Plasmodium falciparum malaria challenge by the bite of aseptic Anopheles stephensi mosquitoes: results of a randomized infectivity trial.

Background: Experimental infection of malaria-naïve volunteers by the bite of Plasmodium falciparum-infected mosquitoes is a preferred means to test the protective effect of malaria vaccines and drugs. The standard model relies on the bite of five infected mosquitoes to induce malaria. We examined the efficacy of malaria transmission using mosquitoes raised aseptically in compliance with current Good Manufacturing Practices (cGMPs).

Development of a metabolically active, non-replicating sporozoite vaccine to prevent Plasmodium falciparum malaria.

Immunization of volunteers by the bite of mosquitoes carrying radiation-attenuated Plasmodium falciparum sporozoites protects greater than 90% of such volunteers against malaria, if adequate numbers of immunizing biting sessions and sporozoite-infected mosquitoes are used. Nonetheless, until recently it was considered impossible to develop, license and commercialize a live, whole parasite P. falciparum sporozoite (PfSPZ) vaccine.

Inhibition of in-vitro growth of Plasmodium falciparum by Pseudocedrela kotschyi extract alone and in combination with Fagara zanthoxyloides extract.

Roots of Pseudocedrela kotschyi are commonly used as chewing sticks in West Africa. This study examined the effects of the plant extract on the in-vitro growth of Plasmodium falciparum. Ring-stage synchronised cultures of the malaria parasite were exposed to 30 and 60 microg/ml of P.

Association of serum transferrin receptor concentration with markers of inflammation in Zimbabwean children.

Background: Clinical studies have shown that degree of erythropoiesis, the hypoxic response, and iron status each independently influences transferrin receptor concentration, but there is conflicting information regarding the effect of inflammation on transferrin receptor expression.

Subjects And Methods: Levels of hemoglobin, reticulocytes, serum ferritin, transferrin receptors and inflammatory markers (C-reactive protein, interleukin-6 and neutrophils) were determined in 208 Zimbabwean children
Results: In linear regression models among 147 children with ferritin >10 ng/mL that adjusted for erythropoiesis with log(10) reticulocyte count, the hypoxic response with hemoglobin concentration and iron status with log(10) ferritin concentration, positive correlations were found between log(10) transferrin receptor concentration and log(10) C-reactive protein concentration (P=0.

Effect of ferroportin Q248H polymorphism on iron status in African children.

Background: Iron deficiency is common in African children, but genetic variations affecting susceptibility have not been identified. The Q248H mutation in ferroportin, a cellular iron exporter regulated by iron status and inflammation, may be associated with high iron stores in African adults.

Objective: The study examined the prevalence of iron deficiency in African children in an area where malaria transmission is low to absent and investigated whether ferroportin Q248H provides protection from iron deficiency.

An iron regulatory-like protein expressed in Plasmodium falciparum displays aconitase activity.

Plasmodium falciparum iron regulatory-like protein (PfIRPa) has homology to both mammalian iron regulatory proteins and aconitases and is capable of binding RNA iron response elements. We examined the subcellular localization of PfIRPa and its enzymatic properties at low oxygen tension. Differential digitonin permeabilization of isolated trophozoites with subsequent Western blot analysis suggests that the localization of PfIRPa is predominantly in the membranous compartments of the parasite, such as the mitochondrion.

Effects of root extracts of Fagara zanthoxyloides on the in vitro growth and stage distribution of Plasmodium falciparum.

The development of resistance by Plasmodium falciparum to conventional drugs poses a threat to malaria control. There is therefore a need to find new, effective, and affordable remedies for malaria, including those derived from plants. This study demonstrates that crude, reverse-phase high-pressure liquid chromatography (RP-HPLC)-semipurified, and RP-HPLC-purified root extracts of Fagara zanthoxyloides inhibit the growth of P.

Targeting malaria with polyamines.

During the asexual cycle of Plasmodium falciparum within the host erythrocyte, the parasite induces a stage-dependent elevation in the levels of polyamines by increased metabolism and uptake of extracellular pools. Polyamine amides of N-methylanthranilic acid have been synthesized which have embedded within them putrescine, spermidine, or spermine and from a charge perspective mimic natural polyamines. The interaction of these polyamine conjugates with human erythrocytes infected with malaria is described using fluorescent microscopy.

Novel aroylhydrazone and thiosemicarbazone iron chelators with anti-malarial activity against chloroquine-resistant and -sensitive parasites.

Iron (Fe) is crucial for cellular proliferation, and Fe chelators have shown activity at preventing the growth of the malarial parasite in cell culture and in animal and human studies. We investigated the anti-malarial activity of novel aroylhydrazone and thiosemicarbazone Fe chelators that show high activity at inhibiting the growth of tumour cells in cell culture [Blood 100 (2002) 666]. Experiments with the chelators were performed using the chloroquine-sensitive, 3D7, and chloroquine-resistant, 7G8, strains of Plasmodium falciparum in vitro.

Fluorescence measurements of the labile iron pool of sickle erythrocytes.

Sickle erythrocytes have increased ferritin and increased molecular iron on the inner membrane leaflet, and we postulated that cytosolic labile iron is also elevated. We used the fluorescent metallosensor, calcein, and a permeant Fe2+ chelator to estimate labile cytoslic Fe2+, and calcein plus an Fe3+ chelator to estimate total cytosolic labile iron (Fe2+ + Fe3+). We measured membrane nonheme iron by its reactivity with ferrozine.

Expression of a recombinant IRP-like Plasmodium falciparum protein that specifically binds putative plasmodial IREs.

Plasmodium falciparum iron regulatory-like protein (PfIRPa, accession AJ012289) has homology to a family of iron-responsive element (IRE)-binding proteins (IRPs) found in different species. We have previously demonstrated that erythrocyte P. falciparum PfIRPa binds a mammalian consensus IRE and that the binding activity is regulated by iron status.