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International Journal for Parasitology, Drugs and Drug Resistance

Swarna Bais, Robert M Greenberg
Ion channels are membrane protein complexes that underlie electrical excitability in cells, allowing ions to diffuse through cell membranes in a regulated fashion. They are essential for normal functioning of the neuromusculature and other tissues. Ion channels are also validated targets for many current anthelmintics, yet the properties of only a small subset of ion channels in parasitic helminths have been explored in any detail. Transient receptor potential (TRP) channels comprise a widely diverse superfamily of ion channels with important roles in sensory signaling, regulation of ion homeostasis, organellar trafficking, and other functions...
September 8, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Daniel Yasur-Landau, Charles L Jaffe, Lior David, Adi Doron-Faigenboim, Gad Baneth
Leishmania infantum is one of the causative agents of visceral leishmaniasis (VL), a widespread, life-threatening disease. This parasite is responsible for the majority of human VL cases in Brazil, the Middle East, China, Central Asia and the Mediterranean basin. Its main reservoir are domestic dogs which, similar to human patients, may develop severe visceral disease and die if not treated. The drug allopurinol is used for the long-term maintenance of dogs with canine leishmaniasis. Following our report of allopurinol resistance in treated relapsed dogs, we investigated the mechanisms and markers of resistance to this drug...
August 23, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Marie Jalovecka, David Hartmann, Yukiko Miyamoto, Lars Eckmann, Ondrej Hajdusek, Anthony J O'Donoghue, Daniel Sojka
Babesiosis is a tick-transmitted zoonosis caused by apicomplexan parasites of the genus Babesia. Treatment of this emerging malaria-related disease has relied on antimalarial drugs and antibiotics. The proteasome of Plasmodium, the causative agent of malaria, has recently been validated as a target for anti-malarial drug development and therefore, in this study, we investigated the effect of epoxyketone (carfilzomib, ONX-0914 and epoxomicin) and boronic acid (bortezomib and ixazomib) proteasome inhibitors on the growth and survival of Babesia...
August 7, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Craig Wang, Paul R Torgerson, Ray M Kaplan, Melissa M George, Reinhard Furrer
The same anthelmintic treatment can have variable efficacy on individual animals even if the parasite population is homogenously susceptible. An extension of the R package eggCounts is proposed to take individual efficacy into account using a Bayesian hierarchical model. A simulation study is conducted to compare the performance of five different methods on estimating faecal egg count reduction and its uncertainty interval. Simulation results showed the individual efficacy model offered robust inference to two different data simulation procedures with low root mean squared error on the reduction estimate and appropriate uncertainty estimates...
August 3, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Cristina Ballesteros, Cassan N Pulaski, Catherine Bourguinat, Kathy Keller, Roger K Prichard, Timothy G Geary
Prophylaxis with macrocyclic lactone (ML) endectocides is the primary strategy for heartworm control. Recent evidence has confirmed that ML-resistant Dirofilaria immitis isolates have evolved. Comparison of genomes of ML-resistant isolates show they are genetically distinct from wild-type populations. Previously, we identified single nucleotide polymorphisms (SNPs) that are correlated with phenotypic ML resistance. Since reliable in vitro assays are not available to detect ML resistance in L3 or microfilarial stages, the failure to reduce microfilaraemia in infected dogs treated with an ML has been proposed as a surrogate clinical assay for this purpose...
July 18, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Kathrin K Geyer, Sabrina E Munshi, Martin Vickers, Michael Squance, Toby J Wilkinson, Daniel Berrar, Cristian Chaparro, Martin T Swain, Karl F Hoffmann
No abstract text is available yet for this article.
July 17, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Pierre H H Schneeberger, Jean T Coulibaly, Morgan Gueuning, Wendelin Moser, Bryan Coburn, Jürg E Frey, Jennifer Keiser
Soil-transmitted helminths infect 1.5 billion people worldwide. Treatment with anthelminthics is the key intervention but interactions between anthelminthic agents and the gut microbiota have not yet been studied. In this study, the effects of four anthelminthic drugs and combinations (tribendimidine, tribendimidine plus ivermectin, tribendimidine plus oxantel-pamoate, and albendazole plus oxantel-pamoate) on the gut microbiota were assessed. From each hookworm infected adolescent, one stool sample was collected prior to treatment, 24 h post-treatment and 3 weeks post-treatment, and a total of 144 stool samples were analyzed...
