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[rapid malaria tests--good complement to microscopy. high sensitivity for plasmodium falciparum in swedish travellers]. 201122165534
Larvicidal and pupicidal activity of spinosad against the malarial vector Anopheles stephensi.To investigate the larvicidal and pupicidal activity of spinosad against Anopheles stephensi Listen.201121914537
Plasmodium falciparum MLH is schizont stage specific endonuclease.Malaria is one of the most important infectious diseases in many regions around the world including India. Plasmodium falciparum is the cause of most lethal form of malaria while Plasmodium vivax is the major cause outside Africa. Regardless of considerable efforts over the last many years there is still no commercial vaccine against malaria and the disease is mainly treated using a range of established drugs. With time, the malaria parasite is developing drug resistance to most of the commonly ...201122079692
A scalable pipeline for highly effective genetic modification of a malaria parasite.In malaria parasites, the systematic experimental validation of drug and vaccine targets by reverse genetics is constrained by the inefficiency of homologous recombination and by the difficulty of manipulating adenine and thymine (A+T)-rich DNA of most Plasmodium species in Escherichia coli. We overcame these roadblocks by creating a high-integrity library of Plasmodium berghei genomic DNA (>77% A+T content) in a bacteriophage N15-based vector that can be modified efficiently using the lambda Re ...201122020067
stage-specific depletion of myosin a supports an essential role in motility of malarial ookinetes.functional analysis of plasmodium genes by classical reverse genetics is currently limited to mutants that are viable during erythrocytic schizogony, the pathogenic phase of the malaria parasite where transfection is performed. here, we describe a conceptually simple experimental approach to study the function of genes essential to the asexual blood stages in a subsequent life cycle stage by a promoter-swap approach. as a proof of concept we targeted the unconventional class xiv myosin myoa, whi ...201121899701
malaria-related anaemia: a latin american perspective.malaria is the most important parasitic disease worldwide, responsible for an estimated 225 million clinical cases each year. it mainly affects children, pregnant women and non-immune adults who frequently die victims of cerebral manifestations and anaemia. although the contribution of the american continent to the global malaria burden is only around 1.2 million clinical cases annually, there are 170 million inhabitants living at risk of malaria transmission in this region. on the african conti ...201121881762
[advances in research of dihydroartemisinin against parasitic diseases].dihydroartemisinin, the main metabolite of artemisinin and two artemisinin derivatives, artemether and artesunate, is a broad-spectrum anti-parasitic drug. the present paper systematically reviews the advances in research of dihydroartemisinin against plasmodium, schistosoma, pneumocystis, toxoplasma, trichomonas vaginalis, leishmania, giardia lamblia.201122164870
shotgun isotope array for rapid, substrate-specific detection of microorganisms in a microbial community.the shotgun isotope array method has been proposed to be an effective new tool for use in substrate-specific microbe exploration without any prior knowledge of the community composition. proof of concept was demonstrated by detection of acetate-degrading microorganisms in activated sludge and further verified by independent stable isotope probing (sip).201121873478
biomarkers for susceptibility to infection and disease severity in human malaria.malaria remains a major infectious disease that affects millions of people. once infected with plasmodium parasites, a host can develop a broad range of clinical presentations, which result from complex interactions between factors derived from the host, the parasite and the environment. intense research has focused on the identification of reliable predictors for exposure, susceptibility to infection and the development of severe complications during malaria. although most promising markers are ...201121881759
a head-to-head comparison of four artemisinin-based combinations for treating uncomplicated malaria in african children: a randomized trial.artemisinin-based combination therapies (acts) are the mainstay for the management of uncomplicated malaria cases. however, up-to-date data able to assist sub-saharan african countries formulating appropriate antimalarial drug policies are scarce.201122087077
A thirteen-year analysis of Plasmodium falciparum populations reveals high conservation of the mutant pfcrt haplotype despite the withdrawal of chloroquine from national treatment guidelines in Gabon.Chloroquine resistance (CR) decreased after the removal of chloroquine from national treatment guidelines in Malawi, Kenia and Tanzania. In this investigation the prevalence of the chloroquine resistance (CQR) conferring mutant pfcrt allele and its associated chromosomal haplotype were determined before and after the change in Gabonese national treatment guidelines from chloroquine (CQ) to artesunate plus amodiaquine (AQ) in 2003.201122004584
