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International Journal for Parasitology, Drugs and Drug Resistance

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https://www.readbyqxmd.com/read/27915061/modelling-the-consequences-of-targeted-selective-treatment-strategies-on-performance-and-emergence-of-anthelmintic-resistance-amongst-grazing-calves
#1
Zoe Berk, Yan C S M Laurenson, Andrew B Forbes, Ilias Kyriazakis
The development of anthelmintic resistance by helminths can be slowed by maintaining refugia on pasture or in untreated hosts. Targeted selective treatments (TST) may achieve this through the treatment only of individuals that would benefit most from anthelmintic, according to certain criteria. However TST consequences on cattle are uncertain, mainly due to difficulties of comparison between alternative strategies. We developed a mathematical model to compare: 1) the most 'beneficial' indicator for treatment selection and 2) the method of selection of calves exposed to Ostertagia ostertagi, i...
November 16, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27888770/the-effect-of-the-disulfideisomerase-domain-containing-protein-in-the-defense-against-polyhexamethylene-biguanide-of-highly-tolerant-acanthamoeba-at-the-trophozoite-stage
#2
Fu-Chin Huang, Tao-Shen Liu, Sung-Chou Li, Min-Hsiu Shih, Jyh-Wei Shin, Wei-Chen Lin
Acanthamoeba castellanii is a free-living protozoan pathogen capable of causing a blinding keratitis and fatal granulomatous encephalitis. Current treatment generally involves an hourly application of polyhexamethylene biguanide (PHMB) over a period of several days but this is not entirely effective against all strains/isolates. The tolerance mechanisms of PHMB in Acanthamoeba cells remain unclear. In this study, we found that the mRNA expression level of disulfideisomerase domain containing protein (PDI) increased rapidly in surviving cells of the highly PHMB-tolerant Acanthamoeba castellanii strain, NCKH_D, during PHMB treatment, but not in the ATCC standard strain...
November 14, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27835769/efficacy-of-ivermectin-against-gastrointestinal-nematodes-of-cattle-in-denmark-evaluated-by-different-methods-for-analysis-of-faecal-egg-count-reduction
#3
Miguel Peña-Espinoza, Stig M Thamsborg, Matthew J Denwood, Markus Drag, Tina V Hansen, Vibeke F Jensen, Heidi L Enemark
The efficacy of ivermectin (IVM) against gastrointestinal nematodes in Danish cattle was assessed by faecal egg count reduction test (FECRT). Six cattle farms with history of clinical parasitism and avermectin use were included. On the day of treatment (Day 0), 20 naturally infected calves per farm (total n = 120) were stratified by initial faecal egg counts (FEC) and randomly allocated to a treatment group dosed with 0.2 mg IVM kg(-1) body weight s.c. (IVM; n = 10) or an untreated control group (CTL; n = 10)...
October 13, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27770751/effects-of-a-novel-%C3%AE-lapachone-derivative-on-trypanosoma-cruzi-parasite-death-involving-apoptosis-autophagy-and-necrosis
#4
Danielle Oliveira Dos Anjos, Eliomara Sousa Sobral Alves, Vinicius Tomaz Gonçalves, Sheila Suarez Fontes, Mateus Lima Nogueira, Ana Márcia Suarez-Fontes, João Batista Neves da Costa, Fabricio Rios-Santos, Marcos André Vannier-Santos
Natural products comprise valuable sources for new antiparasitic drugs. Here we tested the effects of a novel β-lapachone derivative on Trypanosoma cruzi parasite survival and proliferation and used microscopy and cytometry techniques to approach the mechanism(s) underlying parasite death. The selectivity index determination indicate that the compound trypanocidal activity was over ten-fold more cytotoxic to epimastigotes than to macrophages or splenocytes. Scanning electron microscopy analysis revealed that the R72 β-lapachone derivative affected the T...
October 12, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27821282/benzimidazole-resistance-survey-for-haemonchus-teladorsagia-and-trichostrongylus-in-three-european-countries-using-pyrosequencing-including-the-development-of-new-assays-for-trichostrongylus
#5
Sabrina Ramünke, Lynsey Melville, Laura Rinaldi, Hubertus Hertzberg, Theo de Waal, Georg von Samson-Himmelstjerna, Giuseppe Cringoli, Fabien Mavrot, Philip Skuce, Jürgen Krücken, Janina Demeler
Resistance to benzimidazoles (BZs) in trichostrongyloid nematodes is a worldwide problem for livestock production, particularly regarding small ruminants. Sensitive and reliable methods are required to assess anthelmintic resistance status. Currently available methods for BZ resistance detection can be divided into three main groups, in vivo (e.g. faecal egg count reduction test), in vitro (e.g. egg hatch assay) and molecular tests. Three single nucleotide polymorphisms (SNPs) in the isotype-1 β-tubulin gene of various nematode species correlate with BZ resistance...
