scholarly journals Re-defining the Golgi complex in Plasmodium falciparum using the novel Golgi marker PfGRASP

2005 ◽  
Vol 118 (23) ◽  
pp. 5603-5613 ◽  
Author(s):  
N. S. Struck
Keyword(s):  
Plasmodium Falciparum ◽  
Golgi Complex ◽  
The Novel

scholarly journals Deep Profiling of the Novel Intermediate-Size Noncoding RNAs in Intraerythrocytic Plasmodium falciparum

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e92946 ◽  
Author(s):  
Chunyan Wei ◽  
Tengfei Xiao ◽  
Peng Zhang ◽  
Zhensheng Wang ◽  
Xiaowei Chen ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Noncoding Rnas ◽  
The Novel ◽  
Intermediate Size

scholarly journals A multiplex qPCR approach for detection of pfhrp2 and pfhrp3 gene deletions in multiple strain infections of Plasmodium falciparum

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tobias Schindler ◽  
Anna C. Deal ◽  
Martina Fink ◽  
Etienne Guirou ◽  
Kara A. Moser ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Control ◽  
High Throughput Screening ◽  
Malaria Diagnosis ◽  
The Novel ◽  
Essential Factor ◽  
Gene Deletions ◽  
Control Programs ◽  
Sub Saharan ◽  
Insight Into

Abstract The rapid and accurate diagnosis of Plasmodium falciparum malaria infection is an essential factor in malaria control. Currently, malaria diagnosis in the field depends heavily on using rapid diagnostic tests (RDTs) many of which detect circulating parasite-derived histidine-rich protein 2 antigen (PfHRP2) in capillary blood. P. falciparum strains lacking PfHRP2, due to pfhrp2 gene deletions, are an emerging threat to malaria control programs. The novel assay described here, named qHRP2/3-del, is well suited for high-throughput screening of P. falciparum isolates to identify these gene deletions. The qHRP2/3-del assay identified pfhrp2 and pfhrp3 deletion status correctly in 93.4% of samples with parasitemia levels higher than 5 parasites/µL when compared to nested PCR. The qHRP2/3-del assay can correctly identify pfhrp2 and pfhrp3 gene deletions in multiple strain co-infections, particularly prevalent in Sub-Saharan countries. Deployment of this qHRP2/3-del assay will provide rapid insight into the prevalence and potential spread of P. falciparum isolates that escape surveillance by RDTs.

scholarly journals Modelling the population dynamics of Plasmodium falciparum gametocytes in humans during malaria infection

2019 ◽  
Author(s):  
Pengxing Cao ◽  
Katharine A. Collins ◽  
Sophie Zaloumis ◽  
Thanaporn Wattanakul ◽  
Joel Tarning ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Plasmodium Falciparum ◽  
Population Dynamics ◽  
Malaria Infection ◽  
Credible Interval ◽  
The Novel ◽  
Reliable Prediction ◽  
Bayesian Hierarchical ◽  
Kinetics Of

AbstractEvery year over two hundred million people are infected with the malaria parasite. Renewed efforts to eliminate malaria has highlighted the potential to interrupt transmission from humans to mosquitoes which is mediated through the gametocytes. Reliable prediction of transmission requires an improved understanding of in vivo kinetics of gametocytes. Here we study the population dynamics of Plasmodium falciparum gametocytes in human hosts by establishing a framework which incorporates improved measurements of parasitaemia in humans, a novel mathematical model of gametocyte dynamics, and model validation using a Bayesian hierarchical inference method. We found that the novel mathematical model provides an excellent fit to the available clinical data from 17 volunteers infected with P. falciparum, and reliably predicts observed gametocyte levels. We estimated the P. falciparum’s sexual commitment rate and gametocyte sequestration time in humans to be 0.54% (95% credible interval: 0.30-1.00) per life cycle and 8.39 (6.54-10.59) days respectively. Furthermore, we used the data-calibrated model to predict the effects of those gametocyte dynamics parameters on human-to-mosquito transmissibility, providing a method to link within-human host kinetics of malaria infection to epidemiological-scale infection and transmission patterns.

