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suboptimal erythropoietin production in adult severe falciparum malaria. 201121751602
characterization of in vivo metabolites of wr319691, a novel compound with activity against plasmodium falciparum.wr319691 has been shown to exhibit reasonable plasmodium falciparum potency in vitro and exhibits reduced permeability across mdck cell monolayers, which as part of our screening cascade led to further in vivo analysis. single-dose pharmacokinetics was evaluated after an iv dose of 5 mg/kg in mice. maximum bound and unbound brain levels of wr319691 were 97 and 0.05 ng/g versus approximately 1,600 and 3.2 ng/g for mefloquine. the half-life of wr319691 in plasma was approximately 13 h versus 23 h ...201121751074
screening a fragment cocktail library using ultrafiltration.ultrafiltration provides a generic method to discover ligands for protein drug targets with millimolar to micromolar k (d), the typical range of fragment-based drug discovery. this method was tailored to a 96-well format, and cocktails of fragment-sized molecules, with molecular masses between 150 and 300 da, were screened against medical structural genomics target proteins. the validity of the method was confirmed through competitive binding assays in the presence of ligands known to bind the t ...201121750879
gene gain and loss during evolution of obligate parasitism in the white rust pathogen of arabidopsis thaliana.biotrophic eukaryotic plant pathogens require a living host for their growth and form an intimate haustorial interface with parasitized cells. evolution to biotrophy occurred independently in fungal rusts and powdery mildews, and in oomycete white rusts and downy mildews. biotroph evolution and molecular mechanisms of biotrophy are poorly understood. it has been proposed, but not shown, that obligate biotrophy results from (i) reduced selection for maintenance of biosynthetic pathways and (ii) g ...201121750662
peristaltic transport and mixing of cytosol through the whole body of physarum plasmodium.we study how the net transport and mixing of chemicals occur in a relatively large amoeba, the true slime mold physarum polycephalum. the shuttle streaming of the amoeba is characterized by a rhythmic flow of the order of 1 µm/s in which the protoplasm streams back and forth. to explain the experimentally observed transport of chemicals, we formulate a simplified model to consider the mechanism by which net transport can be induced by shuttle (or periodic) motion inside the amoeba. this model is ...201121750121
evaluation of four rapid diagnostic tests for the diagnosis of plasmodium vivax in korea.objective to evaluate 4 rapid malaria diagnostic kits (rdts) in korea: optimal test, sd bioline malaria ag p.f/pan test, humasis malaria p.f/pan antigen test and carestartâ„¢ malaria pf/pv combo test. methods hundred malaria patients with plasmodium vivax (p. vivax) and 100 healthy volunteers were recruited. the results from earlier four rdts were compared with the reference standard, the giemsa-stained traditional microscopic diagnosis. results compared with the reference standard, the sensiti ...201121749585
in vitro antimalarial activity and cytotoxicity of some selected cuban medicinal plants.terrestrial plants have been demonstrated to be sources of antimalarial compounds. in cuba, little is known about antimalarial potentials of plant species used as medicinals. for that reason, we evaluated the antimalarial activity of 14 plant species used in cuba as antimalarial, antipyretic and/or antiparasitic. hydroalcoholic extracts were prepared and tested in vitro for the antimalarial activity against plasmodium falciparum ghana strain and over human cell line mrc-5 to determine cytotoxici ...201021748227
serological evidence of discrete spatial clusters of plasmodium falciparum parasites.malaria transmission may be considered to be homogenous with well-mixed parasite populations (as in the classic ross/macdonald models). marked fine-scale heterogeneity of transmission has been observed in the field (i.e., over a few kilometres), but there are relatively few data on the degree of mixing. since the plasmodium falciparum erythrocyte membrane protein 1 (pfemp1) is highly polymorphic, the host's serological responses may be used to infer exposure to parasite sub-populations.201121747921
gametocytes of plasmodium falciparum in the megakaryocytes. 201121747877
antiprotozoal activities of organic extracts from french marine seaweeds.marine macrophytes contain a variety of biologically active compounds, some reported to have antiprotozoal activity in vitro. as a part of a screening program to search for new natural antiprotozoals, we screened hydroalcoholic and ethyl acetate extracts of 20 species of seaweeds from three phyla (rhodophyta, heterokontophyta and chlorophyta), sampled along the normandy (france) coast. we tested them in vitro against the protozoa responsible for three major endemic parasitic diseases: plasmodium ...201121747738
evasion of immunity to plasmodium falciparum malaria by igm masking of protective igg epitopes in infected erythrocyte surface-exposed pfemp1.plasmodium falciparum malaria is a major cause of mortality and severe morbidity. its virulence is related to the parasite's ability to evade host immunity through clonal antigenic variation and tissue-specific adhesion of infected erythrocytes (ies). the p. falciparum erythrocyte membrane protein 1 (pfemp1) family is central to both. here, we present evidence of a p. falciparum evasion mechanism not previously documented: the masking of pfemp1-specific igg epitopes by nonspecific igm. nonspecif ...201121746929
identifying apicoplast-targeting antimalarials using high-throughput compatible approaches.malarial parasites have evolved resistance to all previously used therapies, and recent evidence suggests emerging resistance to the first-line artemisinins. to identify antimalarials with novel mechanisms of action, we have developed a high-throughput screen targeting the apicoplast organelle of plasmodium falciparum. antibiotics known to interfere with this organelle, such as azithromycin, exhibit an unusual phenotype whereby the progeny of drug-treated parasites die. our screen exploits this ...201121746861
plasmodium falciparum isolates from southern ghana exhibit polymorphisms in the serca-type pfatpase6 though sensitive to artesunate in vitro.abstract:201121745377
analysis of chloroquine resistance transporter (crt) isoforms and orthologues in s. cerevisiae yeast.previous work from our laboratory optimized meoh-inducible expression of the p. falciparum malarial parasite transporter pfcrt in p. pastoris yeast. these strains are useful for many experiments but do not allow for inducible protein expression under ambient growth conditions. we have therefore optimized galactose-inducible expression of pfcrt in s. cerevisiae yeast. we find that expression of pfcrt confers cq hypersensitivity to growing yeast and that this is due to plasma membrane localization ...201121744797
