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Query: UMLS:C0024530 (malaria)
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Artemether-lumefantrine (A-L), a new fixed-dose oral antimalarial drug, combines the fast onset of action of artemether (an artemisinin derivative) in terms of parasite clearance with the high cure rate of lumefantrine in the treatment of acute uncomplicated Plasmodium falciparum malaria. The extensive clinical trial database of A-L has allowed a comprehensive evaluation of its tolerability and safety in a total of 1869 patients (including 243 children aged 5-12 years and 368 children aged < 5 years). The most commonly reported and possibly related adverse effects following A-L therapy involved the gastro-intestinal (abdominal pain, anorexia, nausea, vomiting, diarrhoea) and central nervous (headache, dizziness) systems. Pruritus and rash were reported by < 2% of patients. More than 90% of the reported adverse events, many of which overlapped considerably with the clinical symptomatology or evolution of acute malaria, were rated mild to moderate in intensity. Compared to A-L, significantly higher incidences of vomiting and pruritus were observed with chloroquine, dizziness, nausea and vomiting with mefloquine, somnolence with pyrimethamine + sulfadoxine, and vomiting and dizziness with quinine. There were no serious or persistent neurological side-effects related to A-L administration. A-L did not lead to any clinically relevant alterations of the laboratory parameters. Serial electrocardiographic data were available for 713 patients. The frequency of QT interval prolongations was similar to or lower than that observed with chloroquine, mefloquine, or artesunate + mefloquine; these changes were considerably less frequent than with quinine or halofantrine. All patients with QT prolongation remained asymptomatic and no adverse clinical cardiac events were reported. Artemether-lumefantrine can thus be expected to show, both in children and in adults, a favourable safety profile for the treatment of acute, uncomplicated, P. falciparum malaria; it could as well be a reserve treatment option for travellers to endemic countries.
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PMID:An integrated assessment of the clinical safety of artemether-lumefantrine: a new oral fixed-dose combination antimalarial drug. 1112 48

The efficacy-safety and pharmacokinetics of the six-dose regimen of artemether-lumefantrine (Coartem/Riamet; Novartis Pharma AG, Basel, Switzerland) were assessed in a randomized trial in 219 patients (> or = 12 years old) with acute, uncomplicated Plasmodium falciparum malaria in Thailand. One hundred and sixty-four patients received artemether-lumefantrine and 55 received the standard treatment combination of mefloquine-artesunate. Both drugs induced rapid clearance of parasites and malaria symptoms. The 28-day cure rates were 95.5% (90% confidence interval [CI] = 91.7, 97.9%) for artemether-lumefantrine and 100% (90% CI = 94.5, 100%) for mefloquine-artesunate. This high-dose regimen of artemether-lumefantrine was very well tolerated, with very good compliance. The most frequent adverse events were headache, dizziness, nausea, abdominal pain, dyspepsia, vomiting, and skin rash. Overall, only 2% of patients in both groups showed QTc prolongations but without any cardiac complication, and no differences were seen between patients with and without measurable baseline plasma levels of quinine or mefloquine. Plasma levels of artemether, dihydroartemisinin, and lumefantrine were consistent with historical data for the same dose regimen, and were higher, particularly for lumefantrine, than those previously observed with the four-dose regimen, explaining the greater efficacy of the six-dose regimen in a drug-resistant setting. These results confirm the excellent safety and efficacy of the six-dose regimen of artemether-lumefantrine in the treatment of multidrug-resistant P. falciparum malaria.
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PMID:A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand. 1146 11

Highly effective medicinal herbs are being used successfully in China to treat malaria, for example, using Ching Hao Su, an extract from wormwood. There are 5000 varieties of medicinal herbs cataloged, some more effective than western drugs. China's barefoot doctors investigate diseases and collect effective drugs, one of which is Muching which has been highly effective in treating chronic bronchitis. Salvia miltiorrhiza, used in ancient times to activate blood circulation, is used to treat coronary artery diseases and has proved effective in 87% of angina pectoris cases. Medicinal herbs are used to treat burns, hypertension, and cancer and, although the herbs are readily available and inexpensive, they work slowly. Using medicinal herbs, a Shansi Medical College affiliated hospital successfully treated over 800 cases of extra-uterine pregnancy and, in 90% of the cases, no surgery was performed. Treatment showed medicinal herbs checked bleeding, improved circulation, and eradicated blood clots. Research is being conducted with herbal prescriptions to find safer, more effective and convenient contraceptives for men and women. A breakthrough for the Institute of Medicine of the Chinese Academy of Medicine Sciences was seen in the successful cultivation of gastrodia elata which has been used for 2000 years to treat dizziness, headaches, and infantile coma.
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PMID:China: a new medicine born of tradition. 1230 32

