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)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in humans and has an X-linked inheritance. It has been reported from India more than 30 years ago and the prevalence varies from 0-27% in different caste, ethnic and linguistic groups. The major clinical manifestations are drug induced hemolytic anemia, neonatal jaundice and chronic non-spherocytic hemolytic anemia. Individuals with G6PD deficiency have a selective advantage against falciparum malaria. Thirteen biochemically characterized variants have been reported from India. At the molecular level, G6PD Mediterranean is the most common deficient variant in the caste groups whereas, G6PD Orissa is more prevalent among the tribal of India. The third common variant seen in India is G6PD Kerala-Kalyan.
 ...
PMID:Glucose-6-phosphate dehydrogenase deficiency in India. 1522 63

The need to consider using dapsone in pregnant women for its antimalarial activity is becoming greater in areas where Plasmodium falciparum resistance to chloroquine and pyrimethamine-sulfadoxine is rapidly increasing. Dapsone in combination with other antimalarials might provide a valuable alternative for both treatment and prophylaxis. This review assesses the clinical pharmacology of dapsone and its adverse drug reactions in relation to haemolysis, glucose-6-phosphate dehydrogenase (G6PD) deficiency, blood dyscrasias and methaemoglobinaemia. Studies are summarised reporting its use in leprosy, dermatological and other conditions, and malaria, in relation to maternal and infant outcomes. A total of 924 pregnancies were identified during which dapsone therapy was taken. Only limited data are available and this precludes a meaningful quantitative benefit-risk analysis. Mild degrees of haemolysis consistently occur with continued therapy, although adverse effects may be less likely with intermittent treatment, as most reported adverse effects have occurred with long-term use of dapsone. There are a number of gaps in knowledge where more data are needed. These include no data on pharmacokinetics in pregnancy and whether these are altered with co-administration of chlorproguanil. Potential complications in women with severe anaemia are unknown and there is no information on haemolytic effects in women or the fetus with G6PD deficiency. The use of dapsone in HIV-infected women in malarious areas could carry increased risks because of the immunosuppressive actions of the drug. Trials of dapsone therapy in pregnancy should be considered in malarious areas where there is good reason for its deployment. Controlled trials have provided data on maternal tolerance, and dapsone in combination with other antimalarial drugs can offer clear benefit in terms of improved birthweight. The use of dapsone combinations should be considered when no good alternative is available and the threat of malaria is the greater risk.
 ...
PMID:Dapsone therapy for malaria during pregnancy: maternal and fetal outcomes. 1523 Jun 45

High frequency of erythrocyte (red blood cell [RBC]) genetic disorders such as sickle cell trait, thalassemia trait, homozygous hemoglobin C (Hb-C), and glucose-6-phosphate dehydrogenase (G6PD) deficiency in regions with high incidence of Plasmodium falciparum malaria and case-control studies support the protective role of those conditions. Protection has been attributed to defective parasite growth or to enhanced removal of the parasitized RBCs. We suggested enhanced phagocytosis of rings, the early intraerythrocytic form of the parasite, as an alternative explanation for protection in G6PD deficiency. We show here that P falciparum developed similarly in normal RBCs and in sickle trait, beta- and alpha-thalassemia trait, and HbH RBCs. We also show that membrane-bound hemichromes, autologous immunoglobulin G (IgG) and complement C3c fragments, aggregated band 3, and phagocytosis by human monocytes were remarkably higher in rings developing in all mutant RBCs considered except alpha-thalassemia trait. Phagocytosis of ring-parasitized mutant RBCs was predominantly complement mediated and very similar to phagocytosis of senescent or damaged normal RBCs. Trophozoite-parasitized normal and mutant RBCs were phagocytosed similarly in all conditions examined. Enhanced phagocytosis of ring-parasitized mutant RBCs may represent the common mechanism for malaria protection in nonimmune individuals affected by widespread RBC mutations, while individuals with alpha-thalassemia trait are likely protected by a different mechanism.
 ...
PMID:Enhanced phagocytosis of ring-parasitized mutant erythrocytes: a common mechanism that may explain protection against falciparum malaria in sickle trait and beta-thalassemia trait. 1528 Feb 4

Sickle cell genotype prevalence was 26% in a malaria-holoendemic lowland area compared with 3% in a highland area of Kenya. The prevalence of glucose-6-phosphate dehydrogenase deficiency was 7% and 1% in holoendemic lowland and highland areas, respectively. Lack of protective polymorphisms may contribute to morbidity and mortality during outbreaks of malaria in the highlands.
 ...
PMID:Frequencies of sickle cell trait and glucose-6-phosphate dehydrogenase deficiency differ in highland and nearby lowland malaria-endemic areas of Kenya. 1530 13

The adverse effects of primaquine (0.50 mg/kg/day) were investigated in eleven patients with vivax malaria (three patients with glucose-6-phosphate dehydrogenase deficiency). Clinical and laboratorial alterations indicated acute hemolysis in only the enzymopenic patients and treatment was interrupted. Our results suggest that screening for G6PD deficiency should be carried out in patients with vivax malaria infection in order to avoid complications due to primaquine.
 ...
PMID:[Clinical and laboratorial alterations in Plasmodium vivax malaria patients and glucose-6-phosphate dehydrogenase deficiency treated with primaquine at 0.50 mg/kg/day]. 1533 59

