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in vitro adaptation of plasmodium falciparum reveal variations in cultivability.culture-adapted plasmodium falciparum parasites can offer deeper understanding of geographic variations in drug resistance, pathogenesis and immune evasion. to help ground population-based calculations and inferences from culture-adapted parasites, the complete range of parasites from a study area must be well represented in any collection. to this end, standardized adaptation methods and determinants of successful in vitro adaption were sought.201626794408
investigation of ototoxicity of artesunate as add-on therapy in patients with metastatic or locally advanced breast cancer: new audiological results from a prospective, open, uncontrolled, monocentric phase i study.artesunate (art) has been used for a long time in the treatment of plasmodium falciparum malaria and has been considered safe. the present phase i study aimed to determine the daily dose of art that is well tolerated as add-on therapy in patients with breast cancer for 4 weeks of therapy. ototoxicity could be a potential safety concern in settings different from malaria. therefore, comprehensive audiological assessment was essential.201626793976
novel 2-phenoxyanilide congeners derived from a hit structure of the tcams: synthesis and evaluation of their in vitro activity against plasmodium falciparum.the tres cantos antimalarial compound set (tcams) is a publicly available compound library which contains 13533 hit structures with confirmed activity against plasmodium falciparum, the infective agent responsible for malaria tropica. the tcams provides a variety of starting points for the investigation of new antiplasmodial drug leads. one of the promising compounds is tcmdc-137332, which seemed to be a good starting point due to its antiplasmodial potency and its predicted physicochemical prop ...201626901174
mrp1 mediates folate transport and antifolate sensitivity in plasmodium falciparum.multidrug resistance-associated proteins (mrp) of plasmodium falciparum have been associated with altered drug sensitivity. knowledge on mrp substrate specificity is indispensible for the characterization of resistance mechanisms and identifying its physiological roles. an untargeted metabolomics approach detected decreased folate concentrations in red blood cells infected with schizont stage parasites lacking expression of mrp1. furthermore, a tenfold decrease in sensitivity toward the folate a ...201626900081
[pulmonary complications of malaria: an update].malaria is the most important parasitic disease worldwide, being a public health challenge in more than 90 countries. the incidence of pulmonary manifestations has increased in recent years. acute respiratory distress syndrome is the most severe form within the pulmonary complications of malaria, with high mortality despite proper management. this syndrome manifests with sudden dyspnoea, cough and refractory hypoxaemia. patients should be admitted to intensive care units and treated with parente ...201626897507
plasmodium falciparum hsp70-z, an hsp110 homologue, exhibits independent chaperone activity and interacts with hsp70-1 in a nucleotide-dependent fashion.the role of molecular chaperones, among them heat shock proteins (hsps), in the development of malaria parasites has been well documented. hsp70s are molecular chaperones that facilitate protein folding. hsp70 proteins are composed of an n-terminal nucleotide binding domain (nbd), which confers them with atpase activity and a c-terminal substrate binding domain (sbd). in the adp-bound state, hsp70 possesses high affinity for substrate and releases the folded substrate when it is bound to atp. th ...201626894764
imported plasmodium vivax malaria with severe thrombocytopaenia: can it be severe malaria or not?thrombocytopaenia is the most frequent malaria-associated haematologic alteration observed with all five plasmodium parasites causing disease in humans. although not included in the world health organization criteria for severe plasmodium falciparum malaria, severe thrombocytopaenia has been increasingly mentioned as an indicator of p. vivax malaria severity.201626893220
an external sensing system in plasmodium falciparum-infected erythrocytes.a number of experiments have previously indicated that plasmodium falciparum-infected erythrocytes (prbc) were able to sense host environment. the basis of this ability to detect external cues is not known but in screening signalling molecules from prbc using commercial antibodies, a 34 kda phosphorylated molecule that possesses such ability was identified.201626893139
a versatile strategy for rapid conditional genome engineering using loxp sites in a small synthetic intron in plasmodium falciparum.conditional genome engineering in the human malaria pathogen plasmodium falciparum remains highly challenging. here we describe a strategy for facile and rapid functional analysis of genes using an approach based on the cre/lox system and tailored for organisms with short and few introns. our method allows the conditional, site-specific removal of genomic sequences of essential and non-essential genes by placing loxp sites into a short synthetic intron to produce a module (loxpint) can be placed ...201626892670
plasmodium falciparum histidine rich protein-2 diversity and the implications for pfhrp 2: based malaria rapid diagnostic tests in ghana.malaria rapid diagnostic tests (rdts) play a key role in malaria management and control. the pfhrp-2 based rdt is the most widely used rdt for malaria diagnosis in ghana. deletion of pfhrp2 in plasmodium falciparum parasites affect the diagnostic accuracy of pfhrp-2 based rdt kits. identifying the prevalence and distribution of p. falciparum parasites with deleted pfhrp2 is important for malaria control.201626891848
a dna aptamer recognising a malaria protein biomarker can function as part of a dna origami assembly.dna aptamers have potential for disease diagnosis and as therapeutics, particularly when interfaced with programmable molecular technology. here we have combined dna aptamers specific for the malaria biomarker plasmodium falciparum lactate dehydrogenase (pfldh) with a dna origami scaffold. twelve aptamers that recognise pfldh were integrated into a rectangular dna origami and atomic force microscopy demonstrated that the incorporated aptamers preserve their ability to specifically bind target pr ...201626891622
safety, tolerability and pharmacokinetic properties of coadministered azithromycin and piperaquine in pregnant papua new guinean women.the aim of the present study was to investigate the safety, tolerability and pharmacokinetics of coadministered azithromycin (azi) and piperaquine (pq) for treating malaria in pregnant papua new guinean women.201626889763
a chemical susceptibility profile of the plasmodium falciparum transmission stages by complementary cell-based gametocyte assays.as most available antimalarial drugs are ineffective against the plasmodium falciparum transmission stages, new drugs against the parasite's gametocytes are urgently needed to combat malaria globally. the unique biology of gametocytes requires assays that need to be specific, to faithfully monitor anti-gametocyte activity, and to be easy to perform, cheap and scalable to high-throughput screening (hts).201626888912
