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)

Chloroquine is thought to act against falciparum malaria by accumulating in the acid vesicles of the parasite and interfering with their function. Parasites resistant to chloroquine expel the drug rapidly in an unaltered form, thereby reducing levels of accumulation in the vesicles. The discovery that verapamil partially reverses chloroquine resistance in vitro led to the proposal that efflux may involve an ATP-driven P-glycoprotein pump similar to that in mammalian multidrug-resistant (mdr) tumor cell lines. Indeed, Plasmodium falciparum contains at least two mdr-like genes, one of which has been suggested to confer the chloroquine resistant (CQR) phenotype. To determine if either of these genes is linked to chloroquine resistance, we performed a genetic cross between CQR and chloroquine-susceptible (CQS) clones of P. falciparum. Examination of 16 independent recombinant progeny indicated that the rapid efflux phenotype is controlled by a single gene or a closely linked group of genes. But, there was no linkage between the rapid efflux, CQR phenotype and either of the mdr-like P. falciparum genes or amplification of those genes. These data indicate that the genetic locus governing chloroquine efflux and resistance is independent of the known mdr-like genes.
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PMID:Chloroquine resistance not linked to mdr-like genes in a Plasmodium falciparum cross. 218 23

We examined the malaria situation among 489 children under 5 years of age in the rural villages of Aboh Mbaise, Nigeria, using a combination of a standard questionnaire technique and laboratory diagnosis to confirm clinical observations. The results show a high prevalence rate of 52.8% for Plasmodium falciparum in this area. The geometric mean parasite density (GMPD) was 19,361.4/mm3. The proportion of children with fever and/or parasitaemia was not related to age, although the numbers in the febrile group appeared to increase with age. Using 37.5 degrees C as the threshold for fever, 48.7% of the heavily infected group (more than 1000/mm3) were afebrile while 51.3% were febrile. High grade temperatures above 38 degrees C were associated with high parasitaemia above 10,000 parasites/mm3. Of the 911 children who died in the area within the last five years, 22.4% died of fever of unknown origin, 39.7% from malaria, 22.5% from convulsion, 10.5% from diarrhoea and 4.6% from cough. Chloroquine is the drug of choice for the treatment of malaria and there were many cases of drug abuse, and use of sub-curative doses prescribed by non-medically qualified staff.
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PMID:Malaria and its treatment in rural villages of Aboh Mbaise, Imo State, Nigeria. 198 Aug

Weekly oral chloroquine prophylaxis for malaria has been associated with impaired antibody response to intradermal rabies vaccination. Experimental data indicate that chloroquine may inhibit yellow fever virus in vitro, yet there has been no clinical evidence to suggest that antibody response to yellow fever vaccine is impaired by concomitant oral administration of chloroquine. A prospective trial was undertaken to evaluate the antibody response to yellow fever 17D vaccine (Connaught Laboratories) of volunteers who were randomized to taking either chloroquine or no drug. Of fifty subjects, 28 were randomized to taking chloroquine, 22 were randomized to taking no drug. Yellow fever 17D vaccine was administered on day 0 and blood sampled on days 0, 14, 35 and 210. Chloroquine was administered weekly for four weeks. There was no significant difference in peak antibody titer by plaque reduction neutralization testing (PRNT) between the group that took chloroquine (mean log peak of reciprocal titer 1.43 +/- SD 0.60) with vaccine subcutaneously compared to vaccine-only group (mean log peak of reciprocal titer = 1.21 +/- 0.55). All fifty subjects seroconverted to yellow fever vaccine by day 210. ELISA testing was also performed on all subjects. The two tests showed good correlation (Spearman r = 0.675), although ELISA readings were positive by day 14 in significantly more subjects (p = .01). We conclude that routine anti-malarial doses of chloroquine do not affect antibody response to yellow fever 17D vaccine. ELISA testing, a less complex and less time-consuming test, correlates well with PRNT and is proposed for additional trials to measure yellow fever 17D vaccine response in flavivirus non-immune subjects.
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PMID:The effect of chloroquine prophylaxis on yellow fever vaccine antibody response: comparison of plaque reduction neutralization test and enzyme-linked immunosorbent assay. 199 43

Malaria infections by Plasmodium (P.) vivax. P. ovale or P. malariae follow mostly a benign course, and ambulatory treatment is safe, provided there is no other significant morbidity. Ambulatory treatment for falciparum malaria must be considered only if a number of conditions are met, making potential complications most unlikely. Furthermore, it is imperative that the patient can be reliably supervised at home. Taking into account the increase of P. falciparum strains resistant to chloroquine, cases meeting the criteria for ambulatory care can mostly be treated with mefloquine, pyrimethamine/sulfadoxine or pyrimethamine/sulfadoxine/mefloquine. Chloroquine remains the first choice for treatment of malaria due to P. vivax, P. ovale or P. malariae.
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PMID:[Possibilities and limitations of malaria therapy in general practice]. 199 80

Compliance with malaria prophylaxis or reserve drugs was investigated in 477 individuals travelling to regions with endemic malaria. Correct intake of prophylactic medication was confirmed in 225 out of 285 (= 78%). Compliance was independent of type of drug (Mefloquine, Sulfadoxine-Pyrimethamine, Chloroquine). Two tourists missed to start prophylaxis one week before the onset of their travel. 14 travellers stopped prophylactic medication too early after their return, 31 tourists took too high doses of mefloquine. None of the tourists travelling to countries with a therapeutic reserve only became sick, whereas two travelling to Africa contracted malaria.
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PMID:[Malaria study]. 199 82

