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1.
BMC Infect Dis ; 22(1): 48, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022031

RESUMO

BACKGROUND: Leishmaniasis, a disease caused by a protozoan, causes numerous deaths in humans each year. After malaria, leishmaniasis is known to be the deadliest parasitic disease globally. Direct visual detection of leishmania parasite through microscopy is the frequent method for diagnosis of this disease. However, this method is time-consuming and subject to errors. This study was aimed to develop an artificial intelligence-based algorithm for automatic diagnosis of leishmaniasis. METHODS: We used the Viola-Jones algorithm to develop a leishmania parasite detection system. The algorithm includes three procedures: feature extraction, integral image creation, and classification. Haar-like features are used as features. An integral image was used to represent an abstract of the image that significantly speeds up the algorithm. The adaBoost technique was used to select the discriminate features and to train the classifier. RESULTS: A 65% recall and 50% precision was concluded in the detection of macrophages infected with the leishmania parasite. Also, these numbers were 52% and 71%, respectively, related to amastigotes outside of macrophages. CONCLUSION: The developed system is accurate, fast, easy to use, and cost-effective. Therefore, artificial intelligence might be used as an alternative for the current leishmanial diagnosis methods.


Assuntos
Leishmania , Leishmaniose Cutânea , Leishmaniose , Algoritmos , Inteligência Artificial , Humanos , Leishmaniose/diagnóstico , Aprendizado de Máquina
2.
Int J Dermatol ; 61(1): 89-98, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34510406

RESUMO

The World Health Organization (WHO) classifies leishmaniasis as a disease for which the development of new treatments is a priority. Available drugs are not fully effective in all cases; they have parenteral administration and exhibit serious and common adverse effects. The only oral drug available (miltefosine) has shown resistance, is expensive, and is not available in many endemic countries. Thus, the development of an oral medicine may solve many of these issues. Based on that, this review aimed to investigate which therapeutic alternatives have been studied for the development of oral drugs for the treatment of cutaneous leishmaniasis. A literature search for keywords "leishmania and oral" was performed in PubMed and ScienceDirect, considering articles published in the last 5 years. The articles were selected based on the objective of the review. The main problem in the current treatment of leishmaniasis is the administration of injectables, since it requires patients to travel to health centers, hospitalization, and professional administration, conditions that are not adapted to the socioeconomic reality of patients. Therefore, many research studies have evaluated oral alternatives for the treatment of cutaneous leishmaniasis. The main tested approaches were obtaining new molecules, repositioning drugs, and new formulations of old drugs. The prospects are encouraging but still require more in vivo bioavailability and clinical trials.


Assuntos
Antiprotozoários , Leishmania , Leishmaniose Cutânea , Leishmaniose , Antiprotozoários/uso terapêutico , Composição de Medicamentos , Humanos , Leishmaniose Cutânea/tratamento farmacológico
3.
Methods Mol Biol ; 2410: 463-480, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34914063

RESUMO

Visceral leishmaniasis (VL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. Systemic VL is fatal if untreated and there are no prophylactic human vaccines available. Several studies suggest that Th1 cell-mediated immunity plays a major role in protecting against VL. In this chapter we describe a method for designing recombinant chimera vaccines in silico based on the prediction of T cell epitopes within protein antigens identified as potential protective immunogens. Development of a recombinant chimera protein (RCP) vaccine using T cell epitope peptides identified from four Leishmania proteins is used as an exemplar of this method.


Assuntos
Vacinas contra Leishmaniose , Leishmaniose Visceral , Antígenos de Protozoários/genética , Quimera , Epitopos de Linfócito T , Humanos , Leishmania/genética , Leishmaniose Visceral/prevenção & controle , Peptídeos , Proteínas de Protozoários/genética , Linfócitos T , Vacinas Sintéticas/genética
4.
Methods Mol Biol ; 2410: 481-502, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34914064