Optimization of propafenone analogues as antimalarial leads.Propafenone, a class Ic antiarrythmic drug, inhibits growth of cultured Plasmodium falciparum. While the drug's potency is significant, further development of propafenone as an antimalarial would require divorcing the antimalarial and cardiac activities as well as improving the pharmacokinetic profile of the drug. A small array of propafenone analogues was designed and synthesized to address the cardiac ion channel and PK liabilities. Testing of this array revealed potent inhibitors of the 3D7 ...201121955244
Vivax malaria in Mauritania includes infection of a Duffy-negative individual.ABSTRACT:201122050867
Study of the efficacy of antimalarial drugs delivered inside targeted immunoliposomal nanovectors.ABSTRACT: Paul Ehrlich's dream of a 'magic bullet' that would specifically destroy invading microbes is now a major aspect of clinical medicine. However, a century later, the implementation of this medical holy grail continues being a challenge in three main fronts: identifying the right molecular or cellular targets for a particular disease, having a drug that is effective against it, and finding a strategy for the efficient delivery of sufficient amounts of the drug in an active state exclusiv ...201122151840
standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator.a significant reduction in parasite clearance rates following artesunate treatment of falciparum malaria, and increased failure rates following artemisinin combination treatments (act), signaled emergent artemisinin resistance in western cambodia. accurate measurement of parasite clearance is therefore essential to assess the spread of artemisinin resistance in plasmodium falciparum. the slope of the log-parasitaemia versus time relationship is considered to be the most robust measure of anti-ma ...201122074219
a single injection of 19 kda carboxy-terminal fragment of plasmodium yoelii merozoite surface protein 1 (pymsp1(19)) formulated with montanide isa and cpg odn induces protective immune response in mice.to investigate the efficacy of a vaccine formulation of the 19 kda conserved carboxyl-terminal fragment of plasmodium yoelii merozoite surface protein-1 (pymsp1(19)) formulated with cpg odn 1826 and montanide isa51 or isa720 when used to immunize mice by a single injection.201122053595
experimentally controlled downregulation of the histone chaperone fact in plasmodium berghei reveals that it is critical to male gamete fertility.human fact (facilitates chromatin transcription) consists of the proteins spt16 and ssrp1 and acts as a histone chaperone in the (dis)assembly of nucleosome (and thereby chromatin) structure during transcription and dna replication. we identified a plasmodium berghei protein, termed fact-l, with homology to the spt16 subunit of fact. epitope tagging of fact-l showed nuclear localization with high expression in the nuclei of (activated) male gametocytes. the gene encoding fact-l could not be dele ...201121899698
Roles of Apicomplexan protein kinases at each life cycle stage.Inhibitors of cellular protein kinases have been reported to inhibit the development of Apicomplexan parasites, suggesting that the functions of protozoan protein kinases are critical for their life cycle. However, the specific roles of these protein kinases cannot be determined using only these inhibitors without molecular analysis, including gene disruption. In this report, we describe the functions of Apicomplexan protein kinases in each parasite life stage and the potential of pre-existing p ...201122209882
Dramatic decrease in malaria transmission after large-scale indoor residual spraying with bendiocarb in Benin, an area of high resistance of Anopheles gambiae to pyrethroids.In 2008, the National Malaria Control Program in Benin implemented a vector control intervention based on indoor residual spraying (IRS). Four districts of high resistance of Anopheles gambiae to pyrethroids were sprayed with bendiocarb. More than 350,000 inhabitants have been protected. Entomologic parameters in the control area were compared with those in intervention sites. The study has shown a drastic decrease in the An. gambiae biting rate in the sprayed areas. Results of an enzyme-linked ...201121976555
Redox-active antiparasitic drugs.Significance: Parasitic diseases affect hundreds of millions of people worldwide and represent major health problems. Treatment is becoming extremely difficult due to the emergence of drug-resistance, the absence of effective vaccines and the spread of insecticide-resistant vectors. Thus, identification of affordable and readily available drugs against resistant parasites is of global demand. Recent Advances: Susceptibility of many parasites to oxidative stress is a well-known phenomenon. There ...201122122517
Screening medicinal plants for the detection of novel antimalarial products applying the inhibition of ß-hematin formation.The identification of novel scaffolds for the development of effective and safe treatments to fight malaria is urgently needed. One of the main opportunities is the discovery of new molecules from natural origin. A simple, robust and cost-effective colorimetric assay based on the inhibition of ß-hematin has been adapted to routinely screen plant extracts with the ultimate goal to identify novel antimalarial ingredients. The development of this assay has included a careful optimization of all cri ...201121872416