biochemistry of the non-mevalonate isoprenoid pathway.the non-mevalonate pathway of isoprenoid (terpenoid) biosynthesis is essential in many eubacteria including the major human pathogen, mycobacterium tuberculosis, in apicomplexan protozoa including the plasmodium spp. causing malaria, and in the plastids of plants. the metabolic route is absent in humans and is therefore qualified as a promising target for new anti-infective drugs and herbicides. biochemical and structural knowledge about all enzymes involved in the pathway established the basis ...201121744068
plasmodium falciparum infection-induced changes in erythrocyte membrane proteins.over the past decade, advances in proteomic and mass spectrometry techniques and the sequencing of the plasmodium falciparum genome have led to an increasing number of studies regarding the parasite proteome. however, these studies have focused principally on parasite protein expression, neglecting parasite-induced variations in the host proteome. here, we investigated p. falciparum-induced modifications of the infected red blood cell (irbc) membrane proteome, taking into account both host and p ...201121744020
a microfluidic system to study cytoadhesion of plasmodium falciparum infected erythrocytes to primary brain microvascularendothelial cells.the cellular events leading to severe and complicated malaria in some plasmodium falciparum infections are poorly understood. additional tools are required to better understand the pathogenesis of this disease. in this technical report, we describe a microfluidic culture system and image processing algorithms that were developed to observe cytoadhesion interactions of p. falciparum parasitized erythrocytes rolling on primary brain microvascularendothelial cells. we isolated and cultured human pr ...201121743938
dimerization of plasmodium vivax dbp is induced upon receptor binding and drives recognition of darc.plasmodium vivax and plasmodium knowlesi invasion depends on the parasite duffy-binding protein dbl domain (rii-pvdbp or rii-pkdbp) engaging the duffy antigen receptor for chemokines (darc) on red blood cells. inhibition of this key interaction provides an excellent opportunity for parasite control. there are competing models for whether plasmodium ligands engage receptors as monomers or dimers, a question whose resolution has profound implications for parasite biology and control. we report cry ...201121743458
structural basis for the regulation of cysteine-protease activity by a new class of protease inhibitors in plasmodium.plasmodium cysteine proteases are essential for host-cell invasion and egress, hemoglobin degradation, and intracellular development of the parasite. the temporal, site-specific regulation of cysteine-protease activity is a prerequisite for survival and propagation of plasmodium. recently, a new family of inhibitors of cysteine proteases (icps) with homologs in at least eight plasmodium species has been identified. here, we report the 2.6-á+à x-ray crystal structure of the c-terminal, inhibitory ...201121742259
potential of a khaya ivorensis -alstonia boonei extract combination as antimalarial prophylactic remedy.the decoction of the combined stem barks of khaya ivorensis a. chev. (meliaceae) and alstonia boonei de wild (apocynaceae) has a history of use in traditional medicine of central cameroon for malaria treatment but also for the prevention of the disease.201121742022
in the eye of experimental cerebral malaria.cerebral malaria is the most severe complication of plasmodium falciparum infection, accounting for 1 million deaths per year. we characterized the murine disease using in vivo magnetic resonance imaging (mri) at 4.7 t, proving that ischemic edema is responsible for fatality. the aim of the present study was to identify early markers of experimental cerebral malaria using very high field conventional mri (11.75 t). cba/j mice infected with plasmodium berghei anka were observed at an early stage ...201121741941
plasmodium falciparum and helminth coinfections among schoolchildren in relation to agro-ecosystems in mvomero district, tanzania.in sub-saharan africa, some individuals infected with malaria are also infected with helminths. however, the magnitude and distribution of such coinfections in relation to eco-systems remains poorly defined. this study was undertaken to determine the prevalence of plasmodium falciparum and helminth coinfections among schoolchildren in relation to agro-ecosystems in mvomero district, tanzania.201121741929
investigations on the role of a lysozyme from the malaria vector anopheles dirus during malaria parasite development.a cdna encoding a lysozyme was obtained by rapid amplification of cdna ends-polymerase chain reaction (race-pcr) from females of the malaria vector anopheles dirus a (diptera: culicidae). the 623bp lysozyme (adlys c-1) cdna encodes the 120 amino acid mature protein with a predicted molecular mass of 13.4kda and theoretical pi of 8.45. six cysteine residues and a potential calcium binding motif that are present in adlys c-1 are highly conserved relative to those of c-type lysozymes found in other ...201121741400
malaria in selected non-amazonian countries of latin america.approximately 170 million inhabitants of the american continent live at risk of malaria transmission. although the continent's contribution to the global malaria burden is small, at least 1-1.2 million malaria cases are reported annually. sixty percent of the malaria cases occur in brazil and the other 40% are distributed in 20 other countries of central and south america. plasmodium vivax is the predominant species (74.2%) followed by p. falciparum (25.7%) and p. malariae (0.1%), and no less th ...201121741349
protein translation in plasmodium parasites.the protein translation machinery of the parasite plasmodium is the target of important anti-malarial drugs, and encompasses many promising targets for future drugs. plasmodium parasites have three subcellular compartments that house genomes; the nucleus, mitochondrion and apicoplast, and each requires its own compartmentalized transcription and translation apparatus for survival. despite the availability of the complete genome sequence that should reveal the requisite elements for all three com ...201121741312
evaluation of fkbp and dhfr based destabilizing domains in saccharomyces cerevisiae.two orthogonal destabilizing domains have been developed based on mutants of human fkbp12 as well as bacterial dhfr and these engineered domains have been used to control protein concentration in a variety of contexts in vitro and in vivo. fkbp12 based destabilizing domains cannot be rescued in the yeast saccharomyces cerevisiae; ecdhfr based destabilizing domains are not degraded as efficiently in s. cerevisiae as in mammalian cells or plasmodium, but provide a starting point for the developmen ...201121741238