alternative methods for the plasmodium falciparum artemisinin ring-stage survival assay with increased simplicity and parasite stage-specificity.artemisinin-based combination therapy is recommended to treat plasmodium falciparum worldwide, but observations of longer artemisinin (art) parasite clearance times (pcts) in southeast asia are widely interpreted as a sign of potential art resistance. in search of an in vitro correlate of in vivo pct after art treatment, a ring-stage survival assay (rsa) of 0-3 h parasites was developed and linked to polymorphisms in the kelch propeller protein (k13). however, rsa remains a laborious process, in ...201626888201
activated neutrophils are associated with pediatric cerebral malaria vasculopathy in malawian children.most patients with cerebral malaria (cm) sustain cerebral microvascular sequestration of plasmodium falciparum-infected red blood cells (irbcs). although many young children are infected with p. falciparum, cm remains a rare outcome; thus, we hypothesized that specific host conditions facilitate irbc cerebral sequestration. to identify these host factors, we compared the peripheral whole-blood transcriptomes of malawian children with irbc cerebral sequestration, identified as malarial-retinopath ...201626884431
serological conservation of parasite-infected erythrocytes predicts plasmodium falciparum erythrocyte membrane protein 1 gene expression but not severity of childhood malaria.plasmodium falciparum erythrocyte membrane protein 1 (pfemp1), expressed on p. falciparum-infected erythrocytes, is a major family of clonally variant targets of naturally acquired immunity to malaria. previous studies have demonstrated that in areas where malaria is endemic, antibodies to infected erythrocytes from children with severe malaria tend to be more seroprevalent than antibodies to infected erythrocytes from children with nonsevere malaria. these data have led to a working hypothesis ...201626883585
copper homeostasis for the developmental progression of intraerythrocytic malarial parasite.malaria is one of the world's most devastating diseases, particularly in the tropics. in humans, plasmodium falciparum lives mainly within red blood cells, and malaria pathogenesis depends on the red blood cells being infected with the parasite. nonesterified fatty acids (nefas), including cis-9-octadecenoic acid, and phospholipids have been critical for complete parasite growth in serum-free culture, although the efficacy of nefas in sustaining the growth of p. falciparum has varied markedly. h ...201626881705
altered drug susceptibility during host adaptation of a plasmodium falciparum strain in a non-human primate model.infections with plasmodium falciparum, the most pathogenic of the plasmodium species affecting man, have been reduced in part due to artemisinin-based combination therapies. however, artemisinin resistant parasites have recently emerged in south-east asia. novel intervention strategies are therefore urgently needed to maintain the current momentum for control and elimination of this disease. in the present study we characterize the phenotypic and genetic properties of the multi drug resistant (m ...201626880111
uk malaria treatment guidelines 2016.1.malaria is the tropical disease most commonly imported into the uk, with 1300-1800 cases reported each year, and 2-11 deaths. 2. approximately three quarters of reported malaria cases in the uk are caused by plasmodium falciparum, which is capable of invading a high proportion of red blood cells and rapidly leading to severe or life-threatening multi-organ disease. 3. most non-falciparum malaria cases are caused by plasmodium vivax; a few cases are caused by the other species of plasmodium: pl ...201626880088
population pharmacokinetic properties of artemisinin in healthy male vietnamese volunteers.artemisinin-based combination therapy is recommended as first-line anti-malarial treatment worldwide. a combination of artemisinin with the long acting drug piperaquine has shown high efficacy and tolerability in patients with uncomplicated plasmodium falciparum infections. the aim of this study was to characterize the population pharmacokinetic properties of artemisinin in healthy male vietnamese volunteers after two different dose sizes, formulations and in a combination with piperaquine. a se ...201626879816
indocyanine green liposomes for diagnosis and therapeutic monitoring of cerebral malaria.cerebral malaria (cm) is a major cause of death of plasmodium falciparum infection. misdiagnosis of cm often leads to treatment delay and mortality. conventional brain imaging technologies are rarely applicable in endemic areas. here we address the unmet need for a simple, non-invasive imaging methodology for early diagnosis of cm. this study presents the diagnostic and therapeutic monitoring using liposomes containing the fda-approved fluorescent dye indocyanine green (icg) in a cm murine model ...201626877776
clinical manifestations and molecular mechanisms in the changing paradigm of vivax malaria in india.plasmodium vivax once considered benign is now being increasingly associated with complicated malaria where the spectrum of complications is vast and like plasmodium falciparum. the clinical data is important with respect to the immunopathological status of the patient. several genes like the vir genes and pvcrt-o are speculated to be attributing to the severity of p. vivax malaria.201626876067
molecular surveillance of antimalarial drug resistance related genes in plasmodium falciparum isolates from eritrea.the introduction of artemisinin-based combination therapy has led to extraordinary results in malaria control, however the recent emergence of partial resistance to artemisinin therapy in southeast asia jeopardizes these successes. this study aimed at investigating resistance to the antimalarial drugs by evaluating the polymorphisms in the pfk13, pfcrt and pfmdr1 genes in plasmodium falciparum isolates obtained from patients in eritrea.201626875763
immunogenicity of dimorphic and c-terminal fragments of plasmodium falciparum msp2 formulated with different adjuvants in mice.plasmodium falciparum msp2 is a blood stage protein that is associated with protection against malaria. it was shown that the msp2 dimorphic (d) and constant (c) regions were well recognized by immune human antibodies, and were characterized by major conserved epitopes in different endemic areas and age groups. these abs recognized merozoite-derived proteins in wb and ifa. here, the goal was to determine in mice the immunogenicity of the two allelic msp2 d and c domains formulated with different ...201626874325
earthworm-mediated synthesis of silver nanoparticles: a potent tool against hepatocellular carcinoma, plasmodium falciparum parasites and malaria mosquitoes.the development of parasites and pathogens resistant to synthetic drugs highlighted the needing of novel, eco-friendly and effective control approaches. recently, metal nanoparticles have been proposed as highly effective tools towards cancer cells and plasmodium parasites. in this study, we synthesized silver nanoparticles (ew-agnp) using eudrilus eugeniae earthworms as reducing and stabilizing agents. ew-agnp showed plasmon resonance reduction in uv-vis spectrophotometry, the functional groups ...201626873539
