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)

Two randomised double-blind trials were conducted to examine the activity and tolerability of mefloquine alone and in combination with sulfadoxine/pyrimethamine (MSP). In one trial mefloquine was compared with chloroquine in 40 patients with Plasmodium vivax malaria and in the other one mefloquine was compared with MSP in 40 patients with P falciparum malaria. The former trial showed that both a single oral dose of 250 mg mefloquine and a single oral dose of 450 mg chloroquine (base) were highly effective in relieving symptoms of malaria and in clearing P vivax parasitaemia. No side-effects and no changes in laboratory variables attributable to the test drugs were observed. The other trial showed that a single oral dose of 750 mg mefloquine and a single oral dose of MSP (750 mg mefloquine plus 3 tablets of 'Fansidar', were equally effective in the treatment of falciparum malaria. 2/4 treatment failures in the mefloquine group and 2/3 treatment failures in the MSP group were due to low plasma drug levels resulting from vomiting soon after ingestion of the tablets. Gametocytes of P falciparum were unaffected by either mefloquine or MSP. 5 patients in each group had side-effects such as vomiting, skin rash, diarrhoea, and transient mental confusion. Mefloquine was well tolerated by patients with glucose-6-phosphate dehydrogenase deficiency or heterozygous haemoglobin E.
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PMID:Trials of mefloquine in vivax and of mefloquine plus 'fansidar' in falciparum malaria. 285 43

A study of the distribution of alpha-thalassemia in Papua New Guinea (PNG) was carried out by DNA analysis. A total of 664 DNA samples were screened for alpha-thalassemia 2 and alpha-thalassemia 1 caused respectively by either deletion of one or both of the duplicated alpha-globin genes. alpha-Thalassemia 2 was detected in high frequencies in coastal and lowland regions where malaria has been holo- to hyperendemic but in low frequencies in non-malarious highland regions. The highest frequency was observed in the north coast of PNG. The distribution of alpha-thalassemia 2 seems to be in accordance with other conditions such as ovalocytosis and G6PD deficiency which are also prevalent in this population, suggesting that they may interact in protection against malaria. However, it appears to be negatively correlated with beta-thalassemia and alpha-thalassemia 1, the latter being extremely rare in this population. Analysis of the types and subtypes of the single alpha-globin gene deletion revealed a predominance of the -alpha 4.2 type in general, except in some regions in the south where the -alpha 3.7 type is prevalent. The -alpha 3.7 I subtype is the common form of the -alpha 3.7 deletion in the PNG mainland. The -alpha 3.7 III subtype, previously reported to be unique in Melanesians and Polynesians, was detected in an offshore island of PNG. However, this subtype is very rare in Melanesians from the PNG mainland.
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PMID:Alpha-thalassemia in Papua New Guinea. 287 71

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

This paper reports the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the male and female population of A1-Ula in the northwestern province of Saudi Arabia. The frequency of G6PD deficiency in the male population was 0.098 and in the females it was 0.028. This frequency is significantly lower than those reported for other malaria endemic regions in Arabia. The population was further subgrouped on the basis of their haemoglobin phenotypes and the highest frequency of G6PD deficiency was obtained in male Hb S heterozygotes followed by the male Hb S homozygotes. Phenotyping of G6PD revealed the presence of G6PD-Mediterranean, G6PDA+, G6PDA- and G6PD Mediterranean-like, and the frequency of these variants in Al-Ula was different from those reported in other regions of Saudi Arabia.
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PMID:Glucose-6-phosphate dehydrogenase deficiency in Saudi Arabia. A study in Al-Ula. 323 96

BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] and its less toxic derivative HeCNU [1-(2-chloroethyl)-3-(2-hydroxyethyl)-1-nitrosourea] are clinically-used antitumour drugs. In erythrocytes BCNU is a highly specific inhibitor of the enzyme glutathione reductase [H. Frischer and T. Ahmad, J. Lab. clin. Med. 89, 1080 (1977)]. When treating erythrocytes in vitro, 50% enzyme inhibition was obtained with 1 microM BCNU or 3 microM HeCNU within 2 hr. The two drugs were used for preparing red cell populations with various levels of glutathione reductase activity; complete inhibition (greater than or equal to 98%) was only achieved when the medium contained glucose as a source of reducing equivalents. The erythrocytes were then tested in drug-free media as host cells for the malaria parasite Plasmodium falciparum. In the range of 0-300 mU/ml cells, there was a correlation between glutathione reductase activity and parasite growth; erythrocytes with an activity of less than 20 mU/ml did not serve as host cells for P. falciparum at all although these erythrocytes were viable. When the culture medium was supplemented with 20 mM glutathione (GSH), parasite growth was normal irrespective of the glutathione reductase level in the erythrocytes. This is consistent with the finding that poisoning glutathione reductase led to a 10-fold decrease of the cytosolic GSH level. Our results corroborate the concept that intraerythrocytic inhibition of glutathione reductase mimicks the biochemistry of drug-sensitive glucose-6-phosphate dehydrogenase deficiency (favism), an inherited condition which confers protection from malaria.
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PMID:Glutathione reductase-deficient erythrocytes as host cells of malarial parasites. 327 13

