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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two hundred Hausa primigravidae at Zaria were divided into five groups in a randomized double-blind trial of antenatal oral antimalarial prophylaxis, and haematinic supplements. Group 1 received no active treatment. Groups 2 to 5 were given chloroquine 600 mg base once, followed by proguanil 100 mg per day. In addition, group 3 received iron 60 mg daily, group 4 folic acid 1 mg daily, and group 5 iron plus folic acid. Forty-five percent were anaemic (haemoglobin (Hb) less than 11.0 g dl-1) at first attendance before 24 weeks of gestation, and malaria parasitaemia (predominantly Plasmodium falciparum) was seen in 27%, of whom 60% were anaemic. The mean Hb fell during pregnancy in group 1, and seven patients in this group had to be removed from the trial and treated for severe anaemia (packed cell volume (PCV) less than 0.26). Only five patients in the other groups developed severe anaemia (P = 0.006), two of whom had malaria following failure to take treatment. Patients in group 1 had the lowest mean Hb at 28 and 36 weeks of gestation, and patients receiving antimalarials and iron (groups 3 and 5) had the highest Hb at 28 weeks, but differences were not significant, possibly due to removal from the trial of patients with severe anaemia. Anaemia (Hb less than 12.0 g dl-1) at six weeks after delivery was observed in 61% of those not receiving active treatment (group 1), in 39% of those protected against malaria but not receiving iron supplements (groups 2 and 4) and in only 18% of patients receiving both antimalarials and iron (groups 3 and 5). Folic acid had no significant effect on mean Hb. Proguanil was confirmed to be a highly effective causal prophylaxis. Prevention of malaria, without folic acid supplements, reduced the frequency of megaloblastic erythropoiesis from 56% to 25%. Folic acid supplements abolished megaloblastosis, except in three patients who were apparently not taking the treatment prescribed. Red cell folate (RCF) concentrations were higher in subjects with malaria, probably due to intracellular synthesis by plasmodia. Infants of mothers not receiving antimalarials appeared to have an erythroid hyperplasia. Maternal folate supplements raised infants' serum folate and RCF. Fourteen per cent had low birth weight (less than 2500 g), and the perinatal death rate was 11%; the greatest number were in group 1, but not significantly. A regime is proposed for the prevention of malaria, iron deficiency, folate deficiency and anaemia in pregnancy in the guinea savanna of Nigeria.
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PMID:The prevention of anaemia in pregnancy in primigravidae in the guinea savanna of Nigeria. 353 Jan 58

Folacin deficiency in malaria endemic areas is not reported other than in severely malnourished children. This is surprising in view of the high incidence in these areas of malaria in pregnancy, with its complications of prematurity and low birth weight, all of which can predispose to folacin deficiency. This paper reports results of folacin and cobalamin activities of blood samples collected from women at parturition and their newborns in a holoendemic area in West Kenya. Evidence is given that Plasmodium falciparum infection has little influence on cord plasma or red cell folacin activities. Mean values for folacin and cobalamin are not low when compared with reported values from neonates from temperate climates.
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PMID:A comparison of maternal and foetal folacin and cobalamin activities at parturition in relation to Plasmodium falciparum infection. 409 47

Folic acid metabolism was studied in forty-four febrile children aged 2 months -9 years by measuring their serum and red cell folate levels. In all the children, there was a significant reduction in red cell folate along with a steady rise in serum folate as the body temperature increased above 39 degrees C. There was no correlation between the folate parameters and the pathological cause of the pyrexia (malaria or broncho-pneumonia). These results suggest that a rise in body temperature causes a breakdown of folate stores, which leads to some disturbance of folate metabolism. The extent of this disturbance is not known but it may have some detrimental effects on growing children.
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PMID:Increase of body temperature and folic acid metabolism. 734 90