rapid evaluation of artesunate quality with a specific monoclonal antibody-based lateral flow dipstick.artesunate is a frontline antimalarial drug for treating plasmodium falciparum malaria. to produce specific antibodies to artesunate, the carboxyl group of artesunate was directly conjugated to carrier protein as the immunogen. a specific monoclonal antibody (mab) 3d82g6 against artesunate was obtained by high-throughput screening of positive hybridoma clones. this monoclonal antibody had 4.0, 0.5, and 0.9 % cross reactivities with artemisinin, dihydroartemisinin, and artemether, respectively. a ...201626873200
correction: evasion of immunity to plasmodium falciparum: rosettes of blood group a impair recognition of pfemp1. 201626872046
h3.3 demarcates gc-rich coding and subtelomeric regions and serves as potential memory mark for virulence gene expression in plasmodium falciparum.histones, by packaging and organizing the dna into chromatin, serve as essential building blocks for eukaryotic life. the basic structure of the chromatin is established by four canonical histones (h2a, h2b, h3 and h4), while histone variants are more commonly utilized to alter the properties of specific chromatin domains. h3.3, a variant of histone h3, was found to have diverse localization patterns and functions across species but has been rather poorly studied in protists. here we present the ...201627555062
complicated malaria symptoms associated with plasmodium vivax among patients visiting health facilities in mendi town, northwest ethiopia.malaria is still a major health problem in some parts of the world. plasmodium falciparum is the common pathogenic parasite and is responsible for majority of malaria associated deaths. recently the other benign parasite, p. vivax, is reported to cause life threatening severe malaria complications. thus, this study was aimed to assess incidence of severe malaria symptoms caused by p. vivax parasite in some malaria endemic areas of ethiopia.201627549864
expression of complement and toll-like receptor pathway genes is associated with malaria severity in mali: a pilot case control study.the host response to infection by plasmodium falciparum, the parasite most often responsible for severe malaria, ranges from asymptomatic parasitaemia to death. the clinical trajectory of malaria is influenced by host genetics and parasite load, but the factors determining why some infections produce uncomplicated malaria and some proceed to severe disease remain incompletely understood.201626961973
the effect of aqueous extract of cinnamon on the metabolome of plasmodium falciparum using (1)hnmr spectroscopy.malaria is responsible for estimated 584,000 deaths in 2013. researchers are working on new drugs and medicinal herbs due to drug resistance that is a major problem facing them; the search is on for new medicinal herbs. cinnamon is the bark of a tree with reported antiparasitic effects. metabonomics is the simultaneous study of all the metabolites in biological fluids, cells, and tissues detected by high throughput technology. it was decided to determine the mechanism of the effect of aqueous ex ...201626904134
transmission-blocking potential of mefas, a hybrid compound derived from artesunate and mefloquine.most antimalarial drugs target asexual parasites without reducing gametocyte formation or development. drugs with dual roles, i.e., those that can target both asexual parasites and gametocytes, would improve the control of malaria. in the current study, mefas, a hybrid drug derived from mefloquine and artesunate that has been shown to be an active blood schizonticidal drug, was assessed to determine its ability to block the infectivity of plasmodium falciparum gametocytes. mefas was 280 and 15 t ...201626902763
profoundly reduced cd1c+ myeloid dendritic cell hla-dr and cd86 expression and increased tumor necrosis factor production in experimental human blood-stage malaria infection.dendritic cells (dcs) are sentinels of the immune system that uniquely prime naive cells and initiate adaptive immune responses. cd1c (bdca-1) myeloid dcs (cd1c(+) mdcs) highly express hla-dr, have a broad toll-like receptor (tlr) repertoire, and secrete immune modulatory cytokines. to better understand immune responses to malaria, cd1c(+) mdc maturation and cytokine production were examined in healthy volunteers before and after experimental intravenous plasmodium falciparum infection with 150- ...201626902728
plasmodium falciparum epigenome: a distinct dynamic epigenetic regulation of gene expression.histone modification profiles are predictive of gene expression and most of the knowledge gained is acquired through studies done in higher eukaryotes. however, genome-wide studies involving plasmodium falciparum, the causative agent of malaria, have been rather few, at lower resolution (mostly using chip-on-chip), and covering limited number of histone modifications. in our recent study [1], we have performed extensive genome-wide analyses of multiple histone modifications including the active ...201626981368
relative susceptibilities of abo blood groups to plasmodium falciparum malaria in ghana.the clinical outcome of falciparum malaria in endemic areas is influenced by erythrocyte polymorphisms including the abo blood groups. studies have reported association of abo blood group to resistance, susceptibility, and severity of p. falciparum malaria infection. individuals with blood group "a" have been found to be highly susceptible to falciparum malaria whereas blood group "o" is said to confer protection against complicated cases. we analyzed samples from 293 young children less than si ...201626981125
isolation and co-cultivation of human macrophages and neutrophils with plasmodium falciparum-parasitized erythrocytes: an optimized system to study the phagocytic activity to malarial parasites.macrophages and neutrophils are our front line of defense against invading pathogens. they are professional phagocytic cells that play a key role in the clearance of plasmodium falciparum-parasitized erythrocytes from the host circulation. a stable in vitro culture system for these cells and parasitized erythrocytes would provide the means to study their immunological responses to infection, potentially revealing important clues for new therapeutic interventions for malaria. here, we present an ...201626979627
health workers' compliance to rapid diagnostic tests (rdts) to guide malaria treatment: a systematic review and meta-analysis.the world health organization recommends malaria to be confirmed by either microscopy or a rapid diagnostic test (rdt) before treatment. the correct use of rdts in resource-limited settings facilitates basing treatment onto a confirmed diagnosis; contributes to speeding up considering a correct alternative diagnosis, and prevents overprescription of anti-malarial drugs, reduces costs and avoids unnecessary exposure to adverse drug effects. this review aims to evaluate health workers' compliance ...201626979286
effect of mild medical hypothermia on in vitro growth of plasmodium falciparum and the activity of anti-malarial drugs.cerebral malaria remains a medical emergency with high mortality. hypo-perfusion due to obstructed blood vessels in the brain is thought to play a key role in the pathophysiology of cerebral malaria leading to neurological impairment, long-term neuro-cognitive sequelae and, potentially, death. due to the rapid reversibility of vascular obstruction caused by sequestered plasmodium falciparum, it is hypothesized that mild medical hypothermia--a standard intervention for other medical emergencies-- ...201626979163
