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International Journal for Parasitology, Drugs and Drug Resistance

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https://www.readbyqxmd.com/read/29777962/field-evaluation-of-anticoccidial-efficacy-a-novel-approach-demonstrates-reduced-efficacy-of-toltrazuril-against-ovine-eimeria-spp-in-norway
#1
Ane Odden, Matthew J Denwood, Snorre Stuen, Lucy J Robertson, Antonio Ruiz, Inger Sofie Hamnes, Lisbeth Hektoen, Heidi L Enemark
Ovine Eimeria spp. infections cause reduced welfare, increased mortality, and substantial economic losses, and anticoccidials are crucial for their control. Recent reports of toltrazuril resistance in pigs, and anecdotal reports of reduced anticoccidial efficacy in lambs, necessitate evaluation of anticoccidial efficacy. Due to the substantial lifecycle differences between nematodes and coccidia, current WAAVP methods for assessing anthelmintic efficacy are not suitable for such evaluations. Faecal samples were collected from 8 pairs of twin lambs from 36 Norwegian sheep farms 6-8 days after turnout...
May 16, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29775797/functional-screening-of-selective-mitochondrial-inhibitors-of-plasmodium
#2
Maria G Gomez-Lorenzo, Ane Rodríguez-Alejandre, Sonia Moliner-Cubel, María Martínez-Hoyos, Noemí Bahamontes-Rosa, Rubén Gonzalez Del Rio, Carolina Ródenas, Jesús de la Fuente, Jose Luis Lavandera, Jose F García-Bustos, Alfonso Mendoza-Losana
Phenotypic screening has produced most of the new chemical entities currently in clinical development for malaria, plus many lead compounds active against Plasmodium falciparum asexual stages. However, lack of knowledge about the mode of action of these compounds delays and may even hamper their future development. Identifying the mode of action of the inhibitors greatly helps to prioritise compounds for further development as novel antimalarials. Here we describe a whole-cell method to detect inhibitors of the mitochondrial electron transport chain, using oxygen consumption as high throughput readout in 384-well plate format...
May 9, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29772478/bacillus-thuringiensis-cry5b-protein-as-a-new-pan-hookworm-cure
#3
Yan Hu, Thanh-Thanh Nguyen, Alice C Y Lee, Joseph F Urban, Melanie M Miller, Bin Zhan, David J Koch, Jason B Noon, Ambily Abraham, Ricardo Toshio Fujiwara, Dwight D Bowman, Gary R Ostroff, Raffi V Aroian
Hookworms are intestinal nematode parasites that infect nearly half a billion people and are globally one of the most important contributors to iron-deficiency anemia. These parasites have significant impacts in developing children, pregnant women and working adults. Of all the soil-transmitted helminths or nematodes (STNs), hookworms are by far the most important, with disease burdens conservatively estimated at four million DALYs (Disability-Adjusted Life Years) and with productivity losses of up to US$139 billion annually...
May 4, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29738984/physiological-aspects-of-nitro-drug-resistance-in-giardia-lamblia
#4
Joachim Müller, Andrew Hemphill, Norbert Müller
For over 50 years, metronidazole and other nitro compounds such as nitazoxanide have been used as a therapy of choice against giardiasis and more and more frequently, resistance formation has been observed. Model systems allowing studies on biochemical aspects of resistance formation to nitro drugs are, however, scarce since resistant strains are often unstable in culture. In order to fill this gap, we have generated a stable metronidazole- and nitazoxanide-resistant Giardia lamblia WBC6 clone, the strain C4...
April 28, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29758488/genetic-variants-in-dyf-7-validated-by-droplet-digital-pcr-are-not-drivers-for-ivermectin-resistance-in-haemonchus-contortus
#5
Safaa T Elmahalawy, Peter Halvarsson, Moa Skarin, Johan Höglund
Resistance to ivermectin (IVM) in the nematode Haemonchus contortus in small ruminants is an increasing problem throughout the world. Access to molecular diagnostics will allow early detection of IVM resistance, which in turn can limit the spread of resistant isolates. One candidate gene which has recently been suggested as a marker for IVM resistance is that for dye-filling protein (dyf-7). In this study, we critically investigated the suitability of A141G and G153T single nucleotide polymorphisms (SNP) of dyf-7 as a marker in larval cultures collected from sheep farms in Sweden, involving several isolates for which resistance status had been characterised by the faecal egg count reduction test (FECRT)...
