in a 78-year-old male, who presented with chronic hoarseness. Histologic examination of biopsies taken...

  14. Oronasal leishmaniasis caused by a parasite with an unusual isoenzyme profile

    DEFF Research Database (Denmark)

    Ibrahim, M.; Suliman, A.; Hashim, F.A.

    1997-01-01

    A 45-year-old Sudanese man from western Sudan presented with oronasal leishmaniasis of three years duration. He had no history of previous kala-azar or cutaneous leishmaniasis. The parasite isolated from the oral mucosa was characterized by isoenzymes using 12 enzymes and by polymerase chain...

  15. Immunopathology of post kala-azar dermal leishmaniasis (PKDL): T-cell phenotypes and cytokine profile

    DEFF Research Database (Denmark)

    Ismail, A; El Hassan, A M; Kemp, K

    1999-01-01

    In Sudan, post kala-azar dermal leishmaniasis (PKDL) caused by Leishmania donovani develops in half of the patients treated for visceral leishmaniasis (kala-azar). In most patients lesions heal spontaneously, but in others symptoms are severe and persist for years. This study examined...

  16. Cutaneous Leishmaniasis: The Truth about the 'Flesh-Eating Disease' in Syria.

    Science.gov (United States)

    Mondragon-Shem, Karina; Acosta-Serrano, Alvaro

    2016-06-01

    Recent news headlines claimed that corpses thrown into Syrian streets are causing cutaneous leishmaniasis (CL) outbreaks. However, leishmaniasis is only transmitted by blood-feeding sandflies, not through human remains. High CL prevalence in Syria may instead be attributed to the absence of disease control programs due to the disruption of health services.

  17. Chemotherapy of leishmaniasis: recent advances in the treatment of visceral disease.

    Science.gov (United States)

    Berman, J

    1998-12-01

    New lipid formulations of amphotericin B--AmBisome, Amphotec, and Abelcet--have dramatically decreased the toxicity associated with amphotericin B and have made this group of agents the treatment of choice for visceral leishmaniasis. An agent of a completely different chemical class, the aminoglycoside aminosidine, was 97% curative in India. This agent too may be used for visceral leishmaniasis.

  18. Visceral Leishmaniasis and HIV co-infection in patients admitted to ...

    African Journals Online (AJOL)

    Administrator

    the number of visceral leishmaniasis cases in Ethiopia has increased in the last decade. Objective: To assess the ... Out of 212 visceral leishmaniasis cases tested for. HIV, 87(41.0%) were .... and dragging abdominal pain. Hematocrit level of ...

  19. Zinc/copper imbalance reflects immune dysfunction in human leishmaniasis: an ex vivo and in vitro study

    Directory of Open Access Journals (Sweden)

    Carvalho Edgar M

    2004-11-01

    Full Text Available Abstract Background The process of elimination of intracellular pathogens, such as Leishmania, requires a Th1 type immune response, whereas a dominant Th2 response leads to exacerbated disease. Experimental human zinc deficiency decreases Th1 but not Th2 immune response. We investigated if zinc and copper levels differ in different clinical forms of leishmaniasis, and if these trace metals might be involved in the immune response towards the parasite. Methods Blood was collected from 31 patients with either localized cutaneous (LCL, mucosal (ML or visceral (VL leishmaniasis, as well as from 25 controls from endemic and non-endemic areas. Anti-Leishmania humoral and cellular immune response were evaluated by quantifying specific plasma IgG, lymphoproliferation and cytokine production, respectively. Plasma levels of Cu and Zn were quantified by atomic absorption spectrophotometry. Results A significant decrease in plasma Zn was observed in all three patient groups (p Leishmania IgG (Spearman r = 0.65, p = 0.0028. Cu/Zn ratios were highest in patients with deficient cellular (VLLCL>ML immune response. Ex vivo production of parasite-induced IFN-γ was negatively correlated to plasma Cu levels in LCL (r = -0.57, p = 0.01. In vitro, increased Cu levels inhibited IFN-γ production. Conclusions 1. Zn deficiency in VL and ML indicate possible therapeutic administration of Zn in these severe forms of leishmaniasis. 2. Plasma Cu positively correlates to humoral immune response across patient groups. 3. Environmentally or genetically determined increases in Cu levels might augment susceptibility to infection with intracellular pathogens, by causing a decrease in IFN-γ production.

  20. Evaluation of the in vivo leishmanicidal activity of amphotericin B emulgel: An alternative for the treatment of skin leishmaniasis.

    Science.gov (United States)

    Pinheiro, Iluska Martins; Carvalho, Ivana Pereira; de Carvalho, Camila Ernanda Sousa; Brito, Lucas Moreira; da Silva, Andrezza Braga Soares; Conde Júnior, Airton Mendes; de Carvalho, Fernando Aécio Amorim; Carvalho, André Luis Menezes

    2016-05-01

    The American Cutaneous Leishmaniasis (ACL) is an infectious disease that can be fatal. The first line of treatment is pentavalent antimonies. However, due to its potential to develop resistance, Amphotericin B (AmB) started to be used as an alternative medicine. Current treatments are limited, a fact that has led to a growing interesting in developing new therapies. This study aims to evaluate the therapeutic potential in vivo of an amphotericin B + oleic acid (OA) emulgel in the treatment of cutaneous leishmaniasis in an experimental model. Strains of Leishmania major MHOM/IL/80/Friendlin of Leishmania major were used. The animals were inoculated subcutaneously. After the development of leishmanial, nodular or ulcerative lesions, the animals were divided into three groups (control, Group A and Group B) and treated twice a day for twelve days. The weight of the animals was measured and the size of the lesions was observed. A histopathological analysis was performed with skin fragments of lesions and with the spleen of animals treated with different treatments (emulgel, AmB 3% emulgel and AmB 3% plus OA 5% emulgel). It was observed that when subjected to treatment with AmB 3% emulgel during the study period using both formulations, with enhancer and without enhancer, ulcerative lesions regress gradually or even complete cure. The quantification of the average number of parasites recovered from the inoculation site was made after the treatment in each group and the differences were considered significant. The treatment with AmB 3% and OA 5% emulgel had the best in vivo therapeutic response, showing good prospects for cutaneous leishmaniasis therapy as an alternative therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Feline leishmaniasis due to Leishmania (Leishmania) amazonensis in Mato Grosso do Sul State, Brazil.

    Science.gov (United States)

    de Souza, Alda Izabel; Barros, Evânia Marcia Silva; Ishikawa, Edna; Ilha, Iêda Maria Novaes; Marin, Glaucia Rosely Barbosa; Nunes, Vânia Lúcia Brandão

    2005-03-10

    A case of leishmaniasis in a domestic cat (Felis domesticus) is described. The animal showed a single, nodular lesion on the nose and many nodules of different size on the ears and digital regions of all the paws. Diagnosis was made by microscopic detection of amastigotes in Giemsa-stained smears from the lesions. By monoclonal antibodies the aetiological agent was identified as Leishmania (Leishmania) amazonensis, one of the seven species implicated in human leishmaniasis in Brazil. The clinical signs in feline leishmaniasis are unspecific and similar to those observed in other diseases such as cryptococcosis and in sporotrichosis, commonly found in cats. Leishmaniasis should therefore, be added to the differential diagnosis by feline veterinary practitioners and adequate investigations should carried out for dermal leishmaniasis in the area where the feline infection is detected.

  2. A rapid molecular diagnosis of cutaneous leishmaniasis by colorimetric malachite green-loop-mediated isothermal amplification (LAMP) combined with an FTA card as a direct sampling tool.

    Science.gov (United States)

    Nzelu, Chukwunonso O; Cáceres, Abraham G; Guerrero-Quincho, Silvia; Tineo-Villafuerte, Edwin; Rodriquez-Delfin, Luis; Mimori, Tatsuyuki; Uezato, Hiroshi; Katakura, Ken; Gomez, Eduardo A; Guevara, Angel G; Hashiguchi, Yoshihisa; Kato, Hirotomo

    2016-01-01

    Leishmaniasis remains one of the world's most neglected diseases, and early detection of the infectious agent, especially in developing countries, will require a simple and rapid test. In this study, we established a quick, one-step, single-tube, highly sensitive loop-mediated isothermal amplification (LAMP) assay for rapid detection of Leishmania DNA from tissue materials spotted on an FTA card. An FTA-LAMP with pre-added malachite green was performed at 64°C for 60min using a heating block and/or water bath and DNA amplification was detected immediately after incubation. The LAMP assay had high detection sensitivity down to a level of 0.01 parasites per μl. The field- and clinic-applicability of the colorimetric FTA-LAMP assay was demonstrated with 122 clinical samples collected from patients suspected of having cutaneous leishmaniasis in Peru, from which 71 positives were detected. The LAMP assay in combination with an FTA card described here is rapid and sensitive, as well as simple to perform, and has great potential usefulness for diagnosis and surveillance of leishmaniasis in endemic areas.

  3. Linear B-cell epitope mapping of MAPK3 and MAPK4 from Leishmania braziliensis: implications for the serodiagnosis of human and canine leishmaniasis.

    Science.gov (United States)

    Menezes-Souza, Daniel; de Oliveira Mendes, Tiago Antônio; de Araújo Leão, Ana Carolina; de Souza Gomes, Matheus; Fujiwara, Ricardo Toshio; Bartholomeu, Daniella Castanheira

    2015-02-01

    The correct and early identification of humans and dogs infected with Leishmania are key steps in the control of leishmaniasis. Additionally, a method with high sensitivity and specificity at low cost that allows the screening of a large number of samples would be extremely valuable. In this study, we analyzed the potential of mitogen-activated protein kinase 3 (MAPK3) and mitogen-activated protein kinase 4 (MAPK4) proteins from Leishmania braziliensis to serve as antigen candidates for the serodiagnosis of human visceral and tegumentary leishmaniasis, as well as canine visceral disease. Moreover, we mapped linear B-cell epitopes in these proteins and selected those epitopes with sequences that were divergent in the corresponding orthologs in Homo sapiens, in Canis familiaris, and in Trypanosoma cruzi. We compared the performance of these peptides with the recombinant protein using ELISA. Both MAPK3 and MAPK4 recombinant proteins showed better specificity in the immunodiagnosis of human and canine leishmaniasis than soluble parasite antigens and the EIE-leishmaniose-visceral-canina-bio-manguinhos (EIE-LVC) kit. Furthermore, the performance of this serodiagnosis assay was improved using synthetic peptides corresponding to B-cell epitopes derived from both proteins.

  4. Post Kala-Azar Dermal Leishmaniasis following Treatment with 20 mg/kg Liposomal Amphotericin B (Ambisome) for Primary Visceral Leishmaniasis in Bihar, India

    OpenAIRE

    Sakib Burza; Prabhat Kumar Sinha; Raman Mahajan; Marta González Sanz; María Angeles Lima; Gaurab Mitra; Neena Verma; Pradeep Das

    2014-01-01

    BACKGROUND: The skin disorder Post Kala-Azar Dermal Leishmaniasis (PKDL) occurs in up to 10% of patients treated for visceral leishmaniasis (VL) in India. The pathogenesis of PKDL is not yet fully understood. Cases have been reported in India following therapy with most available treatments, but rarely in those treated with liposomal amphotericin B (Ambisome). Between July 2007 and August 2012 with the support of the Rajendra Memorial Research Institute (RMRI), Médecins Sans Frontières (MSF) ...

  5. Polymorphisms in the TOLLIP Gene Influence Susceptibility to Cutaneous Leishmaniasis Caused by Leishmania guyanensis in the Amazonas State of Brazil.

    Science.gov (United States)

    de Araujo, Felipe Jules; da Silva, Luan Diego Oliveira; Mesquita, Tirza Gabrielle; Pinheiro, Suzana Kanawati; Vital, Wonei de Seixas; Chrusciak-Talhari, Anette; Guerra, Jorge Augusto de Oliveira; Talhari, Sinésio; Ramasawmy, Rajendranath

    2015-01-01

    The clinical outcome to Leishmania-infection is determined by the individual adaptive immune T helper cell responses and their interactions with parasitized host cells. An early development of a proinflammatory immune response (Th1 response) is necessary for Leishmania-infection resolution. The Toll-interacting protein (TOLLIP) regulates human Toll-like receptors signaling pathways by down regulating the proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) and inducing the ant-inflammatory cytokine interleukin-10 (IL-10). Polymorphisms in the TOLLIP gene are associated with infectious diseases. The polymorphisms rs5743899 and rs3750920 in the TOLLIP gene were genotyped by polymerase chain reaction and restriction fragment length polymorphism (RFLP) analysis in 631 patients with cutaneous leishmaniasis (CL) caused by L. guyanensis and 530 individuals with no history of leishmaniasis. The G and T alleles of the rs5743899 and rs3750920 were more common in patients with CL than in healthy individuals (P = 2.6 x10(-8) ; odds ratio [OR], 1.7 [ 95% confidence interval (CI) 1.4-2.0] and P = 1.9 x10(-8) ; OR, 1.6 [95% CI 1.4-1.9] respectively). The r2 and D' linkage disequilibrium between the two polymorphisms are 0.05 and 0.473 with a confidence bounds of 0.37 to 0.57 respectively. The two polymorphisms are independently associated with an increased risk of developing CL.

