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1.
Eur J Protistol ; 77: 125760, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33340850

RESUMO

Protistan parasites have an undisputed global health impact. However, outside of a few key exceptions, e.g. the agent of malaria, most of these infectious agents are neglected as important health threats. The Symposium entitled "Free-living amoebae and neglected pathogenic protozoa: health emergency signals?" held at the European Congress of Protistology in Rome, July 2019, brought together researchers addressing scientific and clinical questions about some of these fascinating organisms. Topics presented included the molecular basis of pathogenicity in Acanthamoeba; genomics of Naegleria fowleri; and epidemiology of poorly diagnosed enteric protistan species, including Giardia, Cryptosporidium, Blastocystis, Dientamoeba. The Symposium aim was to excite the audience about the opportunities and challenges of research in these underexplored organisms and to underline the public health implications of currently under-appreciated protistan infections. The major take home message is that any knowledge that we gain about these organisms will allow us to better address them, in terms of monitoring and treatment, as sources of future health emergencies.


Assuntos
Amoeba/patogenicidade , Eucariotos/patogenicidade , Saúde Global , Humanos , Infecções por Protozoários/parasitologia , Virulência/genética
2.
Parasitol Res ; 119(10): 3503-3515, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32772176

RESUMO

Malaria, babesiosis, trypanosomosis, and leishmaniasis are some of the most life-threatening parasites, but the range of drugs to treat them is limited. An effective, safe, and low-cost drug with a large activity spectrum is urgently needed. For this purpose, an aryl amino alcohol derivative called Alsinol was resynthesized, screened in silico, and tested against Plasmodium, Babesia, Trypanosoma, and Leishmania. In silico Alsinol follows the Lipinski and Ghose rules. In vitro it had schizontocidal activity against Plasmodium falciparum and was able to inhibit gametocytogenesis; it was particularly active against late gametocytes. In malaria-infected mice, it showed a dose-dependent activity similar to chloroquine. It demonstrated a similar level of activity to reference compounds against Babesia divergens, and against promastigotes, and amastigotes stages of Leishmania in vitro. It inhibited the in vitro growth of two African animal strains of Trypanosoma but was ineffective in vivo in our experimental conditions. It showed moderate toxicity in J774A1 and Vero cell models. The study demonstrated that Alsinol has a large spectrum of activity and is potentially affordable to produce. Nevertheless, challenges remain in the process of scaling up synthesis, creating a suitable clinical formulation, and determining the safety margin in preclinical models.


Assuntos
Amino Álcoois/farmacologia , Antiprotozoários/farmacologia , Amino Álcoois/síntese química , Amino Álcoois/química , Animais , Antiprotozoários/síntese química , Antiprotozoários/química , Babesia/efeitos dos fármacos , Babesia/crescimento & desenvolvimento , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Modelos Animais de Doenças , Leishmania/efeitos dos fármacos , Leishmania/crescimento & desenvolvimento , Estágios do Ciclo de Vida/efeitos dos fármacos , Camundongos , Plasmodium/efeitos dos fármacos , Plasmodium/crescimento & desenvolvimento , Infecções por Protozoários/tratamento farmacológico , Infecções por Protozoários/parasitologia , Resultado do Tratamento , Trypanosoma/efeitos dos fármacos , Trypanosoma/crescimento & desenvolvimento , Células Vero
3.
BMC Infect Dis ; 20(1): 350, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32414337