Periconceptual use of folic acid supplements by women is effective in preventing neural tube defects in the fetus. Folic acid supplements also may prevent atherosclerosis and some malignant neoplasms. Nevertheless, safety concerns have delayed recommendations to increase folic acid consumption by the general population. Among the potential safety issues of folic acid supplementation are (1) difficulty identifying cobalamin deficiency, precipitation of neurologic complications of cobalamin deficiency, and lowering of cobalamin levels; (2) folate neurotoxicity; (3) antagonism of drugs that inhibit folate metabolism; (4) reduced zinc absorption; (5) association with malignant neoplasms; (6) hypersensitivity reactions; and (7) increased susceptibility to malaria. The data that suggest that folic acid supplements are unsafe are weak and consist predominantly of case series and reports. Nevertheless, greater difficulty diagnosing cobalamin deficiency due to "masking" of hematologic abnormalities by folic acid is a potential risk. Strict vegetarians need to be informed that they are at risk of cobalamin deficiency. Physicians need to be aware that routine hematologic indexes have a low sensitivity for cobalamin deficiency, especially in patients who are receiving folic acid supplements. Because no high-quality data exclude specific adverse effects, physicians should be vigilant in identifying detrimental effects when patients increase their consumption of folic acid.
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PMID:How safe are folic acid supplements? 869 61

Experimental cerebral malaria (ECM) can be induced in C57B1 mice by infection with Plasmodium berghei K173 parasites. Behavioral changes shortly before they die of ECM may reflect disturbance of the integrity of the blood-brain barrier (BBB). Folic acid elicits strong convulsive activity if the permeability of the BBB is increased. Administration of folic acid to mice during development of ECM induced convulsions. Interventions known to prevent fatal outcome from ECM, such as splenectomy or treatment with anti-CD4 or anti-CD8 monoclonal antibodies, also prevented sensitivity to folic acid-induced convulsions. In addition, infected mice with ECM and sensitive to folic acid-induced convulsions, recovered from this sensitivity after treatment with anti-T cell antibodies within 4 h. These data suggest that disturbance of the permeability of the BBB can be reversed and depends on the involvement of T cells.
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PMID:Convulsions due to increased permeability of the blood-brain barrier in experimental cerebral malaria can be prevented by splenectomy or anti-T cell treatment. 980 67

Folate metabolism in the human malaria parasite Plasmodium falciparum is an essential activity for cell growth and replication, and the target of an important class of therapeutic agents in widespread use. However, resistance to antifolate drugs is a major health problem in the developing world. To date, only two activities in this complex pathway have been targeted by antimalarials. To more fully understand the mechanisms of antifolate resistance and to identify promising targets for new chemotherapies, we have cloned genes encoding as yet uncharacterised enzymes in this pathway. By means of complementation experiments using 1-carbon metabolism mutants of both Escherichia coli and Saccharomyces cerevisiae, we demonstrate here that one of these parasite genes encodes both dihydrofolate synthetase (DHFS) and folylpolyglutamate synthetase (FPGS) activities, which catalyse the synthesis and polyglutamation of folate derivatives, respectively. The malaria parasite is the first known example of a eukaryote encoding both DHFS and FPGS activities in a single gene. DNA sequencing of this gene in antifolate-resistant strains of P. falciparum, as well as drug-inhibition assays performed on yeast and bacteria expressing PfDHFS--FPGS, indicate that current antifolate regimes do not target this enzyme. As PfDHFS--FPGS harbours two activities critical to folate metabolism, one of which has no human counterpart, this gene product offers a novel chemotherapeutic target with the potential to deliver a powerful blockage to parasite growth.
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PMID:A bifunctional dihydrofolate synthetase--folylpolyglutamate synthetase in Plasmodium falciparum identified by functional complementation in yeast and bacteria. 1122 31

