Publications

differences in affinity of monoclonal and naturally acquired polyclonal antibodies against plasmodium falciparum merozoite antigens.	malaria is a major global cause of deaths and a vaccine is urgently needed.	2015	26149471
mitochondrial population genomic analyses reveal population structure and demography of indian plasmodium falciparum.	inference on the genetic diversity of plasmodium falciparum populations could help in better management of malaria. a very recent study with mitochondrial (mt) genomes in global p. falciparum had revealed interesting evolutionary genetic patterns of indian isolates in comparison to global ones. however, no population genetic study using the whole mt genome sequences of p. falciparum isolates collected in the entire distribution range in india has yet been performed. we herewith have analyzed 85 ...	2015	26149324
phosphoproteomics reveals malaria parasite protein kinase g as a signalling hub regulating egress and invasion.	our understanding of the key phosphorylation-dependent signalling pathways in the human malaria parasite, plasmodium falciparum, remains rudimentary. here we address this issue for the essential cgmp-dependent protein kinase, pfpkg. by employing chemical and genetic tools in combination with quantitative global phosphoproteomics, we identify the phosphorylation sites on 69 proteins that are direct or indirect cellular targets for pfpkg. these pfpkg targets include proteins involved in cell signa ...	2015	26149123
applying chemical genetic tools to the study of phospho-signalling pathways in malaria parasites.	until very recently there has been very little information about the phospho-signalling pathways in apicomplexan parasites including the most virulent species of human malaria parasite, plasmodium falciparum. with the advancement of mass spectrometry-based phosphoproteomics and the development of chemical genetic approaches to target specific parasite protein kinases, the complexity of the essential role played by phosphorylation in maintaining the viability of apicomplexan parasites is now bein ...	2015	26143498
synthesis, antimalarial activity and molecular docking of hybrid 4-aminoquinoline-1,3,5-triazine derivatives.	a series of novel hybrid 4-aminoquinoline 1,3,5-triazine derivatives was synthesized in a five-steps reaction and evaluated for their in vitro antimalarial activity against chloroquine-sensitive (3d7) and chloroquine-resistant (rkl-2) strains of plasmodium falciparum. entire synthetic derivatives showed higher antimalarial activity on the sensitive strain while two compounds, viz., 9a and 9c displayed good activity against both the strains of p. falciparum. the observed activity was further subs ...	2015	26164360
clarithromycin enhances the antimalarial efficacy of mefloquine via its increased bioavailability and disrupting p. falciparum apicoplast.	many important drugs like mefloquine are not being used because of the development of resistance and other related issues. in the present study, we aimed to control drug resistance by using combination therapy and tried to understand the mechanism involved.	2015	26164186
intraleukocytic hemozoin pigments in complicated plasmodium falciparum cerebral malaria.		2015	26157775
deletion of plasmodium falciparum histidine-rich protein 2 (pfhrp2) and histidine-rich protein 3 (pfhrp3) genes in colombian parasites.	a number of studies have analyzed the performance of malaria rapid diagnostic tests (rdts) in colombia with discrepancies in performance being attributed to a combination of factors such as parasite levels, interpretation of rdt results and/or the handling and storage of rdt kits. however, some of the inconsistencies observed with results from plasmodium falciparum histidine-rich protein 2 (pfhrp2)-based rdts could also be explained by the deletion of the gene that encodes the protein, pfhrp2, a ...	2015	26151448
identification of β-hematin inhibitors in the mmv malaria box.	the malaria box, assembled by the medicines for malaria venture, is a set of 400 structurally diverse, commercially available compounds with demonstrated activity against blood-stage plasmodium falciparum. the compounds are a representative subset of the 20,000 in vitro antimalarials identified from the high-throughput screening efforts of st. jude children's research hospital (tn, usa), novartis and glaxosmithkline. in addition, a small set of active compounds from commercially available librar ...	2015	26150923
samvisterin, a new natural antiplasmodial betulin derivative from uapaca paludosa (euphorbiaceae).	uapaca paludosa is used in african traditional medicine for the treatment of malaria.	2015	26192809
potential role of plasmodium falciparum-derived ammonia in the pathogenesis of cerebral malaria.	cerebral malaria (cm) is the most severe complication associated with plasmodium falciparum infection. the exact pathogenic mechanisms leading to the development of cm remains poorly understood while the mortality rates remain high. several potential mechanisms including mechanical obstruction of brain microvasculature, inflammation, oxidative stress, cerebral energy defects, and hemostatic dysfunction have been suggested to play a role in cm pathogenesis. however, these proposed mechanisms, eve ...	2015	26190968
plasmodium falciparum coronin organizes arrays of parallel actin filaments potentially guiding directional motility in invasive malaria parasites.	gliding motility in plasmodium parasites, the aetiological agents of malaria disease, is mediated by an actomyosin motor anchored in the outer pellicle of the motile cell. effective motility is dependent on a parasite myosin motor and turnover of dynamic parasite actin filaments. to date, however, the basis for directional motility is not known. whilst myosin is very likely orientated as a result of its anchorage within the parasite, how actin filaments are orientated to facilitate directional f ...	2015	26187846
intravenous artesunate reduces parasite clearance time, duration of intensive care, and hospital treatment in patients with severe malaria in europe: the tropnet severe malaria study.	intravenous artesunate improves survival in severe malaria, but clinical trial data from nonendemic countries are scarce. the tropnet severe malaria database was analyzed to compare outcomes of artesunate vs quinine treatment. artesunate reduced parasite clearance time and duration of intensive care unit and hospital treatment in european patients with imported severe malaria.	2015	26187021
a molecular survey of acute febrile illnesses reveals plasmodium vivax infections in kedougou, southeastern senegal.	control efforts towards malaria due to plasmodium falciparum significantly decreased the incidence of the disease in many endemic countries including senegal. surprisingly, in kedougou (southeastern senegal) p. falciparum malaria remains highly prevalent and the relative contribution of other plasmodium species to the global malaria burden is very poorly documented, partly due to the low sensitivity of routine diagnostic tools. molecular methods offer better estimate of circulating plasmodium sp ...	2015	26186936