July 2, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Shogo Furutani, Makoto Ihara, Kristin Lees, Steven D Buckingham, Frederick A Partridge, Jonathan A David, Rohit Patel, Scott Warchal, Ian R Mellor, Kazuhiko Matsuda, David B Sattelle
A novel L-glutamate-gated anion channel (IscaGluCl1) has been cloned from the black-legged tick, Ixodes scapularis, which transmits multiple pathogens including the agents of Lyme disease and human granulocytic anaplasmosis. When mRNA encoding IscaGluCl1 was expressed in Xenopus laevis oocytes, we detected robust 50-400 nA currents in response to 100 μM L-glutamate. Responses to L-glutamate were concentration-dependent (pEC50 3.64 ± 0.11). Ibotenate was a partial agonist on IscaGluCl1. We detected no response to 100 μM aspartate, quisqualate, kainate, AMPA or NMDA...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
Cristina Ballesteros, James F Geary, Charles D Mackenzie, Timothy G Geary
Lymphatic filariasis and onchocerciasis are neglected parasitic diseases which pose a threat to public health in tropical and sub-tropical regions. Strategies for control and elimination of these diseases by mass drug administration (MDA) campaigns are designed to reduce symptoms of onchocerciasis and transmission of both parasites to eventually eliminate the burden on public health. Drugs used for MDA are predominantly microfilaricidal, and prolonged rounds of treatment are required for eradication. Understanding parasite biology is crucial to unravelling the complex processes involved in host-parasite interactions, disease transmission, parasite immune evasion, and the emergence of drug resistance...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
Reto Rufener, Dominic Ritler, Jana Zielinski, Luca Dick, Emerson Teixeira da Silva, Adriele da Silva Araujo, Deborah Elisabeth Joekel, David Czock, Christine Goepfert, Adriana Marques Moraes, Marcus Vinicius Nora de Souza, Joachim Müller, Meike Mevissen, Andrew Hemphill, Britta Lundström-Stadelmann
The cestode E. multilocularis causes the disease alveolar echinococcosis (AE) in humans. The continuously proliferating metacestode (larval stage) of the parasite infects mostly the liver and exhibits tumor-like growth. Current chemotherapeutical treatment options rely on benzimidazoles, which are rarely curative and have to be applied daily and life-long. This can result in considerable hepatotoxicity and thus treatment discontinuation. Therefore, novel drugs against AE are urgently needed. The anti-malarial mefloquine was previously shown to be active against E...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
Jürgen Krücken, Kira Fraundorfer, Jean Claude Mugisha, Sabrina Ramünke, Kevin C Sifft, Dominik Geus, Felix Habarugira, Jules Ndoli, Augustin Sendegeya, Caritas Mukampunga, Toni Aebischer, Janina McKay-Demeler, Jean Bosco Gahutu, Frank P Mockenhaupt, Georg von Samson-Himmelstjerna
A recent publication by Levecke et al. (Int. J. Parasitol, 2018, 8, 67-69) provides important insights into the kinetics of worm expulsion from humans following treatment with albendazole. This is an important aspect of determining the optimal time-point for post treatment sampling to examine anthelmintic drug efficacy. The authors conclude that for the determination of drug efficacy against Ascaris, samples should be taken not before day 14 and recommend a period between days 14 and 21. Using this recommendation, they conclude that previous data (Krücken et al...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
Yao Bai, Jiaqi Zhang, Jinting Geng, Shiling Xu, Shuang Deng, Weilin Zeng, Zenglei Wang, Huguette Gaelle Ngassa Mbenda, Jie Zhang, Na Li, Yanrui Wu, Cuiying Li, Huae Liu, Yonghua Ruan, Yaming Cao, Zhaoqing Yang, Liwang Cui
Multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion of Southeast Asia is a major threat to malaria elimination and requires close surveillance. In this study, we collected 107 longitudinal clinical samples of P. falciparum in 2007-2012 from the malaria hypoendemic region of the China-Myanmar border and measured their in vitro susceptibilities to 10 antimalarial drugs. Overall, parasites had significantly different IC50 values to all the drugs tested as compared to the reference 3D7 strain...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
Pauline Fontaine, Keith Choe
Parasitic nematodes infect over 1/4 th of the human population and are a major burden on livestock and crop production. Benzimidazole class anthelmintics are widely used to treat infections, but resistance is a widespread problem. Mutation of genes encoding the benzimidazole target β-tubulin is a well-established mechanism of resistance, but recent evidence suggests that metabolism of the drugs may also occur. Our objective was to investigate contributions of the detoxification-response transcription factor SKN-1 to anthelmintic drug resistance using C...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
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...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
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...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
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...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
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)...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
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...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
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...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
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)...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
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