RESUMO

Leishmaniases are neglected diseases caused by Leishmania parasites and affect millions of people worldwide. The induction of protective immunity against infection by some species of Leishmania has stimulated the development of vaccine candidates against the disease. In this chapter we describe protocols for immunizing mice with a recombinant chimera vaccine containing selected epitopes that specifically stimulate a Th1-type immune response. We describe protocols for challenging mice with live Leishmania parasite and for measuring parameters of the immune response to vaccination and parasite infection, including the production of cytokines, nitric oxide, and IgG antibodies, and the contribution of CD4+ and CD8+ T cells. We also provide protocols for isolating mouse organs for cell culture and for quantifying parasite loads in unvaccinated control animals and in vaccine-protected animals. These protocols can form the basis of immunological studies of candidate Leishmania vaccines in the mouse, as a step toward further vaccine development for human use.


Assuntos
Leishmania , Vacinas contra Leishmaniose , Leishmaniose , Animais , Linfócitos T CD8-Positivos/imunologia , Citocinas , Leishmaniose/prevenção & controle , Leishmaniose Visceral , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Protozoários , Vacinas Sintéticas
5.
J Mol Graph Model ; 110: 108039, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34736055

RESUMO

Leishmaniasis is a parasitic disease with frequent annual incidence. An important issue in chemotherapy is the emergence of resistance, toxicity and lack of cost-effectiveness within current drugs. Therefore, it is of utmost importance to design effective drugs against disease. Current contribution was devoted to the in-silico analysis of binding a few flavonoids/alkaloids to relevant leishmanial targets. Docking scores were used to prioritize acquired affinities and top ranked binders were subjected to subsequent 100-ns MD simulation in explicit water. Binding trajectories revealed the tightest interaction modes for two flavonoid molecules (acerosin and nevadensin) in the uracil DNA glycolase (UDG) active site. Acerosin showed less conformational changes whereas, nevadensin interacted stably during longer simulation time. Conserved interactions of Gln205 and His331 to acerosin indicated their dominant biological role in complex stability. No conserved residues were perceived for nevadensin interactions and a completely new and stable binding conformation could be retrieved after 12 ns simulation. Moreover; acerosin was subjected to DFT analysis for pairwise decomposition evaluations of interacted residues. Although primary mechanisms of action are yet to be discovered, UDG may be a promising target for developing antileishmanial flavonoids.


Assuntos
Antiprotozoários , Leishmania , Antiprotozoários/farmacologia , Domínio Catalítico , Simulação por Computador , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular
6.
Colloids Surf B Biointerfaces ; 209(Pt 1): 112169, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34752985

RESUMO

Two platforms based on reduced graphene oxide (rGO) functionalized with Pluronic® P123 (rGO-P123) and polyethyleneimine - PEI (rGO-PEI) polymers and loaded with amphotericin B (AmB) were fabricated and tested against Leishmania amazonensis, which can cause cutaneous and diffuse cutaneous leishmaniasis. The materials rGO-P123 and rGO-PEI were efficiently loaded with AmB - a polyene antibiotic - which resulted in rGO-P123-AmB (0.078 mg per mg of material) and rGO-PEI-AmB (0.086 mg per mg of material). Under near-infrared (NIR) light irradiation, the amount of AmB released from rGO-PEI-AmB at pH 5.0 and 7.4 doubled in comparison to AmB released in the absence of NIR light under identical conditions. It was accompanied by a photothermal effect. Otherwise, rGO-P123-AmB did not show a significant change in AmB released in the presence and absence of NIR light. Cytotoxicity studies in mammalian host macrophages revealed that rGO-PEI and rGO-PEI-AmB were nontoxic to the host cells, whereas rGO-123 and rGO-P123-AmB were very toxic, particularly the latter. Therefore, only rGO-PEI and rGO-PEI-AmB were tested against L. amazonensis promastigotes in the presence and absence of NIR light. In vitro antiproliferative effects revealed that rGO-PEI-AmB showed a more pronounced activity against the parasite than rGO-PEI, which was improved under NIR light irradiation. Scanning-transmission electron microscopy of L. amazonensis promastigotes after incubation with rGO-PEI or rGO-PEI-AmB suggested autophagic and necrotic cell death. Thus, the facile synthesis, high AmB loading capacity and good photothermal effect make the rGO-PEI-AmB platform a promising candidate for the topical treatment of cutaneous leishmaniasis.


