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Ifedayo Victor Ogungbe, William N Setzer
Malaria, leishmaniasis, Chagas disease, and human African trypanosomiasis continue to cause considerable suffering and death in developing countries. Current treatment options for these parasitic protozoal diseases generally have severe side effects, may be ineffective or unavailable, and resistance is emerging. There is a constant need to discover new chemotherapeutic agents for these parasitic infections, and natural products continue to serve as a potential source. This review presents molecular docking studies of potential phytochemicals that target key protein targets in Leishmania spp...
October 19, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Vanessa Bellini Bardella, Sebastián Pita, André Luis Laforga Vanzela, Cleber Galvão, Francisco Panzera
The subfamily Triatominae (Hemiptera, Reduviidae) includes 150 species of blood-sucking insects, vectors of Chagas disease or American trypanosomiasis. Karyotypic information reveals a striking stability in the number of autosomes. However, this group shows substantial variability in genome size, the amount and distribution of C-heterochromatin, and the chromosome positions of 45S rDNA clusters. Here, we analysed the karyotypes of 41 species from six different genera with C-fluorescence banding in order to evaluate the base-pair richness of heterochromatic regions...
October 2016: Memórias do Instituto Oswaldo Cruz
Verónica Seguel, Lorena Castro, Chantal Reigada, Leonel Cortes, María V Díaz, Mariana R Miranda, Claudio A Pereira, Michel Lapier, Carolina Campos-Estrada, Antonio Morello, Ulrike Kemmerling, Juan D Maya, Rodrigo López-Muñoz
Benznidazole is the first-line drug used in treating Chagas disease, which is caused by the parasite Trypanosoma cruzi (T. cruzi). However, benznidazole has limited efficacy and several adverse reactions. Pentamidine is an antiprotozoal drug used in the treatment of leishmaniasis and African trypanosomiasis. In T. cruzi, pentamidine blocks the transport of putrescine, a precursor of trypanothione, which constitutes an essential molecule in the resistance of T. cruzi to benznidazole. In the present study, we describe the effect of the combination of benznidazole and pentamidine on isolated parasites, mammalian cells and in mice infected with T...
October 8, 2016: Experimental Parasitology
Sanofar Abdeen, Nilshad Salim, Najiba Mammadova, Corey M Summers, Karen Goldsmith-Pestana, Diane McMahon-Pratt, Peter G Schultz, Arthur L Horwich, Eli Chapman, Steven M Johnson
Trypanosoma brucei are protozoan parasites that cause African sleeping sickness in humans (also known as Human African Trypanosomiasis-HAT). Without treatment, T. brucei infections are fatal. There is an urgent need for new therapeutic strategies as current drugs are toxic, have complex treatment regimens, and are becoming less effective owing to rising antibiotic resistance in parasites. We hypothesize that targeting the HSP60/10 chaperonin systems in T. brucei is a viable anti-trypanosomal strategy as parasites rely on these stress response elements for their development and survival...
September 22, 2016: Bioorganic & Medicinal Chemistry Letters
Harriet Auty, Sarah Cleaveland, Imna Malele, Joseph Masoy, Tiziana Lembo, Paul Bessell, Stephen Torr, Kim Picozzi, Susan C Welburn
BACKGROUND: Identifying hosts of blood-feeding insect vectors is crucial in understanding their role in disease transmission. Rhodesian human African trypanosomiasis (rHAT), also known as acute sleeping sickness is caused by Trypanosoma brucei rhodesiense and transmitted by tsetse flies. The disease is commonly associated with wilderness areas of east and southern Africa. Such areas hold a diverse range of species which form communities of hosts for disease maintenance. The relative importance of different wildlife hosts remains unclear...
2016: PloS One
Mary Carter Denny, Leon L Lai, Robert Laureno
It is important to recognize the signs and symptoms of human African trypanosomiasis (HAT) in order to facilitate early diagnosis and treatment. A 36-year-old man developed encephalitis caused by HAT. This encephalitis can appear many years after well-tolerated systemic infection. The neurologic manifestations developed 7 years after he had emigrated from Cameroon to the United States. We demonstrate the magnetic resonance imaging before, during, and after his treatment with intravenous eflornithine. Clinical signs and symptoms of HAT can be nonspecific and precede abnormalities on magnetic resonance imaging...
