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plasmodium falciparum

Functional characterization of 5′ UTR cis-acting sequence elements that modulate translational efficiency in Plasmodium falciparum and humans

January 19, 2022 - 20:42 -- Open Access
Valentina E. Garcia, Rebekah Dial and Joseph L. DeRisi
Malaria Journal 2022 21:15, 6 January 2022

The eukaryotic parasite Plasmodium falciparum causes millions of malarial infections annually while drug resistance to common anti-malarials is further confounding eradication efforts. Translation is an attractive therapeutic target that will benefit from a deeper mechanistic understanding. As the rate limiting step of translation, initiation is a primary driver of translational efficiency. It is a complex process regulated by both cis and trans acting factors, providing numerous potential targets. Relative to model organisms and humans, P. falciparum mRNAs feature unusual 5′ untranslated regions suggesting cis-acting sequence complexity in this parasite may act to tune levels of protein synthesis through their effects on translational efficiency.

A practical approach for geographic prioritization and targeting of insecticide-treated net distribution campaigns during public health emergencies and in resource-limited settings

January 19, 2022 - 20:30 -- Open Access
Alyssa J. Young, Will Eaton, Matt Worges, Honelgn Hiruy, Kolawole Maxwell, Bala Mohammed Audu, Madeleine Marasciulo, Charles Nelson, James Tibenderana and Tarekegn A. Abeku
Malaria Journal 2022 21:10, 4 January 2022

The use of data in targeting malaria control efforts is essential for optimal use of resources. This work provides a practical mechanism for prioritizing geographic areas for insecticide-treated net (ITN) distribution campaigns in settings with limited resources.

Naturally acquired antibody response to a Plasmodium falciparum chimeric vaccine candidate GMZ2.6c and its components (MSP-3, GLURP, and Pfs48/45) in individuals living in Brazilian malaria-endemic areas

January 19, 2022 - 20:27 -- Open Access
Barbara Oliveira Baptista, Ana Beatriz Lopes de Souza, Lilian Rose Pratt-Riccio, et al.
Malaria Journal 2022 21:6, 4 January 2022

The GMZ2.6c malaria vaccine candidate is a multi-stage Plasmodium falciparum chimeric protein which contains a fragment of the sexual-stage Pfs48/45-6C protein genetically fused to GMZ2, a fusion protein of GLURP and MSP-3, that has been shown to be well tolerated, safe and immunogenic in clinical trials performed in a malaria-endemic area of Africa. However, there is no data available on the antigenicity or immunogenicity of GMZ2.6c in humans. Considering that circulating parasites can be genetically distinct in different malaria-endemic areas and that host genetic factors can influence the immune response to vaccine antigens, it is important to verify the antigenicity, immunogenicity and the possibility of associated protection in individuals living in malaria-endemic areas with different epidemiological scenarios. Herein, the profile of antibody response against GMZ2.6c and its components (MSP-3, GLURP and Pfs48/45) in residents of the Brazilian Amazon naturally exposed to malaria, in areas with different levels of transmission, was evaluated.

Molecular identification and anti-malarial drug resistance profile of Plasmodium falciparum from patients attending Kisoro Hospital, southwestern Uganda

January 18, 2022 - 21:17 -- Open Access
Manirakiza G, Kassaza K, Taremwa IM, Bazira J, Byarugaba F
Malar J. 2022 Jan 15;21(1):21

The evolution of malaria infection has necessitated the development of highly sensitive diagnostic assays, as well as the use of dried blood spots (DBS) as a potential source of deoxyribonucleic acid (DNA) yield for polymerase chain reaction (PCR) assays. This study identified the different Plasmodium species in malaria-positive patients, and the anti-malarial drug resistance profile for Plasmodium falciparum using DBS samples collected from patients attending Kisoro Hospital in Kisoro district, Southwestern Uganda.

