The Synaptic Leap

The pathogenesis of coma in severe Plasmodium falciparum malaria remains poorly understood. . . .

The pathogenesis of coma in severe Plasmodium falciparum malaria remains poorly understood. . . .

ABSTRACT: BACKGROUND: Levels of complement regulatory proteins (CrP) on the surface of red blood cells (RBC) decrease during severe malarial anaemia and as part of cell ageing process. . . .

Kiné Sow is a home caregiver in the Senegalese village of Ndienné. . . .

Enzymes of the glutathione S-transferase (GST) family play critical roles in detoxification of xenobiotics across many taxa. . . .

The expression of the clonally variant virulence factor PfEMP1 mediates the sequestration of Plasmodium falciparum infected erythrocytes in the host vasculature and contributes to chronic infection. . . .

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In 2010, the Global Fund provided more than 75% of external international financing for malaria control. . . .

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Malaria caused by several species of Plasmodium is major parasitic disease of humans, causing 1-3 million deaths worldwide annually. . . .

Infection with the malaria parasite, Plasmodium, is characterized by excessive inflammation. . . .

In a recent paper, we have described the discovery of antimalarial compounds derived from tadalafil, thanks to a Drug-to-Genome-to-Drug approach1 (J. . . .

The origin of Plasmodium falciparum in South America is controversial. . . .

Recombinant viruses hold promise as vectors for vaccines to prevent infectious diseases with significant global health impacts. . . .

Context: Malaria is still a major public health problem. . . .

The sickle cell (HbS) gene occurs at a variable frequency in the Middle Eastern Arab countries, with characteristic distribution patterns and representing an overall picture of blood genetic disorders in the region. . . .

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The American journal of tropical medicine and hygiene, Vol. 86, No. 2. (February 2012), pp. 194-198.

Abstract. We identified 480 persons with positive thick smears for asexual Plasmodium falciparum parasites, of whom 454 had positive rapid diagnostic tests (RDTs) for the histidine-rich protein 2 (HRP2) product of the hrp2 gene and 26 had negative tests. Polymerase chain reaction (PCR) amplification for the histidine-rich repeat region of that gene was negative in one-half (10/22) of false-negative specimens available, consistent with spontaneous deletion. False-negative RDTs were found only in persons with asymptomatic infections, and multiplicities of infection (MOIs) were lower in persons with false-negative RDTs (both P < 0.001). These results show that parasites that fail to produce HRP2 can cause patent bloodstream infections and false-negative RDT results. The importance of these observations is likely to increase as malaria control improves, because lower MOIs are associated with false-negative RDTs and false-negative RDTs are more frequent in persons with asymptomatic infections. These findings suggest that the use of HRP2-based RDTs should be reconsidered.
Ousmane Koita, Ogobara Doumbo, Amed Ouattara, Lalla Tall, Aoua Konaré, Mahamadou Diakité, Mouctar Diallo, Issaka Sagara, Godfred Masinde, Safiatou Doumbo, Amagana Dolo, Anatole Tounkara, Issa Traoré, Donald Krogstad

Malaria Journal, Vol. 11, No. 1. (2012), 33.

BACKGROUND:Cytoadherence of infected red blood cells to brain endothelium is causally implicated in malarial coma, one of the severe manifestations of falciparum malaria. Cytoadherence is mediated by specific binding of variant parasite antigens, expressed on the surface of infected erythrocytes, to endothelial receptors including, ICAM-1, VCAM and CD36. In fatal cases of severe falciparum malaria with coma, blood vessels in the brain are characteristically congested with infected erythrocytes. Brain sections from a fatal case of knowlesi malaria, but without coma, were similarly congested with infected erythrocytes. The objective of this study was to determine the binding phenotype of Plasmodium knowlesi infected human erythrocytes to recombinant human ICAM-1, VCAM and CD36.METHODS:Five patients with PCR-confirmed P. knowlesi malaria were recruited into the study with consent between April and August 2010. Pre-treatment venous blood was washed and cultured ex vivo to increase the proportion of schizont-infected erythrocytes. Cultured blood was seeded into Petri dishes with triplicate areas coated with ICAM-1, VCAM and CD36. Following incubation at 37degreesC for one hour the dishes were washed and the number of infected erythrocytes bound/mm2 to PBS control areas and to recombinant human ICAM-1 VCAM and CD36 coated areas were recorded. Each assay was performed in duplicate. Assay performance was monitored with the Plasmodium falciparum clone HB3.RESULTS:Blood samples were cultured ex vivo for up to 14.5 h (mean 11.3 +/- 1.9 h) to increase the relative proportion of mature trophozoite and schizont-infected red blood cells to at least 50 (mean 65.8 +/- 17.51%). Three (60%) isolates bound significantly to ICAM-1 and VCAM, one (20%) isolate bound to VCAM and none of the five bound significantly to CD36.CONCLUSIONS:Plasmodium knowlesi infected erythrocytes from human subjects bind in a specific but variable manner to the inducible endothelial receptors ICAM-1 and VCAM. Binding to the constitutively-expressed endothelial receptor CD36 was not detected. Further work will be required to define the pathological consequences of these interactions.
Farrah Fatih, Angela Siner, Atique Ahmed, Lu Woon, Alister Craig, Balbir Singh, Sanjeev Krishna, Janet Singh

Journal of ethnopharmacology, Vol. 112, No. 1. (30 May 2007), pp. 132-137.

Stephania rotunda (Menispermaceae) is used in traditional medicine for the treatment of fever. Four major alkaloids: dehydroroemerine, tetrahydropalmatine, xylopinine, cepharanthine as well as aqueous extract (SA), dichloromethane extracts (SD1 and SD2) from this plant were tested against Plasmodium falciparum W2 in vitro. Dehydroroemerine, cepharanthine and SD1 were the most active against W2 with IC(50) of 0.36, 0.61microM and 0.7microg/mL, respectively. Their IC(50) on human monocytic THP1 cells were 10.8, 10.3microM and >250microg/mL, respectively. Cepharanthine, SD1 and SA were selected for in vivo antimalarial test against Plasmodium berghei in mice. The results of SD1 and SA at dose of 150mg/kg showed a decrease of 89 and 74% of parasitaemia by intra-peritoneal injection and 62.5 and 46.5% of parasitaemia by oral administration, respectively. The result of cepharanthine at dose of 10mg/kg showed a decrease of 47% of parasitaemia by intra-peritoneal injection and 50% of parasitaemia by oral administration. Drug interaction of chloroquine and major alkaloids indicates that cepharanthine-chloroquine and tetrahydropalmatine-xylopinine associations are synergistic. These results are in agreement with the use of this plant in the treatment of malaria. This is the first report on in vivo antimalarial investigation for Stephania rotunda.
Aun Chea, Sotheara Hout, Sok-Siya Bun, Nino Tabatadze, Monique Gasquet, Nadine Azas, Riad Elias, Guy Balansard