A field trial to assess a blood-stage malaria vaccine.Blood-stage malaria vaccines are intended to prevent clinical disease. The malaria vaccine FMP2.1/AS02(A), a recombinant protein based on apical membrane antigen 1 (AMA1) from the 3D7 strain of Plasmodium falciparum, has previously been shown to have immunogenicity and acceptable safety in Malian adults and children.201121916638
malaria therapy in hiv: drug interactions between nevirapine and quinine.we report the case of an hiv-positive nigerian man on antiretroviral therapy (art) with an undetectable viral load who presented with rigors, fever and back pain after returning to the uk from a three-week trip to nigeria. infection with plasmodium falciparum malaria was confirmed and treatment with quinine commenced together with amoxicillin/clavulanic acid and clarithromycin for possible respiratory infection. at the time of admission the patient could not remember the names of his art medicat ...201122174067
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
multi-targeted activity of maslinic acid as an antimalarial natural compound.most drugs against malaria that are available or under development target a single process of the parasite infective cycle, favouring the appearance of resistant mutants which are easily spread in areas under chemotherapeutic treatments. maslinic acid (ma) is a low toxic natural pentacyclic triterpene for which a wide variety of biological and therapeutic activities have been reported. previous work revealed that plasmodium falciparum erythrocytic cultures were inhibited by ma, which was able to ...201121689375
consequences of hiv infection on malaria and therapeutic implications: a systematic review.despite recent changes in the epidemiology of hiv infection and malaria and major improvements in their control, these diseases remain two of the most important infectious diseases and global health priorities. as they have overlapping distribution in tropical areas, particularly sub-saharan africa, any of their clinical, diagnostic, and therapeutic interactions might have important effects on patient care and public health policy. the biological basis of these interactions is well established. ...201121700241
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
the nucleosome (histone-dna complex) is the tlr9-specific immunostimulatory component of plasmodium falciparum that activates dcs.the systemic clinical symptoms of plasmodium falciparum infection such as fever and chills correspond to the proinflammatory cytokines produced in response to the parasite components released during the synchronized rupture of schizonts. we recently demonstrated that, among the schizont-released products, merozoites are the predominant components that activate dendritic cells (dcs) by tlr9-specific recognition to induce the maturation of cells and to produce proinflammatory cytokines. we also de ...201121687712
bestatin-based chemical biology strategy reveals distinct roles for malaria m1- and m17-family aminopeptidases.malaria causes worldwide morbidity and mortality, and while chemotherapy remains an excellent means of malaria control, drug-resistant parasites necessitate the discovery of new antimalarials. peptidases are a promising class of drug targets and perform several important roles during the plasmodium falciparum erythrocytic life cycle. herein, we report a multidisciplinary effort combining activity-based protein profiling, biochemical, and peptidomic approaches to functionally analyze two genetica ...201121844374
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
clinical trial of extended-dose chloroquine for treatment of resistant falciparum malaria among afghan refugees in pakistan.falciparum malaria is a significant problem for afghan refugees in pakistan. refugee treatment guidelines recommended standard three-day chloroquine treatment (25 mg/kg) for first episodes and extended five-day treatment (40 mg/kg) for recrudescent infections, based on the assumption that a five-day course would more likely achieve a cure. an in-vivo randomized controlled trial was conducted among refugees with uncomplicated falciparum malaria to determine whether five-day treatment (cq40) was m ...201121699697
plasmodium falciparum merozoite invasion is inhibited by antibodies that target the pfrh2a and b binding domains.plasmodium falciparum, the causative agent of the most severe form of malaria in humans invades erythrocytes using multiple ligand-receptor interactions. the p. falciparum reticulocyte binding-like homologue proteins (pfrh or pfrbl) are important for entry of the invasive merozoite form of the parasite into red blood cells. we have analysed two members of this protein family, pfrh2a and pfrh2b, and show they undergo a complex series of proteolytic cleavage events before and during merozoite inva ...201121698217