RESUMO

BACKGROUND: Pediatric diarrhea caused by a range of pathogens, including intestinal parasites, is one of main causes of death among children under 5 years of age. The distribution of these parasitic infections overlaps in many environmental, socioeconomic and epidemiological settings. Their distribution and prevalence varies from region to region. In the current study, we assess the prevalence of intestinal parasites among pediatric patients with syndromic diarrheal disease living in Franceville, Gabon. METHODS: A cross-sectional study conducted in the Amissa Bongo Regional Hospital and Chinese-Gabonese Friendship Hospital in Franceville, between November 2016 and August 2017, enrolled a total of 100 diarrheic children between 0 and 180 months of age. Parasite detection in stool samples was performed using molecular diagnostic by PCR. Difference in means were tested by Student's t test and ANOVA while principal component analysis was used to determine the correlation between parasite distributions and age groups. RESULTS: The overall prevalence of intestinal parasite infection was 61% (61/100). Hymenolepis sp and Cryptosporidium hominis/parvum were the most common parasites (31 and 19%, respectively), followed by Encephalitozoon intestinalis (15%), Trichuris trichiura (4%), Dientamoeba fragilis (4%), and Enterocytozoon bieneusi (2%). The polyparasitism rate was 19.7%, with 83.3% double and 16.7% triple infections. Protozoan infections (66.7%) were more prevalent than helminths infections (33.3%). Seasonal association of the circulation of intestinal parasite was statistically significant (p = 0.03). Correlations between different parasites was also observed. CONCLUSION: The prevalence of intestinal parasitic infections is highest in diarrheic pediatric children. The prevalence of parasitic infections indicates that protozoa and helminths are the most common parasites in the Franceville environment. This study reinforces the importance of routine examination of diarrheic stool samples for the diagnostic of intestinal parasites. Further analyses are required to better understand the local epidemiology and risk factors associated with the transmission of intestinal parasites in Franceville, Gabon. KEYSWORDS: diarrhea, children, intestinal parasitic infections, molecular diagnostic, Franceville, Gabon.


Assuntos
Diarreia/parasitologia , Helmintíase/epidemiologia , Enteropatias Parasitárias/epidemiologia , Infecções por Protozoários/epidemiologia , Animais , Pré-Escolar , Estudos Transversais , Criptosporidiose/epidemiologia , Criptosporidiose/parasitologia , Cryptosporidium/genética , Diarreia/epidemiologia , Fezes/parasitologia , Feminino , Gabão/epidemiologia , Humanos , Lactente , Masculino , Reação em Cadeia da Polimerase , Prevalência , Infecções por Protozoários/parasitologia , Fatores de Risco
4.
Trends Parasitol ; 36(5): 459-472, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32298633

RESUMO

Inflammasomes are cytosolic complexes that assemble in response to cellular stress or upon sensing microbial molecules, culminating in cytokine processing and an inflammatory form of cell death called pyroptosis. Inflammasomes are usually composed of a sensor molecule, an adaptor protein, and an inflammatory caspase, such as Caspase-1, which cleaves and activates multiple substrates, including Gasdermin-D, pro-IL-1ß, and pro-IL-18. Ultimately, inflammasome activation promotes inflammation and restriction of the microbial infection. In recent years, many studies have addressed the role of inflammasomes during fungal, bacterial, viral, and parasitic diseases, revealing sophisticated aspects of the host-pathogen interaction. In this review, we summarize recent advances on inflammasome activation in response to intracellular parasites, including Leishmania spp., Plasmodium spp., Trypanosoma cruzi, and Toxoplasma gondii.


Assuntos
Interações Hospedeiro-Patógeno/imunologia , Inflamassomos/imunologia , Infecções por Protozoários/imunologia , Animais , Eucariotos/imunologia , Humanos , Leishmaniose/imunologia , Leishmaniose/parasitologia , Malária/imunologia , Malária/parasitologia , Infecções por Protozoários/parasitologia , Pesquisa/tendências , Toxoplasmose/imunologia , Toxoplasmose/parasitologia , Tripanossomíase/imunologia , Tripanossomíase/parasitologia
6.
Int J Mol Sci ; 21(4)2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32054133

RESUMO

Dictyostelium discoideum is gaining increasing attention as a model organism for the study of calcium binding and calmodulin function in basic biological events as well as human diseases. After a short overview of calcium-binding proteins, the structure of Dictyostelium calmodulin and the conformational changes effected by calcium ion binding to its four EF hands are compared to its human counterpart, emphasizing the highly conserved nature of this central regulatory protein. The calcium-dependent and -independent motifs involved in calmodulin binding to target proteins are discussed with examples of the diversity of calmodulin binding proteins that have been studied in this amoebozoan. The methods used to identify and characterize calmodulin binding proteins is covered followed by the ways Dictyostelium is currently being used as a system to study several neurodegenerative diseases and how it could serve as a model for studying calmodulinopathies such as those associated with specific types of heart arrythmia. Because of its rapid developmental cycles, its genetic tractability, and a richly endowed stock center, Dictyostelium is in a position to become a leader in the field of calmodulin research.


