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malaria polymorphism

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
Vinicius A Sortica, Juliana D Lindenau, Maristela G Cunha, Maria DO Ohnishi, Ana Maria R Ventura, Ândrea Kc Ribeiro-Dos-Santos, Sidney Eb Santos, Luciano Sp Guimarães, Mara H Hutz
BACKGROUND: Chloroquine/primaquine is the current therapy to eliminate Plasmodium vivax infection in the Amazon region. AIMS: This study investigates CYP1A2, CYP2C8, CYP2C9, CYP3A4 and CYP3A5 genetic polymorphisms influence on cloroquine/primaquine treatment. PATIENTS & METHODS: Generalized estimating equations analyses were performed to determine the genetic influence in parasitemia and/or gametocytemia clearance over treatment time in 164 patients...
October 21, 2016: Pharmacogenomics
R Rebecca Love, Aaron M Steele, Mamadou B Coulibaly, Sékou F Traore, Scott J Emrich, Michael C Fontaine, Nora J Besansky
The molecular mechanisms and genetic architecture that facilitate adaptive radiation of lineages remain elusive. Polymorphic chromosomal inversions, due to their recombination-reducing effect, are proposed instruments of ecotypic differentiation. Here we study an ecologically diversifying lineage of An. gambiae, known as the Bamako chromosomal form based on its unique complement of three chromosomal inversions, to explore the impact of these inversions on ecotypic differentiation. We used pooled and individual genome sequencing of Bamako, typical (non-Bamako) An...
October 19, 2016: Molecular Ecology
Benjamin D Menze, Jacob M Riveron, Sulaiman S Ibrahim, Helen Irving, Christophe Antonio-Nkondjio, Parfait H Awono-Ambene, Charles S Wondji
BACKGROUND: Despite the recent progress in establishing the patterns of insecticide resistance in the major malaria vector Anopheles funestus, Central African populations of this species remain largely uncharacterised. To bridge this important gap and facilitate the implementation of suitable control strategies against this vector, we characterised the resistance patterns of An. funestus population from northern Cameroon. METHODS AND FINDINGS: Collection of indoor-resting female mosquitoes in Gounougou (northern Cameroon) in 2012 and 2015 revealed a predominance of An...
2016: PloS One
Olufunmilayo E Adejumo, Taiwo R Kotila, Adeyinka G Falusi, Boladale O Silva, Jacinta N Nwogu, Pius S Fasinu, Chinedum P Babalola
Polymorphic expression of metabolic enzymes have been identified as one of the key factors responsible for the interindividual/ethnic/racial variability in drug metabolism and effect. In Nigeria, there is a disproportionately high incidence of sickle-cell disease (SCD), a condition characterized by painful crisis frequently triggered by malaria. Proguanil, a substrate of the polymorphic CYP2C19, is a chemoprophylactic antimalarial drug widely used among SCD patients in Nigeria. This study aimed to conduct a comparative CYP2C19 phenotyping among SCD patients and healthy controls and to compare the results with those previously reported...
October 2016: Pharmacology Research & Perspectives
Saw Thu Wah, Hathairad Hananantachai, Usanee Kerdpin, Chotiros Plabplueng, Virapong Prachayasittikul, Pornlada Nuchnoi
Cerebral malaria is still a deleterious health problem in tropical countries. The wide spread of malarial drug resistance and the lack of an effective vaccine are obstacles for disease management and prevention. Parasite and human genetic factors play important roles in malaria susceptibility and disease severity. The malaria parasite exerted a potent selective signature on the human genome, which is apparent in the genetic polymorphism landscape of genes related to pathogenesis. Currently, much genomic data and a novel body of knowledge, including the identification of microRNAs, are being increasingly accumulated for the development of laboratory testing cassettes for cerebral malaria prevention...
2016: Tropical Medicine and Health
Bart W Faber, Stephan Hellwig, Sophie Houard, Nicolas Havelange, Jürgen Drossard, Hubert Mertens, Alexander Croon, Robin Kastilan, Richard Byrne, Nicole van der Werff, Marjolein van der Eijk, Alan W Thomas, Clemens H M Kocken, Edmond J Remarque
Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a leading asexual blood stage vaccine candidate for malaria. In preparation for clinical trials, three Diversity Covering (DiCo) PfAMA1 ectodomain proteins, designed to overcome the intrinsic polymorphism that is present in PfAMA1, were produced under Good Manufacturing Practice (GMP) in Pichia pastoris. Using identical methodology, the 3 strains were cultivated in 70-L scale fed-batch fermentations and PfAMA1-DiCos were purified by two chromatography steps, an ultrafiltration/diafiltration procedure and size exclusion chromatography, resulting in highly pure (>95%) PfAMA1-DiCo1, PfAMA1 DiCo2 and PfAMA1 DiCo3, with final yields of 1...
