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)

Pyrimethamine resistance in cultivated laboratory isolates of Plasmodium falciparum is linked to the dihydrofolate reductase mutation Asn-108, a mutation that acts by interrupting drug binding within the active site of the enzyme. To determine the prevalence of this mutation in endemic regions harboring pyrimethamine-resistant malaria, we used a mutation-specific polymerase chain reaction assay to survey P. falciparum strains from a wide section of the Brazilian Amazon. Mutations were identified directly from blood samples without intervening steps of in vitro cultivation. Of 42 samples collected from four states in Brazil, 38 (90%) contained the Asn-108 codon AAC that confers pyrimethamine resistance, four samples contained only the wild-type Ser-108 codon AGC, and none contained the Thr-108 codon ACC found in cycloguanil-resistant pyrimethamine-sensitive strains. These findings indicate that a very high incidence of the Asn-108 DHFR mutation is responsible for pyrimethamine resistance in the Amazon, and they are consistent with recent failure rates reported for Fansidar (pyrimethamine-sulfadoxine). We suggest that limited use of proguanil be evaluated as an alternative to pyrimethamine.
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PMID:Prevalence of the dihydrofolate reductase Asn-108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the Brazilian Amazon. 195 58

We reported a rare case of Plasmodium vivax malaria who showed findings of disseminated intravascular coagulation (DIC). A 50-year-old Japanese male was sent to our hospital with the diagnosis of Plasmodium vivax malaria on the 26th of April, 1990. He had stayed in the Solomon Islands from Oct. 1987 to Dec. 1989, and had febrile episodes during his stay in the island. On April 18, 1990, he complained of a high fever with chills, and showed the same episodes on the 20th, 22th and was diagnosed as malaria. He was treated successfully with the sulfadoxine 500 mg and pyrimethamine 25mg (Fansidar), following the normal temperature on the 4th day and disappearance of malarial parasites in the peripheral blood smear on the 6th day. Interestingly, he had thrombocytopenia and a high titer serum level of fibrin degradation product (FDP) supporting the questionable diagnosis of DIC. Even on the 12th day after improved thrombocytopenia by treatment with Gabexate (FOY), the serum level of FDP, D-dimer and thrombin-nati-thrombin (TAT)III complex still remained at high titer levels. One month later he was readmitted for a relapse of Plasmodium vivax malaria, when he showed thrombocytopenia but the serum level of FDP, D-dimer, TAT III complex and PM.alpha 2 PI complex were normal levels. We concluded that the thrombocytopenia and the high titer of FDP at his first admission was a manifestation of DIC.
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PMID:[A case of Plasmodium vivax malaria with findings of DIC]. 207 64

Recommendations for the prevention of malaria among travelers have been developed by CDC in consultation with representatives from the Offices of Medical Services of the Department of State and the Peace Corps; the Division of Experimental Therapeutics of the Walter Reed Army Institute of Research; the Office of the Surgeon General, U.S. Army; the Office of the Surgeon General, U.S. Air Force; and the Bureau of Medicine and Surgery, U.S. Navy. Resistance of Plasmodium falciparum to chloroquine has spread to most areas with malaria. Alternative drugs to chloroquine are either associated with adverse reactions, are of limited efficacy, or require complex and detailed instructions for use that reduce compliance. These factors have contributed to a threefold increase in the number of reported P. falciparum infections among U.S. travelers to malarious areas since 1980. A new drug, mefloquine (Lariam), is expected to be highly effective against both chloroquine-resistant and Fansidar-resistant P. falciparum infections. Mefloquine is now recommended as the drug of choice for travelers at risk of infection with chloroquine-resistant P. falciparum. Alternative drugs for travelers who cannot take mefloquine include 1) doxycycline alone or 2) chloroquine alone, with Fansidar available for standby treatment while medical care is sought for evaluation of febrile illness when travelers are in a malarious area. Prospective travelers and health-care providers are advised to call the CDC Malaria Hotline at (404) 332-4555 for detailed recommendations for the prevention of malaria.
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PMID:Recommendations for the prevention of malaria among travelers. 215 46

Recommendations for the prevention of malaria among travelers have been developed by CDC in consultation with representatives from the Offices of Medical Services of the Department of State and the Peace Corps; the Division of Experimental Therapeutics of the Walter Reed Army Institute of Research; the Office of the Surgeon General, U.S. Army; the Office of the Surgeon General, U.S. Air Force; and the Bureau of Medicine and Surgery, U.S. Navy. Resistance of Plasmodium falciparum to chloroquine has spread to most areas with malaria. Alternative drugs to chloroquine are either associated with adverse reactions, are of limited efficacy, or require complex and detailed instructions for use that reduce compliance. These factors have contributed to a threefold increase in the number of reported P. falciparum infections among U.S. travelers to malarious areas since 1980. A new drug, mefloquine (Lariam), is expected to be highly effective against both chloroquine-resistant and Fansidar-resistant P. falciparum infections. Mefloquine is now recommended as the drug of choice for travelers at risk of infection with chloroquine-resistant P. falciparum. Alternative drugs for travelers who cannot take mefloquine include 1) doxycycline alone or 2) chloroquine alone, with Fansidar available for standby treatment while medical care is sought for evaluation of febrile illness when travelers are in a malarious area. Prospective travelers and health-care providers are advised to call the CDC Malaria Hotline at (404) 332-4555 for detailed recommendations for the prevention of malaria.
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PMID:From the Centers for Disease Control. Recommendations for the prevention of malaria among travelers. 215 78

