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)

Quinine dihydrochloride (10 mg salt/kg infused over one hour) and mefloquine (15 mg base/kg) were given simultaneously to 13 adults with uncomplicated falciparum malaria. Supine and standing blood pressures were recorded and the electrocardiogram monitored. Plasma concentrations of the 2 drugs were similar to those reported previously for the 2 compounds given individually to a similar group of patients. Although postural hypotension was common (6 cases before treatment and 7 after) and the electrocardiogram QTc interval was prolonged by a mean of 12% (SD = 8) following drug treatment, there was no evidence of a clinically significant cardiovascular pharmacodynamic interaction between these 2 structurally related antimalarial compounds.
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PMID:Lack of a significant adverse cardiovascular effect of combined quinine and mefloquine therapy for uncomplicated malaria. 950 82

Two patients, a 25-year-old woman and a 62-year-old man, with Plasmodium vivax infection, suffered repeated attacks of malaria despite standard treatment with chloroquine and subsequently primaquine. The relapses were due to a combination of decreased primaquine sensitivity and incorrect prescription of primaquine. Primaquine is administered as diphosphate (salt), but the required amount has to be prescribed as base (26.3 mg diphosphate corresponds to 15 mg base).
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PMID:[Recurrent Plasmodium vivax malaria in spite of primaquine follow-up treatment]. 954 28

Proplasmepsin II is the zymogen of plasmepsin II, an aspartic proteinase used by Plasmodiumfalciparum to digest hemoglobin during the blood stage of malaria. A large shift between the N-domain and the central and C-domains of proplasmepsin II opens the active site cleft, preventing the formation of a functional aspartic proteinase active site. This mode of inhibition of catalytic activity has not been observed in any other aspartic proteinase zymogen. Instead of occluding a pre-formed active site, as in the gastric aspartic proteinase zymogens, the prosegment of proplasmepsin II interacts extensively with the C-domain and serves as a 'harness' to keep the domains apart. Disruption of key salt bridges at low pH may be important in activation.
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PMID:Crystal structure of the novel aspartic proteinase zymogen proplasmepsin II from plasmodium falciparum. 988 89

A 23 year old man with no history of neurological or psychiatric illness ingested three weekly 228 mg doses of mefloquine base (250 mg salt) as malaria prophylaxis while in India. He experienced an increasingly severe adverse reaction after each dose, including symptoms of paranoia, hallucinations, and suicidal ideation. The man discontinued mefloquine and continued malaria prophylaxis with chloroquine. Shortly after the first 300 mg dose of chloroquine base (500 mg chloroquine phosphate salt), symptoms acutely intensified and became debilitating. Severe symptoms persisted for 12 months following the discontinuation of both antimalarial drugs.
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PMID:A severe adverse reaction to mefloquine and chloroquine prophylaxis. 1033 Jul 49

Oviposition preference of the Australasian coastal malaria vector Anopheles farauti s.s. for water of varying salinity was determined in the laboratory to help understand the distribution and control of this species in the field. Numbers of eggs laid showed an inverse relationship with salinity; of 5 NaCl concentrations most eggs were laid in distilled water but some were laid in 3.17% NaCl (the salinity of seawater). The association of An. farauti with coastal areas occurs in spite of an aversion to salt water by ovipositing females. Factors other than salinity must be the primary determinants of distribution. Increasing the salinity of larval habitats will not totally prevent An. farauti from laying eggs. Elimination of this species may not occur unless salinity is kept high enough to prevent complete larval development.
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PMID:Oviposition preference for freshwater in the coastal malaria vector, Anopheles farauti. 1048 Jan 17

The recommended dose of 10 mg quinine/kg bodyweight 3 times a day for 7 days for treatment of malaria is so high that many patients experience cinchonism. We have earlier obtained good results with 7 days' treatment with 20 mg Quinimax/kg bodyweight divided into 2 daily doses. In order to identify the lowest effective dose, children with symptomatic malaria were treated with quinine twice a day for 7 days. They were assigned to 1 of 3 groups treated daily with 10 mg/kg, 15 mg/kg, or 20 mg/kg bodyweight, respectively; 42, 46, and 34 children, respectively, received treatment and completed 5 weeks of follow-up. The cumulative percentages of all children with parasitaemia during follow-up on day 28 or before were 33%, 13% and 12%, respectively. Treatment with 10 mg quinine salt/kg daily for 7 days gave a significantly higher rate of recrudescence than did treatment with 15 or 20 mg/kg daily. Thus at least 15 mg of quinine salt/kg bodyweight daily should be recommended for treatment of symptomatic Plasmodium falciparum malaria in Guinea-Bissau.
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PMID:Low-dose quinine for treatment of Plasmodium falciparum malaria in Guinea-Bissau. 1069 19

