Profiles of Kelch mutations in Plasmodium falciparum across South Asia and their implications for tracking drug resistance
Publication date: Available online 4 October 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Jyoti Chhibber-Goel, Amit SharmaAbstractArtemisinin-based combination therapy (ACT) offers highly successful treatment of malaria. Emergence and spread of Plasmodium falciparum (Pf) parasites with decreased susceptibility to ACT in South-East Asia has caused concern worldwide. The current accepted criteria to assess artemisinin (ART) resistance relies upon data on treatment failure, delayed parasite clearance at day 3 (DPC3), parasite clearance half-life (PCHL) and in-vitro/ex-vivo ring stage...
Source: International Journal for Parasitology: Drugs and Drug Resistance - October 6, 2019 Category: Parasitology Source Type: research

Development of a topical liposomal formulation of Amphotericin B for the treatment of cutaneous leishmaniasis
Publication date: Available online 23 September 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Mahmoud Reza Jaafari, Mahdi Hatamipour, Seyedeh Hoda Alavizadeh, Azam Abbasi, Zahra Saberi, Sima Rafati, Yasaman Taslimi, Akram Miramin Mohammadi, Ali KhamesipourAbstractBackgroundCurrently, there is no topical treatment available for any form of cutaneous leishmaniasis (CL) in most of the endemic areas. The aim of the current study was to develop a topical nano-liposomal Amphotericin B (AmB) for the treatment of CL.Methodology/Principal Findings: Liposomes containing 0.1, 0.2 and 0.4% AmB...
Source: International Journal for Parasitology: Drugs and Drug Resistance - September 24, 2019 Category: Parasitology Source Type: research

Topoisomerase IB poisons induce histone H2A phosphorylation as a response to DNA damage in Leishmania infantum
This report shows for the first time the effect of a series of synthetic indenoisoquinolines on histone H2A phosphorylation, which represents a primary signal of double stranded DNA break in genus Leishmania.Graphical abstract (Source: International Journal for Parasitology: Drugs and Drug Resistance)
Source: International Journal for Parasitology: Drugs and Drug Resistance - September 21, 2019 Category: Parasitology Source Type: research

Anti-schistosomal action of the calcium channel agonist FPL-64176
Publication date: Available online 14 September 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Paul McCusker, John D. ChanAbstractSubversion of parasite neuromuscular function is a key strategy for anthelmintic drug development. Schistosome Ca2+ signaling has been an area of particular interest for decades, with a specific focus on L-type voltage-gated Ca2+ channels (Cavs). However, the study of these channels has been technically challenging. One barrier is the lack of pharmacological probes that are active on flatworms, since the dihydropyridine (DHP) based ligands typically used ...
Source: International Journal for Parasitology: Drugs and Drug Resistance - September 15, 2019 Category: Parasitology Source Type: research

Impaired development of a miltefosine-resistant Leishmania infantum strain in the sand fly vectors Phlebotomus perniciosus and Lutzomyia longipalpis
ConclusionThe MIL resistant L. infantum LEM3323 line is significantly hampered in its development and transmissibility potential in two sand fly vector species. Additional studies are warranted to evaluate whether this applies to other visceral Leishmania parasites with acquired MIL-resistance.Graphical abstract (Source: International Journal for Parasitology: Drugs and Drug Resistance)
Source: International Journal for Parasitology: Drugs and Drug Resistance - September 12, 2019 Category: Parasitology Source Type: research

Similarities and differences in the biotransformation and transcriptomic responses of Caenorhabditis elegans and Haemonchus contortus to five different benzimidazole drugs
Publication date: Available online 9 September 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): S.J. Stasiuk, G. MacNevin, M. Workentine, D. Gray, E. Redman, D. Bartley, A. Morrison, N. Sharma, D. Colwell, D.K. Ro, J.S. GilleardAbstractWe have undertaken a detailed analysis of the biotransformation of five of the most therapeutically important benzimidazole anthelmintics - albendazole (ABZ), mebendazole (MBZ), thiabendazole (TBZ), oxfendazole (OxBZ) and fenbendazole (FBZ) - in Caenorhabditis elegans and the ruminant parasite Haemonchus contortus. Drug metabolites were detected by LC-M...
Source: International Journal for Parasitology: Drugs and Drug Resistance - September 10, 2019 Category: Parasitology Source Type: research

