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)

Artemether has the potential to be an alternative antimalarial for multiple drug resistant falciparum malaria. However, it has been associated with high recrudescent rates which may be due to incorrect dosage regimens. The dosage regimens are varied from country to contry. We have carried out a comparative study of two dosage regimens, ie 480 mg and 600 mg total dose given over 5 days in uncomplicated and severe falciparum malaria. 167 patients were included in the study, 61 with acute uncomplicated falciparum malaria and 106 with severe malaria. All patients showed a good initial response. The difference in total dose had no effect on the parasite or fever clearance time (PCT or FCT). However, the severity of the disease did have some influence of these times. The PCT and FCT from either regimen of uncomplicated malaria were significantly faster than those of severe malaria (p < 0.005 and = 0.05, respectively). The cure rate seems to have some correlation with the amount of drug given and severity of the disease. The cure rates in uncomplicated malaria were 84 and 92%, respectively, for 480 mg and 600 mg. In severe malaria the cure rates dropped to 65 and 76%, respectively, for 480 and 600 mg. We conclude that artemether can be considered as an alternative antimalarial for multiple drug resistant falciparum malaria. However, the cure rate of severe falciparum malaria in this study is not considered satisfactory in areas with multiple drug resistant falciparum malaria. Further studies are needed to assess the curative efficacy with different dosage regimens.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Artemether in the treatment of multiple drug resistant falciparum malaria. 129 86

A comparative trial of the combination of mefloquine or MSP with tetracycline was carried out in fifty-one adult Thai male patients with acute falciparum malaria. The patients were randomized to receive either the combination of tetracycline (250 mg qid for 7 days) with mefloquine 4 tablets (1,000 mg) or with MSP 4 tablets (one tablet contains 250 mg mefloquine, 500 mg sulfadoxine and 25 mg pyrimethamine). Fifty patients had a complete 28-day follow-up period. Both regimens produced similar efficacy with no difference in adverse effects. In the mefloquine plus tetracycline group, the cure rate was 72% (18/25). One patient had an RIII response, the others showed initial response to the treatment with FCT and PCT of 40.7 +/- 27.4 and 76.2 +/- 34.2 hours (mean +/- SD) respectively. However, 6 patients developed recrudescence between days 17 and 29 (RI), 3 of these had vomiting. In the MSP plus tetracycline group, the cure rate was 76% (19/25). The means (+/- SD) of FCT and PCT were 44.7 +/- 38.0 and 80.6 +/- 25.0 hours, respectively. Six patients had recrudescence between days 17 and 31 (RI), 2 of these had vomiting. Although the addition of tetracycline improved the cure rate of mefloquine when compared with standard dose of mefloquine alone (3 tablets), these combinations seem to be useful in areas where alternative drugs are not available.
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PMID:Clinical trials of mefloquine with tetracycline. 148 88

The pharmacokinetics of mefloquine at the therapeutic dose of 750 mg single orally were compared between cured and recrudescent patients with acute uncomplicated falciparum malaria. Mefloquine was well-tolerated during the study. The side-effects found were nausea, vomiting and diarrhea. Five patients showed R-I and two showed R-II types of response. All recrudescent patients came from the eastern border of Thailand. The time taken to clear the parasites (PCT) was significantly longer in patients with recrudescence (99.6 +/- 36.9 and 63.0 +/- 8.9 hours); however, there was no difference regarding fever clearance time (FCT: 39.0 +/- 16.1 and 31.0 +/- 21.3 hours). The maximum concentration (Cmax) and the concentration on the first and second days in cured patients were significantly higher than those of treatment failure patients. Other pharmacokinetic parameters appeared to be similar in both groups. The present study indicates the existence of mefloquine-resistant falciparum malaria in the eastern border of Thailand. Inadequate mefloquine concentration may play an important role in this aspect. In addition, this study also suggests that Cmax or the concentrations on the first or second day of treatment may be used as guidelines to predict the outcome of treatment.
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PMID:Pharmacokinetics of mefloquine in treatment failure. 182 Jun 38

