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immunodominance of adenovirus-derived cd8(+) t cell epitopes interferes with the induction of transgene-specific immunity in adenovirus-based immunization.adenovirus (ad)-based immunization is a popular approach in vaccine development, and ad-based vectors are renowned for their potential to induce strong cd8(+) t cell responses to the encoded transgene. surprisingly, we found before in the mouse friend retrovirus (fv) model that ad-based immunization did not induce cd8(+) t cell responses to the fv leader-gag-derived immunodominant epitope gagl85-93 we show now that induction of gagl85-93-specific cd8(+) t cells was highly effective when leader-g ...201728768877
iron is a substrate of the plasmodium falciparum chloroquine resistance transporter pfcrt in xenopus oocytes.the chloroquine resistance transporter of the human malaria parasite plasmodium falciparum, pfcrt, is an important determinant of resistance to several quinoline and quinoline-like antimalarial drugs. pfcrt also plays an essential role in the physiology of the parasite during development inside erythrocytes. however, the function of this transporter besides its role in drug resistance is still unclear. using electrophysiological and flux experiments conducted on pfcrtexpressing xenopus laevis oo ...201728768767
evaluation of antiplasmodial properties of a cyanobacterium, spirulina platensis and its mechanism of action.the rapid emergence of antimalarial drug resistance necessitates a continual effort on novel drug discovery. a cyanobacterium, spirulina platensis, is a potential antimalarial agent that has been widely consumed as food supplement in the form of crude extract. it is known to possess antiviral, antibacterial and antifungi activities. this study examined the antimalarial activities of several spirulina formulas against plasmodium falciparum 3d7, in vitro. the tested spirulina formulas included com ...201728768428
bifurcatriol, a new antiprotozoal acyclic diterpene from the brown alga bifurcaria bifurcata.linear diterpenes that are commonly found in brown algae are of high chemotaxonomic and ecological importance. this study reports bifurcatriol (1), a new linear diterpene featuring two stereogenic centers isolated from the irish brown alga bifurcariabifurcata. the gross structure of this new natural product was elucidated based on its spectroscopic data (ir, 1d and 2d-nmr, hrms). its absolute configuration was identified by experimental and computational vibrational circular dichroism (vcd) spec ...201728767061
a longitudinal cohort study of malaria exposure and changing serostatus in a malaria endemic area of rural tanzania.measurements of anti-malarial antibodies are increasingly used as a proxy of transmission intensity. most serological surveys are based on the use of cross-sectional data that, when age-stratified, approximates historical patterns of transmission within a population. comparatively few studies leverage longitudinal data to explicitly relate individual infection events with subsequent antibody responses.201728764717
norepinephrine alkaloids as antiplasmodial agents: synthesis of syncarpamide and insight into the structure-activity relationships of its analogues as antiplasmodial agents.syncarpamide 1, a norepinephrine alkaloid isolated from the leaves of zanthoxylum syncarpum (rutaceae) exhibited promising antiplasmodial activities against plasmodium falciparum with reported ic50 values of 2.04 μm (d6 clone), 3.06 μm (w2 clone) and observed by us 3.90 μm (3d7 clone) and 2.56 μm (k1 clone). in continuation of our work on naturally occurring antimalarial compounds, synthesis of syncarpamide 1 and its enantiomer, (r)-2 using sharpless asymmetric dihydroxylation as a key step has ...201728763644
development of novel peptide-based michael acceptors targeting rhodesain and falcipain-2 for the treatment of neglected tropical diseases (ntds).this paper describes the development of a class of peptide-based inhibitors as novel antitrypanosomal and antimalarial agents. the inhibitors are based on a characteristic peptide sequence for the inhibition of the cysteine proteases rhodesain of trypanosoma brucei rhodesiense and falcipain-2 of plasmodium falciparum. we exploited the reactivity of novel unsaturated electrophilic functions such as vinyl-sulfones, -ketones, -esters, and -nitriles. the michael acceptors inhibited both rhodesain an ...201728763614
genetic evidence for erythrocyte receptor glycophorin b expression levels defining a dominant plasmodium falciparum invasion pathway into human erythrocytes.plasmodium falciparum, the parasite that causes the deadliest form of malaria, has evolved multiple proteins known as invasion ligands that bind to specific erythrocyte receptors to facilitate invasion of human erythrocytes. the eba-175/glycophorin a (gpa) and rh5/basigin ligand-receptor interactions, referred to as invasion pathways, have been the subject of intense study. in this study, we focused on the lesser characterized sialic acid-containing receptors glycophorin b (gpb) and glycophorin ...201728760933
preliminary efficacy investigations of oral fipronil against anopheles arabiensis when administered to zebu cattle (bos indicus) under field conditions.globally, malaria remains one of the most important vector-borne diseases despite the extensive use of vector control, including indoor residual spraying (irs) and insecticide-treated nets (itns). these control methods target endophagic vectors, whereas some malaria vectors, such as anopheles arabiensis, preferentially feed outdoors on cattle, making it a complicated vector to control using conventional strategies. our study evaluated whether treating cattle with a capsule containing the active ...201728760483
t-dependent b cell responses to plasmodium induce antibodies that form a high-avidity multivalent complex with the circumsporozoite protein.the repeat region of the plasmodium falciparum circumsporozoite protein (csp) is a major vaccine antigen because it can be targeted by parasite neutralizing antibodies; however, little is known about this interaction. we used isothermal titration calorimetry, x-ray crystallography and mutagenesis-validated modeling to analyze the binding of a murine neutralizing antibody to plasmodium falciparum csp. strikingly, we found that the repeat region of csp is bound by multiple antibodies. this repeati ...201728759640
proteogenomic analysis of the total and surface-exposed proteomes of plasmodium vivax salivary gland sporozoites.plasmodium falciparum and plasmodium vivax cause the majority of human malaria cases. research efforts predominantly focus on p. falciparum because of the clinical severity of infection and associated mortality rates. however, p. vivax malaria affects more people in a wider global range. furthermore, unlike p. falciparum, p. vivax can persist in the liver as dormant hypnozoites that can be activated weeks to years after primary infection, causing relapse of symptomatic blood stages. this feature ...201728759593
