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falciparum polymorphism

Frances Rocamora, Lei Zhu, Kek Yee Liong, Arjen Dondorp, Olivo Miotto, Sachel Mok, Zbynek Bozdech
Due to their remarkable parasitocidal activity, artemisinins represent the key components of first-line therapies against Plasmodium falciparum malaria. However, the decline in efficacy of artemisinin-based drugs jeopardizes global efforts to control and ultimately eradicate the disease. To better understand the resistance phenotype, artemisinin-resistant parasite lines were derived from two clones of the 3D7 strain of P. falciparum using a selection regimen that mimics how parasites interact with the drug within patients...
March 14, 2018: PLoS Pathogens
Andrew J Guy, Vashti Irani, James G Beeson, Benjamin Webb, Andrej Sali, Jack S Richards, Paul A Ramsland
Humoral immune responses against the malaria parasite are an important component of a protective immune response. Antibodies are often directed towards conformational epitopes, and the native structure of the antigenic region is usually critical for antibody recognition. We examined the structural features of various Plasmodium antigens that may impact on epitope location, by performing a comprehensive analysis of known and modelled structures from P. falciparum. Examining the location of known polymorphisms over all available structures, we observed a strong propensity for polymorphic residues to be exposed on the surface and to occur in particular secondary structure segments such as hydrogen-bonded turns...
March 12, 2018: Scientific Reports
Tryphena Adams, Nana Aba A Ennuson, Neils B Quashie, Godfred Futagbi, Sena Matrevi, Oheneba C K Hagan, Benjamin Abuaku, Kwadwo A Koram, Nancy O Duah
BACKGROUND: Plasmodium falciparum delayed clearance with the use of artemisinin-based combination therapy (ACTs) has been reported in some African countries. Single nucleotide polymorphisms (SNPs) in two genes, P. falciparum adaptor protein complex 2 mu subunit (pfap2mu) and ubiquitin specific protease 1 (pfubp1), have been linked to delayed clearance with ACT use in Kenya and recurrent imported malaria in Britain. With over 12 years of ACT use in Ghana, this study investigated the prevalence of SNPs in the pfap2mu and pfubp1 in Ghanaian clinical P...
March 12, 2018: Parasites & Vectors
Mathieu Gendrot, Francis Tsombeng Foguim, Marie Gladys Robert, Rémy Amalvict, Joel Mosnier, Nicolas Benoit, Marylin Madamet, Bruno Pradines
BACKGROUND: Plasmodium falciparum resistance to artemisinin-based combination therapy has emerged and spread in Southeast Asia. In areas where artemisinin resistance is emerging, the efficacy of combination is now based on partner drugs. In this context, the identification of novel markers of resistance is essential to monitor the emergence and spread of resistance to these partner drugs. The ubiquitylation pathway could be a possible target for anti-malarial compounds and might be involved in resistance...
March 12, 2018: Malaria Journal
Dragan Ljolje, Pedro Rafael Dimbu, Julia Kelley, Ira Goldman, Douglas Nace, Aleixo Macaia, Eric S Halsey, Pascal Ringwald, Filomeno Fortes, Venkatachalam Udhayakumar, Eldin Talundzic, Naomi W Lucchi, Mateusz M Plucinski
BACKGROUND: Artemisinin-based combination therapy is the first-line anti-malarial treatment for uncomplicated Plasmodium falciparum infection in Angola. To date, the prevalence of polymorphisms in the pfk13 gene, associated with artemisinin resistance, and pfmdr1, associated with lumefantrine resistance, have not been systematically studied in Angola. METHODS: DNA was isolated from pretreatment and late treatment failure dried blood spots collected during the 2015 round of therapeutic efficacy studies in Benguela, Lunda Sul, and Zaire Provinces in Angola...
February 20, 2018: Malaria Journal
Bo Huang, Fei Tuo, Yuan Liang, Wanting Wu, Guangchao Wu, Shiguang Huang, Qirun Zhong, Xin-Zhuan Su, Hongying Zhang, Mingqiang Li, Affane Bacar, Kamal Said Abdallah, Ahamada M S A Mliva, Qi Wang, Zhaoli Yang, Shaoqin Zheng, Qin Xu, Jianping Song, Changsheng Deng
BACKGROUND: Malaria is still one of the serious public health problems in Grande Comore Island, although the number of annual cases has been greatly reduced in recent years. A better understanding of malaria parasite population diversity and transmission dynamics is critical for assessing the effectiveness of malaria control measures. The objective of this study is to investigate temporal changes in genetic diversity of Plasmodium falciparum populations and multiplicity of infection (MOI) in Grande Comore 10 years after introduction of ACT...
February 20, 2018: Malaria Journal
Giovanni Widmer
Genome sequencing has greatly contributed to our understanding of parasitic protozoa. This is particularly the case for Cryptosporidium species (phylum Apicomplexa) which are difficult to propagate. Because of their polymorphic nature, simple sequence repeats have been used extensively as genotypic markers to differentiate between isolates, but no global analysis of amino acid repeats in Cryptosporidium genomes has been reported. Taking advantage of several newly sequenced Cryptosporidium genomes, a comparative analysis of single-amino-acid repeats (SAARs) in seven species was undertaken...