generation of plasmodium falciparum parasite-inhibitory antibodies by immunization with recombinantly-expressed cyrpa.the pathogenesis of malaria is primarily associated with blood-stage infection and there is strong evidence that antibodies specific for parasite blood-stage antigens can control parasitaemia. this provides a strong rationale for incorporation of asexual blood-stage antigen components into an effective multivalent malaria subunit vaccine. on the basis of available genome-wide transcriptomic and proteomic data, previously uncharacterized plasmodium falciparum open reading frames were screened for ...201626979066
indolyl-3-ethanone-α-thioethers: a promising new class of non-toxic antimalarial agents.the success of chemotherapeutics in easing the burden of malaria is under continuous threat from ever-evolving parasite resistance, including resistance to artemisinin combination therapies. therefore, the discovery of new classes of antimalarials which inhibit new biological targets is imperative to controlling malaria. accordingly, we report here the discovery of indolyl-3-ethanone-α-thioethers, a new class of antimalarial compounds with encouraging activity. synthesis of a focused library of ...201626974377
hemolytic and antimalarial effects of tight-binding glyoxalase 1 inhibitors on the host-parasite unit of erythrocytes infected with plasmodium falciparum.glyoxalases prevent the formation of advanced glycation end products by converting glycolysis-derived methylglyoxal to d-lactate with the help of glutathione. vander jagt and colleagues previously showed that erythrocytes release about thirty times more d-lactate after infection with the human malaria parasite plasmodium falciparum. functional glyoxalases in the host-parasite unit might therefore be crucial for parasite survival. here, we determined the antimalarial and hemolytic activity of two ...201626972115
new insights into host-parasite ubiquitin proteome dynamics in p. falciparum infected red blood cells using a tubes-ms approach.malaria, caused by plasmodium falciparum (p. falciparum), ranks as one of the most baleful infectious diseases worldwide. new antimalarial treatments are needed to face existing or emerging drug resistant strains. protein degradation appears to play a significant role during the asexual intraerythrocytic developmental cycle (idc) of p. falciparum. inhibition of the ubiquitin proteasome system (ups), a major intracellular proteolytic pathway, effectively reduces infection and parasite replication ...201626972027
the sudden death of alaric i (c. 370-410ad), the vanquisher of rome: a tale of malaria and lacking immunity.alaric i (c. 370-410ad), king of the visigoths, sacked rome for the second time in over eight centuries of history. historians suggest that malaria, probably contracted either in rome or in the pontine marshes, was responsible for his sudden death in cosenza (calabria) in the autumn of 410ad, where he was allegedly buried in the river busento. in this article, we aim to examine this hypothesis through a full pathographic reassessment of the most likely cause of alaric's demise.201626970917
plasmodium vivax malaria presenting with multifocal hemorrhagic brain infarcts in a school-going child.cerebral malaria is a well-known complication of plasmodium falciparum malaria. over recent years, however, plasmodium vivax also has been reported to cause cerebral malaria with or without co-infection with p. falciparum here, we report a boy aged 10 years presenting with acute febrile encephalopathy with raised intracranial pressure to the emergency, who was later diagnosed to have p. vivax malaria. his neurological status improved gradually during 6 weeks of pediatric intensive care unit stay ...201626966243
new antimalarial norterpene cyclic peroxides from xisha islands sponge diacarnus megaspinorhabdosa.four new norterpene cyclic peroxides (1-4), together with three known norterpene cyclic peroxides were isolated from the xisha islands sponge diacarnus megaspinorhabdosa. their structures were elucidated on the basis of spectroscopic analyses and comparison with the related model compounds. the compounds (1-7) were evaluated for the inhibitory activity against the malaria parasite plasmodium falciparum, all of them showed significant antimalarial activity with ic50 values in the range of 1.6-8.6 ...201626965857
the growing pipeline of natural aminoacyl-trna synthetase inhibitors for malaria treatment.malaria remains a major global health problem. parasite resistance to existing drugs makes development of new antimalarials an urgency. the protein synthesis machinery is an excellent target for the development of new anti-infectives, and aminoacyl-trna synthetases (aars) have been validated as antimalarial drug targets. however, avoiding the emergence of drug resistance and improving selectivity to target aars in apicomplexan parasites, such as plasmodium falciparum, remain crucial challenges. ...201626963157
antioxidant and antiplasmodial activities of bergenin and 11-o-galloylbergenin isolated from mallotus philippensis.two important biologically active compounds were isolated from mallotus philippensis. the isolated compounds were characterized using spectroanalytical techniques and found to be bergenin (1) and 11-o-galloylbergenin (2). the in vitro antioxidant and antiplasmodial activities of the isolated compounds were determined. for the antioxidant potential, three standard analytical protocols, namely, dpph radical scavenging activity (rsa), reducing power assay (rpa), and total antioxidant capacity (tac) ...201626998192
ticket to ride: export of proteins to the plasmodium falciparum-infected erythrocyte.the malaria parasite plasmodium falciparum exports numerous proteins to its chosen host cell, the mature human erythrocyte. many of these proteins are important for parasite survival. to reach the host cell, parasites must cross multiple membrane barriers and then furthermore be targeted to their correct sub-cellular localisation. this novel transport pathway has received much research attention in the past decades, especially as many of the mechanisms are expected to be parasite-specific and th ...201626996123
hollow-fiber methodology for pharmacokinetic/pharmacodynamic studies of antimalarial compounds.knowledge of pharmacokinetic/pharmacodynamic (pk/pd) relationships can enhance the speed and economy of drug development by enabling informed and rational decisions at every step, from lead selection to clinical dosing. for anti-infective agents in particular, dynamic in vitro hollow-fiber cartridge experiments permit exquisite control of kinetic parameters and the study of their consequent impact on pharmacodynamic efficacy. such information is of great interest for the cost-restricted but much ...201626995353
in vitro inhibition of plasmodium falciparum early and late stage gametocyte viability by extracts from eight traditionally used south african plant species.extracts of plant species, used traditionally to treat malaria, have been extensively investigated for their activity against plasmodium intraerythrocytic asexual parasites in search of new antimalarial drugs. however, less effort has been directed towards examining their efficacy in blocking transmission. here, we report the results of the in vitro screening of extracts from eight selected plant species used traditionally to treat malaria in south africa for activity against plasmodium falcipar ...201626994818
