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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Relapses may occur with long standard treatment of vivax malaria, and these are caused by incomplete patient's compliance. The use of reduced schedules may further better patient compliance, while maintaining the same efficacy, tolerance and minimal adverse reactions. The objective of this study was to test two schedules with reduced doses of chloroquine for vivax malaria and comparing these with the classical schedule. The authors studied 120 outpatients, with vivax malaria, aged over 12 years, submitted to three therapeutic schemes: scheme I: chloroquine phosphate (150 mg) in a dose of 25mg/kg/day for three days (10mg/kg/ day in the first day, 7.5mg/kg/day in the second and third day), plus primaquine (15 mg) in a dose of 0.25mg/kg/day for fourteen days; scheme II: chloroquine, in a single dose of 10mg/kg, plus primaquine in a dose of 0.5mg/kg/day for seven days; scheme III: chloroquine, 10mg/kg in a single dose plus primaquine in a dose 0.5mg/kg/ day for five days. The clinical response to all three therapeutic schemes was satisfactory. The disappearance of malarial symptoms occurred after a maximum 96 hours of treatment, while the asexual parasitaemia clearance occurred within 72 hours, in all therapeutic schemes.
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PMID:[Assessment of the response to reduced treatment schemes for vivax malaria]. 1156 27

Isoprenoids are biosynthesized from isopentenyl diphosphate and the isomeric dimethylallyl diphosphate via the mevalonate pathway or a mevalonate-independent pathway that was identified during the last decade. The non-mevalonate pathway is present in many bacteria, some algae and in certain protozoa such as the malaria parasite Plasmodium falciparum and in the plastids of higher plants, but not in mammals and archaea. Therefore, these enzymes have been recognised as promising drug targets. We report the crystal structure of Escherichia coli 2C- methyl-d-erythritol-2,4-cyclodiphosphate synthase (IspF), which converts 4-diphosphocytidyl-2C-methyl-d-erythritol 2-phosphate into 2C-methyl-d-erythritol 2,4-cyclodiphosphate and CMP in a Mg-dependent reaction. The protein forms homotrimers that tightly bind one zinc ion per subunit at the active site, which helps to position the substrate for direct attack of the 2-phosphate group on the beta-phosphate.
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PMID:Structure of 2C-methyl-d-erythritol-2,4-cyclodiphosphate synthase involved in mevalonate-independent biosynthesis of isoprenoids. 1182 4

Higher plants, several algae, bacteria, some strains of Streptomyces and possibly malaria parasite Plasmodium falciparum contain the novel, plastidic DOXP/MEP pathway for isoprenoid biosynthesis. This pathway, alternative with respect to the classical mevalonate pathway, starts with condensation of pyruvate and glyceraldehyde-3-phosphate which yields 1-deoxy-D-xylulose 5-phosphate (DOXP); the latter product can be converted to isopentenyl diphosphate (IPP) and eventually to isoprenoids or thiamine and pyridoxal. Subsequent reactions of this pathway involve transformation of DOXP to 2-C-methyl-D-erythritol 4-phosphate (MEP) which after condensation with CTP forms 4-diphosphocytidyl-2-amethyl-D-erythritol (CDP-ME). Then CDP-ME is phosphorylated to 4-diphosphocytidyl-2-amethyl-D-erythritol 2-phosphate (CDP-ME2P) and to 2-C-methyl-D-erythritol-2,4-cyclodiphosphate (ME-2,4cPP) which is the last known intermediate of the DOXP/MEP pathway. For- mation of IPP and dimethylallyl diphosphate (DMAPP) from ME-2,4cPP still requires clarification. This novel pathway appears to be involved in biosynthesis of carotenoids, phytol (side chain of chlorophylls), isoprene, mono-, di-, tetraterpenes and plastoquinone whereas the mevalonate pathway is responsible for formation of sterols, sesquiterpenes and triterpenes. Several isoprenoids were found to be of mixed origin suggesting that some exchange and/or cooperation exists between these two pathways of different biosynthetic origin. Contradictory results described below could indicate that these two pathways are operating under different physiological conditions of the cell and are dependent on the developmental state of plastids.
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PMID:Isoprenoid biosynthesis via 1-deoxy-D-xylulose 5-phosphate/2-C-methyl-D-erythritol 4-phosphate (DOXP/MEP) pathway. 1183 75

