Journals International Journal for Para...

International Journal for Parasitology, Drugs and Drug Resistance
Christian M Leutenegger, Cecilia E Lozoya, Jeffrey Tereski, Christian Savard, Jennifer Ogeer, Rene Lallier
BACKGROUND: Anthelmintic resistance to benzimidazole has been detected in the canine hookworm, Ancylostoma caninum. Benzimidazole resistance is believed to have developed originally in greyhounds, but has also been detected in non-greyhound pet dogs. The aim of this study was to validate a probe-based allele-specific real-time PCR tests for the F167Y polymorphism on the β-tubulin isotype-1 gene and to determine the geographic distribution. METHODS: Allele-specific real-time PCR tests were established and validated to detect the codon 167 polymorphism in the Ancylostoma caninum β-tubulin isotype-1gene...
March 14, 2023: International Journal for Parasitology, Drugs and Drug Resistance
Roman Memedovski, Matías Preza, Joachim Müller, Tobias Kämpfer, Reto Rufener, Marcus Vinicius Nora de Souza, Emerson Teixeira da Silva, Gabriel Fernandes de Andrade, Sophie Braga, Anne-Christine Uldry, Natasha Buchs, Manfred Heller, Britta Lundström-Stadelmann
Alveolar echinococcosis (AE) is caused by infection with the fox tapeworm E. multilocularis. The disease affects humans, dogs, captive monkeys, and other mammals, and it is caused by the metacestode stage of the parasite growing invasively in the liver. The current drug treatment is based on non-parasiticidal benzimidazoles. Thus, they are only limitedly curative and can cause severe side effects. Therefore, novel and improved treatment options for AE are needed. Mefloquine (MEF), an antimalarial agent, was previously shown to be effective against E...
March 9, 2023: International Journal for Parasitology, Drugs and Drug Resistance
K E Bull, K J Allen, J E Hodgkinson, L E Peachey
In recent years, resistance to the benzimidazole (BZ) and tetrahydropyrimidine (PYR) anthelmintics in global cyathostomin populations, has led to reliance on the macrocyclic lactone drugs (ML-of which ivermectin and moxidectin are licensed in horses) to control these parasites. Recently, the first confirmed case of resistance to both ivermectin (IVM) and moxidectin (MOX) was reported in the USA in yearlings imported from Ireland. This suggests that ML resistance in cyathostomins has emerged, and raises the possibility that regular movement of horses may result in rapid spread of ML resistant cyathostomins...
March 7, 2023: International Journal for Parasitology, Drugs and Drug Resistance
Kotaro Takano, Lachlan de Hayr, Scott Carver, Robert J Harvey, Kate E Mounsey
Sarcoptes scabiei is the microscopic burrowing mite responsible for sarcoptic mange, which is reported in approximately 150 mammalian species. In Australia, sarcoptic mange affects a number of native and introduced wildlife species, is particularly severe in bare-nosed wombats (Vombatus ursinus) and an emerging issue in koala and quenda. There are a variety of acaricides available for the treatment of sarcoptic mange which are generally effective in eliminating mites from humans and animals in captivity. In wild populations, effective treatment is challenging, and concerns exist regarding safety, efficacy and the potential emergence of acaricide resistance...
March 5, 2023: International Journal for Parasitology, Drugs and Drug Resistance
Paulius Baltrušis, Peter Halvarsson, Claude L Charvet, Johan Höglund
Parasitic sheep nematodes, among which Haemonchus contortus is often considered to be the most clinically important, exact a significant toll on the animals, not least because of their capacity to evolve drug resistance. Despite decades of research, our understanding of the mechanism of resistance to compounds such as levamisole is fairly limited, which therefore constrains our ability to develop sensitive and efficient molecular diagnostic tools for rapid and accurate resistance detection in field settings...