targeting the human malaria parasite plasmodium falciparum: in vitro identification of a new antiplasmodial hit in 4-phenoxy-2-trichloromethylquinazoline series.from the promising results we previously obtained in quinazoline series and to complete the evaluation of the in-ávitro antiplasmodial activity of original 2-trichloromethylquinazolines, we synthesized new quinazolines possessing a variously substituted phenoxy group at position 4 through a simple and efficient two-step-synthesis approach. the studies of their activity toward the multi-resistant w2 plasmodium falciparum strain and of their cytotoxicity on the human hepatocyte hepg2 cell line hig ...201121741131
etiopathogenesis of burkitt's lymphoma: a lesson from a bl-like in cd1 mouse immune to plasmodium yoelii yoelii.abstract:201121740585
comparative study of the efficacy and tolerability of dihydroartemisinin - piperaquine - trimethoprim versus artemether - lumefantrine in the treatment of uncomplicated plasmodium falciparum malaria in cameroon, ivory coast and senegal.abstract:201121740570
highly co-ordinated var gene expression and switching in clinical plasmodium falciparum isolates from non-immune malaria patients.antigenic variation to fool the immune system is one of the molecular tricks plasmodium uses to maintain infection in its human host. the exclusive expression of the surface-exposed pfemp1 molecules, encoded by var genes, is the best example for this. central questions regarding the dynamics of antigenic variation, namely the rate of switching and the regulation of var gene expression in plasmodium falciparum, are yet unanswered. to elucidate the in vivo situation, we studied var gene switching ...201121740496
in vitro sensitivity of plasmodium falciparum field isolates to extracts from cameroonian annonaceae plants.in a search for new plant-derived antimalarial extracts, 19 fractions were obtained from three annonaceae species, uvariopsis congolana (leaf, stem), polyalthia oliveri (stem bark), and enantia chlorantha (stem, stem bark) with yields ranging from 0.33% to 4.60%. the extracts were prepared from 500-ág of each plant part, using organic solvents to afford five methanolic fractions (acetogenin rich), five water fractions, five hexane fractions, and four interface precipitates. evaluation of the act ...201121739316
in vitro activity of antifungal drugs against plasmodium falciparum field isolates.the increasing resistance of the malaria parasite plasmodium falciparum to currently available drugs necessitates a continuous effort to develop new antimalarial agents. we therefore aimed to assess the in vitro activity of the antifungal drugs clotrimazole, fluconazole, ketoconazole, itraconazole, voriconazole, flucytosine, amphotericin b, and caspofungin against field isolates of p. falciparum from lambar+®n+®, gabon. using the histidin-rich protein 2 (hrp-2) assay we determined the drug susce ...201121739204
why is plasmodium vivax a neglected tropical disease? 201121738804
plasmodium falciparum malaria endemicity in indonesia in 2010.malaria control programs require a detailed understanding of the contemporary spatial distribution of infection risk to efficiently allocate resources. we used model based geostatistics (mbg) techniques to generate a contemporary map of plasmodium falciparum malaria risk in indonesia in 2010.201121738634
ethnodiagnostic skills of the digo community for malaria: a lead to traditional bioprospecting.malaria is a major public health problem that is presently complicated by the development of resistance by plasmodium falciparum to the mainstay drugs. thus, new drugs with unique structures and mechanism of action are required to treat drug-resistant strains of malaria. historically, compounds containing a novel structure from natural origin represent a major source for the discovery and development of new drugs for several diseases. this paper presents ethnophytotherapeutic remedies, ethnodiag ...201121738507
plasmodium vivax dhfr mutations among isolates from malarious areas of iran.the use of sulfadoxine and pyrimethamine (sp) for treatment of vivax malaria is uncommon in most malarious areas, but plasmodium vivax isolates are exposed to sp because of mixed infections with other plasmodium species. as p. vivax is the most prevalent species of human malaria parasites in iran, monitoring of resistance of the parasite against the drug is necessary. in the present study, 50 blood samples of symptomatic patients were collected from 4 separated geographical regions of south-east ...201121738267
first record of avian plasmodium dna from mosquitoes collected in the yaeyama archipelago, southwestern border of japan.we studied the prevalence of avian plasmodium in 509 mosquitoes of 9 species collected from the ishigaki and iriomote islands in the yaeyama archipelago, located southwest from the mainland of japan. two identical avian plasmodium lineages were detected from culex (culiciomyia) nigropunctatus. detected lineages were phylogenetically classified into different clade to avian plasmodium lineages from birds and mosquitoes in the mainland of japan but identical to a lineage detected from a resident b ...201121737963
Targeting Plasmodium liver stages: better late than never.The worldwide burden of malaria can be substantially reduced using existing public health interventions. However, elimination of Plasmodium will require fundamentally different approaches. Novel experimental attenuation strategies for active immunization using knockout strains have recently stimulated renewed interest in whole-parasite vaccine approaches. Preventive drug administration during transmission of wild-type sporozoites is a complementary strategy for eliciting protective immune respon ...201121737347
the influence of mosquito resting behaviour and associated microclimate for malaria risk.abstract:201121736735
azithromycin plus chloroquine: combination therapy for protection against malaria and sexually transmitted infections in pregnancy.introduction: the first-line therapy for the intermittent preventive treatment of malaria in pregnancy (iptp) is sulphadoxine-pyrimethamine (sp). there is an urgent need to identify safe, well-tolerated and efficacious alternatives to sp due to widespread plasmodium falciparum resistance. combination therapy using azithromycin and chloroquine is one possibility that has demonstrated adequate parasitological response > 95% in clinical trials of non-pregnant adults in sub-saharan africa and where ...201121736423
