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)

I describe a model which posits the molecular basis of some malaria-resistance genes in the interaction between oxidized hemoglobin and membrane components. The model is supported by a considerable body of evidence which indicates that erythrocytes of genetically protected individuals (carriers of sickle cell trait, alpha- and beta-thalassemia, and G6PD deficiency) are susceptible to the increase of oxidation of hemoglobin following H2O2 release in the host cell by Plasmodium falciparum. I suggest that the irreversible interaction between oxidized hemoglobin and the red cell membrane could trigger mechanisms that: (i) reduce invasion of erythrocytes by the falciparum parasite; (ii) impair parasite survival and development within the cell; (iii) accelerate infected erythrocyte clearance by phagocytosis.
 ...
PMID:Genetic resistance to malaria, oxidative stress and hemoglobin oxidation. 1069 57

Malaria control by chemotherapy has been established in rural villages of Guadalcanal, the Solomon Islands, following field trials. As a selective primary health care activity, mobile unit teams visited villages once or twice a year to detect malaria positives and gave chloroquine and primaquine to treat the infection and interrupt the transmission. On site diagnosis was by the use of acridine orange fluorescent staining or the ICTPf commercial diagnostic kit. To avoid possible haemolytic crises, a new single step screening method of G6PD deficiency was introduced. This approach has been accepted well by villagers and proved to be an efficient and feasible control method even in remote rural villages with endemic malaria transmission. Epidemiological modelling of the situation predicts reduction of prevalence in five years.
 ...
PMID:Chemotherapeutic malaria control as a selective primary health care activity in the Solomon Islands. 1069 88

To determine whether hemoglobin E trait influences the antimalarial effect of artemisinin derivatives, we retrospectively compared 32 case patients with hemoglobin E trait to 32 control patients who did not have hemoglobin E, beta-thalassemia, glucose-6-phosphate dehydrogenase deficiency, or alpha-thalassemia trait on the basis of a mean corpuscular volume > or =78 femtoliters. All patients were admitted to the Hospital for Tropical Diseases in Bangkok, Thailand, with acute falciparum malaria. Control patients were matched to case patients with hemoglobin E trait by treatment with artemisinin derivatives versus other antimalarial drugs, by ethnic group, and by parasite count. Among 38 patients treated with artemisinin derivatives, the presence of hemoglobin E trait was associated with significantly faster parasite clearance (2.9-fold; 95% confidence interval [CI], 1.4-6.3; P=.006). Among 26 patients treated only with other antimalarial drugs, hemoglobin E trait did not significantly enhance parasite clearance (hazards ratio, 1.1; 95% CI, 0.5-2.5; P=. 8). Hemoglobin E trait may potentiate the antimalarial effect of artemisinin derivatives.
 ...
PMID:Influence of hemoglobin E trait on the antimalarial effect of artemisinin derivatives. 1076 87

To investigate host factors affecting the delay of reappearance of malaria parasites after radical treatment, a study was undertaken in Dielmo, Senegal, an area of intense perennial malaria transmission. A 7-day course of quinine was administered to 173 asymptomatic persons from 1 to 85 years of age and reappearance of malaria parasites in the peripheral blood was monitored weekly for 14 weeks. Additional thick blood films were made in case of fever as part of a daily clinical surveillance. The median times before reappearance of Plasmodium falciparum were 22, 39, and 53 days among persons 1-6, 7-14, and > or = 15 years of age, respectively (P < 0.0001). Multivariate analysis indicated that the daily rate of reappearance of P. falciparum was 2.2 (95% confidence interval [CI] = 1.2-4.5) times lower in sickle cell trait carriers than in AA individuals, and 1.5 (95% CI = 1.1-2.1) times lower in bed nets users than in non-users. The risk ratio for the daily risk of reappearance was significantly related to the level of parasitemia before treatment. No influence of glucose-6-phosphate dehydrogenase deficiency, HLA-B53, and DR13 were observed. Findings show that monitoring during a few weeks the reappearance of malaria parasites after treatment among a small cohort of individuals naturally exposed to malaria is relevant for investigating host resistance factors. This suggest that small, low-cost, field trials may be very informative on the potential of new malaria vaccine candidates.
 ...
PMID:Host factors affecting the delay of reappearance of Plasmodium falciparum after radical treatment among a semi-immune population exposed to intense perennial transmission. 1081 83

In regions highly endemic for Plasmodium falciparum malaria, red cell polymorphisms that confer resistance to severe disease are widespread. Sickle cell trait, alpha-thalassemia, glucose-6-phosphate dehydrogenase deficiency, and blood groups were determined in 100 children from Gabon with severe malaria who were matched with 100 children with mild malaria and followed up for evaluation of reinfections. The sickle cell trait was significantly associated with mild malaria and blood group A with severe malaria. During follow-up, the original severe cases had significantly higher rates of reinfection than the original mild cases, with higher parasitemia and lower hematocrit values. Incidence rates did not differ in the context of erythrocyte polymorphisms, but patients with sickle cell trait presented with markedly lower levels of parasitemia than those without. Thus, the severity of malaria is partly determined by the presence of blood group A and the sickle cell trait. The different presentation of reinfections in severe versus mild cases probably reflects different susceptibility to malaria.
 ...
PMID:The role of red blood cell polymorphisms in resistance and susceptibility to malaria. 1082 41