characterization of a new phosphatase from plasmodium.plasmodium falciparum malaria is the most important parasitic disease worldwide, responsible for an estimated 1 million deaths annually. two p. falciparum genes code for putative phosphoglycerate mutases (pgmases), a widespread protein group characterized by the involvement of histidine residues in their catalytic mechanism. pgmases are responsible for the interconversion between 2 and 3-phosphoglycerate, an intermediate step in the glycolysis pathway. we have determined the crystal structures o ...201121689687
high-speed shaking of frozen blood clots for extraction of human and malaria parasite dna.abstract:201121824391
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
characterization and application of the fe(ii) and +¦-ketoglutarate dependent hydroxylase frbj.the fe(ii) and +¦-ketoglutarate-dependent hydroxylase frbj was previously demonstrated to utilize fr-900098 synthesizing a second phosphonate fr-33289. here we assessed its ability to hydroxylate other possible substrates, generating a library of potential antimalarial compounds. through a series of bioassays and in vitro experiments, we identified two new antimalarials.201121829824
environmental constraints guide migration of malaria parasites during transmission.migrating cells are guided in complex environments mainly by chemotaxis or structural cues presented by the surrounding tissue. during transmission of malaria, parasite motility in the skin is important for plasmodium sporozoites to reach the blood circulation. here we show that sporozoite migration varies in different skin environments the parasite encounters at the arbitrary sites of the mosquito bite. in order to systematically examine how sporozoite migration depends on the structure of the ...201121698220
non-apical membrane antigen 1 (ama1) iggs from malian children interfere with functional activity of ama1 iggs as judged by growth inhibition assay.apical membrane antigen 1 (ama1) is one of the best-studied blood-stage malaria vaccine candidates. when an ama1 vaccine was tested in a malaria na+»ve population, it induced functionally active antibodies judged by growth inhibition assay (gia). however, the same vaccine failed to induce higher growth-inhibitory activity in adults living in a malaria endemic area. vaccination did induce functionally active antibodies in malaria-exposed children with less than 20% inhibition in gia at baseline, ...201121695140
6questionnaire-based approach to assess schoolchildren's physical fitness and its potential role in exploring the putative impact of helminth and plasmodium spp. infections in c+¦te d'ivoire.abstract:201121702903
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
randomized trials of artemisinin-piperaquine, dihydroartemisinin-piperaquine phosphate and artemether-lumefantrine for the treatment of multi-drug resistant falciparum malaria in cambodia-thailand border area.abstract:201121827706
resistance of a rodent malaria parasite to a thymidylate synthase inhibitor induces an apoptotic parasite death and imposes a huge cost of fitness.the greatest impediment to effective malaria control is drug resistance in plasmodium falciparum, and thus understanding how resistance impacts on the parasite's fitness and pathogenicity may aid in malaria control strategy.201121698180
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
effectiveness of acts in cases of resistance to partner drugs. 201121700240
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
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
imported malaria in belgrade, serbia, between 2001 and 2009.since 2000, travel of serbian citizens to tropical areas has been slowly but steadily increasing. to determine the epidemiological and clinical characteristics of imported malaria in serbia, we analyzed clinical history data of all travelers who presented at the clinic for infectious and tropical diseases in belgrade after their return from tropical and subtropical areas between 2001 and 2009. the study series involved a total of 2981 travelers, and included both those with (847) and without (21 ...201121826415
real-time pcr assay and rapid diagnostic tests for the diagnosis of clinically suspected malaria patients in bangladesh.abstract:201121703009
why is plasmodium vivax a neglected tropical disease? 201121738804
new insights into the mechanism of odorant detection by the malaria - transmitting mosquito anopheles gambiae.anopheles gambiae mosquitoes that transmit plasmodium falciparum malaria use a series of olfactory cues present in human sweat to locate their hosts for a blood meal. recognition of these odor cues occurs through the interplay of odorant receptors and odorant binding proteins (obps) that bind to odorant molecules and transport and present them to the receptors. recent studies have implicated potential heterodimeric interactions between two obps, obp1 and obp4, as important for perception of indo ...201121816826
measuring single-cell density.we have used a microfluidic mass sensor to measure the density of single living cells. by weighing each cell in two fluids of different densities, our technique measures the single-cell mass, volume, and density of approximately 500 cells per hour with a density precision of 0.001 g ml(-1). we observe that the intrinsic cell-to-cell variation in density is nearly 100-fold smaller than the mass or volume variation. as a result, we can measure changes in cell density indicative of cellular process ...201121690360