Prevalence of Plasmodium falciparum Pfcrt and Pfmdr1 alleles in settings with different levels of Plasmodium vivax co-endemicity in Ethiopia
This study thus assessed the prevalence of Pfcrt-K76T and Pfmdr1-N86Y point mutations in P. falciparum. 18S RNA gene based nested PCR confirmed P. falciparum samples (N = 183) collected through community and health facility targeted cross-sectional surveys from settings with varying P. vivax and P. falciparum endemicity were used. The proportion of Plasmodium infections that were P. vivax was 62.2% in Adama, 41.4% in Babile, 30.0% in Benishangul-Gumuz to 6.9% in Gambella. The Pfcrt-76T mutant haplotype was observed more from samples with higher endemicity of P. vivax as being 98.4% (61/62), 100% (31/31), 65.2% (15/23) ...
Source: International Journal for Parasitology: Drugs and Drug Resistance - September 10, 2019 Category: Parasitology Source Type: research

Successful treatment by adding thalidomide to meglumine antimoniate in a case of refractory anthroponotic mucocutaneous leishmaniasis
Publication date: Available online 27 August 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Vahid Mashayekhi Goyonlo, Sadegh Vahabi-Amlashi, Faezeh TaghaviAbstractMucosal leishmaniasis (ML) is mostly associated with Leishmania braziliensis; however, a few cases of Leishmania tropica induced mucocutaneous leishmaniasis have been reported. The standard treatment for leishmaniasis is pentavalent antimonials, but several other drugs for resistant cases have been proposed including amphotericin and miltefosine. Here we present a case of multiple treatment resistant mucocutaneous leishman...
Source: International Journal for Parasitology: Drugs and Drug Resistance - September 3, 2019 Category: Parasitology Source Type: research

Managing anthelmintic resistance in cyathostomin parasites: Investigating the benefits of refugia-based strategies
This study made use of the cyathostomin model to evaluate the influence of treatment strategies with between 1 and 8 yearly treatment occasions, where either 1) all horses were treated, 2) a predetermined proportion of the herd remained untreated, or 3) horses were treated if their FEC exceeded thresholds between 100 and 600 strongyle eggs per gram. Weather data representing four different climatic zones was used and three different herd age structures were compared; 1) all yearlings, 2) all mature horses 10–20 years old, and 3) a mixed age structure of 1–20 years of age. Results indicated a consistent effect o...
Source: International Journal for Parasitology: Drugs and Drug Resistance - August 29, 2019 Category: Parasitology Source Type: research

Successful treatment by adding thalidomide to glucantime in a case of refractory anthroponotic mucocutaneous leishmaniasis
Publication date: Available online 27 August 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Vahid Mashayekhi Goyonlo, Sadegh Vahabi-Amlashi, Faezeh TaghaviAbstractMucosal leishmaniasis (ML) is mostly associated with Leishmania braziliensis; however, a few cases of Leishmania tropica induced mucocutaneous leishmaniasis have been reported. The standard treatment for leishmaniasis is pentavalent antimonials, but several other drugs for resistant cases have been proposed including amphotericin and miltefosine. Here we present a case of multiple treatment resistant mucocutaneous leishman...
Source: International Journal for Parasitology: Drugs and Drug Resistance - August 28, 2019 Category: Parasitology Source Type: research

