Publications
| Title | Abstract | Year Filter | PMID(sorted descending) Filter |
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| malaria parasite clearance. | following anti-malarial drug treatment asexual malaria parasite killing and clearance appear to be first order processes. damaged malaria parasites in circulating erythrocytes are removed from the circulation mainly by the spleen. splenic clearance functions increase markedly in acute malaria. either the entire infected erythrocytes are removed because of their reduced deformability or increased antibody binding or, for the artemisinins which act on young ring stage parasites, splenic pitting of ... | 2017 | 28231817 |
| three chalconoids and a pterocarpene from the roots of tephrosia aequilata. | in our search for new antiplasmodial agents, the ch₂cl₂/ch₃oh (1:1) extract of the roots of tephrosia aequilata was investigated, and observed to cause 100% mortality of the chloroquine-sensitive (3d7) strain of plasmodium falciparum at a 10 mg/ml concentration. from this extract three new chalconoids, e-2',6'-dimethoxy-3',4'-(2'',2''-dimethyl)pyranoretrochalcone (1, aequichalcone a), z-2',6'-dimethoxy-3',4'-(2'',2''-dimethyl)pyranoretrochalcone (2, aequichalcone b), 4''-ethoxy-3''-hydroxypraeca ... | 2017 | 28230755 |
| dynamic protein s-palmitoylation mediates parasite life cycle progression and diverse mechanisms of virulence. | eukaryotic parasites possess complex life cycles and utilize an assortment of molecular mechanisms to overcome physical barriers, suppress and/or bypass the host immune response, including invading host cells where they can replicate in a protected intracellular niche. protein s-palmitoylation is a dynamic post-translational modification in which the fatty acid palmitate is covalently linked to cysteine residues on proteins by the enzyme palmitoyl acyltransferase (pat) and can be removed by lyso ... | 2017 | 28228066 |
| plasmodium falciparum ligand binding to erythrocytes induce alterations in deformability essential for invasion. | the most lethal form of malaria in humans is caused by plasmodium falciparum. these parasites invade erythrocytes, a complex process involving multiple ligand-receptor interactions. the parasite makes initial contact with the erythrocyte followed by dramatic deformations linked to the function of the erythrocyte binding antigen family and p. falciparum reticulocyte binding-like families. we show eba-175 mediates substantial changes in the deformability of erythrocytes by binding to glycophorin a ... | 2017 | 28226242 |
| emergence of indigenous artemisinin-resistant plasmodium falciparum in africa. | 2017 | 28225668 | |
| plasmodium vivax cell-traversal protein for ookinetes and sporozoites: naturally acquired humoral immune response and b-cell epitope mapping in brazilian amazon inhabitants. | the cell-traversal protein for ookinetes and sporozoites (celtos), a highly conserved antigen involved in sporozoite motility, plays an important role in the traversal of host cells during the preerythrocytic stage of plasmodium species. recently, it has been considered an alternative target when designing novel antimalarial vaccines against plasmodium falciparum. however, the potential of plasmodium vivax celtos as a vaccine target is yet to be explored. this study evaluated the naturally acqui ... | 2017 | 28223984 |
| attenuated pfspz vaccine induces strain-transcending t cells and durable protection against heterologous controlled human malaria infection. | a live-attenuated malaria vaccine, plasmodium falciparum sporozoite vaccine (pfspz vaccine), confers sterile protection against controlled human malaria infection (chmi) with plasmodium falciparum (pf) parasites homologous to the vaccine strain up to 14 mo after final vaccination. no injectable malaria vaccine has demonstrated long-term protection against chmi using pf parasites heterologous to the vaccine strain. here, we conducted an open-label trial with pfspz vaccine at a dose of 9.0 × 10(5) ... | 2017 | 28223498 |
| molecular evidence of drug resistance in asymptomatic malaria infections, myanmar, 2015. | artemisinin resistance containment in myanmar was initiated in 2011 after artemisinin-resistant plasmodium falciparum malaria was reported. molecular evidence suggests that asymptomatic malaria infections harboring drug resistance genes are present among residents of the myanmar artemisinin resistance containment zone. this evidence supports efforts to eliminate these hidden infections. | 2017 | 28221121 |
| submicroscopic falciparum malaria in febrile individuals in urban and rural areas of gabon. | characterization of the parasite reservoir is required to improve malaria control. asymptomatic patients with subpatent parasitemia have been identified in gabon, but the prevalence of such infections among febrile subjects is unclear. we assessed the prevalence of submicroscopic plasmodium falciparum infections on an island (port-gentil), and in urban (libreville), semiurban (melen), and rural (oyem) settings in gabon. blood samples (n = 310) from febrile patients were tested for malaria parasi ... | 2017 | 28219989 |
| changing the policy for intermittent preventive treatment with sulfadoxine-pyrimethamine during pregnancy in malawi. | the growing resistance of plasmodium falciparum to sulfadoxine-pyrimethamine (sp) treatment for uncomplicated malaria led to a recommendation by the world health organization for the use of artemisinin-based combination therapy. inevitably, concerns were also raised surrounding the use of sp for intermittent prevention treatment of malaria during pregnancy (iptp) amidst the lack of alternative drugs. malawi was the first country to adopt intermittent prevention treatment with sp in 1993, and upd ... | 2017 | 28219435 |
| a high pct level correlates with disease severity in plasmodium falciparum malaria in children. | most clinicians in developed countries have limited experience in making clinical assessments of malaria disease severity and/or monitoring high-level parasitemia in febrile patients with imported malaria. hyperparasitemia is a risk factor for severe p. falciparum malaria, and procalcitonin (pct) has recently been related to the severity of malaria. in developed countries, where not all hospital have skilled personnel to count parasitemia, a rapid test might be useful for the prompt diagnosis of ... | 2017 | 28217817 |
| acute pancreatitis due to malaria: a case report of five patients and review of literature. | malaria is endemic in large parts of india and can cause multiorgan failure and death. acute pancreatitis as a complication is rare and is potentially fatal. this case series describes five adult patients between 2005 and 2010 who presented with a short duration febrile illness and diagnosed to have malaria with acute pancreatitis. the mean age of the five patients with acute pancreatitis was 40.4 years and four of them were males. none of them were alcohol consumers and did not have any other r ... | 2017 | 28217609 |