The death of a 23-year-old female patient is reported. She was being treated for porphyria cutanea tarda (p.c.t.) and was mistakenly given a single dose of 1250 mg chloroquine (instead of the intended dose of 125 mg). The course differed from the typical course of chloroquine toxification, which involves cardiac arrhythmias as the main complication (reported in adults only after much higher doses); in spite of intensive care, this patient died 13 days after the ingestion of chloroquine, in a coma caused by irreversible, acute decompensation of the liver. Forensic autopsy and histological and toxicological investigations confirmed the clinical findings. Starting from the chloroquine's pharmacological mechanism of effect in p.c.t., the severe hepatotoxic effect of this drug in the present case is explained. The authors give a serious warning against exceeding the dose of chloroquine now usually recommended for the treatment of the p.c.t., which is 125-250 mg twice weekly. The presence of chronic porphyria hepatica, at least in its clinically manifest form, (= p.c.t.), should be considered a contraindication for chloroquine in prophylaxis and treatment of other illnesses (e.g. malaria and rheumatism).
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PMID:[Death following administration of 1,250 mg chloroquine in porphyria cutanea tarda]. 357 36

The antimalarials, chloroquine, hydroxychloroquine, and quinacrine, are used primarily for malaria; but they can be beneficial for cutaneous lupus erythematosus (LE), polymorphous light eruption, solar urticaria, and porphyria cutanea tarda. Antimalarials bind to deoxyribonucleic acid (DNA) which prevents DNA and ribonucleic acid (RNA) polymerase reactions and DNA heat inactivation; and they inhibit the LE cell phenomenon, antinuclear antibody reactions, and suppress lymphocyte transformation. By competing with calcium ion, they stabilize membranes and have an anesthetic effect. Their anti-inflammatory potential is due to their inhibition of hydrolytic enzymes, stabilization of lysosomes, interference with prostaglandin synthesis, blocking of chemotaxis, and antagonism of histamine responses. The antimalarials have no sunscreening properties. The most common toxic effects are cutaneous pigmentation, nausea, vomiting, diarrhea, mild ileus, and cycloplegia. There has been a reluctance to use chloroquine and hydroxychloroquine because of the possibility of retinopathy. However, if the "safe" daily dose limit of chloroquine, 2 mg per pound of body weight, and of hydroxychloroquine, 3.5 mg per pound of body weight, is followed, the chance of retinopathy is slight. Quinacrine does not cause retinopathy, but it has more cutaneous side effects than the other two agents.
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PMID:Antimalarials. 616 44

Twenty-eight male Thai patients with severe falciparum malaria were randomized to receive either artemether for a 5 (300 mg initial dose followed by 100 mg for another 4 days) or a 7 days regimen (160 mg initial dose, followed by 80 mg daily for another 6 days). Thirteen patients received a 5 day regimen and 15 received 7 day regimen. The follow-up period was 28 days. The patients in both groups were comparable in age, body weight, admission parasitemia, hematocrit and white cell count. There were 4 patients in each group who presented with cerebral malaria. The median values of parasite and fever clearance times (PCT and FCT) in the 5 and 7 days regimens were 52 vs 60 hours, and 85 vs 68 hours, respectively. There were 8 and 4 patients, respectively who had recrudescence during days 15 to 25. The cure rates were 38% (95% CI = 14-68%) and 73% (95% CI - 50-96%), respectively for 5 and 7 day regimens. None died in either group. No patients in either group had neurological sequelae after recovery of consciousness. Clinically adverse effects in either group were transient pain at the site of injection. No drug related biochemical or ECG changes were noted in either group. The duration of treatment is the determinant of the cure rate; however, the duration of even 7 days still resulted in high recrudescence rate. It may be necessary to combine artemether with other longer half-life antimalarials to improve the cure rate.
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PMID:Artemether 5 versus 7 day regimen for severe falciparum malaria. 766 17

At the Bangkok Hospital for Tropical Diseases in Thailand, health workers collected blood samples from male patients with acute uncomplicated falciparum malaria so researchers could compare the efficacy of artesunate (700 mg over 5 days) with the standard antimalarial treatment (600 mg quinine at 8 hour intervals plus 250 mg tetracycline at 6 hour intervals for 7 days). All 31 patients in the artesunate group had a much more rapid initial response than the 33 in the quinine-tetracycline group (mean parasite clearance time [PCT] = 37 hours; mean fever clearance time [FCT] = 31 vs. 73 and 55 hours, respectively) (p = 0.000001 for PCT; p = 0.000041 for FCT). In both groups, the mean PCT and mean FCT did not differ with level of pretreatment parasitemia. The cure rates on day 28 did not differ significantly (96.7% for the artesunate group, 100% for the quinine-tetracycline group). Five men in the artesunate group and nine in the quinine-tetracycline group had Plasmodium vivax in the peripheral blood between days 13 and 24, suggesting that these two regimens are not effective during the intrahepatic stage of plasmodia. 29 patients in the quinine-tetracycline group had tinnitus, while no one in the artesunate group did (p = 0.000001). Nausea and dizziness were common in both groups (45% for the artesunate group and 60% for the quinine-tetracycline group; 52% and 48%, respectively). Vomiting was more common in the quinine-tetracycline group (91% vs. 26%; p = 0.000005). Seven patients in the artesunate group had bradycardia, mostly during days 2-7. Convulsions occurred in one patient in the artesunate group 21 days after the first dose. They may have been caused by malaria, but artemisinin compounds have had central nervous system effects. These findings suggest that 700 mg artesunate is an effective antimalarial in areas with multiple-drug resistant parasites. Health workers should monitor its side effects, especially neurotoxicity, closely.
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PMID:Comparison of oral artesunate and quinine plus tetracycline in acute uncomplicated falciparum malaria. 820 43

