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)

Human malaria is caused by four species of the genus plasmodium. The sexual stage of the parasite occurs in the mosquito and asexual reproduction occurs in man. Symptoms of fever, chills, headache, and myalgia result from the invasion and rupture of erythrocytes. Merozoites are released from erythrocytes and invade other cells, thus propagating the infection. The most vulnerable hosts are nonimmune travelers, young children living in the tropics, and pregnant women. P. falciparum causes the most severe infections because it infects RBCs of all ages and has the propensity to develop resistance to antimalarials. Rapid diagnosis can be made with a malarial smear, and treatment should be initiated promptly. In some regions (Mexico, Central America except Panama, and North Africa) chloroquine phosphate is effective therapy. In subsaharan Africa, South America, and Southeast Asia, chloroquine resistance has become widespread, and other antimalarials are necessary. The primary care physician should have a high index of suspicion for malaria in the traveler returning from the tropics. Malaria should also be suspected in the febrile transfusion recipient and newborns of mothers with malaria.
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PMID:Malaria. 201 38

This prospective study contains clinical and experimental parts. In the clinical study, 125 patients given intramuscular chloroquine for malaria were followed for 2 months in order to detect local injection site complications. Adequate local antiseptic conditions were ensured before giving the injection. Twenty-three patients (18.4%) had minimal local reaction in the form of redness, induration and/or a lump. No pyogenic abscess was noted in contrast to a previous report. In the second part of the study, an experimental animal (Green monkey) was given either chloroquine phosphate, Ampiclox or normal saline intramuscularly. The injection site was later biopsied and histologically examined. Intramuscular chloroquine was found to cause severe inflammatory reactions and muscle necrosis, whereas other injections had very minimal local effects. It is concluded that intramuscular chloroquine causes muscle necrosis which may lead to acute pyogenic abscess if minimal contamination takes place.
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PMID:Acute gluteal abscess following intramuscular chloroquine injection: a clinical and experimental study. 205 27

The energy metabolism of the blood stage form of the human malaria parasite Plasmodium falciparum is adapted to the host cell. Like erythrocytes, P. falciparum merozoites lack a functional citric acid cycle. Generation of ATP depends therefore fully on the glycolytic pathway. Aldolase is a key enzyme of this pathway and a high degree of sequence diversity between parasite and host makes it a potential drug target. We have expressed the enzyme in its tetrameric form in Escherichia coli and the catalytic constants Vmax and Km of the recombinant enzyme correspond to the constants of parasite-derived aldolase. Rabbit antibodies against the recombinant P. falciparum aldolase inhibit the natural enzyme and no cross-reaction with human aldolase is detectable. Both the recombinant and the natural protein bind to the cytosolic domain of the band 3 membrane protein in vitro. A 19-residue synthetic peptide corresponding to the sequence of the binding domain of band 3 is an inhibitor when included in the binding assay. In addition, this peptide inhibits the catalytic activity of recombinant P. falciparum aldolase when assayed in a buffer system devoid of anions such as chloride or phosphate. The band 3-derived peptides compete with the aldolase substrate fructose-1,6-diphosphate for binding, suggesting that both reagents have a high affinity for the substrate pocket. A similar sequence motif exists in P. falciparum actin II. A 19-residue peptide corresponding to this sequence is also an inhibitor which could suggest that the P. falciparum aldolase can associate with the cytoskeleton of the parasite or of the host.
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PMID:Expression, purification, biochemical characterization and inhibition of recombinant Plasmodium falciparum aldolase. 220 32

A competitive antibody binding inhibition ELISA to detect Plasmodium falciparum-infected cells in clinical specimens was developed. Optimum conditions developed included: 12.5 micrograms/ml of P. falciparum antigen for plate coating, 25 micrograms/ml of polyclonal rabbit anti-P. falciparum IgG, 30 minute incubation of a mixture of infected red blood cell extract with anti-P. falciparum IgG, dilution of 1:500 of alkaline phosphatase-conjugated anti-rabbit IgG, and reading of the absorbance values 60 min after adding the p-nitrophenyl phosphate substrate. Reproducibility of the assay against cultured P. falciparum-infected red blood cells varied according to parasitemia, the higher the parasitemia, the better the reproducibility. The sensitivity of the assay was approximately 110 parasites/10(6) red blood cells. The assay was applied to field conditions involving 103 cases with falciparum malaria, 38 cases with vivax malaria and 30 healthy controls. With the 10% antibody binding inhibition as a cutoff, 87.4% of falciparum cases and 26.3% of vivax cases were positive. After treatment, the majority of cases became parasitologically negative with the corresponding negative assay. Regression analysis showed only weak but statistically significant correlation between the percent inhibition with parasitemia (r = 0.38, p less than 0.001), and this was more clearly shown in patients with high parasitemia.
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PMID:Competitive antibody binding inhibition ELISA for the detection of Plasmodium falciparum antigen. 223 93