  6. Impact of leishmaniasis in women: a practical review with an update on my ISD-supported initiative to combat leishmaniasis in Yemen (ELYP

    Directory of Open Access Journals (Sweden)

    Mohamed A. Al-Kamel, MD

    2016-09-01

    Full Text Available Stigma is synonymous with leishmaniasis, an endemic deadly flesh-eating disease in Yemen that affects predominantly poor rural women and children. Women with leishmaniasis often present late and experience not only physical deformities and the risk of death, but also the painful stigma of the disease and its consequences, a similar situation to that of leprosy decades ago. The International Society of Dermatology–sponsored community dermatology project Eradication of Leishmaniasis from Yemen Project has made a difference in the leishmaniasis situation in Yemen and addressed its magnitude. The program eradicated leishmaniasis from some areas, dealt with and improved its alarming prevalence among children and women who are the neglected and highest risk groups, and solved some issues associated with poor access to proper drugs. Medicine donation has enabled women with leishmaniasis to freely receive medicine they otherwise would not have been able to afford, reduced their mortality and morbidity, and minimized the extensive impact the socio-aesthetic stigma has on their lives. Our cause has attracted local and global attention to these problematic issues.

  7. Protective Effect of Vitamin D3 and Gp63 Conjugated with Tetanus Toxoid on Outcome of Cutaneous Leishmaniasis Lesions in Balb/C Mice

    Directory of Open Access Journals (Sweden)

    S Soudi

    2006-01-01

    Full Text Available Introduction: GP63 is a major surface protease of Leishmania promastigotes that plays an important role in its virulance. As GP63 on its own can not develop an effective protection against leishmaniasis, the goal of this study was to evaluate the protective effect of GP63 conjugated with tetanus toxoid (TT and Vitamin D3 in susceptible BALB/c mice against cutaneous leishmaniasis. Methods: This study was a basic-applied experimental study performed in Tarbiat Modarres University from September 2002 to April 2005. Cloned virulant Leishmania (L. major [MRHO / IR / 75 / ER] strain was cultured and 5109 cells were harvested. GP63 Molecule was purified and conjugated with TT and conjugated molecule was used for immunization of 8 groups of female BALB/c mice. Results: Results showed that the group of mice receiving conjugated molecule with Vitamin D3 had significant differences from other groups regarding lesion progression (P0.05. The culture of spleen cells showed that the disease did not become systemic in this group. Conclusion: Conjugation of GP63 with TT strengthens cell immunity and its use along with vitamin D3 provokes macrophages activity. This basis can be used for production of an appropriate preparation for protection against Leishmaniasis.

  8. A Poly(Lactic-co-Glycolic) Acid Nanovaccine Based on Chimeric Peptides from Different Leishmania infantum Proteins Induces Dendritic Cells Maturation and Promotes Peptide-Specific IFNγ-Producing CD8+ T Cells Essential for the Protection against Experimental Visceral Leishmaniasis

    Science.gov (United States)

    Athanasiou, Evita; Agallou, Maria; Tastsoglou, Spyros; Kammona, Olga; Hatzigeorgiou, Artemis; Kiparissides, Costas; Karagouni, Evdokia

    2017-01-01

    Visceral leishmaniasis, caused by Leishmania (L.) donovani and L. infantum protozoan parasites, can provoke overwhelming and protracted epidemics, with high case-fatality rates. An effective vaccine against the disease must rely on the generation of a strong and long-lasting T cell immunity, mediated by CD4+ TH1 and CD8+ T cells. Multi-epitope peptide-based vaccine development is manifesting as the new era of vaccination strategies against Leishmania infection. In this study, we designed chimeric peptides containing HLA-restricted epitopes from three immunogenic L. infantum proteins (cysteine peptidase A, histone H1, and kinetoplastid membrane protein 11), in order to be encapsulated in poly(lactic-co-glycolic) acid nanoparticles with or without the adjuvant monophosphoryl lipid A (MPLA) or surface modification with an octapeptide targeting the tumor necrosis factor receptor II. We aimed to construct differentially functionalized peptide-based nanovaccine candidates and investigate their capacity to stimulate the immunomodulatory properties of dendritic cells (DCs), which are critical regulators of adaptive immunity generated upon vaccination. According to our results, DCs stimulation with the peptide-based nanovaccine candidates with MPLA incorporation or surface modification induced an enhanced maturation profile with prominent IL-12 production, promoting allogeneic T cell proliferation and intracellular production of IFNγ by CD4+ and CD8+ T cell subsets. In addition, DCs stimulated with the peptide-based nanovaccine candidate with MPLA incorporation exhibited a robust transcriptional activation, characterized by upregulated genes indicative of vaccine-driven DCs differentiation toward type 1 phenotype. Immunization of HLA A2.1 transgenic mice with this peptide-based nanovaccine candidate induced peptide-specific IFNγ-producing CD8+ T cells and conferred significant protection against L. infantum infection. Concluding, our findings supported that encapsulation

  9. Maxadilan-simile expression in Nyssomyia neivai, a sandfly vector in an endemic region of Brazil, and its immunogenicity in patients with American tegumentary leishmaniasis

    Science.gov (United States)

    Aires, Juliana; Casanova, Claudio; Vernal, Sebastian; Nascimento, Margarida; Rodrigues, Sandra; Lerner, Ethan A; Roselino, Ana Maria

    2017-01-01

    BACKGROUND Maxadilan (Max) is a salivary component in the sandfly Lutzomyia longipalpis (Lutz & Neiva 1912), a vector of visceral leishmaniasis. Max has a powerful vasodilatory effect and is a candidate vaccine that has been tested in experimental leishmaniasis. Nyssomyia neivai (Pinto 1926) is a vector of the pathogen responsible for American tegumentary leishmaniasis (ATL) in Brazil. OBJECTIVE We searched for Max expression in Ny. neivai and for antibodies against Max in ATL patients. METHODS cDNA and protein were extracted from the cephalic segment, including salivary glands, of Ny. neivai and analysed by polymerase chain reaction, DNA sequencing, and blotting assays. The results were compared with data obtained from Lu. longipalpis samples. We quantified antibodies against Max in serum samples from 41 patients with ATL (31 and 10 with the cutaneous and mucocutaneous forms, respectively) and 63 controls from the endemic northeastern region of São Paulo state, using enzyme-linked immunosorbent assay. FINDINGS Recognition of a Max-simile peptide by specific antibodies confirmed expression of a Max sequence in Ny. neivai (GenBank EF601123.1). Compared to controls, patients with ATL presented higher levels of antibodies against Max (p = 0.004); 24.4% of the patients with ATL and 3.2% of the controls presented anti-Max levels above the cutoff index (p = 0.014). The anti-Max levels were not associated with the specific clinical form of ATL, leishmanin skin test response, absence or presence of amastigotes in histopathologic exam, results of indirect immunofluorescence testing for leishmaniasis, or duration of cutaneous form disease. MAIN CONCLUSION High serum anti-Max levels did not protect patients against ATL, but confirmed previous natural exposure to Ny. neivai bites in this ATL endemic region. PMID:28177045

  10. SIRT3 Expression Decreases with Reactive Oxygen Species Generation in Rat Cortical Neurons during Early Brain Injury Induced by Experimental Subarachnoid Hemorrhage

    Science.gov (United States)

    Huang, Wei; Huang, Yong; Huang, Ren-qiang; Gu, Jin-mao; Dong, Yan

    2016-01-01

    Sirtuin3 (SIRT3) is an important protein deacetylase which predominantly presents in mitochondria and exhibits broad bioactivities including regulating energy metabolism and counteracting inflammatory effect. Since inflammatory cascade was proved to be critical for pathological damage following subarachnoid hemorrhage (SAH), we investigated the overall expression and cell-specific distribution of SIRT3 in the cerebral cortex of Sprague-Dawley rats with experimental SAH induced by internal carotid perforation. Results suggested that SIRT3 was expressed abundantly in neurons and endothelia but rarely in gliocytes in normal cerebral cortex. After experimental SAH, mRNA and protein expressions of SIRT3 decreased significantly as early as 8 hours and dropped to the minimum value at 24 h after SAH. By contrast, SOD2 expression increased slowly as early as 12 hours after experimental SAH, rose up sharply at the following 12 hours, and then was maintained at a higher level. In conclusion, attenuated SIRT3 expression in cortical neurons was associated closely with enhanced reactive oxygen species generation and cellular apoptosis, implying that SIRT3 might play an important neuroprotective role during early brain injury following SAH. PMID:28053989

  11. Health economic evaluations of visceral leishmaniasis treatments: a systematic review.

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    Daniel S Marinho

    2015-02-01

    Full Text Available OBJECTIVE: The main objective of this study was to identify, describe, classify and analyze the scientific health economic evidence of VL-related technologies. METHODS: A web search of combinations of free text and Mesh terms related to the economic evaluation of visceral leishmaniasis was conducted on scientific publication databases (Web of Science, Scopus, Medline via the Pubmed and Lilacs. A manual search of references lists of articles previously identified by the authors was also included. Articles written in English, Portuguese, Spanish or French were considered suitable for inclusion. Articles that matched the inclusion criteria were screened by at least two researchers, who extracted information regarding the epidemiologic scenario and methodological issues on a standardized form. RESULTS: The initial search retrieved 107 articles, whose abstracts were inspected according to the inclusion criteria leading to a first selection of 49 (46% articles. After the elimination of duplicates, the list was reduced to 21 (20% articles. After careful reading and application of exclusion criteria, 14 papers were eligible according to the description, classification and analysis process proposed by the study. When classified by type of economic evaluation, articles were 7 (50% cost-effectiveness, 5 (36% cost-minimization, 1(7% cost-benefit, and 1(7% budget impact. When classified by methodology, studies were mainly nested to clinical-trials ("piggy back" 8(57%. Discount rates for outcomes and costs were present in 3 (43% of the cost-effectiveness studies, and according to WHO's recommendations, the discount rate of 3% was used in all studies. CONCLUSIONS: This article showed that health economic evaluations on visceral leishmaniasis used a wide range of technologies and methods. Nevertheless it is important to point out the geographic concentration of studies, which makes their transferability uncertain to different epidemiological scenarios

  12. Feline Leishmania infection in a canine leishmaniasis endemic region, Portugal.

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    Maia, C; Gomes, J; Cristóvão, J; Nunes, M; Martins, A; Rebêlo, E; Campino, L

    2010-12-15

    Canine leishmaniasis (CanL) caused by Leishmania infantum is a serious zoonotic public health and veterinary problem in the Mediterranean basin. Leishmania infection in domestic cats (Felis catus domesticus) has been reported in several countries where this zoonosis is endemic, such as Portugal, Spain, Italy, France, Greece, Israel, Palestine and Brazil. The aim of this study was to contribute to the knowledge of the role played by cats in Leishmania epidemiology, in an endemic focus of zoonotic leishmaniasis, the Lisbon metropolitan area, Portugal. L. infantum DNA was detected in peripheral blood of 28 out of 138 cats (20.3%). The result of PCR in blood of cats was not closely associated with the level of specific circulating antibodies in their sera. Positive serology was observed only in one cat out of 76. In the same geographic region and time period the indirect immunofluorescent test revealed 20.4% (31/152) of dogs with antibodies and PCR detected Leismania DNA on 34.9% (53/152) animals. Despite the fact that specific antibodies have been validated for diagnosis of CanL, their detection does not seem to be sensitive enough to predict Leishmania infection in cats. On the other hand, the presence of parasite DNA in cat's peripheral blood during the transmission season and out of the season suggests that these animals living in endemic areas are frequently exposed or infected with the parasite. Although dogs have been universally regarded as the major domestic/peridomestic reservoir hosts, the present data allow us to hypothesize that cats can act as an alternative reservoir host of L. infantum, rather than an accidental host. However, in order to evaluate the existence of a transmission cycle with cats sustaining and spreading zoonotic leishmaniasis is necessary to prove that these animals can transmit the parasite to the vector in nature. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Elimination of taphonomic bias in late Paleocene to early Eocene paleoenvironmental reconstructions by means of experimental dissolution studies on foraminifera

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    Nguyen, T. M. P.; Petrizzo, M. R.; Speijer, R. P.