Evidences of protection against blood-stage infection of Plasmodium falciparum by the novel protein vaccine SE36

2010 ◽  
Vol 59 (3) ◽  
pp. 380-386 ◽  
Author(s):  
Toshihiro Horii ◽  
Hiroki Shirai ◽  
Li Jie ◽  
Ken J. Ishii ◽  
Nirianne Q. Palacpac ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Blood Stage ◽  
The Novel ◽  
Protein Vaccine ◽  
Blood Stage Infection ◽  
Stage Infection ◽  
Novel Protein

scholarly journals Identification of Protective B-Cell Epitopes within the Novel Malaria Vaccine Candidate Plasmodium falciparum Schizont Egress Antigen 1

2017 ◽  
Vol 24 (7) ◽  
Author(s):  
Christina E. Nixon ◽  
Sangshin Park ◽  
Sunthorn Pond-Tor ◽  
Dipak Raj ◽  
Lynn E. Lambert ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
B Cell ◽  
The Novel ◽  
B Cell Epitopes ◽  
Content Type ◽  
Peptide Microarrays ◽  
Malaria Vaccine Candidate ◽  
Antibody Levels ◽  
Longitudinal Treatment ◽  
The Relationship

ABSTRACT Naturally acquired antibodies to Plasmodium falciparum schizont egress antigen 1 (PfSEA-1A) are associated with protection against severe malaria in children. Vaccination of mice with SEA-1A from Plasmodium berghei (PbSEA-1A) decreases parasitemia and prolongs survival following P. berghei ANKA challenge. To enhance the immunogenicity of PfSEA-1A, we identified five linear B-cell epitopes using peptide microarrays probed with antisera from nonhuman primates vaccinated with recombinant PfSEA-1A (rPfSEA-1A). We evaluated the relationship between epitope-specific antibody levels and protection from parasitemia in a longitudinal treatment-reinfection cohort in western Kenya. Antibodies to three epitopes were associated with 16 to 17% decreased parasitemia over an 18-week high transmission season. We are currently designing immunogens to enhance antibody responses to these three epitopes.

scholarly journals ComparativeEx VivoActivity of Novel Endoperoxides in Multidrug-Resistant Plasmodium falciparum and P. vivax

2012 ◽  
Vol 56 (10) ◽  
pp. 5258-5263 ◽  
Author(s):  
Jutta Marfurt ◽  
Ferryanto Chalfein ◽  
Pak Prayoga ◽  
Frans Wabiser ◽  
Grennady Wirjanata ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Ex Vivo ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Intrinsic Activity ◽  
Drug Resistant ◽  
The Novel ◽  
Content Type ◽  
Artemisinin Derivatives

ABSTRACTThe declining efficacy of artemisinin derivatives againstPlasmodium falciparumhighlights the urgent need to identify alternative highly potent compounds for the treatment of malaria. In Papua Indonesia, where multidrug resistance has been documented against bothP. falciparumandP. vivaxmalaria, comparativeex vivoantimalarial activity againstPlasmodiumisolates was assessed for the artemisinin derivatives artesunate (AS) and dihydroartemisinin (DHA), the synthetic peroxides OZ277 and OZ439, the semisynthetic 10-alkylaminoartemisinin derivatives artemisone and artemiside, and the conventional antimalarial drugs chloroquine (CQ), amodiaquine (AQ), and piperaquine (PIP).Ex vivodrug susceptibility was assessed in 46 field isolates (25P. falciparumand 21P. vivax). The novel endoperoxide compounds exhibited potentex vivoactivity against both species, but significant differences in intrinsic activity were observed. Compared to AS and its active metabolite DHA, all the novel compounds showed lower or equal 50% inhibitory concentrations (IC50s) in both species (median IC50s between 1.9 and 3.6 nM inP. falciparumand 0.7 and 4.6 nM inP. vivax). The antiplasmodial activity of novel endoperoxides showed different cross-susceptibility patterns in the twoPlasmodiumspecies: whereas theirex vivoactivity correlated positively with CQ, PIP, AS, and DHA inP. falciparum, the same was not apparent inP. vivax. The current study demonstrates for the first time potent activity of novel endoperoxides against drug-resistantP. vivax. The high activity against drug-resistant strains of bothPlasmodiumspecies confirms these compounds to be promising candidates for future artemisinin-based combination therapy (ACT) regimens in regions of coendemicity.