Quinoline-containing drugs such as chloroquine and quinine have had a long and successful history in antimalarial chemotherapy. Identification of ferriprotoporphyrin IX ([Fe(III)PPIX], haematin) as the drug receptors for these antimalarials called for investigations of the binding affinity, mode of interaction, and the conditions affecting the interaction. The parameters obtained are significant in recent times with the emergence of chloroquine resistant strains of the malaria parasites. This has underlined the need to unravel the molecular mechanism of their action so as to meet the requirement of an alternative to the existing antimalarial drugs. The isothermal titration calorimetric studies on the interaction of chloroquine with haematin lead us to propose an altered mode of binding. The initial recognition is ionic in nature mediated by the propionyl group of haematin with the quaternary nitrogen on CQ. This ionic interaction induces a conformational change, such as to favour binding of subsequent CQ molecules. On the contrary, conditions emulating the cytosolic environment (pH 7.4 and 150 mM salt) reveal the hydrophobic force to be the sole contributor driving the interaction. Interaction of a carefully selected panel of quinoline antimalarial drugs with monomeric ferriprotoporphyrin IX has also been investigated at pH 5.6 mimicking the acidic environment prevalent in the food vacuoles of parasite, the center of drug activity, which are consistent with their antimalarial activity.
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PMID:Interaction of chloroquine and its analogues with heme: An isothermal titration calorimetric study. 1102 92

To assess the salt tolerance of the malaria vector Anopheles farauti sensu stricto, larvae were collected from a freshwater environment on the outskirts of Honiara, Solomon Islands and placed in trays containing water with salinity varying from freshwater to seawater. Dead larvae and pupae and emerged adults were recorded and preserved. Most adults and nearly half of the larvae and pupae were then subjected to DNA analysis for species identification. No adult An. farauti emerged after prolonged immersion of larvae in undiluted seawater (3.5% salinity), although temporary immersion before pupation was compatible with survival. Salinities of up to 2.2% to 2.5% were compatible with good survival and adult emergence, at least from fourth instars. The results suggest that higher salinities may slow larval development and show that mortality at a given salinity is not uniform.
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PMID:Salinity tolerance of Anopheles farauti Laveran sensu stricto. 1106 Oct 1

Artesunate is the most widely used of the artemisinin derivatives. These drugs are being used increasingly throughout the tropical world, and are an essential component of the treatment of multi-drug resistant malaria. The recent and widespread appearance of counterfeit artesunate tablets in several countries in Southeast Asia poses a serious threat to health in this region. We have developed a simple, inexpensive colorimetric test to determine artesunate authenticity in tablets. The test is based on a reaction between an alkali decomposition product of artesunate and a diazonium salt, fast red TR (FRTR). The appearance of a yellow color indicates the presence of artesunate. The specificity of the test is dependent on the pH of the reaction. Among other antimalarials tested, (i.e. artemisinin, artemether, chloroquine, quinine, primaquine, sulfadoxine, and pyrimethamine) only artesunate produced a positive color reaction at pH 4. The assay requires only 1% of the total weight of a standard tablet containing 50 mg of artesunate and can be completed within 10 min. The method was tested on six genuine artesunate tablets and six counterfeit artesunate tablets obtained in Southeast Asia. The average amount of artesunate in the genuine tablets was determined to be 50.8 +/- 2.9 mg while the counterfeit tablets were found to contain no artesunate.
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PMID:A colorimetric field method to assess the authenticity of drugs sold as the antimalarial artesunate. 1110 40

Since no effective malaria prevention measures have been identified for pregnant women living on the western border of Thailand, prompt diagnosis and efficient treatment are paramount, although drug resistance in Plasmodium falciparum has narrowed the treatment options. An open randomized comparison of supervised quinine (10 mg salt/kg every 8 h) for 7 days (Q7) versus mefloquine 25 mg base/kg (total dose) plus artesunate 4 mg/kg per day for 3 days (MAS3) was conducted in 1995-97 in 108 Karen women with acute uncomplicated falciparum malaria in the second or third trimesters of pregnancy. The MAS3 regimen was more effective than the Q7 regimen: day 63 cure rates were 98.2% (95% CI 94.7-100) (n = 65) for MAS3 and 67.0% (95% CI 43x3-90x8) (n = 41) for Q7, P = 0x001. The MAS3 regimen was also associated with less gametocyte carriage; the average person-gametocyte-weeks for MAS3 was 2.3 (95% CI 0-11) and for Q7 was 46x9 (95% CI 26-78) per 1000 person-weeks, respectively (P < 0.001). MAS3 was significantly better tolerated. These evident advantages must be balanced against a possible increased risk of stillbirth with the use of mefloquine in pregnancy. Further randomized studies assessing the safety and efficacy of other artemisinin-containing combination regimens in pregnancy are needed urgently.
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PMID:Randomized comparison of mefloquine-artesunate versus quinine in the treatment of multidrug-resistant falciparum malaria in pregnancy. 1119 58


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