antimalarial activity of natural and synthetic prodiginines.prodiginines are a family of linear and cyclic oligopyrrole red-pigmented compounds. herein we describe the in vitro antimalarial activity of four natural (ic(50) = 1.7-8.0 nm) and three sets of synthetic prodiginines against plasmodium falciparum. set 1 compounds replaced the terminal nonalkylated pyrrole ring of natural prodiginines and had diminished activity (ic(50) > 2920 nm). set 2 and set 3 prodiginines were monosubstituted or disubstituted at either the 3 or 5 position of the right-hand ...201121736388
comparison of microscopical examination and semi-nested multiplex polymerase chain reaction in diagnosis of plasmodium falciparum and p. vivax.we compared light microscopy examination and a semi-nested multiplex pcr (snm-pcr) assay in endemic areas of the islamic republic of iran. a total of 68 individuals with malaria-positive and suspected malaria symptoms were included in the study. giemsa-stained thick blood films were examined under a light microscope for malaria parasites in 100 and 200 fields. dna was extracted from blood samples and snm-pcr based on the amplification of the small sub-unit ribosomal rna (ssrrna) gene sequences w ...201121735802
artemisinin-based combination therapy for treating uncomplicated plasmodium vivax malaria.plasmodium vivax is an important cause of malaria in many parts of asia and south america, and resistance to the standard treatment (chloroquine) is now high in some parts of oceania. this review aims to assess the current treatment options in the light of rising chloroquine resistance.201121735431
rapid diagnostic tests for diagnosing uncomplicated p. falciparum malaria in endemic countries.rapid diagnostic tests (rdts) for plasmodium falciparum malaria use antibodies to detect either hrp-2 antigen or pldh antigen, and can improve access to diagnostics in developing countries.201121735422
malaria caused by plasmodium vivax complicated by acalculous cholecystitis.we report the first adult cases of acute acalculous cholecystitis (aac) exclusively caused by infections with plasmodium vivax. we reviewed the previous cases of aac occurring during malaria, compared and contrasted the variables of previously reported cases with the cases reported here, examined the pathogenic link between malaria and aac, and considered the diagnostic pitfalls and treatment implications as they applied to clinical outcomes in patients with this serious and potentially underrec ...201121734122
Antimalarial drug sensitivity profile of western Kenya Plasmodium falciparum field isolates determined by a SYBR Green I in vitro assay and molecular analysis.In vitro drug sensitivity and molecular analyses of Plasmodium falciparum track drug resistance. DNA-binding fluorescent dyes like SYBR Green I may allow field laboratories, proximal to P. falciparum collection sites, to conduct drug assays. In 2007-2008, we assayed 121 P. falciparum field isolates from western Kenya for 50% inhibitory concentrations (IC(50)) against 6 antimalarial drugs using a SYBR Green I in vitro assay: 91 immediate ex vivo (IEV) and 30 culture-adapted, along with P. falcipa ...201121734121
molecular epidemiology of malaria in cameroon. xxx. sequence analysis of plasmodium falciparum atpase 6, dihydrofolate reductase, and dihydropteroate synthase resistance markers in clinical isolates from children treated with an artesunate-sulfadoxine-pyrimethamine combination.plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes are reliable molecular markers for antifolate resistance. the p. falciparum atpase 6 (pfatp6) gene has been proposed to be a potential marker for artemisinin resistance. in our previous clinical study, we showed that artesunate-sulfadoxine-pyrimethamine is highly effective against uncomplicated malaria in yaound+®, cameroon. in the present study, dhfr, dhps, and pfatp6 mutations in p. falciparum isolat ...201121734119
intermittent preventive treatment with sulfadoxine-pyrimethamine against malaria and anemia in pregnant women.the effectiveness of intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine (iptp-sp) against malaria and anemia is unclear because of the spread of sp-resistant plasmodium falciparum. this study evaluates the effectiveness of iptp-sp among pregnant women attending the antenatal clinic at korle-bu teaching hospital in accra, ghana. a cross-sectional study comparing malaria and anemia prevalence among pregnant women using iptp-sp with non-iptp-sp users was conducted dur ...201121734118
ivermectin mass drug administration to humans disrupts malaria parasite transmission in senegalese villages.ivermectin mass drug administration (mda) to humans is used to control onchocerciasis and lymphatic filariasis. recent field studies have shown an added killing effect of ivermectin mda against malaria vectors. we report that ivermectin mda reduced the proportion of plasmodium falciparum infectious anopheles gambiae sensu stricto (s.s.) in treated villages in southeastern senegal. ivermectin mda is a different delivery method and has a different mode of action from current malaria control agents ...201121734116
quantitative disease resistance: to better understand parasite-mediated selection on major histocompatibility complex.we outline a descriptive framework of how candidate alleles of the immune system associate with infectious diseases in natural populations of animals. three kinds of alleles can be separated when both prevalence of infection and infection intensity are measured-qualitative disease resistance, quantitative disease resistance and susceptibility alleles. our descriptive framework demonstrates why alleles for quantitative resistance and susceptibility cannot be separated based on prevalence data alo ...201121733902
how selection forces dictate the variant surface antigens used by malaria parasites.red blood cells infected by the malaria parasite plasmodium falciparum express variant surface antigens (vsas) that evade host immunity and allow the parasites to persist in the human population. there exist many different vsas and the differential expression of these vsas is associated with the virulence (damage to the host) of the parasites. the aim of this study is to unravel the differences in the effect key selection forces have on parasites expressing different vsas such that we can better ...201121733875
bromophycolideôçàa targets heme crystallization in the human malaria parasite plasmodium falciparum. 201121732541
relevant assay to study the adhesion of plasmodium falciparum-infected erythrocytes to the placental epithelium.in placental malaria, plasmodium falciparum-infected erythrocytes adhere to the apical plasma membrane of the placental epithelium, triggering an impairment of placental function detrimental to the fetus. the design of anti-adhesion intervention strategies requires a detailed understanding of the mechanisms involved. however, most adhesion assays lack in vivo relevance and are hardly quantitative. here, we describe a flow cytometry-based adhesion assay that is fully relevant by using apical epit ...201121731654