February 12, 2018: Parasitology
Diego Garzón-Ospina, Sindy P Buitrago, Andrea E Ramos, Manuel A Patarroyo
Parasite antigen genetic diversity represents a great obstacle when designing a vaccine against malaria caused by Plasmodium vivax. Selecting vaccine candidate antigens has been focused on those fulfilling a role in invasion and which are conserved, thus avoiding specific-allele immune responses. Most antigens described to date belong to the blood stage, thereby blocking parasite development within red blood cells, whilst studying antigens from other stages has been quite restricted. Antigens from different parasite stages are required for developing a completely effective vaccine; thus, pre-erythrocyte stage antigens able to block the first line of infection becoming established should also be taken into account...
2018: Frontiers in Genetics
Jung-Mi Kang, Jinyoung Lee, Mya Moe, Hojong Jun, Hương Giang Lê, Tae Im Kim, Thị Lam Thái, Woon-Mok Sohn, Moe Kyaw Myint, Khin Lin, Ho-Joon Shin, Tong-Soo Kim, Byoung-Kuk Na
BACKGROUND: Plasmodium falciparum apical membrane antigen-1 (PfAMA-1) is one of leading blood stage malaria vaccine candidates. However, genetic variation and antigenic diversity identified in global PfAMA-1 are major hurdles in the development of an effective vaccine based on this antigen. In this study, genetic structure and the effect of natural selection of PfAMA-1 among Myanmar P. falciparum isolates were analysed. METHODS: Blood samples were collected from 58 Myanmar patients with falciparum malaria...
February 7, 2018: Malaria Journal
Supriya Sharma, Ram Suresh Bharti, Nitin Bhardwaj, Anupkumar R Anvikar, Neena Valecha, Neelima Mishra
BACKGROUND: Antimalarial drug resistance is a potential threat for control and elimination of malaria. To ascertain the status of antimalarial drug resistance at the study sites, correlation between in vitro drug sensitivity pattern and drug resistance molecular markers in Plasmodium falciparum malaria was undertaken. MATERIALS AND METHODS: Polymorphisms in P. falciparum chloroquine resistance transporter (pfcrt) K76T and pfmdr1 N86Y were studied in relation to the in vitro susceptibility of P...
October 2017: Indian Journal of Medical Microbiology
Gora Diop, Céline Derbois, Cheikh Loucoubar, Babacar Mbengue, Bineta Niakhana Ndao, Fatou Thiam, Alassane Thiam, Rokhaya Ndiaye, Yakhya Dieye, Robert Olaso, Jean-Francois Deleuze, Alioune Dieye
BACKGROUND: Severe forms of malaria (SM) are an outcome of Plasmodium falciparum infection and can cause death especially in children under 4 years of age. RNASE3 (ECP) has been identified as an inhibitor of Plasmodium parasites growth in vitro, and genetic analysis in hospitalized Ghanaian subjects has revealed the RNASE3 +371G/C (rs2073342) polymorphism as a susceptibility factor for cerebral malaria. The +371 C allele results in an Arg/Thr mutation that abolishes the cytotoxic activity of the ECP protein...
February 5, 2018: Malaria Journal
Christine E Figan, Juliana M Sá, Jianbing Mu, Viviana A Melendez-Muniz, Chia Hao Liu, Thomas E Wellems
BACKGROUND: Four Plasmodium falciparum genetic crosses (HB3×3D7, HB3×Dd2, 7G8×GB4, and 803×GB4) have produced sets of recombinant progeny that are widely used for malaria research, including investigations of anti-malarial drug resistance. It is critical to maintain the progeny free from cross-contamination. Microsatellite polymorphisms can be used to validate parasite identity. RESULTS: A set of 12 markers was developed that differentiates the parents of the four P...
February 2, 2018: Malaria Journal
Vito Baraka, Hypolite Muhindo Mavoko, Carolyn Nabasumba, Filbert Francis, Pascal Lutumba, Michael Alifrangis, Jean-Pierre Van Geertruyden
BACKGROUND: The emergence of resistance against artemisinin combination treatment is a major concern for malaria control. ACTs are recommended as the rescue treatment, however, there is limited evidence as to whether treatment and re-treatment with ACTs select for drug-resistant P. falciparum parasites. Thus, the purpose of the present study is to investigate the impact of (re-)treatment using artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) on the selection of P. falciparum multidrug resistance-1 (Pfmdr1) alleles in clinical settings...
2018: PloS One
Matt Ravenhall, Susana Campino, Nuno Sepúlveda, Alphaxard Manjurano, Behzad Nadjm, George Mtove, Hannah Wangai, Caroline Maxwell, Raimos Olomi, Hugh Reyburn, Christopher J Drakeley, Eleanor M Riley, Taane G Clark
Significant selection pressure has been exerted on the genomes of human populations exposed to Plasmodium falciparum infection, resulting in the acquisition of mechanisms of resistance against severe malarial disease. Many host genetic factors, including sickle cell trait, have been associated with reduced risk of developing severe malaria, but do not account for all of the observed phenotypic variation. Identification of novel inherited risk factors relies upon high-resolution genome-wide association studies (GWAS)...