Evaluation of synergy between host and pathogen-directed therapies against intracellular Leishmania donovani
Publication date: Available online 21 August 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): M. Shamim Hasan Zahid, Monica M. Johnson, Robert J. Tokarski, Abhay R. Satoskar, James R. Fuchs, Eric M. Bachelder, Kristy M. AinslieAbstractVisceral leishmaniasis (VL) is associated with treatment complications due to the continued growth of resistant parasites toward currently available pathogen-directed therapeutics. To limit the emergence and combat resistant parasites there is a need to develop new anti-leishmanial drugs and alternative treatment approaches, such as host-directed therape...
Source: International Journal for Parasitology: Drugs and Drug Resistance - August 22, 2019 Category: Parasitology Source Type: research

In-situ immune profile of polymorphic vs. macular Indian Post Kala-azar Dermal Leishmaniasis
Publication date: Available online 22 August 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Ritika Sengupta, Shibabrata Mukherjee, Srija Moulik, Sneha Mitra, Surya Jyati Chaudhuri, Nilay Kanti Das, Uttara Chatterjee, Mitali ChatterjeeAbstractPost Kala-azar Dermal Leishmaniasis (PKDL), a sequel of apparently cured Visceral Leishmaniasis presents in South Asia with papulonodular (polymorphic) or hypomelanotic lesions (macular). Till date, the polymorphic variant was considered predominant, constituting 85–90%. However, following active-case surveillance, the proportion of macula...
Source: International Journal for Parasitology: Drugs and Drug Resistance - August 22, 2019 Category: Parasitology Source Type: research

Development of amplicon sequencing for the analysis of benzimidazole resistance allele frequencies in field populations of gastrointestinal nematodes
This study provides proof of concept of a practical, accurate, sensitive and scalable method to determine frequency of anthelmintic resistance mutations in gastrointestinal nematodes in field studies and as a management tool for livestock farmers.Graphical abstract (Source: International Journal for Parasitology: Drugs and Drug Resistance)
Source: International Journal for Parasitology: Drugs and Drug Resistance - August 15, 2019 Category: Parasitology Source Type: research

The combination therapy of meglumine antimoniate and oxiranes (epoxy-α-lapachone and epoxymethyl-lawsone) enhance the leishmanicidal effect in mice infected by Leishmania (Leishmania) amazonensis
In this study we analyzed the potential of the association of meglumine antimoniate (MA) with the oxiranes epoxy-α-lapachone (LAP) or epoxymethyl-lawsone (LAW). Results demonstrated that association between these drugs enhanced leishmanicidal activity on Leishmania (Leishmania) amazonensis infection. The compounds were tested in monotherapy or in combinations (3:1; 1:1 and 1:3) and reduced intracellular parasite numbers, measured by the endocytic index, in all tested conditions. The most effective combination regimens were MA/LAP or MA/LAW in 3:1 ratio, which achieved a reduction of 98.3% and 93.6% in the endocytic i...
Source: International Journal for Parasitology: Drugs and Drug Resistance - August 13, 2019 Category: Parasitology Source Type: research

Activity of methylgerambullin from Glycosmis species (Rutaceae) against Entamoeba histolytica and Giardia duodenalis in vitro
Publication date: Available online 10 August 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Mirjana Drinić, Adriane Raninger, Andrea Zraunig, Florian Astelbauer, David Leitsch, Andreas Obwaller, Julia Walochnik, Harald Greger, Michael DuchêneAbstractEntamoeba histolytica and Giardia duodenalis are widespread intestinal protozoan parasites which both spread via cysts that have to be ingested to infect a new host. Their environment, the small intestine for G. duodenalis and the colon for E. histolytica, contains only very limited amounts of oxygen, so both parasites generate en...
Source: International Journal for Parasitology: Drugs and Drug Resistance - August 12, 2019 Category: Parasitology Source Type: research

Erratum to ‘Combining bioinformatics, cheminformatics, functional genomics and whole organism approaches for identifying epigenetic drug targets in Schistosoma mansoni’ [IJP: Drugs and Drug Resistance 8 (2018) 559–570]
Publication date: Available online 2 July 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Gilda Padalino, Salvatore Ferla, Andrea Brancale, Iain W. Chalmers, Karl F. Hoffmann (Source: International Journal for Parasitology: Drugs and Drug Resistance)
Source: International Journal for Parasitology: Drugs and Drug Resistance - July 3, 2019 Category: Parasitology Source Type: research