Assuntos
Proteínas de Ligação a Calmodulina/metabolismo , Calmodulina/metabolismo , Dictyostelium/metabolismo , Proteínas de Protozoários/metabolismo , Sítios de Ligação , Cálcio/metabolismo , Sinalização do Cálcio , Calmodulina/química , Proteínas de Ligação a Calmodulina/química , Dictyostelium/química , Motivos EF Hand , Humanos , Modelos Moleculares , Ligação Proteica , Infecções por Protozoários/parasitologia , Proteínas de Protozoários/química
7.
Sci Rep ; 10(1): 2531, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054950

RESUMO

As critical primary producers and recyclers of organic matter, the diversity of marine protists has been extensively explored by high-throughput barcode sequencing. However, classification of short metabarcoding sequences into traditional taxonomic units is not trivial, especially for lineages mainly known by their genetic fingerprints. This is the case for the widespread Amoebophrya ceratii species complex, parasites of their dinoflagellate congeners. We used genetic and phenotypic characters, applied to 119 Amoebophrya individuals sampled from the same geographic area, to construct practical guidelines for species delineation that could be applied in DNA/RNA based diversity analyses. Based on the internal transcribed spacer (ITS) regions, ITS2 compensatory base changes (CBC) and genome k-mer comparisons, we unambiguously defined eight cryptic species among closely related ribotypes that differed by less than 97% sequence identity in their SSU rDNA. We then followed the genetic signatures of these parasitic species during a three-year survey of Alexandrium minutum blooms. We showed that these cryptic Amoebophrya species co-occurred and shared the same ecological niche. We also observed a maximal ecological fitness for parasites having narrow to intermediate host ranges, reflecting a high cost for infecting a broader host range. This study suggests that a complete taxonomic revision of these parasitic dinoflagellates is long overdue to understand their diversity and ecological role in the marine plankton.


Assuntos
Dinoflagelados/genética , DNA Ribossômico/genética , Dinoflagelados/classificação , Óperon , Fenótipo , Infecções por Protozoários/parasitologia , Ribossomos/genética , Ribotipagem , Sequenciamento Completo do Genoma
8.
BMC Infect Dis ; 20(1): 12, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906872

RESUMO

BACKGROUND: Determination of the prevalence and distribution pattern of intestinal parasites is a fundamental step to set up an effective control program to improve the health status. This study aimed to determine the prevalence of intestinal parasitic infections and associated risk factors among inhabitants of Rudbar-e Jonub county, southeast of Kerman province, southeastern Iran. METHODS: In this cross-sectional study, 861 stool specimens were collected from inhabitants of Rudbar-e Jonub county through a multistage cluster sampling method in 2018. The collected specimens were examined by parasitological methods including, direct wet-mounting (for the fresh specimens with a watery consistency), formalin-ethyl acetate sedimentation and agar plate culture. RESULTS: The prevalence of intestinal parasites was 34.2% (95% CI 30.1 to 38.2). The prevalence of protozoan parasites 32.3% (95% CI 28.4 to 36.5) was significantly higher than helminthic parasites 3.2% (95% CI 2.1 to 4.7). Blastocystis sp. (13.3%), Entamoeba coli (11.4%) and Giardia lamblia (10.6%) as protozoan parasite and Hymenolepis nana (2.4%) as helminthic parasite were the most common detected intestinal parasites in the study. Entamoeba histolytica/dispar (1.5%), Iodamoeba bütschlii (1.0%), Chilomastix mesnili (0.5%), Entamoeba hartmanni (0.4%), Enterobius vermicularis (0.3%) and Ascaris lambercoides (0.3%) were other detected parasites. Multiple logistic regression revealed a significant association of intestinal parasitic infections with source of drinking water and residency status (rural/urban). Multiple infections with 2 or 3 parasitic agents constituted 22.7% of 295 infected cases. CONCLUSIONS: This study revealed a high prevalence of intestinal protozoan infections among inhabitants of Rudbar-e Jonub county. Intestinal parasites especially protozoans remain a challenging public health problem wherever sanitation and health measures are limited in Iran.


Assuntos
Enteropatias Parasitárias/epidemiologia , Adolescente , Adulto , Animais , Criança , Estudos Transversais , Fezes/parasitologia , Feminino , Helmintíase/epidemiologia , Helmintíase/parasitologia , Humanos , Enteropatias Parasitárias/parasitologia , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Parasitos/classificação , Prevalência , Infecções por Protozoários/epidemiologia , Infecções por Protozoários/parasitologia , Fatores de Risco , Adulto Jovem
9.
Trends Parasitol ; 36(3): 232-235, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31982329

RESUMO

Histomonas meleagridis is an extracellular protozoan parasite and the aetiological agent of histomonosis, an important poultry disease whose impact is greatly accentuated by inaccessibility of any treatment. A special feature of the parasite is its intricate interplay with bacteria in vitro and in vivo, the focus of this article.