| safety and efficacy of pfspz vaccine against plasmodium falciparum via direct venous inoculation in healthy malaria-exposed adults in mali: a randomised, double-blind phase 1 trial. | plasmodium falciparum sporozite (pfspz) vaccine is a metabolically active, non-replicating, whole malaria sporozoite vaccine that has been reported to be safe and protective against p falciparum controlled human malaria infection in malaria-naive individuals. we aimed to assess the safety and protective efficacy of pfspz vaccine against naturally acquired p falciparum in malaria-experienced adults in mali. | 2017 | 28216244 |
| the effect and mechanism of inhibiting glucose-6-phosphate dehydrogenase activity on the proliferation of plasmodium falciparum. | we screened >40,000 patients with glucose-6-phosphate dehydrogenase (g6pd) deficiency and found that the g6pd kaiping allele was under the most positive selection for fighting against malaria in the chinese population. however, the mechanism is unknown. the current study was designed to investigate the anti-malarial effect and mechanism of g6pd deficiency. dehydroepiandrosterone (dhea) was utilised for inhibiting the g6pd activity of erythrocytes. giemsa staining of blood smears and quantitative ... | 2017 | 28214533 |
| population genetic structure and adaptation of malaria parasites on the edge of endemic distribution. | to determine whether the major human malaria parasite plasmodium falciparum exhibits fragmented population structure or local adaptation at the northern limit of its african distribution where the dry sahel zone meets the sahara, samples were collected from diverse locations within mauritania over a range of ~1000 km. microsatellite genotypes were obtained for 203 clinical infection samples from eight locations, and illumina paired-end sequences were obtained to yield high coverage genomewide si ... | 2017 | 28214367 |
| host cell tropism and adaptation of blood-stage malaria parasites: challenges for malaria elimination. | plasmodium falciparum and plasmodium vivax account for most of the mortality and morbidity associated with malaria in humans. research and control efforts have focused on infections caused by p. falciparum and p. vivax, but have neglected other malaria parasite species that infect humans. additionally, many related malaria parasite species infect nonhuman primates (nhps), and have the potential for transmission to humans. for malaria elimination, the varied and specific challenges of all of thes ... | 2017 | 28213436 |
| malaria during pregnancy. | one hundred and twenty-five million women in malaria-endemic areas become pregnant each year (see dellicour et al. plos med7: e1000221 [2010]) and require protection from infection to avoid disease and death for themselves and their offspring. chloroquine prophylaxis was once a safe approach to prevention but has been abandoned because of drug-resistant parasites, and intermittent presumptive treatment with sulfadoxine-pyrimethamine, which is currently used to protect pregnant women throughout a ... | 2017 | 28213434 |
| anti-malarial effect of novel chloroquine derivatives as agents for the treatment of malaria. | the widespread emergence of anti-malarial drug resistance has necessitated the discovery of novel anti-malarial drug candidates. in this study, chloroquine derivatives were evaluated for the improved anti-malarial activity. | 2017 | 28212631 |
| plasmodium falciparum crk4 directs continuous rounds of dna replication during schizogony. | plasmodium parasites, the causative agents of malaria, have evolved a unique cell division cycle in the clinically relevant asexual blood stage of infection(1). dna replication commences approximately halfway through the intracellular development following invasion and parasite growth. the schizont stage is associated with multiple rounds of dna replication and nuclear division without cytokinesis, resulting in a multinucleated cell. nuclei divide asynchronously through schizogony, with only the ... | 2017 | 28211852 |
| arylmethylamino steroids as antiparasitic agents. | in search of antiparasitic agents, we here identify arylmethylamino steroids as potent compounds and characterize more than 60 derivatives. the lead compound 1o is fast acting and highly active against intraerythrocytic stages of chloroquine-sensitive and resistant plasmodium falciparum parasites (ic50 1-5 nm) as well as against gametocytes. in p. berghei-infected mice, oral administration of 1o drastically reduces parasitaemia and cures the animals. furthermore, 1o efficiently blocks parasite t ... | 2017 | 28211535 |
| the deubiquitinating enzyme cylindromatosis dampens cd8(+) t cell responses and is a critical factor for experimental cerebral malaria and blood-brain barrier damage. | cerebral malaria is a severe complication of human malaria and may lead to death of plasmodium falciparum-infected individuals. cerebral malaria is associated with sequestration of parasitized red blood cells within the cerebral microvasculature resulting in damage of the blood-brain barrier and brain pathology. although cd8(+) t cells have been implicated in the development of murine experimental cerebral malaria (ecm), several other studies have shown that cd8(+) t cells confer protection agai ... | 2017 | 28203236 |
| cerebral malaria: insight into pathogenesis, complications and molecular biomarkers. | cerebral malaria is a medical emergency. all patients with plasmodium falciparum malaria with neurologic manifestations of any degree should be urgently treated as cases of cerebral malaria. pathogenesis of cerebral malaria is due to damaged vascular endothelium by parasite sequestration, inflammatory cytokine production and vascular leakage, which result in brain hypoxia, as indicated by increased lactate and alanine concentrations. the levels of the biomarkers' histidine-rich protein ii, angio ... | 2017 | 28203097 |
| alternative transmission routes in the malaria elimination era: an overview of transfusion-transmitted malaria in the americas. | transfusion-transmitted (tt) malaria is an alternative infection route that has gained little attention from authorities, despite representing a life-threatening condition. there has been no systematic review of this health problem in american countries. the aim of this study was to describe the clinical and epidemiological characteristics of tt malaria in the americas and identify factors associated with lethality based on the studies published in the literature. | 2017 | 28202065 |
| a novel pfs38 protein complex on the surface of plasmodium falciparum blood-stage merozoites. | the plasmodium genome encodes for a number of 6-cys proteins that contain a module of six cysteine residues forming three intramolecular disulphide bonds. these proteins have been well characterized at transmission as well as hepatic stages of the parasite life cycle. in the present study, a large complex of 6-cys proteins: pfs41, pfs38 and pfs12 and three other merozoite surface proteins: glutamate-rich protein (glurp), sera5 and msp-1 were identified on the plasmodium falciparum merozoite surf ... | 2017 | 28202027 |
| plasmodium falciparum heat shock protein 70 lacks immune modulatory activity. | heat shock protein 70 (hsp70) family are conserved molecules that constitute a major part of the cell's protein folding machinery. the role of hsp70s of parasitic origin in host cell immune modulation has remained contentious. this is largely due to the fact that several studies implicating hsp70 in immune modulation rely on the use of recombinant protein derived from bacteria which is often fraught contamination. thus, in the current study, we expressed recombinant plasmodium falciparum hsp70 ( ... | 2017 | 28201964 |
