Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 1993, Malawi introduced sulphadoxine-pyrimethamine (SP) for the treatment of uncomplicated, Plasmodium falciparum malaria and became the first country in Africa to abandon chloroquine for first-time therapy. This decision produced an urgent need to monitor local P. falciparum for resistance to SP and to establish both clinical and parasitological criteria for drug failure. The parasitological and haematological responses to treatment of malaria in southern Malawi with SP have now been investigated. Children, aged 6-59 months, who attended health-care facilities with uncomplicated infections of P. falciparum alone were enrolled in the study. Each received standard treatment with SP and paracetamol and was followed-up on days 3, 7, 14, 21 and 28 post-treatment. Haemoglobin (Hb) was measured on days 0, 14 and 28. Zinc erythroprotoporphyrin (ZP) was estimated once during follow-up, as an indicator of iron status. Of 107 children enrolled, 84 children (78.5%) were followed for 14 days or until clinical failure. The parasitological success rate amongst the latter was 90.5% (76/84). One child showed poor parasite clearance (with a parasitaemia at day 3 > 25% of that at day 0), one had a low level of persistent parasitemia, and six were parasitaemic on day 14 after being parasite free on day 7. A 14-day follow-up increased the detection of parasitological failure by 7.2%. Haematological recovery on day 14 was not significantly different for parasitological successes or failures. The geometric mean parasite density (GMPD) was significantly lower in children classified as iron deficient (ZP > or = 3.0 micrograms/g Hb) and these children were significantly more likely to be severely anaemic (Hb < 8 g/dl) at day 0. Parasitological responses and haemoglobin levels 28 days after SP treatment were independent of ZP levels. These results show that, 2 years after the introduction of SP in Malawi for the treatment of uncomplicated, P. falciparum malaria, the drug combination remains effective in 90.5% of cases. Iron status did not affect parasitological recovery. Although iron-deficient children were at greater risk of severe anaemia they did not show significantly reduced recovery from malarial anaemia.
 ...
PMID:Parasitological and haematological responses to treatment of Plasmodium falciparum malaria with sulphadoxine-pyrimethamine in southern Malawi. 930 54

A study of 152 rural Malawian women aged 23.2+/-5.5 y (x+/-SD) at 24 wk gestation included measurements of biochemical indexes of zinc (plasma and hair), protein (serum albumin), and infection (serum C-reactive protein, white blood cell count, and malaria), and dietary intakes (via three interactive 24-h dietary recalls). Data on health, demographic and socioeconomic status, family characteristics, reproductive history, and anthropometry were also collected. The study revealed a high prevalence of suboptimal zinc status: 36% of the women had low plasma and 46% had low hair zinc values. Median daily intake of zinc (9.0 mg) was low and poorly available: 61% was provided by cereals and 20% by flesh foods. Median intake of animal protein was only 5.6 g/d, and phytate intakes were high (1.4 g/d). Women consuming diets with phytate-zinc ratios > 17 (the median) had lower hair zinc concentrations (1.6 compared with 1.8 micromol/g, P < 0.03), were older (24 compared with 20 y, P < 0.02), and had a higher number of pregnancies (3 compared with 2, P < 0.02) than those consuming diets with a phytate-zinc ratio < 17. Frequent reproductive cycling was related to zinc status; hair zinc was higher for a prima- than for a multigravida (2.0 compared with 1.6 micromol/g, P < 0.01). Malaria prevalence was also associated with hair zinc (P < 0.05) but not with plasma zinc, after the number of pregnancies was controlled for. We conclude that low intakes of poorly available dietary zinc, frequent reproductive cycling, and malaria prevalence are three major factors in the etiology of suboptimal zinc status in these rural, pregnant Malawian women.
 ...
PMID:Suboptimal zinc status in pregnant Malawian women: its association with low intakes of poorly available zinc, frequent reproductive cycling, and malaria. 953 17

Copper/zinc superoxide dismutase (CuZnSOD) catalyses the conversion of O2.- into H2O2. Constitutive overexpression of CuZnSOD in cells and animals creates an indigenous oxidative stress that predisposes them to added insults. In this study, we used transgenic CuZnSOD (Tg-CuZnSOD) mice with elevated levels of CuZnSOD to determine whether overexpression of CuZnSOD affected the susceptibility of these mice to plasmodium infection. Acute malaria is associated with oxidative stress, mediated by redox-active iron released from the infected RBC. Two independently derived Tg-CuZnSOD lines showed higher sensitivity than control mice to infection by Plasmodium berghei (P. berghei), reflected by an earlier onset and increased rate of mortality. Nevertheless, while Tg-CuZnSOD mice were more vulnerable than control mice, the levels of parasitemia were comparable in both strains. Moreover, treatment of infected red blood cells (RBC) with oxidative stress inducers, such as ascorbate or paraquat, reduced the viability of parasites equally in both transgenic and control RBC. This further confirms that increased CuZnSOD does not support plasmodia development. The data are consistent with the possibility that the combination of increased redox-active iron and elevated H2O2 in the plasmodium-infected Tg-CuZnSOD mice, led to an enhanced Fenton's reaction-mediated HO. production, and the resulting oxidative injury renders the transgenic mice more vulnerable to parasite infection.
 ...
PMID:Transgenic mice with elevated level of CuZnSOD are highly susceptible to malaria infection. 964 Dec 69

