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https://www.readbyqxmd.com/read/28069653/the-molecular-epidemiology-of-pf-k13-mutations-in-senegal-using-targeted-amplicon-deep-sequencing
#1
Eldin Talundzic, Yaye D Ndiaye, Awa B Deme, Christian Olsen, Dhruviben S Patel, Shweta Biliya, Rachel Daniels, Fredrik O Vannberg, Sarah K Volkman, Venkatachalam Udhayakumar, Daouda Ndiaye
The emergence of Plasmodium falciparum (Pf) resistance to artemisinin in Southeast Asia threatens malaria control and elimination activities worldwide. Multiple polymorphisms in the Pf kelch gene found in chromosome 13 (Pfk13) have been associated with artemisinin resistance. Surveillance of potential drug resistance loci within a population that may emerge under increasing drug pressure is an important public health activity. In this context, P. falciparum infections from an observational surveillance study in Senegal were genotyped using targeted amplicon deep sequencing (TADS) for Pfk13 polymorphisms...
January 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28068997/absence-of-in-vivo-selection-for-k13-mutations-after-artemether-lumefantrine-treatment-in-uganda
#2
Betty Balikagala, Toshihiro Mita, Mie Ikeda, Miki Sakurai, Shouki Yatsushiro, Nobuyuki Takahashi, Shin-Ichiro Tachibana, Mary Auma, Edward H Ntege, Daisuke Ito, Eizo Takashima, Nirianne Marie Q Palacpac, Thomas G Egwang, Joseph Okello Onen, Masatoshi Kataoka, Eisaku Kimura, Toshihiro Horii, Takafumi Tsuboi
BACKGROUND: Individual drug treatment may select resistant parasites in the human body, a process termed in vivo selection. Some single nucleotide polymorphisms in Plasmodium falciparum chloroquine-resistance transporter (pfcrt) and multidrug resistance gene 1 (pfmdr1) genes have been reportedly selected after artemether-lumefantrine treatment. However, there is a paucity of data regarding in vivo selection of P. falciparum Kelch propeller domain (pfkelch13) polymorphisms, responsible for artemisinin-resistance in Asia, and six putative background mutations for artemisinin resistance; D193Y in ferredoxin, T484I in multiple resistance protein 2, V127M in apicoplast ribosomal protein S10, I356T in pfcrt, V1157L in protein phosphatase and C1484F in phosphoinositide-binding protein...
January 9, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28067620/characterisation-of-the-opposing-effects-of-g6pd-deficiency-on-cerebral-malaria-and-severe-malarial-anaemia
#3
Geraldine M Clarke, Kirk Rockett, Katja Kivinen, Christina Hubbart, Anna E Jeffreys, Kate Rowlands, Muminatou Jallow, David J Conway, Kalifa A Bojang, Margaret Pinder, Stanley Usen, Fatoumatta Sisay-Joof, Giorgio Sirugo, Ousmane Toure, Mahamadou A Thera, Salimata Konate, Sibiry Sissoko, Amadou Niangaly, Belco Poudiougou, Valentina D Mangano, Edith C Bougouma, Sodiomon B Sirima, David Modiano, Lucas N Amenga-Etego, Anita Ghansah, Kwadwo A Koram, Michael D Wilson, Anthony Enimil, Jennifer Evans, Olukemi K Amodu, Subulade Olaniyan, Tobias Apinjoh, Regina Mugri, Andre Ndi, Carolyne M Ndila, Sophie Uyoga, Alexander Macharia, Norbert Peshu, Thomas N Williams, Alphaxard Manjurano, Nuno Sepúlveda, Taane G Clark, Eleanor Riley, Chris Drakeley, Hugh Reyburn, Vysaul Nyirongo, David Kachala, Malcolm Molyneux, Sarah J Dunstan, Nguyen Hoan Phu, Nguyen Ngoc Quyen, Cao Quang Thai, Tran Tinh Hien, Laurens Manning, Moses Laman, Peter Siba, Harin Karunajeewa, Steve Allen, Angela Allen, Timothy Me Davis, Pascal Michon, Ivo Mueller, Síle F Molloy, Susana Campino, Angeliki Kerasidou, Victoria J Cornelius, Lee Hart, Shivang S Shah, Gavin Band, Chris Ca Spencer, Tsiri Agbenyega, Eric Achidi, Ogobara K Doumbo, Jeremy Farrar, Kevin Marsh, Terrie Taylor, Dominic P Kwiatkowski
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual's level of enzyme activity from their genotype...