2016: PloS One
Zenglei Wang, Mynthia Cabrera, Jingyun Yang, Lili Yuan, Bhavna Gupta, Xiaoying Liang, Karen Kemirembe, Sony Shrestha, Awtum Brashear, Xiaolian Li, Stephen F Porcella, Jun Miao, Zhaoqing Yang, Xin-Zhuan Su, Liwang Cui
Drug resistance has emerged as one of the greatest challenges facing malaria control. The recent emergence of resistance to artemisinin (ART) and its partner drugs in ART-based combination therapies (ACT) is threatening the efficacy of this front-line regimen for treating Plasmodium falciparum parasites. Thus, an understanding of the molecular mechanisms that underlie the resistance to ART and the partner drugs has become a high priority for resistance containment and malaria management. Using genome-wide association studies, we investigated the associations of genome-wide single nucleotide polymorphisms with in vitro sensitivities to 10 commonly used antimalarial drugs in 94 P...
October 3, 2016: Scientific Reports
Bhavna Gupta, Daniel M Parker, Qi Fan, B P Niranjan Reddy, Guiyun Yan, Jetsumon Sattabongkot, Liwang Cui
Malaria transmission along international borders of the Greater Mekong Subregion is a big challenge for regional malaria elimination. At the Thai-Myanmar border, Plasmodium falciparum cases have dropped dramatically; however, increasing P. vivax prevalence and the emerging reports on hidden malaria burden due to asymptomatic infections demand attention. We conducted cross-sectional surveys to detect asymptomatic malaria infections in a small village located at Thai-Myanmar border and genotyped P. vivax infections in order to understand the level of genetic diversity on such a microgeographic scale...
September 28, 2016: Infection, Genetics and Evolution
Edward H Ntege, Nobuko Arisue, Daisuke Ito, Tomoyuki Hasegawa, Nirianne M Q Palacpac, Thomas G Egwang, Toshihiro Horii, Eizo Takashima, Takafumi Tsuboi
Genetic variability in Plasmodium falciparum malaria parasites hampers current malaria vaccine development efforts. Here, we hypothesize that to address the impact of genetic variability on vaccine efficacy in clinical trials, conserved antigen targets should be selected to achieve robust host immunity across multiple falciparum strains. Therefore, suitable vaccine antigens should be assessed for levels of polymorphism and genetic diversity. Using a total of one hundred and two clinical isolates from a region of high malaria transmission in Uganda, we analyzed extent of polymorphism and genetic diversity in four recently reported novel blood-stage malaria vaccine candidate proteins: Rh5 interacting protein (PfRipr), GPI anchored micronemal antigen (PfGAMA), rhoptry-associated leucine zipper-like protein 1 (PfRALP1) and Duffy binding-like merozoite surface protein 1 (PfMSPDBL1)...
September 28, 2016: Vaccine
Selorme Adukpo, Ben A Gyan, Michael F Ofori, Daniel Dodoo, Thirumalaisamy P Velavan, Christian G Meyer
BACKGROUND: Malaria elicits inflammatory responses, which, if not well regulated, may exert detrimental effects. When activated, triggering receptor expressed on myeloid cells (TREM)-1 enhances inflammatory responses by increasing secretion of IL-8 and other Th1 cytokines. In contrast, TREM-like transcript 1 (TREML-1) promotes anti-inflammatory responses by binding to TREM-1 ligands and competing with TREM-1, thus antagonizing TREM-1 activation to reduce inflammation. Endothelial protein C receptor (EPCR) also mediates anti-inflammatory responses by activating endothelial protein C (PC)...
September 27, 2016: Tropical Medicine & International Health: TM & IH
Anju Verma, Hema Joshi, Vineeta Singh, Anup Anvikar, Neena Valecha
BACKGROUND: Plasmodium vivax is the most widely distributed human malaria parasite and accounts for approximately the same number of malaria cases as Plasmodium falciparum in India. Compared with P. falciparum, P. vivax is difficult to eradicate because of its tendency to cause relapses, which impacts treatment and control strategies. The genetic diversity of these parasites, particularly of the merozoite surface protein-3 alpha (msp-3α) gene, can be used to help develop a potential vaccine...
2016: Malaria Journal
Damien R Drew, Danny W Wilson, Salenna R Elliott, Nadia Cross, Ulrich Terheggen, Anthony N Hodder, Peter M Siba, Kiprotich Chelimo, Arlene E Dent, James W Kazura, Ivo Mueller, James G Beeson
BACKGROUND: The polymorphic nature of many malaria vaccine candidates presents major challenges to achieving highly efficacious vaccines. Presently, there is very little knowledge on the prevalence and patterns of functional immune responses to polymorphic vaccine candidates in populations to guide vaccine design. A leading polymorphic vaccine candidate against blood-stage Plasmodium falciparum is apical membrane antigen 1 (AMA1), which is essential for erythrocyte invasion. The importance of AMA1 as a target of acquired human inhibitory antibodies, their allele specificity and prevalence in populations is unknown, but crucial for vaccine design...
