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International Journal for Parasitology, Drugs and Drug Resistance

Aruna Shrestha, Kayode K Ojo, Florian Koston, Bärbel Ruttkowski, Rama S R Vidadala, Carlie S Dorr, Edelmar D Navaluna, Grant R Whitman, Kayleigh F Barrett, Lynn K Barrett, Matthew A Hulverson, Ryan Choi, Samantha A Michaels, Dustin J Maly, Andrew Hemphill, Wesley C Van Voorhis, Anja Joachim
Cystoisosporosis is a leading diarrheal disease in suckling piglets. With the confirmation of resistance against the only available drug toltrazuril, there is a substantial need for novel therapeutics to combat the infection and its negative effects on animal health. In closely related apicomplexan species, bumped kinase inhibitors (BKIs) targeting calcium-dependent protein kinase 1 (CDPK1) were shown to be effective in inhibiting host-cell invasion and parasite growth. Therefore, the gene coding for Cystoisospora suis CDPK1 (CsCDPK1) was identified and cloned to investigate activity and thermal stabilization of the recombinant CsCDPK1 enzyme by BKI 1369...
April 2, 2019: International Journal for Parasitology, Drugs and Drug Resistance
Rubén Martín-Escolano, Rubén Cebrián, Javier Martín-Escolano, Maria J Rosales, Mercedes Maqueda, Manuel Sánchez-Moreno, Clotilde Marín
Chagas disease caused by the protozoan parasite Trypanosoma cruzi represents a significant public health problem in Latin America, affecting around 8 million cases worldwide. Nowadays is urgent the identification of new antichagasic agents as the only therapeutic options available, Nifurtimox and Benznidazole, are in use for >40 years, and present high toxicity, limited efficacy and frequent treatment failures in the chronic phase of the disease. Recently, it has been described the antiparasitic effect of AS-48, a bacteriocin produced by Enterococcus faecalis, against Trypanosoma brucei and Leishmania spp...
March 29, 2019: International Journal for Parasitology, Drugs and Drug Resistance
Joachim Müller, Sophie Braga, Manfred Heller, Norbert Müller
In order to elucidate the question whether resistance to nitro drugs in G. lamblia is due to common resistance markers, trophozoites of three resistant G. lamblia strains, namely C4, 1062ID10, and 713M3 were grown in the presence of the two nitro drugs metronidazole and nitazoxanide and compared to their corresponding wild-types WBC6, 106, and 713 by mass spectometry shotgun analysis of their proteomes. Depending on the strain and the nitro drug, more than 200 to 500 differentially expressed proteins were identified, but there were no common patterns across strains and drugs...
March 15, 2019: International Journal for Parasitology, Drugs and Drug Resistance
Guilherme M Klafke, Robert J Miller, Jason P Tidwell, Donald B Thomas, Daniela Sanchez, Teresa P Feria Arroyo, Adalberto A Pérez de León
The southern cattle fever tick, Rhipicephalus (Boophilus) microplus, is the most economically important ectoparasite of cattle worldwide. A limitation for sustainable control and eradication is the emergence of acaricide resistance among tick populations. Molecular diagnostic tools offer the opportunity to detect resistance rapidly, which can be complemented with confirmatory bioassays with larvae and adult ticks that are more resource and time consuming to generate. Synthetic pyrethroid resistance is one of the most prevalent and well-studied forms of resistance in arthropods, being linked with target site alterations in the sodium ion channel gene...
March 13, 2019: International Journal for Parasitology, Drugs and Drug Resistance
Katrien Van Bocxlaer, Diana Caridha, Chad Black, Brian Vesely, Susan Leed, Richard J Sciotti, Gert-Jan Wijnant, Vanessa Yardley, Stéphanie Braillard, Charles E Mowbray, Jean-Robert Ioset, Simon L Croft
OBJECTIVES: Drugs for Neglected Diseases initiative (DNDi) has identified three chemical lead series, the nitroimidazoles, benzoxaboroles and aminopyrazoles, as innovative treatments for visceral leishmaniasis. The leads discovered using phenotypic screening, were optimised following disease- and compound-specific criteria. Several leads of each series were progressed and preclinical drug candidates have been nominated. Here we evaluate the efficacy of the lead compounds of each of these three chemical classes in in vitro and in vivo models of cutaneous leishmaniasis...