Assuntos
Grafite , Leishmania , Anfotericina B/farmacologia , Animais , Óxidos , Terapia Fototérmica , Polímeros
7.
J Pharm Biomed Anal ; 207: 114402, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34634528

RESUMO

Miltefosine is the only oral drug approved for the treatment of various clinical presentations of the neglected parasitic disease leishmaniasis. In cutaneous leishmaniasis and post-kala-azar dermal leishmaniasis, Leishmania parasites reside and multiply in the dermis of the skin. As miltefosine is orally administered and this drug is currently studied for the treatment of these skin-related types of leishmaniasis, there is an urgent need for an accurate assay to determine actual miltefosine levels in human skin tissue to further optimize treatment regimens through target-site pharmacokinetic studies. We describe here the development and validation of a sensitive method to quantify miltefosine in 4-mm human skin biopsies utilizing high-performance liquid chromatography coupled to tandem mass spectrometry. After the skin tissues were homogenized overnight by enzymatic digestion using collagenase A, the skin homogenates were further processed by protein precipitation and phenyl-bonded solid phase extraction. Final extracts were injected onto a Gemini C18 column using alkaline eluent for separation and elution. Detection was performed by positive ion electrospray ionization followed by a quadrupole - linear ion trap mass spectrometer, using deuterated miltefosine as an internal standard. The method was validated over a linear calibration range of 4-1000 ng/mL (r2 ≥ 0.9996) using miltefosine spiked digestion solution for calibration and quality control samples. Validation parameters were all within internationally accepted criteria, including intra- and inter-assay accuracies and precisions within± 15% and ≤ 15% (within± 20% and ≤ 20% at the lower limit of quantitation). There was no significant matrix effect of the human skin tissue matrix and the recovery for miltefosine, and internal standard were comparable. Miltefosine in human skin tissue homogenates was stable during the homogenization incubation (37 °C,± 16 h) and after a minimum of 10 days of storage at - 20 °C after the homogenization process. With our assay we could successfully detect miltefosine in skin biopsies from patients with post-kala azar dermal leishmaniasis who were treated with this drug in Bangladesh.


Assuntos
Antiprotozoários , Leishmania , Preparações Farmacêuticas , Cromatografia Líquida de Alta Pressão , Humanos , Fosforilcolina/análogos & derivados , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
8.
Informe de LeishmaniasisOPS/CDE/VT/21-0019.
Monografia em Espanhol | PAHO-IRIS | ID: phr-55344

RESUMO

Este informe presenta un análisis detallado de los datos de las leishmaniasis en la Región de las Américas correspondientes al 2020 e incluye una serie de infográficos con datos específicos de las leishmaniasis cutánea y mucosa en los países endémicos. A raíz de la pandemia de COVID-19, las actividades de búsqueda activa, de detección temprana y de tratamiento de los casos, así como otras actividades de campo, se han reducido. Entre los retos que afronta la Región, destaca la necesidad de que los países retomen las actividades y avancen con el diagnóstico y el tratamiento de los casos de las distintas formas clínicas de la enfermedad. Además, es necesario identificar estrategias para el seguimiento y monitoreo de los casos, a fin de alcanzar el objetivo de tratar al menos a 90% de los pacientes diagnosticados.


Assuntos
Doenças Transmissíveis , Leishmaniose , Leishmaniose Cutânea , Leishmania , Psychodidae , Leishmaniose Mucocutânea , Pandemias , COVID-19
9.
PLoS One ; 16(12): e0261192, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34914742

