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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
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...
June 20, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Samantha Baron, Roberto A Barrero, Michael Black, Matthew I Bellgard, Ellie van Dalen, Christine Maritz-Olivier
The widespread geographical distribution of Rhipicephalus decoloratus in southern Africa and its ability to transmit the pathogens causing redwater, gallsickness and spirochaetosis in cattle makes this hematophagous ectoparasite of economic importance. In South Africa, the most commonly used chemical acaricides to control tick populations are pyrethroids and amitraz. The current amitraz resistance mechanism described in R. microplus, from South Africa and Australia, involves mutations in the octopamine receptor, but it is unlikely that this will be the only contributing factor to mediate resistance...
June 18, 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...
June 15, 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...
May 21, 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...
May 18, 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...
May 16, 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...
May 9, 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...
May 4, 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...
April 28, 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)...
April 26, 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...
April 25, 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
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...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
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...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
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...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
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...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
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...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
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...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
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...
August 2018: International Journal for Parasitology, Drugs and Drug Resistance
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