ascorbic-acid and Malaria--Falciparum

HIV and malaria infections occur in the same individuals, particularly in sub-Saharan Africa. We examined whether daily multivitamin supplementation (vitamins B complex, C, and E) or vitamin A supplementation altered malaria incidence in HIV-infected women of reproductive age.. HIV-infected pregnant Tanzanian women recruited into the study were randomly assigned to daily multivitamins (B complex, C, and E), vitamin A alone, both multivitamins and vitamin A, or placebo. Women received malaria prophylaxis during pregnancy and were followed monthly during the prenatal and postpartum periods. Malaria was defined in 2 ways: presumptive diagnosis based on a physician's or nurse's clinical judgment, which in many cases led to laboratory investigations, and periodic examination of blood smears for malaria parasites.. Multivitamin supplementation compared with no multivitamins significantly lowered women's risk of presumptively diagnosed clinical malaria (relative risk: 0.78, 95% confidence interval: 0.67 to 0.92), although multivitamins increased their risk of any malaria parasitemia (relative risk: 1.24, 95% confidence interval: 1.02 to 1.50). Vitamin A supplementation did not change malaria incidence during the study.. Multivitamin supplements have been previously shown to reduce HIV disease progression among HIV-infected women, and consistent with that, these supplements protected against development of symptomatic malaria. The clinical significance of increased risk of malaria parasitemia among supplemented women deserves further research, however. Preventive measures for malaria are warranted as part of an integrated approach to the care of HIV-infected individuals exposed to malaria.

Topics: Adolescent; Adult; Ascorbic Acid; Comorbidity; Dietary Supplements; Female; HIV Infections; Humans; Incidence; Malaria, Falciparum; Middle Aged; Postnatal Care; Pregnancy; Pregnancy Complications, Infectious; Prenatal Care; Tanzania; Vitamin A; Vitamin B Complex; Vitamin E; Young Adult

The redox metabolism of the malaria parasite Plasmodium falciparum and its human host has been suggested to play a central role for parasite survival and clearance. A common approach to test hypotheses in redox research is to challenge or rescue cells with pro- and antioxidants. However, quantitative data on the susceptibility of infected erythrocytes towards standard redox agents is surprisingly scarce. Here we determined the IC

Topics: Acetylcysteine; Antioxidants; Ascorbic Acid; Benzothiazoles; Diamide; Diamines; Dithiothreitol; Dose-Response Relationship, Drug; Erythrocytes; Fluorescent Dyes; Host-Parasite Interactions; Humans; Hydrogen Peroxide; Inhibitory Concentration 50; Malaria, Falciparum; Organic Chemicals; Oxidants; Oxidation-Reduction; Oxidative Stress; Parasitemia; Plasmodium falciparum; Quinolines; tert-Butylhydroperoxide; Time Factors

Topics: Artemisinins; Ascorbic Acid; Drug Combinations; Humans; Malaria, Falciparum

The antimalarial combination drug artemether/lumefantrine has been shown to be effective against malaria parasite through its haemolytic action. This drug is sometimes co-administered with vitamin C in patients with malaria. Vitamin C is associated with antioxidant properties which would be expected to protect against haemolytic effects of this antimalarial drug. This study was designed to investigate in vitro effects of co-incubation of artemether/lumefantrine with vitamin C on the viscosity and elasticity of blood.. Blood was collected from 12 healthy female volunteers with normal haemoglobin genotype (HbAA). A Bioprofiler was used to measure the viscosity and elasticity of untreated blood samples (control) and samples exposed to artemether/lumefantrine (0.06/0.36 mg/ml) alone and with low or high dose vitamin C (equivalent to adult doses of 100 or 500 mg).. artemether/lumefantrine significantly (p<0.05) reduced viscosity of blood from 4.72 ± 0.38 to 3.78 ± 0.17 mPa.s. Addition of vitamin C (500 mg) further reduced blood viscosity to 2.67 ± 0.05 mPa.s. The elasticity of blood was significantly (p<0.05) reduced from 0.33 ± 0.04 mPa.s to 0.24 ± 0.03 mPa.s by the antimalarial drug, and further reduced to 0.13 ± 0.02 mPa.s in the presence of vitamin C (500 mg).. Co-incubation of blood with vitamin C and antimalarial combination drug potentiates the haemolytic effects of the latter on reducing blood viscosity and elasticity in vitro. This may possibly have implications in relation to haemolysis in patients receiving vitamin C supplementation with artemether/lumefantrine during malaria therapy.