genome-wide diversity and differentiation in new world populations of the human malaria parasite plasmodium vivax.the americas were the last continent colonized by humans carrying malaria parasites. plasmodium falciparum from the new world shows very little genetic diversity and greater linkage disequilibrium, compared with its african counterparts, and is clearly subdivided into local, highly divergent populations. however, limited available data have revealed extensive genetic diversity in american populations of another major human malaria parasite, p. vivax.201728759591
prevalence, risk factors, and antimalarial resistance patterns of falciparum plasmodiasis among pregnant women in kaduna metropolis, nigeria.pregnant women infected with malaria represent a significant obstetric problem, especially in the face of antimalarial resistance. this cross-sectional study investigated the prevalence of malaria parasitemia, associated risk factors as well as the antimalarial resistance pattern of plasmodium isolates from pregnant women attending four selected secondary health facilities in kaduna state, nigeria.201728757774
plasmodium falciparum exflagellation in a patient with ovalocytosis. 201728755738
an in silico strategy for identification of novel drug targets against plasmodium falciparum.the apicomplexan parasite plasmodium falciparum is responsible for global malaria burden. with the reported resistance to artemisinin chemotherapy, there is an urgent need to maintain early phase drug discovery and identify novel drug targets for successful eradication of the pathogen from the host. in our previous work on comparative genomics study for identification of putative essential genes and therapeutic candidates in p. falciparum, we predicted 11 proteins as anti-malarial drug targets f ...201728755265
synergistic blending of high-valued heterocycles inhibits growth of plasmodium falciparum in culture and p. berghei infection in mouse model.a series of phthalimide analogues, novelized with high-valued bioactive scaffolds was synthesized by means of click-chemistry under non-conventional microwave heating and evaluated as noteworthy growth inhibitors of plasmodium falciparum (3d7 and w2) in culture. analogues 6a, 6h and 6 u showed highest activity to inhibit the growth of the parasite with ic50 values in submicromolar range. structure-activity correlation indicated the necessity of unsubstituted triazoles and leucine linker to obtai ...201728751747
the n-terminal extension of the p. falciparum gbp130 signal peptide is irrelevant for signal sequence function.the malaria parasite p. falciparum exports a large number of proteins to its host cell, the mature human erythrocyte. although the function of the majority of these proteins is not well understood, many exported proteins appear to play a role in modification of the erythrocyte following invasion. protein export to the erythrocyte is a secretory process that begins with entry to the endoplasmic reticulum. for most exported proteins, this step is mediated by hydrophobic signal peptides found towar ...201728750796
population-level estimates of the proportion of plasmodium vivax blood-stage infections attributable to relapses among febrile patients attending adama malaria diagnostic centre, east shoa zone, oromia, ethiopia.malaria is ranked as the leading communicable disease in ethiopia, where plasmodium falciparum and plasmodium vivax are co-endemic. the incidence of p. vivax is usually considered to be less seasonal than p. falciparum. clinical cases of symptomatic p. falciparum exhibit notable seasonal variation, driven by rainfall-dependent variation in the abundance of anopheles mosquitoes. a similar peak of clinical cases of p. vivax is usually observed during the rainy season. however, the ability of p. vi ...201728750669
plasmodium vivax infections over 3 years in duffy blood group negative malians in bandiagara, mali.plasmodium vivax was thought to infect only the erythrocytes of duffy blood group positive people. in the last decade, p. vivax has appeared throughout africa, both in areas where duffy positive and negative people live side by side as in madagascar and ethiopia and in areas where people are primarily duffy negative, such as in western kenya. we performed quantitative polymerase chain reaction on blood samples dried onto filter paper to determine the prevalence of p. vivax and plasmodium falcipa ...201728749772
molecular characterization of a cluster of imported malaria cases in puerto rico.the caribbean island of hispaniola is targeted for malaria elimination. currently, this is the only island with ongoing transmission of malaria in the caribbean. in 2015, six patients from puerto rico and one from massachusetts, who traveled to punta cana, dominican republic, were confirmed to be infected with plasmodium falciparum. additional molecular analysis was performed at the centers for disease control and prevention to characterize the drug-resistant alleles and plasmodium population ge ...201728749761
efficacy of different primaquine regimens to control plasmodium falciparum gametocytemia in colombia.treatment against plasmodium falciparum malaria includes blood schizonticides to clear asexual parasites responsible for disease. the addition of gametocytocidal drugs can eliminate infectious sexual stages with potential for transmission and the world health organization recommends a single dose (sd) of primaquine (pq) to this end. the efficacy of pq at 0.75 mg/kg to suppress gametocytemia when administered in single or fractionated doses was evaluated. a clinical controlled study with an open- ...201728749756
hiv-malaria interactions in north-east india: a prospective cohort study.the interactions between hiv and malaria co-infection have been shown to influence each other in their clinical outcomes in sub-saharan africa. this study was carried out in the two states of north east india endemic for both hiv and malaria infections, to study the interactions between the two diseases in the hiv-infected population.201728749403
effect of l-arginine on the growth of plasmodium falciparum and immune modulation of host cells.malaria is a life-threatening disease caused by plasmodium parasites. the life-cycle of plasmodium species involves several stages both in mosquito and the vertebrate host. in the erythrocytic stage, plasmodium resides inside the red blood cells (rbcs), where it meets most of its nutritional requirement by degrad- ing host's haemoglobin. l-arginine is required for growth and division of cells. the present study was aimed to demonstrate the effect of supplementation of different concentrations of ...201728748834
antiplasmodial activity and cytotoxicity of ethanol extract of zea mays root.zea mays root decoction that has been traditionally used for the treatment of malaria by various tribes in nigeria, was evaluated for antimalarial potential against malaria parasites using in vivo and in vitro models.201728748174
return of chloroquine sensitivity to africa? surveillance of african plasmodium falciparum chloroquine resistance through malaria imported to china.chloroquine (cq) was the cornerstone of anti-malarial treatment in africa for almost 50 years, but has been widely withdrawn due to the emergence and spread of resistance. recent reports have suggested that cq-susceptibility may return following the cessation of cq usage. here, we monitor cq sensitivity and determine the prevalence of genetic polymorphisms in the cq resistance transporter gene (pfcrt) of plasmodium falciparum isolates recently imported from africa to china.201728747223