comparison of two real-time pcr assays for the detection of malaria parasites from hemolytic blood samples - short communication.	we compared the performance of an in-house and a commercial malaria polymerase chain reaction (pcr) assay using freeze-thawed hemolytic blood samples. a total of 116 freeze-thawed ethylenediamine tetraacetic acid (edta) blood samples of patients with suspicion of malaria were analyzed by an in-house as well as by a commercially available real-time pcr. concordant malaria negative pcr results were reported for 39 samples and malaria-positive pcr results for 67 samples. the in-house assay further ...	2015	26185684
a crucial piece in the puzzle of the artemisinin resistance mechanism in plasmodium falciparum.	the spread of resistance of malaria infections to artemisinin is a major concern for the future. the plasmodium falciparum phosphatidylinositol-3-kinase (pfpi3k) may be a potential target of artemisinin and effector of resistance. this could be mediated by the kelch13 protein, the molecular marker of resistance that modulates pfpi3k ubiquitination.	2015	26169358
multifaceted role of heme during severe plasmodium falciparum infections in india.	several immunomodulatory factors are involved in malaria pathogenesis. among them, heme has been shown to play a role in the pathophysiology of severe malaria in rodents, but its role in human severe malaria remains unclear. circulating levels of total heme and its main scavenger, hemopexin, along with cytokine/chemokine levels and biological parameters, including hemoglobin and creatinine levels, as well as transaminase activities, were measured in the plasma of 237 plasmodium falciparum-infect ...	2015	26169278
phosphoantigen burst upon plasmodium falciparum schizont rupture can distantly activate vγ9vδ2 t cells.	malaria induces potent activation and expansion of the vγ9vδ2 subpopulation of γδt cells, which inhibit the plasmodium falciparum blood cycle through soluble cytotoxic mediators, abrogating merozoite invasion capacity. intraerythrocytic stages efficiently trigger vγ9vδ2 t-cell activation and degranulation through poorly understood mechanisms. p. falciparum blood-stage extracts are known to contain phosphoantigens able to stimulate vγ9vδ2 t cells, but how these are presented by intact infected re ...	2015	26169273
in silico attempt for adduct agent(s) against malaria: combination of chloroquine with alkaloids of adhatoda vasica.	with the aim of controlling drug resistant plasmodium falciparum, a computational attempt of designing novel adduct antimalarial drugs through the molecular docking method of combining chloroquine with five alkaloids, individually is presented. these alkaloids were obtained from the medicinal plant, adhatoda vasica. from the obtained individual docking values of important derivatives of quinine and chloroquine, as well as, individual alkaloids and adduct agents of chloroquine with adhatoda alkal ...	2015	26142781
wanted plasmodium falciparum, dead or alive.	mechanisms of cell death in unicellular parasites have been subjects of debate for the last decade, with studies demonstrating evidence of apoptosis or non-apoptosis like mechanisms, including necrosis, and autophagy. recent clarifications on the definition of regulated or accidental cell death by the nomenclature committee on cell death provides an opportunity to reanalyze some data, re-evaluate conclusions in the light of parasite diversity, and to propose alternative arguments in the context ...	2015	28357297
synthesis and antiplasmodial activity of novel chloroquine analogues with bulky basic side chains.	chloroquine is commonly used in the treatment and prevention of malaria, but plasmodium falciparum, the main species responsible for malaria-related deaths, has developed resistance against this drug. twenty-seven novel chloroquine (cq) analogues characterized by a side chain terminated with a bulky basic head group, i.e., octahydro-2h-quinolizine and 1,2,3,4,5,6-hexahydro-1,5-methano-8h-pyrido[1,2-a][1,5]diazocin-8-one, were synthesized and tested for activity against d-10 (cq-susceptible) and ...	2015	26213237
concurrent infection with dengue type 4 and plasmodium falciparum acquired in haiti.	we report one laboratory-confirmed coinfection by dengue type 4 and plasmodium falciparum imported to spain from haiti. diagnosis was made by real-time polymerase chain reaction (rt-pcr), serology, quantitative buffy coat, and thick blood smear. in areas where both infections are present, diagnosis of both diseases should be considered because a delay in the treatment of malaria could be fatal.	2015	26212051
early biting of the anopheles gambiae s.s. and its challenges to vector control using insecticide treated nets in western kenya highlands.	long term use of insecticides in malaria vector control has been shown to alter the behavior of vectors. such behavioral shifts have the potential of undermining the effectiveness of insecticide-based control interventions. the effects of insecticide treated nets (itns) use on the composition, biting/feeding and sporozoite rates of anopheles gambiae s.l. mosquitoes in musilongo village, vihiga county of western kenya highlands were investigated. adult mosquitoes were collected in selected sleepi ...	2015	26209103
coexistence of malaria and thalassemia in malaria endemic areas of thailand.	hemoglobinopathy and malaria are commonly found worldwide particularly in malaria endemic areas. thalassemia, the alteration of globin chain synthesis, has been reported to confer resistance against malaria. the prevalence of thalassemia was investigated in 101 malaria patients with plasmodium falciparum and plasmodium vivax along the thai-myanmar border to examine protective effect of thalassemia against severe malaria. hemoglobin typing was performed using low pressure liquid chromatography (l ...	2015	26174819
in vitro antiplasmodial activity of triazole-linked chloroquinoline derivatives synthesized from 7-chloro-n-(prop-2-yn-1-yl)quinolin-4-amine.	the synthesis and in vitro evaluation of novel triazole-linked chloroquinoline derivatives as potential antiplasmodial agents against plasmodium falciparum is reported. the 15 synthesized target compounds were obtained by means of a copper(i)-mediated click reaction between a variety of 1,2- and 1,3-azidoamines and 7-chloro-n-(prop-2-yn-1-yl)quinolin-4-amine in moderate to good yields (53-85%). the compounds were screened for antiplasmodial activity against nf54 chloroquine-sensitive and dd2 chl ...	2015	26174655
sero-epidemiological evaluation of plasmodium falciparum malaria in senegal.	in senegal, a significant decrease of malaria transmission intensity has been noted the last years. parasitaemia has become lower and, therefore, more difficult to detect by microscopy. in the context of submicroscopic parasitaemia, it has become relevant to rely on relevant malaria surveillance tools to better document malaria epidemiology in such settings. serological markers have been proposed as an essential tool for malaria surveillance. this study aimed to evaluate the sero-epidemiological ...	2015	26173958