Assuntos
Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/parasitologia , Aves Domésticas/microbiologia , Aves Domésticas/parasitologia , Infecções por Protozoários/microbiologia , Infecções por Protozoários/parasitologia , Trichomonadida/microbiologia , Animais , Fenômenos Fisiológicos Bacterianos , Simbiose
10.
Parasitology ; 147(2): 225-230, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31559930

RESUMO

We investigated intestinal trichomonads in western lowland gorillas, central chimpanzees and humans cohabiting the forest ecosystem of Dzanga-Sangha Protected Area in Central African Republic, using the internal transcribed spacer (ITS) region and SSU rRNA gene sequences. Trichomonads belonging to the genus Tetratrichomonas were detected in 23% of the faecal samples and in all host species. Different hosts were infected with different genotypes of Tetratrichomonas. In chimpanzees, we detected tetratrichomonads from 'novel lineage 2', which was previously reported mostly in captive and wild chimpanzees. In gorillas, we found two different genotypes of Tetratrichomonas. The ITS region sequences of the more frequent genotype were identical to the sequence found in a faecal sample of a wild western lowland gorilla from Cameroon. Sequences of the second genotype from gorillas were almost identical to sequences previously obtained from an anorexic French woman. We provide the first report of the presence of intestinal tetratrichomonads in asymptomatic, apparently healthy humans. Human tetratrichomonads belonged to the lineage 7, which was previously reported in domestic and wild pigs and a domestic horse. Our findings suggest that the ecology and spatial overlap among hominids in the tropical forest ecosystem has not resulted in exchange of intestinal trichomonads among these hosts.


Assuntos
Doenças dos Símios Antropoides/parasitologia , Gorilla gorilla/parasitologia , Pan troglodytes/parasitologia , Infecções Protozoárias em Animais/parasitologia , Infecções por Protozoários/parasitologia , Trichomonadida/classificação , Animais , Doenças dos Símios Antropoides/epidemiologia , República Centro-Africana/epidemiologia , Fezes/parasitologia , Especificidade de Hospedeiro , Humanos , Filogenia , Infecções por Protozoários/epidemiologia , Infecções Protozoárias em Animais/epidemiologia
11.
Infect Dis (Lond) ; 52(2): 87-96, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31656115

RESUMO

Background: Nucleic acid-based methods are increasingly used for screening of gastrointestinal parasites. Microscopy is still used and Swedish routine protocol consists of formalin ethyl-acetate concentration and do not include screening for trophozoites or Cryptosporidium spp. This study aimed to compare detection with the Swedish routine microscopy method to an extended method that includes screening for trophozoites and Cryptosporidium. Furthermore, we also developed a method for DNA recovery from SAF-fixed faecal samples and compared the real-time PCR detection of Giardia intestinalis, Dientamoeba fragilis, Cryptosporidium spp., Entamoeba histolytica and Entamoeba dispar from SAF-fixed and unpreserved faecal samples. PCR results were then compared with microscopy results.Methods: SAF-fixed and unpreserved faecal samples from 1000 patients at the Clinical microbiology laboratory in Region Jönköping County, Sweden, were included. Samples were analysed with routine formalin ethyl-acetate concentration, wet mounts from both concentrated and unconcentrated samples, Ziehl-Neelsen staining on patients with certain symptoms and real-time PCR.Results: We found a significant higher detection rate of parasites with the extended microscopy method compared to the Swedish routine microscopy method when SAF-fixed samples were used. The detection rate with real-time PCR in SAF-fixed samples was equal to the detection rate in unpreserved samples. There was no significant difference in detection comparing extended microscopy and real-time PCR.Conclusion: In conclusion, this study showed that the extended microscopy method increased detection of intestinal protozoa with detection of both trophozoites and Cryptosporidium spp. We also showed that SAF-fixative can be used for detection of parasite-DNA with real-time PCR.