February 8, 2023: International Journal for Parasitology, Drugs and Drug Resistance
Jiao Mo, Hongfei Si, Siyang Liu, Qingyuan Zeng, Minghao Cai, Zhendi Liu, Jiyu Zhang, Jingjing Fang, Jili Zhang
Toxoplasmosis is a widespread disease in humans and animals. Currently, toxoplasmosis chemotherapy options are limited due to severe side effects. There is an urgent need to develop new drugs with better efficacy and few side effects. HQNO, a cytochrome bc1 and type II NADH inhibitor in eukaryotes and bacteria, possesses extensive bioactivity. In this study, the cytotoxicity of HQNO was evaluated in Vero cells. The in vitro effects of HQNO were determined by plaque assay and qPCR assay. To determine the in vivo effect of HQNO, pharmacokinetic experiments and in vivo infection assays were performed in mice...
February 4, 2023: International Journal for Parasitology, Drugs and Drug Resistance
Yu Yu, Wenhao Huang, Qingjie Wang, Hui Dong, Qiping Zhao, Shunhai Zhu, Bing Huang, Hongyu Han
Eimeria tenella, an intestinal parasite, has brought huge economic losses to the poultry industry. The prevalence and severity of the development of drug resistance has increased the challenge of coccidiosis control. We previously identified the enolase 2 of E. tenella (EtENO2) was differentially expressed in drug-sensitive (DS) and drug-resistant strains using RNA-seq. In this study, the expression of EtENO2 in diclazuril-resistant (DZR), maduramicin-resistant (MRR), and salinomycin-resistant (SMR) strains was analyzed by quantitative real-time PCR (qRT-PCR) and western blots...
February 3, 2023: International Journal for Parasitology, Drugs and Drug Resistance
Katalin Toth, Sevan Alwan, Susan Khan, Stanton F McHardy, Philip T LoVerde, Michael D Cameron
The antischistosomal drug oxamniquine, OXA, requires activation by a sulfotransferase within the parasitic worm to enable killing. Examination of the pharmacokinetic/pharmacodynamic (PK/PD) relationship for OXA identified an in vitro-in vivo paradox with the maximal clinical plasma concentrations five-to ten-times lower than the efficacious concentration for in vitro schistosomal killing. The parasite resides in the vasculature between the intestine and the liver, and modeling the PK data to determine portal concentrations fits with in vitro studies and explains the required human dose...
January 30, 2023: International Journal for Parasitology, Drugs and Drug Resistance
Saranya Auparakkitanon, Prapon Wilairat
The appearance in 2008 in western Cambodia of Plasmodium falciparum tolerant to artemisinin, defined by longer parasite clearance time following drug administration and in vitro by a slightly higher survival rate of the ring stage after a 3-h treatment with 700 nM artemisinin (or analogues, collectively termed ART), has raised concerns of the possible loss of this frontline antimalarial [used in the form of an artemisinin combination therapy (ACT)], with its low IC50 value against the ring stage and pleiotropic pro-drug/poison property...
January 16, 2023: International Journal for Parasitology, Drugs and Drug Resistance
Christina S Saghaug, Astrid L Gamlem, Kirsti B Hauge, Juha Vahokoski, Christian Klotz, Toni Aebischer, Nina Langeland, Kurt Hanevik
The effectiveness of metronidazole against the tetraploid intestinal parasite Giardia lamblia is dependent on its activation/inactivation within the cytoplasm. There are several activating enzymes, including pyruvate ferredoxin reductase (PFOR) and nitroreductase (NR) 1 which metabolize metronidazole into toxic forms, while NR2 on the other hand inactivates it. Metronidazole treatment failures have been increasing rapidly over the last decade, indicating genetic resistance mechanisms. Analyzing genetic variation in the PFOR and NR genes in susceptible and refractory Giardia isolates may help identify potential markers of resistance...
December 21, 2022: International Journal for Parasitology, Drugs and Drug Resistance
Stephanie L Macdonald, Ghazanfar Abbas, Abdul Ghafar, Charles G Gauci, Jenni Bauquier, Charles El-Hage, Brett Tennent-Brown, Edwina J A Wilkes, Anne Beasley, Caroline Jacobson, Lucy Cudmore, Peter Carrigan, John Hurley, Ian Beveridge, Kristopher J Hughes, Martin K Nielsen, Abdul Jabbar
Cyathostomins are the most common and highly prevalent parasites of horses worldwide. Historically, the control of cyathostomins has mainly relied on the routine use of anthelmintic products. Increasing reports on anthelmintic resistance (AR) in cyathostomins are concerning. A potential method proposed for detecting emerging AR in cyathostomins has been estimating the egg reappearance period (ERP). This paper reviews the data available for the ERP of cyathostomins against the three major classes of anthelmintics, macrocyclic lactones, tetrahydropyrimidines, and benzimidazoles...
