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)

A factory for producing the pesticide hexachlorocyclohexane (HCR) in its technical grade (mix of the alpha, beta, gamma, and delta isomers), that belonged to the former Institute of Malaria Sciences, then Ministry of Education and Health, located in the "Cidade dos Meninos", county of Duque de Caxias, State of Rio de Janeiro, was closed down in 1955. Part of its production and wastes - many tons this mix - were left behind on the site. The action of winds and rain as well as the movement of the local inhabitants - approximately 1,000 people, including 400 children, have caused the scaltering of this agent. Blood specimens from the inhabitants showed a high human contamination levels, with the highest concentration (beta isomers) being found in people living within a 100 meter radius of the ruin of the factory. Local soil and pasture samples taken at distances of less than 100 m from the ruin of the former factory showed HCH isomer concentrations of the order of thousands of ppb, thus providing evidence of high environmental contamination.
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PMID:[Hexachlorocyclohexane contamination in urban areas of the south eastern region of Brazil]. 853 35

alpha, beta-Arteether is an ethyl ether derivative of artemisinin which is an efficient schizontocidal drug in mild falciparum malaria. The present study reports the efficacy of the drug in severe falciparum malaria. Fifty patients with severe falciparum malaria were given intramuscular arteether, 150 mg, once daily on 3 consecutive days. The median fever clearance time was 72 h (range 12-120 h) and the median parasite clearance time was 2 d (range 1-4 d). Rapid recovery from coma was observed in cerebral malaria patients (after a median of 18 h, range 6-72 h). The recovery from other complications was also faster and complete. Two patients died; both had cerebral malaria and haemolytic jaundice, one had respiratory distress needing ventilatory support and the other had severe anaemia. Recrudescence within 28 d was observed in 7 patients. Drug toxicity or significant side effects were not noticed in any patient.
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PMID:alpha, beta-Arteether for the treatment of complicated falciparum malaria. 923 Dec 10

A phase-III clinical trial was conducted in 50 patients (42M + 8F) with acute uncomplicated falciparum malaria from Delhi during the period of September to November 1995. Their mean age was 27.2 years, and the mean parasitaemia on day 0 was 0.65%. Patients were hospitalized and treated with a new ethyl derivative of artemisinin developed at CDRI called alpha, beta-arteether, at the dosage of 150 mg l/M for three consecutive days. Peripheral smears were examined every day for 4 days and then weekly up to 28 days. The results of the study showed that the mean parasite and fever clearance times were respectively 19.94 +/- 6.87 and 37.81 +/- 21.67 hours. Within 48 h, 70% of the cases became afebrile and the peripheral smear was negative in 100% of the cases. The drug was well tolerated. Three cases (6%) had recrudescence within 28 days. It is concluded that alpha, beta-arteether is a safe, effective and rapidly acting antimalarial.
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PMID:Efficacy of alpha,beta-arteether in acute uncomplicated P. falciparum malaria. 940 48

Two alkamides E,E-2,4-octadienamide and E,Z-2,4-decadienamide have been isolated from Phyllanthus fraternus, a plant used in Ghanaian traditional medicine to treat malaria. The compounds possess an alpha, beta, gamma, delta-unsaturated conjugated amide, a feature believed to enhance antiplasmodial activity. By means of an in vitro assay the two alkamides have been shown to possess moderate antiplasmodial activity.
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PMID:Alkamides from Phyllanthus fraternus. 952 13

Binding of infected erythrocytes to brain venules is a central pathogenic event in the lethal malaria disease complication, cerebral malaria. The only parasite adhesion trait linked to cerebral sequestration is binding to intercellular adhesion molecule-1 (ICAM-1). In this report, we show that Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) binds ICAM-1. We have cloned and expressed PfEMP1 recombinant proteins from the A4tres parasite. Using heterologous expression in mammalian cells, the minimal ICAM-1 binding domain was a complex domain consisting of the second Duffy binding-like (DBL) domain and the C2 domain. Constructs that contained either domain alone did not bind ICAM-1. Based on phylogenetic criteria, there are five distinct PfEMP1 DBL types designated alpha, beta, gamma, delta, and epsilon. The DBL domain from the A4tres that binds ICAM-1 is DBLbeta type. A PfEMP1 cloned from a distinct ICAM-1 binding variant, the A4 parasite, contains a DBLbeta domain and a C2 domain in tandem arrangement similar to the A4tres PfEMP1. Anti-PfEMP1 antisera implicate the DBLbeta domain from A4var PfEMP1 in ICAM-1 adhesion. The identification of a P. falciparum ICAM-1 binding domain may clarify mechanisms responsible for the pathogenesis of cerebral malaria and lead to interventions or vaccines that reduce malarial disease.
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PMID:Identification of a Plasmodium falciparum intercellular adhesion molecule-1 binding domain: a parasite adhesion trait implicated in cerebral malaria. 1067 32

The Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) family of cytoadherent proteins has a central role in disease from malaria infection. This highly diverse gene family is involved in binding interactions between infected erythrocytes and host cells and is expressed in a clonally variant pattern at the erythrocyte surface. We describe by sequence analysis the structure and domain organization of 20 PfEMP1 from the GenBank database. Four domains comprise the majority of PfEMP1 extracellular sequence: the N-terminal segment (NTS) located at the amino terminus of all PfEMP1, the C2, the Cysteine-rich Interdomain Region (CIDR) and the Duffy Binding-like (DBL) domains. Previous work has shown that CIDR and DBL domains can possess adhesive properties. CIDR domains grouped as three distinct sequence classes (alpha, beta, and gamma) and DBL domains as five sequence classes (alpha, beta, gamma, delta, and epsilon). Consensus motifs are described for the different DBL and CIDR types. Whereas the number of DBL and CIDR domains vary between PfEMP1, PfEMP1 domain architecture is not random in that certain tandem domain associations--such as DBLalphaCIDRalpha, DBLdeltaCIDRbeta, and DBLbetaC2--are preferentially observed. This conservation may have functional significance for PfEMP1 folding, transport, or binding activity. Parasite binding phenotype appears to be a determinant of infected erythrocyte tissue tropism that contributes to parasite survival, transmission, and disease outcome. The sequence classification of DBL and CIDR types may have predictive value for identifying PfEMP1 domains with a particular binding property. This information might be used to develop interventions targeting parasite binding variants that cause disease.
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PMID:Classification of adhesive domains in the Plasmodium falciparum erythrocyte membrane protein 1 family. 1107 Dec 84

Two hundred and sixty seven patients of uncomplicated P. falciparum malaria completed study in a multicentric phase III clinical trial of Arteether. Arteether was given intramuscularly in a dose of 150 mg daily for three consecutive days. Each patient was followed upto 28 days of alpha, beta arteether therapy. The cure rate was 97% with fever clearance time between 1-7 days (24-168 hours) and parasite clearance time between 1-3 days (24-72 hours). Parasite reappearance rate was found to be 3% and reported at only three of the centres. Following the treatment no adverse effect was observed on haematological, biochemical and vital clinical parameters.
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PMID:A multicentric study with arteether in patients of uncomplicated falciparum malaria. 1157 52

Protection against Plasmodium falciparum malaria is largely mediated by IgG against surface Ags such as the erythrocyte membrane protein 1 family (PfEMP1) responsible for antigenic variation and sequestration of infected erythrocytes. PfEMP1 molecules can be divided into groups A, B/A, B, C, and B/C. We have previously suggested that expression of groups A and B/A PfEMP1 is associated with severe disease and that Abs to these molecules are acquired earlier in life than Abs to PfEMP1 belonging to groups B, B/C, and C PfEMP1. In this study, we compared the acquisition of IgG to 20 rPfEMP1 domains derived from 3D7 in individuals living under markedly different malaria transmission intensity and were unable to find differences in the Ab acquisition rate to PfEMP1 of different groupings (A, B, or C) or domain type (alpha, beta, gamma, delta, epsilon, or x). Abs were acquired early in life in individuals living in the high transmission village and by the age of 2-4 years most individuals had Abs against most constructs. This level of reactivity was found at the age of 10-20 years in the medium transmission village and was never reached by individuals living under low transmission. Nevertheless, the sequence by which individuals acquired Abs to particular constructs was largely the same in the three villages. This indicates that the pattern of PfEMP1 expression by parasites transmitted at the different sites was similar, suggesting that PfEMP1 expression is nonrandom and shaped by host-parasite relationship factors operating at all transmission intensities.
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PMID:3D7-Derived Plasmodium falciparum erythrocyte membrane protein 1 is a frequent target of naturally acquired antibodies recognizing protein domains in a particular pattern independent of malaria transmission intensity. 1718 81

The aim of study was to evaluate efficacy and safety of alpha, beta-arteether injection 150 mg/ml by performing a phase III, multicentre, open label, and single treatment study in patients with P falciparum malaria. A total of 145 patients with P falciparum malaria were screened to achieve patient pool of 101 subjects based on inclusion and exclusion criteria, from which 100 patients completed the study successfully. Mean cure rate was calculated as primary efficacy parameter, while mean parasite clearance time (hours) and mean fever clearance time (hours) were calculated as secondary efficacy parameters, to evaluate efficacy of alpha, beta-arteether injection 150 mg/ml. Safety evaluation was measured by observing and monitoring adverse events, clinical examination, assessment of vitals and haematology laboratory parameters. Statistical analysis was performed with 5% level of significance. Mean cure rate, mean parasite clearance time (hours) and mean fever clearance time (hours) were 99.01%, 24.72 +/- 0.41 hours and 46.86 +/- 0.97 hours respectively. A total of 6 patients were observed with pain at injection site out of 101 enrolled patients. There were no clinically significant vitals and haematology changes. There were no abnormal posttreatment values observed. The study confirmed that alpha, gamma-arteether injection 150 mg/ml is highly effective in treatment of P falciparum malaria.
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PMID:A phase III clinical trial of alpha, beta-arteether injection 150 mg/ml in patients of P falciparum malaria. 2231 75