February 26, 2019: International Journal for Parasitology, Drugs and Drug Resistance
Caroline R Espada, Rubens M Magalhães, Mario C Cruz, Paulo R Machado, Albert Schriefer, Edgar M Carvalho, Valentín Hornillos, João M Alves, Angela K Cruz, Adriano C Coelho, Silvia R B Uliana
In Brazil, cutaneous leishmaniasis is caused predominantly by L. (V.) braziliensis. The few therapeutic drugs available exhibit several limitations, mainly related to drug toxicity and reduced efficacy in some regions. Miltefosine (MF), the only oral drug available for leishmaniasis treatment, is not widely available and has not yet been approved for human use in Brazil. Our group previously reported the existence of differential susceptibility among L. (V.) braziliensis clinical isolates. In this work, we further characterized three of these isolates of L...
February 25, 2019: International Journal for Parasitology, Drugs and Drug Resistance
Hugo R Vaca, Ana M Celentano, Natalia Macchiaroli, Laura Kamenetzky, Federico Camicia, Mara C Rosenzvit
Cestode parasites cause neglected diseases, such as echinococcosis and cysticercosis, which represent a significant problem in human and animal health. Benzimidazoles and praziquantel are the only available drugs for chemotherapy and it is therefore important to identify new alternative drugs against cestode parasites. Histone deacetylases (HDACs) are validated drug targets for the treatment of cancer and other diseases, including neglected diseases. However, knowledge of HDACs in cestodes is very scarce. In this work, we investigated cestode HDACs as potential drug targets to develop new therapies against neglected diseases caused by cestodes...
February 23, 2019: International Journal for Parasitology, Drugs and Drug Resistance
Donelly A van Schalkwyk, Benjamin Blasco, Rocio Davina Nuñez, Jonathan W K Liew, Amirah Amir, Yee L Lau, Didier Leroy, Robert W Moon, Colin J Sutherland
New antimalarial agents are identified and developed after extensive testing on Plasmodium falciparum parasites that can be grown in vitro. These susceptibility studies are important to inform lead optimisation and support further drug development. Until recently, little was known about the susceptibility of non-falciparum species as these had not been adapted to in vitro culture. The recent culture adaptation of P. knowlesi has therefore offered an opportunity to routinely define the drug susceptibility of this species, which is phylogenetically closer to all other human malarias than is P...
February 22, 2019: International Journal for Parasitology, Drugs and Drug Resistance
Bumduuren Tuvshintulga, Thillaiampalam Sivakumar, Naoaki Yokoyama, Ikuo Igarashi
Diminazene aceturate (DA) is commonly used in the treatment of bovine babesiosis caused by Babesia bovis. In this study, we attempted to develop resistance in B. bovis in vitro to DA and clofazimine (CF, a novel antibabesial agent) using short- and long-term drug pressures. In the short term, we found that 6.7 ± 2 (0.54 ± 0.16 μM)-, 12.9 ± 8.6 (1.05 ± 0.7 μM)-, and 14 ± 5.9 (1.14 ± 0.48 μM)-fold increases in the half-maximal inhibitory concentration (IC50 ) of DA were demonstrated on B...
February 13, 2019: International Journal for Parasitology, Drugs and Drug Resistance
James Nyagwange, Elias Awino, Edwin Tijhaar, Nicholas Svitek, Roger Pelle, Vishvanath Nene
Chemotherapy of East Coast fever, a lymphoproliferative cancer-like disease of cattle causing significant economic losses in Africa, is largely dependent on the use of buparvaquone, a drug that was developed in the late 1980's. The disease is caused by the tick-borne protozoan pathogen Theileria parva. Buparvaquone can be used prophylactically and it is also active against tropical theileriosis, caused by the related parasite Theileria annulata. Recently, drug resistance was reported in T. annulata, and could occur in T...