Topics: Adult; Antimalarials; Artemether; Artemisinins; Ascorbic Acid; Blood Viscosity; Drug Combinations; Ethanolamines; Female; Fluorenes; Humans; In Vitro Techniques; Lumefantrine; Malaria, Falciparum

Present investigations focused on the antioxidant defense in malaria caused by plasmodium Falciparum and plasmodium Vivax the mean±SEM values of Vitamin C, Vitamin E and GSH very highly significantly decreased as compared with normal individuals in both malaria species which cause malaria disease. The antioxidant levels in female were decreased very significantly due to decreased levels of antioxidant as compared with the male patients. The results are shown as mean±SME, the antioxidant levels in malarial patients was compared with normal individuals, in both genders. The antioxidant levels of vitamin C, Vitamin E and glutathione decreased in malaria caused by both species, a much greater decrease in patients infected by Plasmodium Vivax. P>001 was considered significant. The decrease of antioxidant levels was higher in female patients as compared with male patients. Antioxidant supplements like Vitamin C, Vitamin E and GHS may be used with anti malarial therapy,as a preventive measure because malaria affects the secondary antioxidant defense system of the body.

Topics: Adult; Antioxidants; Ascorbic Acid; Female; Glutathione; Humans; Malaria, Falciparum; Malaria, Vivax; Male; Middle Aged; Vitamin E

Apoptotic endothelial damage contributes to multiorgan failure in Plasmodium falciparum malaria and in sepsis. In malaria, endothelial apoptosis is amplified by neutrophils and their secretory products, and reduced by inhibitors of neutrophil-derived substances in vitro. We compared the mechanisms of endothelial apoptosis in malaria and in sepsis, using the human umbilical vein endothelial cell as a model.. Endothelial cells were incubated with patient sera (P. falciparum malaria, Escherichia coli sepsis, Staphylococcus aureus sepsis) or culture supernatants of the respective organisms, with or without neutrophils. Ascorbic acid or ulinastatin was used to neutralize reactive oxygen species or elastase secreted by neutrophils. Transwell sieve inserts or antibodies against leukocyte function antigen 1 or intercellular adhesion molecule 1 was used to study the effect of direct interaction between neutrophils and endothelial cells. The rate of apoptotic endothelial cells was determined by TUNEL and annexin staining.. Incubation of endothelial cells with patient sera or culture supernatants (P. falciparum, E. coli, S. aureus) lead to higher apoptosis rates, compared with incubation with control sera or control supernatants. Addition of neutrophils augmented the apoptosis rate further. Addition of ascorbic acid or ulinastatin reduced endothelial apoptosis in the presence of neutrophils. Separation of neutrophils from endothelial cells with Transwell sieve inserts, or addition of anti-leukocyte function antigen-1 antibodies also reduced endothelial cell apoptosis. However, addition of anti-intercellular adhesion molecule-1 antibodies restored high apoptosis rates that had been reduced by Transwell inserts.. These in vitro results show how neutrophils can contribute to endothelial damage in malaria and in sepsis, both by their secretory products and by binding to intercellular adhesion molecule-1 on endothelial cells. The presence of similar pathomechanisms suggests that similar antiapoptotic strategies may offer potential benefit in malaria and in sepsis.

Topics: Antioxidants; Apoptosis; Ascorbic Acid; Cells, Cultured; Coculture Techniques; Endothelial Cells; Endothelium, Vascular; Escherichia coli; Glycoproteins; Humans; Malaria, Falciparum; Neutrophils; Pancreatic Elastase; Reactive Oxygen Species; Sepsis; Staphylococcus aureus

Malaria remains a major cause of human morbidity and mortality worldwide. Plasmodium falciparum, the most virulent of the 4 human Plasmodium species causing malaria, is potentially life threatening, is increasing in prevalence and is becoming even more resistant to in-use drugs. In light of the growing problem of multi-drug resistance to malarial parasites, the development of new drugs or the use of a combination therapy is of primary importance. A previous report describes a remarkable synergistic antimalarial interaction between 2 structurally similar compounds, rufigallol, an anthraquinone derivative and exifone, a benzophenone derivative, in vitro. The synergistic antimalarial activity of exifone and vitamin C was also reported. To extend the same analogy to other ketones, we carried out antimalarial testing of 20 benzophenone derivatives, individually, in combination with rufigallol, and also in combination with vitamin C, in mice infected with Plasmodium berghei. Five ketones, out of 20, showed good antimalarial activity, in vivo, when tested individually. Nine ketones, out of 20, showed good antimalarial activity, in vivo, when tested in combination with rufigallol, indicating the synergism between them. However, synergism between ketones and vitamin C was not satisfactory since only 2 ketones showed good antimalarial activity when tested in combination with vitamin C.

