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p. falciparum

NOT Open Access | A Concise Total Synthesis of Dehydroantofine and the Antimalarial Activity against Chloroquine-Resistant P. falciparum

January 26, 2021 - 15:09 -- NOT Open Access
Yamasaki N, Iwasaki I, Sakumi K, Hokari R, Ishiyama A, Iwatsuki M, Nakahara M, Higashibayashi S, Sugai T, Imagawa H, Kubo M, Fukuyama Y, Ōmura S, Yamamoto H
Chemistry. 2021 Jan 2

A total synthesis of dehydroantofine was achieved by employing a novel, regioselective azahetero Diels-Alder reaction of the easily accessible 3,5-dichloro-2 H -1,4-oxazin-2-one with 4-ethynyl-1,2-dimethoxybenzene as a key step.

Development and Clinical Validation of Iso-IMRS: A Novel Diagnostic Assay for P. falciparum Malaria

January 20, 2021 - 07:05 -- Open Access
Kolluri N, Kamath S, Lally P, Zanna M, Galagan J, Gitaka J, Kamita M, Cabodi M, Lolabattu SR, Klapperich CM
Anal Chem. 2021 Jan 19

In many countries targeting malaria elimination, persistent malaria infections can have parasite loads significantly below the lower limit of detection (LLOD) of standard diagnostic techniques, making them difficult to identify and treat. The most sensitive diagnostic methods involve amplification and detection of Plasmodium DNA by polymerase chain reaction (PCR), which requires expensive thermal cycling equipment and is difficult to deploy in resource-limited settings. Isothermal DNA amplification assays have been developed, but they require complex primer design, resulting in high nonspecific amplification, and show a decrease in sensitivity than PCR methods. Here, we have used a computational approach to design a novel isothermal amplification assay with a simple primer design to amplify P. falciparum DNA with analytical sensitivity comparable to PCR.

NOT Open Access | Comparative study between the anti-P. falciparum activity of triazolopyrimidine, pyrazolopyrimidine and quinoline derivatives and the identification of new PfDHODH inhibitors

January 6, 2021 - 13:03 -- NOT Open Access
Silveira FF, de Souza JO, Pinheiro LCS, et al.
Eur J Med Chem. 2021 Jan 1;209:112941

In this work, we designed and synthesized 35 new triazolopyrimidine, pyrazolopyrimidine and quinoline derivatives as P. falciparum inhibitors (3D7 strain). Thirty compounds exhibited anti-P. falciparum activity, with IC50 values ranging from 0.030 to 9.1 μM. The [1,2,4]triazolo[1,5-a]pyrimidine derivatives were more potent than the pyrazolo[1,5-a]pyrimidine and quinoline analogues. Compounds 20, 21, 23 and 24 were the most potent inhibitors, with IC50 values in the range of 0.030-0.086 μM and were equipotent to chloroquine. In addition, the compounds were selective, showing no cytotoxic activity against the human hepatoma cell line HepG2. All [1,2,4]triazolo[1,5-a]pyrimidine derivatives inhibited PfDHODH activity in the low micromolar to low nanomolar range (IC50 values of 0.08-1.3 μM) and did not show significant inhibition against the HsDHODH homologue (0-30% at 50 μM).

The molecular basis for peptide-based antimalarial vaccine development targeting erythrocyte invasion by P. falciparum

December 15, 2020 - 14:15 -- Open Access
Aza-Conde J, Reyes C, Suárez CF, Patarroyo MA, Patarroyo ME
Biochem Biophys Res Commun. 2020 Dec 10;534:86-93

This work describes a methodology for developing a minimal, subunit-based, multi-epitope, multi-stage, chemically-synthesised, anti-Plasmodium falciparum malaria vaccine. Some modified high activity binding peptides (mHABPs) derived from functionally relevant P. falciparum MSP, RH5 and AMA-1 conserved amino acid regions (cHABPs) for parasite binding to and invasion of red blood cells (RBC) were selected.