In children in developing countries, zinc deficiency may be common and associated with immune impairment and increased risk of serious infectious diseases such as diarrhea, pneumonia, and malaria. Studies have evaluated the therapeutic effects of zinc supplementation during acute or persistent diarrhea. In studies of acute diarrhea, the illness duration has been found to be 9-23% shorter in zinc-supplemented than in control children. Diarrhea was also less severe in zinc-supplemented children. In studies of persistent diarrhea, the effect sizes were similar but were often not statistically significant, perhaps because of the small number of children participating in these studies. Trials that provided continuous daily zinc supplementation for 5-15 mo evaluated effects on the incidence of diarrhea and in some studies acute lower respiratory infections and malaria. The reduction in the incidence of diarrhea in the zinc-supplemented group in these studies ranged from 8% to 45%. A study that gave 2 wk of zinc supplementation found preventive effects against diarrhea for the 3 mo of surveillance. More limited data also suggest that the incidence of acute lower respiratory infection and clinical attacks of malaria may also be reduced by zinc supplementation. If these results are confirmed by meta-analysis of the existing trials and additional research, improvement of zinc nutriture should become a priority intervention to reduce the high burden of serious infectious disease in children in developing countries.
 ...
PMID:Therapeutic and preventive effects of zinc on serious childhood infectious diseases in developing countries. 970 Nov 63

In a cross sectional survey based in an antenatal clinic at Kilifi District Hospital, Coast Province, Kenya, 154 of 275 pregnant women (56%) reported eating soil regularly. Geophagous women had lower haemoglobin and serum ferritin concentrations than non-geophagous women (mean haemoglobin level 9.1 vs. 10.0 g/dL, P < 0.001; median ferritin level 4.5 vs. 9.0 micrograms/L, P < 0.001). In multiple linear regression analyses, geophagy was a significant predictor of haemoglobin (beta = -6.4, P = 0.01) and serum ferritin concentrations (beta = -6.6, P = 0.002), while controlling for gestational age and malaria and hookworm infection. Another 38 pregnant women, who reported eating soil regularly, participated in focus group discussions and were interviewed on geophagy. The most commonly eaten soil was from the walls of houses. The median estimated daily intake was 41.5 g (range 2.5-219.0 g). Twenty-seven of these women assisted in the collection of soil samples which were then analysed for their content of iron, zinc and aluminium after extraction with 0.1 M HC1. The average daily soil intake supplied the geophagous women with 4.3 mg of iron, corresponding to 14% of the recommended dietary allowance of iron for pregnant women. The study revealed a strong negative association between geophagy and both haemoglobin and ferritin status. At the same time it demonstrated the potential of soil as a source of dietary iron for geophagous women. These seemingly contradictory results might be due to other components in the soil interfering with iron uptake or metabolism. Alternatively, it may be that the geophagous women had extremely depleted iron stores before starting to eat soil. From these cross-sectional data, no inference about causality could be made.
 ...
PMID:Geophagy, iron status and anaemia among pregnant women on the coast of Kenya. 986 77

The malaria parasite affects millions of people each year, lives and multiplies in two different hosts, and synthesizes a large number of proteases and heat shock proteins (HSPs) for its survival. We describe here the characterization of a metalloprotease activity which resides in the small HSP (PVHSP28) of the common but noncultivable human malaria parasite Plasmodium vivax. The protein is expressed by erythrocytic stages of the parasite. It is expressed as a approximately 55-kDa polypeptide which is then processed to the 28-kDa mature protein. The latter was found to be an active protease in gelatin zymography. This protease showed its optimal activity at 37 degrees C (pH 7.6). It also retained its proteolytic activity at higher temperatures of up to 55 degrees C. The enzyme belongs to the metalloprotease class, as its proteolytic activity was most effectively blocked by 1,10-phenanthroline and was restored to a maximal level by the addition of zinc metal ions. Inhibitors for the cysteine, serine, and aspartate classes of proteases were ineffective against this enzyme. A homology search indicates that PVHSP28 probably belongs to a new class of HSPs which possess the metalloprotease signature sequence.
 ...
PMID:Metalloprotease activity in a small heat shock protein of the human malaria parasite Plasmodium vivax. 1067 27

Expression of recombinant proteins with poly-histidine tags enables their convenient capture and purification using immobilized metal affinity chromatography (IMAC). The 6 x His-tagged protein binds to a chelating resin charged with metal ions such as Ni2+, Cu2+ or Zn2+, and can therefore be separated from proteins which have lower, or no, affinity for the resin. Two recombinant proteins, a malaria transmission-blocking vaccine candidate secreted extracellularly by S. cerevisiae and a modified diphtheria toxin produced intracellularly by E. coli, were expressed with 6 x His tags and could therefore be purified using IMAC. In an effort to further simplify the initial capture of these proteins, an expanded bed adsorption technique using a chelating resin (Streamline Chelating) was introduced. It was possible to capture the intracellular diphtheria protein from E. coli directly after cell lysis, without prior centrifugation or filtration. The extracellular malaria vaccine candidate was also directly captured from a high cell density yeast culture. Detailed information on the experimental work performed, and the capture processes developed, is provided.
 ...
PMID:Use of streamline chelating for capture and purification of poly-His-tagged recombinant proteins. 1073 66