malaria epidemiology in low-endemicity areas of the northern coast of ecuador: high prevalence of asymptomatic infections.the recent scale-up in malaria control measures in latin america has resulted in a significant decrease in the number of reported cases in several countries including ecuador, where it presented a low malaria incidence in recent years (558 reported cases in 2015) with occasional outbreaks of both plasmodium falciparum and plasmodium vivax in the coastal and amazonian regions. this success in malaria control in recent years has led ecuador to transition its malaria policy from control to eliminat ...201728747199
biophysical characterization of the calmodulin-like domain of plasmodium falciparum calcium dependent protein kinase 3.calcium dependent protein kinases are unique to plants and certain parasites and comprise an n-terminal segment and a kinase domain that is regulated by a c-terminal calcium binding domain. since the proteins are not found in man they are potential drug targets. we have characterized the calcium binding lobes of the regulatory domain of calcium dependent protein kinase 3 from the malaria parasite plasmodium falciparum. despite being structurally similar, the two lobes differ in several other reg ...201728746405
transmission dynamics of co-endemic plasmodium vivax and p. falciparum in ethiopia and prevalence of antimalarial resistant genotypes.ethiopia is one of the few african countries where plasmodium vivax is co-endemic with p. falciparum. malaria transmission is seasonal and transmission intensity varies mainly by landscape and climate. although the recent emergence of drug resistant parasites presents a major issue to malaria control in ethiopia, little is known about the transmission pathways of parasite species and prevalence of resistant markers. this study used microsatellites to determine population diversity and gene flow ...201728746333
synthesis and antimalarial activity of new enantiopure aminoalcoholpyrrolo[1,2-a]quinoxalines.backgroung: we prepared a novel series of enantiopure mefloquine analogues with pyrrolo[1,2-a]quinoxaline core in order to fight plasmodium falciparum resistant strain.201728745231
multiplication rate variation in the human malaria parasite plasmodium falciparum.it is important to understand intrinsic variation in asexual blood stage multiplication rates of the most virulent human malaria parasite, plasmodium falciparum. here, multiplication rates of long-term laboratory adapted parasite clones and new clinical isolates were measured, using a newly standardised assay of growth from low starting density in replicate parallel cultures with erythrocytes from multiple different donors, across multiple cycles. multiplication rates of long-term established cl ...201728743888
non-falciparum malaria imported mainly from africa: a review from a portuguese hospital.non-falciparum malaria (nfm) has been reported to be responsible for around 25% of imported malaria cases in europe but is often neglected due to its less severe clinical course when compared to plasmodium falciparum. differentiation between species is however crucial for a correct approach. the objective of this study is to report the cases of this often missed aetiology of malaria in a tertiary hospital in portugal.201728743266
challenges to replace act as first-line drug.the spread of artemisinin and partner drug resistance through asia requires changes in first-line therapy. the traditional modus has been the replacement of one first-line anti-malarial regimen with another. the number of anti-malarial drug candidates currently in development may have given false confidence in the expectation that resistance to artemisinin-based combination therapy (act) can be solved with a switch to the next anti-malarial drug regimen. a number of promising anti-malarial drug ...201728738892
terpenoids from the oleo-gum-resin of boswellia serrata and their antiplasmodial effects in vitro.in the course of our ongoing search for new natural products as leads against protozoal diseases, the dichloromethane extract of indian frankincense, the oleo-gum-resin obtained from boswellia serrata, showed in vitro activity against plasmodium falciparum. bioactivity-guided fractionation led to the isolation of eight diterpenes: (1s,3e,7e,11r)-verticilla-3,7,12(18)-triene (1), cembrene a (2), serratol (3), 1s,3e,7r,8r,11e-7,8-epoxy-cembra-3,11-dien-1-ol (4), incensole oxide (5), rel (1s,3r,7e, ...201728738439
plasmodium falciparum in vitro continuous culture conditions: a comparison of parasite susceptibility and tolerance to anti-malarial drugs throughout the asexual intra-erythrocytic life cycle.the continuous culture of plasmodium falciparum is often seen as a means to an end, that end being to probe the biology of the parasite in question, and ultimately for many in the malaria drug discovery arena, to identify means of killing the parasite in order to treat malaria. in vitro continuous culture of plasmodium falciparum is a fundamental requirement when undertaking malaria research where the primary objectives utilise viable parasites of a desired lifecycle stage. this investigation, a ...201728738214
malaria parasite proteins involved in nutrient channels at the host erythrocyte membrane: advances and questions for future research.erythrocytes infected malaria parasites have increased permeability to nutrients and other solutes, as mediated by an unusual ion channel known as the plasmodial surface anion channel (psac). although the increased permeability of infected erythrocytes was identified more than 70 years ago and subsequently characterized with tracer studies, its mechanism and role in parasite biology remained unclear until the introduction of patch-clamp methods and high-throughput screening technologies. these m ...201728736757
synthesis of a bicyclic azetidine with in vivo antimalarial activity enabled by stereospecific, directed c(sp(3))-h arylation.the development of new antimalarial therapeutics is necessary to address the increasing resistance to current drugs. bicyclic azetidines targeting plasmodium falciparum phenylalanyl-trna synthetase comprise one promising new class of antimalarials, especially due to their activities against three stages of the parasite's life cycle, but a lengthy synthetic route to these compounds may affect the feasibility of delivering new therapeutic agents within the cost constraints of antimalarial drugs. h ...201728732448
the exported chaperone hsp70-x supports virulence functions for plasmodium falciparum blood stage parasites.malaria is caused by five different plasmodium spp. in humans each of which modifies the host erythrocyte to survive and replicate. the two main causes of malaria, p. falciparum and p. vivax, differ in their ability to cause severe disease, mainly due to differences in the cytoadhesion of infected erythrocytes (ie) in the microvasculature. cytoadhesion of p. falciparum in the brain leads to a large number of deaths each year and is a consequence of exported parasite proteins, some of which modif ...201728732045