RESUMO

BACKGROUND: The insecticide treated bed net (ITN) has been proven for malaria control. Evidence from systematic review also suggests benefits of ITN roll out in reducing the incidence of cutaneous leishmaniasis (CL) and other vector borne diseases. METHODS: Using a community-based cross-sectional study design, ITN use, factors associated with non-use of ITNs, and occurrence of sand flies were investigated in three communities with reported cases of CL in the Oti region of Ghana. RESULTS: A total of 587 households comprising 189 (32.2%), 200 (34.1%), and 198 (33.7%) households from Ashiabre, Keri, and Sibi Hilltop communities with de facto population of 3639 participated in this study. The proportion of households that owned at least one ITN was 97.1%. The number of households having at least one ITN for every two members was 386 (65.8%) and 3159 (86.8%) household population had access to ITN. The household population that slept in ITN the night before this survey was 2370 (65.1%). Lack of household access to ITN (AOR = 1.80; CI: 1.31, 2.47), having a family size of more than 10 members (AOR = 2.53; CI: 1.20, 4.24), having more than 10 rooms for sleeping in a household (AOR = 10.18; CI: 1.28, 81.00), having 2-4 screened windows (AOR = 1.49; CI: 1.00, 2.20), and having 8-10 screened windows (AOR = 3.57; CI: 1.25, 10.17) were significantly associated with increased odds of not sleeping in ITN the night before the survey. A total of 193 female sand flies were trapped from various locations within the study communities. CONCLUSIONS: Factors associated with ITN non-use such as lack of household access to ITN should be incorporated into future efforts to improve ITN use. Species of sand flies and their potential vectorial role in the study communities should also be investigated.


Assuntos
Mosquiteiros Tratados com Inseticida/estatística & dados numéricos , Leishmania/isolamento & purificação , Leishmaniose Cutânea/epidemiologia , Malária/complicações , Controle de Mosquitos/métodos , Mosquitos Vetores/parasitologia , Psychodidae/parasitologia , Adulto , Idoso , Animais , Estudos Transversais , Características da Família , Feminino , Gana/epidemiologia , Humanos , Leishmaniose Cutânea/parasitologia , Malária/parasitologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
PLoS Negl Trop Dis ; 15(12): e0010014, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34910720

RESUMO

Biting midges of genus Culicoides (Diptera: Ceratopogonidae) are the vectors of several pathogenic arboviruses and parasites of humans and animals. Several reports have suggested that biting midges might be a potential vector of Leishmania parasites. In this study, we screened for Leishmania and Trypanosoma DNA in biting midges collected from near the home of a leishmaniasis patient in Lamphun province, northern Thailand by using UV-CDC light traps. The identification of biting midge species was based on morphological characters and confirmed using the Cytochrome C oxidase subunit I (COI) gene. The detection of Leishmania and Trypanosoma DNA was performed by amplifying the internal transcribed spacer 1 (ITS1) and small subunit ribosomal RNA (SSU rRNA) genes, respectively. All the amplified PCR amplicons were cloned and sequenced. The collected 223 biting midges belonged to seven species (Culicoides mahasarakhamense, C. guttifer, C. innoxius, C. sumatrae, C. huffi, C. oxystoma, and C. palpifer). The dominant species found in this study was C. mahasarakhamense (47.53%). Leishmania martiniquensis DNA was detected in three samples of 106 specimens of C. mahasarakhamense tested indicating a field infection rate of 2.83%, which is comparable to reported rates in local phlebotomines. Moreover, we also detected Trypanosoma sp. DNA in one sample of C. huffi. To our knowledge, this is the first molecular detection of L. martiniquensis in C. mahasarakhamense as well as the first detection of avian Trypanosoma in C. huffi. Blood meal analysis of engorged specimens of C. mahasarakhamense, C. guttifer, and C. huffi revealed that all specimens had fed on avian, however, further studies of the host ranges of Culicoides are needed to gain a better insight of potential vectors of emerging leishmaniasis. Clarification of the vectors of these parasites is also important to provide tools to establish effective disease prevention and control programs in Thailand.