This review critically examines the relationship between nutritional status and malaria. The data indicate that protein-energy malnutrition is associated with greater malaria morbidity and mortality in humans. In addition, controlled trials of either vitamin A or zinc supplementation show that these nutrients can substantially reduce clinical malaria attacks. Data for iron indicate that supplementation may minimally aggravate certain malariometric indices in some settings and also strongly improve hematologic status. Withholding of iron supplements from deficient population is, therefore, not currently indicated. Available evidence for other nutrients describe varied effects, with some deficiencies being exacerbative (e.g., thiamine), protective (e.g., vitamin E), or both exacerbative and protective in different settings (e.g., riboflavin, vitamin C). The roles of folate, other B vitamins, unsaturated fatty acids, amino acids, and selenium are also examined. Study of the interactions between nutrition and malaria may provide insight to protective mechanisms and result in nutrient-based interventions as low-cost and effective adjuncts to current methods of malaria prevention and treatment.
 ...
PMID:Nutritional modulation of malaria morbidity and mortality. 1094 83

Research has not provided unequivocal support for the recommendation to continue breastfeeding until children reach at least age 24 months. In many circumstances, breastfeeding duration is chosen or conditioned by factors other than scientific evidence and recommendations. Even in communities where breastfeeding into the second year is the norm, a significant number of toddlers are weaned before the recommended age. The research reported here was conducted in a rural community of western Kenya. We prospectively followed a cohort of 264 children for 6 months (mean age at baseline, 14.1 +/- 2.4 months) to examine the effect of variable breastfeeding duration on length and weight gain. We found that breastfeeding was positively associated with growth in a manner that we inferred to be causal, the effect being stronger on linear growth than on weight gain. This was despite the fact that in a cohort where 95% were breastfeeding at baseline, the prevalence of stunting (height-for-age below -2 standard deviations of the WHO-NCHS reference) was already 48%. The present paper examines the socioeconomic characteristics, sanitation, morbidity, and complementary feeding practices that define the context of this apparently contradictory relationship. The population was poor, no household had running water, and malaria is endemic in the study area. Complementary feeding was initiated for 93% of the cohort before age 3 months. The weaning diet was bulky (77% energy from carbohydrate), and high in phytate content ([phytate]:[zinc] molar ratio, 28). Diet quality, judged by diversity and animal source food intake, was low. Several micronutrient intakes were below current recommendations, including riboflavin (63%), niacin equivalents (64%), calcium (72%), iron (74%) and zinc (33%). Based on a locally defined socioeconomic status scale, children in higher SES households were breastfed for a shorter duration than were children from poorer households. Sanitation and water consumption modified the effect of breastfeeding duration on growth: the effect was stronger in the absence of a pit latrine and at low water consumption. Our results support the recommendation to sustain breastfeeding in the second year, particularly in economically depressed environments with inadequate sanitation and water supplies.
 ...
PMID:Breastfeeding and growth in rural Kenyan toddlers. 1106 68

Zinc is crucial for normal immune function and can reduce morbidity from multiple infectious diseases. To determine the influence of zinc on malaria morbidity we conducted a randomized placebo-controlled trial of daily zinc supplementation in children residing in a malaria endemic region of Papua New Guinea. A total of 274 preschool children aged 6 to 60 months were given 10 mg elemental zinc (n = 136) or placebo (n = 138) for 6 days a week for 46 weeks. Slide-confirmed malaria episodes were detected by surveillance of cases self-reporting to a local health center. Cross-sectional surveys were conducted at the beginning, middle, and end of the study to assess infection rates, parasite density, spleen enlargement, and hemoglobin levels. Zinc supplementation resulted in a 38% (95% CI 3-60, P = 0.037) reduction in Plasmodium falciparum health center-based episodes, defined as parasitemia > or = 9200 parasites/microl with axial temperature > or = 37.5 degreesC or reported fever. Episodes accompanied by any parasitemia were also reduced by 38% (95% CI 5-60, P = 0.028), and episodes with parasitemia > or = 100,000/microl were reduced by 69% (95% CI 25-87, P = 0.009). There was no evidence of the effects of zinc on Plasmodium vivax morbidity or on health center attendance for causes other than P. falciparum. Zinc had no consistent effect on cross-sectional malariometric indices. Although P. falciparum prevalence tended to be lower at the end of the study in children given the placebo, such changes were absent at the mid-study survey. These results suggest that improved dietary zinc intake may reduce morbidity due to P. falciparum.
 ...
PMID:The influence of zinc supplementation on morbidity due to Plasmodium falciparum: a randomized trial in preschool children in Papua New Guinea. 1130 51


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>