September 23, 2016: BMC Medicine
Fredrick Kateera, Sam L Nsobya, Steven Tukwasibwe, Emmanuel Hakizimana, Leon Mutesa, Petra F Mens, Martin P Grobusch, Michèle van Vugt, Nirbhay Kumar
Faced with intense levels of chloroquine (CQ) resistance in Plasmodium falciparum malaria, Rwanda replaced CQ with amodiaquine (AQ)+sulfadoxine-pyrimethamine (SP) in 2001, and subsequently with artemether-lumefantrine (AL) in 2006, as first-line treatments for uncomplicated malaria. Following years of discontinuation of CQ use, re-emergence of CQ-susceptible parasites has been reported in countries including Malawi, Kenya and Tanzania. In contrast, high levels of SP resistant mutant parasites continue to be reported even in countries of presumed reduced SP drug selection pressure...
September 17, 2016: Acta Tropica
Jean Baptiste Roseau, Bruno Pradines, Nicolas Paleiron, Serge Vedy, Marylin Madamet, Fabrice Simon, Emilie Javelle
BACKGROUND: Artemisinin-based combination therapy (ACT) introduced in the mid-1990s has been recommended since 2005 by the World Health Organization as first-line treatment against Plasmodium falciparum in all endemic countries. In 2010, the combination dihydroartemisinin-piperaquine (DP) was recommended for the treatment of uncomplicated P. falciparum malaria. DP is one of the first-line treatments used by the French army since 2013. CASE PRESENTATION: A case of P...
2016: Malaria Journal
Sylvatrie-Danne Dinzouna-Boutamba, Sanghyun Lee, Ui-Han Son, Su-Min Song, Hye Soo Yun, So-Young Joo, Dongmi Kwak, Man Hee Rhee, Dong-Il Chung, Yeonchul Hong, Youn-Kyoung Goo
OBJECTIVES: Plasmodium vivax merozoite surface protein 1 (PvMSP1) is the most intensively studied malaria vaccine candidate. Although high antibody response-inducing two C-terminal fragments of PvMSP1 (PvMSP1-19 and PvMSP1-42) are currently being developed as candidate malaria vaccine antigens, their high genetic diversity in various isolates is a major hurdle. The sequence polymorphism of PvMSP1 has been investigated; however, the humoral immune responses induced by different portions of this protein have not been evaluated in Korea...
August 2016: Osong Public Health and Research Perspectives
E Venanzi, R López-Vélez
Severe malaria is a diagnostic and therapeutic emergency with great impact worldwide for incidence and mortality. The clinical presentation of severe malaria can be very polymorphic and rapidly progressing. Therefore a correct diagnosis and an early and adequate antiparasitic and support therapy are essential. This paper attempts to outline the diagnosis frame and the treatment of severe malaria for adults, paediatric patients and for pregnant.
September 2016: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
Sabina Dahlström Otienoburu, Oumou Maïga-Ascofaré, Birgit Schramm, Vincent Jullien, Joel J Jones, Yah M Zolia, Pascal Houzé, Elizabeth A Ashley, Jean-René Kiechel, Philippe J Guérin, Jacques Le Bras, Sandrine Houzé
BACKGROUND: Plasmodium falciparum uncomplicated malaria can successfully be treated with an artemisinin-based combination therapy (ACT). However resistance is spreading to the different ACT compounds; the artemisinin derivative and the partner drug. Studies of P. falciparum polymorphisms associated with drug resistance can provide a useful tool to track resistance and guide treatment policy as well as an in-depth understanding of the development and spread of resistance. METHODS: The role of P...
2016: Malaria Journal
Costanza Tacoli, Prabhanjan P Gai, Claude Bayingana, Kevin Sifft, Dominik Geus, Jules Ndoli, Augustin Sendegeya, Jean Bosco Gahutu, Frank P Mockenhaupt
Emerging artemisinin resistance is a threat to global malaria control. Mutations in the Plasmodium falciparum Kelch 13 (K13) propeller domain confer artemisinin resistance and constitute molecular markers for its detection and monitoring. We sequenced 222 P. falciparum isolates obtained from community children in the Huye District of southern Rwanda in 2010, 2014, and 2015 to investigate the presence of K13 polymorphisms. No polymorphisms were observed in 2010 but they were present in 2.5% and 4.5% in 2014 and 2015, respectively...
August 29, 2016: American Journal of Tropical Medicine and Hygiene
Jung-Mi Kang, Jinyoung Lee, Pyo-Yun Cho, Tae Im Kim, Woon-Mok Sohn, Jae-Won Park, Tong-Soo Kim, Byoung-Kuk Na
The vivax malaria epidemic has persisted in South Korea since its reemergence in 1993. Although there has been a significant decrease in the number of malaria cases in recent years, vivax malaria is still a major public health concern. To gain in-depth insight into the genetic makeup of Korean Plasmodium vivax, we analyzed polymorphic patterns of two major antigens, merozoite surface protein-1 (MSP-1) and MSP-3α, in 255 Korean P. vivax isolates collected over an extended period from 1998 to 2013. Combinational genetic analysis of polymorphic patterns of MSP-1 and MSP-3α in the isolates suggests that the P...
August 22, 2016: Infection, Genetics and Evolution
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