January 9, 2017: ELife
https://www.readbyqxmd.com/read/28052850/association-between-polymorphisms-in-pfmdr6-gene-and-ex-vivo-susceptibility-to-quinine-in-plasmodium-falciparum-parasites-from-dakar-senegal
#4
Mathieu Gendrot, Silman Diawara, Marylin Madamet, Mame Bou Kounta, Sébastien Briolant, Khalifa Ababacar Wade, Mansour Fall, Nicolas Benoit, Aminata Nakoulima, Rémy Amalvict, Yaya Diémé, Bécaye Fall, Boubacar Wade, Bakary Diatta, Bruno Pradines
Polymorphisms and overexpression of transporter genes, especially of the ATP-binding cassette superfamily, have been involved in antimalarial drug resistance. The objective of this study was to use 77 Senegalese P. falciparum isolates to evaluate the association between the number of Asn residues in the polymorphic microsatellite region of pfmdr6 and the ex vivo susceptibility to antimalarials. A significant association was observed between the presence of 7 or 9 Asn repeats and reduced susceptibility to quinine...
January 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28049516/genetic-clustering-and-polymorphism-of-the-merozoite-surface-protein-3-of-plasmodium-knowlesi-clinical-isolates-from-peninsular-malaysia
#5
Jeremy Ryan De Silva, Yee Ling Lau, Mun Yik Fong
BACKGROUND: The simian malaria parasite Plasmodium knowlesi has been reported to cause significant numbers of human infection in South East Asia. Its merozoite surface protein-3 (MSP3) is a protein that belongs to a multi-gene family of proteins first found in Plasmodium falciparum. Several studies have evaluated the potential of P. falciparum MSP3 as a potential vaccine candidate. However, to date no detailed studies have been carried out on P. knowlesi MSP3 gene (pkmsp3). The present study investigates the genetic diversity, and haplotypes groups of pkmsp3 in P...
January 3, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28044042/influence-of-the-pfmdr1-gene-on-in-vitro-sensitivities-of-piperaquine-in-thai-isolates-of-plasmodium-falciparum
#6
Mathirut Mungthin, Ekularn Watanatanasup, Naruemon Sitthichot, Nantana Suwandittakul, Rommanee Khositnithikul, Stephen A Ward
Piperaquine combined with dihydroartemisinin is one of the artemisinin derivative combination therapies, which can replace artesunate-mefloquine in treating uncomplicated falciparum malaria in Thailand. The aim of this study was to determine the in vitro sensitivity of Thai Plasmodium falciparum isolates against piperaquine and the influence of the pfmdr1 gene on in vitro response. One hundred and thirty-seven standard laboratory and adapted Thai isolates of P. falciparum were accessed for in vitro piperaquine sensitivity...
January 2, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27998292/genetic-evidence-that-the-makira-region-in-northeastern-madagascar-is-a-hotspot-of-malaria-transmission
#7
Benjamin L Rice, Christopher D Golden, Evelin Jean Gasta Anjaranirina, Carolina Mastella Botelho, Sarah K Volkman, Daniel L Hartl
BACKGROUND: Encouraging advances in the control of Plasmodium falciparum malaria have been observed across much of Africa in the past decade. However, regions of high relative prevalence and transmission that remain unaddressed or unrecognized provide a threat to this progress. Difficulties in identifying such localized hotspots include inadequate surveillance, especially in remote regions, and the cost and labor needed to produce direct estimates of transmission. Genetic data can provide a much-needed alternative to such empirical estimates, as the pattern of genetic variation within malaria parasite populations is indicative of the level of local transmission...
December 20, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27992481/molecular-analysis-of-pfs47-mediated-plasmodium-evasion-of-mosquito-immunity
#8
Gaspar E Canepa, Alvaro Molina-Cruz, Carolina Barillas-Mury
Malaria is a life-threatening disease caused by Plasmodium falciparum parasites that is transmitted through the bites of infected anopheline mosquitoes. P. falciparum dispersal from Africa, as a result of human migration, required adaptation of the parasite to several different indigenous anopheline species. The mosquito immune system can greatly limit infection and P. falciparum evolved a strategy to evade these responses that is mediated by the Pfs47 gene. Pfs47 is a polymorphic gene with signatures of diversifying selection and a strong geographic genetic structure at a continental level...
2016: PloS One
https://www.readbyqxmd.com/read/27938356/plasmodium-falciparum-genotype-and-gametocyte-prevalence-in-children-with-uncomplicated-malaria-in-coastal-ghana
#9
Ruth Ayanful-Torgby, Akua Oppong, Joana Abankwa, Festus Acquah, Kimberly C Williamson, Linda Eva Amoah
BACKGROUND: Plasmodium falciparum gametocytes are vital to sustaining malaria transmission. Parasite densities, multiplicity of infection as well as asexual genotype are features that have been found to influence gametocyte production. Measurements of the prevalence of Plasmodium sp. gametocytes may serve as a tool to monitor the success of malaria eradication efforts. METHODS: Whole blood was collected from 112 children aged between 6 months and 13 years with uncomplicated P...