    2009-04-01

    dissolution in foraminiferal assemblages used in early Paleogene paleoenvironmental reconstructions, with an emphasis on the PETM. Our experiments confirm two general observations on modern foraminifera: 1) planktonic foraminifera are much more vulnerable to dissolution than benthic foraminifera, leading to depressed P/B ratios and 2) dissolution susceptibility differs between size fractions, with the smaller specimens (less calcite) dissolving more rapidly than bigger ones, leading to a larger average size of the remaining specimens. During the experiment, the planktonic assemblage becomes more and more enriched in the resistant muricate genera Acarinina and Morozovella. Smooth taxa such as Globanomalina and Zeauvigerina disappear first, followed by the cancellate Subbotina. The high relative susceptibility of Subbotina is unexpected, since poorly preserved assemblages often contain abundant specimens of this genus. Our experimental data suggest that Subbotina must have been strongly dominant in the primary assemblages, which could be indicative of strong upwelling. Amongst the benthic assemblage of Dababiya dissolution leads to a relative enrichment of Lenticulina and the agglutinated Gaudryina. Biserial, triserial and porcelaneous taxa are most susceptible to dissolution, whereas thick-shelled rotaliines, such as Alabamina, Cibicidoides and Anomalinoides, have an intermediate susceptibility. Our data enable to objectively identify various degrees of dissolution in foraminiferal assemblages retrieved from Paleocene-Eocene transitions. In this way taphonomic artifacts can be readily distinguished from primary paleoenvironmental signals affecting the composition of the assemblages. When applied to studied PETM sequences in Egypt, we observe that 25-30% of the samples analyzed for foraminiferal assemblages show signs of strong dissolution. An evaluation of published records across the PETM and other postulated hyperthermals (LDE, ELPE, Elmo, X-event) reveals that partial

  14. Leishmaniasis Panamensis Masquerading as Myiasis and Sporotrichosis: A Clinical Pitfall

    Science.gov (United States)

    Pavlidakey, Peter G.; Huynh, Thy; McKay, Kristopher Michael; Sami, Naveed

    2015-01-01

    We report a case of cutaneous leishmaniasis panamensis in nonendemic Costa Rica. A 19-year-old female presented with nonhealing, unilateral eruption of erythematous papules with superficial central ulceration in a sporotrichoid pattern on right upper arm and back. Given the clinical picture and geographic locale, the patient was initially diagnosed with myiasis or human botfly infestation; however, the sporotrichoid pattern of the bites is an unlikely finding in myiasis. Peripheral blood smear, Giemsa stain, and polymerase chain reaction (PCR) were consistent for Leishmania spp. Ulceration resolved with 20-day course of IV sodium stibogluconate. PMID:26413365

  15. Leishmaniasis Panamensis Masquerading as Myiasis and Sporotrichosis: A Clinical Pitfall

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    Peter G. Pavlidakey

    2015-01-01

    Full Text Available We report a case of cutaneous leishmaniasis panamensis in nonendemic Costa Rica. A 19-year-old female presented with nonhealing, unilateral eruption of erythematous papules with superficial central ulceration in a sporotrichoid pattern on right upper arm and back. Given the clinical picture and geographic locale, the patient was initially diagnosed with myiasis or human botfly infestation; however, the sporotrichoid pattern of the bites is an unlikely finding in myiasis. Peripheral blood smear, Giemsa stain, and polymerase chain reaction (PCR were consistent for Leishmania spp. Ulceration resolved with 20-day course of IV sodium stibogluconate.

  16. Wound healing genes and susceptibility to cutaneous leishmaniasis in Brazil

    OpenAIRE

    Castellucci, Léa; Jamieson, Sarra E; Almeida, Lucas; Oliveira, Joyce; Guimarães, Luiz Henrique; Lessa, Marcus; Fakiola, Michaela; Jesus, Amélia Ribeiro de; Miller, E. Nancy; Carvalho, Edgar M.; Blackwell, Jenefer M.

    2012-01-01

    Leishmania braziliensis causes cutaneous (CL) and mucosal (ML) leishmaniasis. In the mouse, Fli1 was identified as a gene influencing enhanced wound healing and resistance to CL caused by L. major. Polymorphism at FLI1 is associated with CL caused by L. braziliensis in humans, with an inverse association observed for ML disease. Here we extend the analysis to look at other wound healing genes, including CTGF, TGFB1, TGFBR1/2, SMADS 2/3/4/7 and FLII, all functionally linked along with FLI1 in ...

  17. Antissaliva Antibodies of Lutzomyia Longipalpis in area of Visceral Leishmaniasis.

    Science.gov (United States)

    Fraga, Thiago Leite; Fernandes, Magda Freitas; Pontes, Elenir Rose Jardim Cury; Levay, Ana Paula Silva; Almeida da Cunha, Elenice Brandão; França, Adriana de Oliveira; Dorval, Maria Elizabeth Cavalheiros

    2016-07-01

    The aim of the present study was to assess the presence of antissaliva antibodies of Lutzomyia longipalpis in human hosts living in area of visceral leishmaniasis, located in the Center-West region of Brazil. The presence of antissaliva antibodies of L. longipalpis exhibited a strong correlation with the protection and development of antibodies against Leishmania sp. Of the 492 children studied, elevated antissaliva antibodies of L. longipalpis were detected in 38.4% of the participants. There was a higher percentage of positivity (64.7%) among children who exhibited anti-Leishmania sp. antibodies and among those who were positive in the delayed hypersensitivity test (34.8%).

  18. Early development conditions and the oxidative cost of social context in adulthood: an experimental study in birds

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    Ana eRomero-Haro

    2015-04-01

    Full Text Available Environmental conditions during early life may shape phenotype in adulthood. Early adverse conditions may increase the oxidative stress in adults, which could affect their reproductive output and survival. It has also been hypothesized that the larger the reproductive investment, the higher the oxidative stress. We tested this and the potential influence of early oxidative stress on how individuals respond to a reproductive stimulation. The synthesis of the antioxidant glutathione was inhibited in captive zebra finches (Taeniopygia guttata during growth. In adulthood, the expression of a carotenoid-based sexual signal, bill redness, increased in both sexes, with females also being heavier than controls. The social context of control and glutathione-inhibited males was then manipulated to stimulate precopulatory reproductive investments. Males were individually caged in front of a female or another male. We predicted that males enduring lower early antioxidant levels and placed close to a female should pay the highest cost of a hypothetical increase in bill redness in terms of oxidative damage. However, early conditions only influenced the male’s phenotype via their partners. Males caged with females showed increases in circulating pigment (carotenoid levels, but only when females endured early low antioxidant values. This was probably related to the higher attractiveness of these females. Nevertheless, the bill redness of males did not differ during the social manipulation. Moreover, males facing females from any early condition group showed lower oxidative damage levels in plasma lipids. This result agrees with some findings in rodents, also in captivity. However, the effect may be due to increased triglyceride levels and body mass in males not facing females, as variation in these traits explained oxidative damage variability. The importance of considering housing conditions and life history when interpreting oxidative stress-related trade

  19. Spatially Correlated Time Series and Ecological Niche Analysis of Cutaneous Leishmaniasis in Afghanistan

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    Oyelola A. Adegboye

    2017-03-01

    Full Text Available Leishmaniasis is the third most common vector-borne disease and a very important protozoan infection. Cutaneous leishmaniasis is one of the most common types of leishmaniasis infectious diseases with up to 1.2 million occurrences of new cases each year worldwide. A dynamic transmission multivariate time series model was applied to the data to account for overdispersion and evaluate the effects of three environmental layers as well as seasonality in the data. Furthermore, ecological niche modeling was used to study the geographically suitable conditions for cutaneous leishmaniasis using temperature, precipitation and altitude as environmental layers, together with the leishmaniasis presence data. A retrospective analysis of the cutaneous leishmaniasis spatial data in Afghanistan between 2003 and 2009 indicates a steady increase from 2003 to 2007, a small decrease in 2008, and then another increase in 2009. An upward trend and regularly repeating patterns of highs and lows were observed related to the months of the year, which suggests seasonality effect in the data. Two peaks were observed in the disease occurrence—January to March and September to December—which coincide with the cold period. Ecological niche modelling indicates that precipitation has the greatest contribution to the potential distribution of leishmaniasis.

  20. Ecological and social determinants of leishmaniasis in the Legal Amazon, Brazil

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    Kamila Mendes de Oliveira

    2014-01-01

    Full Text Available Leishmaniasis is a reemerging disease of worldwide distribution and has a public health importance. It is an infectious disease, parasitical and clinical severity ranging from a healthy appearance to a severe stage. Features two major forms, such as cutaneous leishmaniasis (cutaneous and mucocutaneous and visceral leishmaniasis. This form can be deadly for reaching the organs. The four main protozoa that cause such clinical manifestations are Leishmania chagasi, Leishmania braziliensis, Leishmania amazonensis and Leishmania guyanensis. Environment, social and demographic factors are key for the transmission of leishmaniasis, due to its vector being a sand fly - insect with hematophagous habits - and its main reservoir are dogs. In Brazil, leishmaniasis is endemic and widely distributed. 80% of reported cases are in children under 10 years. The Legal Amazon region is an area of study of public health, having suffered anthropogenic actions that undermine the ecological balance of the site. In this area, visceral leishmaniasis is increasing in western Pará state due to its economic development, which involves the public health. This study aims to relate environmental and health factors with the incidence of leishmaniasis in the Legal Amazon and this relationship will be used secondary data from publications in the National Health Information System (NHIS.

  1. Dispersal of Lutzomyia longipalpis and expansion of canine and human visceral leishmaniasis in São Paulo State, Brazil.

    Science.gov (United States)

    Oliveira, Agda Maria; Vieira, Carolina Portugal; Dibo, Margareth Regina; Guirado, Marluci Monteiro; Rodas, Lilian Aparecida Colebrusco; Chiaravalloti-Neto, Francisco

    2016-12-01

    Visceral leishmaniasis (VL), a neglected disease, is a serious public health problem that affects millions of people worldwide. The objectives of the study were to evaluate the sensitivity of Lutzomyia longipalpis and canine VL (CVL) autochthony early detection and describe the spatial and temporal dispersal of vector and expansion of VL in a Brazilian state. We obtained data on the leishmaniasis vector and VL cases in São Paulo State (SP), Brazil, from the Division of Endemic Disease Control and from the Epidemiological Surveillance Center of the São Paulo State Department of Health. Data were analyzed for 645 municipalities and 63 microregions and presented as thematic and flow maps. Following the verified presence of L. longipalpis in Araçatuba in 1997, the first autochthonous cases of canine VL (CVL) (1998) and of human VL (HVL) (1999) in São Paulo were reported, both in Araçatuba. From 1997 to 2014, the urban presence of the leishmaniasis vector was verified in 167 (25.9%) municipalities with cases of CVL reported in 108 (16.7%) and cases of HVL in 84 (13%). The sensitivities for vector presence early detection in relation to the identification of CVL and HVL autochthony were, respectively, equal to 76.4 and 92.5%. The sensitivity for CVL autochthony early detection in relation to the HVL autochthony identification was 75.8%. Vector dispersal and expansion of CVL and HVL were from the northwest to the southeast of the state, primarily flanking the Marechal Rondon highway at a constant rate of progression of 10, seven, and six new municipalities affected per year, respectively. We concluded that the sensitivity for vector presence and CVL autochthony presented reasonable accuracy and most of the time the vector presence and, specially, the CVL and HVL autochthony were identified in the main cities of the microregions of SP. Vector dispersal and expansion of VL started in 1997 near the state border of SP with the state of Mato Grosso do Sul. It has advanced

  2. T cell-derived IL-10 determines leishmaniasis disease outcome and is suppressed by a dendritic cell based vaccine.

    Science.gov (United States)

    Schwarz, Tobias; Remer, Katharina A; Nahrendorf, Wiebke; Masic, Anita; Siewe, Lisa; Müller, Werner; Roers, Axel; Moll, Heidrun

    2013-01-01

    In the murine model of Leishmania major infection, resistance or susceptibility to the parasite has been associated with the development of a Th1 or Th2 type of immune response. Recently, however, the immunosuppressive effects of IL-10 have been ascribed a crucial role in the development of the different clinical correlates of Leishmania infection in humans. Since T cells and professional APC are important cellular sources of IL-10, we compared leishmaniasis disease progression in T cell-specific, macrophage/neutrophil-specific and complete IL-10-deficient C57BL/6 as well as T cell-specific and complete IL-10-deficient BALB/c mice. As early as two weeks after infection of these mice with L. major, T cell-specific and complete IL-10-deficient animals showed significantly increased lesion development accompanied by a markedly elevated secretion of IFN-γ or IFN-γ and IL-4 in the lymph nodes draining the lesions of the C57BL/6 or BALB/c mutants, respectively. In contrast, macrophage/neutrophil-specific IL-10-deficient C57BL/6 mice did not show any altered phenotype. During the further course of disease, the T cell-specific as well as the complete IL-10-deficient BALB/c mice were able to control the infection. Furthermore, a dendritic cell-based vaccination against leishmaniasis efficiently suppresses the early secretion of IL-10, thus contributing to the control of parasite spread. Taken together, IL-10 secretion by T cells has an influence on immune activation early after infection and is sufficient to render BALB/c mice susceptible to an uncontrolled Leishmania major infection.

  3. Leishmaniasis cutánea difusa en un paciente con sida Diffuse cutaneous leishmaniasis in a patient with AIDS

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    Carlos Pérez

    2006-12-01

    Full Text Available Objetivo. Estudiar un paciente con leishmaniasis cutánea difusa y sida y comentar el tema.
    Materiales y métodos. Soldado de 29 años, procedente de San José del Guaviare, con pérdida de 18 kilos de peso en los últimos 10 meses y erupción generalizada de dos meses de evolución. El Elisa y el Western blot fueron positivos para virus de inmunodeficiencia humana. Tenía 92 LT CD4/mm3. Presentaba máculas, pápulas y placas eritematoescamosas, psoriasiformes y generalizadas, cuyas biopsias demostraron abundantes microorganismos fagocitados por macrófagos, que se teñían de negro con la coloración de Gomory. Se diagnosticó histoplasmosis diseminada. Se inició tratamiento antirretroviral y antimicótico con itraconazol sin observar mejoría.
    Resultados. La anfotericina B produjo mejoría, pero las lesiones recidivaron más numerosas y nodulares con compromiso oral. Once meses después del comienzo de su enfermedad, nuevas biopsias de piel y la revisión de las anteriores confirmaron que el paciente tenía leishmaniasis cutánea difusa. El cultivo no permitió aislar el parásito. La miltefosina produjo mejoría importante. Las pápulas y máculas recidivaron varios meses después; recibió 52 ampollas de glucantime® durante dos meses, consiguiéndose la curación clínica, situación que permanece dos años y medio después de iniciada la enfermedad.
    Conclusiones. La leishmaniasis cutánea difusa debe plantear sospecha de sida. El tratamiento es difícil; debe ser antirretroviral y antileishmaniásico, con profilaxis antiparasitaria. Los amastigotes de Leishmania no son positivos con la coloración de Gomory en técnicas controladas; se diferencian del histoplasma por morfología, cultivo, inmunohistoquímica, anticuerpos específicos y reacción en cadena de la polimerasa. La asociación leishmaniasissida es beneficiosa para ambos gérmenes; es posible el aumento de casos en Colombia por el auge de ambas entidades

  4. Diffuse cutaneous leishmaniasis: Co-infection with human immunodeficiency virus (HIV

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    Chaudhary Raju

    2008-01-01

    Full Text Available Cutaneous leishmaniasis is a disease caused by intracellular protozoal parasites belonging to the genus Leishmania. Immune suppression caused by HIV infection is an important factor for atypical presentation and widespread progression of cutaneous leishmaniasis. Diffuse (disseminated cutaneous leishmaniasis and HIV co-infection is emerging as an extremely serious new disease. A 38-year-old HIV-positive man presented with a 12-month history of a progressive papule and nodular eruptions on face and extremities with infiltrations of nasal and oral mucosa. We report the case due to its atypical, widespread muco-cutaneous presentation masquerading as lepromatous leprosy.

