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Trypanosomiasis

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https://www.readbyqxmd.com/read/28325371/the-role-of-spatial-statistics-in-the-control-and-elimination-of-neglected-tropical-diseases-in-sub-saharan-africa-a-focus-on-human-african-trypanosomiasis-schistosomiasis-and-lymphatic-filariasis
#1
M C Stanton
Disease control and elimination programmes can benefit greatly from accurate information on the spatial variability of disease risk, particularly when risk is highly spatially heterogeneous. Due to advances in statistical methodology, coupled with the increased availability of geospatial technology, this information is becoming increasingly accessible. In this chapter we describe recent advancements in spatial methods associated with the analysis of disease data measured at the point-level and demonstrate their application to the control and elimination of neglected tropical diseases (NTDs)...
2017: Advances in Parasitology
https://www.readbyqxmd.com/read/28321260/loop-mediated-isothermal-amplification-test-for-trypanosoma-gambiense-group-1-with-stem-primers-a-molecular-xenomonitoring-test-for-sleeping-sickness
#2
Zablon K Njiru, Cecilia K Mbae, Gitonga N Mburugu
The World Health Organization has targeted Human African Trypanosomiasis (HAT) for elimination by 2020 with zero incidence by 2030. To achieve and sustain this goal, accurate and easy-to-deploy diagnostic tests for Gambian trypanosomiasis which accounts for over 98% of reported cases will play a crucial role. Most needed will be tools for surveillance of pathogen in vectors (xenomonitoring) since population screening tests are readily available. The development of new tests is expensive and takes a long time while incremental improvement of existing technologies that have potential for xenomonitoring may offer a shorter pathway to tools for HAT surveillance...
2017: Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28306721/developing-photoreceptor-based-models-of-visual-attraction-in-riverine-tsetse-for-use-in-the-engineering-of-more-attractive-polyester-fabrics-for-control-devices
#3
Roger D Santer
Riverine tsetse transmit the parasites that cause the most prevalent form of human African trypanosomiasis, Gambian HAT. In response to the imperative for cheap and efficient tsetse control, insecticide-treated 'tiny targets' have been developed through refinement of tsetse attractants based on blue fabric panels. However, modern blue polyesters used for this purpose attract many less tsetse than traditional phthalogen blue cottons. Therefore, colour engineering polyesters for improved attractiveness has great potential for tiny target development...
March 17, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28302040/trypanothione-reductase-a-target-for-the-development-of-anti-trypanosoma-cruzi-drugs
#4
Karina Vázquez, Margot Paulino, Cristian O Salas, Juan J Zarate-Ramos, Brenda Vera, Gildardo Rivera
Chagas disease or American trypanosomiasis is a major parasitic disease in Latin America with treatment available via two drugs: nifurtimox and benznidazole. These two treatments are ineffective in the chronic phase of the disease. Therefore, there is a need for the development of new, efficient and safe drugs for the treatment of these diseases. With this goal, one of the promising targets proposed is the trypanothione reductase (TR), a key enzyme important in the metabolism of Trypanosoma cruzi. In this review, we analyze the importance of TR as a drug target, as well as their compounds inhibitors reported in the last decade as potential therapeutic agents for Chagas disease...
March 15, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28286708/transcriptomic-analysis-reveals-metabolic-switches-and-surface-remodeling-as-key-processes-for-stage-transition-in-trypanosoma-cruzi
#5
Luisa Berná, Maria Laura Chiribao, Gonzalo Greif, Matias Rodriguez, Fernando Alvarez-Valin, Carlos Robello
American trypanosomiasis is a chronic and endemic disease which affects millions of people. Trypanosoma cruzi, its causative agent, has a life cycle that involves complex morphological and functional transitions, as well as a variety of environmental conditions. This requires a tight regulation of gene expression, which is achieved mainly by post-transcriptional regulation. In this work we conducted an RNAseq analysis of the three major life cycle stages of T. cruzi: amastigotes, epimastigotes and trypomastigotes...