December 9, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27933195/cr1-exon-variants-are-associated-with-lowered-cr1-expression-and-increased-susceptibility-to-sle-in-a-plasmodium-falciparum-endemic-population
#10
Aditya K Panda, Balachandran Ravindran, Bidyut K Das
BACKGROUND: Complement receptor 1 (CR1) plays an important role in immune complex clearance by opsonisation and possibly protects subjects from development of autoantibodies. Lower CR1 expression has been associated with susceptibility to systemic lupus erythematosus (SLE). In contrast, subjects displaying lower CR1 expression are protected against severe manifestations of falciparum malaria. This study is the first of its kind to investigate the association of CR1 variants with development of SLE in a P...
2016: Lupus Science & Medicine
https://www.readbyqxmd.com/read/27912758/emerging-polymorphisms-in-falciparum-kelch-13-gene-in-northeastern-region-of-india
#11
Neelima Mishra, Ram Suresh Bharti, Prashant Mallick, Om Prakash Singh, Bina Srivastava, Roma Rana, Sobhan Phookan, Hardev Prasad Gupta, Pascal Ringwald, Neena Valecha
BACKGROUND: Recent reports of emergence and spread of artemisinin resistance in the Southeast Asia region, including Myanmar, pose a greater threat to malaria control and elimination in India. Whole genome sequencing studies have associated mutations in the K13 propeller gene (k13), PF3D7_1343700 with artemisinin resistance both in vitro and in vivo. The aim of the present study was to find the k13 gene polymorphisms in Plasmodium falciparum parasites from the three sites in the Northeast region of India, bordering Bangladesh and Myanmar...
December 3, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27887614/insight-into-k13-propeller-gene-polymorphism-and-ex-vivo-dha-response-profiles-from-cameroonian-isolates
#12
Sandie Menard, Joëlle Njila Tchoufack, Christelle Ngou Maffo, Sandrine E Nsango, Xavier Iriart, Luc Abate, Majoline Tchioffo Tsapi, Parfait H Awono-Ambéné, Francis A Abega Mekongo, Isabelle Morlais, Antoine Berry
BACKGROUND: The spread of Plasmodium falciparum resistance to artemisinin derivatives in Southeast Asia is a major source of concern and the emergence of resistance in Africa would have dramatic consequences, by increasing malaria mortality and morbidity. It is therefore urgent to implement regular monitoring in sentinel sites in sub-Saharan Africa using robust and easy-to-implement tools. The prevalence of k13-propeller mutations and the phenotypic profiles are poorly known in sub-Saharan Africa...
November 26, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27872816/evidence-of-triple-mutant-pfdhps-isgnga-haplotype-in-plasmodium-falciparum-isolates-from-north-east-india-an-analysis-of-sulfadoxine-resistant-haplotype-selection
#13
Manuj K Das, Sumi Chetry, Mohan C Kalita, Prafulla Dutta
BACKGROUND: North-east region of India has consistent role in the spread of multi drug resistant Plasmodium (P.) falciparum to other parts of Southeast Asia. After rapid clinical treatment failure of Artemisinin based combination therapy-Sulphadoxine/Pyrimethamine (ACT-SP) chemoprophylaxis, Artemether-Lumefantrine (ACT-AL) combination therapy was introduced in the year 2012 in this region for the treatment of uncomplicated P. falciparum malaria. In a DNA sequencing based polymorphism analysis, seven codons of P...
December 2016: Genomics Data
https://www.readbyqxmd.com/read/27853513/south-east-asian-strains-of-plasmodium-falciparum-display-higher%C3%A2-ratio-of-non-synonymous-to-synonymous-polymorphisms-compared-to-african-strains
#14
Gajinder Pal Singh, Amit Sharma
Resistance to frontline anti-malarial drugs, including artemisinin, has repeatedly arisen in South-East Asia, but the reasons for this are not understood. Here we test whether evolutionary constraints on Plasmodium falciparum strains from South-East Asia differ from African strains. We find a significantly higher ratio of non-synonymous to synonymous polymorphisms in P. falciparum from South-East Asia compared to Africa, suggesting differences in the selective constraints on P. falciparum genome in these geographical regions...
2016: F1000Research
https://www.readbyqxmd.com/read/27846879/plasmodium-malariae-and-plasmodium-ovale-infections-in-the-china-myanmar-border-area
#15
Peipei Li, Zhenjun Zhao, Hua Xing, Wenli Li, Xiaotong Zhu, Yaming Cao, Zhaoqing Yang, Jetsumon Sattabongkot, Guiyun Yan, Qi Fan, Liwang Cui
BACKGROUND: The Greater Mekong Subregion is aiming to achieve regional malaria elimination by 2030. Though a shift in malaria parasite species predominance by Plasmodium vivax has been recently documented, the transmission of the two minor Plasmodium species, Plasmodium malariae and Plasmodium ovale spp., is poorly characterized in the region. This study aims to determine the prevalence of these minor species in the China-Myanmar border area and their genetic diversity. METHODS: Epidemiology study was conducted during passive case detection in hospitals and clinics in Myanmar and four counties in China along the China-Myanmar border...