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
a sub-microscopic gametocyte reservoir can sustain malaria transmission.novel diagnostic tools, including pcr and high field gradient magnetic fractionation (hfgmf), have improved detection of asexual plasmodium falciparum parasites and especially infectious gametocytes in human blood. these techniques indicate a significant number of people carry gametocyte densities that fall below the conventional threshold of detection achieved by standard light microscopy (lm).201121695129
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
microvascular sequestration of plasmodium falciparum. 201121823261
functional characterization of a sumo deconjugating protease of plasmodium falciparum using newly identified small molecule inhibitors.small ubiquitin-related modifier (sumo) is implicated in the regulation of numerous biological processes including transcription, protein localization, and cell cycle control. protein modification by sumo is found in plasmodium falciparum; however, its role in the regulation of the parasite life cycle is poorly understood. here we describe functional studies of a sumo-specific protease (senp) of p.-áfalciparum, pfsenp1 (pfl1635w). expression of the catalytic domain of pfsenp1 and biochemical pro ...201121700207
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
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
[application of nested pcr in diagnosis of imported malaria].to evaluate the usefulness of nested pcr method in the diagnosis of imported malaria.201121823324
selective antimicrobial activity associated with sulfur nanoparticles.many sulfur compounds are known to exhibit widespread antimicrobial activity. the latter is often the result of an intricate redox biochemistry whereby reactive sulfur species, such as organic polysulfanes, interact with pivotal cellular signaling pathways. the s8 unit in elemental sulfur resembles certain aspects of the chemistry of polysulfanes. as a consequence, water-soluble s8-sulfur nanoparticles are active against some smaller organisms, including nematodes, yet are non-toxic against huma ...201121830480
potent antimalarial 4-pyridones with improved physico-chemical properties.antimalarial 4-pyridones are a novel class of inhibitors of the plasmodial mitochondrial electron transport chain targeting cytochrome bc1 (complex iii). in general, the most potent 4-pyridones are lipophilic molecules with poor solubility in aqueous media and low oral bioavailability in pre-clinical species from the solid dosage form. the strategy of introducing polar hydroxymethyl groups has enabled us to maintain the high levels of antimalarial potency observed for other more lipophilic analo ...201121824778
computational reverse-engineering of a spider-venom derived peptide active against plasmodium falciparum sub1.psalmopeotoxin i (pcfk1), a protein of 33 aminoacids derived from the venom of the spider psalmopoeus cambridgei, is able to inhibit the growth of plasmodium falciparum malaria parasites with an ic[formula: see text] in the low micromolar range. pcfk1 was proposed to act as an ion channel inhibitor, although experimental validation of this mechanism is lacking. the surface loops of pcfk1 have some sequence similarity with the parasite protein sequences cleaved by pfsub1, a subtilisin-like protea ...201121818266
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
bromophycolideôçàa targets heme crystallization in the human malaria parasite plasmodium falciparum. 201121732541
efficacy of integrated school based de-worming and prompt malaria treatment on helminths -plasmodium falciparum co-infections: a 33 months follow up study.abstract:201121696629
the stability and complexity of antibody responses to the major surface antigen of plasmodium falciparum are associated with age in a malaria endemic area.individuals that are exposed to malaria eventually develop immunity to the disease with one possible mechanism being the gradual acquisition of antibodies to the range of parasite variant surface antigens in their local area. major antibody targets include the large and highly polymorphic plasmodium falciparum erythrocyte membrane protein 1 (pfemp1) family of proteins. here, we use a protein microarray containing 123 recombinant pfemp1-dbl+¦ domains (var) from papua new guinea (png) to seroprofi ...201121825279
spatial patterns of malaria in a land reform colonization project, juruena municipality, mato grosso, brazil.in brazil, 99% of malaria cases are concentrated in the amazon, and malaria's spatial distribution is commonly associated with socio-environmental conditions on a fine landscape scale. in this study, the spatial patterns of malaria and its determinants in a rural settlement of the brazilian agricultural reform programme called "vale do amanhecer" in the northern mato grosso state were analysed.201121703018
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
