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1.
Washington, D.C.; OPS; 2020-09-09.
em Espanhol | PAHO-IRIS | ID: phr-52645

RESUMO

El Atlas interactivo de leishmaniasis en las Américas: aspectos clínicos y diagnósticos diferenciales es una publicación innovadora en la que se abordan los principales conceptos, conocimientos y diferencias clínicas de las leishmaniasis en distintos países endémicos de la Región de las Américas. Además, presenta las principales enfermedades de la piel y las mucosas que deben considerarse en el diagnóstico diferencial de las diversas manifestaciones clínicas de las leishmaniasis, lo cual representa uno de los principales desafíos para los profesionales responsables del diagnóstico de la enfermedad.Esta publicación es el resultado de un trabajo conjunto de la Organización Panamericana de la Salud (OPS) con expertos y colaboradores en el tema, que ha contado con el apoyo del Hospital Universitario Centro Dermatológico Federico Lleras Acosta de Colombia y de los Ministerios de Salud de los Estados Miembros de la OPS. El objetivo de esta obra es facilitar a los profesionales de salud la posibilidad de buscar, conocer y analizar de forma interactiva las 1.029 fotografías e ilustraciones de leishmaniasis y de las 55 principales enfermedades que se consideran en el diagnostico diferencial. Esperamos que sea de gran valor para estudiantes, profesores, investigadores y profesionales del sistema de atención de salud de nuestra Región y de todos los demás continentes cuando atiendan pacientes infectados en las Américas.


Assuntos
Leishmaniose , Dermatopatias , Doenças Transmissíveis , América
2.
Parasitol Res ; 119(7): 2025-2037, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32504119

RESUMO

Leishmaniasis is a neglected tropical disease with no effective vaccines to date. Globally, it affects around 14 million people living in undeveloped and developing countries. Leishmania, which is the causative eukaryotic organism, possesses unique enzymes and pathways that deviates from its mammalian hosts. The control strategy against leishmaniasis currently depends on chemotherapeutic methods. But these chemotherapeutic therapies possess several side effects, and therefore, the identification of potential drug targets has become very crucial. Identification of suitable drug targets is necessary to design specific inhibitors that can target and control the parasite. These unique enzymes can be used as possible drug targets after biochemical characterization and understanding the role of these enzymes. In this review, the authors discuss various metabolic pathways that are essential for the survival of the parasite and can be exploited as potential drug targets against leishmaniasis.


Assuntos
Antiparasitários , Leishmania/metabolismo , Leishmaniose/tratamento farmacológico , Redes e Vias Metabólicas/efeitos dos fármacos , Terapia de Alvo Molecular , Animais , Antiparasitários/farmacologia , Antiparasitários/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos , Leishmania/efeitos dos fármacos
3.
Rev Bras Parasitol Vet ; 29(2): e003520, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520088

RESUMO

Blood samples and swabs from ocular conjunctiva and mouth were obtained from 64 cats. Of 64 serum samples, 19 were positive for Leishmania antibodies by ELISA (29.80%). Eight cats were positive by PCR (12.5%) in swab samples from mouth and/or ocular mucosa. Poor kappa agreement between serological and molecular results (k = 0.16) was obtained. From five positive PCR samples one was L. braziliensis and four were L. infantum. Phylogenetic analysis performed with the five isolates of Leishmania, showed that samples of L. infantum isolated from the cats were phylogenetically close to those isolated from domestic dogs in Brazil, while the L. braziliensis is very similar to the one described in humans in Venezuela. The study demonstrated that, despite high seropositivity for Leishmania in cats living in the study region, poor agreement between serological and molecular results indicate that positive serology is not indicative of Leishmania infection in cats. Parasite DNA can be detected in ocular conjunctiva and oral swabs from cats, indicating that such samples could be used for diagnosis. Results of phylogenetic analyzes show that L. infantum circulating in Brazil is capable of infecting different hosts, demonstrating the parasite's ability to overcome the interspecies barrier.