  5. Post-kala-azar dermal Leishmaniasis in two different clinical contexts*

    Science.gov (United States)

    Barroso, Daniel Holanda; Silva, Claúdia Elise Ferraz; Vasconcelos, Ana Carolina Depes Perdigao e; Cavalcanti, Silvana Maria de Morais; de Brito, Maria Edileuza Felinto; Medeiros, Angela Cristina Rapela

    2015-01-01

    In Brazil, visceral Leishmaniasis is caused by Leishmania chagasi. The development of cutaneous lesions in visceral leishmaniasis patients has been described in two different clinical contexts. Patients with compromised immunity can develop skin lesions as a direct consequence of a current visceral disease. Equally, patients with a history of kala-azar and progressive, immune improvement occasionally develop skin lesions as a consequence of immune reconstitution infl ammatory syndrome. These cases manifest in similar fashion to the classic form of post-kala-azar dermal Leishmaniasis. We describe different cases that exemplify these two clinical presentations. PMID:26312689

  6. Differential Expression of the Eicosanoid Pathway in Patients With Localized or Mucosal Cutaneous Leishmaniasis.

    Science.gov (United States)

    França-Costa, Jaqueline; Andrade, Bruno B; Khouri, Ricardo; Van Weyenbergh, Johan; Malta-Santos, Hayna; da Silva Santos, Claire; Brodyskn, Cláudia I; Costa, Jackson M; Barral, Aldina; Bozza, Patrícia T; Boaventura, Viviane; Borges, Valeria M

    2016-04-01

    Unfettered inflammation is thought to play critical role in the development of different clinical forms of tegumentary leishmaniasis. Eicosanoids are potent mediators of inflammation and tightly associated with modulation of immune responses. In this cross-sectional exploratory study, we addressed whether targets from the eicosanoid biosynthetic pathway, assessed by multiplexed expression assays in lesion biopsy and plasma specimens, could highlight a distinct biosignature in patients with mucocutaneous leishmaniasis (MCL) or localized cutaneous leishmaniasis (LCL). Differences in immunopathogenesis between MCL and LCL may result from an imbalance between prostaglandins and leukotrienes, which may serve as targets for future host-directed therapies.

  7. Imported cutaneous leishmaniasis caused by Leishmania major in a Chinese laborer who worked in Saudi Arabia*

    Science.gov (United States)

    Zhang, Min; Liu, Fang; Liu, Haibo; Hu, Wenxing; Sang, Hong

    2016-01-01

    We report an imported case of cutaneous leishmaniasis in a 37-year-old man from Saudi Arabia caused by Leishmania major. He presented with non-healing nodulo-ulcerative lesions with a "volcanic crater" on the lower limbs. It was clearly cutaneous leishmaniasis - a rare disease in China - as reflected by the patient's clinical history, the lesions' morphology, histopathological examination, culture and PCR analysis of the lesions. The patient was completely cured after two cycles of sodium stibogluconate treatment. This case report demonstrates that dermatologists should be aware of sporadic cutaneous leishmaniasis cases in non-endemic areas. PMID:27438208

  8. [Mucocutaneous leishmaniasis. Histologic classification and anatomoclinical correlations. Apropos of 102 cases].

    Science.gov (United States)

    Huaman, J A; Castillo, M C

    1990-01-01

    Two hundred and three skin and mucosal biopsies performed in 162 patients suffering from leishmaniasis, were studied retrospectively. They were classified according to Ridley into 5 histological groups of increasing severity. In cutaneous leishmaniasis, a high proportion of the biopsies belonged to groups III and IV. In mucocutaneous leishmaniasis, the percentage of groups III and VI was lower and group V was present in 20% of cases. In 16 patients, followed by repeated biopsies, we detected some variations of the histological group during the course of the disease. However, there were no positive correlations between clinicopathological features and prognosis.

  9. Seasonal Dynamics of Phlebotomine Sand Fly Species Proven Vectors of Mediterranean Leishmaniasis Caused by Leishmania infantum.

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    Bulent Alten

    2016-02-01

    Full Text Available The recent geographical expansion of phlebotomine vectors of Leishmania infantum in the Mediterranean subregion has been attributed to ongoing climate changes. At these latitudes, the activity of sand flies is typically seasonal; because seasonal phenomena are also sensitive to general variations in climate, current phenological data sets can provide a baseline for continuing investigations on sand fly population dynamics that may impact on future scenarios of leishmaniasis transmission. With this aim, in 2011-2013 a consortium of partners from eight Mediterranean countries carried out entomological investigations in sites where L. infantum transmission was recently reported.A common protocol for sand fly collection included monthly captures by CDC light traps, complemented by sticky traps in most of the sites. Collections were replicated for more than one season in order to reduce the effects of local weather events. In each site, the trapping effort was left unchanged throughout the survey to legitimate inter-seasonal comparisons. Data from 99,000 collected specimens were analyzed, resulting in the description of seasonal dynamics of 56,000 sand flies belonging to L. infantum vector species throughout a wide geographical area, namely P. perniciosus (Portugal, Spain and Italy, P. ariasi (France, P. neglectus (Greece, P. tobbi (Cyprus and Turkey, P. balcanicus and P. kandelakii (Georgia. Time of sand fly appearance/disappearance in collections differed between sites, and seasonal densities showed variations in each site. Significant correlations were found between latitude/mean annual temperature of sites and i the first month of sand fly appearance, that ranged from early April to the first half of June; ii the type of density trend, varying from a single peak in July/August to multiple peaks increasing in magnitude from May through September. A 3-modal trend, recorded for P. tobbi in Cyprus, represents a novel finding for a L. infantum vector

  10. Seasonal Dynamics of Phlebotomine Sand Fly Species Proven Vectors of Mediterranean Leishmaniasis Caused by Leishmania infantum

    Science.gov (United States)

    Alten, Bulent; Maia, Carla; Afonso, Maria Odete; Campino, Lenea; Jiménez, Maribel; González, Estela; Molina, Ricardo; Bañuls, Anne Laure; Prudhomme, Jorian; Vergnes, Baptiste; Toty, Celine; Cassan, Cécile; Rahola, Nil; Thierry, Magali; Sereno, Denis; Bongiorno, Gioia; Bianchi, Riccardo; Khoury, Cristina; Tsirigotakis, Nikolaos; Dokianakis, Emmanouil; Antoniou, Maria; Christodoulou, Vasiliki; Mazeris, Apostolos; Karakus, Mehmet; Ozbel, Yusuf; Arserim, Suha K.; Erisoz Kasap, Ozge; Gunay, Filiz; Oguz, Gizem; Kaynas, Sinan; Tsertsvadze, Nikoloz; Tskhvaradze, Lamzira; Gramiccia, Marina; Volf, Petr; Gradoni, Luigi

    2016-01-01

    Background The recent geographical expansion of phlebotomine vectors of Leishmania infantum in the Mediterranean subregion has been attributed to ongoing climate changes. At these latitudes, the activity of sand flies is typically seasonal; because seasonal phenomena are also sensitive to general variations in climate, current phenological data sets can provide a baseline for continuing investigations on sand fly population dynamics that may impact on future scenarios of leishmaniasis transmission. With this aim, in 2011–2013 a consortium of partners from eight Mediterranean countries carried out entomological investigations in sites where L. infantum transmission was recently reported. Methods/Principal Findings A common protocol for sand fly collection included monthly captures by CDC light traps, complemented by sticky traps in most of the sites. Collections were replicated for more than one season in order to reduce the effects of local weather events. In each site, the trapping effort was left unchanged throughout the survey to legitimate inter-seasonal comparisons. Data from 99,000 collected specimens were analyzed, resulting in the description of seasonal dynamics of 56,000 sand flies belonging to L. infantum vector species throughout a wide geographical area, namely P. perniciosus (Portugal, Spain and Italy), P. ariasi (France), P. neglectus (Greece), P. tobbi (Cyprus and Turkey), P. balcanicus and P. kandelakii (Georgia). Time of sand fly appearance/disappearance in collections differed between sites, and seasonal densities showed variations in each site. Significant correlations were found between latitude/mean annual temperature of sites and i) the first month of sand fly appearance, that ranged from early April to the first half of June; ii) the type of density trend, varying from a single peak in July/August to multiple peaks increasing in magnitude from May through September. A 3-modal trend, recorded for P. tobbi in Cyprus, represents a novel

  11. Early-Life Toxic Insults and Onset of Sporadic Neurodegenerative Diseases-an Overview of Experimental Studies.

    Science.gov (United States)

    Tartaglione, Anna Maria; Venerosi, Aldina; Calamandrei, Gemma

    2016-01-01

    The developmental origin of health and disease hypothesis states that adverse fetal and early childhood exposures can predispose to obesity, cardiovascular, and neurodegenerative diseases (NDDs) in adult life. Early exposure to environmental chemicals interferes with developmental programming and induces subclinical alterations that may hesitate in pathophysiology and behavioral deficits at a later life stage. The mechanisms by which perinatal insults lead to altered programming and to disease later in life are still undefined. The long latency between exposure and onset of disease, the difficulty of reconstructing early exposures, and the wealth of factors which the individual is exposed to during the life course make extremely difficult to prove the developmental origin of NDDs in clinical and epidemiological studies. An overview of animal studies assessing the long-term effects of perinatal exposure to different chemicals (heavy metals and pesticides) supports the link between exposure and hallmarks of neurodegeneration at the adult stage. Furthermore, models of maternal immune activation show that brain inflammation in early life may enhance adult vulnerability to environmental toxins, thus supporting the multiple hit hypothesis for NDDs' etiology. The study of prospective animal cohorts may help to unraveling the complex pathophysiology of sporadic NDDs. In vivo models could be a powerful tool to clarify the mechanisms through which different kinds of insults predispose to cell loss in the adult age, to establish a cause-effect relationship between "omic" signatures and disease/dysfunction later in life, and to identify peripheral biomarkers of exposure, effects, and susceptibility, for translation to prospective epidemiological studies.

  12. Early Social Deprivation and the Social Buffering of Cortisol Stress Responses in Late Childhood: An Experimental Study

    Science.gov (United States)

    Hostinar, Camelia E.; Johnson, Anna E.; Gunnar, Megan R.

    2015-01-01

    The goal of the present study was to investigate the role of early social deprivation in shaping the effectiveness of parent support to alleviate hypothalamic-pituitary-adrenal (HPA)-axis-stress responses of children (ages 8.9-11, M = 9.83 years, SD = 0.55). The sample was equally divided between children who had been adopted internationally from…

  13. Epidemiology of visceral leishmaniasis in Algeria: an update.

    Science.gov (United States)

    Adel, Amel; Boughoufalah, Amel; Saegerman, Claude; De Deken, Redgi; Bouchene, Zahida; Soukehal, Abdelkrim; Berkvens, Dirk; Boelaert, Marleen

    2014-01-01

    Visceral leishmaniasis (VL), a zoonotic disease caused by Leishmania infantum, is endemic in Algeria. This report describes a retrospective epidemiological study conducted on human VL to document the epidemiological profile at national level. All human VL cases notified by the National Institute of Public Health between 1998 and 2008 were investigated. In parallel all VL cases admitted to the university hospitals of Algiers were surveyed to estimate the underreporting ratio. Fifteen hundred and sixty-two human VL cases were reported in Algeria between 1998-2008 with an average annual reported incidence rate of 0.45 cases per 100,000 inhabitants, of which 81.42% were in the age range of 0-4 years. Cases were detected year-round, with a peak notification in May and June. One hundred and seventy patients were admitted to the university hospitals in Algiers in the same period, of which less than one in ten had been officially notified. Splenomegaly, fever, pallor and pancytopenia were the main clinical and laboratory features. Meglumine antimoniate was the first-line therapy for paediatric VL whereas the conventional amphotericin B was used for adult patients. Visceral leishmaniasis in Algeria shows the epidemiological profile of a paediatric disease with a decrease of the annual reported incidence rate. However, vigilance is required because of huge underreporting and an apparent propagation towards the south.

