Ex vivo susceptibility to antimalarial drugs and polymorphisms in drug resistance genes of African Plasmodium falciparum, 2016-2023: a genotype-phenotype association study.

Given the altered responses to both artemisinins and lumefantrine in Eastern Africa, monitoring antimalarial drug resistance in all African countries is paramount. We measured the susceptibility to six antimalarials using growth inhibition assays (IC ) for a total of 805 isolates obtained from travelers returning to France (2016-2023), mainly from West and Central Africa. Isolates were sequenced using molecular inversion probes (MIPs) targeting fourteen drug resistance genes across the parasite genome.

Evaluation of two commercial kits and two laboratory-developed qPCR assays compared to LAMP for molecular diagnosis of malaria.

Background: Malaria is an infectious disease considered as one of the biggest causes of mortality in endemic areas. This life-threatening disease needs to be quickly diagnosed and treated. The standard diagnostic tools recommended by the World Health Organization are thick blood smears microscopy and immuno-chromatographic rapid diagnostic tests.

Plasmodium falciparum proteins involved in cytoadherence of infected erythrocytes to chemokine CX3CL1.

Malaria caused by Plasmodium falciparum is associated with cytoadherence of infected red blood cells (iRBC) to endothelial cells. Numerous host molecules have been involved in cytoadherence, including the adhesive chemokine CX3CL1. Most of the identified parasite ligands are from the multigenic and hypervariable Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) family which makes them poor targets for the development of a broadly protective vaccine.

Plasmodium falciparum clearance is rapid and pitting independent in immune Malian children treated with artesunate for malaria.

Background: In Plasmodium falciparum-infected patients treated with artemisinins, parasitemia declines through so-called pitting, an innate splenic process that transforms infected red blood cells (iRBCs) into once-infected RBCs (O-iRBCs).

Methods: We measured pitting in 83 French travelers and 42 Malian children treated for malaria with artesunate.

Results: In travelers, O-iRBCs peaked at 107.

Postartesunate delayed hemolysis is a predictable event related to the lifesaving effect of artemisinins.

Patients with severe malaria treated with artesunate sometimes experience a delayed hemolytic episode. Artesunate (AS) induces pitting, a splenic process whereby dead parasites are expelled from their host erythrocytes. These once-infected erythrocytes then return to the circulation.

Reduced erythrocyte deformability associated with hypoargininemia during Plasmodium falciparum malaria.

The mechanisms underlying reduced red blood cell (RBC) deformability during Plasmodium falciparum (Pf) malaria remain poorly understood. Here, we explore the possible involvement of the L-arginine and nitric oxide (NO) pathway on RBC deformability in Pf-infected patients and parasite cultures. RBC deformability was reduced during the acute attack (day0) and returned to normal values upon convalescence (day28).

Metabolic acidosis induced by Plasmodium falciparum intraerythrocytic stages alters blood-brain barrier integrity.

The pathogenesis of cerebral malaria (CM) remains largely unknown. There is growing evidence that combination of both parasite and host factors could be involved in blood-brain barrier (BBB) breakdown. However, lack of adequate in vitro model of human BBB so far hampered molecular studies.

Rho kinase inhibition in severe malaria: thwarting parasite-induced collateral damage to endothelia.

Acute clinical manifestations of falciparum malaria, such as multiorgan failure and cerebral malaria, occur unpredictably and lead to coma and death within hours if left untreated. Despite the emergency administration of effective antimalarial drugs, 15%-20% of patients die. Other therapeutic approaches are therefore urgently needed.

Whole-transcriptome analysis of Plasmodium falciparum field isolates: identification of new pathogenicity factors.

Background: Severe malaria and one of its most important pathogenic processes, cerebral malaria, involves the sequestration of parasitized red blood cells (pRBCs) in brain postcapillary venules. Although the pathogenic mechanisms underlying malaria remain poorly characterized, it has been established that adhesion of pRBCs to endothelial cells (ECs) can result in cell apoptosis, which in turn may lead to disruption of the blood-brain barrier. The nature of the parasite molecules involved in the pathogenesis of severe malaria remains elusive.

A plant-derived morphinan as a novel lead compound active against malaria liver stages.

Background: The global spread of multidrug-resistant malaria parasites has led to an urgent need for new chemotherapeutic agents. Drug discovery is primarily directed to the asexual blood stages, and few drugs that are effective against the obligatory liver stages, from which the pathogenic blood infection is initiated, have become available since primaquine was deployed in the 1950s.

Methods And Findings: Using bioassay-guided fractionation based on the parasite's hepatic stage, we have isolated a novel morphinan alkaloid, tazopsine, from a plant traditionally used against malaria in Madagascar.

Identification of new antimalarial drugs by linear discriminant analysis and topological virtual screening.

Objectives: A quantitative structure-activity relationship study using a database of 395 compounds previously tested against chloroquine-susceptible strains of the blood stages of Plasmodium falciparum to predict new in vitro antimalarial drugs has been developed.

Methods: Topological indices were used as structural descriptors and were related to antimalarial activity by using linear discriminant analysis (LDA) and multilinear regression (MLR). Two discriminant equations were obtained (FD1 and FD2), which allowed us to carry out successful classification of 90% and 80% of compounds, respectively.

Alkylation of manganese(II) tetraphenylporphyrin by a synthetic antimalarial trioxane.

The synthesis and the antimalarial activity of a new kind of polycyclic 1,2,4-trioxanes are reported. The alkylation of the heme model MnIITPP by the biologically active (IC 50 = 320 nmol L-1) hemiperketal 2 is presented.

In vitro activities of 25 quinolones and fluoroquinolones against liver and blood stage Plasmodium spp.

The in vitro activities of 25 quinolones and fluoroquinolones against erythrocytic stages of Plasmodium falciparum and against liver stages of Plasmodium yoelii yoelii and P. falciparum were studied. All compounds were inhibitory for chloroquine-sensitive and chloroquine-resistant P.

Synthesis and antimalarial activity of 2-methoxyprop-2-yl peroxides derivatives.

2-Methoxyprop-2-yl peroxides were synthesized and evaluated in vitro against Plasmodium falciparum. These acyclic artemisinin-related peroxides revealed moderate to good activity but were devoid of alkylating property towards the synthetic model of heme Mn(II)-TPP.