October 8, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27760394/two-benzimidazole-resistance-associated-snps-in-the-isotype-1-%C3%AE-tubulin-gene-predominate-in-haemonchus-contortus-populations-from-eight-regions-in-china
#6
Zongze Zhang, Robin B Gasser, Xin Yang, Fangyuan Yin, Guanghui Zhao, Min Bao, Baoliang Pan, Weiyi Huang, Chunren Wang, Fengcai Zou, Yanqin Zhou, Junlong Zhao, Rui Fang, Min Hu
Haemonchus contortus is one of the most important parasitic nematodes of small ruminants around the world, particularly in tropical and subtropical regions. The control of haemonchosis relies mainly on anthelmintics, but the excessive and prolonged use of anthelmintics is causing serious drug resistance issues in many countries. As benzimidazole (BZ) anthelmintics have been broadly used in China, we hypothesized that resistance is widespread. Given the link between three known single nucleotide polymorphisms (SNPs, designated F167Y, E198A and F200Y) in the isotype-1 β-tubulin gene and BZ resistance, our goal here was to explore the presence of these mutations in H...
October 5, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27733308/profiling-the-macrofilaricidal-effects-of-flubendazole-on-adult-female-brugia-malayi-using-rnaseq
#7
Maeghan O'Neill, Cristina Ballesteros, Lucienne Tritten, Erica Burkman, Weam I Zaky, Jianguo Xia, Andrew Moorhead, Steven A Williams, Timothy G Geary
The use of microfilaricidal drugs for the control of onchocerciasis and lymphatic filariasis (LF) necessitates prolonged yearly dosing. Prospects for elimination or eradication of these diseases would be enhanced by the availability of a macrofilaricidal drug. Flubendazole (FLBZ), a benzimidazole anthelmintic, is an appealing candidate. FLBZ has demonstrated potent macrofilaricidal effects in a number of experimental rodent models and in one human trial. Unfortunately, FLBZ was deemed unsatisfactory for use in mass drug administration campaigns due to its limited oral bioavailability...
October 1, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27821281/molecular-determinants-of-sulfadoxine-pyrimethamine-resistance-in-plasmodium-falciparum-in-nigeria-and-the-regional-emergence-of-dhps-431v
#8
Mary C Oguike, Catherine O Falade, Elvis Shu, Izehiuwa G Enato, Ismaila Watila, Ebenezer S Baba, Jane Bruce, Jayne Webster, Prudence Hamade, Sylvia Meek, Daniel Chandramohan, Colin J Sutherland, David Warhurst, Cally Roper
There are few published reports of mutations in dihydropteroate synthetase (dhps) and dihydrofolate reductase (dhfr) genes in P. falciparum populations in Nigeria, but one previous study has recorded a novel dhps mutation at codon 431 among infections imported to the United Kingdom from Nigeria. To assess how widespread this mutation is among parasites in different parts of the country and consequently fill the gap in sulfadoxine-pyrimethamine (SP) resistance data in Nigeria, we retrospectively analysed 1000 filter paper blood spots collected in surveys of pregnant women and children with uncomplicated falciparum malaria between 2003 and 2015 from four sites in the south and north...
September 29, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27814986/anthelmintics-from-discovery-to-resistance-ii-san-diego-2016
#9
REVIEW
Richard J Martin, Adrian J Wolstenholme, Conor R Caffrey
The second scientific meeting in the series: "Anthelmintics: From Discovery to Resistance" was held in San Diego in February, 2016. The focus topics of the meeting, related to anthelmintic discovery and resistance, were novel technologies, bioinformatics, commercial interests, anthelmintic modes of action and anthelmintic resistance. Basic scientific, human and veterinary interests were addressed in oral and poster presentations. The delegates were from universities and industries in the US, Europe, Australia and New Zealand...
September 29, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27718413/exploring-the-scope-of-new-arylamino-alcohol-derivatives-synthesis-antimalarial-evaluation-toxicological-studies-and-target-exploration
#10
Miguel Quiliano, Adela Mendoza, Kim Y Fong, Adriana Pabón, Nathan E Goldfarb, Isabelle Fabing, Ariane Vettorazzi, Adela López de Cerain, Ben M Dunn, Giovanny Garavito, David W Wright, Eric Deharo, Silvia Pérez-Silanes, Ignacio Aldana, Silvia Galiano
Synthesis of new 1-aryl-3-substituted propanol derivatives followed by structure-activity relationship, in silico drug-likeness, cytotoxicity, genotoxicity, in silico metabolism, in silico pharmacophore modeling, and in vivo studies led to the identification of compounds 22 and 23 with significant in vitro antiplasmodial activity against drug sensitive (D6 IC50 ≤ 0.19 μM) and multidrug resistant (FCR-3 IC50 ≤ 0.40 μM and C235 IC50 ≤ 0.28 μM) strains of Plasmodium falciparum. Adequate selectivity index and absence of genotoxicity was also observed...
