***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: BACKGROUND In the treatment of severe malaria , intravenous artesunate is more rapidly acting than intravenous quinine in terms of parasite clearance , is safer , and is simpler to administer , but whether it can reduce mortality is uncertain . METHODS We did an open-label r and omised controlled trial in patients admitted to hospital with severe falciparum malaria in Bangladesh , India , Indonesia , and Myanmar . We assigned individuals intravenous artesunate 2.4 mg/kg bodyweight given as a bolus ( n=730 ) at 0 , 12 , and 24 h , and then daily , or intravenous quinine ( 20 mg salt per kg loading dose infused over 4 h then 10 mg/kg infused over 2 - 8 h three times a day ; n=731 ) . Oral medication was substituted when possible to complete treatment . Our primary endpoint was death from severe malaria , and analysis was by intention to treat . FINDINGS We assessed all patients r and omised for the primary endpoint . Mortality in artesunate recipients was 15 % ( 107 of 730 ) compared with 22 % ( 164 of 731 ) in quinine recipients ; an absolute reduction of 34.7 % ( 95 % CI 18.5 - 47.6 % ; p=0.0002 ) . Treatment with artesunate was well tolerated , whereas quinine was associated with hypoglycaemia ( relative risk 3.2 , 1.3 - 7.8 ; p=0.009 ) . INTERPRETATION Artesunate should become the treatment of choice for severe falciparum malaria in adults BACKGROUND Artemisinin ( qinghaosu ) and its derivatives are rapidly effective antimalarial drugs derived from a Chinese plant . Preliminary studies suggest that these drugs may be more effective than quinine in the treatment of severe malaria . We studied artemether in Vietnam , where Plasmodium falciparum has reduced sensitivity to quinine . METHODS We conducted a r and omized , double-blind trial in 560 adults with severe falciparum malaria . Two hundred seventy-six received intramuscular quinine dihydrochloride ( 20 mg per kilogram of body weight followed by 10 mg per kilogram every eight hours ) , and 284 received intramuscular artemether ( 4 mg per kilogram followed by 2 mg per kilogram every eight hours ) . Both drugs were given for a minimum of 72 hours . RESULTS There were 36 deaths in the artemether group ( 13 percent ) and 47 in the quinine group ( 17 percent ; P = 0.16 ; relative risk of death in the patients given artemether , 0.74 ; 95 percent confidence interval , 0.5 to 1.11 ) . The parasites were cleared more quickly from the blood in the artemether group ( mean , 72 vs. 90 hours ; P < 0.001 ) ; however , in this group fever resolved more slowly ( 127 vs. 90 hours , P < 0.001 ) , the time to recovery from coma was longer ( 66 vs. 48 hours , P = 0.003 ) , and the hospitalization was longer ( 288 vs. 240 hours , P = 0.005 ) . Quinine treatment was associated with a higher risk of hypoglycemia ( relative risk , 2.7 ; 95 percent confidence interval , 1.7 to 4.4 ; P < 0.001 ) , but there were no other serious side effects in either group . CONCLUSIONS Artemether is a satisfactory alternative to quinine for the treatment of severe malaria in adults The effect of artemether plus mefloquine versus quinine on 35 patients with complicated falciparum malaria including 5 patients with cerebral malaria were studied . All patients treated with the artemether-mefloquine combination  survived and all were free from toxic effects of the drugs . Three patients on quinine therapy died . The mortality rate was 8.5 % . The mean parasite clearance time of patients treated with artemether plus mefloquine was significantly shorter than those treated with quinine but there was no significant difference in the mean fever clearance of the two groups of patients . There was no recrudescence with artemether and mefloquine ; the recrudescence rate was 5.5 % with quinine . The study showed that the artemether-mefloquine combination is superior to quinine for the treatment of patients with complicated falciparum malaria , including cerebral malaria Background Chlorproguanil-dapsone ( Lapdap ) , developed as a low-cost antimalarial , was withdrawn in 2008 after concerns about safety in G6PD deficient patients . This trial was conducted in 2004 to evaluate the safety and effectiveness of CD and comparison with artemether-lumefantrine ( AL ) under conditions of routine use in G6PD normal and G6PD deficient patients with uncomplicated malaria in The Gambia . We also examined the effects of a common genetic variant that affects chlorproguanil metabolism on risk of treatment failure . Methods 1238 children aged 6 months to 10 years with uncomplicated malaria were r and omized to receive CD or artemether-lumefantrine ( AL ) and followed for 28 days . The first dose was supervised , subsequent doses given unsupervised at home . G6PD genotype was determined to assess the interaction between treatment and G6PD status in their effects on anaemia . The main endpoints were clinical treatment failure by day 28 , incidence of severe anaemia ( Hb<5 g/dL ) , and haemoglobin concentration on day 3 . Findings One third of patients treated with AL , and 6 % of patients treated with CD , did not complete their course of medication . 18 % ( 109/595 ) of children treated with CD and 6.1 % ( 36/587 ) with AL required rescue medication within 4 weeks , risk difference 12 % ( 95%CI 8.9%–16 % ) . 23 children developed severe anaemia ( 17 ( 2.9 % ) treated with CD and 6 ( 1.0 % ) with AL , risk difference 1.8 % , 95%CI 0.3%–3.4 % , P = 0.02 ) . Haemoglobin concentration on day 3 was lower among children treated with CD than AL ( difference 0.43 g/dL , 95 % CI 0.24 to 0.62 ) , and within the CD group was lower among those children who had higher parasite density at enrolment . Only 17 out of 1069 children who were typed were G6PD A- deficient , of these 2/9 treated with CD and 1/8 treated with AL developed severe anaemia . 