Peroxide Antimalarial Drugs Target Redox Homeostasis in Plasmodium falciparum Infected Red Blood Cells

January 18, 2022 - 21:07 -- Open Access
Siddiqui G, Giannangelo C, Creek DJ, et al.
ACS Infect Dis. 2022 Jan 14;8(1):210-226

Plasmodium falciparum causes the most lethal form of malaria. Peroxide antimalarials based on artemisinin underpin the frontline treatments for malaria, but artemisinin resistance is rapidly spreading. Synthetic peroxide antimalarials, known as ozonides, are in clinical development and offer a potential alternative. Here, we used chemoproteomics to investigate the protein alkylation targets of artemisinin and ozonide probes, including an analogue of the ozonide clinical candidate, artefenomel.

Evaluation of a parasite-density based pooled targeted amplicon deep sequencing (TADS) method for molecular surveillance of Plasmodium falciparum drug resistance genes in Haiti

January 18, 2022 - 21:03 -- Open Access
Louha S, Herman C, Talundzic E, et al.
PLoS One. 2022 Jan 14;17(1):e0262616

Sequencing large numbers of individual samples is often needed for countrywide antimalarial drug resistance surveillance. Pooling DNA from several individual samples is an alternative cost and time saving approach for providing allele frequency (AF) estimates at a population level. Using 100 individual patient DNA samples of dried blood spots from a 2017 nationwide drug resistance surveillance study in Haiti, we compared codon coverage of drug resistance-conferring mutations in four Plasmodium falciparum genes (crt, dhps, dhfr, and mdr1), for the same deep sequenced samples run individually and pooled.

A Novel Malaria Lateral Flow Assay for Detecting Plasmodium falciparum Lactose Dehydrogenase in Busia, Uganda

January 18, 2022 - 20:58 -- Open Access
Bachman CM, Cate DM, Greenhouse B, et al.
Am J Trop Med Hyg. 2022 Jan 17:tpmd210956

Rapid diagnostic tests (RDTs) for Plasmodium falciparum commonly detect histidine-rich protein 2 (HRP-2), but HRP-2 deletions are increasingly recognized. We evaluated a prototype test detecting parasite lactate dehydrogenase (pLDH) and compared it to commercially available RDTs at a health facility in Uganda, using quantitative polymerase chain reaction as a gold standard.

C-type lectin 4 regulates broad-spectrum melanization-based refractoriness to malaria parasites

January 18, 2022 - 20:49 -- Open Access
Simões ML, Dong Y, Mlambo G, Dimopoulos G
PLoS Biol. 2022 Jan 13;20(1):e3001515

Anopheles gambiae melanization-based refractoriness to the human malaria parasite Plasmodium falciparum has rarely been observed in either laboratory or natural conditions, in contrast to the rodent model malaria parasite Plasmodium berghei that can become completely melanized by a TEP1 complement-like system-dependent mechanism.

Elucidating functional epitopes within the N-terminal region of malaria transmission blocking vaccine antigen Pfs230

January 18, 2022 - 20:44 -- Open Access
Miura K, Takashima E, Tsuboi T, et al.
NPJ Vaccines. 2022 Jan 13;7(1):4

Pfs230 is a leading malaria transmission blocking vaccine (TBV) candidate. Comprising 3135 amino acids (aa), the large size of Pfs230 necessitates the use of sub-fragments as vaccine immunogens.

N-terminal phosphorylation regulates the activity of Glycogen Synthase Kinase 3 from Plasmodium falciparum

January 18, 2022 - 20:43 -- Open Access
Pazicky S, Alder A, Mertens H, Svergun DI, Gilberger T, Löw C
Biochem J. 2022 Jan 13:BCJ20210829

As the decline of malaria cases stalled over the last five years, novel targets in Plasmodium falciparum are necessary for the development of new drugs. Glycogen Synthase Kinase (PfGSK3) has been identified as a potential target, since its selective inhibitors were shown to disrupt the parasite's life cycle. In the uncanonical N‑terminal region of the parasite enzyme, we identified several autophosphorylation sites and probed their role in activity regulation of PfGSK3.


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