September 28, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27705841/human-dihydrofolate-reductase-influences-the-sensitivity-of-the-malaria-parasite-plasmodium-falciparum-to-ketotifen-a-cautionary-tale-in-screening-transgenic-parasites
#11
Phuong N Tran, Cameron J Tate, Melanie C Ridgway, Kevin J Saliba, Kiaran Kirk, Alexander G Maier
Ketotifen has recently been reported to inhibit the growth of both asexual and sexual malaria parasites. A parasite transporter, PfgABCG2, has been implicated in its mechanism of action. Human dihydrofolate reductase (hDHFR) is the most commonly used selectable marker to create transgenic Plasmodium falciparum cell lines. Growth assays using transgenic P. falciparum parasites with different selectable markers revealed that the presence of hDHFR rather than the absence of PfgABCG2 is responsible for a shift in the parasite's sensitivity to ketotifen...
September 22, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27751868/microfluidic-platform-for-electrophysiological-recordings-from-host-stage-hookworm-and-ascaris-suum-larvae-a-new-tool-for-anthelmintic-research
#12
Janis C Weeks, William M Roberts, Kristin J Robinson, Melissa Keaney, Jon J Vermeire, Joseph F Urban, Shawn R Lockery, John M Hawdon
The screening of candidate compounds and natural products for anthelmintic activity is important for discovering new drugs against human and animal parasites. We previously validated in Caenorhabditis elegans a microfluidic device ('chip') that records non-invasively the tiny electrophysiological signals generated by rhythmic contraction (pumping) of the worm's pharynx. These electropharyngeograms (EPGs) are recorded simultaneously from multiple worms per chip, providing a medium-throughput readout of muscular and neural activity that is especially useful for compounds targeting neurotransmitter receptors and ion channels...
September 15, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27746191/in-silico-analysis-of-the-binding-of-anthelmintics-to-caenorhabditis-elegansp-glycoprotein-1
#13
Marion A David, Stéphane Orlowski, Roger K Prichard, Shaima Hashem, François André, Anne Lespine
Macrocyclic lactones (ML) are important anthelmintics used in animals and humans against parasite nematodes, but their therapeutic success is compromised by the spread of ML resistance. Some ABC transporters, such as p-glycoproteins (Pgps), are selected and overexpressed in ML-resistant nematodes, supporting a role for some drug efflux proteins in ML resistance. However, the role of such proteins in ML transport remains to be clarified at the molecular level. Recently, Caenorhabditis elegans Pgp-1 (Cel-Pgp-1) has been crystallized, and its drug-modulated ATPase function characterized in vitro revealed Cel-Pgp-1 as a multidrug transporter...
September 15, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27639945/metabolic-profiling-and-in%C3%A2-vitro-assessment-of-anthelmintic-fractions-of-picria-fel-terrae-lour
#14
Rasika Kumarasingha, Avinash V Karpe, Sarah Preston, Tiong-Chia Yeo, Diana S L Lim, Chu-Lee Tu, Jennii Luu, Kaylene J Simpson, Jillian M Shaw, Robin B Gasser, David J Beale, Paul D Morrison, Enzo A Palombo, Peter R Boag
Anthelmintic resistance is widespread in gastrointestinal nematode populations, such that there is a consistent need to search for new anthelmintics. However, the cost of screening for new compounds is high and has a very low success rate. Using the knowledge of traditional healers from Borneo Rainforests (Sarawak, Malaysia), we have previously shown that some traditional medicinal plants are a rich source of potential new anthelmintic drug candidates. In this study, Picria fel-terrae Lour. plant extract, which has previously shown promising anthelmintic activities, was fractionated via the use of a solid phase extraction cartridge and each isolated fraction was then tested on free-living nematode Caenorhabditis elegans and the parasitic nematode Haemonchus contortus...
August 26, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27639944/assessing-anti-t-%C3%A2-cruzi-candidates-in%C3%A2-vitro-for-sterile-cidality
#15
Monica Cal, Jean-Robert Ioset, Matthia A Fügi, Pascal Mäser, Marcel Kaiser
Total clearance of the T. cruzi infection - referred to herein as "sterile cure" - seems to be a critical prerequisite for new drug candidates for Chagas disease, ensuring long-term beneficial effects for patients in the chronic indeterminate stage. This requirement is notably supported by the recent findings of clinical studies involving posaconazole and fosravuconazole, where the majority of patients treated eventually relapsed after an apparent clearance of parasitaemia at the end of treatment. We have adapted an in vitro system to predict the ability of a compound to deliver sterile cure...