comparison of genomic signatures of selection on plasmodium falciparum between different regions of a country with high malaria endemicity.	genome wide sequence analyses of malaria parasites from widely separated areas of the world have identified contrasting population structures and signatures of selection. to compare relatively closely situated but ecologically contrasting regions within an endemic african country, population samples of plasmodium falciparum clinical isolates were collected in ghana from kintampo in the central forest-savannah area, and navrongo in a drier savannah area ~350 km to the north with more seasonally-r ...	2015	26173872
a comparative study of the localization and membrane topology of members of the rifin, stevor and pfmc-2tm protein families in plasmodium falciparum-infected erythrocytes.	variant surface antigens (vsa) exposed on the membrane of plasmodium falciparum infected erythrocytes mediate immune evasion and are important pathogenicity factors in malaria disease. in addition to the well-studied pfemp1, the small vsa families rifin, stevor and pfmc-2tm are assumed to play a role in this process.	2015	26173856
200 structural insights into the theoretical model of plasmodium falciparum multi drug resistance 1 protein (pfmdr1) and its interaction with phytochemicals as efficacious antimalarial drugs: an in silico and in vitro approach.		2015	26103410
152 molten globule behavior of apicomplexan protein p2 from plasmodium falciparum and toxoplasma gondii.		2015	26103363
hemoglobin e and glucose-6-phosphate dehydrogenase deficiency and plasmodium falciparum malaria in the chittagong hill districts of bangladesh.	hemoglobin e is largely confined to south and southeast asia. the association between hemoglobin e (hbe) and malaria is less clear than that of hemoglobin s and c. as part of a malaria study in the chittagong hill districts of bangladesh, an initial random sample of 202 individuals showed that 39% and 49% of marma and khyang ethnic groups, respectively, were positive for either heterozygous or homozygous hemoglobin e. in this group, 6.4% were also found to be severely deficient and 35% mildly de ...	2015	26101273
network-based gene prediction for plasmodium falciparum malaria towards genetics-based drug discovery.	malaria is the most deadly parasitic infectious disease. existing drug treatments have limited efficacy in malaria elimination, and the complex pathogenesis of the disease is not fully understood. detecting novel malaria-associated genes not only contributes in revealing the disease pathogenesis, but also facilitates discovering new targets for anti-malaria drugs.	2015	26099491
optimization of a multi-well colorimetric assay to determine haem species in plasmodium falciparum in the presence of anti-malarials.	the activity of several well-known anti-malarials, including chloroquine (cq), is attributed to their ability to inhibit the formation of haemozoin (hz) in the malaria parasite. the formation of inert hz, or malaria pigment, from toxic haem acquired from the host red blood cell of the parasite during haemoglobin digestion represents a pathway essential for parasite survival. inhibition of this critical pathway therefore remains a desirable target for novel anti-malarials. a recent publication de ...	2015	26099266
de novo generated human red blood cells in humanized mice support plasmodium falciparum infection.	immunodeficient mouse-human chimeras provide a powerful approach to study host specific pathogens like plasmodium (p.) falciparum that causes human malaria. existing mouse models of p. falciparum infection require repeated injections of human red blood cells (rbcs). in addition, clodronate lipsomes and anti-neutrophil antibodies are injected to suppress the clearance of human rbcs by the residual immune system of the immunodeficient mice. engraftment of nod-scid il2rg-/- mice with human hematopo ...	2015	26098918
regulation of plasmodium falciparum origin recognition complex subunit 1 (pforc1) function through phosphorylation mediated by cdk-like kinase pk5.	plasmodium falciparum origin recognition complex subunit 1 (pforc1) has been implicated in dna replication and var gene regulation. while the c-terminus is involved in dna replication, the specific role of n-terminus has been suggested in var gene regulation in a sir2-dependent manner. pforc1 is localized at the nuclear periphery, where the clustering of chromosomal ends at the early stage of parasite development may be crucial for the regulation of subtelomeric var gene expression. upon disasse ...	2015	26094711
identification of the minimal binding region of a plasmodium falciparum igm binding pfemp1 domain.	binding of host immunoglobulin is a common immune evasion mechanism demonstrated by microbial pathogens. previous work showed that the malaria parasite plasmodium falciparum binds the fc-region of human igm molecules, resulting in a coating of igm on the surface of infected erythrocytes. igm binding is a property of p. falciparum strains showing virulence-related phenotypes such as erythrocyte rosetting. the parasite ligands for igm binding are members of the diverse p. falciparum erythrocyte me ...	2015	26094597
minor oxygenated cannabinoids from high potency cannabis sativa l.	nine oxygenated cannabinoids were isolated from a high potency cannabis sativa l. variety. structure elucidation was achieved using spectroscopic techniques, including 1d and 2d nmr, hrms and gc-ms. these minor compounds include four hexahydrocannabinols, four tetrahydrocannabinols, and one hydroxylated cannabinol, namely 9α-hydroxyhexahydrocannabinol, 7-oxo-9α-hydroxyhexa-hydrocannabinol, 10α-hydroxyhexahydrocannabinol, 10ar-hydroxyhexahydrocannabinol, δ(9)-thc aldehyde a, 8-oxo-δ(9)-thc, 10aα- ...	2015	26093324
computational insights into the suicide inhibition of plasmodium falciparum fk506-binding protein 35.	malaria is a parasite affecting millions of people worldwide. with the risk of malarial resistance reaching catastrophic levels, novel methods into the inhibition of this disease need to be prioritized. the exploitation of active site differences between parasitic and human peptidyl-prolyl cis/trans isomerases can be used for suicide inhibition, effectively poisoning the parasite without affecting the patient. this method of inhibition was explored using plasmodium falciparum and homo sapiens fk ...	2015	26091727
malaria in pregnancy interacts with and alters the angiogenic profiles of the placenta.	malaria in pregnancy remains a substantial public health problem in malaria-endemic areas with detrimental outcomes for both the mother and the foetus. the placental changes that lead to some of these detrimental outcomes have been studied, but the mechanisms that lead to these changes are still not fully elucidated. there is some indication that imbalances in cytokine cascades, complement activation and angiogenic dysregulation might be involved in the placental changes observed. nevertheless, ...	2015	26090803