Route map for the discovery and pre-clinical development of new drugs and treatments for cutaneous leishmaniasis
Publication date: Available online 20 June 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Diana Caridha, Brian Vesely, Katrien van Bocxlaer, Byron Arana, Charlie Mowbray, Sima Rifati, Silvia Uliana, Rosa Regura, Mara Kreishman-Deitrick, Richard Sciotti, Pierre Buffet, Simon L. CroftAbstractAlthough there have been significant advances in the treatment of visceral leishmaniasis (VL) and several novel compounds are currently in pre-clinical and clinical development for this manifestation of leishmaniasis, there have been limited advances in drug research and development (R & D) fo...
Source: International Journal for Parasitology: Drugs and Drug Resistance - June 20, 2019 Category: Parasitology Source Type: research

Screening the Medicines for Malaria Venture Pathogen Box against piroplasm parasites
In this study, the 400 compounds in the Pathogen Box provided by the Medicines for Malaria Venture foundation were screened against Babesia bovis, Babesia bigemina, Babesia caballi, and Theileria equi. A fluorescence-based method using SYBR Green 1 stain was used for initial in vitro screening and determination of the half maximal inhibitory concentration (IC50). The initial in vitro screening performed using a 1 μM concentration as baseline revealed nine effective compounds against four tested parasites. Two “hit” compounds, namely MMV021057 and MMV675968, that showed IC50  100 were selected. The IC50s ...
Source: International Journal for Parasitology: Drugs and Drug Resistance - June 20, 2019 Category: Parasitology Source Type: research

Novel and safe single-dose treatment of cutaneous leishmaniasis with implantable amphotericin B-Loaded microparticles
Publication date: Available online 17 June 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Ariane J. Sousa-Batista, Wallace Pacienza-Lima, Maria Inês Ré, Bartira Rossi-BergmannAbstractThe development of an effective amphotericin B (AmB) topical formulation to replace the systemically toxic injections currently used in cutaneous leishmaniasis (CL) treatment is challenging due to poor absorption through the skin. Aiming at an effective local chemotherapy, we designed PLGA (poly lactide-co-glycolide acid) microspheres loaded with deoxycholate amphotericin B (d-AmB) for both...
Source: International Journal for Parasitology: Drugs and Drug Resistance - June 18, 2019 Category: Parasitology Source Type: research

Perspectives on the utility of moxidectin for the control of parasitic nematodes in the face of developing anthelmintic resistance
Publication date: Available online 15 June 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Roger K. Prichard, Timothy G. GearyAbstractMacrocyclic lactone (ML) anthelmintics are the most important class of anthelmintics because of our high dependence on them for the control of nematode parasites and some ectoparasites in livestock, companion animals and in humans. However, resistance to MLs is of increasing concern. Resistance is commonplace throughout the world in nematode parasites of small ruminants and is of increasing concern in horses, cattle, dogs and other animals. It is suspe...
Source: International Journal for Parasitology: Drugs and Drug Resistance - June 17, 2019 Category: Parasitology Source Type: research

Mining for natural product antileishmanials in a fungal extract library
Publication date: Available online 11 June 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): A.J. Mbekeani, R.S. Jones, M. Bassas Llorens, J. Elliot, C. Regnault, M.P. Barrett, J. Steele, B. Kebede, S.K. Wrigley, L. Evans, P.W. DennyAbstractLeishmaniasis is a Neglected Tropical Disease caused by the insect-vector borne protozoan parasite, Leishmania species. Infection affects millions of the World's poorest, however vaccines are absent and drug therapy limited. Recently, public-private partnerships have developed to identify new modes of controlling leishmaniasis. Most of these collabo...
Source: International Journal for Parasitology: Drugs and Drug Resistance - June 11, 2019 Category: Parasitology Source Type: research

