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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
Ebere Sonoiki, Christian Nsanzabana, Jennifer Legac, Kirthana Mysore Vasudevarao 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, a mutation in a protein of unknown function, but no polymorphisms in plasmepsin genes...
November 7, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27821442/critical-evaluation-of-molecular-monitoring-in-malaria-drug-efficacy-trials-pitfalls-of-length-polymorphic-markers
#9
Camilla Messerli, Natalie E Hofmann, Hans-Peter Beck, Ingrid Felger
Estimating 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 co-infections, potentially leading to misclassification of treatment outcome. We quantified minority clone detectability and competition among msp1, msp2, and glurp amplicons using mixtures of P. falciparum strains and investigated the impact of template competition on genotyping outcomes in forty-four paired field samples...
November 7, 2016: 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
#10
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
#11
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
https://www.readbyqxmd.com/read/27818095/genetic-markers-associated-with-dihydroartemisinin-piperaquine-failure-in-plasmodium-falciparum-malaria-in-cambodia-a-genotype-phenotype-association-study
#12
Roberto Amato, Pharath Lim, Olivo Miotto, Chanaki Amaratunga, Dalin Dek, Richard D Pearson, Jacob Almagro-Garcia, Aaron T Neal, Sokunthea Sreng, Seila Suon, Eleanor Drury, Dushyanth Jyothi, Jim Stalker, Dominic P Kwiatkowski, Rick M Fairhurst
BACKGROUND: As the prevalence of artemisinin-resistant Plasmodium falciparum malaria increases in the Greater Mekong subregion, emerging resistance to partner drugs in artemisinin combination therapies seriously threatens global efforts to treat and eliminate this disease. Molecular markers that predict failure of artemisinin combination therapy are urgently needed to monitor the spread of partner drug resistance, and to recommend alternative treatments in southeast Asia and beyond. METHODS: We did a genome-wide association study of 297 P falciparum isolates from Cambodia to investigate the relationship of 11 630 exonic single-nucleotide polymorphisms (SNPs) and 43 copy number variations (CNVs) with in-vitro piperaquine 50% inhibitory concentrations (IC50s), and tested whether these genetic variants are markers of treatment failure with dihydroartemisinin-piperaquine...
November 3, 2016: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/27816495/simple-detection-of-single-nucleotide-polymorphism-in-plasmodium-falciparum-by-snp-lamp-assay-combined-with-lateral-flow-dipstick
#13
Suganya Yongkiettrakul, Jantana Kampeera, Wanwisa Chareanchim, Roonglawan Rattanajak, Wichai Pornthanakasem, Wansika Kiatpathomchai, Darin Kongkasuriyachai
The significant strides made in reducing global malaria burden over the past decades are being threatened by the emergence of multi-drug resistant malaria. Mechanisms of resistance to several classes of antimalarial drugs have been linked to key mutations in the Plasmodium falciparum genes. Pyrimethamine targets the dihydrofolate reductase of the bifunctional dihydrofolate reductase thymidylate synthase (DHFR-TS), and specific point mutations in the dhfr-ts gene have been assigned to resistant phenotypes. Several molecular methods are available to detect the mutant genotypes including DNA sequencing and PCR-based methods...
November 2, 2016: Parasitology International
https://www.readbyqxmd.com/read/27809837/genetic-diversity-of-the-pvk12-gene-in-plasmodium-vivax-from-the-china-myanmar-border-area
#14
Shuang Deng, Yonghua Ruan, Yao Bai, Yue Hu, Zeshuai Deng, Yongshu He, Rui Ruan, Yanrui Wu, Zhaoqing Yang, Liwang Cui
BACKGROUND: Plasmodium falciparum resistance to artemisinin emerged in the Greater Mekong Sub-region has been associated with mutations in the propeller domain of the kelch gene Pfk13. METHODS: Here the polymorphisms in Pvk12 gene, the orthologue of Pfk13 in Plasmodium vivax, were determined by PCR and sequencing in 262 clinical isolates collected in recent years (2012-2015) from the China-Myanmar border area. RESULTS: Sequencing of full-length Pvk12 genes from these isolates identified three synonymous mutations (N172N, S360S, S697S) and one non-synonymous mutation M124I, all of which were at very low prevalence (2...
November 4, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27799638/longitudinal-pooled-deep-sequencing-of-the-plasmodium-vivax-k12-kelch-gene-in-cambodia-reveals-a-lack-of-selection-by-artemisinin
#15
Nicholas F Brazeau, Nicholas Hathaway, Christian M Parobek, Jessica T Lin, Jeffrey A Bailey, Chanthap Lon, David L Saunders, Jonathan J Juliano
The emergence of artemisinin resistance among Plasmodium falciparum in the Greater Mekong subregion threatens malaria control interventions and is associated with multiple unique mutations in K13 (PF3D7_1343700). The aim of this study was to survey Cambodian Plasmodium vivax for mutations in the K13 ortholog (K12, PVX_083080) that might similarly confer artemisinin resistance. Extracted DNA from Cambodian isolates collected between 2009 and 2012 was pooled by province and year and submitted for next-generation sequencing...