| contribution of plasmodium knowlesi to multi-species human malaria infections in north sumatera, indonesia. | 2017 | 28201638 | |
| sterile protection against human malaria by chemoattenuated pfspz vaccine. | a highly protective malaria vaccine would greatly facilitate the prevention and elimination of malaria and containment of drug-resistant parasites. a high level (more than 90%) of protection against malaria in humans has previously been achieved only by immunization with radiation-attenuated plasmodium falciparum (pf) sporozoites (pfspz) inoculated by mosquitoes; by intravenous injection of aseptic, purified, radiation-attenuated, cryopreserved pfspz ('pfspz vaccine'); or by infectious pfspz ino ... | 2017 | 28199305 |
| recombinant vacuolar iron transporter family homologue pfvit from human malaria-causing plasmodium falciparum is a fe(2+)/h(+)exchanger. | vacuolar iron transporters (vits) are a poorly understood family of integral membrane proteins that can function in iron homeostasis via sequestration of labile fe(2+) into vacuolar compartments. here we report on the heterologous overexpression and purification of pfvit, a vacuolar iron transporter homologue from the human malaria-causing parasite plasmodium falciparum. use of synthetic, codon-optimised dna enabled overexpression of functional pfvit in the inner membrane of escherichia coli whi ... | 2017 | 28198449 |
| identification and mechanistic evaluation of hemozoin-inhibiting triarylimidazoles active against plasmodium falciparum. | in a previous study, target based screening was carried out for inhibitors of β-hematin (synthetic hemozoin) formation, and a series of triarylimidazoles were identified as active against plasmodium falciparum. here, we report the subsequent synthesis and testing of derivatives with varying substituents on the three phenyl rings for this series. the results indicated that a 2-hydroxy-1,3-dimethoxy substitution pattern on ring a is required for submicromolar parasite activity. in addition, cell-f ... | 2017 | 28197312 |
| community engagement and the social context of targeted malaria treatment: a qualitative study in kayin (karen) state, myanmar. | the spread of artemisinin-resistance in plasmodium falciparum is a threat to current global malaria control initiatives. targeted malaria treatment (tmt), which combines mass anti-malarial administration with conventional malaria prevention and control measures, has been proposed as a strategy to tackle this problem. the effectiveness of tmt depends on high levels of population coverage and is influenced by accompanying community engagement activities and the local social context. the article ex ... | 2017 | 28196536 |
| structural basis for inhibition of erythrocyte invasion by antibodies to plasmodium falciparum protein cyrpa. | plasmodium falciparum causes malaria in humans with over 450,000 deaths annually. the asexual blood stage involves invasion of erythrocytes by merozoites, in which they grow and divide to release daughter merozoites, which in turn invade new erythrocytes perpetuating the cycle responsible for malaria. a key step in merozoite invasion is the essential binding of pfrh5/cyrpa/pfripr complex to basigin, a step linked to the formation of a pore between merozoites and erythrocytes. we show cyrpa inter ... | 2017 | 28195530 |
| target elucidation by cocrystal structures of nadh-ubiquinone oxidoreductase of plasmodium falciparum (pfndh2) with small molecule to eliminate drug-resistant malaria. | drug-resistant malarial strains have been continuously emerging recently, which posts a great challenge for the global health. therefore, new antimalarial drugs with novel targeting mechanisms are urgently needed for fighting drug-resistant malaria. nadh-ubiquinone oxidoreductase of plasmodium falciparum (pfndh2) represents a viable target for antimalarial drug development. however, the absence of structural information on pfndh2 limited rational drug design and further development. herein, we r ... | 2017 | 28195463 |
| structure of the malaria vaccine candidate antigen cyrpa and its complex with a parasite invasion inhibitory antibody. | invasion of erythrocytes by plasmodial merozoites is a composite process involving the interplay of several proteins. among them, the plasmodium falciparum cysteine-rich protective antigen (pfcyrpa) is a crucial component of a ternary complex, including reticulocyte binding-like homologous protein 5 (pfrh5) and the rh5-interacting protein (pfripr), essential for erythrocyte invasion. here, we present the crystal structures of pfcyrpa and its complex with the antigen-binding fragment of a parasit ... | 2017 | 28195038 |
| systems analysis of protective immune responses to rts,s malaria vaccination in humans. | rts,s is an advanced malaria vaccine candidate and confers significant protection against plasmodium falciparum infection in humans. little is known about the molecular mechanisms driving vaccine immunity. here, we applied a systems biology approach to study immune responses in subjects receiving three consecutive immunizations with rts,s (rrr), or in those receiving two immunizations of rts,s/as01 following a primary immunization with adenovirus 35 (ad35) (arr) vector expressing circumsporozoit ... | 2017 | 28193898 |
| simplified reversed chloroquines to overcome malaria resistance to quinoline-based drugs. | building on our earlier work of attaching a chemosensitizer (reversal agent) to a known drug pharmacophore, we have now expanded the structure-activity relationship study to include simplified versions of the chemosensitizer. the change from two aromatic rings in this head group to a single ring does not appear to detrimentally affect the antimalarial activity of the compounds. data from in vitro heme binding and β-hematin inhibition assays suggest that the single aromatic rcq compounds retain a ... | 2017 | 28193646 |
| bead-based immunoassay allows sub-picogram detection of histidine-rich protein 2 from plasmodium falciparum and estimates reliability of malaria rapid diagnostic tests. | detection of histidine-rich protein 2 (hrp2) from the malaria parasite plasmodium falciparum provides evidence for active or recent infection, and is utilized for both diagnostic and surveillance purposes, but current laboratory immunoassays for hrp2 are hindered by low sensitivities and high costs. here we present a new hrp2 immunoassay based on antigen capture through a bead-based system capable of detecting hrp2 at sub-picogram levels. the assay is highly specific and cost-effective, allowing ... | 2017 | 28192523 |
| structure and characterisation of a key epitope in the conserved c-terminal domain of the malaria vaccine candidate msp2. | merozoite surface protein 2 (msp2) is an intrinsically disordered antigen that is abundant on the surface of the malaria parasite plasmodium falciparum. the two allelic families of msp2, 3d7 and fc27, differ in their central variable regions, which are flanked by highly conserved c-terminal and n-terminal regions. in a vaccine trial, full-length 3d7 msp2 induced a strain-specific protective immune response despite the detectable presence of conserved region antibodies. this work focuses on the c ... | 2017 | 28189425 |