April 26, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29689532/assessment-of-draxxin-%C3%A2-tulathromycin-as-an-inhibitor-of-in-vitro-growth-of-babesia-bovis-babesia-bigemina-and-theileria-equi
#6
Marta G Silva, Nicolas F Villarino, Donald P Knowles, Carlos E Suarez
Babesia bovis, Babesia bigemina and Theileria equi are worldwide tick-borne hemoprotozoan that cause diseases characterized by fever, anemia, weight loss and abortion. A common feature of these diseases are transition from acute to chronic phases, in which parasites may persist in the host for life, and becoming a reservoir for tick transmission. The live-attenuated vaccines for B. bovis and B. bigemina are not available for worldwide use due to legal restrictions and other concerns such as potential erythrocyte antigen and pathogen contamination, and a vaccine for T...
April 17, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29689531/genomic-and-transcriptomic-alterations-in-leishmania-donovani-lines-experimentally-resistant-to-antileishmanial-drugs
#7
Alberto Rastrojo, Raquel García-Hernández, Paola Vargas, Esther Camacho, Laura Corvo, Hideo Imamura, Jean-Claude Dujardin, Santiago Castanys, Begoña Aguado, Francisco Gamarro, Jose M Requena
Leishmaniasis is a serious medical issue in many countries around the World, but it remains largely neglected in terms of research investment for developing new control and treatment measures. No vaccines exist for human use, and the chemotherapeutic agents currently used are scanty. Furthermore, for some drugs, resistance and treatment failure are increasing to alarming levels. The aim of this work was to identify genomic and trancriptomic alterations associated with experimental resistance against the common drugs used against VL: trivalent antimony (SbIII , S line), amphotericin B (AmB, A line), miltefosine (MIL, M line) and paromomycin (PMM, P line)...
April 13, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29677637/the-prevalence-of-molecular-markers-of-drug-resistance-in-plasmodium-vivax-from-the-border-regions-of-thailand-in-2008-and-2014
#8
Kritpaphat Tantiamornkul, Tepanata Pumpaibool, Jittima Piriyapongsa, Richard Culleton, Usa Lek-Uthai
The prevalence of Plasmodium vivax is increasing in the border regions of Thailand; one potential problem confounding the control of malaria in these regions is the emergence and spread of drug resistance. The aim of this study was to determine the genetic diversity in genes potentially linked to drug resistance in P. vivax parasites isolated from four different border regions of Thailand; Thai-Myanmar (Tak, Mae Hong Son and Prachuap Khiri Khan Provinces), and Thai-Cambodian borders (Chanthaburi Province). Isolates were collected from 345 P...
April 12, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29673889/comparative-efficacy-toxicity-and-biodistribution-of-the-liposomal-amphotericin-b-formulations-fungisome-%C3%A2-and-ambisome-%C3%A2-in-murine-cutaneous-leishmaniasis
#9
Gert-Jan Wijnant, Katrien Van Bocxlaer, Vanessa Yardley, Andy Harris, Mo Alavijeh, Rita Silva-Pedrosa, Sandra Antunes, Isabel Mauricio, Sudaxshina Murdan, Simon L Croft
Fungisome® (F), a liposomal amphotericin B (AmB) product, is marketed in India as a safe and effective therapeutic for the parasitic infection visceral leishmaniasis. Its potential in the treatment of cutaneous leishmaniasis (CL), a disfiguring form of the disease affecting the skin, is currently unknown. Here, we report the evaluation of the efficacy of F in the Leishmania major BALB/c murine model of CL, including a head-to-head comparison with the standard liposomal AmB formulation AmBisome® (A). Upon intravenous administration at dose levels of 5, 10 and 15 mg/kg of body weight (on days 0, 2, 4, 6 and 8), F showed clear signs of toxicity (at 15 mg/kg), while A did not...
April 12, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29649665/the-anti-fecundity-effect-of-5-azacytidine-5-azac-on-schistosoma-mansoni-is-linked-to-dis-regulated-transcription-translation-and-stem-cell-activities
#10
Kathrin K Geyer, Sabrina E Munshi, Martin Vickers, Michael Squance, Toby J Wilkinson, Daniel Berrar, Cristian Chaparro, Martin T Swain, Karl F Hoffmann
Uncontrolled host immunological reactions directed against tissue-trapped eggs precipitate a potentially lethal, pathological cascade responsible for schistosomiasis. Blocking schistosome egg production, therefore, presents a strategy for simultaneously reducing immunopathology as well as limiting disease transmission in endemic or emerging areas. We recently demonstrated that the ribonucleoside analogue 5-azacytidine (5-AzaC) inhibited Schistosoma mansoni oviposition, egg maturation and ovarian development...
