In Vitro Activities of 25 Quinolones and Fluoroquinolones against Liver and Blood Stage Plasmodium spp

ABSTRACT 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. falciparum grown in red blood cells. This inhibitory effect increased with prolonged incubation and according to the logarithm of the drug concentration. Grepafloxacin, trovafloxacin, and ciprofloxacin were the most effective drugs, with 50% inhibitory concentrations of <10 μg/ml against both strains. Only grepafloxacin, piromidic acid, and trovafloxacin had an inhibitory effect against hepatic stages of P. falciparum and P. yoelii yoelii; this effect combined reductions of the numbers and the sizes of schizonts in treated cultures. Thus, quinolones have a potential for treatment or prevention of malaria through their unique antiparasitic effect against erythrocytic and hepatic stages of Plasmodium.

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Plasmodium falciparum in vitro: diminished growth in hemoglobin H disease erythrocytes

Blood ◽

10.1182/blood.v65.2.452.bloodjournal652452 ◽

1985 ◽

Vol 65 (2) ◽

pp. 452-455

Author(s):

TC Ifediba ◽

A Stern ◽

A Ibrahim ◽

RF Rieder

Keyword(s):

Plasmodium Falciparum ◽

Red Blood Cells ◽

Blood Cells ◽

Fetal Hemoglobin ◽

Inhibitory Effect ◽

Beta Thalassemia ◽

Globin Genes ◽

Growth Environment ◽

Alpha Globin

Studies of the ability of Plasmodium falciparum to grow in vitro in the red blood cells of subjects with certain beta-thalassemia syndromes are often difficult to interpret because of the known inhibitory effect of an elevated cellular content of human fetal hemoglobin (HbF). P falciparum therefore was cultured in vitro in the erythrocytes of subjects with hemoglobin H (HbH) disease and various other alpha- thalassemia genotypes that are unaccompanied by increased levels of HbF. Growth of the malaria parasite was markedly retarded in HbH red blood cells, when compared with growth in blood from normal control subjects. No consistent impairment of growth was seen in the erythrocytes of subjects having deletion of only one or two alpha- globin genes. These results indicate that erythrocytes with a severe thalassemia phenotype provide a less hospitable growth environment for P falciparum than normally hemoglobinized red blood cells, even in the absence of increased levels of HbF.

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Plasmodium falciparum in vitro: diminished growth in hemoglobin H disease erythrocytes

Blood ◽

10.1182/blood.v65.2.452.452 ◽

1985 ◽

Vol 65 (2) ◽

pp. 452-455 ◽

Cited By ~ 35

Author(s):

TC Ifediba ◽

A Stern ◽

A Ibrahim ◽

RF Rieder

Keyword(s):

Plasmodium Falciparum ◽

Red Blood Cells ◽

Blood Cells ◽

Fetal Hemoglobin ◽

Inhibitory Effect ◽

Beta Thalassemia ◽

Globin Genes ◽

Growth Environment ◽

Alpha Globin

Abstract Studies of the ability of Plasmodium falciparum to grow in vitro in the red blood cells of subjects with certain beta-thalassemia syndromes are often difficult to interpret because of the known inhibitory effect of an elevated cellular content of human fetal hemoglobin (HbF). P falciparum therefore was cultured in vitro in the erythrocytes of subjects with hemoglobin H (HbH) disease and various other alpha- thalassemia genotypes that are unaccompanied by increased levels of HbF. Growth of the malaria parasite was markedly retarded in HbH red blood cells, when compared with growth in blood from normal control subjects. No consistent impairment of growth was seen in the erythrocytes of subjects having deletion of only one or two alpha- globin genes. These results indicate that erythrocytes with a severe thalassemia phenotype provide a less hospitable growth environment for P falciparum than normally hemoglobinized red blood cells, even in the absence of increased levels of HbF.

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Ultrastructural observations on the in vitro cytoadherence of Plasmodium falciparum infected red blood cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100162132 ◽

1990 ◽

Vol 48 (3) ◽

pp. 914-915

Author(s):

D.J.P. Ferguson ◽

A.R. Berendt ◽

J. Tansey ◽

K. Marsh ◽

C.I. Newbold

Keyword(s):

Plasmodium Falciparum ◽

Red Blood Cells ◽

Blood Cells ◽

Umbilical Vein ◽

Cell Types ◽

Amelanotic Melanoma ◽

Cytoplasmic Process ◽

Umbilical Vein Endothelial Cells

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).

