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

Diferric transferrin reductase, assayed by formation of ferrous - bathophenanthroline, is detectable in the plasmamembrane of intact mature erythrocytes infected with Plasmodium falciparum. The absence of this transmembrane redox system in uninfected mature erythrocytes suggests its synthesis and incorporation by the intraerythrocytic parasite. The presence of diferric transferrin reductase, together with parasite-derived transferrin-receptor in the erythrocyte membrane, suggests a transferrin receptor-mediated uptake of iron by the malaria parasite.
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PMID:Diferric transferrin reductase in Plasmodium falciparum-infected erythrocytes. 264 31

Sera from non-malarial (control) and Plasmodium falciparum-infected (malaria) subjects were assayed for transferrin and iron. The mean serum transferrin concentration in the malaria sera was found to be elevated by 44% above the control value. The mean serum iron was also raised in the malaria sera, but the increase (19%) was found to be well below that of transferrin. The mean saturation of serum transferrin with iron fell from 42 +/- 17% in the control group to 37 +/- 9% in the malaria group. It is suggested that the increase in transferrin concentration in the sera of malaria subjects probably resulted from an increase in the rate of transferrin synthesis, perhaps in response to the raised serum iron and/or the hypoxia which is known to be associated with malaria infection.
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PMID:Changes in serum transferrin and iron concentrations in humans suffering from malaria with parasitaemia. 269 81

Adults claiming resistance to malaria were identified in the Sennar region of central Sudan, where P. falciparum is hyperendemic but seasonal in transmission. Indirect fluorescent antibody (IFA) titers of sera from these individuals were comparable to those of malaria patients with positive blood films, indicating equal exposure, while in vitro antiparasitic activity of their sera tended to be higher, indicating an effective immunological response to falciparum malaria. Hemoglobin S (Hb S) was significantly more prevalent in adults resistant to malaria. This trait offers protection at the erythrocyte level and it is also possible that it could enhance the ability of carrier adults to acquire protective immunity. Erythrocyte 6-phosphogluconate dehydrogenase A (PGDA) and phosphoglucomutase 1 (PGM1), phenotypes of unknown relevance to protection against falciparum malaria, were also significantly more prevalent in those claiming resistance to malaria. A trend of higher prevalence for erythrocyte glucose-6-phosphate dehydrogenase deficiency (G6PD-), Kell (+) and transferrin D (TfD) was detected among resistant individuals and higher KP(a+) and P2 among malaria patients, but the numbers evaluated in this study did not allow determination of statistical significance. No association was found with erythrocyte glyoxalases, ABO and Duffy blood groups and serum haptoglobins.
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PMID:Resistance to falciparum malaria among adults in central Sudan. 293 61

Several observations suggest that iron is essential for the development of malaria parasites but there is evidence that the parasites in erythrocytes do not obtain iron from haemoglobin. The total haemin level in parasitized erythrocytes does not vary during parasite development, indicating that the iron-containing moiety of haemoglobin is not detectably metabolized. Although parasite proteases can degrade the protein part of haemoglobin in red cells, no parasite enzymes that degrade haemin have been identified. In mammalian cells, haemin is degraded to carbon monoxide and bilirubin by the enzyme haeme oxygenase. This enzyme has not been found in malaria parasites. In fact haemin has been found to be toxic to parasite carbohydrate metabolism. Thus, iron apparently cannot be liberated from haemin and instead is sequestered in infected red cells as haemozoin, the characteristic pigment associated with malarial infection. If iron bound to transferrin is the source of ferric ions for malaria parasites within mature erythrocytes, then the parasite must synthesize its own transferrin receptor and localize it on the surface of the infected cell, because the receptors for transferrin are lost during erythrocyte maturation. Our results here suggest that Plasmodium falciparum synthesizes its own transferrin receptors enabling it to take up iron from transferrin by receptor-mediated endocytosis.
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PMID:A protein on Plasmodium falciparum-infected erythrocytes functions as a transferrin receptor. 309 54

A placebo-controlled trial of intramuscular iron dextran prophylaxis for two-month-old infants was carried out on the north coast of Papua New Guinea where there is high transmission of malaria. The results indicate that the placebo group became relatively iron deficient whereas the iron dextran group had adequate iron stores and, in the absence of malaria, a higher mean haemoglobin. However in the iron dextran group there was a higher prevalence of malaria, as judged by parasite and spleen rates at 6- and 12-month follow-up; a lower haemoglobin associated with malaria when compared with the placebo group and a greater reticulocytosis in response to malaria infection. Within the placebo group it was noticed that the malaria rates were lower at follow-up in those infants who had had a low birth haemoglobin. In neither group was there apparent suppression of marrow activity in the presence of malaria. Malaria infection in both groups was associated with a significantly raised serum ferritin level and transferrin saturation. Over-all these data give evidence for a protective role of iron deficiency against malaria and would argue against the injudicious use of iron replacement in areas where malaria is endemic.
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PMID:Iron supplementation increases prevalence and effects of malaria: report on clinical studies in Papua New Guinea. 310 Dec 43

Four protein polymorphisms: haptoglobin (HP), group specific component (GC), third component of complement (C3) and transferrin (TF), were investigated in Baruya tribes and several other Anga tribes living high in the Wonenara and Marawaka valleys in Papua New Guinea Eastern Highlands. A non-Anga tribe, the Aziana or Kenaze was also sampled. TF*D variant was identified in every group except Usarumpia. A number of anhaptoglobinaemic individuals was noticed. Environmental factors causing hemolysis and haptoglobin consumption are suggested. HP*1 and GC*1 frequencies were high, as usually observed in New Guinea. The Anga tribes are protected from malaria and represent a model of human isolates. The present study confirms this situation.
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PMID:Serum protein polymorphism in Papua New Guinea Eastern Highlands. 315 27