plasmodium berghei p47 is essential for ookinete protection from the anopheles gambiae complement-like response.malaria is a mosquito-borne disease affecting millions of people every year. the rodent parasite plasmodium berghei has served as a model for human malaria transmission studies and played a pivotal role in dissecting the mosquito immune response against infection. the 6-cysteine protein p47, known to be important for p. berghei female gamete fertility, is shown to serve a different function in plasmodium falciparum, protecting ookinetes from the mosquito immune response. here, we investigate the ...201728729672
a mechanistic model quantifies artemisinin-induced parasite growth retardation in blood-stage plasmodium falciparum infection.falciparum malaria is a major parasitic disease causing widespread morbidity and mortality globally. artemisinin derivatives-the most effective and widely-used antimalarials that have helped reduce the burden of malaria by 60% in some areas over the past decade-have recently been found to induce growth retardation of blood-stage plasmodium falciparum when applied at clinically relevant concentrations. to date, no model has been designed to quantify the growth retardation effect and to predict th ...201728728995
kbe009: an antimalarial bestatin-like inhibitor of the plasmodium falciparum m1 aminopeptidase discovered in an ugi multicomponent reaction-derived peptidomimetic library.malaria is a global human parasitic disease mainly caused by the protozoon plasmodium falciparum. increased parasite resistance to current drugs determines the relevance of finding new treatments against new targets. a novel target is the m1 alanyl-aminopeptidase from p. falciparum (pfa-m1), which is essential for parasite development in human erythrocytes and is inhibited by the pseudo-peptide bestatin. in this work, we used a combinatorial multicomponent approach to produce a library of peptid ...201728728898
malaria after international travel: a geosentinel analysis, 2003-2016.more than 30,000 malaria cases are reported annually among international travellers. despite improvements in malaria control, malaria continues to threaten travellers due to inaccurate perception of risk and sub-optimal pre-travel preparation.201728728595
accuracy of a plasmodium falciparum specific histidine-rich protein 2 rapid diagnostic test in the context of the presence of non-malaria fevers, prior anti-malarial use and seasonal malaria transmission.it remains challenging to distinguish malaria from other fever causing infections, as a positive rapid diagnostic test does not always signify a true active malaria infection. this study was designed to determine the influence of other causes of fever, prior anti-malarial treatment, and a possible seasonality of the performance of a pfhrp2 rdt for the diagnosis of malaria in children under-5 years of age living in a malaria endemic area.201728728558
qsar modeling, docking and admet studies for exploration of potential anti-malarial compounds against plasmodium falciparum.development of resistance in the plasmodium falciparum to artemisinin, the most effective anti-malarial compound, threatens malaria elimination tactics. to gain more efficacious artemisinin derivatives, qsar modeling and docking was performed. in the present study, 2d-qsar model and molecular docking were used to evaluate the artemisinin compounds and to reveal their binding modes and structural basis of inhibitory activity. moreover, admet-related descriptors have been calculated to predict the ...201628726171
variation in species composition and infection rates of anopheles mosquitoes at different altitudinal transects, and the risk of malaria in the highland of dirashe woreda, south ethiopia.the transmission of malaria is heterogeneous, and varies due to altitude. the information on whether the transmission of malaria is indigenous or imported to highland areas is scarce. therefore, this study aimed to assess the species composition and infection rates of anopheles at different altitudinal transects, and the risk of malaria if any in the highland of dirashe woreda, south ethiopia.201728724450
identification and characterization of the antiplasmodial activity of hsp90 inhibitors.the recent reduction in mortality due to malaria is being threatened by the appearance of plasmodium falciparum parasites that are resistant to artemisinin in southeast asia. to limit the impact of resistant parasites and their spread across the world, there is a need to validate anti-malarial drug targets and identify new leads that will serve as foundations for future drug development programmes targeting malaria. towards that end, the antiplasmodial potential of several hsp90 inhibitors was c ...201728724415
a dual colour fluorescence in situ hybridization (fish) assay for identifying the zoonotic malaria parasite plasmodium knowlesi with a potential application for the specific diagnosis of knowlesi malaria in peripheral-level laboratories of southeast asia.plasmodium knowlesi is primarily responsible for zoonotic malaria in several southeast asian countries. precise identification of the parasite in the blood of patients presently relies on an expensive and elaborate pcr procedure because microscopic examination of blood and other available field identification techniques lack adequate specificity. therefore, the use of a simple and inexpensive dual-colour fluorescence in situ hybridization (fish) assay, analogous to fish assays recently described ...201728724402
novel plasmodium falciparum metabolic network reconstruction identifies shifts associated with clinical antimalarial resistance.malaria remains a major public health burden and resistance has emerged to every antimalarial on the market, including the frontline drug, artemisinin. our limited understanding of plasmodium biology hinders the elucidation of resistance mechanisms. in this regard, systems biology approaches can facilitate the integration of existing experimental knowledge and further understanding of these mechanisms.201728724354
artemisinin-resistant plasmodium falciparum in africa. 201728723328
artemisinin-resistant plasmodium falciparum in africa. 201728723327
estimating the added utility of highly sensitive histidine-rich protein 2 detection in outpatient clinics in sub-saharan africa.most malaria testing is by rapid diagnostic tests (rdts) that detect plasmodium falciparum histidine-rich protein 2 (hrp2). recently, several rdt manufacturers have developed highly sensitive rdts (hsrdts), promising a limit of detection (lod) orders of magnitude lower than conventional rdts. to model the added utility of hsrdts, hrp2 concentration in angolan outpatients was measured quantitatively using an ultrasensitive bead-based assay. the distribution of hrp2 concentration was bimodal in bo ...201728722629
respiratory complications of plasmodium vivax malaria: systematic review and meta-analysis.malaria, a major global public health problem, is mainly caused by plasmodium falciparum and plasmodium vivax, and is responsible for nearly half a million deaths annually. although p. vivax malaria was not believed to cause severe disease, recent robust studies have proved otherwise. however, the clinical spectrum and pathogenesis of severe vivax malaria and, especially, its respiratory complications remain poorly understood. a systematic search for articles reporting respiratory complications ...201728722625