  14. Cutaneous leishmaniasis caused by Leishmania infantum in Southern Israel.

    Science.gov (United States)

    Ben-Shimol, Shalom; Sagi, Orli; Horev, Amir; Avni, Yonat Shemer; Ziv, Mati; Riesenberg, Klaris

    2016-12-01

    Cutaneous leishmaniasis (CL) caused by Leishmania major is common in southern Israel, while Leishmania infantum (sub-strain of L. donovani, causing zoonotic visceral leishmaniasis) infections were rarely reported in Israel and only in other regions. We report the first case of L. infantum infection in southern Israel, presented atypically as CL in an immunosuppressed 47-year old male. The patient was treated with liposomal amphotericin-B and recovered, without extra-cutaneous complications. Diagnosis of L. infantum CL was confirmed by microscopic identification of amastigotes in Gimsa-stained smear of skin lesion, positive blood serology and a positive polymerase chain reaction (PCR) amplification of the internal transcribed spacer 1 genes (ITS1) and restriction fragment length polymorphism (ITS1 PCR-RFLP). We also review the medical literature on old-world CL caused by L. infantum. Multiple L. donovani/infantum CL cases were identified in the literature search. These can be divided schematically to two: 1) In several endemic countries, L. infantum strains are the main causative agents of CL; 2) In other regions, CL is almost exclusively caused by L. major or L. tropica, while L. donovani strains CL cases were reported sporadically or as imported disease.

  15. Comparison of Three Methods for Diagnosis of Cutaneous Leishmaniasis

    Directory of Open Access Journals (Sweden)

    P Habibi

    2010-12-01

    Full Text Available Background: Leishmaniasis is one of the infectious parasitic diseases of highest incidence in the world. Cutaneous Leishmaniasis (CL has long been reported in Shiraz, Southern Iran. There is a need to find a sensitive and specific method for treatment and control of the disease.Methods: We have compared the sensitivity of the conventional methods microscopy and cultiva­tion of lesion scrapes against PCR amplification of parasite kinetoplast DNA from these sam­ples. The samples (n=219 were obtained from the patients clinically suspected of CL. The smears were stained with Giemsa for microscopy and cultured in Novy-Nicolle-McNeal (NNN blood agar for promastigote growth. For PCR, the dry smears were scraped off the slides and DNA was extracted.Results: The positive rates from 219 specimens were 76.71%, 50.68%, and 93.61% for micros­copy, cultivation, and PCR, respectively. The highest correlation was found between PCR and micros­copy method (P= 0.014. In PCR assay, 95.61%, 3.9%, and 0.49% of the samples were identi­fied as Leishmania major, L. tropica, and dermatropic L. infantum, respectively.Conclusion: The PCR method appears to be the most sensitive for the diagnosis of CL and is valu­able for identifying the other species of Leishmania with confusing dermatropic signs.

  16. Research priorities for Chagas disease, human African trypanosomiasis and leishmaniasis.

    Science.gov (United States)

    2012-01-01

    This report provides a review and analysis of the research landscape for three diseases - Chagas disease, human African trypanosomiasis and leishmaniasis - that disproportionately afflict poor and remote populations with limited access to health services. It represents the work of the disease reference group on Chagas Disease, Human African Trypanosomiasis and Leishmaniasis (DRG3) which was established to identify key research priorities through review of research evidence and input from stakeholders' consultations. The diseases, which are caused by related protozoan parasites, are described in terms of their epidemiology and diseases burden, clinical forms and pathogenesis, HIV coinfection, diagnosis, drugs and drug resistance, vaccines, vector control, and health-care interventions. Priority areas for research are identified based on criteria such as public health relevance, benefit and impact on poor populations and equity, and feasibility. The priorities are found in the areas of diagnostics, drugs, vector control, asymptomatic infection, economic analysis of treatment and vector control methods, and in some specific issues such as surveillance methods or transmission-blocking vaccines for particular diseases. This report will be useful to researchers, policy and decision-makers, funding bodies, implementation organizations, and civil society. This is one of ten disease and thematic reference group reports that have come out of the TDR Think Tank, all of which have contributed to the development of the Global Report for Research on Infectious Diseases of Poverty, available at: www.who.int/tdr/stewardship/global_report/en/index.html.

  17. American cutaneous leishmaniasis: presentation and problems of patient management

    Directory of Open Access Journals (Sweden)

    Jeffrey D. Chulay

    1988-12-01

    Full Text Available We report our experience with the diagnosis and treatment of 60 patients with American cutaneous leishmaniasis. They were infected in Panama (55, Brazil (4 or Colombia (I. Among 35 patients with a 3 week exposure in Panama, the mean maximum incubation period was 33 days (range 4-81 days. Diagnosis was delayed an average of 93 days after onset of skin lesions, due to the patient's delay in seeking medical attention (31 days, medical personnel's delay in considering the diagnosis (45 days, and the laboratory's delay in confirming the diagnosis (17 days. Forty-four patients (73% developed ulcers typical of cutaneous leishmaniasis. Sixteen additional patients (27% had atypical macular, papular, squamous, verrucous or acneiform skin lesions that were diagnosed only because leishmanial cultures were obtained. Of the 59 patients treated with pentavalent antimonial drugs, only 34 (58% were cured after the first course of treatment. Lesions which were at least 2 cm in diameter, ulcerated, or caused by Leishmania braziliensis were less likely to be cured after a single course of treatment than were lesions smaller than 2 cm, nonulcerated or caused by Leishmania mexicana or Leishmania donovani.

  18. Recurrent cutaneous leishmaniasis Leishmaniose recidiva cútis

    Directory of Open Access Journals (Sweden)

    Ciro Martins Gomes

    2013-06-01

    Full Text Available We present a case of an 18-year-old male patient who, after two years of inappropriate treatment for cutaneous leishmaniasis, began to show nodules arising at the edges of the former healing scar. He was immune competent and denied any trauma. The diagnosis of recurrent cutaneous leishmaniasis was made following positive culture of aspirate samples. The patient was treated with N-methylglucamine associated with pentoxifylline for 30 days. Similar cases require special attention mainly because of the challenges imposed by treatment.Paciente do sexo masculino, 18 anos. Dois anos após tratamento insuficiente para leishmaniose tegumentar americana, apresentou, na mesma localização, lesão formada por cicatriz atrófica central e nódulos verrucosos na periferia. Era imunocompetente, hígido e negava qualquer trauma local. O diagnóstico de leishmaniose recidiva cutis foi feito através de cultura do aspirado da lesão. Realizou tratamento com N-metilglucamina (20mgSbV/kg/dia associado à pentoxifilina (1200mg/dia durante 30 dias alcançando cura clínica. Os casos semelhantes requerem atenção diferenciada pela dificuldade ao tratamento.

  19. Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Fernanda O Novais

    Full Text Available Disease progression in response to infection can be strongly influenced by both pathogen burden and infection-induced immunopathology. While current therapeutics focus on augmenting protective immune responses, identifying therapeutics that reduce infection-induced immunopathology are clearly warranted. Despite the apparent protective role for murine CD8⁺ T cells following infection with the intracellular parasite Leishmania, CD8⁺ T cells have been paradoxically linked to immunopathological responses in human cutaneous leishmaniasis. Transcriptome analysis of lesions from Leishmania braziliensis patients revealed that genes associated with the cytolytic pathway are highly expressed and CD8⁺ T cells from lesions exhibited a cytolytic phenotype. To determine if CD8⁺ T cells play a causal role in disease, we turned to a murine model. These studies revealed that disease progression and metastasis in L. braziliensis infected mice was independent of parasite burden and was instead directly associated with the presence of CD8⁺ T cells. In mice with severe pathology, we visualized CD8⁺ T cell degranulation and lysis of L. braziliensis infected cells. Finally, in contrast to wild-type CD8⁺ T cells, perforin-deficient cells failed to induce disease. Thus, we show for the first time that cytolytic CD8⁺ T cells mediate immunopathology and drive the development of metastatic lesions in cutaneous leishmaniasis.

  20. Jaundice in pediatric visceral leishmaniasis (kala-azar)pa-tients

    Institute of Scientific and Technical Information of China (English)

    AKMMamunur Rashid; MdAsrafuzzaman; Abdullah Al Mamun; Abdullah Al Mahboob

    2009-01-01

    Objective:Visceral leishmaniasis (Kala-azar)is endemic in many countries including Bangladesh.Clinical presentation of visceral leishmaniasis in children and adult may vary and at time may simulate many tropical and hepatobiliary diseases.Jaundice and ascites are not common in kala-azar patients.Methods:During the period of January 2005 to December 2006,all the records of the confirmed kala-azar patients presented with jaundice were included in this study.Kala-azar was confirmed by serology test ICT (Immuno Chromatography) and Bone Marrow study.Results:Total 12 kala-azar patients were encountered during this period.Among these twelve cases,presenting features were jaundice (7),splenomegaly (12),hepatomegaly (11)and asci-tes (4).Initial clinical diagnosis of chronic liver disease (CLD)was made in (5),Congenital hemolytic a-naemia in (1)and kala-azar in rest of the patients (6).Common leucopenia and relative lymphocytosis was not observed in any patients.Conclusion:Kala-azar may present with various clinical manifestation in chil-dren and adult.Jaundice can be considered to be a common manifestation particularly in pediatric kala-azar patients.Otherwise,it may mislead to another diagnosis if it is taken as a rare feature in kala-azar.

  1. Early life exposure to artificial light at night affects the physiological condition: An experimental study on the ecophysiology of free-living nestling songbirds.

    Science.gov (United States)

    Raap, Thomas; Casasole, Giulia; Pinxten, Rianne; Eens, Marcel

    2016-11-01

    Light pollution or artificial light at night (ALAN) is increasingly recognised to be an important anthropogenic environmental pressure on wildlife, affecting animal behaviour and physiology. Early life experiences are extremely important for the development, physiological status and health of organisms, and as such, early exposure to artificial light may have detrimental consequences for organism fitness. We experimentally manipulated the light environment of free-living great tit nestlings (Parus major), an important model species in evolutionary and environmental research. Haptoglobin (Hp) and nitric oxide (NOx), as important indicators of immunity, health, and physiological condition, were quantified in nestlings at baseline (13 days after hatching) and after a two night exposure to ALAN. We found that ALAN increased Hp and decreased NOx. ALAN may increase stress and oxidative stress and reduce melatonin which could subsequently lead to increased Hp and decreased NOx. Haptoglobin is part of the immune response and mounting an immune response is costly in energy and resources and, trade-offs are likely to occur with other energetically demanding tasks, such as survival or reproduction. Acute inhibition of NOx may have a cascading effect as it also affects other physiological aspects and may negatively affect immunocompetence. The consequences of the observed effects on Hp and NOx remain to be examined. Our study provides experimental field evidence that ALAN affects nestlings' physiology during development and early life exposure to ALAN could therefore have long lasting effects throughout adulthood.

  2. The role of the sonic hedgehog signaling pathway in early brain injury after experimental subarachnoid hemorrhage in rats.

    Science.gov (United States)

    Li, Tao; Zhang, Jie; Liu, Rong-Yao; Lian, Zhi-Gang; Chen, Xiao-Lin; Ma, Li; Sun, Hao-Min; Zhao, Yuan-Li

    2013-09-27

    Previous studies have demonstrated that the sonic hedgehog (Shh) pathway plays a neuro-protective role. However, whether the Shh pathway is induced by subarachnoid hemorrhage (SAH) has not been investigated. We sought to investigate Shh activation in the cortex in the early stage of SAH, and assessed the effect of cyclopamine (a specific inhibitor of the Shh pathway) on Shh pathway regulation and evaluated the impact of cyclopamine on SAH. We found that the Shh pathway was up-regulated in the cortex after SAH, and that blocking the Shh pathway increased cell apoptosis. Early brain damages, including brain edema, blood-brain barrier impairment, and cortical apoptosis were significantly aggravated following with cyclopamine treatment compared with vehicle treatment. Our results suggest that the Shh pathway should be activated in the brain after SAH, and plays a beneficial role in SAH development, possibly by inhibiting cerebral oxidative stress through induction of antioxidant and detoxifying enzymes.

  3. Effects of early and late-onset treatment with carvedilol in an experimental model of aortic regurgitation

    DEFF Research Database (Denmark)

    Eskesen, Kristian; Olsen, Niels Thue; Dimaano, Veronica L;

    2015-01-01

    in several studies. METHOD: Thirty-nine Sprague-Dawley rats with AR were randomized to ten weeks of medical treatment with carvedilol or no treatment. Treatment was initiated either early or late after AR induction. The effect of carvedilol was assessed by serial echocardiography and invasive hemodynamic...... measurements. RESULTS: AR resulted in eccentric hypertrophy and left ventricular (LV) dysfunction. LV remodeling and function as measured by echocardiography was unaffected by treatment. LV dimensions were similar between treated and untreated groups and measures of LV performance (including strain and strain....... CONCLUSION: Carvedilol did not improve left ventricular remodeling or function in rats with surgically induced AR. Despite relative bradycardia, we did not find carvedilol to negatively impact the heart, either when treatment was initiated early or late in the course of disease....

  4. Boys' Cognitive Skill Formation and Physical Growth: Long-term Experimental Evidence on Critical Ages for Early Childhood Interventions

    OpenAIRE

    Barham, Tania; Macours, Karen; John A Maluccio

    2013-01-01

    The effects of early life circumstances on cognitive skill formation are important for later human capital development, labor market outcomes and well-being. In this paper, we test the hypothesis that the first 1,000 days are the critical window for both cognitive skill formation and physical development by exploiting a randomized conditional cash transfer (CCT) program in Nicaragua. We find that boys exposed in utero and during the first 2 years of life, have better cognitive, but not physic...