This study appreciated the efficiency of uncomplicated malaria second line treatment (P. falciparum) in an area with high level of chemoresistance. No therapeutic failure was found with sulfadoxine-pyrimethamine (Fansidar), and mefloquine-sulfadoxine-pyrimethamine (Fansimef), in contrast with a rate of 8% with quinine. The authors discuss the place of these therapeutic, in the treatment of malaria.
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PMID:[Uncomplicated malaria attack in an area with high resistance to chloroquine. 3. The use of second-choice oral drug treatment]. 219 Jul 6

Chloroquine is currently the drug of choice for treatment of acute attacks of Plasmodium falciparum malaria in chloroquine-sensitive areas. In areas of low level resistance, this drug may still be used (25 mg/kg of body weight in three days) in semi-immune patients. In case of failure, or in areas of high level resistance, quinine (25 mg/kg/day for 3 to 5 days) or, in spite of increasing resistance, Fansidar should be prescribed. Mefloquine, Fansimef and Halofantrine ought to be strictly prescribed to delay occurrence of resistance. Severe attacks require quinine by continuous intravenous infusion. Spleen enlargement does not usually require specific treatment unless poor tolerance is observed. Blood transfusions present a considerable risk of HIV transmission. Appropriate malaria treatment may avoid blood transfusions thus preventing HIV dissemination in Africa.
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PMID:[Treatment of Plasmodium falciparum malaria in Africa (except cerebral malaria)]. 219 75

Travelers to malarious areas of the world should take precautions against mosquito bites and take medications to prevent the disease. Chloroquine is the prophylactic agent of choice in areas where malaria remains sensitive. If no contraindications exist, mefloquine is recommended in areas where chloroquine resistance occurs. Alternative regimens would include doxycycline taken as the sole prophylactic agent, or weekly chloroquine with a treatment dose of Fansidar to be taken if symptoms compatible with malaria occur.
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PMID:Emporiatrics: protecting travelers from malaria. 219 9

We have analyzed the clinical data of 189 patients with malaria to establish antimalarial regimens in Japan. The causative parasite species were Plasmodium falciparum in 56 cases (30%), P. vivax in 132 (70%) and P. malariae in 1 (1%). The outcomes f malaria cases are as follows: Cure rats in falciparum and vivax malaria are 86% and 91%, respectively. Two patients died of falciparum malaria and recurrence occurred in 6 cases (11%) of falciparum malaria. Relapse was seen in 12 (9%) of vivax malaria. Chloroquine was most frequently used among antimalarial agents (in 123 cases, 65% of the total) for suppressing acute attacks. The efficacy of chloroquine was evaluated by classifying each case into three groups: chloroquine alone in group one, chloroquine in combination with other antimalarials in group two and other antimalarials except chloroquine in group three. The cure rate among each group is about 80% and there is no difference among them. However, it is noticeable that recurrence occurred when patients were treated with a combination of chloroquine and quinine. We have found a similar result as this in another old report in Japan. Primaquine is effective for eliminating hepatic tissue schizonts but in this study, relapse occurred in 12 cases of vivax, although primaquine had been used in 10 out of 12 cases. In primaquine group, relapse occurred at a similar rate between chloroquine and Fansidar cases. Further studies are needed to decide whether a larger dose of primaquine is appropriate for treatment of vivax malaria. Recovery periods from fever and parasitemia were compared between chloroquine and Fansidar cases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical evaluation of antimalarial drugs]. 220 71

Serious adverse reactions during malaria chemoprophylaxis are reviewed. Three drugs considered to have caused serious reactions in recent years are pyrimethamine/sulfadoxine (Fansidar), pyrimethamine/dapsone (Maloprim) and amodiaquine. These reactions are principally independent of dose and cannot be determined during screening for optimal doses. However, host factors may precipitate dose-dependent reactions, some of which could be avoided with improvements in drug licensing. Since serious and life-threatening reactions are relatively rare (between 1:1000 and 1:20,000), Phase I to III trials cannot identify them. Reliance must therefore be placed on Phase IV post-marketing studies, including ongoing reviews of national registers, and specially tailored studies to identify the risk using prescription-event monitoring in high-risk populations. Occasionally, medical-record linkage, case-control and cohort studies may provide supportive data. Although large numbers of travellers must, of necessity, be exposed to a drug before relatively rare reactions are identified, the ascertainment of risk using post-marketing surveillance was prevented by the following five deficiencies: lack of awareness of early alerts, inadequate use of national registers, poor attention to epidemiological and statistical rigour, inadequate verification of denominators, and inadequacy of data records. Recommendations are given for minimizing such errors in the future.
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PMID:Ascertainment of risk of serious adverse reactions associated with chemoprophylactic antimalarial drugs. 220 62

Plasmodium falciparum is resistant to proguanil, chloroquine and pyrimethamine/sulfadoxine (Fansidar) in many parts of the world. It can be assumed that in the future resistance to mefloquine and quinine will also increase. This will have important consequences for the recommended schemes for drug prophylaxis. No new drugs suitable for prophylaxis will be on the market in the near future. Neither the combination of mefloquine with pyrimethamine/sulfadoxine (Fansimef) nor the new drug halofantrine will solve the impending problems. It has to be accepted that no absolute protection against malaria infection can be guaranteed by the presently available drugs. In regions with low transmission no permanent prophylaxis but only a standby therapy is recommended. Moreover, personal protection against mosquitoes with pyrethrum-impregnated bed-nets and repellents will gain importance.
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PMID:[Malaria prophylaxis: what is safe?]. 226 20


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