Assuntos
Doenças do Gato/parasitologia , Leishmania braziliensis/isolamento & purificação , Leishmania infantum/isolamento & purificação , Leishmaniose/parasitologia , Animais , Anticorpos Antiprotozoários/sangue , Doenças do Gato/diagnóstico , Gatos , DNA de Protozoário/análise , Ensaio de Imunoadsorção Enzimática/veterinária , Leishmania braziliensis/genética , Leishmania braziliensis/imunologia , Leishmania infantum/genética , Leishmania infantum/imunologia , Leishmaniose/diagnóstico , Filogenia , Reação em Cadeia da Polimerase/veterinária
5.
Artigo em Inglês | MEDLINE | ID: mdl-32520213

RESUMO

Although the chemical control against leishmaniasis began in 1953 in Brazil, little information is available on how this strategy has affected populations of phlebotomine sandflies in the field. The objective of this study was to analyze the susceptibility profile of four populations of phlebotomine sandflies to the insecticide alpha-cypermethrin. Sandflies collected in field in four Brazilian municipalities were evaluated using CDC bottles in different concentrations of alpha-cypermethrin. A total of 1,186 phlebotomine sandflies were used in the bioassays. The LD50 ranged from 1.48 to 2.57 ug/mL in the field populations. For a dose of 5 ug/mL of alpha-cypermethrin, the LT50 and LT95 ranged from 17.9 to 27.5 minutes, and LT95 from 39.7 to 61.5 minutes, respectively. All the populations studied were highly susceptible to the insecticide alpha-cypermethrin. Routine studies are needed to detect changes in sandflies susceptibility to insecticides.


Assuntos
Insetos Vetores/efeitos dos fármacos , Inseticidas/farmacologia , Psychodidae/efeitos dos fármacos , Piretrinas/farmacologia , Animais , Brasil , Doenças Endêmicas , Feminino , Insetos Vetores/classificação , Leishmaniose/transmissão , Psychodidae/classificação
6.
PLoS One ; 15(6): e0234445, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32579586

RESUMO

This study aimed to describe the sand fly fauna and detect trypanosomatids in these insects from Casa Branca, state of Minas Gerais, Brazil, an endemic area of both visceral (VL) and tegumentary leishmaniasis (TL). Sand flies were collected bimonthly from May 2013 to July 2014, using automatic light traps exposed for three consecutive nights in peridomiciliary areas of nine houses with previous reports of VL and TL. ITS1-PCR and DNA sequencing were performed for trypanosomatids identification. A total of 16,771 sand flies were collected belonging to 23 species. The most abundant species was Nyssomyia whitmani (Antunes & Coutinho, 1939) (70.9%), followed by Lutzomyia longipalpis (Lutz & Neiva, 1912) (15.2%) and Migonemyia migonei (França, 1920) (9.1%). Leishmania amazonensis DNA was detected in Ny. whitmani (four pools) and Le. braziliensis DNA was detected in Psychodopygus lloydi (one pool). In seven pools of Ny. whitmani and in one pool of Lu. longipalpis positive for Leishmania DNA, the parasite species was not determined due to the low quality of the sequences. Moreover, DNA of Herpetomonas spp. was detected in Ny. whitmani (two pools) and Cortelezzii complex (one pool). DNA of Crithidia spp. was detected in Ny. whitmani and Ps. lloydi (both one pool). Our results suggest that Ny. whitmani may be involved in the transmission of Le. amazonensis in the study area. The molecular detection of Le. amazonensis suggests the presence of this species in a sylvatic cycle between vertebrate and invertebrate hosts in the region of Casa Branca. Our data also reveal the occurrence of other non-Leishmania trypanosomatids in sand flies in Casa Branca District.


Assuntos
Biodiversidade , Insetos Vetores/parasitologia , Leishmania/isolamento & purificação , Phlebotomus/parasitologia , Psychodidae/parasitologia , Animais , Brasil/epidemiologia , DNA de Protozoário/isolamento & purificação , Doenças Endêmicas/prevenção & controle , Feminino , Humanos , Leishmania/genética , Leishmaniose/epidemiologia , Leishmaniose/parasitologia , Leishmaniose/prevenção & controle , Leishmaniose/transmissão , Análise de Sequência de DNA
7.
Exp Parasitol ; 216: 107940, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32562606