2017: PeerJ
https://www.readbyqxmd.com/read/28285268/cardiac-manifestations-of-parasitic-diseases
#6
REVIEW
Maria Carmo P Nunes, Milton Henriques Guimarães Júnior, Adriana Costa Diamantino, Claudio Leo Gelape, Teresa Cristina Abreu Ferrari
The heart may be affected directly or indirectly by a variety of protozoa and helminths. This involvement may manifest in different ways, but the syndromes resulting from impairment of the myocardium and pericardium are the most frequent. The myocardium may be invaded by parasites that trigger local inflammatory response with subsequent myocarditis or cardiomyopathy, as occurs in Chagas disease, African trypanosomiasis, toxoplasmosis, trichinellosis and infection with free-living amoebae. In amoebiasis and echinococcosis, the pericardium is the structure most frequently involved with consequent pericardial effusion, acute pericarditis, cardiac tamponade or constrictive pericarditis...
March 11, 2017: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/28279451/data-driven-models-to-predict-the-elimination-of-sleeping-sickness-in-former-equateur-province-of-drc
#7
K S Rock, A Pandey, M L Ndeffo-Mbah, K E Atkins, C Lumbala, A Galvani, M J Keeling
Approaching disease elimination, it is crucial to be able to assess progress towards key objectives using quantitative tools. For Gambian human African trypanosomiasis (HAT), the ultimate goal is to stop transmission by 2030, while intermediary targets include elimination as a public health problem - defined as <1 new case per 10,000 inhabitants in 90% of foci, and <2000 reported cases by 2020. Using two independent mathematical models, this study assessed the achievability of these goals in the former Equateur province of the Democratic Republic of Congo, which historically had endemic levels of disease...
March 2017: Epidemics
https://www.readbyqxmd.com/read/28274857/bapta-am-decreases-cellular-ph-inhibits-acidocalcisome-acidification-and-autophagy-in-amino-acid-starved-t-brucei
#8
Feng-Jun Li, Kevin S W Tan, Cynthia Y He
To investigate the role of Ca(2+) signaling in starvation-induced autophagy in Trypanosoma brucei, the causative agent of human African trypanosomiasis, we used cell-permeant Ca(2+) chelator BAPTA-AM and cell impermeant chelator EGTA, and examined the potential involvement of several intracellular Ca(2+) signaling pathways in T. brucei autophagy. The results showed an unexpected effect of BAPTA-AM in decreasing cellular pH and inhibiting acidocalcisome acidification in starved cells. The implication of these results in the role of Ca(2+) signaling and cellular/organellar pH in T...
March 6, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28273308/a-study-in-trypanosomiasis-carlos-chagas-and-his-unique-approach
#9
Raghav Gupta, Christopher Kim, Arpan V Prabhu, Thomas G Benedek
No abstract text is available yet for this article.
March 1, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28263991/selective-inhibition-of-rna-polymerase-i-transcription-as-a-potential-approach-to-treat-african-trypanosomiasis
#10
Louise E Kerry, Elaine E Pegg, Donald P Cameron, James Budzak, Gretchen Poortinga, Katherine M Hannan, Ross D Hannan, Gloria Rudenko
Trypanosoma brucei relies on an essential Variant Surface Glycoprotein (VSG) coat for survival in the mammalian bloodstream. High VSG expression within an expression site body (ESB) is mediated by RNA polymerase I (Pol I), which in other eukaryotes exclusively transcribes ribosomal RNA genes (rDNA). As T. brucei is reliant on Pol I for VSG transcription, we investigated Pol I transcription inhibitors for selective anti-trypanosomal activity. The Pol I inhibitors quarfloxin (CX-3543), CX-5461, and BMH-21 are currently under investigation for treating cancer, as rapidly dividing cancer cells are particularly dependent on high levels of Pol I transcription compared with nontransformed cells...
March 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28246189/aee788-inhibits-basal-body-assembly-and-blocks-dna-replication-in-the-african-trypanosome
#11
Catherine Sullenberger, Daniel Pique, Yuko Ogata, Kojo Mensa-Wilmot
Trypanosoma brucei causes human African trypanosomiasis (HAT). The pyrrolopyrimidine AEE788 (a hit for anti-HAT drug discovery) associates with three trypanosome protein kinases. Herein we delineate the effects of AEE788 on T. brucei using chemical biology strategies. AEE788 treatment inhibits DNA replication in the kinetoplast (mitochondrial nucleoid) and nucleus. In addition, AEE788 blocks duplication of the basal body and the bilobe without affecting mitosis. Thus, AEE788 prevents entry into S phase of the cell division cycle...
