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p. falciparum

NOT Open Access | A Proteasome Mutation Sensitizes P. falciparum Cam3.II K13(C580Y) Parasites to DHA and OZ439

May 12, 2021 - 09:25 -- NOT Open Access
Rosenthal MR, Ng CL
ACS Infect Dis. 2021 May 10

Artemisinin-based combination therapies (ACTs), the World Health Organization-recommended first-line therapy for uncomplicated falciparum malaria, has led to significant decreases in malaria-associated morbidity and mortality in the past two decades. Decreased therapeutic efficacy of artemisinins, the cornerstone of ACTs, is threatening the gains made against this disease.

NOT Open Access | Immunoinformatics approach for multi-epitope vaccine design against P. falciparum malaria

April 29, 2021 - 07:23 -- NOT Open Access
Maharaj L, Adeleke VT, Fatoba AJ, Adeniyi AA, Tshilwane SI, Adeleke MA, Maharaj R, Okpeku M
Infect Genet Evol. 2021 Apr 24:104875

Plasmodium falciparum (P. falciparum) is a leading causative agent of malaria, an infectious disease that can be fatal. Unfortunately, control measures are becoming less effective over time. A vaccine is needed to effectively control malaria and lead towards the total elimination of the disease. There have been multiple attempts to develop a vaccine, but to date, none have been certified as appropriate for wide-scale use. In this study, an immunoinformatics method is presented to design a multi-epitope vaccine construct predicted to be effective against P. falciparum malaria.

Nonparametric Binary Classification to Distinguish Closely Related versus Unrelated P. Falciparum Parasites

April 6, 2021 - 14:14 -- Open Access
Plucinski MM, Barratt JLN
Am J Trop Med Hyg. 2021 Apr 5:tpmd210117

Assessing genetic relatedness of Plasmodium falciparum genotypes is a key component of antimalarial efficacy trials. Previous methods have focused on determining a priori definitions of the level of genetic similarity sufficient to classify two infections as sharing the same strain. However, factors such as mixed-strain infections, allelic suppression, imprecise typing methods, and heterozygosity complicate comparisons of apicomplexan genotypes. Here, we introduce a novel method for nonparametric statistical testing of relatedness for P. falciparum parasites.

School-based screening and treatment may reduce P. falciparum transmission

March 31, 2021 - 14:34 -- Open Access
Cohee LM, Valim C, Laufer MK, et al.
Sci Rep. 2021 Mar 25;11(1):6905

In areas where malaria remains entrenched, novel transmission-reducing interventions are essential for malaria elimination. We report the impact screening-and-treatment of asymptomatic Malawian schoolchildren (n = 364 in the rainy season and 341 in the dry season) had on gametocyte-the parasite stage responsible for human-to-mosquito transmission-carriage.

Blood donor variability is a modulatory factor for P. falciparum invasion phenotyping assays

March 31, 2021 - 14:21 -- Open Access
Thiam LG, Nyarko PB, Kusi KA, Niang M, Aniweh Y, Awandare GA
Sci Rep. 2021 Mar 29;11(1):7129

Human erythrocytes are indispensable for Plasmodium falciparum development. Unlike other eukaryotic cells, there is no existing erythroid cell line capable of supporting long-term P. falciparum in vitro experiments. Consequently, invasion phenotyping experiments rely on erythrocytes of different individuals. However, the contribution of the erythrocytes variation in influencing invasion rates remains unknown, which represents a challenge for conducting large-scale comparative studies.

Crystal structure of P. falciparum Cpn60 bound to ATP reveals an open dynamic conformation before substrate binding

March 17, 2021 - 09:29 -- Open Access
Nguyen B, Ma R, Tang WK, Shi D, Tolia NH
Sci Rep. 2021 Mar 15;11(1):5930

Plasmodium falciparum harbors group 1 and group 2 chaperonin systems to mediate the folding of cellular proteins in different cellular locations. Two distinct group 1 chaperonins operate in the organelles of mitochondria and apicoplasts, while group 2 chaperonins function in the cytosol. No structural information has been reported for any chaperonin from plasmodium.

NOT Open Access | Quinoline carboxamide core moiety-based compounds inhibit P. falciparumfalcipain-2: Design, synthesis and antimalarial efficacy studies

March 2, 2021 - 15:34 -- NOT Open Access
Singh A, Kalamuddin M, Maqbool M, Mohmmed A, Malhotra P, Hoda N
Bioorg Chem. 2021 Mar;108:104514

Targeting Falcipain-2 (FP2) for the development of antimalarials is a promising and established concept in antimalarial drug discovery and development. FP2, a member of papain-family cysteine protease of the malaria parasite Plasmodium falciparum holds an important role in hemoglobin degradation pathway. A new series of quinoline carboxamide-based compounds was designed, synthesized and evaluated for antimalarial activity.

Structural and biophysical correlation of anti-NANP antibodies with in vivo protection against P. falciparum

February 25, 2021 - 10:12 -- Open Access
Pholcharee T, Oyen D, Wilson IA, et al.
Nat Commun. 2021 Feb 16;12(1):1063

The most advanced P. falciparum circumsporozoite protein-based malaria vaccine, RTS,S/AS01 (RTS,S), confers partial protection but with antibody titers that wane relatively rapidly, highlighting the need to elicit more potent and durable antibody responses. Here, we elucidate crystal structures, binding affinities and kinetics, and in vivo protection of eight anti-NANP antibodies derived from an RTS,S phase 2a trial and encoded by three different heavy-chain germline genes.

Breakdown in membrane asymmetry regulation leads to monocyte recognition of P. falciparum-infected red blood cells

February 23, 2021 - 12:55 -- Open Access
Fraser M, Jing W, Bröer S, Kurth F, Sander LE, Matuschewski K, Maier AG
PLoS Pathog. 2021 Feb 18;17(2):e1009259

The human malaria parasite Plasmodium falciparum relies on lipids to survive; this makes its lipid metabolism an attractive drug target. The lipid phosphatidylserine (PS) is usually confined to the inner leaflet of the red blood cell membrane (RBC) bilayer; however, some studies suggest that infection with the intracellular parasite results in the presence of this lipid in the RBC membrane outer leaflet, where it could act as a recognition signal to phagocytes. Here, we used fluorescent lipid analogues and probes to investigate the enzymatic reactions responsible for maintaining asymmetry between membrane leaflets, and found that in parasitised RBCs the maintenance of membrane asymmetry was partly disrupted, and PS was increased in the outer leaflet.

NOT Open Access | Distribution and temporal dynamics of P. falciparum chloroquine resistance transporter mutations associated with piperaquine resistance in Northern Cambodia

February 3, 2021 - 15:27 -- NOT Open Access
Shrestha B, Shah Z, Takala-Harrison S, et al.
J Infect Dis. 2021 Feb 2:jiab055

Newly emerged mutations within the Plasmodium falciparum chloroquine resistance transporter (PfCRT) can confer piperaquine resistance in the absence of amplified plasmepsin II (pfpm2). In this study, we estimated the prevalence of co-circulating piperaquine resistance mutations in P. falciparum isolates collected in northern Cambodia from 2009-2017.


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