conditional u1 gene silencing in toxoplasma gondii.	the functional characterisation of essential genes in apicomplexan parasites, such as toxoplasma gondii or plasmodium falciparum, relies on conditional mutagenesis systems. here we present a novel strategy based on u1 snrnp-mediated gene silencing. u1 snrnp is critical in pre-mrna splicing by defining the exon-intron boundaries. when a u1 recognition site is placed into the 3'-terminal exon or adjacent to the termination codon, pre-mrna is cleaved at the 3'-end and degraded, leading to an effici ...	2015	26090798
molecular-docking study of malaria drug target enzyme transketolase in plasmodium falciparum 3d7 portends the novel approach to its treatment.	malaria has been a major life threatening mosquito borne disease from long since. unavailability of any effective vaccine and recent emergence of multi drug resistant strains of malaria pathogen plasmodium falciparum continues to cause persistent deaths in the tropical and sub-tropical region. as a result, demands for new targets for more effective anti-malarial drugs are escalating. transketolase is an enzyme of the pentose phosphate pathway; a novel pathway which is involved in energy generati ...	2015	26089981
ex vivo anti-malarial drug susceptibility of plasmodium falciparum isolates from pregnant women in an area of highly seasonal transmission in burkina faso.	ex vivo assays are usually carried out on parasite isolates collected from patients with uncomplicated plasmodium falciparum malaria, from which pregnant women are usually excluded as they are often asymptomatic and with relatively low parasite densities. nevertheless, p. falciparum parasites infecting pregnant women selectively sequester in the placenta and may have a different drug sensitivity profile compared to those infecting other patients. the drug sensitivity profile of p. falciparum iso ...	2015	26088768
targeting human transmission biology for malaria elimination.	malaria remains one of the leading causes of death worldwide, despite decades of public health efforts. the recent commitment by many endemic countries to eliminate malaria marks a shift away from programs aimed at controlling disease burden towards one that emphasizes reducing transmission of the most virulent human malaria parasite, plasmodium falciparum. gametocytes, the only developmental stage of malaria parasites able to infect mosquitoes, have remained understudied, as they occur in low n ...	2015	26086192
overexpression, purification and characterisation of the plasmodium falciparum hsp70-z (pfhsp70-z) protein.	six hsp70-like genes are represented on the genome of plasmodium falciparum. of these two occur in the cytosol: p. falciparum hsp70-z (pfhsp70-z) and pfhsp70-1. pfhsp70-1 is a well characterised canonical hsp70 that facilitates protein quality control and is crucial for the development of malaria parasites. there is very little known about pfhsp70-z. however, pfhsp70-z is known to be essential and is implicated in suppressing aggregation of asparagine-rich proteins of p. falciparum. in addition, ...	2015	26083397
molecular mechanism for the thermo-sensitive phenotype of cho-mt58 cell line harbouring a mutant ctp:phosphocholine cytidylyltransferase.	control and elimination of malaria still represents a major public health challenge. emerging parasite resistance to current therapies urges development of antimalarials with novel mechanism of action. phospholipid biosynthesis of the plasmodium parasite has been validated as promising candidate antimalarial target. the most prevalent de novo pathway for synthesis of phosphatidylcholine is the kennedy pathway. its regulatory and often also rate limiting step is catalyzed by ctp:phosphocholine cy ...	2015	26083347
[plasmodium falciparum malaria and exchange transfusion application].	malaria caused by p. falciparum, is endemic in tropical and subtropical areas but is seen as sporadic cases in our country. a patient, early diagnosed and succesfully treated with antimalarial drug administration and a patient, with severe clinical manifestations and succesfully treated with antimalarial medication as well as erythrocyte exchange transfusion (eet), who were not applied chemoprophylaxis are presented. the cases are presented in order to emphasize on the necessity of giving educat ...	2015	26081890
modified quaternary ammonium salts as potential antimalarial agents.	a series of new quaternary ammonium salts containing a polyconjugated moiety has been synthesized and characterized; their biological activity as potential antimalarial agents was investigated, as well. all compounds were screened against chloroquine resistant w-2 (cq-r) and chloroquine sensitive, d-10 (cq-s) strains of plasmodium falciparum showing ic50 in the submicromolar range and low toxicity against human endothelial cells.	2015	26081764
the emerging threat of artemisinin resistance in malaria: focus on artemether-lumefantrine.	the development of artemisinin resistance in the greater mekong subregion poses a significant threat to malaria elimination. artemisinin-based combination therapies including artemether-lumefantrine (al) are recommended by who as first-line treatment for uncomplicated plasmodium falciparum malaria. this article provides a comprehensive review of the existing and latest data as a basis for interpretation of observed variability in parasite sensitivity to al over the last 5 years. clinical efficac ...	2015	26081265
slow clearance of plasmodium falciparum in severe pediatric malaria, uganda, 2011-2013.	plasmodium falciparum resistance to artemisinin derivatives is emerging in asia. we examined molecular markers of resistance in 78 children in uganda who had severe malaria and were treated with intravenous artesunate. we observed in the k13-propeller domain, a578s, a low-frequency (3/78), nonsynonymous, single-nucleotide polymorphism associated with prolonged parasite clearance.	2015	26079933
severe malaria not responsive to artemisinin derivatives in man returning from angola to vietnam.		2015	26079727
severe malaria not responsive to artemisinin derivatives in man returning from angola to vietnam.		2015	26079641
original 2-(3-alkoxy-1h-pyrazol-1-yl)azines inhibitors of human dihydroorotate dehydrogenase (dhodh).	following our discovery of human dihydroorotate dehydrogenase (dhodh) inhibition by 2-(3-alkoxy-1h-pyrazol-1-yl)pyrimidine derivatives as well as 2-(4-benzyl-3-ethoxy-5-methyl-1h-pyrazol-1-yl)-5-methylpyridine, we describe here the syntheses and evaluation of an array of azine-bearing analogues. as in our previous report, the structure-activity study of this series of human dhodh inhibitors was based on a phenotypic assay measuring measles virus replication. among other inhibitors, this round of ...	2015	26079043