Novel chemical starting points for drug discovery in leishmaniasis and Chagas disease
Publication date: Available online 22 May 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Irene Roquero, Juan Cantizani, Ignacio Cotillo, M. Pilar Manzano, Albane Kessler, J. Julio Martín, Case W. McNamaraAbstractVisceral leishmaniasis (VL) and Chagas disease (CD) are caused by kinetoplastid parasites that affect millions of people worldwide and impart a heavy burden against human health. Due to the partial efficacy and toxicity-related limitations of the existing treatments, there is an urgent need to develop novel therapies with superior efficacy and safety profiles to succe...
Source: International Journal for Parasitology: Drugs and Drug Resistance - May 24, 2019 Category: Parasitology Source Type: research

Refugia and anthelmintic resistance: Concepts and challenges
Publication date: Available online 17 May 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Jane E. Hodgkinson, Ray M. Kaplan, Fiona Kenyon, Eric R. Morgan, Andrew W. Park, Steve Paterson, Simon A. Babayan, Nicola J. Beesley, Collette Britton, Umer Chaudray, Stephen R. Doyle, Vanessa O. Ezenwa, Andy Fenton, Sue B. Howell, Roz Laing, Barbara K. Mable, Louise Matthews, Jennifer McIntyre, Catherine E. Milne, Thomas A. MorrisonAbstractAnthelmintic resistance is a threat to global food security. In order to alleviate the selection pressure for resistance and maintain drug efficacy, manageme...
Source: International Journal for Parasitology: Drugs and Drug Resistance - May 18, 2019 Category: Parasitology Source Type: research

Macrocyclic lactone anthelmintic-induced leukocyte binding to Dirofilaria immitis microfilariae: Influence of the drug resistance status of the parasite
Publication date: Available online 26 April 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Tessa Berrafato, Ruby Coates, Barbara J. Reaves, Daniel Kulke, Adrian J. WolstenholmeAbstractThe macrocyclic lactone anthelmintics are the only class of drug currently used to prevent heartworm disease. Their extremely high potency in vivo is not mirrored by their activity against Dirofilaria immitis larvae in vitro, leading to suggestions that they may require host immune functions to kill the parasites. We have previously shown that ivermectin stimulates the binding of canine peripheral bloo...
Source: International Journal for Parasitology: Drugs and Drug Resistance - April 27, 2019 Category: Parasitology Source Type: research

In vitro susceptibility of Plasmodium falciparum isolates from the China-Myanmar border area to artemisinins and correlation with K13 mutations
This study followed the dynamics of the K13 polymorphisms in P. falciparum parasites from the China-Myanmar border area obtained in 2007–2016, and their in vitro sensitivities to artesunate (AS) and dihydroartemisinin (DHA). The 50% effective concentration (EC5072h) values of 133 culture-adapted field isolates to AS and DHA, measured by the conventional 72 h SYBR Green I-based assay, varied significantly among the parasites from different years; all were significantly higher than that of the reference strain 3D7. Compared with parasites from 2007 to 2008, ring survival rates almost doubled in parasites obtained in ...
Source: International Journal for Parasitology: Drugs and Drug Resistance - April 10, 2019 Category: Parasitology Source Type: research

Aminoguanidines: New leads for treatment of Giardia duodenalis infection
In this study the in vitro efficacy and selectivity of the aminoguanidine compound robenidine and 2 structural analogues against Giardia were determined. After 5 h exposure to each compound the IC50 was as low as 0.2 μM with corresponding MLCs as low as 2.8 μM. This is in contrast to metronidazole which required 24 h to exhibit inhibitory activity. A modified adherence assay, developed for this study, demonstrated that three of the compounds inhibited in vitro adherence of the parasite. The lead compound exhibited rapid giardicidal activity (
Source: International Journal for Parasitology: Drugs and Drug Resistance - April 10, 2019 Category: Parasitology Source Type: research