chemotherapeutic interaction between khaya grandifoliola (welw) cdc stem bark extract and two anti-malarial drugs in mice.in malarial endemic countries especially in the tropics, conventional antimalarial drugs are used with herbal remedies either concurrently or successively. khaya grandifoliola is one of such popular herbs used in the treatment of malaria.various doses of ethanol extract of k. grandifoliola stem bark (50-400 mg/kg/day) were administered orally to swiss albino mice infected with plasmodium yoelii nigerense. a dose of 100 mg/kg/day of the extract was also combined with 2.5 mg/kg/day of chloroquine ...201021731168
african monkeys are infected by plasmodium falciparum nonhuman primate-specific strains.recent molecular exploration of the plasmodium species circulating in great apes in africa has revealed the existence of a large and previously unknown diversity of plasmodium. for instance, gorillas were found to be infected by parasites closely related to plasmodium falciparum, suggesting that the human malignant malaria agent may have arisen after a transfer from gorillas. although this scenario is likely in light of the data collected in great apes, it remained to be ascertained whether p. f ...201121730135
from the cover: rerooting the evolutionary tree of malaria parasites.malaria parasites (plasmodium spp.) have plagued humans for millennia. less well known are related parasites (haemosporida), with diverse life cycles and dipteran vectors that infect other vertebrates. understanding the evolution of parasite life histories, including switches between hosts and vectors, depends on knowledge of evolutionary relationships among parasite lineages. in particular, inferences concerning time of origin and trait evolution require correct placement of the root of the evo ...201121730128
ex vivo drug susceptibility of ferroquine against chloroquine-resistant isolates of plasmodium falciparum and p. vivax.ferroquine (fq; ssr97193), a ferrocene-containing 4-aminoquinoline derivate, has potent in vitro efficacy against chloroquine (cq)-resistant plasmodium falciparum and cq-sensitive p. vivax. in the current study, ex vivo fq activity was tested in multidrug-resistant p. falciparum and p. vivax field isolates using a schizont maturation assay. although fq showed excellent activity against cq-sensitive and -resistant p. falciparum and p. vivax (median 50% inhibitory concentrations [ic(50)s], 9.6 nm ...201121730116
long-term humoral and cellular immune responses elicited by a heterologous plasmodium vivax apical membrane antigen 1 protein prime/adenovirus boost immunization protocol.apical membrane antigen 1 (ama-1) is an invasion-related plasmodium antigen that is expressed during both intracellular and extracellular asexual stages of the parasite's life cycle, making it an ideal target for induction of humoral and cellular immune responses that can protect against malaria. we show here that when it is administered as a recombinant protein (p) in montanide isa720 adjuvant, followed by a recombinant human type 5 adenovirus (ad), intense and long-lasting plasmodium vivax ama ...201121730090
associations of multi-locus polymorphisms in an immune network with susceptibility to uncomplicated plasmodium falciparum malaria in daraweesh village, eastern sudan.susceptibility to uncomplicated malaria (um), as to other forms of the disease, is genetically determined. over 9-years of clinical and parasitological follow up of inhabitants of daraweesh, in eastern sudan, the relative susceptibility to um was estimated in terms of number of episodes experienced by each individual. previously, we reported that the levels of igg2 and igg3 to pf332-c231 malaria antigen are negatively correlated with number of malaria episodes. in addition, four molecular marker ...201121729768
vital functions of the malarial ookinete protein, ctrp, reside in the a domains.the transformation of malaria ookinetes into oocysts occurs in the mosquito midgut and is a major bottleneck for parasite transmission. the secreted ookinete surface protein, circumsporozoite- and thrombospondin-related adhesive protein (trap)-related protein (ctrp), is essential for this transition and hence constitutes a potential target for malaria transmission blockade. ctrp is a modular multidomain protein containing six tandem von willebrand factor a-like (a) domains and seven tandem throm ...201121729699
prevalence and risk factors of plasmodium falciparum infections in pregnant women of luanda, angola.pregnant women are at increased risk of malaria, but in angola, epidemiologic data from this group is almost inexistent. we conducted a cross-sectional study to determine the prevalence and risk factors of plasmodium falciparum infections in 567 pregnant angolan women living in luanda province. one in five women had p.-áfalciparum at delivery, diagnosed by pcr assay. age, residence and history of malaria during pregnancy were significantly associated with p.-áfalciparum infection, but gravidity ...201121729222
antimalarial peptides: the long and the short of it.antimicrobial peptides include a diverse array of both natural and synthetic molecules varying greatly in size, charge, hydrophobicity and secondary-structural features. although better known as antibacterial agents, many peptides have demonstrated activity against the malarial parasite plasmodium either in its vertebrate blood stages or mosquito stages or both. the antimalarial peptides reviewed here consist of (i) cationic, amphipathic 'host-defence' peptides including some (e.g. defensins and ...201121728986
binding of +¦,+¦-disubstituted amino acids to arginase suggests new avenues for inhibitor design.arginase is a binuclear manganese metalloenzyme that hydrolyzes l-arginine to form l-ornithine and urea, and aberrant arginase activity is implicated in various diseases such as erectile dysfunction, asthma, atherosclerosis, and cerebral malaria. accordingly, arginase inhibitors may be therapeutically useful. continuing our efforts to expand the chemical space of arginase inhibitor design and inspired by the binding of 2-(difluoromethyl)-l-ornithine to human arginase i, we now report the first s ...201121728378
anaemia & expression levels of cd35, cd55 & cd59 on red blood cells in plasmodium falciparum malaria patients from india.severe anaemia in plasmodium falciparum (pf) associated malaria is a leading cause of death despite low levels of parasitaemia. in an effort to understand the pathogenesis of anaemia we studied expression level of rbc complement regulatory proteins, cr1 (cd35), cd55 and cd59 with haemoglobin status in a group of malaria cases from assam, goa and chennai, and in healthy controls.201121727667