  5. Numerical and experimental analysis of high frequency acoustic microscopy and infrared reflectance system for early detection of melanoma

    Science.gov (United States)

    Karagiannis, Georgios; Apostolidis, Georgios; Georgoulias, Panagiotis

    2016-03-01

    Melanoma is a very malicious type of cancer as it metastasizes early and hence its late diagnosis leads to death. Consequently, early diagnosis of melanoma and its removal is considered the most effective way of treatment. We present a design of a high frequency acoustic microscopy and infrared reflectance system for the early detection of melanoma. Specifically, the identification of morphological changes related to carcinogenesis is required. In this work, we simulate of the propagation of the ultrasonic waves of the order of 100 MHz as well as of electromagnetic waves of the order of 100 THz in melanoma structures targeting to the estimation and optimization of the basic characteristics of the systems. The simulation results of the acoustic microscopy subsystem aim to provide information such as the geometry of the transducer, the center frequency of operation, the focal length where the power transmittance is optimum and the spot size in focal length. As far as the infrared is concerned the optimal frequency range and the spot illumination size of the external probe is provided. This information is next used to assemble a properly designed system which is applied to melanoma phantoms as well as real skin lesions. Finally, the measurement data are visualized to reveal the information of the experimented structures, proving noteworthy accuracy.

  6. Sequence of Tissue Responses in the Early Stages of Experimental Allergic Encephalomyelitis (EAE): Immunohistochemical, Light Microscopic, and Ultrastructural Observations in the Spinal Cord

    Science.gov (United States)

    DAmelio, Fernando E.; Smith, Marion E.; Eng, Lawrence F.

    1990-01-01

    Experimental allergic encephalomyelitis (EAE) was induced in adult Lewis rats with purified guinea pig CNS myelin and Freund's adjuvant. As soon as the very earliest clinical signs appeared the animals were perfused with fixatives and the spinal cord analyzed by electron microscopy, silver methods, and immunocytochemistry. Our findings suggest that in the early stages of EAE a sequence of events can be traced, although these events frequently overlap. The earliest morphological change appears to be astrocytic edema in both the cell body and processes. Increased amounts of glycogen particles and dispersion of glial filaments are prominent. These changes seem to occur just prior to the time when inflammatory cells begin to penetrate the capillary walls. Invasion of the neuropil mainly by macrophages and lymphocytes closely follows. Both macrophages and microglia seem to participate in phagocytosis of oligodendrocytes and myelin. Demyelination, however, is not a prominent feature at this early stage.

  7. Isolated cutaneous leishmaniasis over face – A diagnostic dilemma

    African Journals Online (AJOL)

    Santosh K. Swain

    2016-01-08

    Jan 8, 2016 ... b Department of Community Medicine, IMS and SUM Hospital, Siksha ''O” Anusandhan ... Abstract Cutaneous Leishmaniasis (CL) is a disease caused by an intracellular protozoa belong to ... The parasite is transmitted from.

  8. First Cases of Cutaneous Leishmaniasis Caused by Leishmania (Viannia) naiffi Infection in Surinam

    NARCIS (Netherlands)

    P.P.A.M. van Thiel; T. van Gool; P.A. Kager; A. Bart

    2010-01-01

    Cutaneous leishmaniasis in Surinam is generally caused by infection by Leishmania guyanensis. We report three cases of infection with Leishmania (Viannia) naiffi, a Leishmania species not described from Surinam before. Treatment with pentamidine proved to be effective

  9. Seroprevalence of CANINE LEISHMANIASIS AND American trypanosomiasis in dogs from Grenada, West Indies

    Science.gov (United States)

    Canine leishmaniasis and American trypanosomiasis (AT) are caused by related hemoflagellated parasites, Leishmania spp. and Trypanosoma cruzi, which share several common host species. Dogs are reservoirs for human infections with both pathogens. We determined the prevalence of antibodies to Leishman...

  10. Epidemiological role of a rodent in Morocco: Case of cutaneous leishmaniasis

    Directory of Open Access Journals (Sweden)

    Mohamed Echchakery

    2015-08-01

    Full Text Available Commensal rodents as well as wild ones may present a potential risk to public health. They are reservoirs or vectors of many pathogens. This review provides an update on their epidemiological role in the spread of leishmaniasis in Morocco. In Morocco, the order Rodentia is represented by 7 families and 32 species of which Rattus norvegicus, Psammomys obesus, Mastomys erythrolecus, Meriones shawi, Meriones crassus and Meriones libycus are considered reservoirs of leishmaniasis in Asia, Midle East and Africa. With the aim to define the extent of zoonotic leishmaniasis risk in Morocco, we represent and discuss the geographical distribution of these potential reservoirs in relation to that of Phlebotomus papatasi, proven vector of cutaneous leishmaniasis by Leishmania major in Morocco.

  11. Diagnostic methods to cutaneous leishmaniasis detection in domestic dogs and cats

    National Research Council Canada - National Science Library

    Trevisan, Daliah Alves Coelho; Lonardoni, Maria Valdrinez Campana; Demarchi, Izabel Galhardo

    2015-01-01

    Cutaneous leishmaniasis is caused by different species of Leishmania. In domestic animals such as dogs and cats, the diagnostic consists of clinical, epidemiological and serological tests, which changes among countries all around the world...

  12. Establishing a web-based integrated surveillance system for early detection of infectious disease epidemic in rural China: a field experimental study

    Directory of Open Access Journals (Sweden)

    Yan Wei-rong

    2012-02-01

    Full Text Available Abstract Background A crucial goal of infectious disease surveillance is the early detection of epidemics, which is essential for disease control. In China, the current surveillance system is based on confirmed case reports. In rural China, it is not practical for health units to perform laboratory tests to confirm disease and people are more likely to get 'old' and emerging infectious diseases due to poor living conditions and closer contacts with wild animals and poultry. Syndromic surveillance, which collects non-specific syndromes before diagnosis, has great advantages in promoting the early detection of epidemics and reducing the necessities of disease confirmation. It will be especially effective for surveillance in resource poor settings. Methods/Design This is a field experimental study. The experimental tool is an innovative electronic surveillance system, combining syndromic surveillance with the existing case report surveillance in four selected counties in China. In the added syndromic surveillance, three types of data are collected including patients' major symptoms from health clinics, pharmaceutical sales from pharmacies and absenteeism information from primary school. In order to evaluate the early warning capability of the new added syndromic surveillance, the timelines and validity of the alert signals will be analyzed in comparison with the traditional case reporting system. The acceptability, feasibility and economic evaluation of the whole integrated surveillance system will be conducted in a before and after study design. Discussions Although syndromic surveillance system has mostly been established in developed areas, there are opportunities and advantages of developing it in rural China. The project will contribute to knowledge, experience and evidence on the establishment of an integrated surveillance system, which aims to provide early warning of disease epidemics in developing countries.

  13. Current challenges in treatment options for visceral leishmaniasis in India: a public health perspective.

    Science.gov (United States)

    Singh, Om Prakash; Singh, Bhawana; Chakravarty, Jaya; Sundar, Shyam

    2016-03-08

    Visceral leishmaniasis (VL) is a serious parasitic disease causing considerable mortality and major disability in the Indian subcontinent. It is most neglected tropical disease, particularly in terms of new drug development for the lack of financial returns. An elimination campaign has been running in India since 2005 that aim to reduce the incidence of VL to below 1 per 10,000 people at sub-district level. One of the major components in this endeavor is reducing transmission through early case detection followed by complete treatment. Substantial progress has been made during the recent years in the area of VL treatment, and the VL elimination initiatives have already saved many lives by deploying them effectively in the endemic areas. However, many challenges remain to be overcome including availability of drugs, cost of treatment (drugs and hospitalization), efficacy, adverse effects, and growing parasite resistance. Therefore, better emphasis on implementation research is urgently needed to determine how best to deliver existing interventions with available anti-leishmanial drugs. It is essential that the new treatment options become truly accessible, not simply available in endemic areas so that they may promote healing and save lives. In this review, we highlight the recent advancement and challenges in current treatment options for VL in disease endemic area, and discuss the possible strategies to improve the therapeutic outcome.

  14. American Visceral Leishmaniasis: Factors Associated with Lethality in the State of São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Geraldine Madalosso

    2012-01-01

    Full Text Available Objectives. To identify factors associated with death in visceral leishmaniasis (VL cases. Patients and Methodology. We evaluated prognostic factors for death from VL in São Paulo state, Brazil, from 1999 to 2005. A prognostic study nested in a clinical cohort was carried out by data analysis of 376 medical files. A comparison between VL fatal cases and survivors was performed for clinical, laboratory, and biological features. Association between variables and death was assessed by univariate analysis, and the multiple logistic regression model was used to determine adjusted odds ratio for death, controlling confounding factors. Results. Data analysis identified 53 fatal cases out of 376 patients, between 1999 and 2005 in São Paulo state. Lethality was 14.1% (53/376, being higher in patients older than fifty years. The main causes of death were sepsis, bleeding, liver failure, and cardiotoxicity due to treatment. Variables significantly associated with death were severe anemia, bleeding, heart failure, jaundice, diarrhea, fever for more than sixty days, age older than fifty years, and antibiotic use. Conclusion. Educational health measures are needed for the general population and continuing education programs for health professionals working in the affected areas with the purpose of identifying and treating early cases, thus preventing the disease evolution towards death.

  15. Current challenges in treatment options for visceral leishmaniasis in India: a public health perspective

    Institute of Scientific and Technical Information of China (English)

    Om Prakash Singh; Bhawana Singh; Jaya Chakravarty; Shyam Sundar

    2016-01-01

    Visceral leishmaniasis (VL) is a serious parasitic disease causing considerable mortality and major disability in the Indian subcontinent.It is most neglected tropical disease,particularly in terms of new drug development for the lack of financial returns.An elimination campaign has been running in India since 2005 that aim to reduce the incidence of VL to below 1 per 10,000 people at sub-district level.One of the major components in this endeavor is reducing transmission through early case detection followed by complete treatment.Substantial progress has been made during the recent years in the area of VL treatment,and the VL elimination initiatives have already saved many lives by deploying them effectively in the endemic areas.However,many challenges remain to be overcome including availability of drugs,cost of treatment (drugs and hospitalization),efficacy,adverse effects,and growing parasite resistance.Therefore,better emphasis on implementation research is urgently needed to determine how best to deliver existing interventions with available anti-leishmanial drugs.It is essential that the new treatment options become truly accessible,not simply available in endemic areas so that they may promote healing and save lives.In this review,we highlight the recent advancement and challenges in current treatment options for VL in disease endemic area,and discuss the possible strategies to improve the therapeutic outcome.

  16. Comparison of diagnostic methods in cutaneous Leishmaniasis (histopathology compared to skin smears).

    Science.gov (United States)

    Gazozai, Sanaullah; Iqbal, Javeid; Bukhari, Ishrat; Bashir, Sajid

    2010-10-01

    Present study is carried out to compare laboratory diagnostic methods of Cutaneous leishmaniasis (CL) for the outdoor patients of Bolan Medical College Complex Hospital, Quetta, Balochistan. From November 2005 to December 2007, three hundred cases of CL patients were selected without restriction of age and sex. The lesions were divided into two groups. Early with duration less than 2 months and late duration between 2 to 4 months and were noted as nodules, plaques, ulcers and scarring (in case of relapses). Skin smears were taken on first visit of the patients, followed by skin biopsy for histopathological examination. Result showed that out of 300 cases 163 (54.33%) were positive smears for Leishmania donovani (LD) bodies and 137 (45.67%) were negative smears for LD bodies.. While histological examination of all 300 cases showed that only 83 (27.66%) cases were negative for (LD) bodies and no granuloma seen, except with evidence of acute and chronic inflammation. Further analysis of histological observations of positive cases (72.34%) revealed that 91(30.33%) cases had LD bodies,, 78 (26%) cases had only necrotic sloughs showing polymorph neutrophilic infiltration, and 48(16%) cases were having granulomas composed of, epithelioid cells Langhan's type of giant cells and lymphocytes. It is therefore concluded that histopathological examination as compared to skin smears method is more sensitive method for diagnosis of CL.

  17. Visceral leishmaniasis due to Leishmania infantum with renal involvement in HIV-infected patients

    OpenAIRE

    Vassallo, Matteo; Moranne, Olivier; Ambrosetti, Damien; Jeandel, Pierre-Yves; Pomares, Christelle; Cassuto, Elisabeth; Boscagli, Annick; Giraud, Guillaume; Montagne, Nathalie; Dentone, Chiara; Demacina, Ilaria; Villaggio, Barbara; Secondo, Giovanni; Ferrea, Giuseppe; Passeron, Corinne

    2014-01-01

    Background We describe histological, clinical findings and outcomes of renal involvement during Leishmania infantum infection in four HIV-infected patients in South France and North Italy hospital settings. Cases presentation Four HIV-infected Caucasian patients (age 24-49) performed renal biopsy during episodes of visceral leishmaniasis. They presented severe immunosuppression, frequent relapses of visceral leishmaniasis during a follow-up period of several years and partial or complete reco...

  18. First case of cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis in Suriname.

    Science.gov (United States)

    Hu, Ricardo V P F; Kent, Alida D; Adams, Emily R; van der Veer, Charlotte; Sabajo, Leslie O A; Mans, Dennis R A; de Vries, Henry J C; Schallig, Henk D F H; Lai A Fat, Rudy F M

    2012-05-01

    The main causative agent of cutaneous leishmaniasis (CL) in Suriname is Leishmania (Viannia) guyanensis. This case report presents a patient infected with Leishmania (Viannia) braziliensis, a species never reported before in Suriname. This finding has clinical implications, because L. braziliensis has a distinct clinical phenotype characterized by mucocutaneous leishmaniasis, a more extensive and destructive form of CL that requires different treatment. Clinicians should be aware that chronic cutaneous ulcers in patients from the Guyana region could be caused by L. braziliensis.