A high-throughput screen for the identification of compounds that inhibit nematode gene expression by targeting spliced leader trans-splicing
Publication date: Available online 5 April 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): George Cherian Pandarakalam, Michael Speake, Stuart McElroy, Ammar Alturkistani, Lucas Phillipe, Jonathan Pettitt, Berndt Müller, Bernadette ConnollyAbstractInfections with parasitic nematodes are among the most significant of the neglected tropical diseases affecting about a billion people living mainly in tropical regions with low economic activity.The most effective current strategy to control nematode infections involves large scale treatment programs with anthelmintic drugs. This stra...
Source: International Journal for Parasitology: Drugs and Drug Resistance - April 7, 2019 Category: Parasitology Source Type: research

Bumped kinase inhibitor 1369 is effective against Cystoisospora suis in vivo and in vitro
Publication date: Available online 2 April 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): 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 JoachimAbstractCystoisosporosis 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 no...
Source: International Journal for Parasitology: Drugs and Drug Resistance - April 4, 2019 Category: Parasitology Source Type: research

Insights into Chagas treatment based on the potential of bacteriocin AS-48
Publication date: Available online 29 March 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Rubén Martín-Escolano, Rubén Cebrián, Javier Martín-Escolano, Maria J. Rosales, Mercedes Maqueda, Manuel Sánchez-Moreno, Clotilde MarínAbstractChagas 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 Benznida...
Source: International Journal for Parasitology: Drugs and Drug Resistance - March 30, 2019 Category: Parasitology Source Type: research

Resistance formation to nitro drugs in Giardia lamblia: No common markers identified by comparative proteomics
Publication date: Available online 15 March 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Joachim Müller, Sophie Braga, Manfred Heller, Norbert MüllerAbstractIn 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 ...
Source: International Journal for Parasitology: Drugs and Drug Resistance - March 16, 2019 Category: Parasitology Source Type: research

High-resolution melt (HRM) analysis for detection of SNPs associated with pyrethroid resistance in the southern cattle fever tick, Rhipicephalus (Boophilus) microplus (Acari: Ixodidae)
This study highlights the existence of several mutations in the para-sodium channel gene in different combinations in field populations of R. microplus from Mexico.Graphical abstract (Source: International Journal for Parasitology: Drugs and Drug Resistance)
Source: International Journal for Parasitology: Drugs and Drug Resistance - March 13, 2019 Category: Parasitology Source Type: research

Novel benzoxaborole, nitroimidazole and aminopyrazoles with activity against experimental cutaneous leishmaniasis
Publication date: Available online 26 February 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): 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. CroftAbstractObjectivesDrugs 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 fol...
Source: International Journal for Parasitology: Drugs and Drug Resistance - February 26, 2019 Category: Parasitology Source Type: research

Investigation of the pathways related to intrinsic miltefosine tolerance in Leishmania (Viannia) braziliensis clinical isolates reveals differences in drug uptake
Publication date: Available online 25 February 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): 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. UlianaAbstractIn 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 f...
Source: International Journal for Parasitology: Drugs and Drug Resistance - February 25, 2019 Category: Parasitology Source Type: research

Plasmodium knowlesi exhibits distinct in vitro drug susceptibility profiles from those of Plasmodium falciparum
Publication date: Available online 22 February 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): 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. SutherlandAbstractNew 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-falciparu...
Source: International Journal for Parasitology: Drugs and Drug Resistance - February 23, 2019 Category: Parasitology Source Type: research

Histone deacetylase enzymes as potential drug targets of Neglected Tropical Diseases caused by cestodes
This report provides the basis for further studies on cestode HDAC enzymes and for discovery of new HDAC inhibitors for the treatment of neglected diseases caused by cestode parasites.Graphical abstract (Source: International Journal for Parasitology: Drugs and Drug Resistance)
Source: International Journal for Parasitology: Drugs and Drug Resistance - February 23, 2019 Category: Parasitology Source Type: research

Development of unstable resistance to diminazene aceturate in 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. bovis cultivated with 0.04 μM of DA pressure for 4, 8, and 12 days, respectively, as compared to that on parental culture (0.08 ± 0.0065 μM) be...
Source: International Journal for Parasitology: Drugs and Drug Resistance - February 14, 2019 Category: Parasitology Source Type: research

