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Malaria drug resistance

Ahmet Özbilgin, İbrahim Çavuş, Alicem Nuraydın, Tuğba Kaya
OBJECTIVE: The Wolrd Health Organization (WHO) encourages all countries to investigate antimalarial drug substances derived from herbal sources with the slogan "Hunt of the Next Artemisinin" due to the emergence of resistant strains of Plasmodium species to artemisinin. In the broad and simple sense, it was planned to help guide the young researchers set in-vitro and in-vivo models of malaria in order to be used in drug research and active ingredient studies. METHODS: In-vitro study, young Plasmodium berghei trophozoites were removed from the liquid nitrogen tank and resuspended in appropriate conditions, followed by incubation with chloroquine and tetracycline at concentrations of 0...
September 2017: Türkiye Parazitolojii Dergisi
Tamir Kanias, Marion C Lanteri, Grier P Page, Yuelong Guo, Stacy M Endres, Mars Stone, Sheila Keating, Alan E Mast, Ritchard G Cable, Darrell J Triulzi, Joseph E Kiss, Edward L Murphy, Steve Kleinman, Michael P Busch, Mark T Gladwin
Genetic polymorphisms in blood donors may contribute to donor-specific differences in the survival of red blood cells (RBCs) during cold storage and after transfusion. Genetic variability is anticipated to be high in donors with racial admixture from malaria endemic regions such as Africa and Asia. The purpose of this study was to test the hypothesis that donor genetic background, reflected by sex and self-reported ethnicity, significantly modulates RBC phenotypes in storage. High throughput hemolysis assays were developed and used to evaluate stored RBC samples from 11 115 African American, Asian, white, and Hispanic blood donors from 4 geographically diverse regions in the United States...
June 27, 2017: Blood Advances
Manish Chauhan, Mohammed Tarique, Renu Tuteja
Plasmodium falciparum is responsible for most dangerous and prevalent form of malaria. The emergence of multi drug resistant parasite hindered the prevention of malaria burden worldwide. Helicases are omnipresent enzymes, which play important role in nucleic acid metabolism and can be used as potential targets for development of novel therapeutics. The genome wide analysis of P. falciparum 3D7 strain revealed some novel parasite specific helicases, which are not present in human host. Here we report the detailed biochemical characterization of P...
October 13, 2017: Scientific Reports
Leslie Roberts
No abstract text is available yet for this article.
October 13, 2017: Science
Elizabeth Pisani, Stella Botchway
BACKGROUND: Increasingly, biomedical researchers are encouraged or required by research funders and journals to share their data, but there's very little guidance on how to do that equitably and usefully, especially in resource-constrained settings. We performed an in-depth case study of one data sharing pioneer: the WorldWide Antimalarial Resistance Network (WWARN). METHODS: The case study included a records review, a quantitative analysis of WAARN-related publications, in-depth interviews with 47 people familiar with WWARN, and a witness seminar involving a sub-set of 11 interviewees...
2017: Wellcome Open Research
Warangkhana Songsungthong, Supasak Kulawonganunchai, Alisa Wilantho, Sissades Tongsima, Pongpisid Koonyosying, Chairat Uthaipibull, Sumalee Kamchonwongpaisan, Philip J Shaw
BACKGROUND: The current first line drugs for treating uncomplicated malaria are artemisinin (ART) combination therapies. However, Plasmodium falciparum parasites resistant to ART and partner drugs are spreading, which threatens malaria control efforts. Rodent malaria species are useful models for understanding antimalarial resistance, in particular genetic variants responsible for cross resistance to different compounds. METHODS: The Plasmodium berghei RC strain (PbRC) is described as resistant to different antimalarials, including chloroquine (CQ) and ART...
2017: PeerJ
Devendra Bansal, Anushree Acharya, Praveen K Bharti, Mohamed H Abdelraheem, Ashraf Elmalik, Salem Abosalah, Fahmi Y Khan, Mohamed ElKhalifa, Hargobinder Kaur, Pradyumna K Mohapatra, Rakesh Sehgal, Mohammed A Idris, Jagadish Mahanta, Neeru Singh, Hamza A Babiker, Ali A Sultan
Plasmodium vivax is the most prevalent parasite worldwide, escalating by spread of drug resistance. Currently, in Qatar, chloroquine (CQ) plus primaquine are recommended for the treatment of P. vivax malaria. The present study examined the prevalence of mutations in dihydrofolate reductase (dhfr), dihydropteroate synthase (dhps) genes and CQ resistance transporter (crt-o) genes, associated with sulphadoxine-pyrimethamine (SP) and chloroquine resistance, among imported P. vivax cases in Qatar. Blood samples were collected from patients positive for P...