Assuntos
Ceratopogonidae/parasitologia , Insetos Vetores/parasitologia , Leishmania/genética , Trypanosoma/genética , Animais , Ceratopogonidae/anatomia & histologia , Ceratopogonidae/classificação , DNA de Protozoário/genética , Feminino , Especificidade de Hospedeiro , Humanos , Leishmania/isolamento & purificação , Leishmania/patogenicidade , Técnicas de Amplificação de Ácido Nucleico , Tailândia , Trypanosoma/isolamento & purificação , Trypanosoma/patogenicidade
11.
PLoS One ; 16(12): e0262158, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34972189

RESUMO

Leishmaniasis is a disease caused by the protozoan parasite Leishmania and is known to affect millions of individuals worldwide. In recent years, we have established the critical role played by Leishmania zinc-metalloprotease GP63 in the modulation of host macrophage signalling and functions, favouring its survival and progression within its host. Leishmania major lacking GP63 was reported to cause limited infection in mice, however, it is still unclear how GP63 may influence the innate inflammatory response and parasite survival in an in vivo context. Therefore, we were interested in analyzing the early innate inflammatory events upon Leishmania inoculation within mice and establish whether Leishmania GP63 influences this initial inflammatory response. Experimentally, L. major WT (L. majorWT), L. major GP63 knockout (L. majorKO), or L. major GP63 rescue (L. majorR) were intraperitoneally inoculated in mice and the inflammatory cells recruited were characterized microscopically and by flow cytometry (number and cell type), and their infection determined. Pro-inflammatory markers such as cytokines, chemokines, and extracellular vesicles (EVs, e.g. exosomes) were monitored and proteomic analysis was performed on exosome contents. Data obtained from this study suggest that Leishmania GP63 does not significantly influence the pathogen-induced inflammatory cell recruitment, but rather their activation status and effector function. Concordantly, internalization of promastigotes during early infection could be influenced by GP63 as fewer L. majorKO amastigotes were found within host cells and appear to maintain in host cells over time. Collectively this study provides a clear analysis of innate inflammatory events occurring during L. major infection and further establish the prominent role of the virulence factor GP63 to provide favourable conditions for host cell infection.


Assuntos
Leishmania major/metabolismo , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/parasitologia , Leishmaniose/imunologia , Leishmaniose/parasitologia , Metaloendopeptidases/química , Animais , Biologia Computacional , Exossomos/metabolismo , Feminino , Interações Hospedeiro-Parasita/fisiologia , Inflamação/imunologia , Inflamação/metabolismo , Leishmania , Metaloproteases/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Proteômica/métodos , RNA-Seq
12.
Proc Natl Acad Sci U S A ; 118(51)2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34903666

RESUMO

How genome instability is harnessed for fitness gain despite its potential deleterious effects is largely elusive. An ideal system to address this important open question is provided by the protozoan pathogen Leishmania, which exploits frequent variations in chromosome and gene copy number to regulate expression levels. Using ecological genomics and experimental evolution approaches, we provide evidence that Leishmania adaptation relies on epistatic interactions between functionally associated gene copy number variations in pathways driving fitness gain in a given environment. We further uncover posttranscriptional regulation as a key mechanism that compensates for deleterious gene dosage effects and provides phenotypic robustness to genetically heterogenous parasite populations. Finally, we correlate dynamic variations in small nucleolar RNA (snoRNA) gene dosage with changes in ribosomal RNA 2'-O-methylation and pseudouridylation, suggesting translational control as an additional layer of parasite adaptation. Leishmania genome instability is thus harnessed for fitness gain by genome-dependent variations in gene expression and genome-independent compensatory mechanisms. This allows for polyclonal adaptation and maintenance of genetic heterogeneity despite strong selective pressure. The epistatic adaptation described here needs to be considered in Leishmania epidemiology and biomarker discovery and may be relevant to other fast-evolving eukaryotic cells that exploit genome instability for adaptation, such as fungal pathogens or cancer.


Assuntos
Adaptação Fisiológica/genética , Epistasia Genética , Genoma de Protozoário , Instabilidade Genômica , Leishmania/genética , Dosagem de Genes , Aptidão Genética , Humanos , Leishmaniose/parasitologia
13.
Front Cell Infect Microbiol ; 11: 748738, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722338