RESUMO

Therapeutic options for the treatment of leishmaniasis are insufficient and need improvements owing to their low efficiency and high toxicity as well as the emergence of resistant strains. The limited number of new drugs for neglected diseases and lack of innovation in your development are still challenges. In this context, the process of discovery and development of biological assays play a pivotal role for the identification of bioactive compounds. The assays currently used for screening of drugs with cytotoxic activity against Leishmania parasites, include different processes that utilize intact parasite (free or intracellular) or specific enzymes of metabolism as a target cell. These assays allow the screening of large numbers of samples followed by more detailed secondary confirmatory assays to confirm the observed activity and assess their toxicity. In the present study, we described the development of a new functional and more complete assay that enables simultaneous assessment of potential anti-Leishmania compounds through evaluation of internalization of fluorescein-labeled L. braziliensis promastigotes by human peripheral blood monocytes and their cytotoxicity by flow cytometry. We standardized the conditions for parasite labeling to achieve better phagocytosis analysis by setting the ratio of number of parasites per cell as 1 to 2, at incubation time of 6h. The cytotoxicity assessment was performed by the quantification of cells undergoing early/late apoptosis and necrosis using a double labelling platform employing 7AAD for late apoptosis and necrosis analysis and Annexin-V for early apoptosis evaluation. Hemolysis analysis was an additional parameter to test cytotoxicity. Two drugs used on clinic (Amphotericin B and Glucantime®) were used to validate the proposed methodology, and the assay was able to detect their known leishmanicidal activity and immunotoxicity properties. This new predictive assay will contribute to the development of translational medicine strategies in drug discovery for neglected diseases such as leishmaniasis.


Assuntos
Alternativas aos Testes com Animais/métodos , Antiprotozoários/toxicidade , Citometria de Fluxo/métodos , Leishmania/efeitos dos fármacos , Doenças Negligenciadas/tratamento farmacológico , Adulto , Anfotericina B/farmacologia , Anfotericina B/toxicidade , Animais , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Descoberta de Drogas/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Fluoresceína-5-Isotiocianato , Corantes Fluorescentes , Humanos , Leishmania braziliensis/efeitos dos fármacos , Leishmaniose/tratamento farmacológico , Leucócitos/efeitos dos fármacos , Leucócitos/parasitologia , Antimoniato de Meglumina/farmacologia , Antimoniato de Meglumina/uso terapêutico , Antimoniato de Meglumina/toxicidade , Microscopia Confocal , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/parasitologia , Fatores de Tempo , Adulto Jovem
8.
Artigo em Inglês | MEDLINE | ID: mdl-32401957

RESUMO

Immunosuppression is an important risk factor for leishmaniasis. We assessed the clinical profile, geographic distribution and prevalence of leishmaniasis in patients undergoing immunosuppressive therapy for dermatological, rheumatological or gastroenterological autoimmune diseases. We identified relevant studies in PubMed, EMBASE, Scopus, Web of Science and LILACS on July 3rd, 2018. We included articles that reported at least one case of leishmaniasis in patients undergoing immunosuppressive treatment for dermatological, rheumatological or gastroenterological diseases. Our protocol was registered in PROSPERO (CRD42018103050). We assessed the quality of the included studies with the Joanna Briggs Institute Critical Appraisal Tool. After the removal of duplicates, 5,431 articles were collected and screened. We included 138 articles; the prevalence of leishmaniasis in six methodologically similar studies varied from three to 1,282 cases per 100,000 patients using anti-TNFα drugs, but the results were significantly heterogeneous . Leishmaniasis in patients treated with immunosuppressive drugs is a health problem mostly reported in European countries bordering the Mediterranean Sea; sporadic activities, such as travelling, seem not to be associated with a significant risk of leishmaniasis, although effective control measures must always be observed.


Assuntos
Hospedeiro Imunocomprometido/imunologia , Imunossupressores/efeitos adversos , Leishmaniose/imunologia , Gastroenteropatias/tratamento farmacológico , Humanos , Imunossupressores/imunologia , Imunossupressores/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , Dermatopatias/tratamento farmacológico
9.
Cell Host Microbe ; 27(5): 683-684, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32407702

RESUMO

The phagosomal pathogen Leishmania appears unaffected by deliberate changes in the early Th1/Th2 balance. In this issue, Carneiro et al. explain these paradoxical results by showing that manipulations affecting IFN-γ-mediated phagocyte activation are counteracted by effects on IFN-γ-dependent recruitment of CCR2+ monocytes permissive to parasite growth.