October 2016: Neurohospitalist
L N Nsiangani, D Kaimbo Wa Kaimbo, M L Kazumba
We report the case of a 13-year-old girl who consulted for blurred vision, pain, and redness in her left eye. Ophthalmologic examination revealed chronic, hypertensive, and non-granulomatous anterior uveitis. The disease course was marked by a reversal of diurnal rhythm, with daytime sleepiness and behavioral disorders. A neuropsychiatric examination suggested human African trypanosomiasis (HAT), or sleeping sickness. The diagnosis was confirmed by the detection of Trypanosoma in the cerebrospinal fluid. The NECT regimen (nifurtimox-eflornithine combination therapy) was administered as medical treatment and resulted in the disappearance of all clinical signs...
August 1, 2016: Médecine et Santé Tropicales
C Díaz-Luján, M F Triquell, C Castillo, D Hardisson, U Kemmerling, R E Fretes
American trypanosomiasis has long been a neglected disease endemic in LatinAmerica, but congenital transmission has now spread Chagas disease to cause a global health problem. As the early stages of the infection of placental tissue and the vertical transmission by Trypanosoma cruzi are still not well understood, it is important to investigate the relevance of the first structure of the placental barrier in chorionic villi infection by T. cruzi during the initial stage of the infection. Explants of human chorionic villi from healthy pregnant women at term were denuded of their syncytiotrophoblast and co-cultured for 3h, 24h and 96h with 800,000 trypomastigotes (simulating acute infection)...
September 26, 2016: Acta Tropica
Raghavendran Ramaswamy, Sarah Goomeshi Nobary, Brett A Eyford, Terry W Pearson, Martin J Boulanger
African trypanosomiasis, caused by parasites of the genus Trypanosoma, is a complex of devastating vector-borne diseases of humans and livestock in sub-Saharan Africa. Central to the pathogenesis of African trypanosomes is their transmission by the arthropod vector, Glossina spp. (tsetse fly). Intriguingly, the efficiency of parasite transmission through the vector is reduced following depletion of Trypanosoma brucei Procyclic-Specific Surface Antigen-2 (TbPSSA-2). To investigate the underlying molecular mechanism of TbPSSA-2, we determined the crystal structures of its ectodomain and that of its homolog T...
September 27, 2016: Protein Science: a Publication of the Protein Society
Víctor M Castillo-Acosta, Luis M Ruiz-Pérez, Juan Etxebarria, Niels C Reichardt, Miguel Navarro, Yasuhiro Igarashi, Sandra Liekens, Jan Balzarini, Dolores González-Pacanowska
Current treatments available for African sleeping sickness or human African trypanosomiasis (HAT) are limited, with poor efficacy and unacceptable safety profiles. Here, we report a new approach to address treatment of this disease based on the use of compounds that bind to parasite surface glycans leading to rapid killing of trypanosomes. Pradimicin and its derivatives are non-peptidic carbohydrate-binding agents that adhere to the carbohydrate moiety of the parasite surface glycoproteins inducing parasite lysis in vitro...
September 2016: PLoS Pathogens
Isaiah O Ademola, Paul O Odeniran
CONTEXT: Control of African trypanosomiasis relies on chemotherapy, but the development of resistance and the problem of drug residues require research for alternatives. Triterpenes and phenolics, the major constituents of Pleurotus sajor-caju (Fr.) Singer (Pleurotaceae), are reported to be effective against trypanosomiasis. OBJECTIVE: Trypanocidal effect of whole Pleurotus sajor-caju aqueous extract was investigated in vivo against Trypanosoma congolense. MATERIALS AND METHODS: Mice (25-32 g) were divided into seven groups of six animals...
September 21, 2016: Pharmaceutical Biology
Samuel J Black, John M Mansfield
African trypanosomes cause human and animal African trypanosomiasis, which are chronic, debilitating and often fatal diseases of people and livestock in sub-Saharan Africa. The extracellular protozoan parasites are exemplars of antigenic variation. They direct host protective B cell and T cell immune responses towards hypervariable components of their variable surface glycoprotein coat, and evade immune elimination by generating new surface coat antigenic variants at a rate that supersedes immune destruction...
September 16, 2016: Parasite Immunology
Barbara V da Silva, Bianca N M Silva
BACKGROUND: Trypanosomiasis and leishmaniasis cause severe infections in humans and domestic animals in the tropics. Although typical diseases in Latin America, globalization and the migration of infected people has spread these diseases to countries in North America, Asia and Europe. Currently available drugs are not effective in the chronic phase, as well as causing side effects and the development of resistance. RESULTS: Among the chemical groups studied as potential anti-T...
