Nanoparticle tracking analysis of natural hemozoin from Plasmodium parasites.

Background: Hemozoin is a byproduct of hemoglobin digestion crucial for parasite survival. It forms crystals that can be of interest as drug targets or biomarkers of malaria infection. However, hemozoin has long been considered as an amorphous crystal of simple morphology.

Pre-referral intranasal artesunate powder for cerebral malaria: a proof-of-concept study.

Background: Malaria still kills young children in rural endemic areas because early treatment is not available. Thus, the World Health Organization recommends the administration of artesunate suppositories as pre-referral treatment before transportation to the hospital in case of severe symptoms with an unavailable parenteral and oral treatment. However, negative cultural perception of the rectal route, and limited access to artesunate suppositories, could limit the use of artesunate suppositories.

Evaluation of ferrocenyl-containing γ-hydroxy-γ-lactam-derived tetramates as potential antiplasmodials.

A series of ferrocenyl-containing γ-hydroxy-γ-lactam tetramates were prepared in 2-3 steps through ring opening-ring closure (RORC) process of γ-ylidene-tetronate derivatives in the presence of ferrocenyl alkylamines. The compounds were screened in vitro for their antiplasmodial activity against chloroquine-sensitive (3D7) and chloroquine-resistant (W2) clones of P. falciparum, displaying activity in the range of 0.

Paper functionalization for detection of Plasmodium falciparum DNA using square waves voltammetry.

Malaria elimination is a major goal to be reached in the next decade. Significant progress were made in the past, and the prevalence decreased in many areas while the positive trend stalled in the last years. The exact number of asymptomatic carriers of Plasmodium parasites is unknown since this population is not detected by conventional diagnosis methods and participate in the maintenance of transmission.

Assessment of quantitative and semi-quantitative biological test methods of artesunate in vitro.

Artesunate is the current most potent antimalarial drug widely used for the treatment of malaria. Considering the emergence of artemisinin resistance, several situations may require a simple method for artesunate quantification. We thus developed a quantitative and a semi-quantitative biological method for the determination of artesunate in liquid samples.

Systematic review of artesunate pharmacokinetics: Implication for treatment of resistant malaria.

Background: Artesunate (ART) is an artemisinin derivative used as monotherapy for the treatment of severe malaria and in combination with a partner drug for non-severe malaria. Resistance of malaria parasites to artemisinins have emerged in Southeast Asia. Adjustment of drug regimen may be an option to prevent therapeutic failures considering the relative favourable safety profile of ART high doses.

Interaction between environment, nutrient-derived metabolites and immunity: A possible role in malaria susceptibility/resistance in Fulani and Dogon of Mali.

The role of some nutrient-derived metabolites on the innate and adaptive immune responses is now established. Global research approach investigating the interplay between environment, lifestyle and the host's immune responses is crucial in the understanding of malaria susceptibility. Advanced Glycation end products (AGE), which are food-derived metabolites result from the link between reducing sugar and amino group of proteins, lipids or nucleic acids.

Diagnostic accuracy of loop-mediated isothermal amplification (LAMP) for screening patients with imported malaria in a non-endemic setting.

Background: Sensitive and easy-to-perform methods for the diagnosis of malaria are not yet available. Improving the limit of detection and following the requirements for certification are issues to be addressed in both endemic and non-endemic settings. The aim of this study was to test whether loop-mediated isothermal amplification of DNA (LAMP) may be an alternative to microscopy or real-time PCR for the screening of imported malaria cases in non-endemic area.

7-Chloro-4-aminoquinoline γ-hydroxy-γ-lactam derived-tetramates as a new family of antimalarial compounds.

In this Letter we report on an efficient and short 2-3 steps synthesis of γ-hydroxy-γ-lactam derived-tetramates bearing a 7-chloro-4-aminoquinoline skeleton and their evaluation as potent antimalarials. These molecules were obtained through ring opening-ring closure (RORC) process of γ-ylidene-tetronate derivatives in the presence of 7-chloro-4-aminoquinoline-derived amines. In vitro antimalarial activity of these new γ-lactams was evaluated against Plasmodium falciparum clones of variable sensitivity (3D7 and W2) and they were found to be active in the range of 14-827nM with generally good resistance index.

Drying anti-malarial drugs in vitro tests to outsource SYBR green assays.

Background: Measurement of anti-malarial drug efficacy and resistance relies mainly on in vivo clinical trials, in vitro/ex vivo assays and molecular markers detection. The existing in vitro/ex vivo assays, in particular those that are using non-radioactive devices, need to be standardized and adapted to field conditions. SYBR Green assay offers a rapid and cheap alternative to other in vitro assays, but it requires tools not commonly available in field laboratories.

Efficacy of intranasal administration of artesunate in experimental cerebral malaria.

Background: Improving management of patients suffering from cerebral malaria is needed to reduce the devastating mortality and morbidity of the disease in endemic areas. Intravenous artesunate is currently the first-line treatment, but the lack of material and skills in the field make it difficult to implement in endemic areas. Intranasal route provides a very easy and direct gateway to blood and brain to deliver medications, by-passing the brain blood barrier.

New route to the 5-((arylthio- and heteroarylthio)methylene)-3-(2,2,2-trifluoroethyl)-furan-2(5H)-ones--key intermediates in the synthesis of 4-aminoquinoline γ-lactams as potent antimalarial compounds.

In this Letter we report on a multi-step synthesis of 5-((arylthio- and heteroarylthio)-methylene)-3-(2,2,2-trifluoroethyl)furan-2(5H)-ones starting from γ-keto thiolester or γ-keto carboxylic acid. The key intermediate γ-lactones were then reacted with 4-aminoquinoline-derived amines via ring opening-ring closure (RORC) process affording the corresponding γ-hydroxy-γ-lactams in moderate to good yields. In vitro antimalarial activity of the resulting new 4-aminoquinoline γ-lactams were evaluated against Plasmodium falciparum clones of variable sensitivity (3D7 and W2) and were found to be active in the range of 89-1600 nM with good resistance index and did not show cytotoxicity in vitro when tested against human umbilical vein endothelial cells (HUVEC) up to concentration of 50 μM.