February 28, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28241112/lysine-deacetylase-inhibitors-in-parasites-past-present-and-future-perspectives
#12
Gebremedhin Solomon Hailu, Dina Robaa, Mariantonietta Forgione, Wolfgang Sippl, Dante Rotili, Antonello Mai
Current therapies for human parasite infections rely on a few drugs, most of which have severe side effects, and their helpfulness is being seriously compromised by the drug resistance problem. Globally, this is pushing discovery research of anti-parasitic drugs towards new agents endowed with new mechanisms of action. By using a "drug repurposing" strategy, histone deacetylase inhibitors (HDACi), which are presently clinically approved for cancer use, are now under investigation for various parasite infections...
February 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28239154/anti-trypanosomatid-drug-discovery-an-ongoing-challenge-and-a-continuing-need
#13
REVIEW
Mark C Field, David Horn, Alan H Fairlamb, Michael A J Ferguson, David W Gray, Kevin D Read, Manu De Rycker, Leah S Torrie, Paul G Wyatt, Susan Wyllie, Ian H Gilbert
The WHO recognizes human African trypanosomiasis, Chagas disease and the leishmaniases as neglected tropical diseases. These diseases are caused by parasitic trypanosomatids and range in severity from mild and self-curing to near invariably fatal. Public health advances have substantially decreased the effect of these diseases in recent decades but alone will not eliminate them. In this Review, we discuss why new drugs against trypanosomatids are required, approaches that are under investigation to develop new drugs and why the drug discovery pipeline remains essentially unfilled...
February 27, 2017: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/28237731/rhenium-i-tricarbonyl-compounds-of-bioactive-thiosemicarbazones-synthesis-characterization-and-activity-against-trypanosoma-cruzi
#14
Esteban Rodríguez Arce, Ignacio Machado, Belén Rodríguez, Michel Lapier, María Carolina Zúñiga, Juan Diego Maya, Claudio Olea Azar, Lucía Otero, Dinorah Gambino
American Trypanosomiasis is a chronic infection discovered and described in 1909 by the Brazilian scientist Carlos Chagas. It is caused by the protozoan parasite Trypanosoma cruzi. Although it affects about 10million people in Latin America, the current chemotherapy is still inadequate. The discovery of new drugs is urgently needed. Our group is focused on the development of prospective metal-based drugs mainly based on bioactive ligands and pharmacologically interesting metal ions. In this work three new rhenium(I) tricarbonyl compounds fac-[Re(I)(CO)3Br(HL)] where HL=5-nitrofuryl containing thiosemicarbazones were synthesized and fully characterized in solution and in the solid state...
January 23, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28235390/qsar-analysis-for-6-arylpyrazine-2-carboxamides-as-trypanosoma-brucei-inhibitors
#15
V H Masand, N N E El-Sayed, D T Mahajan, V Rastija
Human African trypanosomiasis (HAT) is prevalent in African countries, covering 37 countries, mostly sub-Saharan. A limited number of drugs are available to cure this neglected disease. In the present work, quantitative structure-activity (toxicity) relationships (QSA(T)R) analysis has been performed for a dataset of 54 6-arylpyrazine-2-carboxamides as Trypanosoma brucei inhibitors to identify the important structural features required for future optimization of lead candidates. The QSA(T)R models satisfy OECD guidelines and have high statistical robustness...
February 2017: SAR and QSAR in Environmental Research
https://www.readbyqxmd.com/read/28225900/chronic-chagas-cardiomyopathy-a-review-of-the-main-pathogenic-mechanisms-and-the-efficacy-of-aetiological-treatment-following-the-benznidazole-evaluation-for-interrupting-trypanosomiasis-benefit-trial
#16
Anis Rassi, José Antonio Marin, Anis Rassi
Chagas cardiomyopathy is the most frequent and most severe manifestation of chronic Chagas disease, and is one of the leading causes of morbidity and death in Latin America. Although the pathogenesis of Chagas cardiomyopathy is incompletely understood, it may involve several mechanisms, including parasite-dependent myocardial damage, immune-mediated myocardial injury (induced by the parasite itself and by self-antigens), and microvascular and neurogenic disturbances. In the past three decades, a consensus has emerged that parasite persistence is crucial to the development and progression of Chagas cardiomyopathy...