5/9 treated with CD had a fall of 2 g/dL or more in haemoglobin concentration by day 3 . Interpretation AL was well tolerated and highly effective and when given under operational conditions despite poor adherence to the six-dose regimen . There were more cases of severe malaria and anaemia after CD treatment although G6PD deficiency was uncommon . Trial Registration Clinical trials.gov Twenty-six patients with severe falciparum malaria were r and omized to be treated with quinine or artemether . Twelve patients received quinine at the st and ard dose and fourteen patients received artemether intramuscularly at a total dose of 640 mg over 7 days . The patients were kept in the hospital for at least 7 days . Peripheral smear was performed 6-hourly until there was no parasitemia , then daily until discharged . Adverse effects were monitored through physical examination , laboratory findings and question naires . Laboratory examination was performed on admission , day 2 , day 4 weekly until discharged . The patients in both groups were comparable in age , body weight , admission parasitemia , hemoglobin and white blood cell count . The survival rates were 93 % and 58 % in artemether and quinine groups , respectively ( p = 0.052 at 95 % confidence , using Fisher 's exact test ) . The parasite and fever clearance times , and the time taken to gain consciousness in cerebral malaria patients were not significantly different between the two groups . Adverse effects in the quinine group consisted of dizziness and vertigo which were found in 4 patients . No adverse effects were noticed in the artemether group . This preliminary report suggests that artemether is a good alternative drug for severe falciparum malaria and seems to be better than quinine regarding survival rate and side effects . Confirmation of these findings in a larger study size is needed ABSTRACT Drug treatment of severe malaria must be rapidly effective . Suppositories may be valuable for childhood malaria when circumstances prevent oral or parenteral therapy . We compared artesunate suppositories ( n = 41 ; 8 to 16 mg/kg of body weight at 0 and 12 h and then daily ) with intramuscular ( i.m . ) artemether ( n = 38 ; 3.2 mg/kg at 0 h and then 1.6 mg/kg daily ) in an open-label , r and omized trial with children with severe Plasmodium falciparum malaria in Papua New Guinea ( PNG ) . Parasite density and temperature were measured every 6 h for ≥72 h. Primary endpoints included times to 50 % and 90 % parasite clearance ( PCT50 and PCT90 ) and the time to per os status . In a subset of 29 patients  , plasma levels of artemether , artesunate , and their common active metabolite dihydroartemisinin were measured during the first 12 h. One suppository-treated patient with multiple complications died within 2 h of admission , but the remaining 78 recovered uneventfully . Compared to the artemether-treated children , those receiving artesunate suppositories had a significantly earlier mean PCT50 ( 9.1 versus 13.8 h ; P = 0.008 ) and PCT90 ( 15.6 versus 20.4 h ; P = 0.011 ) . Mean time to per os status was similar for each group . Plasma concentrations of primary drug plus active metabolite were significantly higher in the artesunate suppository group at 2 h postdose . The earlier initial fall in parasitemia with artesunate is clinical ly advantageous and mirrors higher initial plasma concentrations of active drug/metabolite . In severely ill children with malaria in PNG , artesunate suppositories were at least as effective as i.m . artemether and may , therefore , be useful in setting s where parenteral therapy can not be given A r and omized controlled trial on 51 patients receiving artemether and 54 patients receiving quinine  was undertaken to compare the effectiveness of intramuscular artemether and parenteral quinine in the treatment of cerebral malaria in adults in Bangladesh .  Case fatality , fever and parasite clearance times were not significantly different in the two treatment groups . Coma resolution time was significantly delayed in artemether recipients . Results of the study suggest that treatment with artemether is as effective as parenteral quinine in the treatment of cerebral malaria in adults From June 1993 to June 1994 , a study was carried out to compare artemether and quinine for management of  severe falciparum malaria in adults and adolescents in Cameroon .  Artemether was administered intramuscularly at a dose of 3.6 mg/kg on the first day and 1.6 mg/kg for the following 4 days . Quinine was administered intravenously at a dose of 1.6 mg/kg for the first 4 hours and 8 mg every 8 hours for the next 3 days . The files of 84 of the 95 patients recruited were vali date d for inclusion in the final study . There were 40 patients in the artemether group and 44 in the quinine group . The two groups were comparable with regard to all factors at the time of inclusion . Findings showed that artemether was more effective than quinine with regard to total clearance of parasitemia , 90 p. 100 clearance , and fever control and that it was as effective with regard to 50 p. 100 clearance and recovery of consciousness . In view of its good performance and of the simplicity of its administration by intramuscular injection , artemether would appear to be an excellent alternative for treatment of severe malaria and cerebral malaria in areas with poor medical facilities AIMS To obtain pharmacokinetic data for  artesunate ( ARTS )  and its active metabolite dihydroartemisinin ( DHA )  following i.m . ARTS and rectal DHA administration . METHODS Twelve Vietnamese patients with uncomplicated falciparum malaria were r and omized to receive either i.v . or i.m . ARTS ( 120 mg ) , with the alternative preparation given 8 h later in an open crossover design . A further 12 patients were given i.v . ARTS ( 120 mg ) at 0 h and rectal DHA ( 160 mg ) 8 h later . RESULTS Following i.v . bolus , ARTS had a peak concentration of 42 microm ( 16 mg l(-1 ) , elimination t1/2 = 3.2 min , CL = 2.8 l h(-1 ) kg(-1 ) and V = 0.22 l kg(-1 ) . The Cmax for DHA  was 9.7 microm ( 2.7 mg l(-1 ) ) , t1/2 = 59 min , CL = 0.64 l h(-1 ) kg(-1 ) and V = 0.8 l kg 
    Output:
    
Authors ' conclusions Although there is a lack of direct evidence comparing artemether with artesunate , artemether is probably less effective  than artesunate at preventing deaths from severe malaria .
In circumstances where artesunate is not available , artemether is an alternative to quinine