neonatal plasmodium vivax malaria: an overlooked entity.although malaria is endemic in india, neonatal disease is considered rare. we report a case of neonatal malaria in a 26-day-old neonate with fever and splenomegaly who was diagnosed after a long and unsuccessful battery of tests for splenomegaly. routine screening for malaria is essential for all neonates with fever in endemic areas. early diagnosis and treatment of malaria could effectively prevent infant mortality.201121727650
endectocides for malaria control.systemic endectocidal drugs, used to control nematodes in humans and other vertebrates, can be toxic to anopheles spp. mosquitoes when they take a blood meal from a host that has recently received one of these drugs. recent laboratory and field studies have highlighted the potential of ivermectin to control malaria parasite transmission if this drug is distributed strategically and more often. there are important theoretical benefits to this strategy, as well as caveats. a better understanding o ...201121727027
haemosporidian infection in captive masked bobwhite quail (colinus virginianus ridgwayi), an endangered subspecies of the northern bobwhite quail.the avian haemosporidian parasites (phylum apicomplexa) are taxonomically diverse and cosmopolitan in distribution; infecting most bird families. sources of concern are reports of clinical haemosporidian infections in birds kept as part of zoo and aviary collections. recently, severe and acute mortality episodes have been reported in masked bobwhite quail (colinus virginianus ridgwayi), an endangered subspecies from the american southwest. two hundred and five eggs of the captive flock held in a ...201121726940
safety and immunogenicity of multi-antigen ama1-based vaccines formulated with covaccine htôäó and montanide isa 51 in rhesus macaques.increasing the breadth of the functional antibody response through immunization with plasmodium falciparum apical membrane antigen 1 (pfama1) multi-allele vaccine formulations has been demonstrated in several rodent and rabbit studies. this study assesses the safety and immunogenicity of three pfama1 diversity-covering (dico) vaccine candidates formulated as an equimolar mixture (dico mix) in covaccine htôäó or montanide isa 51, as well as that of a pfama1-msp1ôéüôéë fusion protein formulated in ...201121726452
plasmodiophora brassicae: a review of an emerging pathogen of the canadian canola (brassica napus) crop.plasmodiophora brassicae causes clubroot disease in cruciferous plants, and is an emerging threat to canadian canola (brassica napus) production. this review focuses on recent studies into the pathogenic diversity of p. brassicae populations, mechanisms of pathogenesis and resistance, and the development of diagnostic tests for pathogen detection and quantification. taxonomy: plasmodiophora brassicae is a soil-borne, obligate parasite within the class phytomyxea (plasmodiophorids) of the protist ...201121726396
new salicylamide and sulfonamide derivatives of quinoxaline 1,4-di-n-oxide with antileishmanial and antimalarial activities.continuing with our efforts to identify new active compounds against malaria and leishmaniasis, 14 new 3-amino-1,4-di-n-oxide quinoxaline-2-carbonitrile derivatives were synthesized and evaluated for their in vitro antimalarial and antileishmanial activity against plasmodium falciparum colombian fcr-3 strain and leishmania amazonensis strain mhom/br/76/ltb-012a. further computational studies were carried out in order to analyze graphic sar and adme properties. the results obtained indicate that ...201121724395
synthesis and antimalarial activity of new heterocyclic hybrids based on chloroquine and thiazolidinone scaffolds.a series of new 21 chloroquine heterocyclic hybrids containing either benzylamino fragment or n-(aminoalkyl)thiazolidin-4-one moiety were synthesized and screened for their antimalarial activity against chloroquine (cq)-sensitive 3d7 and multidrug-resistance dd2 strains of plasmodium falciparum. although no compounds more active than cq against 3d7 was found; against dd2 strain, six compounds, four of them with benzylamino fragment, showed an excellent activity, up to 3-fold more active than cq. ...201121723734
synthesis and biological activities of 4-n-(anilinyl-n-[oxazolyl])-7-chloroquinolines (n=3' or 4') against plasmodium falciparum in in vitro models.the synthesis (pd-mediated coupling strategy) and characterization (nmr, ir, elemental analysis, etc.) of a short series of quinoline-oxazole hybrid compounds has been carried out. these materials are found to be moderately active against plasmodium falciparum in vitro, with activities in the sub-micromolar range, and to display acceptable cytotoxicity to mononuclear leukocytes. chemical modification strategies, with the intention to increase the biological potency of this new class of anti-mala ...201121723121
Cellular and humoral immune effector mechanisms required for sterile protection against sporozoite challenge induced with the novel malaria vaccine candidate CelTOS.The malarial protein CelTOS, for cell-traversal protein for ookinetes and sporozoites, from Plasmodium berghei has been shown to mediate malarial invasion of both vertebrate and insect host cells and is required for establishing their successful infections. In the vertebrate host, Plasmodium sporozoites traverse via a complex passage through cellular barriers in the skin and the liver sinusoid to infect hepatocytes. Induction of immunity targeted to molecules involved in sporozoite motility and ...201121722682
interaction between sulphur mobilisation proteins sufb and sufc: evidence for an iron-sulphur cluster biogenesis pathway in the apicoplast of plasmodium falciparum.the plastid of plasmodium falciparum, the apicoplast, performs metabolic functions essential to the parasite. various reactions in the plastid require the assembly of [fe-s] prosthetic groups on participating proteins as well as the reductant activity of ferredoxin that is converted from its apo-form by the assembly of [fe-s] clusters inside the apicoplast. the [fe-s] assembly pathway involving sulphur mobilising suf proteins has been predicted to function in the apicoplast with one component (p ...201121722645
plasmodium berghei nk65 induces cerebral leukocyte recruitment in vivo: an intravital microscopic study.malaria is second only to tuberculosis as the leading cause of morbidity and mortality as a consequence of a single infectious agent. much of the pathology of malaria arises from the inappropriate or excessive immune response mounted by the host in an attempt to eliminate the parasite. we here report the inflammatory changes observed in the cerebral microvasculature of c57bl/6 and balb/c mice that had been inoculated with plasmodium berghei nk65, a lethal strain of rodent malaria. although no ne ...201121722620