| design, in silico and in vitro evaluation of curcumin analogues against plasmodium falciparum. | the polyphenolic compound curcumin has been reported for its antimalarial properties in various scientific studies. plasmodium falciparum atp6, the parasite orthologue of mammalian sarcoplasmic ca(2+) atpase (serca) has been identified as a key molecular target of both artemisinin and curcumin. the work was thereby undertaken to study the anti-malarial properties of two different series of curcumin analogues based on their docking interactions with pfatp6 and correlating the results with their a ... | 2017 | 28188731 |
| p113 is a merozoite surface protein that binds the n terminus of plasmodium falciparum rh5. | invasion of erythrocytes by plasmodium falciparum merozoites is necessary for malaria pathogenesis and is therefore a primary target for vaccine development. rh5 is a leading subunit vaccine candidate because anti-rh5 antibodies inhibit parasite growth and the interaction with its erythrocyte receptor basigin is essential for invasion. rh5 is secreted, complexes with other parasite proteins including cyrpa and ripr, and contains a conserved n-terminal region (rh5nt) of unknown function that is c ... | 2017 | 28186186 |
| a report of cerebral malaria treated with automated red blood cell exchange. | adjunctive automated whole blood or red blood cell exchange (rbcex) can rapidly decrease malarial hyperparasitemia. several case reports and series suggest improvement in clinical symptomatology; however, recent centers of disease control and prevention (cdc) recommendations concluded that rbcex has no efficacy as an adjunctive therapy. we present a case of mental status changes secondary to cerebral malaria treated with automated rbcex resulting in rapid and dramatic neurologic improvement. | 2017 | 28185296 |
| a key malaria metabolite modulates vector blood seeking, feeding, and susceptibility to infection. | malaria infection renders humans more attractive to anopheles gambiae sensu lato mosquitoes than uninfected people. the mechanisms remain unknown. we found that an isoprenoid precursor produced by plasmodium falciparum, (e)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (hmbpp), affects a. gambiae s.l. blood meal seeking and feeding behaviors as well as susceptibility to infection. hmbpp acts indirectly by triggering human red blood cells to increase the release of co2, aldehydes, and monoterpenes, ... | 2017 | 28183997 |
| spectrum-malaria: a user-friendly projection tool for health impact assessment and strategic planning by malaria control programmes in sub-saharan africa. | scale-up of malaria prevention and treatment needs to continue but national strategies and budget allocations are not always evidence-based. this article presents a new modelling tool projecting malaria infection, cases and deaths to support impact evaluation, target setting and strategic planning. | 2017 | 28183343 |
| cellulose filtration of blood from malaria patients for improving ex vivo growth of plasmodium falciparum parasites. | establishing in vitro plasmodium falciparum culture lines from patient parasite isolates can offer deeper understanding of geographic variations of drug sensitivity and mechanisms of malaria pathogenesis and immunity. cellulose column filtration of blood is an inexpensive, rapid and effective method for the removal of host factors, such as leucocytes and platelets, significantly improving the purification of parasite dna in a blood sample. | 2017 | 28183301 |
| avidity of anti-malarial antibodies inversely related to transmission intensity at three sites in uganda. | people living in malaria endemic areas acquire protection from severe malaria quickly, but protection from clinical disease and control of parasitaemia is acquired only after many years of repeated infections. antibodies play a central role in protection from clinical disease; however, protective antibodies are slow to develop. this study sought to investigate the influence of plasmodium falciparum exposure on the acquisition of high-avidity antibodies to p. falciparum antigens, which may be ass ... | 2017 | 28183299 |
| lactate dehydrogenase inhibition: biochemical relevance and therapeutical potential. | lactate dehydrogenase (lhd) is a key enzyme of anaerobic metabolism in almost all living organisms and it is also a functional checkpoint for glucose restoration during gluconeogenesis and single-stranded dna metabolism. this enzyme has a well preserved structure during evolution and among the species, with little, but sometimes very useful, changes in the amino acid sequence, which makes it an attractive target for the design and construction of functional molecules able to modulate its catalyt ... | 2017 | 28183261 |
| antimalarial, antiplasmodial and analgesic activities of root extract of alchornea laxiflora. | alchornea laxiflora (benth.) pax. & hoffman (euphorbiaceae) root decoctions are traditionally used in the treatment of malaria and pain in nigeria. | 2017 | 28183236 |
| a redox-active fluorescent ph indicator for detecting plasmodium falciparum strains with reduced responsiveness to quinoline antimalarial drugs. | mutational changes in the plasmodium falciparum chloroquine resistance transporter (pfcrt) have been associated with differential responses to a wide spectrum of biologically active compounds including current and former quinoline and quinoline-like antimalarial drugs. pfcrt confers altered drug responsiveness by acting as a transport system, expelling drugs from the parasite's digestive vacuole where these drugs exert, at least part of, their antiplasmodial activity. to preserve the efficacy of ... | 2017 | 28183182 |
| the antimicrobial molecule trappin-2/elafin has anti-parasitic properties and is protective in vivo in a murine model of cerebral malaria. | according to the who, and despite reduction in mortality rates, there were an estimated 438 000 malaria deaths in 2015. therefore new antimalarials capable of limiting organ damage are still required. we show that systemic and lung adenovirus (ad)-mediated over-expression of trappin-2 (t-2) an antibacterial molecule with anti-inflammatory activity, increased mice survival following infection with the cerebral malaria-inducing plasmodium berghei anka (pbanka) strain. systemically, t-2 reduced pba ... | 2017 | 28181563 |
| involvement of β-defensin 130 (defb130) in the macrophage microbicidal mechanisms for killing plasmodium falciparum. | understanding the molecular defense mechanism of macrophages and identifying their effector molecules against malarial parasites may provide important clues for the discovery of new therapies. to analyze the immunological responses of malarial parasite-induced macrophages, we used dna microarray technology to examine the gene profile of differentiated macrophages phagocytizing plasmodium falciparum-parasitized erythrocytes (irbc). the transcriptional gene profile of macrophages in response to ir ... | 2017 | 28181499 |