Chloroquine and ammonium chloride, by virtue of their basic properties, have been shown to raise endocytic and lysosomal pH and thereby interfere with normal iron metabolism in a variety of cell types, including mononuclear phagocytes. Cellular iron metabolism is of critical importance to Legionella pneumophila, an intracellular bacterial pathogen whose capacity to multiply in human mononuclear phagocytes is dependent upon the availability of intracellular iron. In view of this, we have studied the effects of chloroquine and ammonium chloride on L. pneumophila intracellular multiplication in human monocytes. Chloroquine, at a concentration of 20 microM, and ammonium chloride, at a concentration of 20 mM, inhibited L. pneumophila intracellular multiplication by 1.4 +/- 0.2 (SEM) logs and 1.5 +/- 0.2 logs, respectively. Chloroquine- and ammonium chloride-induced inhibition of L. pneumophila intracellular multiplication was completely reversed by iron nitrilotriacetate, an iron compound which is soluble in the neutral to alkaline pH range, but not by iron transferrin, which depends upon acidic intracellular conditions to release iron. Chloroquine had no major direct effect on L. pneumophila multiplication in artificial media except at extremely high concentrations (15,000-fold that which inhibited L. pneumophila multiplication in mononuclear phagocytes), and inhibition at such concentrations was not reversed by iron nitrilotriacetate. This study demonstrates that chloroquine and ammonium chloride inhibit the intracellular multiplication of L. pneumophila by limiting the availability of iron to the bacterium. It is possible that such a mechanism of action underlies chloroquine's antimicrobial effect against other intracellular pathogens, such as the agents of malaria and tuberculosis.
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PMID:Chloroquine inhibits the intracellular multiplication of Legionella pneumophila by limiting the availability of iron. A potential new mechanism for the therapeutic effect of chloroquine against intracellular pathogens. 205 29

Chloroquine remains the most commonly antimalaric drug utilized all around the world (340 t in 1988). Its efficiency is linked to its action on the digestive vacuole of plasmodium. Since 1957, the areas of resistance are spreading over of an alarming way, striking all continents. 3,000 cases of malaria are imported in France each year, and 90% of the strains tested in vitro by incorporating tritium hypoxanthine are resistant to chloroquine. The resistant parasites are able to exclude chloroquine from their cytoplasm and produce in great number two genes to synthetize a glycoprotein, probable agent of cellular exclusion of the antimalaric drug. Despite of it, to prescribe chloroquine in prophylaxis remains indispensable, because the risk of severe malaria due to some sensitive strains of Plasmodium falciparum.
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PMID:[Malaria: chloroquine resistance]. 207 46

The authors analyze the recent treatment regimens of malaria, related to Plasmodium strains and clinical manifestation. Chloroquine is the first choice drug for uncomplicated chloroquine-sensitive P. falciparum, whereas for P. malariae, P. vivax and P. ovale infections treatment with chloroquine plus primaquine is also recommended. For uncomplicated chloroquine-resistant P. falciparum infections many treatment regimens are available. Management of complications is also analyzed.
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PMID:[An update on the therapy of malaria]. 207 76

A clinical and entomological survey of malaria was carried out in Bakau, a peri-urban coastal settlement in The Gambia, from June 1988-May 1989. Only 41 of a cohort of 560 children, aged from three months to nine-years-old, experienced a clinical episode of malaria during the observation period. The majority of cases were identified at clinics and not by regular community surveillance. In Bakau Old Town episodes of malaria were more common on the periphery of the settlement, adjacent to typical anopheline breeding sites, than in the centre. Overall malaria cases were not significantly clustered in space and time, although three pairs of cases among children sleeping in the same room at the same time were identified. A cross-sectional survey in November, at the end of the rainy season, revealed a point prevalence parasitaemia of 2.0% and a spleen rate of 0.3%. All malariometric parameters measured were much lower than any found in comparable studies undertaken in rural areas of the country, reflecting the low number of malaria vectors, Anopheles gambiae complex mosquitoes, found in Bakau. Chloroquine consumption, sleeping under bednets, houses with ceilings, the use of insecticide aerosols and burning traditional mosquito repellents may all have contributed to the low prevalence of malaria in the study area.
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PMID:Malaria in a peri-urban area of The Gambia. 207 33

Chloroquine is a weak base which has been shown to inhibit lysosomal acidification. Chloroquine inhibits iron uptake in reticulocytes at a concentration of 0.5 mM. It is also effective in the control of malaria and other parasitic diseases. We now report that chloroquine inhibits NADH diferric transferrin reductase as well as the proton release stimulated by diferric transferrin from liver and HeLa cells. Ammonium chloride which also inhibits endosome acidification does not significantly inhibit the NADH diferric transferrin reduction. NADH diferric transferrin reductase of isolated rat liver plasma membrane is inhibited by chloroquine at concentrations similar to those required for inhibition of diferric transferrin reduction by whole cells. Ferricyanide reduction by whole cells is also inhibited by chloroquine. These observations provide an alternative mechanism for chloroquine control of acidification of endosomes and suggests a new approach to control of protozoal parasites through inhibition of a transmembrane oxidoreductase which controls transmembrane proton movement.
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PMID:Transplasma membrane electron and proton transport is inhibited by chloroquine. 217 87


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