March 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28225894/chronic-chagas-cardiomyopathy-a-review-of-the-main-pathogenic-mechanisms-and-the-efficacy-of-aetiological-treatment-following-the-benznidazole-evaluation-for-interrupting-trypanosomiasis-benefit-trial
#17
Anis Rassi, José Antonio Marin, Anis Rassi
Chagas cardiomyopathy is the most frequent and most severe manifestation of chronic Chagas disease, and is one of the leading causes of morbidity and death in Latin America. Although the pathogenesis of Chagas cardiomyopathy is incompletely understood, it may involve several mechanisms, including parasite-dependent myocardial damage, immune-mediated myocardial injury (induced by the parasite itself and by self-antigens), and microvascular and neurogenic disturbances. In the past three decades, a consensus has emerged that parasite persistence is crucial to the development and progression of Chagas cardiomyopathy...
February 16, 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28212811/polymorphisms-of-blood-forms-and-in%C3%A2-vitro-metacyclogenesis-of-trypanosoma-cruzi-i-ii-and-iv
#18
Camila Piva Abegg, Ana Paula de Abreu, Juliane Lopes da Silva, Silvana Marques de Araújo, Mônica Lúcia Gomes, Érika Cristina Ferreira, Max Jean de Ornelas Toledo
Trypanosoma cruzi is the etiologic agent of American trypanosomiasis has broad biological and genetic diversity. Remaining to be studied are polymorphisms of the blood forms and metacyclogenesis of different T. cruzi discrete typing units (DTUs). Our goal was to evaluate the relationship between T. cruzi DTUs, the morphology of blood trypomastigotes, and in vitro metacyclogenesis. T. cruzi strains that pertained to DTUs TcI, TcII, and TcIV from different Brazilian states were used. Parameters that were related to the morphology of eight strains were assessed in thin blood smears that were obtained from mice that were inoculated with blood or culture forms, depending on strain...
February 14, 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28198632/engineering-oral-and-parenteral-amorphous-amphotericin-b-formulations-against-experimental-trypanosoma-cruzi-infections
#19
Miriam Rolón, Dolores R Serrano, Aikaterini Lalatsa, Esther de Pablo, Juan Jose Torrado, Maria Paloma Ballesteros, Anne Marie Healy, Celeste Vega, Cathia Coronel, Francisco Bolas-Fernández, Maria Auxiliadora Dea-Ayuela
Chagas disease (CD) is a parasitic zoonosis endemic in most mainland countries of Central and South America affecting nearly 10 million people, with 100 million people at high risk of contracting the disease. Treatment is only effective if received at the early stages of the disease. Only two drugs (benznidazole and nifurtimox) have so far been marketed and both share various limitations such as variable efficacy, many side effects and long duration of treatment, thus reducing compliance. The in vitro and in vivo efficacy of poly-aggregated amphotericin B (AmB), encapsulated poly-aggregated AmB in albumin microspheres (AmB-AME) and dimeric AmB - sodium deoxycholate micelles (AmB-NaDC) was evaluated...
February 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28194625/trypanosomiasis-challenge-estimation-using-the-diminazene-aceturate-berenil-index-in-zebu-in-gabon
#20
Brieuc G A Cossic, Brice Adjahoutonon, Pierre Gloaguen, Gui Lov Dibanganga, Gael Maganga, Pascal Leroy, Ewan T MacLeod, Kim Picozzi
A longitudinal study was conducted within a cattle ranch in Gabon to determine the diminazene aceturate (Berenil) index (DAI) in a group of Zebu, raised under low tsetse density; this measure providing an assessment of trypanosomiasis risk. The objective was to evaluate the trypanosomiasis pressure thus informing trypanosomiasis control methods and cattle management. Twenty female adult Zebu were monitored for 24 weeks during the dry season. Blood samples were collected on a weekly basis and subjected to parasitological and haematological analysis (n = 480), using the buffy-coat method and the packed cell volume value (PCV), respectively, infected animals were treated with a single intramuscular injection of diminazene aceturate (8 mg/kg)...
March 2017: Tropical Animal Health and Production
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