Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This randomized, open-label clinical trial compared a fixed-dose combination of atovaquone and proguanil (n=55) with chloroquine (n=23) or a combination of chloroquine, sulfadoxine, and pyrimethamine (n=32) for treatment of acute falciparum malaria in the Philippines. Patients were hospitalized for 28 days to ensure medication compliance and prevent reinfection. Atovaquone-proguanil produced a significantly higher cure rate (100%) compared with that for chloroquine (30.4%; P<.0001) or chloroquine-sulfadoxine-pyrimethamine (87.5%; P<.05). Treatments did not differ significantly with respect to parasite clearance time (mean: 46.7 h for atovaquone-proguanil, 60.0 h for chloroquine, and 42.8 h for chloroquine-sulfadoxine-pyrimethamine) or fever clearance time (mean, 38.8, 46.8, and 34.5 h, respectively). Adverse events were typical of malaria symptoms; the most frequently reported events were vomiting (18% for atovaquone-proguanil, 17% for chloroquine, and 9% for chloroquine-sulfadoxine-pyrimethamine), abdominal pain (15%, 17%, and 3%, respectively), anorexia (11%, 13%, and 0%, respectively), and headache (6%, 17%, and 3%, respectively). Atovaquone-proguanil was well tolerated and more effective than chloroquine or chloroquine-sulfadoxine-pyrimethamine for treatment of multidrug-resistant falciparum malaria in the Philippines.
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PMID:Atovaquone-proguanil compared with chloroquine and chloroquine-sulfadoxine-pyrimethamine for treatment of acute Plasmodium falciparum malaria in the Philippines. 1060 98

The increasing frequency of therapeutic failures in falciparum malaria underscores the need for novel, rapidly effective antimalarial drugs or drug combinations. Atovaquone and proguanil are blood schizonticides that demonstrate synergistic activity against multi-drug-resistant Plasmodium falciparum in vitro. In an open-label, randomized, controlled clinical trial conducted in Thailand, adult patients with acute P. falciparum malaria were randomly assigned to treatment with atovaquone and proguanil/hydrochloride (1,000 mg and 400 mg, respectively, administered orally at 24-hr intervals for three doses) or mefloquine (750 mg administered orally, followed 6 hr later by an additional 500-mg dose). Efficacy was assessed by cure rate (the percentage of patients in whom parasitemia was eliminated and did not recur during 28 days of follow-up), parasite clearance time (PCT), and fever clearance time (FCT). Safety was assessed by sequential clinical and laboratory assessments for 28 days. Atovaquone/proguanil was significantly more effective than mefloquine (cure rate 100% [79 of 79] vs. 86% [68 of 79]; P < 0.002). The atovaquone/proguanil and mefloquine treatments did not differ with respect to PCT (mean = 65 hr versus 74 hr) or FCT (mean = 59 hr versus 51 hr). Adverse events were generally typical of malaria symptoms and each occurred in < 10% of the patients in either group, with the exception of increased vomiting found in the atovaquone/proguanil group. Transient elevations of liver enzyme levels occurred more frequently in patients treated with atovaquone/proguanil than with mefloquine, but the differences were not significant and values returned to normal by day 28 in most patients. The combination of atovaquone and proguanil was well tolerated and more effective than mefloquine in the treatment of acute uncomplicated multidrug-resistant falciparum malaria in Thailand.
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PMID:Efficacy and safety of atovaquone/proguanil compared with mefloquine for treatment of acute Plasmodium falciparum malaria in Thailand. 1034 24

The continuing spread of drug-resistant malaria emphasizes the need for new antimalarial drugs. Atovaquone is a broad-spectrum antiprotozoal drug with a novel mechanism of action, via inhibition of parasite mitochondrial electron transport, and a favorable safety profile. Early studies with atovaquone alone for treatment of malaria demonstrated good initial control of parasitemia but an unacceptable rate of recrudescent parasitemia. Parasites isolated during recrudescence after treatment with atovaquone alone were resistant to atovaquone in vitro. The combination of atovaquone and proguanil is synergistic in vitro, and clinical studies demonstrated enhanced efficacy of the combination compared to either drug alone for treatment of malaria. Malarone, a fixed-dose combination of 250 mg of atovaquone and 100 mg of proguanil hydrochloride, is available in many countries for treatment of acute, uncomplicated malaria caused by Plasmodium falciparum. At the recommended dose (in adults, four tablets once a day for three days), the overall cure rate was > 98% in more than 500 patients with falciparum malaria. In four randomized, controlled clinical trials, treatment with atovaquone and proguanil hydrochloride was significantly more effective than mefloquine (Thailand), amodiaquine (Gabon), chloroquine (Peru and the Philippines) or chloroquine plus pyrimethamine/sulfadoxine (Philippines). In clinical trials where the comparator drug was highly effective, treatment with atovaquone and proguanil hydrochloride was equally effective. Parasites isolated during recrudescence after treatment with the combination of atovaquone and proguanil were not resistant to atovaquone in vitro. The most commonly reported adverse events in clinical trials (abdominal pain, anorexia, nausea, vomiting, diarrhea and coughing) occurred with similar frequency in patients treated with a comparator drug. Malarone is a safe and effective new agent for treatment of malaria.
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PMID:Malarone (atovaquone and proguanil hydrochloride): a review of its clinical development for treatment of malaria. Malarone Clinical Trials Study Group. 1034 25

In Western countries, France accounts for the most concerned by imported malaria. The objective of the present study was to describe the epidemiological and clinical features of imported malaria in adults attending the University Hospital Center (UHC) ofBordeaux and to compare these findings with the French national epidemiological data. A retrospective analysis of all patients aged over 15 years with parasitologically confirmed malaria in patients recruited between January 1, 2000 and December 31, 2007 has been performed. A total of 526 cases fitted the inclusion criteria with two-thirds of males and a mean age of 37 years. Patients were less frequently native from sub-Saharan Africa (SA), Madagascar, and Comoros than those from the French national data register (29 versus 72%). Hence, SA was the main destination (2/3 travelling to Western Africa and 1/3 to Central Africa). The recourse to an adequate chemoprophylaxis (CPL) for stays in areas of chemoresistance had been reported in about one-third of the patients. From these, two thirds were noncompliant. The recourse to chloroquine less frequent (6 versus 24%) among patients from Bordeaux compared to those from the national data register whereas the recourse to mosquito net use more frequent in patients from Bordeaux (36 versus 3%). Plasmodium falciparum was the main infective species.Malaria was more frequently associated with hospitalization (89 versus 71%) and with severe disease (9 versus 4%) in Bordeaux than in national data register. Two deaths were declared. Atovaquone-proguanil (AP) combination therapy wasmore frequently used in Bordeaux compared to the national data (64 versus 20%). This AP combination treatment was the most frequently prescribed for uncomplicated malaria, whereas intravenous quinine was mainly used for complicated malaria and for patients with vomiting. The lack of CPL, the diagnosis or therapeutic delay, and the lethality of malaria among travellers infected by malaria imported from SA argue for the implementation of continuing medical training and health education targeted at travellers from France to high malaria-endemic areas such as SA, Madagascar, and Comoros.
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PMID:[Imported malaria in University Hospital Center of Bordeaux, France, 2000-2007. A comparison study with the French national epidemiological data]. 2034 44