| a pcr method based on 18s rrna gene for detection of malaria parasite in balochistan. | to establish a polymerase chain reaction method based on 18s ribosomal ribonucleic acid gene for the detection of plasmodium deoxyribonucleic acid in patients suffering from malaria symptoms. | 2016 | 28179695 |
| a plasmodium vivax plasmid dna- and adenovirus-vectored malaria vaccine encoding blood-stage antigens ama1 and msp142 in a prime/boost heterologous immunization regimen partially protects aotus monkeys against blood-stage challenge. | malaria is caused by parasites of the genus plasmodium, which are transmitted to humans by the bites of anopheles mosquitoes. after the elimination of plasmodium falciparum, it is predicted that plasmodium vivax will remain an important cause of morbidity and mortality outside africa, stressing the importance of developing a vaccine against p. vivax malaria. in this study, we assessed the immunogenicity and protective efficacy of two p. vivax antigens, apical membrane antigen 1 (ama1) and the 42 ... | 2017 | 28179404 |
| the malaria parasite's lactate transporter pffnt is the target of antiplasmodial compounds identified in whole cell phenotypic screens. | in this study the 'malaria box' chemical library comprising 400 compounds with antiplasmodial activity was screened for compounds that perturb the internal ph of the malaria parasite, plasmodium falciparum. fifteen compounds induced an acidification of the parasite cytosol. two of these did so by inhibiting the parasite's formate nitrite transporter (pffnt), which mediates the h+-coupled efflux from the parasite of lactate generated by glycolysis. both compounds were shown to inhibit lactate tra ... | 2017 | 28178359 |
| substrate-analogous inhibitors exert antimalarial action by targeting the plasmodium lactate transporter pffnt at nanomolar scale. | resistance against all available antimalarial drugs calls for novel compounds that hit unexploited targets in the parasite. here, we show that the recently discovered plasmodium falciparum lactate/proton symporter, pffnt, is a valid druggable target, and describe a new class of fluoroalkyl vinylogous acids that potently block pffnt and kill cultured parasites. the original compound, mmv007839, is derived from the malaria box collection of potent antimalarials with unknown targets and contains a ... | 2017 | 28178358 |
| pfhrp2-deleted plasmodium falciparum parasites in the democratic republic of the congo: a national cross-sectional survey. | 2016 | 28177502 | |
| griseofulvin impairs intraerythrocytic growth of plasmodium falciparum through ferrochelatase inhibition but lacks activity in an experimental human infection study. | griseofulvin, an orally active antifungal drug used to treat dermatophyte infections, has a secondary effect of inducing cytochrome p450-mediated production of n-methyl protoporphyrin ix (n-mpp). n-mpp is a potent competitive inhibitor of the heme biosynthetic-enzyme ferrochelatase, and inhibits the growth of cultured erythrocyte stage plasmodium falciparum. novel drugs against plasmodium are needed to achieve malaria elimination. thus, we investigated whether griseofulvin shows anti-plasmodial ... | 2017 | 28176804 |
| [rapid diagnostic test for malaria]. | the rapid diagnostic tests (rdts) whose main interest lies in their implementation without special equipment by unskilled personnel have grown significantly over the past fifteen years to diagnose malaria. they rely on the detection of specific plasmodium proteins, pfhrp2, pldh and aldolase. if the detection of pfhrp2 has very good sensitivity for the diagnosis of plasmodium falciparum malaria, the detection of pldh or aldolase is less efficient for other species, leaving its place to the refere ... | 2017 | 28176239 |
| pre-travel malaria chemoprophylaxis counselling in a public travel medicine clinic in são paulo, brazil. | malaria is one of the most prevalent parasitic diseases in the world and represents a threat to travellers visiting endemic areas. chemoprophylaxis is the prevention measure used in travel medicine, avoiding clinical manifestations and protecting against the development of severe disease and death. | 2017 | 28173862 |
| therapeutic efficacy and effects of artemisinin-based combination treatments on uncomplicated plasmodium falciparum malaria -associated anaemia in nigerian children during seven years of adoption as first-line treatments. | artemisinin-based combination treatments (acts) are the first-line treatments of uncomplicated plasmodium falciparum malaria in many endemic areas but there are few evaluation of their efficacy in anaemic malarious children. | 2017 | 28173853 |
| coinfection with schistosoma haematobium and plasmodium falciparum and anaemia severity among pregnant women in munyenge, mount cameroon area: a cross-sectional study. | background. malaria and urogenital schistosomiasis are coendemic in mount cameroon area. this study investigated the prevalence of s. haematobium, p. falciparum, and coinfections and their effect on anaemia in pregnancy. methods. pregnant women reporting for antenatal care (anc) clinic visit in munyenge were enrolled. s. haematobium and p. falciparum infections were determined by urine filtration and microscopy, respectively. haemoglobin (hb) levels were measured using haemoglobinometer. of 250 ... | 2017 | 28168042 |
| hidden reservoir of resistant parasites: the missing link in the elimination of falciparum malaria. | to successfully eliminate malaria, an integrated system that includes a number of approaches and interventions-aimed at overcoming the threat of antimalarial drug resistance-is required. significant progress has been made in reducing malaria incidence through large-scale use of artemisinin-based combination therapies and insecticide-treated nets. to consolidate these gains, attention should be paid to the missing links in the elimination of malaria. one of these gaps is the residual reservoir of ... | 2017 | 28166813 |
| an epidemiological study to assess plasmodium falciparum parasite prevalence and malaria control measures in burkina faso and senegal. | malariometric information is needed to decide how to introduce malaria vaccines and evaluate their impact in sub-saharan african countries. | 2017 | 28166794 |
| antibody-independent mechanisms regulate the establishment of chronic plasmodium infection. | malaria is caused by parasites of the genus plasmodium. all human-infecting plasmodium species can establish long-lasting chronic infections(1-5), creating an infectious reservoir to sustain transmission(1,6). it is widely accepted that the maintenance of chronic infection involves evasion of adaptive immunity by antigenic variation(7). however, genes involved in this process have been identified in only two of five human-infecting species: plasmodium falciparum and plasmodium knowlesi. furtherm ... | 2017 | 28165471 |
| evolution of the merozoite surface protein 7 (msp7) family in plasmodium vivax and p. falciparum: a comparative approach. | malaria parasites (genus plasmodium) are a diverse group found in many species of vertebrate hosts. these parasites invade red blood cells in a complex process comprising several proteins, many encoded by multigene families, one of which is merozoite surface protein 7 (msp7). in the case of plasmodium vivax, the most geographically widespread human-infecting species, differences in the number of paralogs within multigene families have been previously explained, at least in part, as potential ada ... | 2017 | 28163236 |