phase 2a, open-label, 4-escalating-dose, randomized multicenter study evaluating the safety and activity of ferroquine (ssr97193) plus artesunate, versus amodiaquine plus artesunate, in african adult men with uncomplicated plasmodium falciparum malaria.artemisinin-based combination therapies are recommended as first-line agents for treating uncomplicated plasmodium falciparum malaria. ferroquine, a 4-aminoquinolone, is a novel long-acting combination partner for fast-acting drugs like artesunate (as). we did a small phase 2a, multicenter, open-label, safety-focused dose-ranging randomized study of ferroquine at three african hospitals: two gabonese and one kenyan. we recruited adult men with symptomatic uncomplicated p. falciparum monoinfectio ...201728722611
optimizing direct membrane and direct skin feeding assays for plasmodium falciparum transmission-blocking vaccine trials in bancoumana, mali.malaria transmission-blocking vaccines (tbv) have been evaluated in field trials in mali, since 2013. however, the assays currently used to measure serum antibody tb activity (tba) after vaccination are highly variable, in part due to the lack of optimization and standardization for field assays in which mosquitoes feed on gametocytemic blood. herein, we report a study conducted in bancoumana village, mali, where we identify and optimize the parameters that contribute to successful mosquito feed ...201728722588
lack of geospatial population structure yet significant linkage disequilibrium in the reservoir of plasmodium falciparum in bongo district, ghana.malaria control in west africa is impeded by the large reservoir of chronic asymptomatic plasmodium falciparum infections in the human population. this study aimed to assess the extent of diversity in the p. falciparum reservoir in bongo district (bd), ghana, at the end of the dry season, the lowest point in malaria transmission over the course of the year. analysis of the variation in 12 microsatellite loci was completed for 200 p. falciparum isolates collected from a cross-sectional survey of ...201728722587
a direct from blood reverse transcriptase polymerase chain reaction assay for monitoring falciparum malaria parasite transmission in elimination settings.we describe a novel one-step reverse transcriptase real-time pcr (direct rt-pcr) for plasmodium falciparum malaria parasites that amplifies rna targets directly from blood. we developed the assay to identify gametocyte-specific transcripts in parasites from patient blood samples, as a means of monitoring malaria parasite transmission in field settings. to perform the test, blood is added directly to a master mix in pcr tubes and analyzed by real-time pcr. the limit of detection of the assay on b ...201728722583
high iron levels are associated with increased malaria risk in infants during the first year of life in benin.the world health organization (who) estimates that 40% of children in low-income countries are anemic. therefore, iron supplements are recommended by who in areas with high anemia rates. however, some studies have set into question the benefits of iron supplementation in malaria-endemic regions. in benin, a west african country with high prevalence of anemia and malaria, no iron supplements are given systematically to infants so far despite the who recommendations. in this context, we wanted to ...201728722565
survey of malaria and anti-dengue virus igg among febrile hiv-infected patients attending a tertiary hospital in abuja, nigeria.dengue and malaria are infections, of great public health concern, especially in sub-saharan africa where the burden of hiv infection is high. this study was conducted to determine the seroprevalence of dengue virus igg antibodies and dengue/malaria coinfection among febrile hiv-infected patients attending the university of abuja teaching hospital, gwagwalada, abuja.201728721101
exploring anti-malarial potential of fda approved drugs: an in silico approach.the critically important issue on emergence of drug-resistant malarial parasites is compounded by cross resistance, where resistance to one drug confers resistance to other chemically similar drugs or those that share mode of action. this aspect requires discovery of new anti-malarial compounds or formulation of new combination therapy. the current study attempts to contribute towards accelerating anti-malarial drug development efforts, by exploring the potential of existing fda-approved drugs t ...201728720135
in vitro antioxidant and antimalarial activities of leaves, pods and bark extracts of acacia nilotica (l.) del.the emergence of drug resistant malaria is threatening our ability to treat and control malaria in the southeast asian region. there is an urgent need to develop novel and chemically diverse antimalarial drugs. this study aimed at evaluating the antimalarial and antioxidant potentials of acacia nilotica plant extracts.201728720134
effect of seasonal malaria chemoprevention on the acquisition of antibodies to plasmodium falciparum antigens in ouelessebougou, mali.seasonal malaria chemoprevention (smc) is a new strategy to reduce malaria burden in young children in sahelian countries. it consists of the administration of full treatment courses of sulfadoxine-pyrimethamine plus amodiaquine to children at monthly intervals during the malaria season. however, it is not clear if there is a cumulative effect of smc over time on acquisition of antibodies to malaria antigens.201728720100
malaria-related hospitalizations in the united states, 2000-2014.few data are available on the burden of malaria hospitalization in the united states. study of malaria using hospital-based data can better define the impact of malaria and help inform prevention efforts. u.s. malaria cases identified from hospitalization discharge records in the 2000-2014 nationwide inpatient sample were examined. frequencies and population rates were reported by demographics, infecting species, clinical, financial, institutional, geographic, and seasonal characteristics, and d ...201728719326
molecular epidemiology of malaria in cameroon and côte d'ivoire. xxxi. kelch 13 propeller sequences in plasmodium falciparum isolates before and after implementation of artemisinin-based combination therapy.artemisinin-resistant malaria has not been reported from africa, but resistance can possibly spread from asia or arise independently in africa. the emergence of artemisinin resistance in africa can be monitored by molecular assay of kelch 13 (k13) propeller sequences. a total of 251 archived dna samples of plasmodium falciparum isolates collected in 2002, 2003, and 2006 in yaounde, cameroon, and 47 samples collected in 2006 and 2013 in abidjan, côte d'ivoire, were analyzed for k13-propeller sequ ...201728719312
seasonal variation in the epidemiology of asymptomatic plasmodium falciparum infections across two catchment areas in bongo district, ghana.understanding the epidemiology of asymptomatic plasmodium falciparum infections is critical for countries to move toward malaria elimination. using different methods for parasite detection, we evaluated how seasonality, spatial location, and other factors affect the age-specific epidemiology of asymptomatic malaria in bongo district, ghana. asymptomatic prevalence by microscopy decreased significantly from 42.5% at the end of the wet to 27.5% at the end of the dry season (p < 0.001). using the 1 ...201728719306