anti-plasmodial activity of bradykinin and analogs.	to find effective new candidate antimalarial drugs, bradykinin and its analogs were synthesized and tested for effectiveness against plasmodium gallinaceum sporozoites and plasmodium falciparum on erythrocytes. among them, bradykinin and its p2 analog presented high activity against plasmodium gallinaceum, but they degrade in plasma. on the other hand, ri-bbki did not degrade and reached high activity. no analog was active against plasmodium falciparum.	2015	26077496
plasmodium cellular effector mechanisms and the hepatic microenvironment.	plasmodium falciparum malaria remains one of the most serious health problems globally. immunization with attenuated parasites elicits multiple cellular effector mechanisms capable of eliminating plasmodium liver stages. however, malaria liver stage (ls) immunity is complex and the mechanisms effector t cells use to locate the few infected hepatocytes in the large liver in order to kill the intracellular ls parasites remain a mystery to date. here, we review our current knowledge on the behavior ...	2015	26074888
co-evolutionary analysis implies auxiliary functions of hsp110 in plasmodium falciparum.	plasmodium falciparum encounters frequent environmental challenges during its life cycle which makes productive protein folding immensely challenging for its metastable proteome. to identify the important components of protein folding machinery involved in maintaining p. falciparum proteome, we performed a proteome-wide phylogenetic profiling across various species. we found that except hsp110, the parasite lost all other cytosolic nucleotide exchange factors essential for regulating hsp70 which ...	2015	26052682
development of a genetic tool for functional screening of anti-malarial bioactive extracts in metagenomic libraries.	the chemical treatment of plasmodium falciparum for human infections is losing efficacy each year due to the rise of resistance. one possible strategy to find novel anti-malarial drugs is to access the largest reservoir of genomic biodiversity source on earth present in metagenomes of environmental microbial communities.	2015	26040274
developing vaccines to prevent malaria in pregnant women.	placental malaria (pm) is a major public health problem that constitutes a significant health concern for the mother, and especially for the developing fetus and offspring. current means of prevention have limitations, including a restricted window of intervention that excludes the first trimester of pregnancy, and the fact that very few drugs can be used for this purpose. the identification of the var2csa antigen, specific to pm parasites, offers an excellent opportunity to develop a vaccine ag ...	2015	26051589
the evolutionary origins of southeast asian ovalocytosis.	southeast asian ovalocytosis (sao) is a common red blood cell disorder that is maintained as a balanced polymorphism in human populations. in individuals heterozygous for the sao-causing mutation there are minimal detrimental effects and well-documented protection from severe malaria caused by plasmodium vivax and plasmodium falciparum; however, the sao-causing mutation is fully lethal in utero when homozygous. the present-day high frequency of sao in island southeast asia indicates the trait is ...	2015	26047685
assessment of therapeutic efficacy and safety of artemether-lumefantrine (coartem®) in the treatment of uncomplicated plasmodium falciparum malaria patients in bahir dar district, northwest ethiopia: an observational cohort study.	malaria is a complex disease, which varies in its epidemiology and clinical manifestation. although artemether-lumefantrine has been used as first-line drug for uncomplicated plasmodium falciparum malaria in bahir dar district since 2004, its efficacy has not yet been assessed. the main objective of this study was to quantify the proportion of patients with uncomplicated falciparum malaria who were prescribed artemether-lumefantrine and who failed treatment after a 28-day follow-up.	2015	26045199
genome-wide collation of the plasmodium falciparum wdr protein superfamily reveals malarial parasite-specific features.	despite a significant drop in malaria deaths during the past decade, malaria continues to be one of the biggest health problems around the globe. wd40 repeats (wdrs) containing proteins comprise one of the largest and functionally diverse protein superfamily in eukaryotes, acting as scaffolds for assembling large protein complexes. in the present study, we report an extensive in silico analysis of the wdr gene family in human malaria parasite plasmodium falciparum. our genome-wide identification ...	2015	26043001
use of plasmodium falciparum culture-adapted field isolates for in vitro exflagellation-blocking assay.	a major requirement for malaria elimination is the development of transmission-blocking interventions. in vitro transmission-blocking bioassays currently mostly rely on the use of very few plasmodium falciparum reference laboratory strains isolated decades ago. to fill a piece of the gap between laboratory experimental models and natural systems, the purpose of this work was to determine if culture-adapted field isolates of p. falciparum are suitable for in vitro transmission-blocking bioassays ...	2015	26040313
structural basis for specific inhibition of trna synthetase by an atp competitive inhibitor.	pharmaceutical inhibitors of aminoacyl-trna synthetases demand high species and family specificity. the antimalarial atp-mimetic cladosporin selectively inhibits plasmodium falciparum lysrs (pflysrs). how the binding to a universal atp site achieves the specificity is unknown. here we report three crystal structures of cladosporin with human lysrs, pflysrs, and a pf-like human lysrs mutant. in all three structures, cladosporin occupies the class defining atp-binding pocket, replacing the adenosi ...	2015	26074468
inhaled nitric oxide as an adjunctive treatment for cerebral malaria in children: a phase ii randomized open-label clinical trial.	background. children with cerebral malaria (cm) have high rates of mortality and neurologic sequelae. nitric oxide (no) metabolite levels in plasma and urine are reduced in cm. methods. this randomized trial assessed the efficacy of inhaled no versus nitrogen (n2) as an adjunctive treatment for cm patients receiving intravenous artesunate. we hypothesized that patients treated with no would have a greater increase of the malaria biomarker, plasma angiopoietin-1 (ang-1) after 48 hours of treatm ...	2015	26309894
is asymptomatic malaria really asymptomatic? hematological, vascular and inflammatory effects of asymptomatic malaria parasitemia.	asymptomatic malaria infections are highly prevalent in malaria endemic regions and most of these infections remain undiagnosed and untreated. whereas conventional malaria symptoms are by definition absent, little is known on the more subtle health consequences of these infections. the aim of our study was to analyze the hematologic, vascular and inflammatory effects of patent and subpatent asymptomatic malaria parasitemia in children and adults on the indonesian island sumba. both children and ...	2015	26304688
