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falciparum polymorphism

Jasweer Kaur, Rachna Hora
Malaria is a disease that affects millions of people annually. An intracellular habitat and lack of protein synthesizing machinery in erythrocytes pose numerous difficulties for survival of the human pathogen Plasmodium falciparum . The parasite refurbishes the infected red blood cell (iRBC) by synthesis and export of several proteins in an attempt to suffice its metabolic needs and evade the host immune response. Immune evasion is largely mediated by surface display of highly polymorphic protein families known as variable surface antigens...
2018: PeerJ
Esmael Besufikad Belachew
Malaria causes approximately 212 million cases and 429 thousand deaths annually. Plasmodium falciparum is responsible for the vast majority of deaths (99%) than others. The virulence of P. falciparum is mostly associated with immune response-evading ability. It has different mechanisms to evade both Anopheles mosquito and human host immune responses. Immune-evading mechanisms in mosquito depend mainly on the Pfs47 gene that inhibits Janus kinase-mediated activation. Host complement factor also protects human complement immune attack of extracellular gametes in Anopheles mosquito midgut...
2018: Journal of Immunology Research
Vrushali Pathak, Roshan Colah, Kanjaksha Ghosh
Background & objectives: High prevalence of certain polymorphic alleles of erythrocytes in malaria endemic area has been linked to the resistance provided by these alleles against parasitic infestations. Numerous studies undertaken to demonstrate this correlation have generated conflicting results. This study was undertaken to investigate the abilities of various polymorphic erythrocytes to support in vitro growth of Plasmodium falciparum parasites. Methods: In this study under in vitro condition the ability of P...
January 2018: Indian Journal of Medical Research
Lalita Lumkul, Vorthon Sawaswong, Phumin Simpalipan, Morakot Kaewthamasorn, Pongchai Harnyuttanakorn, Sittiporn Pattaradilokrat
Development of an effective vaccine is critically needed for the prevention of malaria. One of the key antigens for malaria vaccines is the apical membrane antigen 1 ( AMA -1) of the human malaria parasite Plasmodium falciparum , the surface protein for erythrocyte invasion of the parasite. The gene encoding AMA -1 has been sequenced from populations of P. falciparum worldwide, but the haplotype diversity of the gene in P. falciparum populations in the Greater Mekong Subregion (GMS), including Thailand, remains to be characterized...
April 2018: Korean Journal of Parasitology
Nicaise Tuikue Ndam, Bernard Tornyigah, Akpéyédjé Yannelle Dossou, Guillaume Escriou, Morten A Nielsen, Ali Salanti, Saadou Issifou, Achille Massougbodji, Jean-Philippe Chippaux, Philippe Deloron
Background: Pregnant women are more susceptible to P. falciparum than before pregnancy, and infection has consequences for both mother and offspring. WHO recommends that pregnant woman in areas of transmission receive intermittent preventive treatment starting in the second trimester. Consequently, women are not protected during the first trimester, although P. falciparum infections are both frequent and harmful. Methods: A cohort of nulligravidae women was followed during subsequent pregnancy...
May 4, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Kimberly E Mace, Paul M Arguin, Kathrine R Tan
PROBLEM/CONDITION: Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles species mosquito. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. However, malaria is occasionally acquired by persons who have not traveled out of the country through exposure to infected blood products, congenital transmission, laboratory exposure, or local mosquitoborne transmission...
May 4, 2018: MMWR. Surveillance Summaries: Morbidity and Mortality Weekly Report. Surveillance Summaries
Luyi Ye, Fengyong Zhao, Qixiu Yang, Jiamin Zhang, Qin Li, Chen Wang, Zhonghui Guo, Ying Yang, Ziyan Zhu
BACKGROUND: Recently, basigin (BSG), which carries OK antigens on red blood cells (RBCs), was reported to be the receptor of the Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRh5). BSG-PfRh5 is the only essential receptor-ligand pair in P. falciparum invasion that is known to date. However, the kind of OK/BSG polymorphism involved in the selection pressure caused by P. falciparum malaria has not been determined. STUDY DESIGN AND METHODS: Blood samples were collected to detect the expression of OK/BSG...
April 29, 2018: Transfusion
Abu Naser Mohon, Didier Menard, Mohammad Shafiul Alam, Kevin Perera, Dylan R Pillai
Background: Artemisinin-resistant malaria (ARM) remains a significant threat to malaria elimination. In the Greater Mekong subregion, the prevalence of ARM in certain regions has reached greater than 90%. Artemisinin-resistant malaria is clinically identified by delayed parasite clearance and has been associated with mutations in the propeller domain of the kelch 13 gene. C580Y is the most prevalent mutation. The detection of ARM currently relies on labor-intensive and time-consuming methods such as clinical phenotyping or in vitro susceptibility testing...
April 2018: Open Forum Infectious Diseases
Anne Kessler, Joseph J Campo, Visopo Harawa, Wilson L Mandala, Stephen J Rogerson, Wenzhu B Mowrey, Karl B Seydel, Kami Kim
BACKGROUND: Antibody immunity is thought to be essential to prevent severe Plasmodium falciparum infection, but the exact correlates of protection are unknown. Over time, children in endemic areas acquire non-sterile immunity to malaria that correlates with development of antibodies to merozoite invasion proteins and parasite proteins expressed on the surface of infected erythrocytes. RESULTS: A 1000 feature P. falciparum 3D7 protein microarray was used to compare P...