In an open-label trial carried out on the northwest border of Thailand, 1596 patients with uncomplicated multidrug-resistant falciparum malaria were randomly assigned to receive atovaquone-proguanil, atovaquone-proguanil-artesunate, or artesunate-mefloquine and were followed up for 42 days. All 3 regimens were highly effective and well tolerated. Fever duration and parasite clearance times were significantly shorter among patients who received artesunate (P<.001). Polymerase chain reaction genotyping confirmed that recrudescence occurred in 13 patients who received artesunate-mefloquine (2.4%), 5 who received atovaquone-proguanil-artesunate (0.9%), and 15 who received atovaquone-proguanil (2.8%). Adding artesunate to atovaquone-proguanil reduced the risk of failure 3-fold (95% confidence interval [CI], 1.1-8.2) and subsequent gametocyte carriage 21-fold (95% CI, 14-30). Gastrointestinal complaints in the first 48 h after initiation of treatment were more common among artesunate recipients, but after day 2, dizziness, sleep disturbance, nausea, vomiting, and anorexia were more common among mefloquine recipients (P< or =.014). Artesunate-atovaquone-proguanil is a highly effective and well-tolerated treatment for multidrug-resistant falciparum malaria.
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PMID:Treatment of uncomplicated multidrug-resistant falciparum malaria with artesunate-atovaquone-proguanil. 1247 69

A cross-sectional study performed in Temeke District (Dar es Salaam, Tanzania) showed that 5.5% of the traditional healers have knowledge for the treatment of epilepsy. Of the 100 healers interviewed, 30 (30%) believed that epilepsy was caused by witchcraft, while 19 (19%) thought epilepsy has a genetic origin which can be inherited. Other healers thought epilepsy can be caused by head injury or malaria (24%), and the remaining 27% did not know the cause. Most of the healers (92%) could present an accurate account on the symptoms of the disease, including dizziness, loss of consciousness, abrupt falling down, frothing from the mouth, loss of memory, biting of the tongue, confusion, and restlessness. They showed competence in the treatment of the disease, whereby 60 plants that are commonly used were mentioned. Abrus precatorius L. (Leguminosae), Clausena anisata (Willd.) Oliv. (Rutaceae) and Hoslundia opposita Vahl (Lamiaceae), which are among the plants mentioned, have proven anticonvulsant activity, while a few other species on their list have been reported to be useful in the treatment of epilepsy. Biological testing of these plants, using different models of convulsions is, suggested.
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PMID:Plants used to treat epilepsy by Tanzanian traditional healers. 1570 73

A questionnaire-based study was conducted on 189 Traditional Birth Attendants (TBAs) on their knowledge and practices in prenatal services. Only 86 (45.5%) of them associated cessation of menstrual period with pregnancy while others use mystic power 46 (24.3%), early morning sickness, pallor of conjunctiva and reaction to herbs 56 (29.6%) to detect pregnancy. Fundal height n=76 (40.2%), palpation n=82 (43.4%), special soaps and soups n=52 (27.5%) and special devices n=8 (4.2%) are used to determine stages of pregnancy. Foetal health status is determined by regular foetal movements n=95 (50.3%), mystic power n=15 (8%), soap n=2 (1.1%), special concoction 9 (4.8%), health status of mother n=67 (35.4%) and foetal heart beat n=24 (12.7%). Ninety seven (51.3%) of them used herbal treatment, 77 (40.7%) used incantations, 189 (100%) used special soaps as their main methods of delivery, while only 18 (9.5%) of respondents refer difficult cases to hospitals. Instruments used for separating cord were blade 123 (65.1%) and scissors 40 (21.1%). Symptoms recognized by the TBAs as signs of complications in pregnancy were dizziness, swollen feet, pallor, tiredness, absent foetal movement, loss of appetite, heaviness, pain in back/stomach/side, weight loss, vomiting, bleeding, fever/malaria, head ache, bad dream, premature or delayed labour. Although some of them recognized some danger signs in pregnancy and labour, only very few would refer difficult cases for emergency obstetric interventions. Clear protocols for management and referral, which are necessary for improved maternal survival, should be provided through regular training of the TBAs.
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PMID:Knowledge and practices of traditional birth attendants in prenatal services in Lagos State, Nigeria. 1597 55

The combination of artesunate and mefloquine is currently one of the most effective treatments for multidrug-resistant Plasmodium falciparum malaria. Simultaneous, rather than sequential treatment with the two drugs, would allow better patient compliance. We therefore evaluated three-day treatment with artesunate combined with either 2 or 3 days of mefloquine co-administered once a day with artesunate. The study was an open, randomized trial for acute, uncomplicated falciparum malaria and was conducted at the Bangkok Hospital for Tropical Diseases. One hundred and twenty adult patients were randomized to two treatment groups. Group 1 patients received 4 mg/kg/day of artesunate for 3 days and 3 daily doses of 8.0 mg/kg/day mefloquine given with artesunate. Group 2 patients received the same dose of artesunate and the same total dose of mefloquine (25 mg/kg). However, the mefloquine was given as 15 mg/kg on the first day and 10 mg/kg/ on the second day, again with artesunate. The baseline demographic and clinical characteristics of the patients in the two groups were similar. The cure rates for the 3-day and 2-day mefloquine regimens were 100% and 99%, respectively. There were no significant differences in either median fever clearance times (group 1=32 hours; group 2=33 hours) or mean parasite clearance times (group 1=42.3 hours; group 2=43.3 hours). Both regimens were well tolerated and there were no significant differences in the incidence of adverse effects. Nausea or vomiting occurred in 3.8% of patients in both groups and transient dizziness occurred in 4% of group 1 and 9% of group 2 patients. These results suggest that a 3-day regimen of mefloquine administered with artesunate is effective and well tolerated. This practical regimen could improve patient compliance.
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PMID:An open, randomized trial of three-day treatment with artesunate combined with a standard dose of mefloquine divided over either two or three days, for acute, uncomplicated falciparum malaria. 1612 22