October 2, 2017: American Journal of Tropical Medicine and Hygiene
Melissa D Conrad, Daniel Mota, Alex Musiime, Maxwell Kilama, John Rek, Moses Kamya, Grant Dorsey, Philip J Rosenthal
Controlling malaria in high transmission areas, such as much of sub-Saharan Africa, will require concerted efforts to slow the spread of drug resistance and to impede malaria transmission. Understanding the fitness costs associated with the development of drug resistance, particularly within the context of transmission, can help guide policy decisions to accomplish these goals, as fitness constraints might lead to decreased transmission of drug-resistant strains. To determine if Plasmodium falciparum resistance-mediating polymorphisms impact on development at different parasite stages, we compared the genotypes of parasites infecting humans and mosquitoes from households in Uganda...
September 25, 2017: American Journal of Tropical Medicine and Hygiene
Pengxing Cao, Nectarios Klonis, Sophie Zaloumis, Con Dogovski, Stanley C Xie, Sompob Saralamba, Lisa J White, Freya J I Fowkes, Leann Tilley, Julie A Simpson, James M McCaw
Artemisinin resistance constitutes a major threat to the continued success of control programs for malaria, particularly in light of developing resistance to partner drugs. Improving our understanding of how artemisinin-based drugs act and how resistance manifests is essential for the optimisation of dosing regimens and the development of strategies to prolong the lifespan of current first-line treatment options. Recent short drug-pulse in vitro experiments have shown that the parasite killing rate depends not only on drug concentration but also the exposure time, challenging the standard pharmacokinetic-pharmacodynamic(PK-PD) paradigm in which the killing rate depends only on drug concentration...
October 9, 2017: Antimicrobial Agents and Chemotherapy
Kayla Ann Andrews, David Wesche, James McCarthy, Jörg J Möhrle, Joel Tarning, Luann Phillips, Steven Kern, Thaddeus Grasela
Malaria is a critical public health problem resulting in substantial morbidity and mortality, particularly in developing countries. Owing to the development of resistance toward current therapies, novel approaches to accelerate the development efforts of new malaria therapeutics are urgently needed. There have been significant advancements in the development of in vitro and in vivo experiments that generate data used to inform decisions about the potential merit of new compounds. A comprehensive disease-drug model capable of integrating discrete data from different preclinical and clinical components would be a valuable tool across all stages of drug development...
October 6, 2017: Annual Review of Pharmacology and Toxicology
Catherine Thériault, Dave Richard
Despite marked reductions in morbidity and mortality in the last ten years, malaria still takes a tremendous toll on human populations throughout tropical and sub-tropical regions of the world. The absence of an effective vaccine and resistance to most antimalarial drugs available demonstrate the urgent need for new intervention strategies. Phosphoinositides are a class of lipids with critical roles in numerous processes and their specific subcellular distribution, generated through the action of kinases and phosphatases, define organelle identity in a wide range of eukaryotic cells...
October 5, 2017: Scientific Reports
ShubaVarshini Alampalli, Manish Grover, Syama Chandran, Utpal Tatu, Pragyan Achary
PURPOSE: The cell membrane of the erythrocytes infected with the malaria parasite Plasmodium falciparum undergoes several changes during the course of parasite life cycle and forms protrusions known as 'knobs' on its surface during the mature trophozoite and schizont stages. The structural organization of knob components especially PfEMP1 on the iRBC surface is the main determinant for the cytoadhesive and rosetting capacity of the iRBC by binding to various host receptors as well as for the variable antigenicity, which is crucial for immunoevasion...
October 5, 2017: Proteomics. Clinical Applications
Shamim Islam, Faizi Hai
Compared with other plasmodium species which cause human malaria, Plasmodium malariae is considered to be relatively infrequent and milder, although recent reports indicate that its prevalence and impact have been under-estimated. A 23-month-old boy, born and previously living in a refugee camp in Liberia who presented with P. malariae 6 weeks after arrival in the USA, is reported. Despite ostensibly effective anti-malarial treatment with artemether/lumefantrine and two courses of hydrochloroquine, he experienced recurrent parasitaemia, refractory anaemia and splenomegaly over a 6-month period; the symptoms resolved after he received atovaquone/proguanil...
October 4, 2017: Paediatrics and International Child Health
Alfred Amambua-Ngwa, Joseph Okebe, Haddijatou Mbye, Sukai Ceesay, Fatima El-Fatouri, Fatou Joof, Nyang Haddy, Janha Ramatoulie, Muna Affara, Abdullahi Ahmad, Olimatou Kolly, Davis Nwakanma, Umberto D'Alessandro
Antimalarial interventions have yielded significant decline in malaria prevalence in The Gambia, where Artemether-Lumefantrine (AL) has been used as first line antimalarial for a decade. Clinical Plasmodium falciparum isolates collected from 2012 to 2015 were analysed ex vivo for antimalarial susceptibility and genotyped for drug resistance markers (pfcrt K76T, pfmdr1-86-184 and 1246 and pfk13) and microsatellite variation. Additionally, allele frequencies of SNPs from other drug resistance-associated genes were compared from genomic sequence datasets from 2008 (n=79) and 2014 (n=168)...