Administration of antimalaria drugs to patients with symptomatic hepatic porphyria (porphyria cutanea tarda) at the First Medical Clinic made it possible due to previous experimental studies, to influence the porphyrim metabolism of yeasts. The effect of trimetoprim was investigated in clinical work in 12 hitherto not treated patients with the manifest form of symptomatic hepatic porphyria. The group comprised 9 men, mean age 56.4 years, and 3 women mean age 43.6 years. During the two-year clinical study dermatological symptoms of the disease became milder or receded. Concurrently there was a significant regression of porphyrinuria. In the whole group porphyrinuria declined to 11% of the original values. The porphyrin content of hepatic tissue declined considerably after two years treatment. In the group as a whole to 40% of the original values. Trimetoprim is another drug which influences porphyrin metabolism. The authors did not detect any undesirable side-effects of trimetoprim treatment. The effect of trimetoprim on clinical and biochemical parameters of the disease is less marked than the effect of chloroquine. This new treatment can be used in patients resistant to chloroquine or in combination with other anti-malaria drugs.
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PMID:[Trimethoprim in the therapy of symptomatic liver porphyria]. 840 17

50 patients (45 males + 5 females) suffering from acute uncomplicated attack of Plasmodium falciparum (Pf) malaria were treated with 1500 mg of halofantrine divided in three doses of 500 mg each given at an interval of 6 h. Results showed there were no primary treatment failures. Average Parasite Clearance Time (av. PCT) was 51.12 h and average Fever Clearance Time (av. FCT) was 31.25 h. Adverse Drug Reactions (ADR) were mild and self limiting. We conclude that halofantrine is a quite safe and effective new antimalarial agent in the treatment of Pf malaria cases.
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PMID:Halofantrine in the treatment of falciparum malaria. 854 34

The study compared the clinical efficacy and safety of oral artemisinin and oral artesunate as well as artemisinin pharmacokinetics during and after resolution of falciparum malaria. Forty adults with symptomatic falciparum malaria were allocated at random to treatment with either oral artemisinin (500 mg single dose on day 1 followed by 250 mg twice daily for 4 d and then another 500 mg single dose on day 6) or with oral artesunate (100 mg single dose on day 1 followed by 50 mg twice daily for 5 d). Patients were admitted to hospital at the Kibaha Designated District Hospital, Kibaha, Tanzania for the duration of treatment. The patients were seen once weekly for 3 more weeks. The time to parasite clearance (PCT) after oral artesunate (26.4 +/- 3.6 h) was shorter (P = 0.002) than after artemisinin (31 +/- 3.6 h). The fever subsidence time (FST) after oral artesunate (18.9 +/- 4.0 h) was also shorter (P = 0.04) than after artemisinin (21.8 +/- 4.6 h). Parasites were detected in 4 (20%) and 7 (35%) patients after completing treatment with artesunate and artemisinin respectively. In these patients the parasitaemia reappeared at the 3rd or 4th week of follow-up. Standard haematology, blood biochemistry and urinalysis, performed before drug intake and again on days 6 and 14, were normal. No clinical abnormality was observed during the study period. Artemisinin plasma concentrations, determined by high performance liquid chromatography with post-column derivatization and detection by ultraviolet light, were followed up to 8 h after drug administration on days 1 and 6. Artemisinin absorption was rapid, the maximum plasma concentrations (Cmax) being attained at about 3 h. Artemisinin areas under the plasma concentration-time curve (AUC) and the Cmax values were about 6 times higher after the first dose on day 1 than on day 6. This decrease in artemisinin plasma concentration is suggestive of an increase in metabolic capacity due to pronounced autoinduction.
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PMID:Multiple dose pharmacokinetics of oral artemisinin and comparison of its efficacy with that of oral artesunate in falciparum malaria patients. 873 Mar 15


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