December 13, 2022: International Journal for Parasitology, Drugs and Drug Resistance
Agriana Rosmalina Hidayati, Melinda, Hilkatul Ilmi, Takaya Sakura, Miako Sakaguchi, Junko Ohmori, Endah Dwi Hartuti, Lidya Tumewu, Daniel Ken Inaoka, Mulyadi Tanjung, Eri Yoshida, Fuyuki Tokumasu, Kiyoshi Kita, Mihoko Mori, Kazuyuki Dobashi, Tomoyoshi Nozaki, Din Syafruddin, Achmad Fuad Hafid, Danang Waluyo, Aty Widyawaruyanti
Nearly half of the world's population is at risk of being infected by Plasmodium falciparum, the pathogen of malaria. Increasing resistance to common antimalarial drugs has encouraged investigations to find compounds with different scaffolds. Extracts of Artocarpus altilis leaves have previously been reported to exhibit in vitro antimalarial activity against P. falciparum and in vivo activity against P. berghei. Despite these initial promising results, the active compound from A. altilis is yet to be identified...
December 8, 2022: International Journal for Parasitology, Drugs and Drug Resistance
Joachim Müller, Carling Schlange, Manfred Heller, Anne-Christine Uldry, Sophie Braga-Lagache, Richard K Haynes, Andrew Hemphill
The sesquiterpene lactone artemisinin and its amino-artemisinin derivatives artemiside (GC008) and artemisone (GC003) are potent antimalarials. The mode of action of artemisinins against Plasmodium sp is popularly ascribed to 'activation' of the peroxide group by heme-Fe(II) or labile Fe(II) to generate C-radicals that alkylate parasite proteins. An alternative postulate is that artemisinins elicit formation of reactive oxygen species by interfering with flavin disulfide reductases resposible for maintaining intraparasitic redox homeostasis...
December 8, 2022: International Journal for Parasitology, Drugs and Drug Resistance
Mehdi Bamorovat, Iraj Sharifi, Setareh Agha Kuchak Afshari, Ali Karamoozian, Amirhossein Tahmouresi, Amireh Heshmatkhah, Ehsan Salarkia, Ahmad Khosravi, Maryam Hakimi Parizi, Maryam Barghi
Leishmaniasis is an overlooked, poverty-stricken, and complex disease with growing social and public health problems. In general, leishmaniasis is a curable disease; however, there is an expansion of unresponsive cases to treatment in cutaneous leishmaniasis (CL). One of the effective and ignored determinants in the treatment outcome of CL is poor treatment adherence (PTA). PTA is an overlooked and widespread phenomenon to proper Leishmania treatment. This study aimed to explore the effect of poor adherence in unresponsiveness to treatment in patients with anthroponotic CL (ACL) by comparing conventional statistical modalities and machine learning analyses in Iran...
December 5, 2022: International Journal for Parasitology, Drugs and Drug Resistance
Sophia Bigot, Philippe Leprohon, Abimael Vasquez, Rohit Bhadoria, Rachid Skouta, Marc Ouellette
Treatments against leishmaniasis are limited and the development of new molecules is crucial. One class of developmental drug that has shown activity against the parasite Leishmania are thiophene derivatives. Here we synthetized thirty-eight novel thiophene compounds and characterized their activity and potential for resistance against L. infantum. Half of the molecules had an EC50 in the low micromolar range, the piperidine derivatives being more potent than the tetramethylpyran derivatives. Resistance was challenging to select for, and resistant cells could only be raised against one (GC1-19) of the four most active compounds...