Assuntos
DNA de Protozoário , Fezes/parasitologia , Tipagem Molecular/métodos , Parasitologia/métodos , Infecções por Protozoários , Ácido Acético/química , DNA de Protozoário/análise , DNA de Protozoário/genética , Dientamoeba/genética , Dientamoeba/isolamento & purificação , Entamoeba histolytica/genética , Entamoeba histolytica/isolamento & purificação , Formaldeído/química , Giardia lamblia/genética , Giardia lamblia/isolamento & purificação , Humanos , Microscopia , Infecções por Protozoários/diagnóstico , Infecções por Protozoários/genética , Infecções por Protozoários/parasitologia , Acetato de Sódio/química , Suécia
12.
Biomed Pharmacother ; 130: 110624, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33503761

RESUMO

Australian tea tree (Melaleuca alternifolia) oil (TTO) and its monoterpene constituents such as terpinen-4-ol (T4O), 1,8-cineole, limonene, p-cymene, and α-terpinene have been shown to be effective in controlling a wide range of parasitic infections. The anti-parasitic effects of these compounds are mainly due to their anti-histamine and anti-acetylcholinesterase activities as well as their ability to modulate host inflammatory responses. This review attempts to summarize recent advances in the uses of TTO and its 15 major monoterpene constituents in treating parasitic infections in both humans and animals. Activities against parasitic protozoans (Plasmodium falciparum, Leishmania spp., Trypanosoma spp., Acanthamoeba castellanii, Trichomonas vaginalis, Eimeria, and Ichthyophthirius multifiliis), nematodes (Haemonchus contortus and Anisakis simplex), cestode (Echinococcus ortleppi), and monogeneans (Gasterosteus spp. and Dactylogyrus minutus) have been reported, showing good potentials in treating parasitic infections. Further studies are necessary for developing anti-parasite therapies using TTO or its monoterpenes constituents.


Assuntos
Anti-Infecciosos Locais/farmacologia , Anti-Infecciosos Locais/uso terapêutico , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Helmintíase/tratamento farmacológico , Monoterpenos/farmacologia , Monoterpenos/uso terapêutico , Infecções por Protozoários/tratamento farmacológico , Óleo de Melaleuca/farmacologia , Óleo de Melaleuca/uso terapêutico , Animais , Anti-Infecciosos Locais/química , Helmintíase/parasitologia , Humanos , Melaleuca/química , Monoterpenos/química , Infecções por Protozoários/parasitologia , Óleo de Melaleuca/química
13.
Rev. bras. parasitol. vet ; 28(4): 779-785, Oct.-Dec. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1057995

RESUMO

Abstract A free-living, adult male maned wolf (Chrysocyon brachyurus) was referred to the Governador "Laudo Natel" - FCAV/Unesp veterinary hospital after being found with skin lesions and a fracture on the right pelvic limb, which had to be amputated due to compromised integrity. Around 20 days later, bilateral accentuated swollen on humerus-radius-ulna articulation was observed. The synovial liquid was drained and sent to the laboratory for synovial cytology with Rosenfeld staining that revealed predominantly degenerated neutrophils with karyolytic chromatin associated with intracellular inclusions suggestive of Hepatozoon sp. gametocytes. Blood and synovial liquid samples were submitted to molecular analysis, aiming to amplify the Hepatozoon spp. 18S rRNA gene fragment. Despite the positioning of the found Hepatozoon sequence together with Hepatozoon canis previously detected in domestic carnivores, the BLAST analysis showed only 98% identity with H. canis. To the best of the authors' knowledge, this is the first time a Hepatozoon was detected in the synovial liquid by clinical pathology and molecular analyses.


Resumo Um lobo guará (Chrysocyon brachyurus) adulto, macho, de vida livre foi encaminhado para atendimento no hospital veterinário Governador "Laudo Natel" - FCAV/Unesp após ser encontrado com lesões de pele e fratura em membro pélvico direito, sendo amputado devido a comprometimento da integridade do membro. Aproximadamente 20 dias após a chegada ao hospital, foi notado acentuado aumento de volume bilateral em região de articulação úmero-rádio-ulnar. O líquido sinovial foi drenado e enviado para análise citológica com coloração de Rosenfeld, revelando a presença de neutrófilos degenerados com cromatina cariolítica associados a inclusões intracelulares sugestivas de gametócitos de Hepatozoon sp. Amostras de sangue e líquido sinovial foram submetidas a análises moleculares visando amplificar um fragmento do gene 18S rRNA de Hepatozoon spp. Apesar da sequência de Hepatozoon detectada se posicionar filogeneticamente no mesmo clado que H. canis previamente detectado em carnívoros domésticos, o resultado da análise do BLAST mostrou somente 98% de identidade com H. canis. De acordo com o conhecimento dos autores, esta é a primeira vez que Hepatozoon foi detectado no líquido sinovial por meio de patologia clínica e análises moleculares.