Assuntos
Leishmaniose , Monócitos , Humanos , Interferon gama , Fagossomos , Pele
10.
Nucleic Acids Res ; 48(11): 6081-6091, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32402089

RESUMO

Herein, we characterize the cellular uptake of a DNA structure generated by rolling circle DNA amplification. The structure, termed nanoflower, was fluorescently labeled by incorporation of ATTO488-dUTP allowing the intracellular localization to be followed. The nanoflower had a hydrodynamic diameter of approximately 300 nanometer and was non-toxic for all mammalian cell lines tested. It was internalized specifically by mammalian macrophages by phagocytosis within a few hours resulting in specific compartmentalization in phagolysosomes. Maximum uptake was observed after eight hours and the nanoflower remained stable in the phagolysosomes with a half-life of 12 h. Interestingly, the nanoflower co-localized with both Mycobacterium tuberculosis and Leishmania infantum within infected macrophages although these pathogens escape lysosomal degradation by affecting the phagocytotic pathway in very different manners. These results suggest an intriguing and overlooked potential application of DNA structures in targeted treatment of infectious diseases such as tuberculosis and leishmaniasis that are caused by pathogens that escape the human immune system by modifying macrophage biology.


Assuntos
DNA/química , DNA/metabolismo , Leishmania infantum/metabolismo , Macrófagos/microbiologia , Macrófagos/parasitologia , Mycobacterium tuberculosis/metabolismo , Fagossomos/metabolismo , DNA/análise , Replicação do DNA , Fluorescência , Meia-Vida , Humanos , Leishmaniose/terapia , Macrófagos/citologia , Macrófagos/imunologia , Nanoestruturas/análise , Nanoestruturas/química , Técnicas de Amplificação de Ácido Nucleico , Fagocitose , Fagossomos/química , Fagossomos/microbiologia , Fagossomos/parasitologia , Tuberculose/terapia
11.
Rev Soc Bras Med Trop ; 53: e20190538, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32267459

RESUMO

INTRODUCTION: Leishmaniasis constitutes a serious but neglected tropical disease. Recently, socio-environmental, biological and physical changes have altered the range of leishmaniasis, causing it to spread into urban areas. In Minas Gerais, the disease is endemic, exhibiting regional differences and reaching urban centers. The purpose of this study was to evaluate entomological aspects related to the ecoepidemiology of leishmaniasis in Itaúna. METHODS: Monthly catches with HP traps were carried out from June 2017 to May 2018, in three ecological areas (urban, rural, and forest). The adaptability of the species to anthropic environments was assessed using the synanthropy index (SI). RESULTS: We collected 1306 specimens of phlebotomine sand flies. Of the species of medical importance, Lutzomyia longipalpis, the vector of Leishmania infantum, represented 90.4% of the specimens identified at species level (n=1260). Nyssomyia whitmani, the vector of Leishmania braziliensis, represented 1.6% of the total. Lu. longipalpis displayed an SI of +95.8, a value that denotes a marked preference for human environments. For Ny. whitmani, the SI was -25, expressing the tendency of this species to occupy uninhabited areas. The population of the three most numerous species captured increased with rain, high temperatures, and high relative humidity. Although captured at low numbers, Ny. whitmani showed a different profile concerning the climate variables analyzed. CONCLUSIONS: Understanding the epidemiology of the disease may assist the health services in formulating effective control measures for improving community health and contributing to the establishment of a dynamic relationship and a global awareness of the health/disease process.


Assuntos
Insetos Vetores/classificação , Psychodidae/classificação , Distribuição Animal , Animais , Brasil , Feminino , Leishmaniose/transmissão , Masculino , População Rural , Estações do Ano , População Urbana
12.
Parasit Vectors ; 13(1): 193, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293524

RESUMO

BACKGROUND: For long time, canine leishmaniosis (CanL) was considered endemic in the southern, central, and insular regions of Italy, whereas heartworm disease (HW) caused by Dirofilaria immitis was considered endemic in the northern region and in the swampy Po Valley. Following the reports of new foci of both diseases, in this study we update the distribution patterns and occurrence of new foci of CanL and HW discussing the main drivers for the changes in the epidemiology of these two important zoonotic canine vector-borne diseases. METHODS: Based on the statistical analyses of serological assays (n = 90,633) on L. infantum exposure and D. immitis infection performed by two reference diagnostic centres in Italy over a ten-year period (2009-2019) irrespective of the anamnesis of dogs. The distribution patterns of both parasites are herein presented along with the occurrence of new foci. RESULTS: Results highlighted the changing distribution patterns of L. infantum vs D. immitis infection in Italy. CanL is endemic in some areas of northern regions and HW has endemic foci in central and southern regions and islands. Significant differences in L. infantum exposure and HW infection prevalence among the study macroareas were detected. The overall results of the positive tested samples were 28.2% in southern Italy and islands, 29.6% in central Italy and 21.6% in northern Italy for L. infantum and 2.83% in northern Italy, 7.75% in central Italy and 4.97% in southern Italy and islands for HW. HW positivity significantly varied over years (χ2 = 108.401, df = 10, P < 0.0001), gradually increasing from 0.77% in 2009 to 8.47% in 2016-2017. CONCLUSIONS: New potential epidemiological scenarios are discussed according to a range of factors (e.g. environmental modifications, occurrence of competent insect vectors, transportation of infected animals to non-endemic areas, chemoprophylaxis or vector preventative measures), which may affect the current distribution. Overall, the results advocate for epidemiological surveillance programmes, more focussed preventative and control measures even in areas where few or no cases of both diseases have been diagnosed.