November 25, 2022: International Journal for Parasitology, Drugs and Drug Resistance
Rosemonde Isabella Power, Jan Šlapeta
Canine heartworm disease is a potentially deadly cardiopulmonary disease caused by the mosquito-borne filarial nematode Dirofilaria immitis. In Australia, the administration of macrocyclic lactone (ML) drugs has successfully reduced the prevalence of D. immitis infection. However, the recent re-emergence of D. immitis in dogs in Queensland, Australia and the identification of ML-resistant isolates in the USA poses an important question of whether ML-resistance has emerged in this parasite in Australia. The aim of this study was to utilise phenotypic and genotypic approaches to examine the sensitivity to ML drugs in D...
November 15, 2022: International Journal for Parasitology, Drugs and Drug Resistance
Ning Wang, Han-Qi Peng, Chang-Zhe Gao, Yu-Heng Cheng, Meng-Tao Sun, Guo-Li Qu, Joanne P Webster, Da-Bing Lu
Schistosomiasis is a major neglected tropical disease mainly caused by Schistosoma haematobium, S. japonicum and S. mansoni, and results in the greatest disease burden. Mass drug administration (MDA) with praziquantel (PZQ), a single drug only available for the disease, has played a vital role in schistosomiasis control. Therefore, any possibility of selection of the parasites for PZQ resistance or low sensitivity may hamper the 2030's target of global disease elimination. We had experimentally demonstrated the long-term survival and reproductive potential of single-sex (of either sex) S...
November 12, 2022: International Journal for Parasitology, Drugs and Drug Resistance
Matthew P Challis, Shane M Devine, Darren J Creek
New antimalarial compounds with novel mechanisms of action are urgently needed to combat the recent rise in antimalarial drug resistance. Phenotypic high-throughput screens have proven to be a successful method for identifying new compounds, however, do not provide mechanistic information about the molecular target(s) responsible for antimalarial action. Current and emerging target identification methods such as in vitro resistance generation, metabolomics screening, chemoproteomic approaches and biophysical assays measuring protein stability across the whole proteome have successfully identified novel drug targets...
November 11, 2022: International Journal for Parasitology, Drugs and Drug Resistance
Thuy-Tien Thi Trinh, Su-Yeon Yun, Gum-Ju Bae, Kwonmo Moon, Hyelee Hong, Tae Hui Eum, Young-Ah Kim, Soon-Ai Kim, Hyun Park, Hak Sung Kim, Seon-Ju Yeo
Malaria is among the most devastating and widespread tropical parasitic diseases in developing countries. To prevent a potential public health emergency, there is an urgent need for new antimalarial drugs, with single-dose cures, broad therapeutic potential, and novel mechanism of action. We synthesized HCl salt of SKM13 (SKM13-2HCl) based on the modification of SKM13 to improve solubility in water. The anti-malarial activity of the synthesized drug was evaluated in both in vitro and in vivo models. The selective index indicated that SKM13-2HCl showed the same effectiveness with SKM13 in Plasmodium falciparum in in-vitro...
November 8, 2022: International Journal for Parasitology, Drugs and Drug Resistance
Wilian A Cortopassi, Emma Gunderson, Yasmin Annunciato, Antony E S Silva, Amália Dos Santos Ferreira, Carolina Bioni Garcia Teles, Andre S Pimentel, Roopa Ramamoorthi, Marcos L Gazarini, Mario R Meneghetti, Rafael V C Guido, Dhelio B Pereira, Matthew P Jacobson, Antoniana U Krettli, Anna Caroline C Aguiar
Malaria is among the tropical diseases that cause the most deaths in Africa. Around 500,000 malaria deaths are reported yearly among African children under the age of five. Chloroquine (CQ) is a low-cost antimalarial used worldwide for the treatment of Plasmodium vivax malaria. Due to resistance mechanisms, CQ is no longer effective against most malaria cases caused by P. falciparum. The World Health Organization recommends artemisinin combination therapies for P. falciparum malaria, but resistance is emerging in Southeast Asia and some parts of Africa...
October 31, 2022: International Journal for Parasitology, Drugs and Drug Resistance
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