RESUMO

Macrophage-Leishmania interactions are central to parasite growth and disease outcome. Macrophages have developed various strategies to fight invaders, including oxidative burst. While some microorganisms seem to survive and even thrive in an oxidative environment, others are susceptible and get killed. To counter oxidative stress, macrophages switch the expressions of cytoprotective and detoxifying enzymes, which are downstream targets of the nuclear factor erythroid 2-related factor 2 (Nrf2), to enhance cell survival. We have explored the transcription of NRF2 and of its target genes and compared the effect of the parasite on their transcription in bone marrow-derived macrophages (BMdMs) from Leishmania-resistant and Leishmania-susceptible mice. While heme oxygenase 1 (HO-1) transcription is independent of the genetic background, the transcription of glutathione reductase (Gsr) and of cysteine/glutamate exchange transporter (Slc7a11), involved in glutathione accumulation, was differentially regulated in BMdMs from both mouse strains. We also show that, except for HO-1, known to favor the survival of the parasite, the transcription of the selected genes, including Gsr, CD36, and catalase (CAT), was actively repressed, if not at all time points at least at the later ones, by the parasite, especially in Balb/c BMdMs. Consistent with these results, we found that the silencing of NRF2 in this study increases the survival and multiplication of the parasite.


Assuntos
Leishmania , Parasitos , Animais , Antioxidantes , Leishmania/genética , Macrófagos , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo
14.
Front Cell Infect Microbiol ; 11: 769933, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722348

RESUMO

Protozoans of the genus Leishmania are the causative agents of an important neglected tropical disease referred to as leishmaniasis. During their lifecycle, the parasites can colonize the alimentary tract of the sand fly vector and the parasitophorous vacuole of the mammalian host, differentiating into distinct stages. Motile promastigotes are found in the sand fly vector and are transmitted to the mammalian host during the insect blood meal. Once in the vertebrate host, the parasites differentiate into amastigotes and multiply inside macrophages. To successfully establish infection in mammalian hosts, Leishmania parasites exhibit various strategies to impair the microbicidal power of the host immune system. In this context, stage-specific class I nucleases play different and important roles related to parasite growth, survival and development. Promastigotes express 3'-nucleotidase/nuclease (3'-NT/NU), an ectoenzyme that can promote parasite escape from neutrophil extracellular traps (NET)-mediated death through extracellular DNA hydrolysis and increase Leishmania-macrophage interactions due to extracellular adenosine generation. Amastigotes express secreted nuclease activity during the course of human infection that may be involved in the purine salvage pathway and can mobilize extracellular nucleic acids available far from the parasite. Another nuclease expressed in amastigotes (P4/LmC1N) is located in the endoplasmic reticulum of the parasite and may be involved in mRNA stability and DNA repair. Homologs of this class I nuclease can induce protection against infection by eliciting a T helper 1-like immune response. These immunogenic properties render these nucleases good targets for the development of vaccines against leishmaniasis, mainly because amastigotes are the form responsible for the development and progression of the disease. The present review aims to present and discuss the roles played by different class I nucleases during the Leishmania lifecycle, especially regarding the establishment of mammalian host infection.


Assuntos
Armadilhas Extracelulares , Leishmania , Leishmaniose , Parasitos , Psychodidae , Animais , Humanos
15.
Zootaxa ; 5032(2): 275-282, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34811128

RESUMO

The Ja National Park, located in the Amazon, is the largest National Park of Brazil and still its insect fauna is barely known. Herein we describe two new species of Psychodinae, Alepia iy sp. nov. and Parasetomima timmirima sp. nov., and report 19 other species of Psychodidae, subfamilies Phlebotominae, Psychodinae and Trichomyiinae collected from this Conservation Unit. Micrommatos Quate Brown, represented by M. stephaniae Quate Brown, and Platyplastinx culmosus Quate Brown are recorded for the first time for Brazil. Among the collected phlebotomine sand fly species, three species have previously been implicated in transmission of Leishmania: Nyssomyia anduzei (Rozeboom), Psychodopygus ayrozai (Barretto Coutinho) and Trichophoromyia ubiquitalis (Mangabeira).