January 2018: PLoS Genetics
Lindsey J Plenderleith, Weimin Liu, Oscar A MacLean, Yingying Li, Dorothy E Loy, Sesh A Sundararaman, Frederic Bibollet-Ruche, Gerald H Learn, Beatrice H Hahn, Paul M Sharp
Plasmodium falciparum, the major cause of malaria morbidity and mortality in humans, has been shown to have emerged after cross-species transmission of one of six host-specific parasites (subgenus Laverania) infecting wild chimpanzees (Pan troglodytes) and western gorillas (Gorilla gorilla). Binding of the parasite-encoded ligand RH5 to the host protein basigin is essential for erythrocyte invasion and has been implicated in host specificity. A recent study claimed to have found two amino acid changes in RH5 that "drove the host shift leading to the emergence of P...
January 23, 2018: MBio
Robert Verity, Nicholas J Hathaway, Andreea Waltmann, Stephanie M Doctor, Oliver J Watson, Jaymin C Patel, Kashamuka Mwandagalirwa, Antoinette K Tshefu, Jeffrey A Bailey, Azra C Ghani, Jonathan J Juliano, Steven R Meshnick
BACKGROUND: The Democratic Republic of the Congo (DRC) bears a high burden of malaria, which is exacerbated in pregnant women. The VAR2CSA protein plays a crucial role in pregnancy-associated malaria (PAM), and hence quantifying diversity at the var2csa locus in the DRC is important in understanding the basic epidemiology of PAM, and in developing a robust vaccine against PAM. METHODS: Samples were taken from the 2013-14 Demographic and Health Survey conducted in the DRC, focusing on children under 5 years of age...
January 24, 2018: Malaria Journal
Sittiporn Pattaradilokrat, Chawinya Trakoolsoontorn, Phumin Simpalipan, Natapot Warrit, Morakot Kaewthamasorn, Pongchai Harnyuttanakorn
BACKGROUND: The glutamate-rich protein (GLURP) of the malaria parasite Plasmodium falciparum is a key surface antigen that serves as a component of a clinical vaccine. Moreover, the GLURP gene is also employed routinely as a genetic marker for malarial genotyping in epidemiological studies. While extensive size polymorphisms in GLURP are well recorded, the extent of the sequence diversity of this gene is rarely investigated. The present study aimed to explore the genetic diversity of GLURP in natural populations of P...
January 22, 2018: Parasites & Vectors
Nilanju Pran Sarmah, Kishore Sarma, Dibya Ranjan Bhattacharyya, Ali Sultan, Devendra Bansal, Neeru Singh, Praveen K Bharti, Hargobinder Kaur, Rakesh Sehgal, Pradyumna Kishore Mohapatra, Jagadish Mahanta
BACKGROUND & OBJECTIVES: Northeast (NE) India is one of the high endemic regions for malaria with a preponderance of Plasmodium falciparum, resulting in high morbidity and mortality. The P. falciparum parasite of this region showed high polymorphism in drug-resistant molecular biomarkers. However, there is a paucity of information related to merozoite surface protein 1 (msp-1) and glutamate-rich protein (glurp) which have been extensively studied in various parts of the world. The present study was, therefore, aimed at investigating the genetic diversity of P...
September 2017: Indian Journal of Medical Research
Shiny Joy, Benudhar Mukhi, Susanta K Ghosh, Rajeshwara N Achur, D Channe Gowda, Namita Surolia
BACKGROUND: Malaria is highly prevalent in many parts of India and is mostly caused by the parasite species Plasmodium vivax followed by Plasmodium falciparum. Chloroquine (CQ) is the first-line treatment for blood stage P. vivax parasites, but cases of drug resistance to CQ have been reported from India. One of the surveillance strategies which is used to monitor CQ drug resistance, is the analysis of single nucleotide polymorphisms (SNPs) of the associated gene markers. Susceptibility to CQ can also be determined by copy number assessment of multidrug resistant gene (mdr-1)...
January 19, 2018: Malaria Journal
Ekpereonne Esu, Costanza Tacoli, Prabhanjan Gai, Nicole Berens-Riha, Michael Pritsch, Thomas Loescher, Martin Meremikwu
Sulfadoxine-pyrimethamine (SP) is the recommended drug for intermittent preventive treatment of malaria in pregnancy in most of sub-Saharan Africa. Resistance to SP is related to mutations in the dhfr and dhps gene of Plasmodium falciparum. This study determined the prevalence of Pfdhfr and Pfdhps polymorphisms found in asymptomatic pregnant women attending antenatal care in Calabar, Nigeria. From October 2013 to November 2014, asymptomatic pregnant women attending antenatal care clinics were enrolled after obtaining informed consent...
January 13, 2018: Parasitology Research
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