artemisinin resistance at the china-myanmar border and association with mutations in the k13 propeller gene.	artemisinin resistance in plasmodium falciparum parasites in southeast asia is a major concern for malaria control. its emergence at the china-myanmar border, where there have been more than 3 decades of artemisinin use, has yet to be investigated. here, we comprehensively evaluated the potential emergence of artemisinin resistance and antimalarial drug resistance status in p. falciparum using data and parasites from three previous efficacy studies in this region. these efficacy studies of dihyd ...	2015	26324266
[microbiological diagnosis of imported malaria].	current diagnosis of malaria is based on the combined and sequential use of rapid antigen detection tests (rdt) of plasmodium and subsequent visualization of the parasite stained with giemsa solution in a thin and thick blood smears. if an expert microscopist is not available, should always be a sensitive rdt to rule out infection by plasmodium falciparum, output the result immediately and prepare thick smears (air dried) and thin extensions (fixed with methanol) for subsequent staining and revi ...	2015	26320995
antiplasmodial and cytotoxic activities of the constituents of turraea robusta and turraea nilotica.	turraea robusta and turraea nilotica are african medicinal plants used for the treatment of a wide variety of diseases, including malaria. the genus turraea is rich in limonoids and other triterpenoids known to possess various biological activities.	2015	26320684
emergence of sulfadoxine-pyrimethamine resistance in indian isolates of plasmodium falciparum in the last two decades.	genotyping the sulfadoxine-pyrimethamine (sp) genes will help in identifying the genes under drug selection and the emergence of resistance in dhfr and dhps genes. india is an important hotspot for studying malaria due to the immense climatic diversity prevalent in the country. the central and eastern parts of the country are most vulnerable sites where malaria cases are reported throughout the year. from different regions of the country 173 field isolates were genotyped at various loci in dhfr ...	2015	26319997
positive selection underlies the species-specific binding of plasmodium falciparum rh5 to human basigin.	plasmodium falciparum, the causative agent of the deadliest form of malaria, is a member of the laverania subgenus, which includes ape-infecting parasites. p. falciparum is thought to have originated in gorillas, although infection is now restricted to humans. laverania parasites display remarkable host-specificity, which is partially mediated by the interaction between parasite ligands and host receptors. we analyse the evolution of bsg (basigin) and gypa (glycophorin a) in primates/hominins, a ...	2015	26302433
interplay between the hinge region of iron sulphur protein and the qo site in the bc1 complex - analysis of plasmodium-like mutations in the yeast enzyme.	the respiratory chain bc1 complex is central to mitochondrial bioenergetics and the target of antiprotozoals. we characterized a modified yeast bc1 complex that more closely resemble plasmodium falciparum enzyme. the mutant version was generated by replacing ten cytochrome b qo site residues by p. falciparum equivalents. the plasmodium-like changes caused a major dysfunction of the catalytic mechanism of the bc1 complex resulting in superoxide overproduction and respiratory growth defect. the de ...	2015	26301481
andrographolide effect on both plasmodium falciparum infected and non infected rbcs membranes.	to explore whether its antiplasmodium effect of andrographolide is attributed to its plausible effect on the plasma membrane of both plasmodium falciparum infected and non-infected rbcs.	2015	26276279
plasmodium falciparum gametocyte-specific antibody profiling reveals boosting through natural infection and identifies potential markers of gametocyte exposure.	malaria elimination efforts would benefit from vaccines that block transmission of plasmodium falciparum gametocytes from humans to mosquitoes. a clear understanding of gametocyte-specific antibody responses in exposed populations could help determine whether transmission-blocking vaccines (tbv) would be boosted by natural gametocyte exposure, and also inform the development of serologic tools to monitor gametocyte exposure in populations targeted for malaria elimination. to this end, plasma was ...	2015	26283330
sleeping on the floor decreases insecticide treated bed net use and increases risk of malaria in children under 5 years of age in mbita district, kenya.	children who sleep on the floor are less likely to use long-lasting insecticidal nets (llins); however, the relationship between sleeping location and plasmodium falciparum infection has not been investigated sufficiently. this study revealed whether sleeping location (bed vs floor) is associated with p. falciparum infection among children 7-59 months old. more than 60% of children slept on the floor. younger children were significantly more likely to sleep in beds [odds ratio, or 2.31 (95% conf ...	2015	26282826
malaria-associated morbidity during the rainy season in saharan and sahelian zones in mauritania.	reliable epidemiological data based on laboratory-confirmed cases are scarce in mauritania. a large majority of reported malaria cases are based on presumptive clinical diagnosis. the present study was conducted to establish a reliable database on malaria morbidity among febrile paediatric and adult patients consulting spontaneously at public health facilities in nouakchott, situated in the saharan zone, and in hodh elgharbi region in the sahelian zone in south-east mauritania during the peak tr ...	2015	26276697
plasmodium infection promotes genomic instability and aid-dependent b cell lymphoma.	chronic infection with plasmodium falciparum was epidemiologically associated with endemic burkitt's lymphoma, a mature b cell cancer characterized by chromosome translocation between the c-myc oncogene and igh, over 50 years ago. whether infection promotes b cell lymphoma, and if so by which mechanism, remains unknown. to investigate the relationship between parasitic disease and lymphomagenesis, we used plasmodium chabaudi (pc) to produce chronic malaria infection in mice. pc induces prolonged ...	2015	26276629
comparison between flow cytometry, microscopy, and lactate dehydrogenase-based enzyme-linked immunosorbent assay for plasmodium falciparum drug susceptibility testing under field conditions.	flow cytometry is an objective method for conducting in vitro antimalarial sensitivity assays with increasing potential for application in field sites. we examined in vitro susceptibility to seven anti-malarial drugs for 40 fresh p. falciparum field isolates via a flow cytometry method (fcm), a colorimetric ldh-based elisa : deli), and standard microscopic slide analysis of growth. for fcm, 184/280 (66%) assays met analytical acceptance criteria, compared to 166/280 (59%) for deli. there was goo ...	2015	26269616