Assuntos
Dirofilaria immitis/parasitologia , Dirofilariose/epidemiologia , Doenças do Cão/epidemiologia , Leishmania infantum/parasitologia , Leishmaniose/veterinária , Animais , Dirofilariose/prevenção & controle , Cães , Insetos Vetores/parasitologia , Itália/epidemiologia , Leishmaniose/epidemiologia , Psychodidae/parasitologia , Testes Sorológicos , Zoonoses
13.
Braz J Infect Dis ; 24(3): 201-207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32343952

RESUMO

Cysteine proteinases are well-known virulence factors of Leishmania spp. with demonstrated actions in both experimental mouse infection and human infection. However, studies on these enzymes in canine leishmaniasis are scarce. Here, we show, for the first time, the reactivity of sera from dogs living in an endemic area to a recombinant protein from the COOH-terminal region of cysteine B protease. In this work, enzyme-linked immunosorbent assays were performed using a 14kDa rcyspep protein obtained through a pET28-a expression system in Escherichia coli. First, 96-well plates were coated with rcyspep (500ng/well) and incubated with sera from dogs (1:100). Subsequently, IgG antibody detection was performed using rabbit anti-dog IgG antibodies conjugated with peroxidase. Sera from dogs (n=114), including suspect (n=30) and positive (n=50) dogs from a leishmaniasis-endemic area and dogs from a nonendemic area, (n=34), negative for leishmaniasis, were assessed. The results showed that sera from the suspect (42%) and positive (68%) groups responded differently to the antigen titers tested above the cut-off (Optical Density=0.166). This finding suggests that the immune response detected against cyspep may be related to clinical disorders present in these animals. Collectively, the data gathered here suggest that cyspep can sensitize the immune systems of dogs from a leishmaniasis-endemic area to elicit a humoral response, an immunological parameter indicating the contribution of this protein in host-parasite interaction.


Assuntos
Cisteína Proteases/sangue , Doenças do Cão/sangue , Leishmania , Leishmaniose/sangue , Animais , Anticorpos Antiprotozoários , Cisteína , Cães , Ensaio de Imunoadsorção Enzimática , Humanos , Leishmania infantum , Leishmaniose/veterinária , Leishmaniose Visceral , Camundongos , Coelhos
14.
PLoS Negl Trop Dis ; 14(4): e0008167, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32275661

RESUMO

Leishmania donovani, an intracellular protozoan parasite upon infection, encounters a range of antimicrobial factors within the host cells. Consequently, the parasite has evolved mechanisms to evade this hostile defense system through inhibition of macrophage activation that, in turn, enables parasite replication and survival. There is growing evidence that epigenetic down-regulation of the host genome by intracellular pathogens leads to acute infection. Epigenetic modification is mediated by chromatin remodeling, histone modifications, or DNA methylation. Histone deacetylases (HDACs) removes acetyl groups from lysine residues on histones, thereby leading to chromatin remodeling and gene silencing. Here, using L. donovani infected macrophages differentiated from THP-1 human monocytic cells, we report a link between host chromatin modifications, transcription of defense genes and intracellular infection with L. donovani. Infection with L. donovani led to the silencing of host defense gene expression. Histone deacetylase 1 (HDAC1) transcript levels, protein expression, and enzyme activity showed a significant increase upon infection. HDAC1 occupancy at the promoters of the defense genes significantly increased upon infection, which in turn resulted in decreased histone H3 acetylation in infected cells, resulting in the down-regulation of mRNA expression of host defense genes. Small molecule mediated inhibition and siRNA mediated down-regulation of HDAC1 increased the expression levels of host defense genes. Interestingly, in this study, we demonstrate that the silencing of HDAC1 by both siRNA and pharmacological inhibitors resulted in decreased intracellular parasite survival. The present data not only demonstrate that up-regulation of HDAC1 and epigenetic silencing of host cell defense genes is essential for L. donovani infection but also provides novel therapeutic strategies against leishmaniasis.