Primaquine is the only available drug for preventing relapse of malaria, and confusion surrounds its use. This review examines the wide range of clinical applications of primaquine described in the medical literature between 1946 and 2004. The risk of relapse of Plasmodium vivax malaria without primaquine therapy ranged from 5% to 80% or more, depending largely upon geographic location. Supervision of therapy profoundly impacts the risk of relapse, and almost all reports of malaria resistant to primaquine are associated with lack of such supervision. We nonetheless suspect that there is widespread resistance to the standard course of primaquine therapy, which is 15 mg primaquine base daily for 14 days. Clinical evidence confirms that a course of 15 mg daily for just 5 days, a regimen widely used in areas where malaria is endemic, has no discernible efficacy. This review supports a recommendation for a regimen of 0.5 mg/kg primaquine daily for 14 days, on the basis of superior efficacy and good tolerability and safety in nonpregnant persons without glucose-6-phosphate dehydrogenase deficiency.
 ...
PMID:Primaquine therapy for malaria. 1623 Dec 75

Glucose 6-phosphate dehydrogenase (G6PD) catalyses the first step of the pentose phosphate pathway, which in the RBC leads to the formation of NADPH, essential to prevent the cell from an oxidative stress. Worldwide, more than 400 million people (90% being males) are affected by G6PD deficiency, in regions that are, or have been, endemic for malaria and in populations originating from these regions. RBCs with low G6PD activity offer a hostile environment to parasite growth and thus an advantage to G6PD deficiency carriers. The counterpart of this protective effect is an increased susceptibility to oxidants such as some foods (fava beans), drugs (anti-malarial or sulphonamides), or various chemicals. In the case of G6PD deficiency, the hypothesis of a convergent evolution between parasite, protecting mutation, and cultural traditions (food, skin painting...) has been proposed. Near to 150 different G6PD variants have been described, which are classified into four types, according to their clinical effects. Several variants, such as the G6PD A- or the Mediterranean variant, reach the polymorphism level in endemic regions. The recent determination of the three-dimensional structure of this enzyme allows one to explain now the mechanisms of the disorders in terms of structure-function relationship.
 ...
PMID:[Glucose 6-phosphate dehydrogenase deficiency: a protection against malaria and a risk for hemolytic accidents]. 1550 19

Certain human genetic variants occur on-ly in areas endemic for malaria. They protect against fatal malaria complications and cause inhibition of growth or development of malaria parasites in vitro. Among these are the haemoglobins (Hb) S and C, alpha-thalassaemias, glucose-6-phosphate dehydrogenase deficiency, as well as a deletion in the erythrocyte band 3 protein. Evidence for similar effects has been obtained for HbD and HbE, glycophorins A and C as well as for a number of immunologically relevant molecules such as human leukocyte antigens,tumour-necrosis-factor a and the inducible nitric oxide synthase. The findings indicate that malaria in endemic areas has caused a substantial selection of the human genome.
 ...
PMID:[Influence of human genetic variants on resistance and immunity against malaria]. 1552 Nov 14

The aim of this study was to determine the frequency of G6PD deficiency and assess its impact on morbidity, especially anemia, in preschool-aged children in Cambodia. A total of 151 children including 82 boys and 69 girls from the Kandal province near Phnom Penh were studied. Ages ranged from 8 to 69 months. Blood was collected in EDTA-coated tubes. Blood counts were performed with an ABX Micros 60 system and G6PD in red blood cells was measured with a Roche Cobas Mira Plus system using Gamma reagents. G6PD deficiency was found in 14 cases (13.4% of boys and 4.3% of girls). Deficiency was complete in 7.3% of children and partial in 2%. Anemia defined as hemoglobin concentration less than 110 g/l was detected in 29.1% of children. No case of anemia could be attributed to enzyme deficiency since no sign of hemolysis was observed in any of the three children presenting both conditions. Further study is needed on G6PD deficiency in Cambodia including malaria-endemic areas and on the frequency and severity of jaundice due to enzyme deficiency in newborns.
 ...
PMID:[Frequency of G6PD deficiency in a group of preschool-aged children in a centrally located area of Cambodia]. 1561 86

New drug combinations against falciparum malaria which are both effective and affordable for Sub-Saharan African populations are urgently needed. The combination of the well-known drugs chloroquine (CQ) and methylene blue (MB) is such a promising new regimen. However, there is some concern that MB could cause development of haemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, a condition which is prevalent in malaria-endemic regions. Against this background, 74 G6PD-deficient but otherwise healthy adult men were given a 3-day oral regimen of a total of 1500 mg CQ and 780 mg MB in the District Hospital of Nouna in north-western Burkina Faso. Haemolysis did not occur, haemoglobin levels remained stable or even rose in the study participants, and the drug regimen was well tolerated. Therefore, standard dosages of MB appear to be safe in G6PD-deficient African populations with predominantly class III G6PD deficiency.
 ...
PMID:Safety of the combination of chloroquine and methylene blue in healthy adult men with G6PD deficiency from rural Burkina Faso. 1565 11


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