January 25, 2019: International Journal for Parasitology, Drugs and Drug Resistance
Anthonius A Eze, John Igoli, Alexander I Gray, Graham G Skellern, Harry P De Koning
The four components present in the trypanocidal treatment Samorin, the commercially available formulation of isometamidium, were separated and purified by column chromatography. These compounds as well as the Samorin mixture and the other phenanthridine trypanocide, homidium, were tested on Trypanosoma congolense and wild type, diamidine- and isometamidium-resistant Trypanosoma brucei brucei strains using an Alamar blue drug sensitivity assay. EC50 values obtained suggest that M&B4180A (2) was the most active of the components, followed by M&B38897 (1) in all the strains tested, whereas M&B4596 (4) was inactive...
January 21, 2019: International Journal for Parasitology, Drugs and Drug Resistance
Sanaa S Botros, Samia William, Abdel-Nasser A Sabra, Naglaa M El-Lakkany, Sayed H Seif El-Din, Alfonso García-Rubia, Victor Sebastián-Pérez, Antoni R Blaazer, Erik de Heuvel, Maarten Sijm, Yang Zheng, Irene G Salado, Jane C Munday, Louis Maes, Iwan J P de Esch, Geert J Sterk, Koen Augustyns, Rob Leurs, Carmen Gil, Harry P De Koning
We report the evaluation of 265 compounds from a PDE-focused library for their antischistosomal activity, assessed in vitro using Schistosoma mansoni. Of the tested compounds, 171 (64%) displayed selective in vitro activity, with 16 causing worm hypermotility/spastic contractions and 41 inducing various degrees of worm killing at 100 μM, with the surviving worms displaying sluggish movement, worm unpairing and complete absence of eggs. The compounds that did not affect worm viability (n = 72) induced a complete cessation of ovipositing...
January 14, 2019: International Journal for Parasitology, Drugs and Drug Resistance
H M P Dilrukshi Herath, Sarah Preston, Abdul Jabbar, Jose Garcia-Bustos, Russell S Addison, Sasha Hayes, Topul Rali, Tao Wang, Anson V Koehler, Bill C H Chang, Andreas Hofmann, Rohan A Davis, Robin B Gasser
Due to the widespread occurrence and spread of anthelmintic resistance, there is a need to develop new drugs against resistant parasitic nematodes of livestock animals. The Nobel Prize-winning discovery and development of the anti-parasitic drugs avermectin and artemisinin has renewed the interest in exploring natural products as anthelmintics. In the present study, we screened 7500 plant extracts for in vitro-activity against the barber's pole worm, Haemonchus contortus, a highly significant pathogen of ruminants...
January 4, 2019: International Journal for Parasitology, Drugs and Drug Resistance
Yaqing Jiao, Sarah Preston, Jose F Garcia-Bustos, Jonathan B Baell, Sabatino Ventura, Thuy Le, Nicole McNamara, Nghi Nguyen, Antony Botteon, Cameron Skinner, Jill Danne, Sarah Ellis, Anson V Koehler, Tao Wang, Bill C H Chang, Andreas Hofmann, Abdul Jabbar, Robin B Gasser
In the present study, the anthelmintic activity of a human tyrosine kinase inhibitor, AG-1295, and 14 related tetrahydroquinoxaline analogues against Haemonchus contortus was explored. These compounds were screened against parasitic larvae - exsheathed third-stage (xL3) and fourth-stage (L4) - using a whole-organism screening assay. All compounds were shown to have inhibitory effects on larval motility, development and growth, and induced evisceration through the excretory pore in xL3s. The estimated IC50 values ranged from 3...
December 30, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Shivani Choudhary, Djordje S Marjianović, Colin R Wong, Xiaoyu Zhang, Melanie Abongwa, Joel R Coats, Saša M Trailović, Richard J Martin, Alan P Robertson
The ongoing and widespread emergence of resistance to the existing anti-nematodal pharmacopeia has made it imperative to develop new anthelminthic agents. Historically, plants have been important sources of therapeutic compounds and offer an alternative to synthetic drugs. Monoterpenoids are phytochemicals that have been shown to produce acute toxic effects in insects and nematodes. Previous studies have shown nicotinic acetylcholine receptors (nAChRs) to be possible targets for naturally occurring plant metabolites such as carvacrol and carveol...