August 26, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27317865/decreased-antimony-uptake-and-overexpression-of-genes-of-thiol-metabolism-are-associated-with-drug-resistance-in-a-canine-isolate-of-leishmania-infantum
#16
Verónica Gómez Pérez, Raquel García-Hernandez, Victoriano Corpas-López, Ana M Tomás, Joaquina Martín-Sanchez, Santiago Castanys, Francisco Gamarro
Visceral leishmaniasis (VL) caused by the protozoan parasite Leishmania infantum, is one of the most important zoonotic diseases affecting dogs and humans in the Mediterranean area. The presence of infected dogs as the main reservoir host of L. infantum is regarded as the most significant risk for potential human infection. We have studied the susceptibility profile to antimony and other anti-leishmania drugs (amphotericin B, miltefosine, paromomycin) in Leishmania infantum isolates extracted from a dog before and after two therapeutic interventions with meglumine antimoniate (subcutaneous Glucantime(®), 100 mg/kg/day for 28 days)...
August 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27183429/supplementation-of-host-response-by-targeting-nitric-oxide-to-the-macrophage-cytosol-is-efficacious-in-the-hamster-model-of-visceral-leishmaniasis-and-adds-to-efficacy-of-amphotericin-b
#17
Sanketkumar Pandya, Rahul Kumar Verma, Prashant Khare, Brajendra Tiwari, Dadi A Srinivasarao, Anuradha Dube, Neena Goyal, Amit Misra
We investigated efficacy of nitric oxide (NO) against Leishmania donovani. NO is a mediator of host response to infection, with direct parasiticidal activity in addition to its role in signalling to evoke innate macrophage responses. However, it is short-lived and volatile, and is therefore difficult to introduce into infected cells and maintain inracellular concentrations for meaningful periods of time. We incorporated diethylenetriamine NO adduct (DETA/NO), a prodrug, into poly(lactide-co-glycolide) particles of ∼200 nm, with or without amphotericin B (AMB)...
August 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27164440/abc-b-transporter-genes-in-dirofilaria-immitis
#18
Catherine Bourguinat, Hua Che, Thangadurai Mani, Kathy Keller, Roger K Prichard
Dirofilaria immitis is a filarial nematode causing infection and heartworm disease in dogs and other canids, cats, and occasionally in humans. Prevention with macrocyclic lactones (ML) is recommended during the mosquito transmission season. Recently, ML resistance has been reported. ABC-B transporter genes are thought to be involved in the mechanism of ML resistance in other nematodes. This study aimed to identify all the ABC-B transporter genes in D. immitis using as a reference the nDi.2.2 D. immitis whole genome, which is not completely annotated...
August 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27164439/effects-of-in%C3%A2-vitro-exposure-to-ivermectin-and-levamisole-on-the-expression-patterns-of-abc-transporters-in-haemonchus-contortus-larvae
#19
Ali Raza, Steven R Kopp, Neil H Bagnall, Abdul Jabbar, Andrew C Kotze
This study investigated the interaction of ATP binding cassette (ABC) transport proteins with ivermectin (IVM) and levamisole (LEV) in larvae of susceptible and resistant isolates of Haemonchus contortus in vitro by measuring transcription patterns following exposure to these anthelmintics. Furthermore, we studied the consequences of drug exposure by measuring the sensitivity of L3 to subsequent exposure to higher drug concentrations using larval migration assays. The most highly transcribed transporter genes in both susceptible and resistant L3 were pgp-9...
August 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27524698/screening-of-the-pathogen-box-identifies-an-approved-pesticide-with-major-anthelmintic-activity-against-the-barber-s-pole-worm
#20
Sarah Preston, Yaqing Jiao, Abdul Jabbar, Sean L McGee, Benoît Laleu, Paul Willis, Timothy N C Wells, Robin B Gasser
There is a substantial need to develop new medicines against parasitic diseases via public-private partnerships. Based on high throughput phenotypic screens of largely protozoal pathogens and bacteria, the Medicines for Malaria Venture (MMV) has recently assembled an open-access 'Pathogen Box' containing 400 well-curated chemical compounds. In the present study, we tested these compounds for activity against parasitic stages of the nematode Haemonchus contortus (barber's pole worm). In an optimised, whole-organism screening assay, using exsheathed third-stage (xL3) and fourth-stage (L4) larvae, we measured the inhibition of larval motility, growth and development of H...
July 28, 2016: International Journal for Parasitology, Drugs and Drug Resistance
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