synthetic tlr4 agonists enhance functional antibodies and cd4+ t-cell responses against the plasmodium falciparum gmz2.6c multi-stage vaccine antigen.a subunit vaccine targeting both transmission and pathogenic asexual blood stages of plasmodium falciparum, i.e., a multi-stage vaccine, could be a powerful tool to combat malaria. here, we report production and characterization of the recombinant protein gmz2.6c, which contains a fragment of the sexual-stage protein pfs48/45-6c genetically fused to gmz2, an asexual vaccine antigen in advanced clinical development. to select the most suitable vaccine formulation for downstream clinical studies, ...201626994314
modeling cytoadhesion of plasmodium falciparum-infected erythrocytes and leukocytes-common principles and distinctive features.cytoadhesion of plasmodium falciparum-infected erythrocytes to the microvascular endothelial lining shares striking similarities to cytoadhesion of leukocytes. in both cases, adhesins are presented in structures that raise them above the cell surface. another similarity is the enhancement of adhesion under physical force (catch bonding). here, we review recent advances in our understanding of the molecular and biophysical mechanisms underlying cytoadherence in both cellular systems. we describe ...201626992823
contribution of brain perfusion spect in the diagnosis of a case of cerebral malaria.cerebral malaria is a serious complication of infection with plasmodium falciparum. its pathophysiological mechanisms and clinical manifestations are still currently being studied. structural imaging techniques such as ct and mri provide non-specific information during the diagnostic process. however, there are hardly any references on the use and potential benefits of radioisotope procedures for this pathology. in this article we present the case of a patient diagnosed with cerebral malaria tre ...201626992642
comparative assessment on the prevalence of mutations in the plasmodium falciparum drug-resistant genes in two different ecotypes of odisha state, india.considering malaria as a local and focal disease, epidemiological understanding of different ecotypes of malaria can help in devising novel control measures. one of the major hurdles in malaria control lies on the evolution and dispersal of the drug-resistant malaria parasite, plasmodium falciparum. we herewith present data on genetic variation at the single nucleotide polymorphism (snp) level in four different genes of p. falciparum (pfcrt, pfmdr1, pfdhfr, and pfdhps) that confer resistance to ...201626988711
analysis of the interactome of the ser/thr protein phosphatase type 1 in plasmodium falciparum.protein phosphatase 1 (pp1) is an enzyme essential to cell viability in the malaria parasite plasmodium falciparum (pf). the activity of pp1 is regulated by the binding of regulatory subunits, of which there are up to 200 in humans, but only 3 have been so far reported for the parasite. to better understand the p. falciparum pp1 (pfpp1) regulatory network, we here report the use of three strategies to characterize the pfpp1 interactome: co-affinity purified proteins identified by mass spectromet ...201626988354
new pentasubstituted pyrrole hybrid atorvastatin-quinoline derivatives with antiplasmodial activity.cerebral malaria is caused by plasmodium falciparum. atorvastatin (ava) is a pentasubstituted pyrrole, which has been tested as an adjuvant in the treatment of cerebral malaria. herein, a new class of hybrids of ava and aminoquinolines (primaquine and chloroquine derivatives) has been synthesized. the quinolinic moiety was connected to the pentasubstituted pyrrole from ava by a linker group (ch2)n=2-4 units. the activity of the compounds increased with the size of the carbons chain. compound wit ...201626988303
identification of plasmodium falciparum specific translation inhibitors from the mmv malaria box using a high throughput in vitro translation screen.a major goal in the search for new anti-malarial compounds is to identify new mechanisms of action or new molecular targets. while cell-based, growth inhibition-based screening have enjoyed tremendous success, an alternative approach is to specifically assay a given pathway or essential cellular process.201626987601
user and provider acceptability of intermittent screening and treatment and intermittent preventive treatment with dihydroartemisinin-piperaquine to prevent malaria in pregnancy in western kenya.the world health organization recommends intermittent preventive treatment in pregnancy (iptp) with sulphadoxine-pyrimethamine (sp) alongside long-lasting insecticide-treated nets (llin) and case management for reducing the risks associated with malaria in pregnancy in areas of moderate-to-high transmission in sub-saharan africa. due to increasing plasmodium falciparum resistance to sp, the search for alternative drugs or strategies to control malaria in pregnancy is a priority. we assessed the ...201626986471
asymmetric dimethylarginine in adult falciparum malaria: relationships with disease severity, antimalarial treatment, hemolysis, and inflammation.background.  endothelial nitric oxide (no) bioavailability is impaired in severe falciparum malaria (sm). asymmetric dimethylarginine (adma), an endogenous inhibitor of no synthase (nos), contributes to endothelial dysfunction and is associated with mortality in adults with falciparum malaria. however, factors associated with adma in malaria, including the nos-substrate l-arginine, hemolysis, and antimalarial treatment, are not well understood. methods.  in a prospective observational study of m ...201626985445
within-host competition and drug resistance in the human malaria parasite plasmodium falciparum.infections with the malaria parasite plasmodium falciparum typically comprise multiple strains, especially in high-transmission areas where infectious mosquito bites occur frequently. however, little is known about the dynamics of mixed-strain infections, particularly whether strains sharing a host compete or grow independently. competition between drug-sensitive and drug-resistant strains, if it occurs, could be a crucial determinant of the spread of resistance. we analysed 1341 p. falciparum i ...201626984625
strain-transcending immune response generated by chimeras of the malaria vaccine candidate merozoite surface protein 2.msp2 is an intrinsically disordered protein that is abundant on the merozoite surface and essential to the parasite plasmodium falciparum. naturally-acquired antibody responses to msp2 are biased towards dimorphic sequences within the central variable region of msp2 and have been linked to naturally-acquired protection from malaria. in a phase iib study, an msp2-containing vaccine induced an immune response that reduced parasitemias in a strain-specific manner. a subsequent phase i study of a va ...201626865062