October 31, 2016: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27788228/prevalence-of-plasmodium-falciparum-molecular-markers-of-antimalarial-drug-resistance-in-a-residual-malaria-focus-area-in-sabah-malaysia
#16
Nor Azrina Norahmad, Mohd Ridzuan Mohd Abd Razak, Noor Rain Abdullah, Umi Rubiah Sastu, Mallika Imwong, Prem Kumar Muniandy, Muhammad Nor Farhan Saat, Amirrudin Muhammad, Jenarun Jelip, Moizin Tikuson, Norsalleh Yusof, Christina Rundi, Rose Nani Mudin, Ami Fazlin Syed Mohamed
Chloroquine (CQ) and fansidar (sulphadoxine-pyrimethamine, SP) were widely used for treatment of Plasmodium falciparum for several decades in Malaysia prior to the introduction of Artemisinin-based Combination Therapy (ACT) in 2008. Our previous study in Kalabakan, located in south-east coast of Sabah showed a high prevalence of resistance to CQ and SP, suggesting the use of the treatment may no longer be effective in the area. This study aimed to provide a baseline data of antimalarial drug resistant markers on P...
2016: PloS One
https://www.readbyqxmd.com/read/27776514/optimal-health-and-disease-management-using-spatial-uncertainty-a-geographic-characterization-of-emergent-artemisinin-resistant-plasmodium-falciparum-distributions-in-southeast-asia
#17
Eric P M Grist, Jennifer A Flegg, Georgina Humphreys, Ignacio Suay Mas, Tim J C Anderson, Elizabeth A Ashley, Nicholas P J Day, Mehul Dhorda, Arjen M Dondorp, M Abul Faiz, Peter W Gething, Tran T Hien, Tin M Hlaing, Mallika Imwong, Jean-Marie Kindermans, Richard J Maude, Mayfong Mayxay, Marina McDew-White, Didier Menard, Shalini Nair, Francois Nosten, Paul N Newton, Ric N Price, Sasithon Pukrittayakamee, Shannon Takala-Harrison, Frank Smithuis, Nhien T Nguyen, Kyaw M Tun, Nicholas J White, Benoit Witkowski, Charles J Woodrow, Rick M Fairhurst, Carol Hopkins Sibley, Philippe J Guerin
BACKGROUND: Artemisinin-resistant Plasmodium falciparum malaria parasites are now present across much of mainland Southeast Asia, where ongoing surveys are measuring and mapping their spatial distribution. These efforts require substantial resources. Here we propose a generic 'smart surveillance' methodology to identify optimal candidate sites for future sampling and thus map the distribution of artemisinin resistance most efficiently. METHODS: The approach uses the 'uncertainty' map generated iteratively by a geostatistical model to determine optimal locations for subsequent sampling...
October 24, 2016: International Journal of Health Geographics
https://www.readbyqxmd.com/read/27769257/genetic-diversity-of-the-merozoite-surface-protein-3-gene-in-plasmodium-falciparum-populations-in-thailand
#18
Sittiporn Pattaradilokrat, Vorthon Sawaswong, Phumin Simpalipan, Morakot Kaewthamasorn, Napaporn Siripoon, Pongchai Harnyuttanakorn
BACKGROUND: An effective malaria vaccine is an urgently needed tool to fight against human malaria, the most deadly parasitic disease of humans. One promising candidate is the merozoite surface protein-3 (MSP-3) of Plasmodium falciparum. This antigenic protein, encoded by the merozoite surface protein (msp-3) gene, is polymorphic and classified according to size into the two allelic types of K1 and 3D7. A recent study revealed that both the K1 and 3D7 alleles co-circulated within P. falciparum populations in Thailand, but the extent of the sequence diversity and variation within each allelic type remains largely unknown...
October 21, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27704030/continued-sensitivity-of-plasmodium-falciparum-to-artemisinin-in-guyana-with-absence-of-kelch-propeller-domain-mutant-alleles
#19
Reyaud Rahman, Maria Jesus Sanchez Martin, Shamdeo Persaud, Nicolas Ceron, Dwayne Kellman, Lise Musset, Keith H Carter, Pascal Ringwald
Because of concerns about possible emergence of artemisinin resistance strains of Plasmodium falciparum in mining areas of the interior of Guyana, a 7-day artesunate trial was conducted from March to December 2014. The day-3 parasite clearance rate, the efficacy of artesunate at day 28, and polymorphism of Kelch 13 (PfK13)-the marker of artemisinin resistance-were assessed. The study confirmed the continued sensitivity of P falciparum to artemisinin. A 7-day course of artesunate was 100% efficacious with only 2% (95% confidence interval, ...
September 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/27698284/far-from-the-madding-crowd-the-molecular-basis-for-immunological-escape-of-plasmodium-falciparum
#20
Manuel E Patarroyo, Jorge Aza-Conde, Armando Moreno-Vranich, Laura Pabón, Yahson Varela, Manuel A Patarroyo
Like Thomas Hardy's famous novel Far from the Madding Crowd, Plasmodium falciparum parasites display their most relevant survival structures (proteins) involved in host cell invasion far away from the immune system's susceptible regions, displaying tremendous genetic variability, to attract the immune response and escape immune pressure. The 3D structure localisation of the conserved amino acid sequences of this deadly parasite's most relevant proteins involved in host cell invasion, as well as the location of the highly polymorphic, highly immunogenic regions, clearly demonstrates that such structures are far apart, sometimes 90° to 180° opposite, thereby rendering the immune response useless...
October 4, 2016: Current Issues in Molecular Biology
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