scholarly journals Cholesterol bound Plasmodium falciparum co-chaperone ‘PFA0660w’ complexes with major virulence factor ‘PfEMP1’ via chaperone ‘PfHsp70-x’

2018 ◽  
Author(s):  
Ankita Behl ◽  
Vikash Kumar ◽  
Anjali Bisht ◽  
Jiban J. Panda ◽  
Rachna Hora ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Direct Interaction ◽  
Lipid Binding ◽  
The Novel ◽  
The Past ◽  
Biochemical Assays ◽  
Erythrocyte Surface ◽  
Parasite Survival

AbstractLethality of Plasmodium falciparum (Pf) caused malaria results from ‘cytoadherence’, which is effected by exported Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. Several exported Pf proteins (exportome) including chaperones alongside cholesterol rich microdomains are crucial for PfEMP1 translocation to infected erythrocyte surface. An exported Hsp40 (heat shock protein 40) ‘PFA0660w’ functions as a co-chaperone of ‘PfHsp70-x’, and these co-localize to specialized intracellular mobile structures termed J-dots. Our studies attempt to understand the function of PFA0660w-PfHsp70-x chaperone pair using recombinant proteins. Biochemical assays reveal that N and C-terminal domains of PFA0660w and PfHsp70-x respectively are critical for their activity. We show the novel direct interaction of PfHsp70-x with the cytoplasmic tail of PfEMP1, and binding of PFA0660w with cholesterol. PFA0660w operates both as a chaperone and lipid binding molecule via its separate substrate and cholesterol binding sites. PfHsp70-x binds cholesterol linked PFA0660w and PfEMP1 simultaneously in vitro to form a complex. Collectively, our results and the past literature support the hypothesis that PFA0660w-PfHsp70-x chaperone pair assists PfEMP1 transport across the host erythrocyte through cholesterol containing ‘J-dots’. Since PFA0660w seems essential for parasite survival, characterization of its interaction with PfHsp70-x and J-dots may form the basis for development of future antimalarials.

scholarly journals Pharmacoinformatics based elucidation and designing of potential inhibitors against Plasmodium falciparum to target importin α/β mediated nuclear importation

2020 ◽  
Author(s):  
Arafat Rahman Oany ◽  
Tahmina Pervin ◽  
Mohammad Ali Moni
Keyword(s):  
Plasmodium Falciparum ◽  
Dynamics Simulation ◽  
The Novel ◽  
Importin Alpha ◽  
Importin Α ◽  
The Stability ◽  
Potential Inhibitors ◽  
Side Pocket

AbstractPlasmodium falciparum, the prime causative agent of malaria, is responsible for 4, 05,000 deaths per year and fatality rates are higher among the children aged below 5 years. The emerging distribution of the multi-drug resistant P. falciparum becomes a worldwide concern, so the identification of unique targets and novel inhibitors is a prime need now. In the present study, we have employed pharmacoinformatics approaches to analyze 265 lead-like compounds from PubChem databases for virtual screening. Thereafter, 15 lead-like compounds were docked within the active side pocket of importin alpha. Comparative ligand properties and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile were also assessed. Finally, a novel inhibitor was designed and assessed computationally for its efficacy. From the comparative analysis we have found that our screened compounds possess better results than the existing lead ivermectin; having the highest binding energy of −15.6 kcal/mol, whereas ivermectin has −12.4kcal/mol. The novel lead compound possessed more fascinating output without deviating any of the rules of Lipinski. It also possessed higher bioavailability and the drug-likeness score of 0.55 and 0.71, respectively compared to ivermectin. Furthermore, the binding study was confirmed by molecular dynamics simulation over 25 ns by evaluating the stability of the complex. Finally, all the screened compounds and the novel compound showed promising ADMET properties likewise. To end, we hope that our proposed screened compounds, as well as the novel compound, might give some advances to treat malaria efficiently in vitro and in vivo.

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