April 25, 2018: Malaria Journal
Judith Recht, Elizabeth A Ashley, Nicholas J White
Primaquine is the only available antimalarial drug that kills dormant liver stages of Plasmodium vivax and Plasmodium ovale malarias and therefore prevents their relapse ('radical cure'). It is also the only generally available antimalarial that rapidly sterilises mature P. falciparum gametocytes. Radical cure requires extended courses of primaquine (usually 14 days; total dose 3.5-7 mg/kg), whereas transmissibility reduction in falciparum malaria requires a single dose (formerly 0.75 mg/kg, now a single low dose [SLD] of 0...
April 2018: PLoS Neglected Tropical Diseases
Shiny Joy, Susanta K Ghosh, Rajeshwara N Achur, D Channe Gowda, Namita Surolia
BACKGROUND: Genes encoding dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) are the targets of sulfadoxine-pyrimethamine (SP) present in artemisinin based combination therapy (ACT; artesunate + sulfadoxine pyrimethamine) for Plasmodium falciparum. Although SP is generally not used to treat vivax infection, mutations in dhfr and dhps that confer antifolate resistance in Plasmodium vivax are common; which may be attributed to its sympatric existence with P. falciparum...
April 16, 2018: Malaria Journal
Faiza A Siddiqui, Mynthia Cabrera, Meilian Wang, Awtum Brashear, Karen Kemirembe, Zenglei Wang, Jun Miao, Thanat Chookajorn, Zhaoqing Yang, Yaming Cao, Gang Dong, Philip J Rosenthal, Liwang Cui
Falcipain-2a (FP2a; PF3D7_1115700) is a Plasmodium falciparum cysteine protease and hemoglobinase. Functional FP2a is required for potent activity of artemisinin, and in vitro selection for artemisinin resistance selected for an FP2a nonsense mutation. To investigate associations between FP2a polymorphisms and artemisinin resistance and to characterize the diversity of the enzyme in parasites from the China-Myanmar border, we sequenced the full-length FP2a gene in 140 P. falciparum isolates collected during 2004-2011...
April 12, 2018: Journal of Infectious Diseases
Gaoqian Feng, Michelle J Boyle, Nadia Cross, Jo-Anne Chan, Linda Reiling, Faith Osier, Danielle Stanisic, Ivo Mueller, Robin F Anders, James S McCarthy, Jack S Richards, James G Beeson
Background: Overcoming antigenic diversity is a key challenge in the development of effective P. falciparum malaria vaccines. Strategies that promote the generation of antibodies targeting conserved epitopes of vaccine antigens may provide protection against diverse parasites strains. Understanding differences between vaccine-induced and naturally-acquired immunity is important to achieving this goal. Methods: We analysed antibodies generated in a phase 1 human vaccine trial, MSP2-C1, which included two allelic forms MSP2, an abundant vaccine antigen on the merozoites surface...
March 23, 2018: Journal of Infectious Diseases
Joseph Osarfo, Harry Tagbor, Pascal Magnussen, Michael Alifrangis
Data on prevalence of antimalarial molecular resistance markers in pregnant women in Ghana is scarce. Prevalence of single nucleotide polymorphisms/haplotypes in the Pfcrt , Pfmdr1 , Pfdhfr , and Pfdhps genes was assessed in a cross-sectional study involving 200 pregnant women. Almost 90% of infections were wild type at the Pfcrt gene whereas the Pfmdr1 NFD mutant haplotype occurred in 43% of samples. Prevalence of Pfdhfr/Pfdhps quadruple mutation was 92.6% whereas Pfdfr/Pfdhps quintuple mutation with K540E was not observed...
March 26, 2018: American Journal of Tropical Medicine and Hygiene
Zaydah R de Laurent, Lorna J Chebon, Luicer A Ingasia, Hoseah M Akala, Ben Andagalu, Lynette Isabella Ochola-Oyier, Edwin Kamau
The development of artemisinin (ART)-resistant parasites in Southeast Asia (SEA) threatens malaria control globally. Mutations in the Kelch 13 (K13)-propeller domain have been useful in identifying ART resistance in SEA. ART combination therapy (ACT) remains highly efficacious in the treatment of uncomplicated malaria in Sub-Saharan Africa (SSA). However, it is crucial that the efficacy of ACT is closely monitored. Toward this effort, this study profiled the prevalence of K13 nonsynonymous mutations in different malaria ecological zones of Kenya and in different time periods, before (pre) and after (post) the introduction of ACT as the first-line treatment of malaria...
March 26, 2018: American Journal of Tropical Medicine and Hygiene
Shehu S Awandu, Jaishree Raman, Takalani I Makhanthisa, Philip Kruger, John Frean, Teun Bousema, Jandeli Niemand, Lyn-Marie Birkholtz
BACKGROUND: Primaquine (PQ) is recommended as an addition to standard malaria treatments in pre-elimination settings due to its pronounced activity against mature Plasmodium falciparum gametocytes, the parasite stage responsible for onward transmission to mosquitoes. However, PQ may trigger haemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. Additional human genetic factors, including polymorphisms in the human cytochrome P450 2D6 (CYP2D6) complex, may negatively influence the efficacy of PQ...
March 20, 2018: Malaria Journal
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
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