An estimated 50% of pregnant women in Africa are anemic-- a condition that has been linked to intrauterine growth retardation, increased perinatal mortality, low birthweight, compromised immunity, and possible psychomotor and cognitive impairments. In tropical Africa, iron and folate deficiencies and malaria are the major causes of anemia in pregnancy. Iron deficiency anemia results from a combination of dietary insufficiency, excessive requirements associated with multiparity, and chronic blood loss from hookworm infestation. An essential component of maternal-child health services in Africa is prevention of anemia and therapeutic management once severe anemia is documented. Since 35% of nonpregnant African women are anemic, many women will enter pregnancy with inadequate iron stores. Thus, the prophylactic dose of iron should be at least 120 mg/day rather than the usual 60 mg dose. Unfortunately, increased dosages of iron increase the side effects of constipation and nausea, so careful counseling is necessary to ensure compliance. Folic acid, which has no side effects, should be administered in doses of 1.5 mg/day. To reduce the risk of malaria, a therapeutic dose of chloroquine should be administered at the 1st prenatal visit (600 mg for 2 days and 300 mg on the 3rd day) followed by proguanil (100 mg/day) until delivery. In cases where anemia persists or emerges, the iron dose should be increased to 200 mg of ferrous sulfate 3 time/day (180 m,g of elemental iron) and 5 mg of folic acid should be provided. Blood transfusion should be used sparingly and only in severe cases, given the risk of transmission of human immunodeficiency virus.
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PMID:Towards a more effective management of pregnancy related anaemias in Africa. 1231 81

Folate antagonizes the antimalarial action of sulfadoxine-pyrimethamine (SP) in vitro, but its role in vivo is not well understood. We measured blood folate concentrations and SP therapeutic outcomes in Malawian children. Children with late treatment failure and those with adequate clinical and parasitologic responses had similar demographic characteristics, prevalence of parasite mutations conferring resistance to SP, and blood concentrations of anti-malarial drugs following treatment. However, a higher folate concentration was associated with late treatment failure. Patients from a low malaria transmission site had higher blood folate concentrations than those in a higher transmission site (mean +/- SEM = 39 +/- 9.3 ng/mL versus 29 +/- 10 ng/mL; P < 0.0001), and there was a higher rate of late treatment failure in the low transmission area (54.4% versus 40.2%; P = 0.010). This study also provides the first evidence of the independent role of physiologic folate concentrations in in vivo SP therapeutic efficacy, and the critical role of pyrimethamine concentrations in the therapeutic efficacy of SP when one controls physiologic folate levels and the frequency of critical dihydrofolate reductase/dihydropteroate synthase mutations.
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PMID:Blood folate concentrations and in vivo sulfadoxine-pyrimethamine failure in Malawian children with uncomplicated Plasmodium falciparum malaria. 1577 19

Malaria and anemia are common conditions in patients presenting to outpatient clinics in Kenya. Anemia is usually due to malaria infection with underlying micronutrient deficiency. Iron therapy has been shown to enhance recovery from anemia in children with malaria, without affecting malaria treatment. Iron and folic acid are often prescribed together for anemic individuals. Until recently in Kenya, the drug of first choice for non-severe malaria was sulfadoxine-pyrimethamine (SP), an antifolate antimalarial drug. In this study, 303 patients of all ages with anemia and uncomplicated Plasmodium falciparum malaria attending an outpatient clinic in an area of seasonal malaria were treated with SP and iron, and were randomized to receive folic acid. Parasite clearance rates were measured using a survival analysis plot for both parasitologic and clinical failure. There was a significant reduction in the efficacy of SP in patients taking standard therapeutic doses of folic acid using the survival curve for parasitologic failure (P < 0.0001), but no difference for clinical failure (P = 0.7008). Folic acid supplementation did not enhance recovery from anemia.
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PMID:Reduction of the efficacy of antifolate antimalarial therapy by folic acid supplementation. 1601 52

Whether administration of folic acid to children with malaria anemia is helpful is controversial. Therefore, we conducted a randomised, placebo-controlled trial of 14 days of treatment with folic acid (1 mg/d) in Zambian children with malaria anemia treated with either sulfadoxine/pyrimethamine (SP) or atovaquone/proguanil (AP). Among children who received SP, the prevalence of parasitemia was higher in children treated with folic acid than among those given placebo at days 3, 7, and 14 after the start of treatment, and the difference at day 3 was statistically significant (P = 0.013). Folic acid treatment had no effect on parasitemia in children treated with AP. Administration of folic acid led to a small increase in packed cell volume over that seen in the placebo group at days 14 and 28 after the start of treatment.
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PMID:Folic acid treatment of Zambian children with moderate to severe malaria anemia. 1676 May 8


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