nephrotic syndrome and unrecognized plasmodium malariae infection in a us navy sailor 14 years after departing nigeria.a 34-year-old nigerian man presented with nephrotic syndrome. renal biopsy revealed chronic membranous glomerulopathy with focal segmental sclerosis. blood giemsa smear contained rare plasmodium sp. trophozoites and small subunit ribosomal rna polymerase chain reaction amplification confirmed the presence of plasmodium malariae. this case highlights the importance of obtaining even remote travel histories from ill immigrants and considering occult quartan malaria in patients from endemic locatio ...201121722243
choice of and adherence to prophylactic antimalarials.there were 1,370 cases of imported malaria and six fatalities in the uk in 2008, the majority of which were due to chloroquine-resistant plasmodium falciparum. poor adherence to prescribed regimens is known to be an important factor in these cases.201121722235
linear amplification for deep sequencing.linear amplification for deep sequencing (lads) is an amplification method that produces representative libraries for illumina next-generation sequencing within 2 d. the method relies on attaching two different sequencing adapters to blunt-end repaired and a-tailed dna fragments, wherein one of the adapters is extended with the sequence for the t7 rna polymerase promoter. ligated and size-selected dna fragments are transcribed in vitro with high rna yields. subsequent cdna synthesis is initiated ...201121720315
protective immunity against malaria by 'natural immunization': a question of dose, parasite diversity, or both?plasmodium undergoes an obligate liver phase before the onset of malaria, which is caused exclusively by cyclic propagation of the parasite inside erythrocytes. the diagnostically inaccessible and clinically silent pre-erythrocytic expansion phase is a promising target for inducing sterilizing immunity against reinfections. recent studies in rodent and human malaria models called attention to the induction of potent protective immunity by administration of anti-malarial drugs during sporozoite e ...201121719266
plasmodium falciparum serine repeat antigen 5 (se36) as a malaria vaccine candidate.a devastating disease spread by mosquitoes with high-efficiency, malaria imposes an enormous burden for which no licensed vaccine currently exists. although the genome complexity of the parasite has made vaccine development tenuous, an effective malaria vaccine would be a valuable tool for control, elimination and eventual eradication. the plasmodium serine repeat antigen 5 (sera5) is an abundant asexual blood stage antigen that does not show any antigenic variation and exhibits limited polymorp ...201121718740
tree-based delimitation of morphologically ambiguous taxa: a study of the lizard malaria parasites on the caribbean island of hispaniola.malaria parasites in the genus plasmodium have been classified primarily on the basis of differences in morphology. these single-celled organisms often lack distinguishing morphological features, and this can encumber both species delimitation and identification. six saurian malaria parasites have been described from the caribbean island of hispaniola. all six infect lizards in the genus anolis, but only two of these parasites can be distinguished using morphology. the remaining four species ove ...201121718698
[tgrom4 and tgama1: a checkpoint in parasite replication]. 201121718637
design of a variant surface antigen-supplemented microarray chip for whole transcriptome analysis of multiple plasmodium falciparum cytoadherent strains, and identification of strain-transcendent rif and stevor genes.abstract:201121718533
in vitro antiplasmodial activity of sesquiterpene lactones from ambrosia tenuifolia.the in vitro antiplasmodial activity of ambrosia tenuifolia organic extract and its isolated sesquiterpene lactones, psilostachyin and peruvin, has been evaluated against plasmodium falciparum f32 and w2 strains. the cytotoxicity of both compounds was determined on lymphoid cells, and their corresponding selectivity indexes (sis) were calculated. peruvin was the most active compound on f32 strain of p. falciparum with a 50% inhibitory concentration value (ic(50)) of 0.3ôçë++g/ml (1.1ôçë++m) wher ...201121716685
detection of malarial byproduct hemozoin utilizing its unique scattering properties.the scattering characteristics of the malaria byproduct hemozoin, including its scattering distribution and depolarization, are modeled using discrete dipole approximation (dda) and compared to those of healthy red blood cells. scattering (or dark-field) spectroscopy and imaging are used to identify hemozoin in fresh rodent blood samples. a new detection method is proposed and demonstrated using dark-field in conjunction with cross-polarization imaging and spectroscopy. snrs greater than 50:1 ar ...201121716456
antagonistic antimalarial properties of pawpaw leaf aqueous extract in combination with artesunic acid in plasmodium berghei-infected mice.artemisinins, the main stay in the treatment of malaria are used in combinations with other antimalarials to forestall resistance, as artemisinin-combination therapies (acts). however, acts are expensive and some of the non-artemisinin components are not well-tolerated by patients. there are several folkloric and scientific proofs of the efficacy of herbal remedies for malaria. mature leaves of carica papaya is widely used to treat malaria in several african countries. an act involving a medicin ...201121715732
cd8+ t effector memory cells protect against liver-stage malaria.identification of correlates of protection for infectious diseases including malaria is a major challenge and has become one of the main obstacles in developing effective vaccines. we investigated protection against liver-stage malaria conferred by vaccination with adenoviral (ad) and modified vaccinia ankara (mva) vectors expressing pre-erythrocytic malaria ags. by classifying cd8(+) t cells into effector, effector memory (t(em)), and central memory subsets using cd62l and cd127 markers, we fou ...201121715686
n-terminal prodomain of pfs230 synthesized using a cell-free system is sufficient to induce complement-dependent malaria transmission-blocking activity.the aim of a malaria transmission-blocking vaccine is to block the development of malaria parasites in the mosquito and thus prevent subsequent infection of the human host. previous studies have demonstrated that the gametocyte/gamete surface protein pfs230 can induce transmission-blocking immunity and have evaluated escherichia coli-produced pfs230 as a transmission-blocking vaccine candidate. in this study, we used the wheat germ cell-free expression system to produce n-terminal fragments of p ...201121715579