November 15, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27825828/dissecting-malaria-biology-and-epidemiology-using-population-genetics-and-genomics
#16
REVIEW
Sarah Auburn, Alyssa E Barry
Molecular approaches have an increasingly recognized utility in surveillance of malaria parasite populations, not only in defining prevalence and incidence with higher sensitivity than traditional methods, but also in monitoring local and regional parasite transmission patterns. In this review, we provide an overview of population genetic and genomic studies of human-infecting Plasmodium species, highlighting recent advances in the field. In accordance with the renewed impetus for malaria eradication, many studies are now using genetic and genomic epidemiology to support local evidence-based intervention strategies...
November 5, 2016: International Journal for Parasitology
https://www.readbyqxmd.com/read/27821443/altered-plasmodium-falciparum-sensitivity-to-the-antiretroviral-protease-inhibitor-lopinavir-associated-with-polymorphisms-in-pfmdr1
#17
Ebere Sonoiki, Christian Nsanzabana, Jennifer Legac, Kirthana M V Sindhe, Joseph DeRisi, Philip J Rosenthal
The HIV protease inhibitor lopinavir inhibits Plasmodium falciparum aspartic proteases (plasmepsins) and parasite development, and children receiving lopinavir-ritonavir experienced fewer episodes of malaria than those receiving other antiretroviral regimens. Resistance to lopinavir was selected in vitro over ∼9 months, with ∼4-fold decreased sensitivity. Whole-genome sequencing of resistant parasites showed a mutation and increased copy number in pfmdr1 and a mutation in a protein of unknown function, but no polymorphisms in plasmepsin genes...
January 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27821442/critical-evaluation-of-molecular-monitoring-in-malaria-drug-efficacy-trials-and-pitfalls-of-length-polymorphic-markers
#18
Camilla Messerli, Natalie E Hofmann, Hans-Peter Beck, Ingrid Felger
Estimation of drug efficacy in antimalarial drug trials requires parasite genotyping to distinguish new infections from treatment failures. When using length-polymorphic molecular markers, preferential amplification of short fragments can compromise detection of coinfections, potentially leading to misclassification of treatment outcome. We quantified minority clone detectability and competition among msp1, msp2, and glurp amplicons using mixtures of Plasmodium falciparum strains and investigated the impact of template competition on genotyping outcomes in 44 paired field samples...
January 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27821166/limited-genetic-diversity-in-the-pvk12-kelch-protein-in-plasmodium-vivax-isolates-from-southeast-asia
#19
Meilian Wang, Faiza Amber Siddiqui, Qi Fan, Enjie Luo, Yaming Cao, Liwang Cui
BACKGROUND: Artemisinin resistance in Plasmodium falciparum has emerged as a major threat for malaria control and elimination worldwide. Mutations in the Kelch propeller domain of PfK13 are the only known molecular markers for artemisinin resistance in this parasite. Over 100 non-synonymous mutations have been identified in PfK13 from various malaria endemic regions. This study aimed to investigate the genetic diversity of PvK12, the Plasmodium vivax ortholog of PfK13, in parasite populations from Southeast Asia, where artemisinin resistance in P...
November 8, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27818097/a-surrogate-marker-of-piperaquine-resistant-plasmodium-falciparum-malaria-a-phenotype-genotype-association-study
#20
Benoit Witkowski, Valentine Duru, Nimol Khim, Leila S Ross, Benjamin Saintpierre, Johann Beghain, Sophy Chy, Saorin Kim, Sopheakvatey Ke, Nimol Kloeung, Rotha Eam, Chanra Khean, Malen Ken, Kaknika Loch, Anthony Bouillon, Anais Domergue, Laurence Ma, Christiane Bouchier, Rithea Leang, Rekol Huy, Grégory Nuel, Jean-Christophe Barale, Eric Legrand, Pascal Ringwald, David A Fidock, Odile Mercereau-Puijalon, Frédéric Ariey, Didier Ménard
BACKGROUND: Western Cambodia is the epicentre of Plasmodium falciparum multidrug resistance and is facing high rates of dihydroartemisinin-piperaquine treatment failures. Genetic tools to detect the multidrug-resistant parasites are needed. Artemisinin resistance can be tracked using the K13 molecular marker, but no marker exists for piperaquine resistance. We aimed to identify genetic markers of piperaquine resistance and study their association with dihydroartemisinin-piperaquine treatment failures...
November 3, 2016: Lancet Infectious Diseases
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