structure-guided lead optimization of triazolopyrimidine-ring substituents identifies potent plasmodium falciparum dihydroorotate dehydrogenase inhibitors with clinical candidate potential.drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance. in an effort to identify new potential antimalarials, we have undertaken a lead optimization program around our previously identified triazolopyrimidine-based series of plasmodium falciparum dihydroorotate dehydrogenase (pfdhodh) inhibitors. the x-ray structure of pfdhodh was used to inform the medicinal chemistry program allowing the identification of a potent and selective i ...201121696174
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
docking studies on the binding of quinoline derivatives and hematin to plasmodium falciparum lactate dehydrogenase.the literature has reported that ferriprotoporphyrin ix (hematin) intoxicates the malarial parasite through competition with nadh for the active site of the enzyme lactate dehydrogenase (ldh). in order to avoid this, the parasite polymerizes hematin to hemozoin. the quinoline derivatives are believed to form complexes with dimeric hematin, avoiding the formation of hemozoin and still inhibiting ldh. in order to investigate this hypothesis we calculated the docking energies of nadh and some quino ...201121696234
genetic diversity in human erythrocyte pyruvate kinase.previously, we have shown that pyruvate kinase, liver and red cell isoform (pklr) deficiency protects mice in vivo against blood-stage malaria, and observed that reduced pklr function protects human erythrocytes against plasmodium falciparum replication ex vivo. here, we have sequenced the human pklr gene in 387 individuals from malaria-endemic and other regions in order to assess genetic variability in different geographical regions and ethnic groups. rich genetic diversity was detected in pklr ...201121833022
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
epidemiological consequences of a newly discovered cryptic subgroup of anopheles gambiae.a cryptic subgroup of anopheles gambiae sensu stricto mosquitoes was recently discovered in west africa. this 'goundry' subgroup has increased susceptibility to plasmodium falciparum, the most deadly form of malaria. unusual for this major malaria vector, goundry mosquitoes also seem to bite exclusively outdoors. a mathematical model is developed to assess the epidemiological implications of current vector control tools, bednets and indoor residual spray, preferentially suppressing the more typi ...201121693489
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
etiopathogenesis of burkitt's lymphoma: a lesson from a bl-like in cd1 mouse immune to plasmodium yoelii yoelii.abstract:201121740585
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
morphology and host-parasite interaction of henneguya azevedoi n. sp., parasite of gills of leporinus obtusidens from mogi-gua+ºu river, brazil.henneguya azevedoi n. sp. is described from the piava (leporinus obtusidens). between 2005 and 2007, 60 fish were collected from the mogi-gua+ºu river near cachoeira de emas falls located in the municipality of pirassununga, state of s+úo paulo, brazil. a total of 70% had plasmodia of the parasite. the plasmodia were white, spherical, and measured 40-200-á++m in diameter. histopathological analysis revealed that the development of the parasite was intralamellar and caused stretching of the epith ...201121842391
the influence of mosquito resting behaviour and associated microclimate for malaria risk.abstract:201121736735
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
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
rodent blood-stage plasmodium survive in dendritic cells that infect naive mice.plasmodium spp. parasites cause malaria in 300 to 500 million individuals each year. disease occurs during the blood-stage of the parasite's life cycle, where the parasite is thought to replicate exclusively within erythrocytes. infected individuals can also suffer relapses after several years, from plasmodium vivax and plasmodium ovale surviving in hepatocytes. plasmodium falciparum and plasmodium malariae can also persist after the original bout of infection has apparently cleared in the blood ...201121690346
insulin-like peptides in the mosquito anopheles stephensi: identification and expression in response to diet and infection with plasmodium falciparum.insulin-like peptides (ilps) regulate a multitude of biological processes, including metabolism and immunity to infection, and share similar structural motifs across widely divergent taxa. insulin/insulin-like growth factor signaling (iis) pathway elements are similarly conserved. we have shown that iis regulates reproduction, innate immunity, and lifespan in female anopheles stephensi, a major mosquito vector of human malaria. to further explore iis regulation of these processes, we identified ...201121703270
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
