Ina study of 10 P. falciparum infected volunteers with submicroscopic parasitemias given a single 200mg dose of artesunate, Rebelo et al (1) report a substantial difference in the ex-vivo growth of sequentially sampled circulating ring stage(2) parasites comparing infections with artemisin insensitive (Pfkelch wild type) and artemisinin resistant(PfkelchR539T)parasites.
The declining effectiveness of the available antimalarial drugs due to drug resistance requires a continued effort to develop new therapeutic approaches. In this context, combination therapies hold a great promise for developing effective first-line antimalarial treatments for reducing malaria mortality. The present study explores the antimalarial efficacy of nanotized formulation of curcumin in combination with benzothiophene compound 6 (3-bromo-N-(4-fluorobenzyl)-benzo[b]thiophene-2-carboxamide) with a view to achieve better efficacy at a very low dose in comparison to that accomplished with monotherapy alone.
There is an urgent need to develop new efficacious antimalarials to address the emerging drug-resistant clinical cases. Our previous phenotypic screening identified styrylquinoline UCF501 as a promising antimalarial compound.
Malarial parasites employ actin dynamics for motility, and any disruption to these dynamics renders the parasites unable to effectively establish infection. Therefore, actin presents a potential target for malarial drug discovery, and naturally occurring actin inhibitors such as latrunculins are a promising starting point.
Metacaspases are novel cysteine proteases found in apicomplexan whose function is poorly understood. Our earlier studies on Plasmodium falciparum metacaspase-2 (PfMCA-2) revealed that the caspase inhibitor, Z-FA-FMK efficiently inhibited PfMCA-2 activity and, expression, and significantly blocked in vitro progression of the parasite developmental cycle via apoptosis-like parasite death.
The disease burden of Plasmodium falciparum malaria illness is generally estimated using one of two distinct approaches: either by transforming P. falciparum infection prevalence estimates into incidence estimates using conversion formulae; or through adjustment of counts of recorded P. falciparum-positive fever cases from clinics. Whilst both ostensibly seek to evaluate P. falciparum disease burden, there is an implicit and problematic difference in the metric being estimated. The first enumerates only symptomatic malaria cases, while the second enumerates all febrile episodes coincident with a P. falciparum infection, regardless of the fever’s underlying cause.
The data suggest that focusing the immune response against defined epitopes displayed on the viral capsid is an effective strategy for transmission-blocking vaccine development.
Tolerability of both formulations was good. For QTcB, a parameter for ECG modifications, increases were modest and due to rising DAQ concentrations and falling heart rates as malaria resolved.
Following invasion of human red blood cells (RBCs) by the malaria parasite, Plasmodium falciparum, a remarkable process of remodeling occurs in the host cell mediated by trafficking of several hundred effector proteins to the RBC compartment.
Malaria caused by Plasmodium falciparum still elicits a substantial burden of disease mainly in sub-Saharan countries, where malaria is still endemic despite many efforts to curb the disease.