Assuntos
Citoplasma/metabolismo , Epigênese Genética , Histona Desacetilase 1/genética , Leishmania donovani/patogenicidade , Leishmaniose/genética , Macrófagos/parasitologia , Linhagem Celular , Montagem e Desmontagem da Cromatina , Citoplasma/parasitologia , Metilação de DNA , Regulação para Baixo , Regulação da Expressão Gênica , Inativação Gênica , Histona Desacetilase 1/metabolismo , Histonas/genética , Histonas/metabolismo , Interações Hospedeiro-Parasita/genética , Humanos , Monócitos/metabolismo , Monócitos/parasitologia , Processamento de Proteína Pós-Traducional , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Células THP-1
15.
J Nat Med ; 74(3): 606-611, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32277328

RESUMO

Six limonoids [kotschyienone A and B (1, 2), 7-deacetylgedunin (3), 7-deacetyl-7-oxogedunin (4), andirobin (5) and methyl angolensate (6)] were investigated for their trypanocidal and leishmanicidal activities using bloodstream forms of Trypanosoma brucei and promastigotes of Leishmania major. Whereas all compounds showed anti-trypanosomal activity, only compounds 1-4 displayed anti-leishmanial activity. The 50% growth inhibition (GI50) values for the trypanocidal and leishmanicidal activity of the compounds ranged between 2.5 and 14.9 µM. Kotschyienone A (1) was found to be the most active compound with a minimal inhibition concentration (MIC) value of 10 µM and GI50 values between 2.5 and 2.9 µM. Only compounds 1 and 3 showed moderate cytotoxicity against HL-60 cells with MIC and GI50 values of 100 µM and 31.5-46.2 µM, respectively. Compound 1 was also found to show activity against intracellular amastigotes of L. major with a GI50 value of 1.5 µM. The results suggest that limonoids have potential as drug candidates for the development of new treatments against trypanosomiasis and leishmaniasis.


Assuntos
Leishmania major/efeitos dos fármacos , Leishmaniose/tratamento farmacológico , Limoninas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacos , Tripanossomíase/tratamento farmacológico , Animais , Células HL-60 , Humanos , Testes de Sensibilidade Microbiana
16.
Parasite Immunol ; 42(7): e12722, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32294247

RESUMO

Leishmaniasis is a neglected infectious disease with clinical presentations ranging from asymptomatic or mild symptoms to chronic infection and eventual death. The mechanisms of disease susceptibility and pathology have been extensively studied, but there are no steadfast rules regarding leishmaniasis. A Th1 response is usually associated with infection control, while a predominant Th2 response is detrimental to the patient. In this scenario, the enzymes arginase and inducible nitric oxide synthase represent two possible pathways of immune response. While the former contributes to parasite replication, the latter is crucial for its control. In the present review, we collected study results that associate arginase expression in patients and in experimental models with disease susceptibility/chronicity and show some proposed mechanisms that explain the role of arginase in maintaining Leishmania infection, including polyamine and thiol synthesis, tissue-resident macrophage (TRM) proliferation and activation and T-cell suppression and exhaustion.


Assuntos
Arginase/metabolismo , Leishmania/imunologia , Leishmaniose/imunologia , Macrófagos/imunologia , Óxido Nítrico Sintase Tipo II/metabolismo , Animais , Linfócitos T CD8-Positivos/imunologia , Humanos , Imunidade Inata/imunologia , Leishmaniose/parasitologia , Neutrófilos/imunologia , Células Th1/imunologia , Células Th2/imunologia
17.
Am J Trop Med Hyg ; 102(6): 1323-1327, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32228793