Tuberculosis and malaria remain the leading causes of mortality among human infectious diseases in the world. It is estimated that 3 to 5 million people die from tuberculosis and malaria each year. Although it is traditionally believed that CD4 and CD8 alphabeta T lymphocytes are mandatory for protective immune responses against Mycobacterium tuberculosis and Plasmodium falciparum (the ethiologic agents of tuberculosis and the most severe form of malaria, respectively), there is still incomplete understanding of the mechanisms of immune protection and of the causes of its failure in the affected patients. Several studies in humans and animal models have suggested that Vgamma9/Vdelta2 T cells may play an important role in the immune responses against Mycobacterium tuberculosis and Plasmodium falciparum. Vgamma9/Vdelta2 T cells represent about 75% of all circulating gammadelta T cells while they can be greatly expanded during the acute phase of Mycobacterium tuberculosis and Plasmodium falciparum malaria. Vgamma9/Vdelta2 T recognize a new class of antigenic molecules which are nonpeptidic in nature and contain critical phosphate moieties (phosphoantigens). Interestingly, phosphoantigens isolated from Mycobacterium tuberculosis and Plasmodium falciparum share strong structural homology and are probably identical. However, despite a large body of data reported in the literature, it is not yet clear whether Vgamma9/Vdelta2 T cells play a protective or pathogenic role in immune responses against Mycobacterium tuberculosis and Plasmodium falciparum. In this review we summarize our current knowledge of the biology of Vgamma9/Vdelta2 T cells in response to the two pathogens, Mycobacterium tuberculosis and Plasmodium falciparum, and provide evidence suggesting definition of a novel and important protective role through which Vgamma9/Vdelta2 T cells can contribute to the killing of microorganisms residing in intracellular compartments.
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PMID:Biology of gammadelta T cells in tuberculosis and malaria. 1189 88

Trypanosomes do not inhabit or grow in anopheles mosquitoes, the vector for the transmission of Plasmodium parasites the causative agent for malaria. The possession of lytic factors by the anopheline mosquito was thus considered. Head and midgut sections prepared in phosphate buffered saline were tested for trypanocidal action against T. congolense. While the head section was inactive towards the trypanosomes, the midgut extract at 0.2 mg ml(-1) diminished the motility of the parasites within 2 min of incubation; killing 50% of the population after 5 min. At 0.5 mg ml(-1) of the extract, about 90% of the parasites were killed within 2 min of incubation. The midgut fraction was subjected to a purification protocol involving successive chromatography on: octyl-sepharose, reactive brown agarose and fetuin-agarose columns. A final trypanocidal active fraction (gp45), which moved homogeneously during electrophoresis as a 45-kDa protein, was recovered from the fetuin-agarose column. The protein reacted positively with thiobarbituric acid, which suggests it is a sialoglycoprotein. Desialylation of the glycoprotein nullified its trypanocidal activity on T. congolense. Similarly, when the saccharides, lactose, methyl-beta-galactoside, lactulose, methyl-umbelliferyl-beta-galactoside (MU-Gal), were included in the culture medium, they inhibited the gp45 trypanocidal activity. Asialo-fetuin and asialo-RBC also inhibited the gp45-induced killing of T. congolense cells. The potential use of anopheline 45 kDa protein in the production of transgenic tsetse flies (Glossina spp.) in the control of trypanosomiasis is discussed.
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PMID:A 45-kDa midgut glycoprotein from Anopheles albimanus mosquito mediates the killing of trypanosomes. 1212 3

Intraerythrocytic malaria parasites produce large amounts of toxic ferriprotoporphyrin IX (FP) during their digestion of host cell haemoglobin. The inhibition of biomineralisation of FP to haemozoin (or beta-haematin) by antimalarial drugs underlies their mode of action. We have developed an in vitro microassay for testing the inhibition of biomineralisation by drugs. It is based on the detection by optical density measurement of solubilised beta-haematin remaining after contact with drugs. The assay uses a 192-microM haemin chloride solution in dimethyl sulfoxide, 96-well filtration microplates as well as normal microplates; it lasts 18-24h and requires a spectrophotometer. We determined by this assay the IC(50) of chloroquine phosphate (28microM) and quinine base (324microM) and showed that unlike previous methods it is insensitive to inorganic anions. We also determined the activity of synthetic dyes and plant extract to determinate the interference of coloured compounds on the accuracy of the test. We found that methylene blue, thionine (IC(50) 38 and 87microM, respectively), and an extract of plants that contains quinoline derivatives, inhibited the biomineralisation of FP regardless of their intrinsic colour.
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PMID:A non-radiolabelled ferriprotoporphyrin IX biomineralisation inhibition test for the high throughput screening of antimalarial compounds. 1212 52

