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Elucidating relationships between P.falciparum prevalence and measures of genetic diversity with a combined genetic-epidemiological model of malaria

August 25, 2021 - 16:03 -- Open Access
Hendry JA, Kwiatkowski D, McVean G
PLoS Comput Biol. 2021 Aug 19;17(8):e1009287

There is an abundance of malaria genetic data being collected from the field, yet using these data to understand the drivers of regional epidemiology remains a challenge. A key issue is the lack of models that relate parasite genetic diversity to epidemiological parameters. Classical models in population genetics characterize changes in genetic diversity in relation to demographic parameters, but fail to account for the unique features of the malaria life cycle.

NOT Open Access | Efficacy of Chininum Sulphuricum 30C against Malaria: An in vitro and in vivo Study

July 28, 2021 - 14:13 -- NOT Open Access
Suri M, Katnoria S, Walter NS, Manchanda RK, Khurana A, Nayak D, Bagai U, Kaur S
Complement Med Res. 2021 Jul 27:1-10

New effective, economical and safe antimalarial drugs are urgently needed due to the development of multi-drug-resistant strains of the parasite. Homeopathy uses ultra-diluted doses of various substances to stimulate autoregulatory and self-healing processes to cure various ailments. The aim of the study was to evaluate the in vitro and in vivo antimalarial efficacy of a homeopathic drug, Chininum sulphuricum 30C.

Assessing field performance of ultrasensitive rapid diagnostic tests for malaria: a systematic review and meta-analysis

June 9, 2021 - 07:34 -- Open Access
Celestin Danwang, Fati Kirakoya-Samadoulougou and Sekou Samadoulougou
Malaria Journal 2021 20:245, 3 June 2021

To overcome the limitations of conventional malaria rapid diagnostic tests (cRDTs) in diagnosing malaria in patients with low parasitaemia, ultrasensitive malaria rapid diagnostic tests (uRDTs) have recently been developed, with promising results under laboratory conditions. The current study is the first meta-analysis comparing the overall sensitivity, and specificity of newly developed ultrasensitive Plasmodium falciparum malaria RDT (Alere™ Ultra-sensitive Malaria Ag P. falciparum RDT) with the cRDT conducted in the same field conditions.

Anopheles ecology, genetics and malaria transmission in northern Cambodia

March 24, 2021 - 14:09 -- Open Access
Vantaux A, Riehle MM, Witkowski B, et al.
Sci Rep. 2021 Mar 19;11(1):6458

In the Greater Mekong Subregion, malaria cases have significantly decreased but little is known about the vectors or mechanisms responsible for residual malaria transmission. We analysed a total of 3920 Anopheles mosquitoes collected during the rainy and dry seasons from four ecological settings in Cambodia (villages, forested areas near villages, rubber tree plantations and forest sites). Using odor-baited traps, 81% of the total samples across all sites were collected in cow baited traps, although 67% of the samples attracted by human baited traps were collected in forest sites. Overall, 20% of collected Anopheles were active during the day, with increased day biting during the dry season.

A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes

March 23, 2021 - 14:35 -- Open Access
Coelho CH, Tang WK, Duffy PE, et al.
Nat Commun. 2021 Mar 19;12(1):1750

Malaria elimination requires tools that interrupt parasite transmission. Here, we characterize B cell receptor responses among Malian adults vaccinated against the first domain of the cysteine-rich 230 kDa gamete surface protein Pfs230, a key protein in sexual stage development of P. falciparum parasites.

Not Open Access | Structure activity refinement of phenylsulfonyl piperazines as antimalarials that block erythrocytic invasion

March 17, 2021 - 09:37 -- NOT Open Access
Nguyen W, Dans MG, Sleebs BE, et al.
Eur J Med Chem. 2021 Mar 15;214:113253

The emerging resistance to combination therapies comprised of artemisinin derivatives has driven a need to identify new antimalarials with novel mechanisms of action. Central to the survival and proliferation of the malaria parasite is the invasion of red blood cells by Plasmodium merozoites, providing an attractive target for novel therapeutics. A screen of the Medicines for Malaria Venture Pathogen Box employing transgenic P. falciparum parasites expressing the nanoluciferase bioluminescent reporter identified the phenylsulfonyl piperazine class as a specific inhibitor of erythrocyte invasion.

NOT Open Access | 3-aryl-indolinones derivatives as antiplasmodial agents: synthesis, biological activity and computational analysis

March 17, 2021 - 09:06 -- NOT Open Access
Luczywo A, González LG, Mellado M, et al.
Nat Prod Res. 2021 Mar 11:1-7

Malaria is an infectious illness, affecting vulnerable populations in Third World countries. Inspired by natural products, indole alkaloids have been used as a nucleus to design new antimalarial drugs. So, eighteen oxindole derivatives, aza analogues were obtained with moderate to excellent yields. Also, the saturated derivatives of oxindole and aza derivatives via H2/Pd/C reduction were obtained in good yields, leading to racemic mixtures of each compound.

NOT Open Access | Synthesis and antiplasmodial evaluation of 1H-1,2,3-triazole grafted 4-aminoquinoline-benzoxaborole hybrids and benzoxaborole analogues

February 25, 2021 - 10:13 -- NOT Open Access
Saini A, Kumar S, Raj R, Chowdhary S, Gendrot M, Mosnier J, Fonta I, Pradines B, Kumar V
Bioorg Chem. 2021 Feb 16;109:104733

A library of 1H-1,2,3-triazole-tethered 4-aminoquinoline-benzoxaborole hybrids as well as aryl substituted benzoxaborole analogues was synthesized and screened for their anti-plasmodial efficacy against both chloroquine-susceptibility 3D7 and chloroquine-resistant W2 strains of P. falciparum. The inclusion of quinoline core among the synthesized analogues resulted in substantial enhancement of anti-plasmodial activities.

A redox-active crosslinker reveals an essential and inhibitable oxidative folding network in the endoplasmic reticulum of malaria parasites

February 9, 2021 - 10:02 -- Open Access
Cobb DW, Kudyba HM, Villegas A, Hoopmann MR, Baptista RP, Bruton B, Krakowiak M, Moritz RL, Muralidharan V
PLoS Pathog. 2021 Feb 3;17(2):e1009293

Malaria remains a major global health problem, creating a constant need for research to identify druggable weaknesses in P. falciparum biology. As important components of cellular redox biology, members of the Thioredoxin (Trx) superfamily of proteins have received interest as potential drug targets in Apicomplexans. However, the function and essentiality of endoplasmic reticulum (ER)-localized Trx-domain proteins within P. falciparum has not been investigated.


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