| the spread of artemisinin-resistant plasmodium falciparum in the greater mekong subregion: a molecular epidemiology observational study. | evidence suggests that the pfkelch13 mutations that confer artemisinin resistance in falciparum malaria have multiple independent origins across the greater mekong subregion, which has motivated a regional malaria elimination agenda. we aimed to use molecular genotyping to assess antimalarial drug resistance selection and spread in the greater mekong subregion. | 2017 | 28161569 |
| evidence of a hard selective sweep for artemisinin resistant plasmodium falciparum. | 2017 | 28161568 | |
| in vitro and in vivo antimalarial potential of oleoresin obtained from copaifera reticulata ducke (fabaceae) in the brazilian amazon rainforest. | in view of the wide variety of the flora of the amazon region, many plants have been studied in the search for new antimalarial agents. copaifera reticulata is a tree distributed throughout the amazon region which contains an oleoresin rich in sesquiterpenes and diterpenes with β-caryophyllene as the major compound. the oleoresin has demonstrated antiparasitic activity against leishmania amazonensis. because of this previously reported activity, this oleoresin would be expected to also have anti ... | 2017 | 28160850 |
| high plasmodium falciparum longitudinal prevalence is associated with high multiclonality and reduced clinical malaria risk in a seasonal transmission area of mali. | the effects of persistent plasmodium falciparum (pf) infection and multiclonality on subsequent risk of clinical malaria have been reported, but the relationship between these 2 parameters and their relative impacts on the clinical outcome of infection are not understood. a longitudinal cohort study was conducted in a seasonal and high-transmission area of mali, in which 500 subjects aged 1-65 years were followed for 1 year. blood samples were collected every 2 weeks, and incident malaria cases ... | 2017 | 28158202 |
| accelerating the clinical development of protein-based vaccines for malaria by efficient purification using a four amino acid c-terminal 'c-tag'. | development of bespoke biomanufacturing processes remains a critical bottleneck for translational studies, in particular when modest quantities of a novel product are required for proof-of-concept phase i/ii clinical trials. in these instances the ability to develop a biomanufacturing process quickly and relatively cheaply, without risk to product quality or safety, provides a great advantage by allowing new antigens or concepts in immunogen design to more rapidly enter human testing. these chal ... | 2017 | 28153778 |
| anti-malarial synergy of secondary metabolites from morinda lucida benth. | the roots, stem and leaves of morinda lucida are used in some african countries as treatment against different types of fevers including yellow fever, malaria, trypanosomiasis and feverish conditions during child birth. | 2017 | 28153468 |
| efficacy of artemether-lumefantrine, artesunate-amodiaquine, and dihydroartemisinin-piperaquine for treatment of uncomplicated plasmodium falciparum malaria in angola, 2015. | recent anti-malarial resistance monitoring in angola has shown efficacy of artemether-lumefantrine (al) in certain sites approaching the key 90% lower limit of efficacy recommended for artemisinin-based combination therapy. in addition, a controversial case of malaria unresponsive to artemisinins was reported in a patient infected in lunda sul province in 2013. | 2017 | 28153004 |
| efficacy of artesunate + sulphadoxine/pyrimethamine and artemether + lumefantrine and dhfr and dhps mutations in somalia: evidence for updating the malaria treatment policy. | to determine the therapeutic efficacy of artesunate + sulphadoxine/pyrimethamine (as + sp) and artemether + lumefantrine (al), and to investigate the presence of molecular mutations associated with resistance, to inform national malaria treatment policy. | 2017 | 28151566 |
| implications from predicted b-cell and t-cell epitopes of plasmodium falciparum merozoite proteins eba175-rii and rh5. | the leading circumsporozoite protein (csp) based malaria vaccine, rts,s, though promising, has shown limited efficacy in field studies. there is therefore, still a need to identify other malaria vaccine targets. merozoite antigens are potential vaccine candidates, since naturally acquired antibodies generated against them inhibit erythrocyte invasion and in some cases result in the clinical protection from disease. we thus used in silico tools (bcpreds, netmhccons and netmhciipan 3.0) to predict ... | 2016 | 28149040 |
| increase in imported malaria in the netherlands in asylum seekers and vfr travellers. | malaria is a notifiable disease in the netherlands, a non-endemic country. imported malaria infections occur regularly among travellers, migrants and visitors. surveillance data were analysed from 2008 to 2015. trends in amounts of notifications among risk groups were analysed using poisson regression. for asylum seekers, yearly incidence was calculated per region of origin, using national asylum request statistics as denominator data. for tourists, denominator data were used from travel statist ... | 2017 | 28148300 |
| reduced ex vivo susceptibility of plasmodium falciparum after oral artemether-lumefantrine treatment in mali. | artemisinin-based combination therapy is the recommended first-line treatment for uncomplicated falciparum malaria worldwide. however, recent studies conducted in mali showed an increased frequency of recurrent parasitaemia following artemether-lumefantrine (al) treatment. | 2017 | 28148267 |
| individuals living in a malaria-endemic area of cameroon do not have an acquired antibody response to plasmodium falciparum histidine-rich protein 2. | diagnosis of plasmodium falciparum is often based on detection of histidine-rich protein 2 (hrp2) in blood. most hrp2-based assays have high sensitivity and specificity; however, authors have suggested that antibodies (ab) to hrp2 could reduce assay sensitivity. this study sought to characterize the antibody response to hrp2 with respect to prevalence, class, subclass, affinity, and age distribution in cameroonian children and adults residing in an area with high p. falciparum transmission. | 2017 | 28148260 |
| role of quinone reductase 2 in the antimalarial properties of indolone-type derivatives. | indolone-n-oxides have antiplasmodial properties against plasmodium falciparum at the erythrocytic stage, with ic50 values in the nanomolar range. the mechanism of action of indolone derivatives involves the production of free radicals, which follows their bioreduction by an unknown mechanism. in this study, we hypothesized that human quinone reductase 2 (hqr2), known to act as a flavin redox switch upon binding to the broadly used antimalarial chloroquine, could be involved in the activity of t ... | 2017 | 28146103 |
| severe malaria in europe: an 8-year multi-centre observational study. | malaria remains one of the most serious infections for travellers to tropical countries. due to the lack of harmonized guidelines a large variety of treatment regimens is used in europe to treat severe malaria. | 2017 | 28143519 |