a plant-produced pfs230 vaccine candidate blocks transmission of plasmodium falciparum.plasmodium falciparum is transmitted to a new host after completing its sexual cycle within a mosquito. developing vaccines against the parasite sexual stages is a critical component in the fight against malaria. we are targeting multiple proteins of p. falciparum which are found only on the surfaces of the sexual forms of the parasite and where antibodies against these proteins have been shown to block the progression of the parasite's life cycle in the mosquito and thus block transmission to t ...201121715576
cananginones a-i, linear acetogenins from the stem bark of cananga latifolia.nine linear c23 and c21 acetogenins, named cananginones a-i (1-9), were isolated from stem bark of cananga latifolia. their structures were established by spectroscopic methods. these compounds showed cytotoxicity against three cancer cell lines (kb, mcf7 and nci-h187) with ic(50) values in the range 16.6-129.7++m. only 5 showed weak antimalarial activity against plasmodium falciparum. in addition, 8 and 9 exhibited weak antifungal activity against candida albicans.201121714976
lessons from sickle cell disease in the treatment and control of malaria. 201121714653
[genotypic survey of plasmodium falciparum based on the msp1, msp2 and glurp genes by multiplex pcr].the genetic diversity of plasmodium falciparum has been one of the major obstacles for the success of anti-malaria drug therapy. it provides the parasite an ability to evade the host's immune response by generating changes in its antigenic composition and resistance to antimalarial drugs.201021713358
correlation between malaria incidence and prevalence of soil-transmitted helminths in colombia: an ecologic evaluation.recent studies have suggested an association between the soil-transmitted helminth infections and malaria incidence. however, published evidence is still insufficient and diverging. since 1977, new ecologic studies have not been carried out to explore this association. ecologic studies could explore this correlation on a population level, assessing its potential importance on public health.201021713354
duffy negative antigen is no longer a barrier to plasmodium vivax--molecular evidences from the african west coast (angola and equatorial guinea).plasmodium vivax shows a small prevalence in west and central africa due to the high prevalence of duffy negative people. however, duffy negative individuals infected with p. vivax have been reported in areas of high prevalence of duffy positive people who may serve as supply of p. vivax strains able to invade duffy negative erythrocytes. we investigated the presence of p. vivax in two west african countries, using blood samples and mosquitoes collected during two on-going studies.201121713024
identification of a highly antigenic linear b cell epitope within plasmodium vivax apical membrane antigen 1 (ama-1).apical membrane antigen 1 (ama-1) is considered to be a major candidate antigen for a malaria vaccine. previous immunoepidemiological studies of naturally acquired immunity to plasmodium vivax ama-1 (pvama-1) have shown a higher prevalence of specific antibodies to domain ii (dii) of ama-1. in the present study, we confirmed that specific antibody responses from naturally infected individuals were highly reactive to both full-length ama-1 and dii. also, we demonstrated a strong association betwe ...201121713006
identification of plant-like galactolipids in chromera velia, a photosynthetic relative of malaria parasites.apicomplexa are protist parasites that include plasmodium spp., the causative agents of malaria, and toxoplasma gondii, responsible for toxoplasmosis. most apicomplexa possess a relict plastid, the apicoplast, which was acquired by secondary endosymbiosis of a red alga. despite being nonphotosynthetic, the apicoplast is otherwise metabolically similar to algal and plant plastids and is essential for parasite survival. previous studies of toxoplasma gondii identified membrane lipids with some str ...201121712377
application of in-situ hybridization for the detection and identification of avian malaria parasites in paraffin wax-embedded tissues from captive penguins.in captive penguins, avian malaria due to plasmodium parasites is a well-recognized disease problem as these protozoa may cause severe losses among valuable collections of zoo birds. in blood films from naturally infected birds, identification and differentiation of malaria parasites based on morphological criteria are difficult because parasitaemia is frequently light and blood stages, which are necessary for identification of parasites, are often absent. post-mortem diagnosis by histological e ...201121711191
artemisinin activity against plasmodium falciparum requires hemoglobin uptake and digestion.combination regimens that include artemisinin derivatives are recommended as first line antimalarials in most countries where malaria is endemic. however, the mechanism of action of artemisinin is not fully understood and the usefulness of this drug class is threatened by reports of decreased parasite sensitivity. we treated plasmodium falciparum for periods of a few hours to mimic clinical exposure to the short half-life artemisinins. we found that drug treatment retards parasite growth and inh ...201121709259
genome-wide scan reveals amplification of mdr1 as a common denominator of resistance to mefloquine, lumefantrine and artemisinin in p. chabaudi malaria parasites.multidrug resistant plasmodium falciparum malaria parasites pose a threat to effective drug control, even to artemisinin-based combination therapies (acts). here we used linkage group selection and solexa whole genome resequencing to investigate the genetic basis of resistance to component drugs of acts. using the rodent malaria parasite p. chabaudi, we analysed the uncloned progeny of a genetic backcross between the mefloquine-, lumefantrine- and artemisinin-resistant mutant as-15mf and a genet ...201121709099
pharmacokinetics of amodiaquine and desethylamodiaquine in pregnant and postpartum women with plasmodium vivax malaria.in order to study the pharmacokinetic properties of amodiaquine and desethylamodiaquine during pregnancy, 24 pregnant women in the second and third trimesters of pregnancy and with plasmodium vivax malaria were treated with amodiaquine (10 mg/kg of body weight/day) for 3 days. the same women were studied again at 3 months postpartum. plasma was analyzed for amodiaquine and desethylamodiaquine by use of a liquid chromatography-tandem mass spectrometry method. individual concentration-time data we ...201121709098
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