immune activation and induction of memory: lessons learned from controlled human malaria infection with plasmodium falciparum.controlled human malaria infections (chmis) are a powerful tool to assess the efficacy of drugs and/or vaccine candidates, but also to study anti-malarial immune responses at well-defined time points after infection. in this review, we discuss the insights that chmi trials have provided into early immune activation and regulation during acute infection, and the capacity to induce and maintain immunological memory. importantly, these studies show that a single infection is sufficient to induce lo ...201626864135
insights into the naturally acquired immune response to plasmodium vivax malaria.plasmodium vivax is the most geographically widespread of the malaria parasites causing human disease, yet it is comparatively understudied compared with plasmodium falciparum. in this article we review what is known about naturally acquired immunity to p. vivax, and importantly, how this differs to that acquired against p. falciparum. immunity to clinical p. vivax infection is acquired more quickly than to p. falciparum, and evidence suggests humans in endemic areas also have a greater capacity ...201626864134
structure- and function-based design of plasmodium-selective proteasome inhibitors.the proteasome is a multi-component protease complex responsible for regulating key processes such as the cell cycle and antigen presentation. compounds that target the proteasome are potentially valuable tools for the treatment of pathogens that depend on proteasome function for survival and replication. in particular, proteasome inhibitors have been shown to be toxic for the malaria parasite plasmodium falciparum at all stages of its life cycle. most compounds that have been tested against the ...201626863983
targeting the plasmodium vivax equilibrative nucleoside transporter 1 (pvent1) for antimalarial drug development.infection with plasmodium falciparum and vivax cause most cases of malaria. emerging resistance to current antimalarial medications makes new drug development imperative. ideally a new antimalarial drug should treat both falciparum and vivax malaria. because malaria parasites are purine auxotrophic, they rely on purines imported from the host erythrocyte via equilibrative nucleoside transporters (ents). thus, the purine import transporters represent a potential target for antimalarial drug devel ...201626862473
erythrocyte invasion receptors for plasmodium falciparum: new and old.understanding the complex process by which the invasive form of the plasmodium falciparum parasite, the merozoite, attaches to and invades erythrocytes as part of its blood stage life cycle represents a key area of research in the battle to combat malaria. central to this are efforts to determine the identity of receptors on the host cell surface, their corresponding merozoite-binding proteins and the functional relevance of these binding events as part of the invasion process. this review will ...201626862042
longitudinal household surveillance for malaria in rakai, uganda.hiv and malaria exert co-pathogenic effects. malaria surveillance data are necessary for public health strategies to reduce the burden of disease in high hiv prevalence settings.201626861943
estimating malaria transmission intensity from plasmodium falciparum serological data using antibody density models.serological data are increasingly being used to monitor malaria transmission intensity and have been demonstrated to be particularly useful in areas of low transmission where traditional measures such as eir and parasite prevalence are limited. the seroconversion rate (scr) is usually estimated using catalytic models in which the measured antibody levels are used to categorize individuals as seropositive or seronegative. one limitation of this approach is the requirement to impose a fixed cut-of ...201626861862
maternal-foetal transfer of plasmodium falciparum and plasmodium vivax antibodies in a low transmission setting.during pregnancy immunoglobulin g (igg) antibodies are transferred from mother to neonate across the placenta. studies in high transmission areas have shown transfer of p. falciparum-specific igg, but the extent and factors influencing maternal-foetal transfer in low transmission areas co-endemic for both p. falciparum and p. vivax are unknown. pregnant women were screened weekly for plasmodium infection. mother-neonate paired serum samples at delivery were tested for igg to antigens from p. fal ...201626861682
major histocompatibility complex and malaria: focus on plasmodium vivax infection.the importance of host and parasite genetic factors in malaria resistance or susceptibility has been investigated since the middle of the last century. nowadays, of all diseases that affect man, malaria still plays one of the highest levels of selective pressure on human genome. susceptibility to malaria depends on exposure profile, epidemiological characteristics, and several components of the innate and adaptive immune system that influences the quality of the immune response generated during ...201626858717
artemisinin activity-based probes identify multiple molecular targets within the asexual stage of the malaria parasites plasmodium falciparum 3d7.the artemisinin (art)-based antimalarials have contributed significantly to reducing global malaria deaths over the past decade, but we still do not know how they kill parasites. to gain greater insight into the potential mechanisms of art drug action, we developed a suite of art activity-based protein profiling probes to identify parasite protein drug targets in situ. probes were designed to retain biological activity and alkylate the molecular target(s) of plasmodium falciparum 3d7 parasites i ...201626858419
towards ultrasensitive malaria diagnosis using surface enhanced raman spectroscopy.we report two methods of surface enhanced raman spectroscopy (sers) for hemozoin detection in malaria infected human blood. in the first method, silver nanoparticles were synthesized separately and then mixed with lysed blood; while in the second method, silver nanoparticles were synthesized directly inside the parasites of plasmodium falciparum. it was observed that the first method yields a smaller variation in sers measurements and stronger correlation between the estimated contribution of he ...201626858127
the plasmodium falciparum chloroquine resistance transporter is associated with the ex vivo p. falciparum african parasite response to pyronaridine.the pyronaridine-artesunate combination is one of the most recent oral artemisinin-based therapeutic combinations (acts) recommended for the treatment of uncomplicated p. falciparum malaria. the emergence of p. falciparum resistance to artemisinin has recently developed in southeast asia. little data are available on the association between pyronaridine susceptibility and polymorphisms in genes involved in antimalarial drug resistance. the objective of the present study was to investigate the as ...201626858119
plasmodium falciparum drug resistance in angola.facing chloroquine drug resistance, angola promptly adopted artemisinin-based combination therapy as the first-line to treat malaria. currently, the country aims to consolidate malaria control, while preparing for the elimination of the disease, along with others african countries in the region. however, the remarkable capacity of plasmodium to develop drug resistance represents an alarming threat for those achievements. herein, the available, but relatively scarce and dispersed, information on ...201626858018