April 1, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29631126/activity-of-bromodomain-protein-inhibitors-binders-against-asexual-stage-plasmodium-falciparum-parasites
#11
Ming Jang Chua, Dina Robaa, Tina S Skinner-Adams, Wolfgang Sippl, Katherine T Andrews
Bromodomain-containing proteins (BDPs) are involved in the regulation of eukaryotic gene expression. Compounds that bind and/or inhibit BDPs are of interest as tools to better understand epigenetic regulation, and as possible drug leads for different diseases, including malaria. In this study, we assessed the activity of 42 compounds demonstrated or predicted (using virtual screening of a pharmacophore model) to bind/inhibit eukaryotic BDPs for activity against Plasmodium falciparum malaria parasites. In silico docking studies indicated that all compounds are predicted to participate in a typical hydrogen bond interaction with the conserved asparagine (Asn1436) of the P...
March 26, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29631127/synergistic-combination-of-alkylphosphocholines-with-peptaibols-in-targeting-leishmania-infantum-in-vitro
#12
Irene Fragiadaki, Anna Katogiritis, Theodora Calogeropoulou, Hans Brückner, Effie Scoulica
Anti-leishmanial treatment increasingly encounters therapeutic limitations due to drug toxicity and development of resistance. The effort for new therapeutic strategies led us to work on combinations of chemically different compounds that could yield enhanced leishmanicidal effect. Peptaibols are a special type of antimicrobial peptides that are able to form ion channels in cell membranes and potentially affect cell viability. We assayed the antileishmanial activity of two well studied helical peptaibols, the 16-residue antiamoebin and the 20-residue alamethicin-analogue suzukacillin, and we evaluated the biological effect of their combination with the alkylphosphocholine miltefosine and its synthetic analogue TC52...
March 20, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29602064/high-throughput-cos-seq-screen-with-intracellular-leishmania-infantum-for-the-discovery-of-novel-drug-resistance-mechanisms
#13
Christopher Fernandez-Prada, Mansi Sharma, Marie Plourde, Eva Bresson, Gaétan Roy, Philippe Leprohon, Marc Ouellette
Increasing drug resistance towards first line antimony-derived compounds has forced the introduction of novel therapies in leishmaniasis endemic areas including amphotericin B and miltefosine. However, their use is threatened by the emergence and spread of drug-resistant strains. In order to discover stage-dependent resistance genes, we have adapted the Cos-Seq approach through the introduction of macrophage infections in the pipeline. A L. infantum intracellular amastigote population complemented with a L...
March 16, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29587237/isothermal-microcalorimetry-a-quantitative-method-to-monitor-trypanosoma-congolense-growth-and-growth-inhibition-by-trypanocidal-drugs-in-real-time
#14
M Gysin, O Braissant, K Gillingwater, R Brun, P Mäser, T Wenzler
Trypanosoma congolense is a protozoan parasite that is transmitted by tsetse flies, causing African Animal Trypanosomiasis, also known as Nagana, in sub-Saharan Africa. Nagana is a fatal disease of livestock that causes severe economic losses. Two drugs are available, diminazene and isometamidium, yet successful treatment is jeopardized by drug resistant T. congolense. Isothermal microcalorimetry is a highly sensitive tool that can be used to study growth of the extracellular T. congolense parasites or to study parasite growth inhibition after the addition of antitrypanosomal drugs...
March 16, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29627513/high-level-efficacy-of-lufenuron-against-sea-lice-lepeophtheirus-salmonis-linked-to-rapid-impact-on-moulting-processes
#15
Jordan D Poley, Laura M Braden, Amber M Messmer, Okechukwu O Igboeli, Shona K Whyte, Alicia Macdonald, Jose Rodriguez, Marta Gameiro, Lucien Rufener, Jacques Bouvier, Dorota W Wadowska, Ben F Koop, Barry C Hosking, Mark D Fast
Drug resistance in the salmon louse Lepeophtheirus salmonis is a global issue for Atlantic salmon aquaculture. Multiple resistance has been described across most available compound classes with the exception of the benzoylureas. To target this gap in effective management of L. salmonis and other species of sea lice (e.g. Caligus spp.), Elanco Animal Health is developing an in-feed treatment containing lufenuron (a benzoylurea) to be administered prior to seawater transfer of salmon smolts and to provide long-term protection of salmon against sea lice infestations...
March 13, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29649664/autophagic-related-cell-death-of-trypanosoma-brucei-induced-by-bacteriocin-as-48
#16
Marta Martínez-García, Jean-Mathieu Bart, Jenny Campos-Salinas, Eva Valdivia, Manuel Martínez-Bueno, Elena González-Rey, Miguel Navarro, Mercedes Maqueda, Rubén Cebrián, José M Pérez-Victoria
The parasitic protozoan Trypanosoma brucei is the causative agent of human African trypanosomiasis (sleeping sickness) and nagana. Current drug therapies have limited efficacy, high toxicity and/or are continually hampered by the appearance of resistance. Antimicrobial peptides have recently attracted attention as potential parasiticidal compounds. Here, we explore circular bacteriocin AS-48's ability to kill clinically relevant bloodstream forms of T. brucei gambiense, T. brucei rhodesiense and T. brucei brucei...