  19. Diagnostic methods to cutaneous leishmaniasis detection in domestic dogs and cats*

    OpenAIRE

    Trevisan, Daliah Alves Coelho; Lonardoni, Maria Valdrinez Campana; DEMARCHI, Izabel Galhardo

    2015-01-01

    Cutaneous leishmaniasis is caused by different species of Leishmania. In domestic animals such as dogs and cats, the diagnostic consists of clinical, epidemiological and serological tests, which changes among countries all around the world. Because of this diversity in the methods selected, we propose this systematic literature review to identify the methods of laboratory diagnosis used to detect cutaneous leishmaniasis in domestic dogs and cats in the Americas. Articles published in the last...

  20. Genetic Control of Canine Leishmaniasis: Genome-Wide Association Study and Genomic Selection Analysis

    OpenAIRE

    Javier Quilez; Verónica Martínez; Woolliams, John A; Armand Sanchez; Ricardo Pong-Wong; Kennedy, Lorna J.; Quinnell, Rupert J.; Ollier, William E R; Xavier Roura; Lluís Ferrer; Laura Altet; Olga Francino

    2012-01-01

    BACKGROUND: The current disease model for leishmaniasis suggests that only a proportion of infected individuals develop clinical disease, while others are asymptomatically infected due to immune control of infection. The factors that determine whether individuals progress to clinical disease following Leishmania infection are unclear, although previous studies suggest a role for host genetics. Our hypothesis was that canine leishmaniasis is a complex disease with multiple loci responsible for...

  1. Treatment of Cutaneous Leishmaniasis Caused by Leishmania aethiopica: A Systematic Review

    OpenAIRE

    Johan van Griensven; Endalamaw Gadisa; Abraham Aseffa; Asrat Hailu; Abate Mulugeta Beshah; Ermias Diro

    2016-01-01

    Leishmania aethiopica is the etiological agent of cutaneous leishmaniasis (CL) in Ethiopia and can cause severe and complicated cases such as diffuse CL (DCL), mucocutaneous leishmaniasis or extensive CL, requiring systemic treatment. Despite the substantial burden, evidence-based treatment guidelines are lacking. We conducted a systematic review of clinical studies reporting on treatment outcomes of CL due to L aethiopica in order to help identify potentially efficacious medications on CL th...

  2. Diagnostic methods to cutaneous leishmaniasis detection in domestic dogs and cats

    OpenAIRE

    Trevisan, Daliah Alves Coelho; Lonardoni,Maria Valdrinez Campana; Demarchi,Izabel Galhardo

    2015-01-01

    Abstract: Cutaneous leishmaniasis is caused by different species of Leishmania. In domestic animals such as dogs and cats, the diagnostic consists of clinical, epidemiological and serological tests, which changes among countries all around the world. Because of this diversity in the methods selected, we propose this systematic literature review to identify the methods of laboratory diagnosis used to detect cutaneous leishmaniasis in domestic dogs and cats in the Americas. Articles published i...

  3. Effects of Sure Start local programmes on children and families: early findings from a quasi-experimental, cross sectional study

    OpenAIRE

    2006-01-01

    Objective To evaluate the effects of Sure Start local programmes (SSLPs) on children and their families. To assess whether variations in the effectiveness of SSLPs are due to differences in implementation. \\ud \\ud Design Quasi-experimental cross sectional study using interviews with mothers and cognitive assessment of children aged 36 months who speak English. \\ud \\ud Setting Socially deprived communities in England: 150 communities with ongoing SSLPs and 50 comparison communities. \\ud \\ud Pa...

  4. [Transmission of cutaneous leishmaniasis associated with cacao (Theobroma cacao) plantations in Tabasco].

    Science.gov (United States)

    Carrada Figueroa, Georgina Del Carmen; Leal Ascencio, Víctor Javier; Jiménez Sastré, Alejandro; López Álvarez, Jorge

    2014-01-01

    Tabasco is the Mexican state that reported the highest number (37.4%) of patients with leishmaniasis during 1990-2011. Close to 90% of these patients lived in Chontalpa, where the municipality of Cunduacán accounted for the majority of the cases. One of the characteristics of this region is that houses are located within cacao plantations. To determine if cacao plantations are a risk factor for leishmaniasis transmission in locations of Cunduacán, Tabasco. We performed an analytical and retrospective study of 115 locations in Cunduacán, analyzing the number of localities with or without patients with leishmaniasis registered between 2000-2011 and, additionally, if they had cacao plantations, using a map where different crops were georeferenced. We measured the magnitude of the association (odds ratio, 95% CI). During the period 2000-2011, cases of leishmaniasis were reported in 77 (67.0%) Cunduacán locations, of these, 55 (71.4%) had cocoa plantations, five (6.5%) of banana, five (6.5%) of cane, and 12 (15.6%) had no crops georeferenced. We found that cocoa crops are a risk factor for the transmission of leishmaniasis (OR: 3.438; 95% CI: 1,526-7,742). The probability of transmission of leishmaniasis in areas with cocoa crops is greater than in communities without this crop.

  5. Diagnostic methods to cutaneous leishmaniasis detection in domestic dogs and cats*

    Science.gov (United States)

    Trevisan, Daliah Alves Coelho; Lonardoni, Maria Valdrinez Campana; Demarchi, Izabel Galhardo

    2015-01-01

    Cutaneous leishmaniasis is caused by different species of Leishmania. In domestic animals such as dogs and cats, the diagnostic consists of clinical, epidemiological and serological tests, which changes among countries all around the world. Because of this diversity in the methods selected, we propose this systematic literature review to identify the methods of laboratory diagnosis used to detect cutaneous leishmaniasis in domestic dogs and cats in the Americas. Articles published in the last 5 years were searched in PubMed, ISI Web of Science, LILACS and Scielo, and we selected 10 papers about cutaneous leishmaniasis in dogs and cats in the Americas. In Brazil, often the indirect immunofluorescence and enzyme immunoassay (ELISA) have been applied. Other countries like United States and Mexico have been using antigenic fractions for antibodies detections by Western blot. ELISA and Western blot showed a higher sensitivity and efficacy in the detection of leishmaniasis. Analysis of sensibility and specificity of the methods was rarely used. Although confirmatory to leishmaniasis, direct methods for parasites detection and polymerase chain reaction showed low positivity in disease detection. We suggested that more than one method should be used for the detection of feline and canine leishmaniasis. Serological methods such as Western blot and enzyme immunoassay have a high efficacy in the diagnosis of this disease. PMID:26734869

  6. Diagnostic methods to cutaneous leishmaniasis detection in domestic dogs and cats.

    Science.gov (United States)

    Trevisan, Daliah Alves Coelho; Lonardoni, Maria Valdrinez Campana; Demarchi, Izabel Galhardo

    2015-01-01

    Cutaneous leishmaniasis is caused by different species of Leishmania. In domestic animals such as dogs and cats, the diagnostic consists of clinical, epidemiological and serological tests, which changes among countries all around the world. Because of this diversity in the methods selected, we propose this systematic literature review to identify the methods of laboratory diagnosis used to detect cutaneous leishmaniasis in domestic dogs and cats in the Americas. Articles published in the last 5 years were searched in PubMed, ISI Web of Science, LILACS and Scielo, and we selected 10 papers about cutaneous leishmaniasis in dogs and cats in the Americas. In Brazil, often the indirect immunofluorescence and enzyme immunoassay (ELISA) have been applied. Other countries like United States and Mexico have been using antigenic fractions for antibodies detections by Western blot. ELISA and Western blot showed a higher sensitivity and efficacy in the detection of leishmaniasis. Analysis of sensibility and specificity of the methods was rarely used. Although confirmatory to leishmaniasis, direct methods for parasites detection and polymerase chain reaction showed low positivity in disease detection. We suggested that more than one method should be used for the detection of feline and canine leishmaniasis. Serological methods such as Western blot and enzyme immunoassay have a high efficacy in the diagnosis of this disease.

  7. Early Reversible Ischemia of Femoral Head Epiphysis in Piglets on Gadolinium-enhanced MRI: An experimental study

    Institute of Scientific and Technical Information of China (English)

    LI Xiaoming; HU Junwu; ZHEN Hongwei; TANG Lihua; XU Anhui

    2006-01-01

    The purpose of this study is to demonstrate if Gadolinium-enhanced MRI can detect early reversible ischemia of the femoral head epiphysis caused by hip hyper-abduction in piglets. Between 3 and 6 h consistent hyper-abduction, gadolinium-enhanced MRI was performed in 20 femoral heads of 10 piglets. After completion of MRI scan, the piglets were allowed to ambulate freely for 1 or 7 days and re-imaged. The enhanced-MRI results of epiphyseal and physeal cartilage and the secondary center of ossification were observed. MRI appearances and histological findings were compared. On Gadolinium-enhanced MRI, decreased or absent enhancement was seen in 14 cartilaginous epiphyses of all 20 femoral heads. Reperfusion was completed in 10 of 14 femoral heads after one day of ambulation and in the rest 4 after 7 days of ambulation. Gadolinium-enhanced MRI can identify early ischemia and its reversal of the capital femoral epiphysis induced by hip hyper-abduction.

  8. Laboratory drop towers for the experimental simulation of dust-aggregate collisions in the early solar system.

    Science.gov (United States)

    Blum, Jürgen; Beitz, Eike; Bukhari, Mohtashim; Gundlach, Bastian; Hagemann, Jan-Hendrik; Heißelmann, Daniel; Kothe, Stefan; Schräpler, Rainer; von Borstel, Ingo; Weidling, René

    2014-06-05

    For the purpose of investigating the evolution of dust aggregates in the early Solar System, we developed two vacuum drop towers in which fragile dust aggregates with sizes up to ~10 cm and porosities up to 70% can be collided. One of the drop towers is primarily used for very low impact speeds down to below 0.01 m/sec and makes use of a double release mechanism. Collisions are recorded in stereo-view by two high-speed cameras, which fall along the glass vacuum tube in the center-of-mass frame of the two dust aggregates. The other free-fall tower makes use of an electromagnetic accelerator that is capable of gently accelerating dust aggregates to up to 5 m/sec. In combination with the release of another dust aggregate to free fall, collision speeds up to ~10 m/sec can be achieved. Here, two fixed high-speed cameras record the collision events. In both drop towers, the dust aggregates are in free fall during the collision so that they are weightless and match the conditions in the early Solar System.

  9. The susceptibility of domestic cats (Felis catus) to experimental infection with Leishmania braziliensis.

    Science.gov (United States)

    Simões-Mattos, L; Mattos, M R F; Teixeira, M J; Oliveira-Lima, J W; Bevilaqua, C M L; Prata-Júnior, R C; Holanda, C M; Rondon, F C M; Bastos, K M S; Coêlho, Z C B; Coêlho, I C B; Barral, A; Pompeu, M M L

    2005-02-28

    Over the last few years, several cases of feline leishmaniasis (FL) with cutaneous and visceral forms have been reported around the world. Nonetheless, the real susceptibility of cats to infection with Leishmania spp. and the outcome of leishmaniasis in these animals are poorly understood. Experimental studies on feline models will contribute to the knowledge of natural FL. Thus, in order to determine the susceptibility of domestic cats (Felis catus) to experimental infection with Leishmania braziliensis, 13 stray cats were infected with 10(7) promastigotes by the intradermal route in the ear and nose simultaneously and followed up for 72 weeks. Soon after infection, the earliest indication of a lesion was a papule on the ear at 2 weeks post-infection (w.p.i.). The emergence of satellite papules around the primary lesion was observed about 4 w.p.i. Two weeks later these papules coalesced and formed a huge and irregular nodule. Thereafter, there was lesion dissemination to the external and marginal surface of the ipsilateral ear, and later to the contralateral ear. At 10 w.p.i., some nodules became ulcerated. Nose lesions presented a similar evolution. At both sites, the largest lesion sizes occurred at 10 w.p.i. and started to decrease 15 days later. Ear and nose nodules healed at 32 and 40 w.p.i., respectively. Specific L. braziliensis IgG antibody titers (optical density> or = 0.01 as positive result) were detected as early as 2 w.p.i. (0.09 +/- 0.02) in only three animals (23%), and all cats had positive titers at 20 w.p.i. (0.34 +/- 0.06). Only three animals (38%) continued to show positive serology at 72 w.p.i. (0.08 +/- 0.02). Up to that time, none of the cats had lesion recurrence. In a feline model of cutaneous leishmaniasis, it seems that there is no correlation between active lesions and positive serology. The implications of these data are discussed.

  10. In-vitro and In-vivo Activities of Phenolic Compounds A gainst Cutaneous Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Lianet Monzote

    2016-05-01

    Full Text Available Phenolic compounds (PCs are well-known phytochemicals found in plants that have been studied for their pharmacological properties. In particular, the potentialities of PCs as anti-leishmanial agents have been reported. In the present study, we evaluated 10 PCs for in-vitro anti-leishmanial activity and two PCs, p-coumaric acid (CA and gentisic acid (GA against experimental cutaneous leishmaniasis in BALB/c mice infected with L. amazonensis. Five doses of each pure compound were administrated every 4 days at 30 mg/kg by intralesional route and disease progression was compared with animals treated with glucantime (GTM. All tested compounds inhibited intracellular amastigotes growing, with IC50 values between 4.4 and 25.5 µM. Treated animals with GA showed a significant reduction (p 0.05 parasite burden as control and GTM treated animals. The present findings established that CA and GA have significant anti-leishmanial effects. Further experiments on formulation design, mechanism of action and probably anti-inflammatory / immune-modulator activity of GA could be encouraged.