September 9, 2016: Medicinal Chemistry
Ermias Mergia, Workineh Shibeshi, Getachew Terefe, Tilahun Teklehaymanot
BACKGROUND: African Trypanosomiasis is a neglected tropical disease with a large impact on the livelihood of the rural poor in Sub-Saharan Africa. The available drugs for managing this disease are old, expensive and are facing the problem of drug resistance. Thus, the aim of this study was to evaluate in vivo antitrypanosomal efficacy of aqueous and absolute methanol leaf extracts of Verbascum sinaiticum Benth. against Trypanosoma congolense field isolate. METHODS: Verbascum sinaiticum (Local name 'qetetina') is a biennial plant, and 60-150 cm tall...
2016: BMC Complementary and Alternative Medicine
Peter M Njogu, Eric M Guantai, Elumalai Pavadai, Kelly Chibale
Despite the tremendous improvement in overall global health heralded by the adoption of the Millennium Declaration in the year 2000, tropical infections remain a major health problem in the developing world. Recent estimates indicate that the major tropical infectious diseases, namely, malaria, tuberculosis, trypanosomiasis, and leishmaniasis, account for more than 2.2 million deaths and a loss of approximately 85 million disability-adjusted life years annually. The crucial role of chemotherapy in curtailing the deleterious health and economic impacts of these infections has invigorated the search for new drugs against tropical infectious diseases...
January 8, 2016: ACS Infectious Diseases
Aziz Filali-Ansary, Cécile Augé, Audrey Abgrall, Marie Souchaud, Franck Pellissier, Olaf Valverde Mordt, Séverine Blesson, Ger-Jan Sanderink
AIM: Fexinidazole (FEX) is a nitroimidazole being developed as a new trypanocide treatment for human African trypanosomiasis/sleeping sickness. Its main metabolites, fexinidazole sulfoxide (M1) and fexinidazole sulfone (M2), show the same in vitro pharmacological activity as FEX. METHODS & RESULTS: An LC-MS/MS assay was developed for quantitation of FEX in DBS, collected via finger-prick from healthy subjects. The DBS assay was specific, accurate and reproducible for FEX, M1 and M2 when validated against the current plasma assay...
October 2016: Bioanalysis
K K Misra, S Roy, A Choudhury
Trypanosoma (Trypanozoon) evansi is a causative agent of the dreadful mammalian disease trypanosomiasis or 'Surra' and carried as a latent parasite in domestic cattle but occasionally proves fatal when transmitted to horses and camel. Sporadic outbreak of 'Surra' to different animals (beside their natural hosts) reminds that T. evansi may be zoonotic, as their close relative cause sleeping sickness to human being. This haemoflagellate is mechanically transmitted by horse fly and its effect on different host varies depending on certain factors including the effectiveness of transmission by mechanical vector, the suitability and susceptibility of the host as well as most importantly the ability of the disease establishment of parasite to adapt itself to the host's resistance, etc...
September 2016: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
Irene Sola, Albert Artigas, Martin C Taylor, F Javier Pérez-Areales, Elisabet Viayna, M Victòria Clos, Belén Pérez, Colin W Wright, John M Kelly, Diego Muñoz-Torrero
Current drugs against human African trypanosomiasis (HAT) suffer from several serious drawbacks. The search for novel, effective, brain permeable, safe, and inexpensive antitrypanosomal compounds is therefore an urgent need. We have recently reported that the 4-aminoquinoline derivative huprine Y, developed in our group as an anticholinesterasic agent, exhibits a submicromolar potency against Trypanosoma brucei and that its homo- and hetero-dimerization can result in to up to three-fold increased potency and selectivity...
November 1, 2016: Bioorganic & Medicinal Chemistry
Ana L Valenciano, Giselle M Knudsen, Zachary B Mackey
The Trypanosoma brucei subspecies T. brucei gambiense and T. brucei rhodesiense are vector-borne pathogens that cause sleeping sickness also known as Human African Trypanosomiasis (HAT), which is fatal if left untreated. The drugs that treat HAT are ineffective and cause toxic side effects. One strategy for identifying safer and more effective HAT drugs is to therapeutically exploit essential gene targets in T. brucei. Genes that make up a basic mitogen-activated protein kinase (MAPK) network are present in T...
October 17, 2016: Cell Cycle
Vicente Abril, José Luis Ramos
No abstract text is available yet for this article.
September 7, 2016: American Journal of Tropical Medicine and Hygiene
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