Artesunate and mefloquine combination treatment has been used since 2000 in Cambodia as the first-line drug for the treatment of uncomplicated falciparum malaria. In order to assess its efficacy and safety, the national malaria control programme conducted 14 therapeutic efficacy studies with the drug combination between 2001 and 2004 at nine sites. In 2001 and 2002, co-blister packs of artesunate and mefloquine were used, whereas in 2003 and 2004, drugs were given individually from a bulk pack at a total dose of 12 mg/kg of artesunate and 25 mg/kg of mefloquine over 3 days. A total of 1025 patients were enrolled over the 4 years and 977 were follow-up during the period of 28 days. The PCR-corrected cure rates ranged from 85.7% to 100% with an overall cure rate of 95.8% (920/960). The studies in 2002 showed also that co-blister packs used on the basis of age and not on the basis of weight could lead to underdosed regimens but without any detectable effect on the treatment outcome. The follow-up period was extended from 28 to 42 days in three sites in 2004. A total of 219 among 255 were follow-up until day 42. The cure rate decreased but not significantly from 90.1% (73/81) with 28 days follow-up to 79.3% (46/58) with 42 days follow-up in Pailin, whereas the cure rate remained at 100% in the two other sites. Side effects were common, especially dizziness, but were mild and transient and patients recovered without any medical intervention.
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PMID:Surveillance of the efficacy of artesunate and mefloquine combination for the treatment of uncomplicated falciparum malaria in Cambodia. 1693 Feb 57

Malaria treatment is becoming increasingly difficult due to the widespread drug resistance of Plasmodium falciparum. In Japan, only three antimalarials are approved for treatment: oral quinine, sulfadoxine-pyrimethamine, and mefloquine. Recently, however, the Research Group on Chemotherapy of Tropical Diseases introduced atovaquone-proguanil for treating drug-resistant P. falciparum malaria. This research group had also introduced mefloquine before it was licensed nationally. Using data obtained from the research group, we analyzed the efficacy and safety of atovaquone-proguanil, as compared with mefloquine, in nonimmune patients with uncomplicated P. falciparum malaria. Cures were attained in all (100%) of 20 atovaquone-proguanil-treated and 49 (98%) of 50 mefloquine-treated adults. The mean fever clearance time (FCT) and parasite clearance time (PCT) appeared to be longer in the atovaquone-proguanil group than in the mefloquine group, but the differences were not statistically significant. Three (15%) of the 20 atovaquone-proguanil-treated adults had adverse events (AEs), all of which were transient elevations of liver enzymes, while 19 (38%) of the 50 mefloquine-treated adults had AEs, including dizziness in 8 (16%) and nausea/vomiting in 7 (14%). All 3 children treated with atovaquone-proguanil were cured without developing AEs. Despite the limitations of this study in not being a formal clinical trial, atovaquone-proguanil seemed to be at least equal to, or even better than, mefloquine for the treatment of uncomplicated P. falciparum malaria in nonimmune patients, including children. Its marketing in Japan could be beneficial in offering an alternative therapeutic option. However, vigilance should be maintained on the possible occurrence of rare but severe AEs, and also of the possible spread of drug resistance.
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PMID:Efficacy and safety of atovaquone-proguanil compared with mefloquine in the treatment of nonimmune patients with uncomplicated P. falciparum malaria in Japan. 1710 92

Post-malaria neurological syndrome (PMNS) is a rare complication of malaria. It follows recovery from an episode of Plasmodium falciparum malaria and is characterised by symptoms and signs of encephalopathy. Patients usually improve without any specific treatment. The pathogenesis is unknown, but it is probably immunologically mediated. The objective of this case study is to describe the first Italian patient with PMNS. A 60-year-old Italian man developed acute P. falciparum malaria after a stay in French Guinea. Twenty days after recovering from malaria, he became confused, developed generalised weakness, limb tremors, shivering and dizziness. These symptoms continued for three days, then resolved spontaneously. Neuroimaging was normal. Cerebrospinal fluid analysis revealed breakdown of the blood/brain barrier, without oligoclonal bands and normal IgG index. Our patient presented a mild diffuse encephalopathy suggestive of a generic activation of the immune system without any specific reaction against antigens within the CNS.
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PMID:Post-malaria neurological syndrome: clinical and laboratory findings in one patient. 1720 33


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