To clarify the distribution of the antimalarial primaquine in human blood, we measured the drug separately in the liquid, cellular, and ultrafiltrate phases. Washed red cells resuspended at a hematocrit of 0.4 were exposed to a submaximal therapeutic level of 250 ng/ml of carbon 14-labeled primaquine. The tracer was recovered quantitatively in separated plasma and red cells. Over 75% of the total labeled drug was found in red cells suspended in saline solution, but only 10% to 30% in red cells suspended in plasma. The plasma effect was not mediated by albumin. Studies with alpha 1-acid glycoprotein (AGP), tris(2-butoxyethyl)phosphate, an agent that displaces AGP-bound drugs, and cord blood known to have decreased AGP established that primaquine binds to physiologic amounts of the glycoprotein in plasma. Red cell primaquine concentration increased linearly as AGP level fell and as the free drug fraction rose. We suggest that clinical blood levels of primaquine include the red cell fraction or whole blood level because (1) erythrocytic primaquine is a sizable and highly variable component of the total drug in blood; (2) this component reflects directly the free drug in plasma, and inversely the extent of binding to AGP; (3) the amount of free primaquine may influence drug transport into specific tissues in vivo; and (4) fluctuations of AGP, an acute-phase reactant that increases greatly in patients with malaria and other infections, markedly affect the partition of primaquine in blood. Because AGP binds many basic drugs, unrecognized primaquine-drug interactions may exist.
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PMID:Distribution of primaquine in human blood: drug-binding to alpha 1-glycoprotein. 224 61

Pre-pregnancy immunization of Swiss albino mice with merozoite antigen of P. berghei entrapped in multilamellar phosphatidyl choline liposomes resulted in (i) increased prepatent period, (ii) either no or low parasitaemic levels, (iii) reduced mortality, and (iv) normal foetal and placental development, upon challenge with P. berghei on 13th gestational day. The unimmunized animals which received either phosphate buffered saline or empty multilamellar phosphatidyl choline liposomes before pregnancy developed high parasitaemic and 30-40 per cent animals died before parturition while 60-70 per cent unimmunized animals revealed foetal abnormalities such as low body weight and larger spleen size. Placentae of unprotected animals had hyperplasia of trophoblastic membrane and plugging of placental sinusoids with parasitized erythrocytes and malarial pigments. The data suggest that prior immunization of animals with merozoite antigen entrapped in multilamellar phosphatidyl choline liposomes could abrogate the ill effects induced by malaria infection under the stress of pregnancy.
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PMID:Prevention of malaria-induced foetal abnormalities following immunization of mice with Plasmodium berghei merozoite antigen. 226 10

Intramuscular chloroquine is rapidly absorbed, even in severe falciparum malaria, and may cause potentially lethal hypotension. Less rapidly absorbed formulations should be safer. A chloroquine phosphate solution containing 2% methylcellulose 1500 released chloroquine 2.6 times more slowly than a commercial aqueous solution in an in-vitro absorption simulator. There was a log linear relationship between viscosity and release rate. The absorption pharmacokinetics of the more viscous chloroquine phosphate solution were then compared with those of a commercial solution after intramuscular injection to eight rabbits in an open cross over comparison. The rate of absorption was over three times slower with the viscous solution; median time to peak whole blood concentration with the commercial aqueous solution was 10 (range 5-20) min compared with 30 (range 10-60) min for the more viscous formulation (P less than 0.05). Peak whole blood concentrations were 66% (95% CI 50-82%) of those with the commercial preparation, but the acute bioavailability of the two solutions was similar. This simple new formulation may be safer than currently available chloroquine preparations and should now be evaluated in man.
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PMID:An improved formulation of chloroquine for intramuscular administration: absorption kinetics in rabbits. 257 56

A rapid and highly sensitive high-performance liquid chromatographic assay for thymidylate synthase activity is described. The assay is based on the separation of the substrate, deoxyuridylate (dUMP), and its product, deoxythymidylate (dTMP), on a LiChrosorb RP-8 reversed-phase column with 44 mM triethylammonium phosphate (pH 7.0) as mobile phase and a flow-rate of 1.0 ml/min. In addition, using a mu Bondapak C18 reversed-phase column with 10 mM potassium phosphate (pH 4.0) and a gradient of 0-28% methanol, dUMP, dTMP and deoxythymidine (dTdR) are well separated within 30 min. The latter system is also applied to assay thymidine kinase activity with dTdR and dTMP as substrate and product, respectively. This method is sensitive enough to measure dTMP at concentrations as low as 25 pmol, and it was used to show that crude extracts of the human malaria parasite Plasmodium falciparum contain thymidylate synthase but not thymidine kinase activity.
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PMID:High-performance liquid chromatographic assay for thymidylate synthase from the human malaria parasite, Plasmodium falciparum. 265 57

Fifty-three cases of falciparum malaria in Linshui County, Baisha County and Sanya Municipality were treated with piperaquine phosphate at a total dose of 1.5g base over 3 days in July to December, 1986. The mean defervescence time was 36 +/- 20.7h; the mean asexual parasite clearance time was 69.7 +/- 20.9h. At 14-28d follow-up recrudescence was observed with asexual parasitemia in 7 of the 47 cases, showing RI resistance to piperaquine. Gametocytemia was positive in 35 cases (74.5%) during the follow-up period.
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PMID:[In vivo sensitivity of Plasmodium falciparum to piperaquine phosphate assayed in Linshui and Baisha counties, Hainan Province]. 268 56

215 patients of vivax malaria were treated with chloroquine phosphate alone at the dose of 1.5g for three days from April 1986 to October 1987 in Cili County in the northwest part of Hunan Province. Among them, 58 cases relapsed, the relapse rate being 27.0%. In patients admitted in April and May, as judged from the interval between treatment and the first relapse, the latent period was short, between 60.8d and 63.5d. On the contrary, when chloroquine treatment was given in August and September, the latent period in all the patients was long, between 292.4d and 297.5d. It is very interesting to note that in patients treated in June and July, both long and short latent periods occurred. 72.7% of the patients treated in June had short latent period (63.7d), while 75.0% of the patients treated in July had long latent period (285.4d).
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PMID:[Field observation on the relapse pattern in patients naturally infected with vivax malaria from spring to autumn seasons in Cili County, Hunan Province]. 268 60


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