[malaria epidemic trend and characteristics at monitoring sites in yunnan province in 2008].malaria situation in 5 monitoring sites of yunnan showed a decline trend from 2005 to 2008. the average malaria incidence in 2008 was 11.84/10,000 with a decrease of 66.1% in comparison to 2005. the seropositive rate with immuno-fluorescence assay (ifa) was 4.61% for pupils. 82% of the cases chose town or township hospitals as the first place of seeking diagnosis and treatment. 83.6% cases were diagnosed over 3 days of symptom appearing. the main clinical manifestation was fever every other day ...201121823327
in vitro and in vivo antimalarial activity assays of seeds from balanites aegyptiaca: compounds of the extract show growth inhibition and activity against plasmodial aminopeptidase.balanites aegyptiaca (balanitaceae) is a widely grown desert plant with multiuse potential. in the present paper, a crude extract from b. aegyptiaca seeds equivalent to a ratio of 1ôçë:ôçë2000 seeds to the extract was screened for antiplasmodial activity. the determined ic(50) value for the chloroquine-susceptible plasmodium falciparum nf54 strain was 68.26ôçë++g/++l -¦ 3.5. analysis of the extract by gas chromatography-mass spectrometry detected 6-phenyl-2(h)-1,2,4-triazin-5-one oxime, an inhib ...201121687598
how can microbial interactions with the blood-brain barrier modulate astroglial and neuronal function?the vascular endothelium of the blood-brain barrier (bbb) is regarded as a part of the neurovascular unit (nvu). this emerging nvu concept emphasizes the need for homeostatic signalling among the neuronal, glial and vascular endothelial cellular compartments in maintaining normal brain function. conversely, dysfunction in any component of the nvu affects another, thus contributing to disease. brain endothelial activation and dysfunction is observed in various neurological diseases, such as (isch ...201121824246
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
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
adaptation of a visualized loop-mediated isothermal amplification technique for field detection of plasmodium vivax infection.loop-mediated isothermal amplification (lamp) is a high performance method for detecting dna and holds promise for use in the molecular detection of infectious pathogens, including plasmodium spp. however, in most malaria-endemic areas, which are often resource-limited, current lamp methods are not feasible for diagnosis due to difficulties in accurately interpreting results with problems of sensitive visualization of amplified products, and the risk of contamination resulting from the high quan ...201121693031
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
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
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
urban malaria and associated risk factors in jimma town, south-west ethiopia.malaria kills millions around the world. until recently it was believed to be a disease of rural areas, since the anopheles mosquito, which transmits plasmodium species breeds in rural areas. urban malaria is emerging as a potential, but "avertable" crisis, in africa. in view of the rapidly growing number of small and medium-sized towns in ethiopia there is a pressing need to improve the understanding of the epidemiology of malaria. therefore, the aim of this study was to determine malaria preva ...201121699741
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
patterns of illness in travelers visiting mexico and central america: the geosentinel experience.background.ôçâmexico and central america are important travel destinations for north american and european travelers. there is limited information on regional differences in travel related morbidity. methods.ôçâwe describe the morbidity among 4779 ill travelers returned from mexico and central america who were evaluated at geosentinel network clinics during december 1996 to february 2010. results.ôçâthe most frequent presenting syndromes included acute and chronic diarrhea, dermatologic diseases ...201121832261
chemical constituents of the new endophytic fungus mycosphaerella sp. nov. and their anti-parasitic activity.chemical investigation of a new endophytic fungus, mycosphaerella sp. nov. strain f2140, associated with the foliage of the plant psychotria horizontalis (rubiaceae) in panama, resulted in the isolation of cercosporin (1) and a new cercosporin analog (3) as the major components. the structures of minor compounds in the extract were elucidated by detailed spectroscopic analysis as 2-(2-butyl)-6-ethyl-3-hydroxy-6-methylcyclohex-2-ene-1,5-dione (4), 3-(2-butyl)-6-ethyl-5-hydroxy-2-methoxy-6-methyl- ...201121815421
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
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
children with retinopathy-negative cerebral malaria: a pathophysiological puzzle.background:: cerebral malaria, defined as otherwise unexplained coma in a patient with circulating parasitemia, is a common disease in the developing world. the clinical diagnosis lacks specificity and children with other underlying causes of coma might be misdiagnosed as having cerebral malaria. the presence of malarial retinopathy can be used to differentiate children whose comas are caused by plasmodium falciparum and its attendant pathophysiologies from those with other reasons for their abn ...201121694660
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