limited degradation of the plasmodium falciparum gametocyte marker pfs25 mrna exposed to tropical temperatures: considerations for malaria transmission field studies.an important aspect of many malaria molecular epidemiology and transmission studies is rna-based detection of gametocytes. ensuring rna stability represents a challenge in tropical, resource-limited environments, as rna may quickly degrade when samples are not preserved under adequate conditions. this study investigated the degradation of pfs25 messenger rna (mrna), the most widely used plasmodium falciparum gametocyte marker, in whole blood spiked with cultured p. falciparum gametocytes, expose ...201626856913
lead selection of a new aminomethylphenol, jpc-3210, for malaria treatment and prevention.structure-activity relationship studies of trifluoromethyl-substituted pyridine and pyrimidine analogues of 2-aminomethylphenols (jpc-2997, jpc-3186, and jpc-3210) were conducted for preclinical development for malaria treatment and/or prevention. of these compounds, jpc-3210 [4-(tert-butyl)-2-((tert-butylamino)methyl)-6-(5-fluoro-6-(trifluoromethyl)pyridin-3-yl)phenol] was selected as the lead compound due to superior in vitro antimalarial activity against multidrug-resistant plasmodium falcipa ...201626856849
delayed onset of plasmodium falciparum malaria after doxycycline prophylaxis in a soldier returning from the central african republic. 201626856842
evidences for the action mechanism of angiotensin ii and its analogs on plasmodium sporozoite membranes.malaria is an infectious disease responsible for approximately one million deaths annually. oligopeptides such as angiotensin ii (aii) and its analogs are known to have antimalarial effects against plasmodium gallinaceum and plasmodium falciparum. however, their mechanism of action is still not fully understood at the molecular level. in the work reported here, we investigated this issue by comparing the antimalarial activity of aii with that of (i) its diastereomer formed by only d-amino acids; ...201626856687
plasmodium falciparum merozoite surface protein-1 polymorphisms among asymptomatic sickle cell anemia patients in nigeria.asymptomatic malaria (asm) has been implicated in the development of hemolytic crisis in infected sickle cell anemia (sca) patients worldwide. this study surveyed steady state sca nigerian patients for asm to investigate the influence of malaria prevention behaviors and age on parasitaemia and multiplicity of infection (moi). a total of 78 steady sca patients aged 5 - 27 years on routine care at three health facilities in lagos were investigated for asm by light microscopy and pcr with a multipl ...201626853290
changes in lipid composition during sexual development of the malaria parasite plasmodium falciparum.the development of differentiated sexual stages (gametocytes) within human red blood cells is essential for the propagation of the malaria parasite, since only mature gametocytes will survive in the mosquito's midgut. hence gametocytogenesis is a pre-requisite for transmission of the disease. physiological changes involved in sexual differentiation are still enigmatic. in particular the lipid metabolism-despite being central to cellular regulation and development-is not well explored.201626852399
what is the value of reactive case detection in malaria control? a case-study in india and a systematic review.reactive case detection (rcd) for malaria is a strategy to identify additional malaria infections in areas of low malaria transmission and can complement passive surveillance. this study describes experiences with rcd in two indian sites, and aimed to synthesize experiences with rcd across endemic countries.201626852118
design, structure prediction and molecular dynamics simulation of a fusion construct containing malaria pre-erythrocytic vaccine candidate, pfceltos, and human interleukin 2 as adjuvant.malaria infection is still widespread in some parts of the world and threatens the lives of millions of people every year. vaccines, especially oral vaccines are considered to be effective in reducing the burden of malaria morbidity and mortality. by using recombinant technology, suitable oral hosts could serve as antigen delivering vehicles in developing oral vaccines. this study was aimed towards designing and computational analysis of a fusion protein consisting of plasmodium falciparum cell- ...201626851942
emerging roles for hemostatic dysfunction in malaria pathogenesis.severe plasmodium falciparum malaria remains a leading cause of mortality, particularly in sub-saharan africa where it accounts for up to 1 million deaths per annum. in spite of the significant mortality and morbidity associated with cerebral malaria (cm), the molecular mechanisms involved in the pathophysiology of severe malaria remain surprisingly poorly understood. previous studies have demonstrated that sequestration of p falciparum-infected erythrocytes within the microvasculature of the br ...201626851291
insight into phagocytosis of mature sexual (gametocyte) stages of plasmodium falciparum using a human monocyte cell line.during natural infection malaria parasites are injected into the bloodstream of a human host by the bite of an infected female anopheles mosquito. both asexual and mature sexual stages of plasmodium circulate in the blood. asexual forms are responsible for clinical malaria while sexual stages are responsible for continued transmission via the mosquitoes. immune responses generated against various life cycle stages of the parasite have important roles in resistance to malaria and in reducing mala ...201626851166
malaria in pregnancy: a passive surveillance study of pregnant women in low transmission areas of colombia, latin america.malaria causes a significant burden in highly endemic areas where children and pregnant women are more susceptible to severe disease and death, however, in low transmission settings malaria in pregnant women is less frequent. the aim of this study was to provide information of clinical profile, anti-parasite host immune responses and parasite genotyping of pregnant women with malaria in low endemic areas of colombia.201626850108
acquired immune responses to three malaria vaccine candidates and their relationship to invasion inhibition in two populations naturally exposed to malaria.malaria still represents a major cause of morbidity and mortality predominantly in several developing countries, and remains a priority in many public health programmes. despite the enormous gains made in control and prevention the development of an effective vaccine represents a persisting challenge. although several parasite antigens including pre-erythrocytic antigens and blood stage antigens have been thoroughly investigated, the identification of solid immune correlates of protection agains ...201626850066
mutations of pvdhfr and pvdhps genes in vivax endemic-malaria areas in kota marudu and kalabakan, sabah.malaria cases persist in some remote areas in sabah and sarawak despite the ongoing and largely successful malaria control programme conducted by the vector borne disease control programme, ministry of health, malaysia. point mutations in the genes that encode the two enzymes involved in the folate biosynthesis pathway, dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) enzymes confer resistance to pyrimethamine and sulfadoxine respectively, in both plasmodium falciparum and p. v ...201626850038