Assuntos
Animais , Masculino , Infecções por Protozoários/parasitologia , Líquido Sinovial/parasitologia , Apicomplexa/genética , Canidae/parasitologia , Filogenia , Brasil , RNA Ribossômico 18S/genética , Apicomplexa/isolamento & purificação , Achados Incidentais
14.
Expert Opin Ther Targets ; 23(11): 903-914, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31679410

RESUMO

Introduction: The proteasome is a multi-subunit enzyme complex responsible for the turnover of short-lived, abnormal or damaged proteins in eukaryotic cells. As organisms that undergo rapid growth and cell division, protozoan parasites exist on the knife-edge of proteotoxic catastrophe and thus rely heavily on their protein quality control machinery for survival. Because of this, the proteasome has recently emerged as a desirable drug target.Area covered: This review focuses on efforts to identify protozoan parasite-specific proteasome inhibitors using substrate profiling, library screening, and in vitro evolution of resistance approaches to inform medicinal chemistry. Targeting the parasite's 20S proteasome chymotrypsin-like (ß5) activity and selectively inhibiting protein turnover in parasites compared to human cells are critical properties of potent, selective inhibitors.Expert opinion: Proteasome inhibitors have the potential for rapid action against all stages, all species and all strains of plasmodium and kinetoplastid parasites. Given the high level of conservation of proteasome active sites in eukaryotes, an important challenge is achieving inhibitors that show sufficient selectivity while maintaining properties consistent with drug development.


Assuntos
Antiprotozoários/farmacologia , Inibidores de Proteassoma/farmacologia , Infecções por Protozoários/tratamento farmacológico , Animais , Desenvolvimento de Medicamentos , Humanos , Parasitos/isolamento & purificação , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Infecções por Protozoários/parasitologia
15.
Int J Mol Sci ; 20(23)2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31775392

RESUMO

Obligate protozoan parasites of the kinetoplastids and apicomplexa infect human cells to complete their life cycles. Some of the members of these groups of parasites develop in at least two systems, the human host and the insect vector. Survival under the varied physiological conditions associated with the human host and in the arthropod vectors requires the parasites to modulate their metabolic complement in order to meet the prevailing conditions. One of the key features of these parasites essential for their survival and host infectivity is timely expression of various proteins. Even more importantly is the need to keep their proteome functional by maintaining its functional capabilities in the wake of physiological changes and host immune responses. For this reason, molecular chaperones (also called heat shock proteins)-whose role is to facilitate proteostasis-play an important role in the survival of these parasites. Heat shock protein 90 (Hsp90) and Hsp70 are prominent molecular chaperones that are generally induced in response to physiological stress. Both Hsp90 and Hsp70 members are functionally regulated by nucleotides. In addition, Hsp70 and Hsp90 cooperate to facilitate folding of some key proteins implicated in cellular development. In addition, Hsp90 and Hsp70 individually interact with other accessory proteins (co-chaperones) that regulate their functions. The dependency of these proteins on nucleotide for their chaperone function presents an Achille's heel, as inhibitors that mimic ATP are amongst potential therapeutic agents targeting their function in obligate intracellular human parasites. Most of the promising small molecule inhibitors of parasitic heat shock proteins are either antibiotics or anticancer agents, whose repurposing against parasitic infections holds prospects. Both cancer cells and obligate human parasites depend upon a robust protein quality control system to ensure their survival, and hence, both employ a competent heat shock machinery to this end. Furthermore, some inhibitors that target chaperone and co-chaperone networks also offer promising prospects as antiparasitic agents. The current review highlights the progress made so far in design and application of small molecule inhibitors against obligate intracellular human parasites of the kinetoplastida and apicomplexan kingdoms.