molecular markers for sensitive detection of plasmodium falciparum asexual stage parasites and their application in a malaria clinical trial.plasmodium falciparum parasite life stages respond differently to antimalarial drugs. sensitive stage-specific molecular assays may help to examine parasite dynamics at microscopically detectable and submicroscopic parasite densities in epidemiological and clinical studies. in this study, we compared the performance of skeleton-binding protein 1 (sbp1), ring-infected erythrocyte surface antigen, hyp8, ring-exported protein 1 (rex1), and phistb mrna for detecting ring-stage trophozoite-specific t ...201728719294
symptomatic falciparum malaria after living in a nonendemic area for 10 years: recrudescence or indigenous transmission?abstractwe report the case of a patient from mali who, after 10 years of living in spain, presented with symptomatic plasmodium falciparum malaria without having visited an endemic area during that time. we cannot completely rule out the possibility of indigenous transmission, but this case most likely represents recrudescence of an infection acquired over 10 years earlier.201728719260
heterologous expression, purification, and functional analysis of plasmodium falciparum phosphatidylinositol 3'-kinase.the plasmodium falciparum malarial parasite genome appears to encode one and only one phosphatidylinositol 3'-kinase (pi3k), and sequence analysis suggests that the enzyme is a "class iii"- or "vps34"-type pi3k. pfvps34 has generated excitement as a possible druggable target and potentially a key target of artemisinin-based antimalarials. in this study, we optimize the pfvps34 gene for heterologous expression in yeast, purify the protein to homogeneity, use a recently validated quantitative assa ...201728719180
development of an immunosensor for pfhrp 2 as a biomarker for malaria detection.plasmodium falciparum histidine-rich protein 2 (pfhrp 2) was selected in this work as the biomarker for the detection and diagnosis of malaria. an enzyme-linked immunosorbent assay (elisa) was first developed to evaluate the immunoreagent's suitability for the sensor's development. a gold-based sensor with an integrated counter and an ag/agcl reference electrode was first selected and characterised and then used to develop the immunosensor for pfhrp 2, which enables a low cost, easy to use, and ...201728718841
an analytical approach to reduce between-plate variation in multiplex assays that measure antibodies to plasmodium falciparum antigens.antibodies play an important role in immunity to malaria. recent studies show that antibodies to multiple antigens, as well as, the overall breadth of the response are associated with protection from malaria. yet, the variability and reliability of antibody measurements against a combination of malarial antigens using multiplex assays have not been well characterized.201728716094
dynamics in multiplicity of plasmodium falciparum infection among children with asymptomatic malaria in central ghana.the determinants of malaria parasite virulence is not entirely known, but the outcome of malaria infection (asymptomatic or symptomatic) has been associated with carriage of distinct parasite genotypes. alleles considered important for erythrocyte invasion and selected as candidate targets for malaria vaccine development are increasingly being shown to have distinct characteristics in infection outcomes. any unique/distinct patterns or alleles linked to infection outcome should be reproducible f ...201728716086
multiplexing detection of igg against plasmodium falciparum pregnancy-specific antigens.pregnant women exposed to plasmodium falciparum generate antibodies against var2csa, the parasite protein that mediates adhesion of infected erythrocytes to the placenta. there is a need of high-throughput tools to determine the fine specificity of these antibodies that can be used to identify immune correlates of protection and exposure. here we aimed at developing a multiplex-immunoassay to detect antibodies against var2csa antigens.201728715465
antiplasmodial prenylated flavanonols from tephrosia subtriflora.the ch2cl2/meoh (1:1) extract of the aerial parts of tephrosia subtriflora afforded a new flavanonol, named subtriflavanonol (1), along with the known flavanone spinoflavanone b, and the known flavanonols ms-ii (2) and mundulinol. the structures were elucidated by the use of nmr spectroscopy and mass spectrometry. the absolute configuration of the flavanonols was determined based on quantum chemical ecd calculations. in the antiplasmodial assay, compound 2 showed the highest activity against chl ...201728714338
antimicrobial activity of organometallic isonicotinyl and pyrazinyl ferrocenyl-derived complexes.isonicotinyl and pyrazinyl ferrocenyl-derived complexes were prepared using various hydrazides and ferrocenyl aldehydes. three heterobimetallic complexes were also synthesized from the schiff base-derived isonicotinyl ferrocene complex using various platinum group metal dimers based on ruthenium, rhodium and iridium. all complexes were evaluated in vitro for antimycobacterial and antiparasitic activity. against mycobacterium tuberculosis h37rv, the platinum group metal complexes showed glycerol- ...201728713884
plasmodium knowlesi: a superb in vivo nonhuman primate model of antigenic variation in malaria.antigenic variation in malaria was discovered in plasmodium knowlesi studies involving longitudinal infections of rhesus macaques (m. mulatta). the variant proteins, known as the p. knowlesi schizont infected cell agglutination (sica) antigens and the p. falciparum erythrocyte membrane protein 1 (pfemp1) antigens, expressed by the sicavar and var multigene families, respectively, have been studied for over 30 years. expression of the sica antigens in p. knowlesi requires a splenic component, and ...201728712361
resisting and tolerating p. falciparum in pregnancy under different malaria transmission intensities.resistance and tolerance to plasmodium falciparum can determine the progression of malaria disease. however, quantitative evidence of tolerance is still limited. we investigated variations in the adverse impact of p. falciparum infections among african pregnant women under different intensities of malaria transmission.201728712360
analytic study in patients presenting to a tertiary care hospital regarding the artemether-lumefantrine induced qtc interval changes in ecg.malaria is one of the most common causes of morbidity and mortality in our part of the world. artemether-lumefantrine (al) combination therapy is widely used for the treatment of malaria both in outpatients and inpatients hospital settings. some of the previous anti-malarial were associated with prolongation of qtc interval. similar query was raised about al therapy. this study was conducted to determine the risk of qtc interval prolongation in ecg of patients with falciparum malaria using oral ...201728712169
updates on k13 mutant alleles for artemisinin resistance in plasmodium falciparum.in the fight against malaria caused by plasmodium falciparum, the successes achieved by artemisinin were endangered by resistance of the parasites to the drug. whole genome sequencing approach on artemisinin resistant parasite line discovered k13 gene associated with drug resistance. in vitro and in vivo studies indicated mutations in the k13 gene were linked to the artemisinin resistance.201728711439