RESUMO

Multiple polymerase chain reaction (PCR)-based approaches have been developed for Leishmania detection in clinical and laboratory samples, and this diversity limits inter-study comparisons, meta-analyses, and generalization of findings. Towards harmonization of a molecular tool for detection of Leishmania (Viannia) for research purposes, we evaluated the concordance of 18SrDNA quantitative polymerase chain reaction (qPCR) and minicircle kinetoplastid DNA (mkDNA) PCR followed by Southern blot (PCR-SB) in in vitro infection systems and in lesion and mucosal swab samples from Colombian patients with cutaneous leishmaniasis caused by L. (Viannia). The lower limit of parasite detection of 18SrDNA qPCR and mkDNA PCR-SB was 10-1 promastigotes and one intracellular amastigote per reaction. From cutaneous lesions (n = 63), an almost perfect concordance was found between the methods (κ = 0.92, 95% CI: 0.82-1.00). Despite equal limits of detection, mkDNA PCR-SB was more efficient for parasite detection in mucosal samples than 18SrDNA qPCR or 18SrDNA digital droplet PCR. The high concordance, sensitivity, scaling potential, and feasibility of implementation of the 18SrDNA qPCR, support its selection as the L. (Viannia) in research laboratories, as a first step towards harmonization of research protocols in the region.


Assuntos
DNA de Protozoário/genética , Leishmania/isolamento & purificação , Leishmaniose/diagnóstico , Leishmaniose/parasitologia , Técnicas de Amplificação de Ácido Nucleico , Linhagem Celular , Túnica Conjuntiva/parasitologia , Feminino , Humanos , Limite de Detecção , Masculino , Monócitos/parasitologia , Mucosa Nasal/parasitologia , Tonsila Palatina/parasitologia , Especificidade da Espécie
18.
Rev. clín. esp. (Ed. impr.) ; 220(2): 109-114, mar. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-186420

RESUMO

Introducción: El síndrome hemofagocítico (SHF) es un trastorno inmunológico grave caracterizado por una inflamación descontrolada con fracaso multiorgánico. Puede estar desencadenado por infecciones víricas, bacterianas, fúngicas o parasitarias. Se describe nuestra experiencia de SHF asociado a infecciones y se estima su incidencia local. Material y método: Estudio retrospectivo observacional de SHF asociado a infecciones en adultos atendidos en el Servicio de Patología Infecciosa de un hospital universitario durante 5años y revisión de las series publicadas en Europa. Resultados: En 2 mujeres con enfermedad de Crohn, el SHF se asoció a infección por citomegalovirus y a leishmaniosis visceral (mieloma múltiple 1, tumor sólido 2, sin enfermedad evidente 1) en 4 pacientes (3 hombres). Fallecieron 2 enfermos. La incidencia estimada fue 0,58/100.000/año. Las series publicadas son heterogéneas. Conclusiones: El SHF asociado a infecciones debe de ser más frecuente de lo descrito. El entorno geográfico puede influir en las infecciones desencadenantes (en nuestro medio, debe buscarse Leishmania)


Background: Haemophagocytic syndrome (HPS) is a severe immunological disorder characterised by uncontrolled inflammation and multiple organ failure. HPS can be triggered by viral, bacterial, fungal and parasitical infections. We report our experience with infection-related HPS and estimate its local incidence. Material and method: We conducted an observational retrospective study of infection-associated HPS in patients treated in the Department of Infectious Diseases of a university hospital within a 5-year period, as well as a review of the published series in Europe. Results: HPS was associated with infection by cytomegalovirus in 2 women with Crohn's disease and was associated with visceral leishmaniosis in 4 patients (3 men, 1 woman; 1 case of multiple myeloma; 2 cases of solid tumours; 1 case of no apparent disease). Two patients died, and the estimated incidence rate was 0.58/100,000 inhabitants/year. The published series are mixed. Conclusions: Infection-related HPS must be more common than reported. The geographical environment can influence the triggering infections (in our environment, Leishmania should be considered)


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Idoso , Linfo-Histiocitose Hemofagocítica/diagnóstico , Insuficiência de Múltiplos Órgãos/diagnóstico , Etoposídeo/uso terapêutico , Glucocorticoides/uso terapêutico , Estudos Retrospectivos , Infecções por Citomegalovirus/diagnóstico , Leishmaniose/diagnóstico , Mieloma Múltiplo/complicações , Doença de Crohn/complicações , Resultado do Tratamento
19.
Infect Dis Poverty ; 9(1): 30, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32183909