December 30, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Ji Li Zhang, Hong Fei Si, Xiao Fei Shang, Xu Kun Zhang, Bing Li, Xu Zheng Zhou, Ji Yu Zhang
Toxoplasma gondii is the causative agent of toxoplasmosis and causes serious public health problems. However, the current treatment drugs have many limitations, such as serious side effects. Niclosamide is a salicylanilide drug commonly used to treat worm infections. Herein, the effectiveness of niclosamide for the treatment of T. gondii infection was demonstrated. This study was to evaluate the in vitro and in vivo activities of niclosamide against T. gondii and to explore its mechanism of action. The in vitro cytotoxicity of niclosamide on human foreskin fibroblast cells was evaluated by MTT test...
December 21, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Ryan C Henrici, Donelly A van Schalkwyk, Colin J Sutherland
Clinical studies suggest that outcomes for hospitalised malaria patients can be improved by managed hypothermia during treatment. We examined the impact of short pulses of low temperature on ring-stage susceptibility of Plasmodium falciparum to artemisinin in vitro. The usually artemisinin-sensitive clone 3D7 exhibited substantially reduced ring-stage susceptibility to a 4-h pulse of 700 nM dihydro-artemisinin administered during a 5-h pulse of low temperature down to 17 °C. Parasite growth through the subsequent asexual cycle was not affected by the temperature pulse...
December 16, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Patrícia Valéria Castelo-Branco, Hugo José Alves, Raissa Lacerda Pontes, Vera Lucia Maciel-Silva, Silma Regina Ferreira Pereira
Leishamaniasis is a neglected disease caused by over 20 Leishmania species, occurring in more than a hundred countries. Miltefosine (hexadecylphosphocholine) is the single oral drug used in treatment for leshmaniases, including cases of infections resistant to pentavalent antimony. Our group has recently demonstrated the ability of miltefosine to cause genomic lesions by DNA oxidation. Acknowledging that antioxidant compounds can potentially modulate Reactive Oxygen Species (ROS), our study verified whether ascorbic acid reduces the genotoxic and mutagenic effects caused by miltefosine, and whether it interferes with drug efficacy...
December 13, 2018: International Journal for Parasitology, Drugs and Drug Resistance
S Hendrickx, D Bulté, M Van den Kerkhof, P Cos, P Delputte, L Maes, G Caljon
Although miltefosine (MIL) has only been approved for the treatment of visceral leishmaniasis (VL) in 2002, its application in monotherapy already led to the development of two confirmed MIL-resistant isolates by 2009. Although liposomal amphotericin B is recommended as first-line treatment in Europe, MIL is still occasionally used in HIV co-infected patients. Since their immune system is incapable of controlling the infection, high parasite burdens and post-treatment relapses are common. Linked to the particular pharmacokinetic profile of MIL, successive treatment of recurrent relapses could in principle facilitate the emergence of drug resistance...
December 11, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Duangkamon Loesbanluechai, Namfon Kotanan, Cristina de Cozar, Theerarat Kochakarn, Megan R Ansbro, Kesinee Chotivanich, Nicholas J White, Prapon Wilairat, Marcus C S Lee, Francisco Javier Gamo, Laura Maria Sanz, Thanat Chookajorn, Krittikorn Kümpornsin
Artemisinin derivatives and their partner drugs in artemisinin combination therapies (ACTs) have played a pivotal role in global malaria mortality reduction during the last two decades. The loss of artemisinin efficacy due to evolving drug-resistant parasites could become a serious global health threat. Dihydroartemisinin-piperaquine is a well tolerated and generally highly effective ACT. The implementation of a partner drug in ACTs is critical in the control of emerging artemisinin resistance. Even though artemisinin is highly effective in parasite clearance, it is labile in the human body...
December 1, 2018: International Journal for Parasitology, Drugs and Drug Resistance
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