The appearance of widespread multiple drug resistance in human malaria has intensified the search for new antimalarial compounds. Metal chelators, especially those with high affinity for iron, represent one presently unexploited class of antimalarials. Unfortunately the use of previously identified chelators as antimalarials has been precluded by their toxicity and, in the case of desferrioxamine, the necessity for parenteral administration. The investigators now report that a new class of orally active iron chelators, namely the derivatives of alpha-ketohydroxypyridines (KHPs), are potent antimalarials against cultured Plasmodium falciparum. The KHPs evidently exert this effect by sequestering iron because a preformed chelator:iron complex has no antimalarial action. The pool(s) of iron being sequestered by the chelators have not been identified but may not include serum transferrin. Preincubation of human serum with KHPs followed by removal of the drug results in the removal of greater than 97% of total serum iron. Nonetheless, this serum effectively supports the growth of P falciparum cultures. Therefore the KHPs may exert antimalarial effect through chelation of erythrocytic rather than serum iron pool(s). The investigators conclude that these powerful, orally active iron chelators may form the basis of a new class of antimalarial drugs.
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PMID:Antimalarial properties of orally active iron chelators. 329 84

The mechanism whereby deferoxamine (DF) inhibits the growth of malaria parasites was studied in rats infected with Plasmodium berghei. Peak parasitemia was 32.6% (day 14) in untreated controls and 0.15% (day 7) in rats receiving 0.33 mg/g in 8 hourly DF injections, subcutaneously. DF inhibition of parasite growth was achieved without any reduction in transferrin saturation or hemoglobin synthesis and with only a partial (56%) depletion of hepatic iron stores. Dietary iron depletion resulted in anemia (hematocrit 25 vs. 46%), microcytosis (MCV 54 vs. 60 fl), and reduced transferrin saturation (17 vs. 96%) without any effect on infection (peak parasitemia 30 vs. 36%). Similarly, parenteral iron loading with ferric citrate over 10 d (75 mg iron/kg) failed to aggravate infection. In a search for evidence of direct interaction between DF and parasitized erythrocytes, gel filtration and ultrafiltration was performed on hemolysates obtained from in vivo 59Fe-labeled parasitized erythrocytes. This showed that 1.1-1.9% of the intracellular radioiron was located in a chelatable, labile iron pool. Incubation of intact cells with 0-500 microM DF resulted in a proportional increase in intracellular iron chelation, and the chelation of all available labile intracellular iron was completed within 6 h. These observations indicate that the severity of P. berghei infection in rats and its in vivo suppression by DF are independent of host iron status and suggest that DF inhibition of malaria involves intracellular chelation of a labile iron pool in parasitized erythrocytes.
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PMID:Deferoxamine inhibition of malaria is independent of host iron status. 329 34

It has been suggested that P. falciparum takes up iron from serum and that desferrioxamine, an iron chelating agent, inhibits parasite growth. We have now shown, however, that when all the iron is transferrin bound, P. falciparum, in culture, takes up less than 7 pmol Fe/10(9) parasites/24 h and that incorporation is increased only in the presence of a high molecular weight iron complex not naturally found in serum. Furthermore, removal of iron serum did not reduce parasite growth, and addition of excess iron was inhibitory. Desferrioxamine inhibited growth, but this inhibition was reduced under conditions in which the transfer of iron from transferrin to desferrioxamine was accelerated. We conclude that P. falciparum does not directly utilize serum iron and that desferrioxamine does not inhibit the parasite by interfering with the supply of iron from the incubation medium. The results are relevant to clinical data which suggest that added nutritional iron enhances the host susceptibility to malaria.
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PMID:A reappraisal of the effects of iron and desferrioxamine on the growth of Plasmodium falciparum 'in vitro': the unimportance of serum iron. 352 14

An assessment of iron and folic acid status, blood thick film and haemoglobin (Hb) electrophoresis was performed on 126 pregnant women (and their newborn infants) and in ninety-five menstruating women in Cotonou (Benin). Anaemia (according to the World Health Organization (1972] was observed in 55% of pregnant women and in 39% of menstruating women. Fe-deficiency was defined as a low serum ferritin concentration (12 micrograms/l or less), combined with a low transferrin saturation (less than 16%) or a high erythrocyte protoporphyrin level (more than 3 micrograms/g Hb), or both. A moderate elevation in the serum ferritin concentration (between 13 and 50 micrograms/l), associated with a low transferrin saturation or a high erythrocyte protoporphyrin level, or both, indicated Fe-deficiency in an inflammatory context. Fe-deficiency was present in 73% of pregnant women and in 41% of menstruating women. Folate deficiency (defined as erythrocyte folate below 160 micrograms/l) was observed in 45% of pregnant women. In pregnant women, anaemia was associated with Fe-deficiency in 83% of cases and with folate deficiency in 48% of cases. Haemoglobinopathies were mainly heterozygous and did not seem to contribute significantly to anaemia. Intensity of malaria was not related to Hb level, but Plasmodium falciparum was found in 99% of subjects. Hb concentration and mean corpuscular volume were significantly lower in babies born of Fe-deficient mothers than in babies born of Fe-sufficient mothers. Hb concentration in newborn infants was positively correlated with maternal serum ferritin.
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PMID:Nutritional anaemia in pregnant Beninese women: consequences on the haematological profile of the newborn. 355 28


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