Assuntos
Leishmania , Psychodidae , Animais , Brasil , Insetos Vetores , Parques Recreativos
16.
Zootaxa ; 5057(2): 271-284, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34811209

RESUMO

Trichophoromyia brachipyga (Mangabeira) (Diptera: Psychodidae: Phlebotominae) is a widely distributed species that has been recently regarded as a putative vector of Leishmania (Viannia) lainsoni Silveira, Shaw, Braga Ishikawa in the Brazilian Amazon region. Currently, no immature stages of the genus Trichophoromyia Barretto have been morphologically described. The present study provided, for the first time, using a light microscopy morpho-taxonomical approach, the description of the egg, fourth-instar larva, and pupa of Th. brachipyga, with comparison of their morphological traits with other phlebotomine species, particularly those of the subtribe Psychodopygina, which is closely related.


Assuntos
Leishmania , Psychodidae , Animais , Insetos Vetores , Pupa
17.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 33(5): 452-456, 2021 Oct 27.
Artigo em Chinês | MEDLINE | ID: mdl-34791841

RESUMO

OBJECTIVE: To develop a fluorescent recombinase-aided isothermal amplification (RAA)-based nucleic acid assay for detection of Leshimania. METHODS: Specific primers and probes were designed targeting Leishmania internal transcribed spacer 1 (ITS1) gene for RAA assay, and a fluorescent RAA assay was developed for detection of Leishmania following screening of primer pairs and optimization of primer and probe concentrations. The sensitivity of RAA assay for detection of Leishmania was evaluated using recombinant plasmid containing Leishmania ITS1 gene sequences at different copies and Leshimania genomic DNA at different concentrations as templates, and the specificity of RAA assay for detection of Leishmania was evaluated using the genomic DNA of transfusion-transmitted parasites, including Babesia microti, Toxoplasma gondii, Plamodium vivax, P. ovale, P. falciparum, P. malariae, L. donovani and L. infantum. RESULTS: After the optimal primer pair was screened from 9 pairs of primer combinations, the final primer and probe concentrations were optimized as 0.3 µmol/L and 0.08 µmol/L, respectively. Nucleic acid detection of Leishmania was completed by the fluorescent RAA assay at an isothermal temperature of 39 °C within 20 min. Remarkable florescent signals were seen within 5 min following RAA detection of genomic DNA of L. donovani and L. infantum, and no cross-reactions were observed with B. microti, T. gondii, P. vivax, P. ovale, P. falciparum or P. malariae. The lowest limitation of detection of the fluorescent RAA assay was 10 copies/µL recombinant plasmid containing Leishmania ITS1 gene sequences and 1 fg/µL Leishmania genomic DNA. CONCLUSIONS: A rapid, simple, sensitive and specific fluorescent RAA assay is successfully developed for detection of L. donovani and L. infantum, which is effective for field screening of leishmaniasis.


Assuntos
Leishmania , Ácidos Nucleicos , Leishmania/genética , Técnicas de Amplificação de Ácido Nucleico , Recombinases , Sensibilidade e Especificidade
18.
Appl Microbiol Biotechnol ; 105(21-22): 8227-8240, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34625819

RESUMO

Leishmania is a complex disease caused by the protozoan parasites and transmitted by female phlebotomine sandfly. The disease affects some of the poorest people on earth with an estimated 700,000 to 1 million new cases annually. The current treatment for leishmaniasis is toxic, long, and limited, in view of the high resistance rate presented by the parasite, necessitating new perspectives for treatment. The discovery of new compounds with different targets can be a hope to make the treatment more efficient. Microbial metabolites and their structural analogues with enormous scaffold diversity and structural complexity have historically played a key role in drug discovery. We found thirty-nine research articles published between 1999 and 2021 in the scientific database (PubMed, Science Direct) describing microbes and their metabolites with activity against leishmanial parasites which is the focus of this review. KEY POINTS: • Leishmania affects the poorest regions of the globe • Current treatments for leishmaniasis are toxic and of limited efficacy • Microbial metabolites are potential sources of antileishmania drugs.