| submicroscopic plasmodium prevalence in relation to malaria incidence in 20 villages in western cambodia. | cambodia has seen a marked reduction in the incidence of plasmodium falciparum over the past decade without a corresponding decline in plasmodium vivax incidence. it is unknown to what extent local transmission is sustained by a chain of clinical and sub-clinical infections or by continued re-introduction via migration. using an ultrasensitive molecular technique, 20 villages in western cambodia were surveyed to detect the low season prevalence of p. falciparum and p. vivax and local treatment r ... | 2017 | 28143518 |
| sickle cell trait is associated with controlled levels of haem and mild proinflammatory response during acute malaria infection. | the controlled induction of haemoxygenase-1 (ho-1), an enzyme that catabolizes haem, has been shown to reduce haem, preventing pathologies associated with haem toxicity. the hemoglobin genotype hbas confers reduced susceptibility to severe complications of malaria by a mechanism that is not well understood. using a longitudinal approach, we investigated the effect of baseline concentrations of ho-1 on the accumulation of haem during acute plasmodium falciparum malaria in hbas and hbaa genotypes. ... | 2017 | 28142190 |
| specific and sensitive detection of plasmodium falciparum lactate dehydrogenase by dna-scaffolded silver nanoclusters combined with an aptamer. | innovative nanomaterials offer significant potential for diagnosis of severe diseases of the developing world such as malaria. small sized silver nanoclusters have shown promise for diagnostics due to their intense fluorescence emission and photo-stabilities. here, double-stranded dna-scaffolded silver nanoclusters (agncs-dsdna) were prepared to detect the established malaria biomarker, plasmodium falciparum lactate dehydrogenase (pfldh). significant luminescence enhancement over a wide concentr ... | 2017 | 28139780 |
| a functional il22 polymorphism (rs2227473) is associated with predisposition to childhood cerebral malaria. | cerebral malaria (cm) is a severe complication of plasmodium falciparum infection. this encephalopathy is characterized by coma and is thought to result from mechanical microvessel obstruction and an excessive activation of immune cells leading to pathological inflammation and blood-brain barrier alterations. il-22 contributes to both chronic inflammatory and infectious diseases, and may have protective or pathogenic effects, depending on the tissue and disease state. we evaluated whether polymo ... | 2017 | 28139719 |
| sc83288 is a clinical development candidate for the treatment of severe malaria. | severe malaria is a life-threatening complication of an infection with the protozoan parasite plasmodium falciparum, which requires immediate treatment. safety and efficacy concerns with currently used drugs accentuate the need for new chemotherapeutic options against severe malaria. here we describe a medicinal chemistry program starting from amicarbalide that led to two compounds with optimized pharmacological and antiparasitic properties. sc81458 and the clinical development candidate, sc8328 ... | 2017 | 28139658 |
| the severity of plasmodium falciparum infection is associated with transcript levels of var genes encoding endothelial protein c receptor-binding p. falciparum erythrocyte membrane protein 1. | by attaching infected erythrocytes to the vascular lining, plasmodium falciparum parasites leave blood circulation and avoid splenic clearance. this sequestration is central to pathogenesis. severe malaria is associated with parasites expressing an antigenically distinct p. falciparum erythrocyte membrane protein 1 (pfemp1) subset mediating binding to endothelial receptors. previous studies indicate that pfemp1 adhesins with so-called cidrα1 domains capable of binding endothelial protein c recep ... | 2017 | 28138022 |
| k13 propeller mutations in plasmodium falciparum populations in regions of malaria endemicity in vietnam from 2009 to 2016. | the spread of artemisinin-resistant plasmodium falciparum compromises the therapeutic efficacy of artemisinin combination therapies (acts) and is considered the greatest threat to current global initiatives to control and eliminate malaria. this is particularly relevant in vietnam, where dihydroartemisinin-piperaquine (dp) is the recommended act for p. falciparum infection. the propeller domain gene of k13, a molecular marker of artemisinin resistance, was successfully sequenced in 1,060 p. falc ... | 2017 | 28137815 |
| pfk13-independent treatment failure in four imported cases of plasmodium falciparum malaria treated with artemether-lumefantrine in the united kingdom. | we present case histories of four patients treated with artemether-lumefantrine for falciparum malaria in uk hospitals in 2015 to 2016. each subsequently presented with recurrent symptoms and plasmodium falciparum parasitemia within 6 weeks of treatment with no intervening travel to countries where malaria is endemic. parasite isolates, all of african origin, harbored variants at some candidate resistance loci. no evidence of pfk13-mediated artemisinin resistance was found. vigilance for signs o ... | 2017 | 28137810 |
| evolution of fseg/cseg dimorphism in region iii of the plasmodium falciparum eba-175 gene. | the 175-kda erythrocyte binding antigen (eba-175) of the malaria parasite plasmodium falciparum is important for its invasion into human erythrocytes. the primary structure of eba-175 is divided into seven regions, namely i to vii. region iii contains highly divergent dimorphic segments, termed fseg and cseg. the allele frequencies of segmental dimorphism within a p. falciparum population have been extensively examined; however, the molecular evolution of segmental dimorphism is not well underst ... | 2017 | 28137625 |
| malaria control and prevention towards elimination: data from an eleven-year surveillance in shandong province, china. | shandong province experienced a declining malaria trend of local-acquired transmission, but the increasing imported malaria remains a challenge. therefore, understanding the epidemiological characteristics of malaria and the control and elimination strategy and interventions is needed for better planning to achieve the overall elimination goal in shandong province. | 2017 | 28137270 |
| mycotoxins from the fungus botryotrichum piluliferum. | two new sterigmatocystin derivatives, oxisterigmatocystins e and f (1 and 2, respectively), along with nine known compounds, oxisterigmatocystins g and h (3 and 4, respectively), sterigmatocystin (5), n-0532b (6), o-methylsterigmatocystin (7), n-0532a (8), 6-o-methylversicolorin a (9), 6,8-o-dimethylversicolorin a (10), and 8-o-methylaverufin (11), were isolated from the fungus botryotrichum piluliferum. the structures of these mycotoxins were elucidated by spectroscopic evidence. among these, c ... | 2017 | 28135416 |