The malaria parasite Plasmodium falciparum infects 5-10% of the world's population and kills two million people annually. Fatalities are thought to result in part from pathological reactions initiated by a malarial toxin. Glycosylphosphatidylinositol (GPI) originating from the parasite has the properties predicted of a toxin; however, a requirement for toxins in general and GPI in particular in malarial pathogenesis and fatality remains unproven. As anti-toxic vaccines can be highly effective public health tools, we sought to determine whether anti-GPI vaccination could prevent pathology and fatalities in the Plasmodium berghei/rodent model of severe malaria. The P. falciparum GPI glycan of the sequence NH(2)-CH(2)-CH(2)-PO(4)-(Man alpha 1-2)6Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcNH(2)alpha 1-6myo-inositol-1,2-cyclic-phosphate was chemically synthesized, conjugated to carriers, and used to immunize mice. Recipients were substantially protected against malarial acidosis, pulmonary oedema, cerebral syndrome and fatality. Anti-GPI antibodies neutralized pro-inflammatory activity by P. falciparum in vitro. Thus, we show that GPI is a significant pro-inflammatory endotoxin of parasitic origin, and that several disease parameters in malarious mice are toxin-dependent. GPI may contribute to pathogenesis and fatalities in humans. Synthetic GPI is therefore a prototype carbohydrate anti-toxic vaccine against malaria.
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PMID:Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria. 1218 69

Fosmidomycin acts through inhibition of 1-deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase, a key enzyme of the nonmevalonate pathway of isoprenoid biosynthesis. It possesses potent antimalarial activity in vitro and in murine malaria. In a recent clinical study, fosmidomycin was effective and well tolerated in the treatment of patients with acute uncomplicated Plasmodium falciparum malaria but resulted in an unacceptably high rate of recrudescence. In order to identify a potential combination partner, the interaction of fosmidomycin with a number of antimalarial drugs in current use was investigated in a series of in vitro experiments. Synergy was observed between fosmidomycin and the lincosamides, lincomycin and clindamycin. The efficacy of a combination of fosmidomycin and clindamycin was subsequently demonstrated in the Plasmodium vinckei mouse model.
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PMID:In vitro and in vivo synergy of fosmidomycin, a novel antimalarial drug, with clindamycin. 1218 43

There were 67.76 million persons belonging to scheduled tribes in about 74 distinct groups in India in 1991, or 7.95% of total population, usually living in remote and ecologically diverse climates and areas. Modern medicine has not been accepted in most tribal areas, where magico-religious health care systems prevail. Health conditions in tribal areas have been described as deficient in sanitary conditions, personal hygiene, and health education. Common diseases are sexually transmitted ones and genetic abnormalities such as sickle cell anemia and Glucose-6 Phosphate Enzyme Deficiency (G-6-PD). Disease incidence for sickle cell anemia has been estimated at more than 19% among 35 tribal population groups. 5 million are estimated to be carriers. G-6-PD shows a genetically carried deficiency in a blood enzyme; persons commonly reject antimalarials, antibiotics, and analgesics. The population estimated to have the deficiency is about 13 million, primarily residing in Madhya Pradesh, Maharashtra, Tamil Nadu, Orissa, and Assam states (15%). The incidence is high in malaria zones. Screening kits are needed by health workers, so that identified people can be tattooed and high risk families counseled accordingly. The Onges, Jarawas, and Shompens of Andaman and Nicobar Islands are facing extinction due to endemic diseases, venereal diseases, and a shortage of women. Health workers need information on the folklore related to health of these and other tribal groups, in order to provide appropriate health and sanitary practices and to document indigenous herbs for medical use. Malnutrition is pervasive among tribals. Deficiencies have been detected in gross amounts of calcium, vitamin A, vitamin C, riboflavin, and animal protein. Southern tribes are known for their caloric and protein deficiencies. Those in rice-eating belts tend to have had higher protein intake. The workload of tribal women is heavy, long, and increasing. Maternal mortality is due to unhygienic conditions and inappropriate tribal practices. Interventions must focus on tribal culture, medical training of indigenous people, a health care delivery system catering to the community needs, and more research.
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PMID:A health profile of tribal India. 1228 63

Malaria is the most common reason that people seek medical care in Ghana. This situation is taken for granted by the people, and there is no organized prevention effort. A World Health Organization-sponsored pilot malaria eradication program (1958-64) was abandoned after a peak period of activity in 1963 when vector control included indoor spraying with DDT. Recently there has been an upward trend in the incidence of malaria, with 15% of all cases becoming complicated. The main vector species are A. gambiae, A. melas, and A. funestus, and the predominant parasite species is Plasmodium falciparum. Treatment of choice is chloroquine phosphate, and although drug resistance has been suspected, it has not been documented. All health facilities are stretched to the limit with regard to the diagnosis and treatment of malaria. Field research is needed to provide a more accurate picture of the current situation. The clinical ability to deliver prompt diagnoses and treatment must be strengthened, and public health education must be instituted. The regional health management system must be improved, and personnel must be taught to use collected data. The use of bed nets, which is common in the south, should be encouraged, and impregnated nets should be introduced.
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PMID:Malaria: developing an action programme. 1228 15


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