RESUMO

BACKGROUND: As of 2015 thousands of refugees are being hosted in temporary refugee camps in Greece. Displaced populations, travelling and living under poor conditions with limited access to healthcare are at a high risk of exposure to vector borne disease (VBD). This study sought to evaluate the risk for VBD transmission within refugee camps in Greece by analyzing the mosquito and sand fly populations present, in light of designing effective and efficient context specific vector and disease control programs. METHODS: A vector/pathogen surveillance network targeting mosquitoes and sand flies was deployed in four temporary refugee camps in Greece. Sample collections were conducted bi-weekly during June-September 2017 with the use of Centers for Disease Control (CDC) light traps and oviposition traps. Using conventional and molecular diagnostic tools we investigated the mosquito/sand fly species composition, population dynamics, pathogen infection rates, and insecticide resistance status in the major vector species. RESULTS: Important disease vectors including Anopheles sacharovi, Culex pipiens, Aedes albopictus and the Leishmania vectors Phlebotomus neglectus, P. perfiliewi and P. tobbi were recorded in the study refugee camps. No mosquito pathogens (Plasmodium parasites, flaviviruses) were detected in the analysed samples yet high sand fly Leishmania infection rates are reported. Culex pipiens mosquitoes displayed relatively high knock down resistance (kdr) mutation allelic frequencies (ranging from 41.0 to 63.3%) while kdr mutations were also detected in Ae. albopictus populations, but not in Anopheles and sand fly specimens. No diflubenzuron (DFB) mutations were detected in any of the mosquito species analysed. CONCLUSIONS: Important disease vectors and pathogens in vectors (Leishmania spp.) were recorded in the refugee camps indicating a situational risk factor for disease transmission. The Cx. pipiens and Ae. albopictus kdr mutation frequencies recorded pose a potential threat against the effectiveness of pyrethroid insecticides in these settings. In contrast, pyrethroids appear suitable for the control of Anopheles mosquitoes and sand flies and DFB for Cx. pipiens and Ae. albopictus larvicide applications. Targeted actions ensuring adequate living conditions and the establishment of integrated vector-borne disease surveillance programs in refugee settlements are essential for protecting refugee populations against VBDs.


Assuntos
Insetos Vetores/efeitos dos fármacos , Insetos Vetores/genética , Resistência a Inseticidas/genética , Leishmania , Controle de Mosquitos , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/genética , Dinâmica Populacional , Campos de Refugiados , Aedes/efeitos dos fármacos , Aedes/genética , Animais , Anopheles/efeitos dos fármacos , Anopheles/genética , Culex/efeitos dos fármacos , Culex/genética , Feminino , Grécia , Leishmania/genética , Leishmania/patogenicidade , Leishmaniose/epidemiologia , Phlebotomus/efeitos dos fármacos , Phlebotomus/genética , Psychodidae
20.
Parasite Immunol ; 42(6): e12713, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32173875

RESUMO

Canine leishmaniasis (CanL) is caused by the intracellular parasite Leishmania infantum. Prostaglandin E2 (PGE2 ) exerts potent regulatory effects on the immune system in experimental model Leishmania infection, but this influence has not yet been studied in CanL. In this study, PGE2 and PGE2 receptor levels and the regulatory effect of PGE2 on arginase activity, NO2 , IL-10, IL-17, IFN-γ, TNF-α and parasite load were evaluated in cultures of splenic leucocytes obtained from dogs with CanL in the presence of agonists and inhibitors. Our results showed that splenic leucocytes from dogs with CanL had lower EP2 receptor levels than those of splenic leucocytes from healthy animals. We observed that NO2 levels decreased when the cells were treated with a PGE2 receptor agonist (EP1/EP2/EP3) or COX-2 inhibitor (NS-398) and that TNF-α, IL-17 and IFN-γ cytokine levels decreased when the cells were treated with a PGE2 receptor agonist (EP2) or PGE2 itself. The parasite load in splenic leucocyte cell cultures from dogs with CanL decreased after stimulation of the cells with PGE2 . We conclude that Leishmania infection of dogs modulates PGE2 receptors and speculate that the binding of PGE2 to its receptors may activate the microbicidal capacity of cells.


Assuntos
Citocinas/imunologia , Dinoprostona/metabolismo , Doenças do Cão/tratamento farmacológico , Leishmania infantum/imunologia , Leishmaniose/veterinária , Receptores de Prostaglandina E/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Dinoprostona/agonistas , Dinoprostona/antagonistas & inibidores , Doenças do Cão/imunologia , Doenças do Cão/parasitologia , Cães , Leishmaniose/tratamento farmacológico , Leishmaniose/imunologia , Óxido Nítrico/análise , Nitrobenzenos/farmacologia , Carga Parasitária , Receptores de Prostaglandina E/agonistas , Receptores de Prostaglandina E/fisiologia , Sulfonamidas/farmacologia , Fator de Necrose Tumoral alfa/imunologia
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