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Variable expression of virulence in the rodent malaria parasitePlasmodium yoelii yoelii

Parasitology ◽

10.1017/s0031182000055165 ◽

1980 ◽

Vol 81 (1) ◽

pp. 211-219 ◽

Cited By ~ 23

Author(s):

G. Knowles ◽

D. Walliker

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Marked Decrease ◽

Plasmodium Yoelii ◽

Intermediate Level ◽

Rodent Malaria ◽

Variable Expression ◽

Plasmodium Yoelii Yoelii

SUMMARYThe expression of the virulence character in the virulent line (YM) ofPlasmodium yoelii yoeliiwas investigated. The level of virulence was measured by counting the parasitaemia of the mature red blood cells. Several sub-clones were isolated from the virulent line YM and each was tested for its level of virulence. Out of 10 sub-clones 1 showed a marked decrease in virulence. However, transmission of this sub-clone through mosquitoes fully restored its virulence. A clone isolated from the progeny of a cross between mild and virulent parents had an intermediate level of virulence. A sub-clone isolated from this intermediate virulent line exhibited greatly reduced virulence. Mosquito transmission of this sub-clone also restored its virulence to a level comparable with the virulent line YM.

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In Vitro Assessment of Antiplasmodial Activity and Cytotoxicity of Polyalthia longifolia Leaf Extracts on Plasmodium falciparum Strain NF54

Malaria Research and Treatment ◽

10.1155/2019/6976298 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Bethel Kwansa-Bentum ◽

Kojo Agyeman ◽

Jeffrey Larbi-Akor ◽

Claudia Anyigba ◽

Regina Appiah-Opong

Keyword(s):

Plasmodium Falciparum ◽

Ethyl Acetate ◽

Red Blood Cells ◽

Blood Cells ◽

Radical Scavenging ◽

Antimalarial Drugs ◽

Antiplasmodial Activity ◽

Leaf Extracts ◽

Polyalthia Longifolia

Background. Malaria is one of the most important life-threatening infectious diseases in the tropics. In spite of the effectiveness of artemisinin-based combination therapy, reports on reduced sensitivity of the parasite to artemisinin in Cambodia and Thailand warrants screening for new potential antimalarial drugs for future use. Ghanaian herbalists claim that Polyalthia longifolia has antimalarial activity. Therefore, antiplasmodial activity, cytotoxic effects, and antioxidant and phytochemical properties of P. longifolia leaf extract were investigated in this study. Methodology/Principal Findings. Aqueous, 70% hydroethanolic and ethyl acetate leaf extracts were prepared using standard procedures. Antiplasmodial activity was assessed in vitro by using chloroquine-sensitive malaria parasite strain NF54. The SYBR® Green and tetrazolium-based calorimetric assays were used to measure parasite growth inhibition and cytotoxicity, respectively, after extract treatment. Total antioxidant activity was evaluated using a free radical scavenging assay. Results obtained showed that extracts protected red blood cells against Plasmodium falciparum mediated damage. Fifty percent inhibitory concentration (IC50) values were 24.0±1.08 μg/ml, 22.5±0.12 μg/ml, and 9.5±0.69 μg/ml for aqueous, hydroethanolic, and ethyl acetate extracts, respectively. Flavonoids, tannins, and saponins were present in the hydroethanolic extract, whereas only the latter was observed in the aqueous extract. Aqueous and hydroethanolic extracts showed stronger antioxidant activities compared to the ethyl acetate extract. Conclusions/Significance. The extracts of P. longifolia have antiplasmodial properties and low toxicities to human red blood cells. The extracts could be developed as useful alternatives to antimalarial drugs. These results support claims of the herbalists that decoctions of P. longifolia are useful antimalarial agents.

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Identification of Proteins from Plasmodium falciparum That Are Homologous to Reticulocyte Binding Proteins inPlasmodium vivax

Infection and Immunity ◽

10.1128/iai.69.2.1084-1092.2001 ◽

2001 ◽

Vol 69 (2) ◽

pp. 1084-1092 ◽

Cited By ~ 97

Author(s):

Tony Triglia ◽

Jenny Thompson ◽

Sonia R. Caruana ◽

Mauro Delorenzi ◽

Terry Speed ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Red Blood Cells ◽

Molecular Mass ◽

Blood Cells ◽

Potential Role ◽

High Molecular Mass ◽

In Vitro Growth ◽

Merozoite Invasion ◽

Genome Databases

ABSTRACT Plasmodium falciparum infections can be fatal, whileP. vivax infections usually are not. A possible factor involved in the greater virulence of P. falciparum is that this parasite grows in red blood cells (RBCs) of all maturities whereasP. vivax is restricted to growth in reticulocytes, which represent only approximately 1% of total RBCs in the periphery. Two proteins, expressed at the apical end of the invasive merozoite stage from P. vivax, have been implicated in the targeting of reticulocytes for invasion by this parasite. A search of the P. falciparum genome databases has identified genes that are homologous to the P. vivax rbp-1 and -2 genes. Two of these genes are virtually identical over a large region of the 5′ end but are highly divergent at the 3′ end. They encode high-molecular-mass proteins of >300 kDa that are expressed in late schizonts and localized to the apical end of the merozoite. To test a potential role in merozoite invasion of RBCs, we analyzed the ability of these proteins to bind to mature RBCs and reticulocytes. No binding to mature RBCs or cell preparations enriched for reticulocytes was detected. We identified a parasite clone that lacks the gene for one of these proteins, showing that the gene is not required for normal in vitro growth. Antibodies to these proteins can inhibit merozoite invasion of RBCs.

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