survival analysis of diagnostic assays in plasmodium falciparum malaria.	rapid diagnostic tests (rdt) and real-time pcr (qpcr) assays are sensitive for diagnosing malaria, but because they detect antigen and dna, respectively, positivity may not reflect active infection. performance characteristics of rdt and qpcr in plasmodium falciparum positive specimens were evaluated over time to elucidate duration of positivity following conversion to microscopy negative.	2015	26377580
surveillance for the safety and effectiveness of artemether-lumefantrine in patients with uncomplicated plasmodium falciparum malaria in the usa: a descriptive analysis.	data from clinical studies show that artemether-lumefantrine (al) is effective and well tolerated in adults and children with uncomplicated plasmodium falciparum malaria. however, data on effectiveness and safety of al in patients in non-endemic settings are limited.	2015	26377423
absence of association between plasmodium falciparum small sub-unit ribosomal rna gene mutations and in vitro decreased susceptibility to doxycycline.	doxycycline is an antibiotic used in combination with quinine or artesunate for malaria treatment or alone for malaria chemoprophylaxis. recently, one prophylactic failure has been reported, and several studies have highlighted in vitro doxycycline decreased susceptibility in plasmodium falciparum isolates from different areas. the genetic markers that contribute to detecting and monitoring the susceptibility of p. falciparum to doxycycline, the pfmdt and pftetq genes, have recently been identif ...	2015	26377329
falciparum malaria molecular drug resistance in the democratic republic of congo: a systematic review.	malaria cases were estimated to 207 million in 2013. one of the problems of malaria control is the emergence and spread of plasmodium falciparum strains that become resistant to almost all drugs available. monitoring drug resistance is essential for early detection and subsequent prevention of the spread of drug resistance by timely changes of treatment policy. this review was performed to gather all data available on p. falciparum molecular resistance in dr congo, as baseline for future assessm ...	2015	26376639
evidence that the malaria parasite plasmodium falciparum putative rhoptry protein 2 localizes to the golgi apparatus throughout the erythrocytic cycle.	invasion of a red blood cell by plasmodium falciparum merozoites is an essential step in the malaria lifecycle. several of the proteins involved in this process are stored in the apical complex of the merozoite, a structure containing secretory organelles that are released at specific times during invasion. the molecular players involved in erythrocyte invasion thus represent potential key targets for both therapeutic and vaccine-based strategies to block parasite development. in our quest to id ...	2015	26375591
the effect of malaria control on plasmodium falciparum in africa between 2000 and 2015.	since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-saharan africa. understanding the effect of this control effort is vital to inform future control planning. however, the effect of malaria interventions across the varied epidemiological settings of africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. here we link a large da ...	2015	26375008
standardization of the antibody-dependent respiratory burst assay with human neutrophils and plasmodium falciparum malaria.	the assessment of naturally-acquired and vaccine-induced immunity to blood-stage plasmodium falciparum malaria is of long-standing interest. however, the field has suffered from a paucity of in vitro assays that reproducibly measure the anti-parasitic activity induced by antibodies in conjunction with immune cells. here we optimize the antibody-dependent respiratory burst (adrb) assay, which assesses the ability of antibodies to activate the release of reactive oxygen species from human neutroph ...	2015	26373337
efficacy and safety of artesunate-amodiaquine versus artemether-lumefantrine in the treatment of uncomplicated plasmodium falciparum malaria in sentinel sites across côte d'ivoire.	two years after the introduction of free artesunate-amodiaquine (asaq) and artemether-lumefantrine (al) for the treatment of uncomplicated malaria in public health facilities in côte d'ivoire, we carried out this study to compare their efficacy and tolerability in three surveillance sites. it was a multicentre open randomised clinical trial of 3-day asaq treatment against al for the treatment of 2 parallel groups of patients aged 2 years and above. the endpoints were (1) adequate clinical and pa ...	2015	26347849
synthesis, characterization and in vitro evaluation of novel enantiomerically-pure sulphonamide antimalarials.	malaria parasites are currently gaining drug-resistance rapidly, across countries and continents. hence, the discovery and development of novel chemical scaffolds, with superior antimalarial activity remain an important priority, for the developing world. our report describes the development, characterization and evaluation of novel bepotastine-based sulphonamide antimalarials inhibiting asexual stage development of plasmodium falciparum parasites in vitro. the screening results showed potent in ...	2015	26347024
discovery of a selective, safe and novel anti-malarial compound with activity against chloroquine resistant strain of plasmodium falciparum.	in recent years the dna minor groove has attracted much attention for the development of anti-malarial agents. in view of this we have attempted to discover novel dna minor groove binders through in-silico and in-vitro workflow. a rigorously validated pharmacophore model comprising of two positive ionizable (pi), one hydrophobic (hy) and one ring aromatic (ra) features was used to mine nci chemical compound database. this led to retrieval of many hits which were screened on the basis of estimate ...	2015	26346444
clinical determinants of early parasitological response to acts in african patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data.	artemisinin-resistant plasmodium falciparum has emerged in the greater mekong sub-region and poses a major global public health threat. slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. this study was designed to establish the baseline values for clearance in patients from sub-saharan african countries with uncomplicated malaria treated with artemisinin-based combination therapies (acts).	2015	26343145
ferroquine and artesunate in african adults and children with plasmodium falciparum malaria: a phase 2, multicentre, randomised, double-blind, dose-ranging, non-inferiority study.	artemisinin-based combination therapies (acts) are the recommended first-line treatment for uncomplicated plasmodium falciparum malaria. ferroquine is a new combination partner for fast-acting acts such as artesunate. we aimed to assess different doses of ferroquine in combination with artesunate against uncomplicated p falciparum malaria in a heterogeneous population in africa.	2015	26342427