October 2, 2017: Antimicrobial Agents and Chemotherapy
Melissa D Conrad, Daniel Mota, Marissa Foster, Stephen Tukwasibwe, Jennifer Legac, Patrick Tumwebaze, Meghan Whalen, Abel Kakuru, Patience Nayebare, Erika Wallender, Diane V Havlir, Prasanna Jagannathan, Liusheng Huang, Francesca Aweeka, Moses R Kamya, Grant Dorsey, Philip J Rosenthal
Background: In a recent trial of intermittent preventive treatment in pregnancy (IPTp) in Uganda, dihydroartemisinin-piperaquine (DP) was superior to sulfadoxine-pyrimethamine (SP) in preventing maternal and placental malaria. Methods: We compared genotypes using sequencing, fluorescent microsphere, and qPCR assays at loci associated with drug resistance in Plasmodium falciparum isolated from subjects receiving DP or SP. Results: Considering aminoquinoline resistance, DP was associated with increased prevalences of mutations at pfmdr1 N86Y, pfmdr1 Y184F, and pfcrt K76T compared to SP (64...
August 22, 2017: Journal of Infectious Diseases
Claudia Viviana Barbosa, Carlos Enrique Muskus, Luz Yaneth Orozco, Adriana Pabón
INTRODUCTION: Due to Plasmodium resistance to antimalarial drugs, it is important to find new therapeutic alternatives for malaria treatment and control. Based on the knowledge of Colombian indigenous communities, we collected extracts of plants with potential antimalarial effects from the middle Vaupés region. OBJECTIVE: To evaluate the mutagenic and genotoxic effects, as well as the gene expression of Rad51C, Xiap, P53 and Nrf2 induced by four ethanolic extracts with antimalarial activity (R001, T002, T015 and T028)...
September 1, 2017: Biomédica: Revista del Instituto Nacional de Salud
Geoffrey Schwertz, Michelle S Frei, Matthias C Witschel, Matthias Rottmann, Ubolsree Leartsakulpanich, Penchit Chitnumsub, Aritsara Jaruwat, Wanwipa Ittarat, Anja Schäfer, Raphael A Aponte, Nils Trapp, Kerstin Mark, Pimchai Chaiyen, François Diederich
Malaria remains a major threat to mankind due to the perpetual emergence of resistance against marketed drugs. Twenty-one pyrazolopyran-based inhibitors bearing terminal biphenyl, aryl sulfonamide, or aryl sulfone motifs were synthesized and tested towards serine hydroxymethyltransferase (SHMT), a key enzyme of the folate cycle. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target, as well as PfNF54 strains in cell-based assays in the low nanomolar range (18-56 nm)...
October 12, 2017: Chemistry: a European Journal
Cristian Koepfli, Ivo Mueller
Genotyping to distinguish between parasite clones is nowadays a standard in many molecular epidemiological studies of malaria. It has become crucial in drug trials and to follow individual clones in epidemiological studies, and to understand how drug resistance emerges and spreads. Here, we review the applications of the increasingly available genotyping tools and whole-genome sequencing data, and argue for a better integration of population genetics findings into malaria-control strategies.
September 28, 2017: Trends in Parasitology
Jane Achan, Julia Mwesigwa, Chinagozi Precious Edwin, Umberto D'alessandro
Antimalarial drugs are essential weapons to fight malaria and have been used effectively since the 17(th) century. However, P.falciparum resistance has been reported to almost all available antimalarial drugs, including artemisinin derivatives, raising concerns that this could jeopardize malaria elimination. Areas covered: In this article, we present a historical perspective of antimalarial drug resistance, review current evidence of resistance to available antimalarial drugs and discuss possible mitigating strategies to address this challenge...
October 11, 2017: Expert Review of Clinical Pharmacology
Sha Joe Zhu, Jacob Almagro-Garcia, Gil McVean
Motivation: The presence ofmultiple infecting strains of the malarial parasite Plasmodium falciparum affects key phenotypic traits, including drug resistance and risk of severe disease. Advances in protocols and sequencing technology have made it possible to obtain high-coverage genome-wide sequencing data from blood samples and blood spots taken in the field. However, analysing and interpreting such data is challenging because of the high rate of multiple infections present. Results: We have developed a statistical method and implementation for deconvolving multiple genome sequences present in an individual with mixed infections...
August 22, 2017: Bioinformatics
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