Mefloquine is a highly effective drug for the treatment of falciparum malaria among adults, but studies of its effects on children are lacking. An open, noncomparative trial of mefloquine was therefore carried out among 84 children aged 5-12 years who were patients at the Hospital for Tropical Diseases, Mahidol University, Bangkok, Thailand. The drug was administered as a single dose of 18-29 mg base per kg body weight. Eighty-two of the 84 children completed a 42-day period of post-treatment observation. The drug was well tolerated also by 11 children with glucose-6-phosphate dehydrogenase deficiency, and all the children in the study cleared their parasitaemia initially (average clearance time, 65 hours). Furthermore, the clinical-chemical parameters measured exhibited no drug-related changes during the study. The radical cure rate of nearly 98% and high tolerance indicate that mefloquine can be used effectively and safely for the treatment of children aged 5-12 years who are suffering from uncomplicated falciparum malaria.
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PMID:A phase-III clinical trial of mefloquine in children with chloroquine-resistant falciparum malaria in Thailand. 330 Oct 42

Plasmodium falciparum growth is impaired in glucose-6-phosphate dehydrogenase (G6PD)-deficient red blood cells (RBCs), and malaria has been implicated in the spreading of deficient variants in malaria-endemic areas. Recent reports suggest that the malaria parasite can adapt itself to grow in these variant RBCs by producing its own G6PD, but studies on parasite G6PD are very limited. In this report, we define the properties of the parasite G6PD. G6PD was partially purified from infected and uninfected variant RBCs associated with severe G6PD deficiency. G6PD from infected RBCs contained two components separable by starch gel electrophoresis: a major component (approximately 90% activity) with a very slow anodal electrophoretic mobility and a minor component (approximately 10% activity) with the same mobility as the host G6PD. Parasite G6PD exhibited much higher affinity (low Km) to G6P and nicotinamide-adenine dinucleotide phosphate (NADP) than did human G6PD. Southern blot hybridization indicated that the parasite genome contained nucleotide sequences that were hybridizable with the human G6PD cDNA. These data indicate that the parasite is capable of adapting to G6PD-deficient RBCs by producing its own G6PD.
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PMID:Glucose-6-phosphate dehydrogenase of malaria parasite Plasmodium falciparum. 355 78

A screening test for glucose-6-phosphate dehydrogenase (G6PD) deficiency was carried out in North Sumatra, Indonesia by using a simple agar plate method. The prevalence of G6PD deficiency in male was 6.0% (9/151) in Nias prefecture, 3.9% (12/307) in Asahan prefecture and 0.9% (1/110) in Medan city (average 3.9%). The prevalence of malaria was investigated at the same time in Nias and Asahan. It was 8.6% (13/151) and 10.4% (32/307) in males. The parasite rate of Plasmodium falciparum in normal and G6PD deficient groups was 4.1% and 9.5%, respectively. There was no statistical significance between them. The usefulness of the system of detecting malaria and G6PD deficiency at the same time was discussed in relation to malaria control.
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PMID:Malaria and glucose-6-phosphate dehydrogenase deficiency in North Sumatra, Indonesia. 357 82

A total of 1,112 randomly selected Saudi Arabs, of both sexes, living in Jeddah and the surrounding areas were screened for the phenotypic distribution of red cell glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD). They were also investigated for haemoglobin and for thalassaemia. Phenotyping of the haemoglobins and the red cell enzymes was carried out by starch gel electrophoresis and the dye-decolouration screening test, while the investigation for thalassaemia was carried out by globin-chain biosynthesis, followed by column chromatography. The red cell Gd- alleles were significantly associated with the sickle-cell gene in both the males (chi 2(1): AS-28.80; SS-4.89) and females (chi 2(1): AS-10.99; SS-13.16). A similar association was also observed between G6PD deficiency and thalassaemias in males (chi 2(1): alpha-thalassaemia - 3.13; beta-thalassaemia - 11.06) and females (chi 2(1): alpha-thalassaemia - 6.63). However, no such association was detected between red cell 6PGD types and haemoglobin genes. The results suggest that the red cell G6PD deficiency, sickle-cell and thalassaemia genes might have evolved as a result of the same ecological factor, probably malaria.
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PMID:Association of red cell glucose-6-phosphate dehydrogenase with haemoglobinopathies. 369 36

Hemoglobin in glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes is abnormally vulnerable to oxidative denaturation, which may release ferriheme, a known cytolytic agent. We found 13.3 nmol of ferriheme in G6PD-deficient erythrocyte membranes (per gram of total erythrocyte hemoglobin) using a spectrophotometric assay, as compared to 9.8 in normal membranes (P less than .05). After incubation of erythrocytes with 250 mumol/L menadione, an oxidant drug, the values increased by 37.4 nmol in G6PD-deficient membranes and by 26 in normal membranes (P less than .005), indicating increased hemoglobin denaturation. To verify that hemoglobin denaturation in G6PD-deficient erythrocytes releases ferriheme in a form available to interact with other ligands, [14C]-chloroquine binding to intact erythrocytes was measured. With an initial concentration of 5 mumol/L chloroquine in a medium containing no menadione, an excess of 14.8 nmol of chloroquine was bound in G6PD-deficient erythrocytes (per gram of hemoglobin) as compared to normal erythrocytes (P less than .005). In the presence of 250 mumol/L menadione, chloroquine binding increased by 17.9 nmol in G6PD-deficient and by 7.2 in normal erythrocytes (P less than .005). These results indicate that ferriheme becomes available to interact with endogenous ligands and, thus, to mediate menadione-induced hemolysis in patients with G6PD deficiency. Furthermore, the increase in ferriheme may mediate the selective toxicity of menadione for Plasmodium falciparum parasites growing in G6PD-deficient erythrocytes. Ferriheme release in response to the intraerythrocytic oxidant stress introduced by malaria parasites also may account for the resistance to malaria afforded by G6PD deficiency. This is a US government work. There are no restrictions on its use.
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PMID:Excess release of ferriheme in G6PD-deficient erythrocytes: possible cause of hemolysis and resistance to malaria. 394 28


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