Assuntos
Antiprotozoários , Leishmania , Leishmaniose , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Descoberta de Drogas , Feminino , Humanos , Leishmaniose/tratamento farmacológico
19.
Parasitol Res ; 120(11): 3915-3923, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34626235

RESUMO

Canine leishmaniasis (CanL) is a zoonosis caused by protozoa of the genus Leishmania and remains an important public health concern in tropical areas. In Brazil, domestic dogs are considered the most relevant reservoir of the parasite and one of the main targets of the disease control actions. Considering this, we aimed herein to evaluate the CanL infection in different canine groups and distribution of cases in the state of Sergipe, an endemic region in Northeastern Brazil. The evaluated 467 animals were classified into four groups: hunting (n = 50), company (n = 64), guard (n = 140), and wandering (n = 213). Samples (blood, bone marrow, conjunctival swab, and lymph node aspirate) were collected from animals in nine municipalities of Sergipe. First, all animals were submitted to general and ophthalmic clinical examination. Next, they were tested serologically by TR-DPP®, and for the presence of Leishmania, amastigotes in samples of bone marrow, conjunctival swab, and lymph node aspirate were diagnosed by PCR and parasitological techniques. It was observed that 34.69% (162) of the evaluated dogs were seropositive. The highest rates of positivity were found in hunting 54% (27/50; OR = 3.52; p-value = 0.001) and guard dogs 42.14% (59/140; OR = 2.18; p-value = 0.01). Otherwise, the highest percentage of symptomatic dogs was observed in wandering animals (85%; OR = 9.63; p-value < 0.0001). The distribution of case analysis showed that the highest positivity rates occurred in inland municipalities situated in arid regions. Taken together, our data demonstrate that hunting and guard dogs are among the animals most exposed and affected by clinical manifestations of CanL, mainly in the inland municipalities of Sergipe State.


Assuntos
Doenças do Cão , Leishmania infantum , Leishmania , Leishmaniose Visceral , Leishmaniose , Animais , Brasil/epidemiologia , Doenças do Cão/epidemiologia , Cães , Leishmaniose/epidemiologia , Leishmaniose/veterinária , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/veterinária
20.
Front Cell Infect Microbiol ; 11: 687633, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660334

RESUMO

Cutaneous leishmaniasis is a zoonotic infectious disease broadly distributed worldwide, causing a range of diseases with clinical outcomes ranging from self-healing infections to chronic disfiguring disease. The effective immune response to this infection is yet to be more comprehensively understood and is fundamental for developing drugs and vaccines. Thus, we used experimental models of susceptibility (BALB/c) and partial resistance (C57BL/6) to Leishmania amazonensis infection to investigate the local profile of mediators involved in the development of cutaneous leishmaniasis. We found worse disease outcome in BALB/c mice than in C57BL/6 mice, with almost 15 times higher parasitic load, ulcerated lesion formation, and higher levels of IL-6 in infected paws. In contrast, C57BL/6 presented higher levels of IFN-γ and superoxide anion ( • O 2 - ) after 11 weeks of infection and no lesion ulcerations. A peak of local macrophages appeared after 24 h of infection in both of the studied mice strains, followed by another increase after 240 h, detected only in C57BL/6 mice. Regarding M1 and M2 macrophage phenotype markers [iNOS, MHC-II, CD206, and arginase-1 (Arg-1)], we found a pronounced increase in Arg-1 levels in BALB/c after 11 weeks of infection, whereas C57BL/6 showed an initial predomination of markers from both profiles, followed by an M2 predominance, coinciding with the second peak of macrophage infiltration, 240 h after the infection. Greater deposition of type III collagen and lesion resolution was also observed in C57BL/6 mice. The adoptive transfer of macrophages from C57BL/6 to infected BALB/c at the 11th week showed a reduction in both edema and the number of parasites at the lesion site, in addition to lower levels of Arg-1. Thus, C57BL/6 mice have a more effective response against L. amazonensis, based on a balance between inflammation and tissue repair, while BALB/c mice have an excessive Arg-1 production at late infection. The worst evolution seems to be influenced by recruitment of Arg-1 related macrophages, since the adoptive transfer of macrophages from C57BL/6 mice to BALB/c resulted in better outcomes, with lower levels of Arg-1.


Assuntos
Leishmania , Leishmaniose Cutânea , Animais , Arginase , Macrófagos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL
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