Glucose-6-phosphate dehydrogenase (G6PD) is expressed in all tissues, where it catalyses the first step in the pentose phosphate pathway. G6PD deficiency is prevalent throughout tropical and subtropical regions of the world because of the protection it affords during malaria infection. Although most affected individuals are asymptomatic, there is a risk of neonatal jaundice and acute haemolytic anaemia, triggered by infection and the ingestion of certain drugs and broad beans (favism). A rare but more severe form of G6PD deficiency is found throughout the world and is associated with chronic non-spherocytic haemolytic anaemia. Many deficient variants of G6PD have been described. DNA sequence analysis has shown that the vast majority of these are caused by single amino acid substitutions. The three-dimensional structure of G6PD shows a classical dinucleotide binding domain and a novel beta + alpha domain involved in dimerization.
 ...
PMID:Glucose-6-phosphate dehydrogenase deficiency. 1091 76

Several human genetic factors, including red blood cell polymorphisms (ABO blood group, sickle-cell trait, G6PD deficiency) as well as point mutations in the mannose binding protein (MBP) and in the promoter regions of both the TNF-alpha and NOS2 genes, influence the severity of disease due to infection with Plasmodium falciparum. We assessed their impact on mild P. falciparum malaria, as part of a longitudinal investigation of clinical, parasitological and immunological parameters in a cohort of 300 Gabonese schoolchildren. We found the following frequencies: blood group O (0.54), sickle-cell trait (0.23), G6PD deficiency (0.09), MBP gene mutations (0.34), TNF-alpha promoter mutations (at positions -238: 0.17 and -308: 0.22) and NOS2 promoter mutation (0.18). Blood group O or hemoglobin AA were associated with protection against higher parasitemia. Girls with normal G6PD enzyme activity were protected against clinical malaria attacks. In addition, we demonstrated for the first time that the mutation at position -238 of the gene coding for the promoter region of TNF-alpha was positively correlated with the level of the antibody response specific for epitopes of the antigens MSA-2 and RAP-1 of P. falciparum.
 ...
PMID:Human genetic factors related to susceptibility to mild malaria in Gabon. 1119 74

All current regimens of malaria chemoprophylaxis have serious drawbacks as a result of either suboptimal efficacy, difficulty with medication compliance, or adverse events. Two 8-aminoquinolines may be approaching registration, with primaquine having completed its prophylactic field testing and tafenoquine having begun advanced field testing at the end of 2000. Primaquine has long been used for management of relapses of malaria, but in the past decade, it has been reexamined for use in malaria prevention in order to stop infection in the liver. In field trials performed in Indonesia and Colombia, the efficacy of primaquine for malaria prevention was approximately 90%, compared with that of placebo. Because of its short half-life, primaquine requires daily administration. For adults, the prevention regimen is 30 mg base daily (0.5 mg base/kg/day), and it can probably be discontinued soon after departure from an area where malaria is endemic. To kill parasites that already exist in the liver, terminal prophylaxis is given after exposure to relapses of malaria infection; for adults, such prophylaxis usually consists of 15 mg base (0.3 mg base/kg/day) given daily for 2 weeks. Primaquine-induced gastrointestinal disturbances can be minimized if the drug is taken with food. Neither primaquine nor tafenoquine should be given to persons with glucose-6-phosphate dehydrogenase deficiency, to avoid the development of potentially severe drug-induced hemolysis. Tafenoquine is an analogue of primaquine that is more potent than the parent drug. Field trials in Kenya, Ghana, Gabon, and Southeast Asia have demonstrated an efficacy rate of approximately 90% for tafenoquine. Its long half-life allows for infrequent dosing (currently tested at 200 mg base/week), and its effect on parasites at the liver stage may allow for drug discontinuation at the time of departure from the area of endemicity.
 ...
PMID:Malaria chemoprophylaxis in the age of drug resistance. II. Drugs that may be available in the future. 1143 8

The occurrence of enlarged spleens and its age distribution has long been used as a crude measure to estimate malaria endemicity in cross-sectional surveys. Spleen size, however, is influenced by several variables that should be considered if they are observed in a population under study. We hypothesized that spleen indices are dependent on distinct red blood cell polymorphisms. Accordingly, we expected a lower prevalence of splenomegaly among patients with the sickle-cell trait (HbAS), HbAC trait and G6PD deficiency than in patients without red cell disorders, possibly due to the lower incidence of malaria attacks in these individuals. In our survey, however, spleen rates and sizes did not differ significantly between HbAA-, HbAS- and HbAC-positive individuals. Furthermore, enlargement of spleens was found at similar frequencies in persons with and without glucose-6-phosphate-dehydrogenase (G6PD)-deficiency (G6PD-A(-)).
 ...
PMID:Spleen size determined by ultrasound in patients with sickle cell trait, HbAC trait and glucose-6-phosphate-dehydrogenase deficiency in a malaria hyperendemic area (Ashanti Region, Ghana). 1160 86

The distribution of 30 HLA-DRB1 alleles in 85 individuals and of 10 HLA-DQB1 alleles in 91 individuals of the Viet Muong population was studied and compared with those of nine other Asian populations, including 103 Viet Kinh belonging to the major ethnic group in Vietnam. In terms of genetic distance, our data are consistent with a close ethnogeographic relationship between Viet Muong, Buyi and Dai Lue, two Southern Chinese ethnic groups. Conversely, these three populations are distant from the Northern Chinese population. The Viet Kinh belong to an intermediate group, together with North-eastern Thais, Thais and present day Thais. The striking presence of the HLA-DQ1*0502 allele (48% frequency) in the Viet Muongs is possibly anthropological or environmental in origin: the Viet Muongs have been submitted to endemic malaria for centuries, and the survivors carry the protective trait of glucose-6-phosphate dehydrogenase deficiency. This raises the hypothesis of a possible resistance to lethal or severe forms of the disease, where the association with a specific HLA-DQB1 allele may play a role.
 ...
PMID:HLA-DRB1 and DQB1 allele distribution in the Muong population exposed to malaria in Vietnam. 1244 16


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