SARS-COV2 and P. falciparum common immunodominant regions may explain low COVID-19 incidence in the malaria-endemic belt

November 25, 2020 - 12:39 -- Open Access
Iesa MA, Osman ME, Hassan MA, Dirar AI, Abuzeid N, Mancuso JJ, Pandey R, Mohammed AA, Borad MJ, Babiker HM, Konozy EH
New Microbes New Infect. 2020 Nov 19:100817

COVID-19 has caused significant morbidity and mortality, and new cases are on the rise globally, yet malaria-endemic areas report statistically significant lower incidences. We identified potential shared targets for an immune response to SARS-CoV-2 by immune determinants shared identities with Plasmodium falciparum using IEDB's Immune browser tool 9.0.

NOT Open Access | Antimicrobial evaluation of neutral and cationic iridium(III) and rhodium(III) aminoquinoline-benzimidazole hybrid complexes

November 19, 2020 - 13:41 -- NOT Open Access
Baartzes N, Jordaan A, Warner DF, Combrinck J, Taylor D, Chibale K, Smith GS
Eur J Med Chem. 2020 Nov 15;206:112694

A series of neutral and cationic Ir(III) and Rh(III) aminoquinoline-benzimidazole hybrid complexes were synthesised and their inhibitory activities evaluated against Plasmodium falciparum and Mycobacterium tuberculosis. In general, the hybrid complexes display good activity against the chloroquine-sensitive NF54 strain of P. falciparum.

The impact of delayed treatment of uncomplicated P. falciparum malaria on progression to severe malaria: A systematic review and a pooled multicentre individual-patient meta-analysis

October 21, 2020 - 08:39 -- Open Access
Mousa A, Al-Taiar A, Okell LC, et al.
PLoS Med. 2020 Oct 19;17(10):e1003359

Delay in receiving treatment for uncomplicated malaria (UM) is often reported to increase the risk of developing severe malaria (SM), but access to treatment remains low in most high-burden areas. Understanding the contribution of treatment delay on progression to severe disease is critical to determine how quickly patients need to receive treatment and to quantify the impact of widely implemented treatment interventions, such as ‘test-and-treat’ policies administered by community health workers (CHWs). We conducted a pooled individual-participant meta-analysis to estimate the association between treatment delay and presenting with SM.

Integrative genomic analysis reveals mechanisms of immune evasion in P. falciparum malaria

October 13, 2020 - 12:48 -- Open Access
Dieng MM, Diawara A, Idaghdour Y, et al.
Nat Commun. 2020 Oct 9;11(1):5093

The mechanisms behind the ability of Plasmodium falciparum to evade host immune system are poorly understood and are a major roadblock in achieving malaria elimination. Here, we use integrative genomic profiling and a longitudinal pediatric cohort in Burkina Faso to demonstrate the role of post-transcriptional regulation in host immune response in malaria.

Not Open Access | Multidose Priming and Delayed Boosting Improve PfSPZ Vaccine Efficacy against Heterologous P. falciparum Controlled Human Malaria Infection

September 15, 2020 - 14:32 -- NOT Open Access
Lyke KE, Singer A, Epstein JE, et al.
Clin Infect Dis. 2020 Sep 12:ciaa1294

A live-attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) vaccine (PfSPZ Vaccine) has shown up to 100% protection against controlled human malaria infection (CHMI) using homologous parasites (same Pf strain as in the vaccine). Using a more stringent CHMI, with heterologous parasites (different Pf strain), we assessed the impact of higher PfSPZ doses, a novel multi-dose prime regimen, and a delayed vaccine boost upon vaccine efficacy.

Sub-optimal Intermittent Preventive Treatment in pregnancy (IPTp) is associated with an increased risk of submicroscopic P. falciparum infection in pregnant women: a prospective cohort study in Benin

September 10, 2020 - 08:51 -- Open Access
Hounkonnou CPA, Ndam NT, Fievet N, Accrombessi M, Yovo E, Mama A, Sossou D, Vianou B, Massougbodji A, Briand V, Cot M, Cottrell G
Clin Infect Dis. 2020 Sep 9:ciaa1355

Harmful maternal and neonatal health outcomes result from malaria in pregnancy, the prevention of which primarily relies on intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP). WHO recommends IPTp-SP in sub-Saharan Africa, but implementation is highly heterogeneous and often sub-optimal in terms of the number of doses and their timing. In this study, we assessed the impact of this heterogeneity on malaria in pregnancy, mainly with respect to submicroscopic Plasmodium falciparum infections.


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