high-throughput and label-free parasitemia quantification and stage differentiation for malaria-infected red blood cells.this work reports a high throughput and label-free microfluidic cell deformability sensor for quantitative parasitemia measurement and stage determination for plasmodium falciparum-infected red blood cells (pf-irbcs). the sensor relies on differentiating the rbc deformability (a mechanical biomarker) that is highly correlated with the infection status. the cell deformability is measured by evaluating the transit time when each individual rbc squeezes through a microscale constriction (cross-sect ...201728711027
rupture and release: a role for soluble erythrocyte content in the pathology of cerebral malaria.cerebral malaria (cm) is the most severe form of malaria and causes high associated mortality. we propose a multistep process for cm pathology that is initiated by cytoadhesion of infected erythrocytes to the brain vasculature, followed by rupture and release of contents that complete the disruption of the blood-brain barrier.201728709836
iron fortified complementary foods containing a mixture of sodium iron edta with either ferrous fumarate or ferric pyrophosphate reduce iron deficiency anemia in 12- to 36-month-old children in a malaria endemic setting: a secondary analysis of a cluster-randomized controlled trial.iron deficiency anemia (ida) is a major public health problem in sub-saharan africa. the efficacy of iron fortification against ida is uncertain in malaria-endemic settings. the objective of this study was to evaluate the efficacy of a complementary food (cf) fortified with sodium iron edta (nafeedta) plus either ferrous fumarate (fefum) or ferric pyrophosphate (fepp) to combat ida in preschool-age children in a highly malaria endemic region. this is a secondary analysis of a nine-month cluster- ...201728708072
malaria, epstein-barr virus infection and the pathogenesis of burkitt's lymphoma.a geographical and causal connection has long been recognized between malaria, epstein-barr virus (ebv) infection and burkitt's lymphoma (bl), but the underlying mechanisms remain obscure. potential clues are that the malaria parasite plasmodium falciparum selectively absorbs vitamin a from the host and depends on it for its biological activities; secondly, alterations in vitamin a (retinoid) metabolism have been implicated in many forms of cancer, including bl. the first author has proposed tha ...201728707393
abscisic acid induces a transient shift in signaling that enhances nf-κb-mediated parasite killing in the midgut of anopheles stephensi without reducing lifespan or fecundity.abscisic acid (aba) is naturally present in mammalian blood and circulating levels can be increased by oral supplementation. we showed previously that oral aba supplementation in a mouse model of plasmodium yoelii 17xnl infection reduced parasitemia and gametocytemia, spleen and liver pathology, and parasite transmission to the mosquito anopheles stephensi fed on these mice. treatment of cultured plasmodium falciparum with aba at levels detected in our model had no effects on asexual growth or g ...201728705245
association of a functional tnf variant with plasmodium falciparum parasitaemia in a congolese population.several studies have provided evidence of both helpful and harmful effects of tnf on the outcome of plasmodium falciparum malaria infection. several tnf polymorphisms that are located within non-coding regions have been associated with parasitaemia, mild malaria or severe malaria. we investigated the association of tnf1304 (rs3093664), tnf-308 (rs1800629), tnf-238 (rs361525) and tnf-244 (rs673) with mild malaria and symptomatic maximum parasitaemia in a population-based design (n=310). we obtain ...201728703132
pulmonary manifestation of plasmodium falciparum malaria: case reports and review of the literature.pulmonary complications, including acute respiratory distress syndrome (ards), are well described in p. falciparum (pf) and to a lesser extent in other malaria species. in non-endemic areas, malaria diagnosis may be overlooked; if a thorough travel history is not obtained on all patients with acute febrile illness. three patients with malaria associated respiratory distress were admitted to our intensive care unit. the diagnosis was delayed; however, all patients received artesunate and intensiv ...201728702342
immunization with the malaria diversity-covering blood-stage vaccine candidate plasmodium falciparum apical membrane antigen 1 dico in complex with its natural ligand pfron2 does not improve the in vitro efficacy.the blood-stage malaria vaccine candidate plasmodium falciparum apical membrane antigen 1 (pfama1) can induce strong parasite growth-inhibitory antibody responses in animals but has not achieved the anticipated efficacy in clinical trials. possible explanations in humans are the insufficient potency of the elicited antibody responses, as well as the high degree of sequence polymorphisms found in the field. several strategies have been developed to improve the cross-strain coverage of pfama1-base ...201728702028
fatal postoperative hemolysis due to severe falciparum malaria.a 60-year-old apparently healthy female patient underwent mastectomy for breast cancer. she had sinus tachycardia and no other abnormal finding in the preoperative period. however, the immediate postoperative course was stormy with the development of anemia, thrombocytopenia, hemolysis, and renal failure with severe metabolic acidosis. peripheral blood smear revealed the presence of ring forms of plasmodium falciparum. multiorgan failure and death occurred within 36 h of surgery in spite of init ...201728701845
structural and biochemical characterization of apicomplexan inorganic pyrophosphatases.inorganic pyrophosphatases (ppase) participate in energy cycling and they are essential for growth and survival of organisms. here we report extensive structural and functional characterization of soluble ppases from the human parasites plasmodium falciparum (pfppase) and toxoplasma gondii (tgppase). our results show that pfppase is a cytosolic enzyme whose gene expression is upregulated during parasite asexual stages. cambialistic pfppase actively hydrolyzes linear short chain polyphosphates li ...201728701714
vangueria infausta root bark: in vivo and in vitro antiplasmodial activity.vangueria infausta burch subsp. infausta (rubiaceae) produces fruits eaten by humans and animals. the leaf, fruit, stem bark and root bark are used as a remedy for many ailments and the roots are used to treat malaria. in this study, concentrations of fractions of the v. infausta root bark extract that produce 50% inhibition (ic50) are determined using the ability of the extract to inhibit the uptake of [g(3)h]-hypoxanthine by p. falciparum cultured in vitro. the root bark extract showed antimal ...200628700877
the gmz2 malaria vaccine: from concept to efficacy in humans.gmz2 is a recombinant protein consisting of conserved domains of glurp and msp3, two asexual blood-stage antigens of plasmodium falciparum, and is designed with the aim of mimicking naturally acquired anti-malarial immunity. the rationale for combining these two antigens is based on a series of immune epidemiological studies from geographically diverse malaria endemic regions; functional in vitro studies; and pre-clinical studies in rodents and new world monkeys. gmz2 adjuvanted with alhydrogel® ...201728699823