| establishment and application of a novel isothermal amplification assay for rapid detection of chloroquine resistance (k76t) in plasmodium falciparum. | chloroquine (cq) resistance in plasmodium falciparum is determined by the mutations in the chloroquine resistance transporter (pfcrt) gene. the point mutation at codon 76 (k76t), which has been observed in more than 91% of p. falciparum isolates in india, is the major determinant of cq resistance. to overcome the limitations and challenges of traditional methods, in this investigation we developed an easy to use loop mediated isothermal amplification (lamp) protocol for rapid detection of the k7 ... | 2017 | 28134241 |
| novel adenovirus encoded virus-like particles displaying the placental malaria associated var2csa antigen. | the malaria parasite plasmodium falciparum presents antigens on the infected erythrocyte surface that bind human receptors expressed on the vascular endothelium. the var2csa mediated binding to a distinct chondroitin sulphate a (csa) is a crucial step in the pathophysiology of placental malaria and the csa binding region of var2csa has been identified as a promising vaccine target against placental malaria. here we designed adenovirus encoded virus-like particles (vlp) by co-encoding simian immu ... | 2017 | 28131394 |
| investigating the antiplasmodial activity of primary sulfonamide compounds identified in open source malaria data. | in the past decade there has been a significant reduction in deaths due to malaria, in part due to the success of the gold standard antimalarial treatment - artemisinin combination therapies (acts). however the potential threat of act failure and the lack of a broadly effective malaria vaccine are driving efforts to discover new chemical entities (nces) to target this disease. the primary sulfonamide (ps) moiety is a component of several clinical drugs, including those for treatment of kidney di ... | 2017 | 28129569 |
| functionally relevant proteins in plasmodium falciparum host cell invasion. | a totally effective, antimalarial vaccine must involve sporozoite and merozoite proteins (or their fragments) to ensure complete parasite blocking during critical invasion stages. this special report examines proteins involved in critical biological functions for parasite survival and highlights the conserved amino acid sequences of the most important proteins involved in sporozoite invasion of hepatocytes and merozoite invasion of red blood cells. conserved high activity binding peptides are lo ... | 2017 | 28128713 |
| in vitro antiplasmodial activity and cytotoxic effect of (z)-2-benzylidene-4, 6-dimethoxybenzofuran-3(2h)-one derivatives. | aurones are naturally occurring compounds that belong to flavenoids family and have antiplasmodial effects. this study investigated some new aurones derivatives against chloroquine sensitive plasmodium falciparum. here we report the synthesis, in vitro antiplasmodial activity and cytotoxic evaluation of 11 compound from derivatives of (z)-2- benzylidene-4, 6-dimethoxybenzofuran-3(2h)-one. | 2017 | 28127343 |
| sex-specific biology of the human malaria parasite revealed from the proteomes of mature male and female gametocytes. | the gametocytes of the malaria parasites are obligate for perpetuating the parasite's life cycle through mosquitoes, but the sex-specific biology of gametocytes is poorly understood. we generated a transgenic line in the human malaria parasite plasmodium falciparum, which allowed us to accurately separate male and female gametocytes by flow cytometry. in-depth analysis of the proteomes by liquid chromatography-tandem mass spectrometry identified 1244 and 1387 proteins in mature male and female g ... | 2017 | 28126901 |
| serology reveals heterogeneity of plasmodium falciparum transmission in northeastern south africa: implications for malaria elimination. | it is widely acknowledged that modifications to existing control interventions are required if south africa is to achieve malaria elimination. targeting indoor residual spraying (irs) to areas where cases have been detected is one strategy currently under investigation in northeastern south africa. this seroprevalence baseline study, nested within a targeted irs trial, was undertaken to provide insights into malaria transmission dynamics in south africa and evaluate whether sero-epidemiological ... | 2017 | 28126001 |
| the impact of urbanization and population density on childhood plasmodium falciparum parasite prevalence rates in africa. | although malaria has been traditionally regarded as less of a problem in urban areas compared to neighbouring rural areas, the risk of malaria infection continues to exist in densely populated, urban areas of africa. despite the recognition that urbanization influences the epidemiology of malaria, there is little consensus on urbanization relevant for malaria parasite mapping. previous studies examining the relationship between urbanization and malaria transmission have used products defining ur ... | 2017 | 28125996 |
| the real mccoil: a method for the concurrent estimation of the complexity of infection and snp allele frequency for malaria parasites. | as many malaria-endemic countries move towards elimination of plasmodium falciparum, the most virulent human malaria parasite, effective tools for monitoring malaria epidemiology are urgent priorities. p. falciparum population genetic approaches offer promising tools for understanding transmission and spread of the disease, but a high prevalence of multi-clone or polygenomic infections can render estimation of even the most basic parameters, such as allele frequencies, challenging. a previous me ... | 2017 | 28125584 |
| cytokine profiles in malawian children presenting with uncomplicated malaria, severe malarial anemia, and cerebral malaria. | proinflammatory cytokines are involved in clearance of plasmodium falciparum, and very high levels of these cytokines have been implicated in the pathogenesis of severe malaria. in order to determine how cytokines vary with disease severity and syndrome, we enrolled malawian children presenting with cerebral malaria (cm), severe malarial anemia (sma), and uncomplicated malaria (ucm) and healthy controls. we analyzed serum cytokine concentrations in acute infection and in convalescence. with the ... | 2017 | 28122790 |
| in vitro activity of anti-malarial ozonides against an artemisinin-resistant isolate. | recently published data suggest that artemisinin derivatives and synthetic peroxides, such as the ozonides oz277 and oz439, have a similar mode of action. here the cross-resistance of oz277 and oz439 and four additional next-generation ozonides was probed against the artemisinin-resistant clinical isolate plasmodium falciparum cam3.i, which carries the k13-propeller mutation r539t (cam3.i(r539t)). | 2017 | 28122617 |
| beyond the entomological inoculation rate: characterizing multiple blood feeding behavior and plasmodium falciparum multiplicity of infection in anopheles mosquitoes in northern zambia. | a commonly used measure of malaria transmission intensity is the entomological inoculation rate (eir), defined as the product of the human biting rate (hbr) and sporozoite infection rate (sir). the eir excludes molecular parameters that may influence vector control and surveillance strategies. the purpose of this study was to investigate anopheles multiple blood feeding behavior (mbf) and plasmodium falciparum multiplicity of infection (moi) within the mosquito host in nchelenge district, northe ... | 2017 | 28122597 |