Topics: Animals; Anthraquinones; Antimalarials; Antioxidants; Ascorbic Acid; Benzophenones; Drug Resistance; Drug Synergism; Drug Therapy, Combination; Humans; Ketones; Malaria; Malaria, Falciparum; Mice; Parasitic Sensitivity Tests; Plasmodium berghei; Treatment Outcome

Falciparum malaria infection is associated with significant destruction of erythrocytes. This leads to the release of toxic metabolic products, including oxidant compounds. We measured the serum concentration of the antioxidant, ascorbic acid, in 129 patients presenting with acute falciparum malaria infection and in 65 healthy individuals. None of the study subjects administered any form of ascorbic acid supplementation within one week prior to participation in this study. The mean serum ascorbate concentration in infected adult males (n = 49, age range 18-50 years) was found to be 2.02 +/- 0.20 mg/dL, and it was 2.03 +/- 0.24 mg/dL in infected adult females (n = 56, age range 18-50 years). These values were significantly greater than the serum ascorbate levels (1.54 +/- 0.10 mg/dL) in healthy adult males (n = 28) and females (n = 28) (p < 0.05). In children (age range 3 to 5 years), the serum ascorbate concentration was significantly lower (1.95 +/- 0.20 mg/dL) during infection (n = 25) than in their healthy counterparts (2.9 +/- 0.24 mg/dL, n = 9) (p < 0.05). It is evident therefore that ascorbic acid plays a significant role in the pathogenesis of acute falciparum malaria in adults. Infected children also need to be given supplemental doses of ascorbate in view of the weakness of their immune system.

Topics: Acute Disease; Adolescent; Adult; Analysis of Variance; Antioxidants; Ascorbic Acid; Case-Control Studies; Child, Preschool; Female; Humans; Malaria, Falciparum; Male; Middle Aged

Crithidia fasciculata was used to replace murine peritoneal wash cells as feeder cells for the adaptation of Plasmodium falciparum isolates to continuous culture in vitro, thus avoiding the need to sacrifice animals. Fourteen of 17 malaria parasite isolates in one study, and 12 of 12 isolates in a second study, were successfully adapted to continuous culture in the presence of C. fasciculata, while only 5 of 17 parallel control isolates in the first study, and 2 of 12 isolates in the second study, were adapted in the absence of any feeder cells. Biochemical assays were performed to investigate various hypotheses put forward to explain the mode of action of feeder cells. No effect of C. fasciculata feeder cells was observed on lactate removal, osmotic pressure, or glucose or amino acid content of the malaria culture media. This feeder cell system was shown to reduce the pH of the malaria culture medium. Neither this feeder system nor another system, murine peritoneal macrophages, had any effect on the cysteine content of the culture medium. C. fasciculata was shown to reduce the redox potential of the culture medium, as were other malaria growth enhancers including cysteine and glutathione. This effect on the redox potential of the culture medium is proposed to be a possible mode of action for the feeder cell systems studied.

Topics: Animals; Ascorbic Acid; Crithidia fasciculata; Culture Media; Cysteine; Glutathione; Humans; Hydrogen-Ion Concentration; Malaria, Falciparum; Osmotic Pressure; Oxidation-Reduction; Parasitemia; Plasmodium falciparum

Serum cholesterol (Total and free) as well as B-carotene and vitamin C level concentrations during and after severe infection by Plasmodium falciparum were determined. The decrease in the concentrations of cholesterol and B-carotene during and after infection was not statistically significant (P > 0.01), while the decrease in vitamin C was statistically significant (P < 0.01) during and after infection.

Topics: Adolescent; Adult; Antimalarials; Ascorbic Acid; beta Carotene; Chloroquine; Cholesterol; Convalescence; Humans; Malaria, Falciparum; Male

To investigate the influence of Plasmodium falciparum malaria on plasma antioxidants and lipid peroxidation, plasma ascorbate, urate, total protein and albumin, ceruloplasmin and malondialdehyde (MDA) were determined in two groups of 42 patients each, one with mild and the other with severe falciparum malaria, and in an equal number of age- and sex-matched control subjects. Plasma MDA was found to be significantly higher in malaria patients, and the increase was proportional to the severity of the disease. Of the antioxidants, ascorbate and albumin decreased with severity of disease while urate and ceruloplasmin increased. Only ascorbate correlated inversely with MDA both in mild (r = -0.341, P < 0.05) and severe malaria (r = 0.545, P < 0.01). While plasma albumin correlated inversely (r = -0.442, P < 0.01), urate and ceruloplasmin correlated directly (r = 0.419, P < 0.01 and r = 0.349, P < 0.05, respectively) only in patients with severe malaria. These antioxidants also correlated well with markers of disease severity, indicating the influence of disease severity in regulating their levels in plasma. The presence of significant quantities of ascorbate and albumin, along with increases in some of the other antioxidants and MDA, indicates ineffectiveness of the antioxidant defense system in controlling plasma lipid peroxide content. Increased amounts of thiobarbituric acid-reactive material could have been the result of spillover from increased tissue peroxidation or the presence of pro-oxidants in malarial plasma.

Topics: Analysis of Variance; Ascorbic Acid; Bilirubin; Blood Proteins; Ceruloplasmin; Cholesterol; Hemoglobins; Humans; Lipid Peroxidation; Malaria, Falciparum; Malondialdehyde; Serum Albumin; Triglycerides; Uric Acid