crispr/cas9 genome editing reveals that the intron is not essential for var2csa gene activation or silencing in plasmodium falciparum.plasmodium falciparum relies on monoallelic expression of 1 of 60 var virulence genes for antigenic variation and host immune evasion. each var gene contains a conserved intron which has been implicated in previous studies in both activation and repression of transcription via several epigenetic mechanisms, including interaction with the var promoter, production of long noncoding rnas (lncrnas), and localization to repressive perinuclear sites. however, functional studies have relied primarily o ...201728698275
biolayer interferometry predicts elisa performance of monoclonal antibody pairs for plasmodium falciparum histidine-rich protein 2.predicting antibody pair performance in a sandwich format streamlines development of antibody-based diagnostics and laboratory research tools, such as enzyme-linked immunosorbent assays (elisas) and lateral flow immunoassays (lfas). we have evaluated panels of monoclonal antibodies against the malarial parasite biomarker plasmodium falciparum histidine rich protein 2 (hrp2), including 9 new monoclonal antibodies, using biolayer interferometry (bli) and screened antibody pairs in a checkerboard e ...201728698001
variant gene expression and antigenic variation by malaria parasites.malaria is a significant threat throughout the developing world. among the most fascinating aspects of the protozoan parasites responsible for this disease are the methods they employ to avoid the immune system and perpetuate chronic infections. key among these is antigenic variation: by systematically altering antigens that are displayed to the host's immune system, the parasite renders the adaptive immune response ineffective. for plasmodium falciparum, the species responsible for the most sev ...201728697665
development of a potent inhibitor of the plasmodium proteasome with reduced mammalian toxicity.naturally derived chemical compounds are the foundation of much of our pharmacopeia, especially in antiproliferative and anti-infective drug classes. here, we report that a naturally derived molecule called carmaphycin b is a potent inhibitor against both the asexual and sexual blood stages of malaria infection. using a combination of in silico molecular docking and in vitro directed evolution in a well-characterized drug-sensitive yeast model, we determined that these compounds target the β5 su ...201728696697
a case of cerebral malaria managed by erythrocyte exchange.plasmodium falciparum may cause serious and sometimes even fatal cerebral malaria. cerebral malaria is a disease characterized by alterations in consciousness and epileptic attacks; therefore, it requires a rapid evaluation and quick intervention. it may progress to a fatal outcome despite administering targeted therapeutic interventions. there are studies indicating that erythrocyte exchange (erythrocytapheresis) can be a treatment modality for managing severe malaria patients. in this case rep ...201728695837
a case series of imported malaria caused by plasmodium falciparum in kayseri and review of literature.malaria is a major worldwide public health problem. in the last years, no domestic cases of malaria have been detected and cases of imported malaria exist only in turkey. in this study, clinical and laboratory findings of five plasmodium falciparum (p. falciparum) malaria patients who were admitted to the emergency department between january 2013 and december 2015 were retrospectively presented. one of the patients was an african student, and the other patients had a history of travelling to afr ...201728695836
[fe-s] cluster assembly in the apicoplast and its indispensability in mosquito stages of the malaria parasite.the relict plastid (apicoplast) of the malaria parasite is the site for important biochemical pathways and is essential for parasite survival. the sulfur mobilization (suf) pathway of iron-sulfur [fe-s] cluster assembly in the apicoplast of plasmodium spp. is of interest due to its absence in the human host suggesting the possibility of antimalarial intervention through apicoplast [fe-s] biogenesis. we report biochemical characterization of components of the plasmodium falciparum apicoplast suf ...201728695709
population pharmacokinetics and electrocardiographic effects of dihydroartemisinin-piperaquine in healthy volunteers.the aims of the present study were to evaluate the pharmacokinetic properties of dihydroartemisinin (dha) and piperaquine, potential drug-drug interactions with concomitant primaquine treatment, and piperaquine effects on the electrocardiogram in healthy volunteers.201728695570
temporal analysis of igg antibody responses to plasmodium falciparum antigens in relation to changing malaria epidemiology in a west african setting.coordinated scaled-up malaria control interventions have substantially contributed to the dramatic decrease of malaria-related morbidity and mortality in several endemic countries, including senegal. however, the impacts of a given malaria control intervention on vector and parasite populations, acquired immunity, and disease burden remain very poorly documented largely due to the lack of continuous surveys. this study took advantage of the sera bank established as part of the dielmo longitudina ...201728693608
progressive increase in point mutations associates chloroquine resistance: even after withdrawal of chloroquine use in india.chloroquine (cq) is highly effective against p. vivax, due to the rapid spread of cq resistance in p. falciparum parasites; it is no longer the drug of choice against p. falciparum. this study elucidates the scenario of chloroquine efficacy at times that coincided with a new drug policy and especially assessed the chloroquine resistant molecular markers after withdrawal of chloroquine in kolkata and purulia, two malaria endemic zones of west bengal, india. in vitro cq susceptibility was tested i ...201728692943
population-based incidence, seasonality and serotype distribution of invasive salmonellosis among children in nanoro, rural burkina faso.bloodstream infections (bsi) caused by salmonella typhi and invasive non-typhoidal salmonella (ints) frequently affect children living in rural sub-saharan africa but data about incidence and serotype distribution are rare.201728692655
an exported protein-interacting complex involved in the trafficking of virulence determinants in plasmodium-infected erythrocytes.the malaria parasite, plasmodium falciparum, displays the p. falciparum erythrocyte membrane protein 1 (pfemp1) on the surface of infected red blood cells (rbcs). we here examine the physical organization of pfemp1 trafficking intermediates in infected rbcs and determine interacting partners using an epitope-tagged minimal construct (pfemp1b). we show that parasitophorous vacuole (pv)-located pfemp1b interacts with components of the ptex (plasmodium translocon of exported proteins) as well as a ...201728691708
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