Assuntos
Apicomplexa/efeitos dos fármacos , Infecções por Euglenozoa/tratamento farmacológico , Proteínas de Choque Térmico/antagonistas & inibidores , Kinetoplastida/efeitos dos fármacos , Proteostase/efeitos dos fármacos , Infecções por Protozoários/tratamento farmacológico , Bibliotecas de Moléculas Pequenas/farmacologia , Infecções por Euglenozoa/parasitologia , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Infecções por Protozoários/parasitologia
16.
Int J Mol Sci ; 20(22)2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31731801

RESUMO

Protozoan diseases continue to be a worldwide social and economic health problem. Increased drug resistance, emerging cross resistance, and lack of new drugs with novel mechanisms of action significantly reduce the effectiveness of current antiprotozoal therapies. While drug resistance associated to anti-infective agents is a reality, society seems to remain unaware of its proportions and consequences. Parasites usually develops ingenious and innovative mechanisms to achieve drug resistance, which requires more research and investment to fight it. In this review, drug resistance developed by protozoan parasites Plasmodium, Leishmania, and Trypanosoma will be discussed.


Assuntos
Antiprotozoários/uso terapêutico , Plasmodium/patogenicidade , Infecções por Protozoários/tratamento farmacológico , Animais , Humanos , Leishmania/efeitos dos fármacos , Leishmania/patogenicidade , Malária/tratamento farmacológico , Malária/fisiopatologia , Plasmodium/efeitos dos fármacos , Infecções por Protozoários/parasitologia
17.
Genome Med ; 11(1): 63, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640748

RESUMO

A major advance in antimalarial drug discovery has been the shift towards cell-based phenotypic screening, with notable progress in the screening of compounds against the asexual blood stage, liver stage, and gametocytes. A primary method for drug target deconvolution in Plasmodium falciparum is in vitro evolution of compound-resistant parasites followed by whole-genome scans. Several of the most promising antimalarial drug targets, such as translation elongation factor 2 (eEF2) and phenylalanine tRNA synthetase (PheRS), have been identified or confirmed using this method. One drawback of this method is that if a mutated gene is uncharacterized, a substantial effort may be required to determine whether it is a drug target, a drug resistance gene, or if the mutation is merely a background mutation. Thus, the availability of high-throughput, functional genomic datasets can greatly assist with target deconvolution. Studies mapping genome-wide essentiality in P. falciparum or performing transcriptional profiling of the host and parasite during liver-stage infection with P. berghei have identified potentially druggable pathways. Advances in mapping the epigenomic regulation of the malaria parasite genome have also enabled the identification of key processes involved in parasite development. In addition, the examination of the host genome during infection has identified novel gene candidates associated with susceptibility to severe malaria. Here, we review recent studies that have used omics-based methods to identify novel targets for interventions against protozoan parasites, focusing on malaria, and we highlight the advantages and limitations of the approaches used. These approaches have also been extended to other protozoan pathogens, including Toxoplasma, Trypanosoma, and Leishmania spp., and these studies highlight how drug discovery efforts against these pathogens benefit from the utilization of diverse omics-based methods to identify promising drug targets.


Assuntos
Antimaláricos/farmacologia , Descoberta de Drogas , Malária Falciparum/tratamento farmacológico , Terapia de Alvo Molecular , Plasmodium falciparum/efeitos dos fármacos , Infecções por Protozoários/tratamento farmacológico , Animais , Epigenômica , Genoma de Protozoário , Genômica , Humanos , Malária Falciparum/parasitologia , Plasmodium falciparum/genética , Plasmodium falciparum/isolamento & purificação , Proteômica , Infecções por Protozoários/parasitologia , Transcriptoma
18.
PLoS One ; 14(10): e0221190, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31589618

RESUMO

BACKGROUND: Intestinal parasitic infection affects 3.5 billion people in the world and mostly affecting the low socio-economic groups. The objectives of this research works were to estimate the prevalence and determinants of intestinal parasitic infection among family members of known intestinal parasite infected patients. METHODS AND MATERIALS: A comparative cross-sectional study design was implemented in the urban and rural settings of Mecha district. The data were collected from August 2017toMarch 2019 from intestinal parasite infected patient household members. Epi-info software was used to calculate the sample size, 4531 household members were estimated to be included. Data were collected using interview technique, and collecting stool samples from each household contact of intestinal parasite patients. Descriptive statistics were used to estimate the prevalence of intestinal parasites among known contacts of intestinal parasite patients/family members. Binary logistic regression was used to identify the determinant factors of intestinal parasitic infection among family members. RESULTS: The prevalence of intestinal parasite among household contacts of intestinal parasite-infected family members was 86.14% [95% CI: 86.14% - 87.15%]. Hookworm infection was the predominant type of infection (18.8%). Intestinal parasitic infection was associated with sex, environmental sanitation, overcrowding, personal hygiene, residence, substandard house, role in the household, source of light for the house, trimmed fingernails, family size, regular handwashing practice. Protozoa infection was associated with habit of ingesting raw vegetable, playing with domestic animals, water source and the presence of household water filtering materials. CONCLUSION: High prevalence of intestinal parasitic infection was observed among household contacts of primary cases.