  11. Strategic evaluation of vaccine candidate antigens for the prevention of Visceral Leishmaniasis.

    Science.gov (United States)

    Duthie, Malcolm S; Favila, Michelle; Hofmeyer, Kimberley A; Tutterrow, Yeung L; Reed, Steven J; Laurance, John D; Picone, Alessandro; Guderian, Jeffrey; Bailor, H Remy; Vallur, Aarthy C; Liang, Hong; Mohamath, Raodoh; Vergara, Julie; Howard, Randall F; Coler, Rhea N; Reed, Steven G

    2016-05-27

    Infection with Leishmania parasites results in a range of clinical manifestations and outcomes, the most severe of which is visceral leishmaniasis (VL). Vaccination will likely provide the most effective long-term control strategy, as the large number of vectors and potential infectious reservoirs renders sustained interruption of Leishmania parasite transmission extremely difficult. Selection of the best vaccine is complicated because, although several vaccine antigen candidates have been proposed, they have emerged following production in different platforms. To consolidate the information that has been generated into a single vaccine platform, we expressed seven candidates as recombinant proteins in E. coli. After verifying that each recombinant protein could be recognized by VL patients, we evaluated their protective efficacy against experimental L. donovani infection of mice. Administration in formulation with the Th1-potentiating adjuvant GLA-SE indicated that each antigen could elicit antigen-specific Th1 responses that were protective. Considering the ability to reduce parasite burden along with additional factors such as sequence identity across Leishmania species, we then generated a chimeric fusion protein comprising a combination of the 8E, p21 and SMT proteins. This E. coli -expressed fusion protein was also demonstrated to protect against L. donovani infection. These data indicate a novel recombinant vaccine antigen with the potential for use in VL control programs. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. Treatment of Cutaneous Leishmaniasis in Murine Model by Alcoholic Extract of Berberis vulgaris

    Directory of Open Access Journals (Sweden)

    Jalalianfard A

    2006-08-01

    Full Text Available In order to evaluate the effect of Berberis vulgaris extract on the experimental ulcers of cutaneous leishmaniasis (CL on Balb/c mice, a study was undertaken over a 12 months period. Forty Balb/c mice were divided into 2 main groups A and B. Each main group in turn was divided into 5 sub groups of 4 mice and each sub group were inoculated subcutaneously by 0.1ml liquid phase culture containing promastigotes of Leishmania major. After 2-3 weeks, nodules and ulcers appeared on 37 of 40 inoculated mice. Ethanol extract of the stem and leaves as well as roots of Berberis vulgaris in different concentrations, were used topically on CL lesions of 4 sub groups A and B, respectively. Ethanol alone was used on the lesions of control mice. The surface area of lesions were measured before and 1-2 weeks after treatment. Direct Geimsa stained smear prepared 20 days after treatment. The results showed that after 2 weeks, a statistically significant decrease of ulcer size of treated mice observed, while in the control group the lesion growth continued. The examinations showed that using higher concentration of the extract caused more decrease in surface area of CL lesions on day 15 and negative direct smear on day 20. Alcoholic extract of B.vulgaris root was more effective than leaves and stem extract. Alcoholic extract of B vulgaris might be further used in animal model.

  13. Photodynamic vaccination of hamsters with inducible suicidal mutants of Leishmania amazonensis elicits immunity against visceral leishmaniasis

    Science.gov (United States)

    Kumari, Shraddha; Samant, Mukesh; Khare, Prashant; Misra, Pragya; Dutta, Sujoy; Kolli, Bala Krishna; Sharma, Sharad; Chang, Kwang Poo; Dube, Anuradha

    2016-01-01

    Leishmania, naturally residing in the phagolysosomes of macrophages, is a suitable carrier for vaccine delivery. Genetic complementation of these trypanosomatid protozoa to partially rectify their defective heme-biosynthesis renders them inducible with δ-aminolevulinate to develop porphyria for selective photolysis, leaving infected host-cells unscathed. Delivery of released “vaccines” to antigen-presenting cells is thus expected to enhance immune response, while their self-destruction presents added advantages of safety. Such suicidal-L. amazonensis was found to confer immunoprophylaxis and immunotherapy on hamsters against L. donovani. Neither heat-killed nor live parasites without suicidal induction were effective. Photodynamic vaccination of hamsters with the suicidal-mutants reduced the parasite loads by 99% and suppressed the development of disease. These suppressions were accompanied by an increase in Leishmania-specific delayed-type hypersensitivity and lymphoproliferation as well as in the levels of splenic iNOS, IFN-γ and IL-12 expressions and of Leishmania-specific IgG2 in the serum. Moreover, a single intravenous administration of T-cells from vaccinated hamsters was shown to confer on naïve animals an effective cellular immunity against L. donovani challenges. The absence of lesion development at vaccination sites and parasites in the draining lymphnodes, spleen and liver further indicates that the suicidal mutants provide a safe platform for vaccine delivery against experimental visceral leishmaniasis. PMID:19053149

  14. Disturbances of visual information processing in early states of psychosis and experimental delta-9-tetrahydrocannabinol altered states of consciousness.

    Science.gov (United States)

    Koethe, Dagmar; Gerth, Christoph W; Neatby, Miriam A; Haensel, Anita; Thies, Martin; Schneider, Udo; Emrich, Hinderk M; Klosterkötter, Joachim; Schultze-Lutter, Frauke; Leweke, F Markus

    2006-12-01

    Recent data on alterations of the endogenous cannabinoid system in schizophrenia have raised the question of its functional role in this disease. The psychoactive compound of Cannabis sativa, delta-9-tetrahydrocannabinol (Delta9-THC), has been shown to induce psychotic symptoms, but it is unknown to what extend prodromal states of psychoses are reflected by these experimental approaches. This study compares four groups of subjects: antipsychotic-naïve patients suffering from acute paranoid schizophrenic or schizophreniform psychosis (SZ), patients in the prodromal state (IPS), healthy controls without any pharmacological intervention (HC) and a second group of healthy volunteers who were orally administered synthetic Delta9-THC (Dronabinol) (HC-THC). Neither SZ and IPS nor HC received the experimental drug. All subjects were assessed using the Brief Psychiatric Rating Scale (BPRS) and the Binocular Depth Inversion Illusion Test (BDII). The latter represents a sensitive measure of impaired visual information processing that manifests in various experimental and naturally occurring psychotic states. BDII values were well comparable in SZ, IPS and HC-THC, and all groups differed significantly to HC. The BPRS revealed no significant difference between HC-THC and IPS while both were significantly different from SZ and HC, respectively. Our results suggest that Delta9-THC-induced altered states of consciousness may serve as a useful tool for modeling psychotic disorders, particularly their prodromal states. Furthermore, they provide insight into the perceptual and psychopathological alterations induced by Delta9-THC, which is essential for the understanding of the pro-psychotic effects of herbal cannabis preparations with highly enriched Delta9-THC content.

  15. Experimental and Quantum Mechanics Investigations of Early Reactions of Monomethylhydrazine with Mixtures of NO2 and N2O4

    Science.gov (United States)

    2013-02-15

    implemented in Jaguar [22], using a dielectric constant of 80.37 and a spherical cavity of radius 1.40A for water. We con- sider that the solvation...were carried out with Jaguar 7.6 [23]. The UCCSD(T) calculation was done with NWChem [24,25]. 3. Experimental results 3.1. Summary of spectroscopic...1994) 11875– 11882. [23] Jaguar , Schrodinger, LLC, New York, NY, 2007. [24] M. Valiev, E.J. Bylaska, N. Govind, K. Kowalski, T.P. Straatsma, H.J.J. Van

  16. Effects of Early IL-17A Neutralization on Disease Induction in a Primate Model of Experimental Autoimmune Encephalomyelitis

    OpenAIRE

    Kap, Yolanda S.; Jagessar, S. Anwar; Driel, Nikki; Blezer, Erwin; Bauer, Jan; van Meurs, Marjan; Smith, Paul; Laman, Jon D.; Bert A. ‘t Hart

    2010-01-01

    We report on the effect of antibody-mediated neutralization of interleukin (IL)-17A in a non-human primate experimental autoimmune encephalomyelitis (EAE) model induced with recombinant human myelin oligodendrocyte glycoprotein (rhMOG). We tested a human-anti-human IL-17A-antibody in two doses (3 and 30 mg/kg) against placebo (PBS). The treatment was started 1 day before EAE induction and continued throughout the experiment. Although all monkeys developed clinically evident EAE, the onset of ...

  17. Early assessment of the efficacy of temozolomide chemotherapy in experimental glioblastoma using [18F]FLT-PET imaging.

    Directory of Open Access Journals (Sweden)

    Thomas Viel

    Full Text Available UNLABELLED: Addition of temozolomide (TMZ to radiation therapy is the standard treatment for patients with glioblastoma (GBM. However, there is uncertainty regarding the effectiveness of TMZ. Considering the rapid evolution of the disease, methods to assess TMZ efficacy early during treatment would be of great benefit. Our aim was to monitor early effects of TMZ in a mouse model of GBM using positron emission tomography (PET with 3'-deoxy-3'-[(18F]fluorothymidine ([(18F]FLT. METHODS: Human glioma cells sensitive to TMZ (Gli36dEGFR-1 were treated with sub-lethal doses of TMZ to obtain cells with lower sensitivity to TMZ (Gli36dEGFR-2, as measured by growth and clonogenic assays. Gli36dEGFR-1 and Gli36dEGFR-2 cells were subcutaneously (s.c. or intracranially (i.c. xenografted into nude mice. Mice were treated for 7 days with daily injection of 25 or 50 mg/kg TMZ. Treatment efficacy was measured using [(18F]FLT-PET before treatment and after 2 days. Computed Tomography (CT or Magnetic Resonance Imaging (MRI were used to determine tumor volumes before treatment and after 7 days. RESULTS: A significant difference was observed between TMZ and DMSO treated tumors in terms of variations of [(18F]FLT T/B ratio as soon as day 2 in the i.c. as well as in the s.c. mouse model. Variations of [(18F]FLT T/B uptake ratio between days 0 and 2 correlated with variations of tumor size between days 0 and 7 (s.c. model: n(tumor = 17 in n(mice = 11, P<0.01; i.c. model: n(tumor/mice = 9, P<0.01. CONCLUSIONS: Our results indicate that [(18F]FLT-PET may be useful for an early evaluation of the response of GBM to TMZ chemotherapy in patients with glioma.

  18. Microstructure of Temporomandibular Joint Cartilage after Intra-Articular Betamethasone Sodium Phosphate/Betamethasone Dipropionate Injection during the Early Stage of Experimental Osteoarthrosis

    Directory of Open Access Journals (Sweden)

    Irina N. Kostina

    2014-06-01

    Full Text Available Objective: to study the morphological changes in cartilage after a single intra-articular betamethasone sodium phosphate (BSP/betamethasone dipropionate (BDP injection during the early stage of experimental osteoarthrosis (OA of the temporomandibular joint (TMJ. Material and Methods: The experiment was performed on 18 male rabbits aged 6 months .The first group consisted of 9 healthy rabbits. The second group included 9 rabbits with mechanically induced TMJ OA. For 5 days, 3 hours daily, a load (with a force of 200N on the TMJ was imposed. In the left TMJ of the second group of rabbits, betamethasone was injected intra-articularly in different doses: 0.1 ml (n=3, 0.3 ml (n=3, and 0.5 ml (n=3. The right TMJ was used for comparison. A combined anesthesia was applied each experimental day. Rabbits of both groups were sacrificed on days 7, 14, and 30 with introductory combined anesthesia and intravenous injection of Zoletil 100® 20 mg/kg to stop their breathing. Results: Betamethasone caused destruction of the chondrocytes, fragmentation of collagen fibers, deficit of proteoglycans (PGs and glycosaminoglycans (GAGs, thinning of the cartilage, and contributed to the progression of TMJ OA. Conclusion: The optimal dose of BSP/BDP for intra-articular injection in the early stages of TMJ OA must be within the range of 0.1-0.3 ml|0.7-1.5 mg.

  19. Leishmania spp. Epidemiology of Canine Leishmaniasis in the Yucatan Peninsula

    Directory of Open Access Journals (Sweden)

    A. López-Céspedes

    2012-01-01

    Full Text Available Canine Leishmaniasis is widespread in various Mexican states, where different species of Leishmania have been isolated from dogs. In the present study, we describe the detection of L. braziliensis, L. infantum, and L. mexicana in serum of dogs from the states of Yucatan and Quintana Roo in the Yucatan Peninsula (Mexico. A total of 412 sera were analyzed by ELISA using the total extract of the parasite and the iron superoxide dismutase excreted by different trypanosomatids as antigens. We found the prevalence of L. braziliensis to be 7.52%, L. infantum to be 6.07%, and L. mexicana to be 20.63%, in the dog population studied. The results obtained with ELISA using iron superoxide dismutase as the antigen were confirmed by western blot analysis with its greater sensitivity, and the agreement between the two techniques was very high.

  20. Liposomal amphotericin B and leishmaniasis: Dose and response

    Directory of Open Access Journals (Sweden)

    Shyam Sundar

    2010-01-01

    Full Text Available Liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL. It is the treatment of choice for immunocompetent patients in the Mediterranean region and the preferred drug for HIV/VL co-infection. Although there is a regional variation in the susceptibility of the parasite a total dose of 20 mg/kg is effective in immunocompetent patients. Randomized clinical trials of liposomal amphotericin B in the treatment and secondary prophylaxis of HIV-VL coinfected patients is urgently needed to optimize treatment in this subset. With the availability of Liposomal amphotericin B at a preferential pricing in the endemic areas, short course combination therapy can become a viable alternative.