March 12, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29684680/licochalcone-a-an-effective-and-low-toxicity-compound-against-toxoplasma-gondii-in-vitro-and-in-vivo
#17
Hongfei Si, Chunyan Xu, Jili Zhang, Xukun Zhang, Bing Li, Xuzheng Zhou, Jiyu Zhang
Toxoplasma gondii, an obligate intracellular protozoan, is the causative agent of toxoplasmosis, which can cause serious public health problems. The current drugs used to treat toxoplasmosis have many limitations. This study evaluated the anti-T. gondii activity and potential mechanism of Licochalcone A (Lico A) in vitro and in vivo. The safe concentration of Lico A in HFF cells was determined by MTT cell viability assays. The presence of T. gondii was assessed by qPCR and Giemsa staining. Azithromycin and sulfadiazine, commonly used effective treatments, served as drug controls...
March 1, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29518650/characterization-and-validation-of-entamoeba-histolytica-pantothenate-kinase-as-a-novel-anti-amebic-drug-target
#18
Arif Nurkanto, Ghulam Jeelani, Takehiro Yamamoto, Yoshiko Naito, Takako Hishiki, Mihoko Mori, Makoto Suematsu, Kazuro Shiomi, Tetsuo Hashimoto, Tomoyoshi Nozaki
The Coenzyme A (CoA), as a cofactor involved in >100 metabolic reactions, is essential to the basic biochemistry of life. Here, we investigated the CoA biosynthetic pathway of Entamoeba histolytica (E. histolytica), an enteric protozoan parasite responsible for human amebiasis. We identified four key enzymes involved in the CoA pathway: pantothenate kinase (PanK, EC 2.7.1.33), bifunctional phosphopantothenate-cysteine ligase/decarboxylase (PPCS-PPCDC), phosphopantetheine adenylyltransferase (PPAT) and dephospho-CoA kinase (DPCK)...
April 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29501973/safety-and-efficacy-of-the-bumped-kinase-inhibitor-bki-1553-in-pregnant-sheep-experimentally-infected-with-neospora-caninum-tachyzoites
#19
Roberto Sánchez-Sánchez, Ignacio Ferre, Michela Re, Patricia Vázquez, Luis Miguel Ferrer, Javier Blanco-Murcia, Javier Regidor-Cerrillo, Manuel Pizarro Díaz, Marta González-Huecas, Enrique Tabanera, Paula García-Lunar, Julio Benavides, Pablo Castaño, Andrew Hemphill, Matthew A Hulverson, Grant R Whitman, Kasey L Rivas, Ryan Choi, Kayode K Ojo, Lynn K Barrett, Wesley C Van Voorhis, Luis Miguel Ortega-Mora
Neospora caninum is one of the main causes of abortion in cattle, and recent studies have highlighted its relevance as an abortifacient in small ruminants. Vaccines or drugs for the control of neosporosis are lacking. Bumped kinase inhibitors (BKIs), which are ATP-competitive inhibitors of calcium dependent protein kinase 1 (CDPK1), were shown to be highly efficacious against several apicomplexan parasites in vitro and in laboratory animal models. We here present the pharmacokinetics, safety and efficacy of BKI-1553 in pregnant ewes and foetuses using a pregnant sheep model of N...
April 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29499568/17-dmag-inhibits-the-multiplication-of-several-babesia-species-and-theileria-equi-on-in-vitro-cultures-and-babesia-microti-in-mice
#20
Azirwan Guswanto, Arifin Budiman Nugraha, Bumduuren Tuvshintulga, Dickson Stuart Tayebwa, Mohamed Abdo Rizk, Gaber El-Saber Batiha, Sambuu Gantuya, Thillaiampalam Sivakumar, Naoaki Yokoyama, Ikuo Igarashi
Heat shock protein 90 (Hsp90) is a chaperone protein that stabilizes cells during stress or non-stress responses. Previous reports have shown that Hsp90 is a potential drug target to suppress the multiplication of several protozoan parasites. In this study, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), an Hsp90 inhibitor, was evaluated for its inhibitory effect on five in vitro cultures of Babesia and Theileria species, including B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi, and on the multiplication of a B...
April 2018: International Journal for Parasitology, Drugs and Drug Resistance
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