Assuntos
Infecções por Uncinaria , Enteropatias Parasitárias , Infecções por Protozoários , População Rural , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Etiópia/epidemiologia , Características da Família , Feminino , Infecções por Uncinaria/epidemiologia , Infecções por Uncinaria/parasitologia , Humanos , Lactente , Recém-Nascido , Enteropatias Parasitárias/epidemiologia , Enteropatias Parasitárias/parasitologia , Masculino , Pessoa de Meia-Idade , Prevalência , Infecções por Protozoários/epidemiologia , Infecções por Protozoários/parasitologia , Saneamento
19.
BMC Res Notes ; 12(1): 697, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653235

RESUMO

OBJECTIVE: Intestinal parasites are present throughout the world in varying degrees of prevalence due to many factors. The aim of this study was to determine the 5-year trend prevalence of intestinal prevalence among patients who had been suspected for intestinal parasite infections. A retrospective study was conducted from 2009 to 2013 at Poly Health Center Gondar, Northwest Ethiopia. Samples were examined using direct saline wet mount methods. Statistical analysis was done using SPSS version 20 software and a P-value of < 0.05 was considered statistically significant. The results were presented in tables and graphs. RESULTS: During the study period, a total of 13,329 stool samples were requested for intestinal parasite diagnose and 5510 (41.3%) laboratory-confirmed cases were reported with a fluctuating trend. Ten different parasites were reported in each year with Entamoeba histolytica/dispar (16.8%) being the predominant parasite followed by Giardia lamblia (11.4%) and Ascaris lumbricoides (6.7%). Both males (49%) and females (51%) were equally affected (P = 0.14). The intestinal parasite was reported in all age groups in the area but the highest and the lowest prevalence were reported in age groups of 20-29 years and 40-49 years, respectively (26.5% vs 6.4%) (P < 0.001).


Assuntos
Fezes/parasitologia , Instalações de Saúde , Enteropatias Parasitárias/parasitologia , Infecções por Protozoários/parasitologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Ascaris lumbricoides/fisiologia , Criança , Pré-Escolar , Entamoeba histolytica/fisiologia , Etiópia/epidemiologia , Feminino , Giardia lamblia/fisiologia , Humanos , Lactente , Enteropatias Parasitárias/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Infecções por Protozoários/epidemiologia , Estudos Retrospectivos , Adulto Jovem
20.
Rev Bras Parasitol Vet ; 28(4): 779-785, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31483033

RESUMO

A free-living, adult male maned wolf (Chrysocyon brachyurus) was referred to the Governador "Laudo Natel" - FCAV/Unesp veterinary hospital after being found with skin lesions and a fracture on the right pelvic limb, which had to be amputated due to compromised integrity. Around 20 days later, bilateral accentuated swollen on humerus-radius-ulna articulation was observed. The synovial liquid was drained and sent to the laboratory for synovial cytology with Rosenfeld staining that revealed predominantly degenerated neutrophils with karyolytic chromatin associated with intracellular inclusions suggestive of Hepatozoon sp. gametocytes. Blood and synovial liquid samples were submitted to molecular analysis, aiming to amplify the Hepatozoon spp. 18S rRNA gene fragment. Despite the positioning of the found Hepatozoon sequence together with Hepatozoon canis previously detected in domestic carnivores, the BLAST analysis showed only 98% identity with H. canis. To the best of the authors' knowledge, this is the first time a Hepatozoon was detected in the synovial liquid by clinical pathology and molecular analyses.


Assuntos
Apicomplexa/genética , Canidae/parasitologia , Infecções por Protozoários/parasitologia , Líquido Sinovial/parasitologia , Animais , Apicomplexa/isolamento & purificação , Brasil , Achados Incidentais , Masculino , Filogenia , RNA Ribossômico 18S/genética
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