Leveraging the medicines for Malaria Venture malaria and pathogen boxes to discover chemical inhibitors of East Coast fever
Publication date: Available online 25 January 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): James Nyagwange, Elias Awino, Edwin Tijhaar, Nicholas Svitek, Roger Pelle, Vishvanath NeneAbstractChemotherapy 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 Theileira parva. Buparvaquone can be used prophylactically and it is also active against tropical theileriosis,...
Source: International Journal for Parasitology: Drugs and Drug Resistance - January 26, 2019 Category: Parasitology Source Type: research

The individual components of commercial isometamidium do not possess stronger trypanocidal activity than the mixture, nor bypass isometamidium resistance
Publication date: Available online 21 January 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Anthonius A. Eze, John Igoli, Alexander I. Gray, Graham G. Skellern, Harry P. De KoningAbstractThe 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 strain...
Source: International Journal for Parasitology: Drugs and Drug Resistance - January 22, 2019 Category: Parasitology Source Type: research

Screening of a PDE-focused library identifies imidazoles with in vitro and in vivo antischistosomal activity
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. 82% of the compounds had an impact on male worms whereas female worms were bar...
Source: International Journal for Parasitology: Drugs and Drug Resistance - January 15, 2019 Category: Parasitology Source Type: research

Selected α-pyrones from the plants Cryptocarya novoguineensis (Lauraceae) and Piper methysticum (Piperaceae) with activity against Haemonchus contortus in vitro
Publication date: Available online 4 January 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): 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. GasserAbstractDue 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...
Source: International Journal for Parasitology: Drugs and Drug Resistance - January 5, 2019 Category: Parasitology Source Type: research

Tetrahydroquinoxalines induce a lethal evisceration phenotype in Haemonchus contortus in vitro
Publication date: Available online 30 December 2018Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): 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. GasserAbstractIn 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 scree...
Source: International Journal for Parasitology: Drugs and Drug Resistance - December 30, 2018 Category: Parasitology Source Type: research

Menthol acts as a positive allosteric modulator on nematode levamisole sensitive nicotinic acetylcholine receptors
In this study we examined the effects of monoterpenoid compounds on a levamisole sensitive nAChR from Oesophagostomum dentatum and a nicotine sensitive nAChR from Ascaris suum. We expressed the receptors in Xenopus laevis oocytes and used two-electrode voltage-clamp to characterize the effect of various compounds on these cys-loop receptors. At 100 μM the majority of these compounds acted as antagonists. Interestingly, further experiments revealed that both 0.1 μM and 10 μM menthol potentiated acetylcholine and levamisole responses in the levamisole sensitive receptor but not the nicotine sensitive receptor....
Source: International Journal for Parasitology: Drugs and Drug Resistance - December 30, 2018 Category: Parasitology Source Type: research

New life for an old drug: In vitro and in vivo effects of the anthelmintic drug niclosamide against Toxoplasma gondii RH strain
In conclusion, our results support the efficacy of niclosamide as a potential compound for the treatment of T. gondii infection.Graphical abstract (Source: International Journal for Parasitology: Drugs and Drug Resistance)
Source: International Journal for Parasitology: Drugs and Drug Resistance - December 21, 2018 Category: Parasitology Source Type: research

Transient temperature fluctuations severely decrease P. falciparum susceptibility to artemisinin in vitro
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. Chloroquine and pyronaridine susceptibility, in a standard 48-h test, was not affected by brief exposures to low temperature. Fever-like temperature pulses up to 40 °C we...
Source: International Journal for Parasitology: Drugs and Drug Resistance - December 16, 2018 Category: Parasitology Source Type: research