correction: an analysis of the binding characteristics of a panel of recently selected icam-1 binding plasmodium falciparum patient isolates. 201626849362
antibody acquisition models: a new tool for serological surveillance of malaria transmission intensity.serology has become an increasingly important tool for the surveillance of a wide range of infectious diseases. it has been particularly useful to monitor malaria transmission in elimination settings where existing metrics such as parasite prevalence and incidence of clinical cases are less sensitive. seroconversion rates, based on antibody prevalence to plasmodium falciparum asexual blood-stage antigens, provide estimates of transmission intensity that correlate with entomological inoculation r ...201626846726
the malarial exported pfa0660w is an hsp40 co-chaperone of pfhsp70-x.plasmodium falciparum, the human pathogen responsible for the most dangerous malaria infection, survives and develops in mature erythrocytes through the export of proteins needed for remodelling of the host cell. molecular chaperones of the heat shock protein (hsp) family are prominent members of the exportome, including a number of hsp40s and a hsp70. pfa0660w, a type ii hsp40, has been shown to be exported and possibly form a complex with pfhsp70-x in the infected erythrocyte cytosol. however, ...201626845441
high-throughput and label-free blood-on-a-chip for malaria diagnosis.the malaria parasite plasmodium falciparum (pf) changes the structure and mechanical properties of red blood cells (rbcs). these changes decrease deformability and increase cytoadherence of pf-infected rbcs to the vascular endothelium, eventually leading to flow occlusions in capillary vessels. in this study, to detect pf-infected rbcs effectively, deformability and viscosity of blood sample are measured simultaneously and indirectly by quantifying blood flow in a microfluidic device. the microf ...201626845250
red blood cell complement receptor one level varies with knops blood group, α(+)thalassaemia and age among kenyan children.both the invasion of red blood cells (rbcs) by plasmodium falciparum parasites and the sequestration of parasite-infected rbcs in the microvasculature are mediated in part by complement receptor one (cr1). rbc surface cr1 level can vary between individuals by more than 20-fold and may be associated with the risk of severe malaria. the factors that influence rbc cr1 level variation are poorly understood, particularly in african populations. we studied 3535 child residents of a malaria-endemic reg ...201626844958
update: malaria, u.s. armed forces, 2015.u.s. service members are at risk of acquiring malaria infection when they are located in endemic areas because of long-term duty assignments, participation in shorter-term contingency operations, or personal travel. the number of malaria cases among u.s. military service members in 2015 (n=30) was the lowest annual count in at least 20 years and follows 3 previous years of greatly reduced incidence. the relatively low numbers of cases during 2012-2015 mainly reflect decreases in cases acquired i ...201626836202
the conserved apicomplexan aurora kinase tgark3 is involved in endodyogeny, duplication rate and parasite virulence.aurora kinases are eukaryotic serine/threonine protein kinases that regulate key events associated with chromatin condensation, centrosome and spindle function and cytokinesis. elucidating the roles of aurora kinases in apicomplexan parasites is crucial to understand the cell cycle control during plasmodium schizogony or toxoplasma endodyogeny. here, we report on the localization of two previously uncharacterized toxoplasma aurora-related kinases (ark2 and ark3) in tachyzoites and of the unchara ...201626833682
analysis of the immune response of a new malaria vaccine based on the modification of cryptic epitopes.malaria is a severe, life-threatening infectious disease that endangers human health. however, there are no vaccines or immune strategy of vaccines succeeding in both erythrocytic and pre-erythrocytic stage. during the liver stage of the plasmodium life cycle, sporozoites invade the host liver cells. the sporozoites, then, induce a cellular immune response via the major histocompatibility complex (mhc) molecules on their surfaces. the cytotoxic t lymphocytes (ctls) then recognize the correspondi ...201626833322
merozoite surface proteins in red blood cell invasion, immunity and vaccines against malaria.malaria accounts for an enormous burden of disease globally, with plasmodium falciparum accounting for the majority of malaria, and p. vivax being a second important cause, especially in asia, the americas and the pacific. during infection with plasmodium spp., the merozoite form of the parasite invades red blood cells and replicates inside them. it is during the blood-stage of infection that malaria disease occurs and, therefore, understanding merozoite invasion, host immune responses to merozo ...201626833236
[malaria and intestinal protozoa].malaria is life threatening and requires urgent diagnosis and treatment. incidence and mortality are being reduced in endemic areas. clinical features are unspecific so in imported cases it is vital the history of staying in a malarious area. the first line treatments for plasmodium falciparum are artemisinin combination therapies, chloroquine in most non-falciparum and intravenous artesunate if any severity criteria. human infections with intestinal protozoa are distributed worldwide with a hig ...201626832999
export of malaria proteins requires co-translational processing of the pexel motif independent of phosphatidylinositol-3-phosphate binding.plasmodium falciparum exports proteins into erythrocytes using the plasmodium export element (pexel) motif, which is cleaved in the endoplasmic reticulum (er) by plasmepsin v (pmv). a recent study reported that phosphatidylinositol-3-phosphate (pi(3)p) concentrated in the er binds to pexel motifs and is required for export independent of pmv, and that pexel motifs are functionally interchangeable with rxlr motifs of oomycete effectors. here we show that the pexel does not bind pi(3)p, and that t ...201626832821
polycyclic amines as chloroquine resistance modulating agents in plasmodium falciparum.pentacycloundecylamines (pcus) and adamantane amines, such as ngp1-01 (1) and amantadine, have shown significant channel blocking activities. they are postulated to act as chemosensitizers and circumvent the resistance of the plasmodia parasite against chloroquine (cq) by inhibiting the p-glycoprotein efflux pump and enabling the accumulation of cq inside the parasite digestive vacuole. twelve polycyclic amines containing either a pcu or adamantane amine moiety conjugated to different aromatic f ...201626832222
distinctive origin of artemisinin-resistant plasmodium falciparum on the china-myanmar border.the artemisinin (art), discovered in china, has been widely used against malaria in china over the last 30 years. understanding the emergence and origin of art resistance in china is therefore of great interest. we analyzed 111 culture-adapted isolates of p. falciparum from china-myanmar (cm) border for their susceptibility to dihydroartemisinin using the ring stage survival assay (rsa0-3h) and genotyped their k13 genes. of the isolates, 59 had a wild type of the k13 marker and a median ring sur ...201626831371
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