profiling the essential nature of lipid metabolism in asexual blood and gametocyte stages of plasmodium falciparum.	during its life cycle, plasmodium falciparum undergoes rapid proliferation fueled by de novo synthesis and acquisition of host cell lipids. consistent with this essential role, plasmodium lipid synthesis enzymes are emerging as potential drug targets. to explore their broader potential for therapeutic interventions, we assayed the global lipid landscape during p. falciparum sexual and asexual blood stage (abs) development. using liquid chromatography-mass spectrometry, we analyzed 304 lipids con ...	2015	26355219
cluster of imported vivax malaria in travelers returning from peru.	we report a cluster of imported vivax malaria in three of five chilean travelers returning from peru in march 2015. the cluster highlights the high risk of malaria in the loreto region in northern peru, which includes popular destinations for international nature and adventure tourism. according to local surveillance data, plasmodium vivax is predominating, but plasmodium falciparum is also present, and the incidence of both species has increased during recent years. travelers visiting this regi ...	2015	26354673
immunogenicity of the rts,s/as01 malaria vaccine and implications for duration of vaccine efficacy: secondary analysis of data from a phase 3 randomised controlled trial.	the rts,s/as01 malaria vaccine targets the circumsporozoite protein, inducing antibodies associated with the prevention of plasmodium falciparum infection. we assessed the association between anti-circumsporozoite antibody titres and the magnitude and duration of vaccine efficacy using data from a phase 3 trial done between 2009 and 2014.	2015	26342424
escape of pathogens from the host immune response by mutations and mimicry. possible means to improve vaccine performance.	the ability of certain pathogens, such as human immunodeficiency, hepatitis c, herpes simplex, influenza viruses, plasmodium falciparum, etc., to escape from host immune response is generally ascribed to high mutation rate of their genome. we challenge this assumption and propose that molecular mimicry of host antigens by these pathogens could also participate to this resistance. several studies show that there is no correlation between the mutation rate value of a pathogen and the possibility t ...	2015	26341417
sequence-specific recognition of dna minor groove by an nir-fluorescence switch-on probe and its potential applications.	in molecular biology, understanding the functional and structural aspects of dna requires sequence-specific dna binding probes. especially, sequence-specific fluorescence probes offer the advantage of real-time monitoring of the conformational and structural reorganization of dna in living cells. herein, we designed a new class of d2a (one-donor-two-acceptor) near-infrared (nir) fluorescence switch-on probe named quinone cyanine-dithiazole ( qcy-dt: ) based on the distinctive internal charge tra ...	2015	26350219
two of a kind--the biosynthetic pathways of chlorotonil and anthracimycin.	chlorotonil a is a novel polyketide isolated from the myxobacterium sorangium cellulosum so ce1525 that features a unique gem-dichloro-1,3-dione moiety. it exhibits potent bioactivity, most notably against the problematic malaria pathogen plasmodium falciparum in the nanomolar range. in addition, strong antibacterial and moderate antifungal activity were determined. the outstanding biological activity of chlorotonil a as well as its unusual chemical structure triggered our interest in elucidatin ...	2015	26348978
liposomes loaded with p. falciparum merozoite-derived proteins are highly immunogenic and produce invasion-inhibiting and anti-toxin antibodies.	the formulation of an effective vaccine against malaria is still a significant challenge and the induction of high anti-parasite antibody titers plus a sustained t cell response is mandatory for the success of such a vaccine. we have developed a nanoliposome-based structure which contains plasma membrane-associated proteins (pfmnp) of plasmodium falciparum merozoites on its surface. incorporation of parasite-derived proteins led to a significant increase in the size and dispersity of particles. ...	2015	26334481
correction: phase i clinical trial of a recombinant blood stage vaccine candidate for plasmodium falciparum malaria based on msp1 and eba175.	[this corrects the article doi: 10.1371/journal.pone.0117820.].	2015	26332825
cap-domain closure enables diverse substrate recognition by the c2-type haloacid dehalogenase-like sugar phosphatase plasmodium falciparum had1.	haloacid dehalogenases (hads) are a large enzyme superfamily of more than 500,000 members with roles in numerous metabolic pathways. plasmodium falciparum had1 (pfhad1) is a sugar phosphatase that regulates the methylerythritol phosphate (mep) pathway for isoprenoid synthesis in malaria parasites. however, the structural determinants for diverse substrate recognition by hads are unknown. here, crystal structures were determined of pfhad1 in complex with three sugar phosphates selected from a pan ...	2015	26327372
the influence of sub-unit composition and expression system on the functional antibody response in the development of a var2csa based plasmodium falciparum placental malaria vaccine.	the disease caused by plasmodium falciparum (pf) involves different clinical manifestations that, cumulatively, kill hundreds of thousands every year. placental malaria (pm) is one such manifestation in which pf infected erythrocytes (ie) bind to chondroitin sulphate a (csa) through expression of var2csa, a parasite-derived antigen. protection against pm is mediated by antibodies that inhibit binding of ie in the placental intervillous space. var2csa is a large antigen incompatible with large sc ...	2015	26327283
molecular mutation profile of pfcrt and pfmdr1 in plasmodium falciparum isolates from bioko island, equatorial guinea.	antimalarial drug resistance is a primary public health problem. haplotypes of pfcrt and pfmdr1 gene have been implicated to be molecular markers of chloroquine (cq) resistance. this study aims to explore mutation distribution of pfcrt and pfmdr1 in bioko island, equatorial guinea (eg).	2015	26325683
influence of malaria transmission intensity and the 581g mutation on the efficacy of intermittent preventive treatment in pregnancy: systematic review and meta-analysis.	to estimate where intermittent preventive treatment (iptp) using sulphadoxine-pyrimethamine (sp) could be withdrawn as an intervention due to declining malaria transmission intensity, or due to increasing prevalence of the plasmodium falciparum dihydropteroate synthetase resistance mutation at codon 581g.	2015	26325263