Ascorbic acid reduces the genetic damage caused by miltefosine (hexadecylphosphocholine) in animals infected by Leishmania (Leishamnia) infantum without decreasing its antileishmanial activity
Publication date: Available online 13 December 2018Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Patrícia Valéria Castelo-Branco, Hugo José Alves, Raissa Lacerda Pontes, Vera Lucia Maciel-Silva, Silma Regina Ferreira PereiraAbstractLeishamaniasis 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 milte...
Source: International Journal for Parasitology: Drugs and Drug Resistance - December 14, 2018 Category: Parasitology Source Type: research

Immunosuppression of Syrian golden hamsters accelerates relapse but not the emergence of resistance in Leishmania infantum following recurrent miltefosine pressure
This study evaluated the effect of immunosuppression (cyclophosphamide 150 mg/kg once weekly) on the development of MIL-resistance in Syrian golden hamsters infected with Leishmania infantum. The hamsters were treated with MIL (20 mg/kg orally for 5 days) whenever clinical signs of infection or relapse were observed. The immunosuppression resulted in a significant depletion of CD4+ lymphocytes and MHCII-expressing cells in peripheral blood, and a concomitant increase in tissue parasite burdens and shorter time to relapse, but the strain's susceptibility upon repeated MIL exposure remained unaltered. This study demonstr...
Source: International Journal for Parasitology: Drugs and Drug Resistance - December 11, 2018 Category: Parasitology Source Type: research

Overexpression of plasmepsin II and plasmepsin III does not directly cause reduction in Plasmodium falciparum sensitivity to artesunate, chloroquine and piperaquine
Publication date: Available online 1 December 2018Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): 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 KümpornsinAbstractArtemisinin 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 ev...
Source: International Journal for Parasitology: Drugs and Drug Resistance - December 2, 2018 Category: Parasitology Source Type: research

Nicotine-sensitive acetylcholine receptors are relevant pharmacological targets for the control of multidrug resistant parasitic nematodes
Publication date: Available online 20 November 2018Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Claude L. Charvet, Fabrice Guégnard, Elise Courtot, Jacques Cortet, Cedric NeveuAbstractThe control of parasitic nematodes impacting animal health relies on the use of broad spectrum anthelmintics. However, intensive use of these drugs has led to the selection of resistant parasites in livestock industry. In that respect, there is currently an urgent need for novel compounds able to control resistant parasites. Nicotine has also historically been used as a de-wormer but was removed f...
Source: International Journal for Parasitology: Drugs and Drug Resistance - November 21, 2018 Category: Parasitology Source Type: research

TPT sulfonate, a single, oral dose schistosomicidal prodrug: In vivo efficacy, disposition and metabolic profiling
Publication date: Available online 20 November 2018Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Alan R. Wolfe, R. Jeffrey Neitz, Mark Burlingame, Brian M. Suzuki, K.C. Lim, Mark Scheideler, David L. Nelson, Leslie Z. Benet, Conor R. CaffreyAbstractTreatment of schistosomiasis relies precariously on just one drug, praziquantel (PZQ). In the search for alternatives, 15 S-[2-(alkylamino)alkane] thiosulfuric acids were obtained from a previous research program and profiled in mice for efficacy against both mature (>42-day-old) and juvenile (21-day-old) Schistosoma mansoni using a scr...
Source: International Journal for Parasitology: Drugs and Drug Resistance - November 21, 2018 Category: Parasitology Source Type: research

Combining bioinformatics, cheminformatics, functional genomics and whole organism approaches for identifying epigenetic drug targets in Schistosoma mansoni
Publication date: Available online 13 November 2018Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Gilda Padalino, Salvatore Ferla, Andrea Brancale, Iain W. Chalmers, Karl F. HoffmannAbstractSchistosomiasis endangers the lives of greater than 200 million people every year and is predominantly controlled by a single class chemotherapy, praziquantel (PZQ). Development of PZQ replacement (to combat the threat of PZQ insensitivity/resistance arising) or combinatorial (to facilitate the killing of PZQ-insensitive juvenile schistosomes) chemotherapies would help sustain this control strategy i...
Source: International Journal for Parasitology: Drugs and Drug Resistance - November 14, 2018 Category: Parasitology Source Type: research