***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 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 We have compared the efficacy of artemether versus quinine as treatment for cerebral malaria in children in an open r and omized clinical trial in Kenya . Children admitted to hospital with coma and Plasmodium falciparum parasitaemia were treated with either intramuscular artemether ( 3.2 mg/kg loading dose followed by 1.6 mg/kg daily ) or intravenous quinine ( 20 mg/kg loading dose followed by 10 mg/kg every 8 h ) . Both drugs were well tolerated and no significant adverse effect was observed . Parasite clearance times ( 50 % and 90 % ) were shorter in patients treated with artemether ( median times [ h ] , with interquartile ranges in brackets , were : 50 % , 7.3 [ 4.2 - 12.4 ] vs. 15.5 [ 9 - 22 ] ; 90 % , 16.9 [ 13.2 - 25 ] vs. 28.5 [ 22 - 35 ] ; P < 0.0001 ) . The total mortality in 160 children with cerebral malaria was 16.25 % , with no overall significant difference between the 2 treatment groups . In a subgroup of children with respiratory distress , mortality was higher in those treated with artemether ( 43.7 % vs. 11.1 % , P < 0.05 ) . The frequency of neurological sequelae and clinical recovery times were similar in both treatment groups . We conclude that there would currently be no advantage in replacing quinine with artemether for the treatment of cerebral malaria in African children Severe malaria remains a major cause of mortality and morbidity for children living in many tropical regions . With the emergence of strains of Plasmodium falciparum resistant to both chloroquine and quinine , alternative antimalarial agents are required . The artemisinin group of compounds are rapidly effective in severe disease when given by intramuscular or intravenous injection . However , these routes of administration are not always available in rural areas . In an open , r and omized comparison 109 Vietnamese children , aged between 3 months and 14 years , with severe P.falciparum malaria , were allocated at r and om to receive artemisinin suppositories followed by mefloquine ( n = 37 ) , intramuscular artesunate followed by mefloquine ( n = 37 ) , or intravenous quinine followed by pyrimethamine/sulfadoxine ( n = 35 ) . There were 9 deaths : 2 artemisinin , 4 artesunate and 5 quinine-treated children . There was no difference in fever clearance time , coma recovery , or length of hospital stay among the 3 groups . However , parasite clearance times were significantly faster in artemisinin and artesunate-treated patients than in those who received quinine ( P < 0.0001 ) . Both artemisinin and artesunate were very well tolerated , but children receiving these drugs had lower peripheral reticulocyte counts by day 5 of treatment than those in the quinine group ( P = 0.011 ) . No other adverse effect or toxicity was found . There was no treatment failure in these 2 groups , but 4 patients in the quinine group failed to clear their parasites within 7 d of starting treatment and required alternative antimalarial therapy . Artemisinin suppositories are easy to administer , cheap , and very effective for treating children with severe malaria . In rural areas where medical facilities are lacking these drugs will allow antimalarial therapy to be instituted earlier in the course of the disease and may therefore save lives The efficacy of a 5-day treatment with intramuscular artemether ( 3.2-mg/kg loading dose followed by 1.6 mg/kg daily ) was compared to that of the st and ard 7-day treatment with quinine ( 20-mg/kg loading dose followed by 10 mg/kg every 8 h ) in a r and omised clinical trial including 103 children aged 12 - 60 months with cerebral malaria between 1994 and 1996 . No statistical difference of immediate efficacy was found between the two treatments . There were 11 ( 20 % ) deaths in the artemether group and 14 ( 28 % ) in the children who received quinine . The respective artemether versus quinine  median fever clearance times ( h ) were 39 ( interquartile ranges [ IQ ] 30 - 54 ) vs. 48 ( IQ 30 - 60 ) , and parasite clearance 42 ( IQ 24 - 60 ) vs. 36 ( IQ 30 - 48 ) . However , one patient who received artemether had a recrudescence on day 14 , which was successfully treated with sulphadoxine-pyrimethamine . Times to recovery from coma were 24 h ( IQ 18 - 45 ) and 33 h ( IQ 19 - 57 ) , respectively . The occurrence of transient neurological sequelae including motor disabilities , cortical blindness , and afebrile seizures was also similar in the two groups . No adverse reactions to the two drugs were recorded during the study period . Artemether represents an important option in the management of cerebral malaria in Nigeria especially in rural areas where facilities for intravenous administration may not yet be optimal OBJECTIVE To compare the clinical efficacy and safety of rectal dihydroartemisinin ( DATM -- Cotecxin ) and intravenous quinine in the treatment of severe malaria in children and adults . SETTING Moi Teaching and Referral Hospital , Eldoret , Kenya between July and November 1998 . PATIENTS A total of sixty seven patients aged two to sixty years with severe malaria were studied . DESIGN This was an open r and omised comparative clinical trial . OUTCOME MEASURES These were parasite clearance time , fever clearance time , efficacy and the side effect profile of the two drugs . RESULTS The two groups were comparable on admission on the clinical and laboratory parameters . The parasite clearance time was shorter in the rectal DATM group than quinine group . There was no statistical difference on the fever clearance time and cure rates in the two groups . The adverse reaction profile was better with rectal DATM than with quinine , tinnitus observed more in the quinine group . CONCLUSION Rectal DATM is faster in parasite clearance than quinine and is a safe and convenient alternative to quinine in the treatment of severe malaria OBJECTIVE To compare the efficacy of artemether and quinine in the treatment of severe malaria in hospitalized children . STUDY DESIGN Open r and omized trial . SETTING Pediatric ward of a tertiary care center . METHODS All children admitted with clinical manifestations of severe malaria ( as per WHO criteria ) and asexual forms of Plasmodium falciparum demonstrated on peripheral smear were r and omized to receive either artemether or quinine . Their clinical status and smears for parasite count were assessed every 12 hours until two successive blood films were negative . The primary end point of the study was death in the hospital and residual damage to the organ involved . The secondary end points were clearance of parasites and fever , length of time of recovery from coma and normal functions of the involved system . RESULTS Forty-six cases completed the study protocol , 23 assigned to each drug group . Cerebral malaria was the commonest manifestation ( 76.1 % ) . Mean age in artemether versus  quinine group ( 6.6 + /- 3.5 and 5.8 + /- 2.4 years ) as well as degree of parasitemia at admission  ( 55,800 and 60,300 per microlitre ) were comparable . The overall mortality rate was 23.9 % with no significant difference between the two groups . Twenty six cases ( 56.5 % ) presented with more than one manifestations of severe malaria . The mortality rate was 100 % with four coexisting manifestations of severe malaria . Fever clearance time in artemether and quinine group was 44.5 and 45.9 hours respectively ( P > 0.05 ) . Parasite clearance time was significantly shorter in artemether group ( 40.9 vs. 51.9 hours ; P<0.001 ) . Recovery from coma was shorter in artemether group ( 34.8 vs. 38.1 hours ; P<0.05 ) . CONCLUSION Cerebral malaria is the most common manifestation of severe malaria in children .  Artemether is a good alternative drug to quinine for P. falciparum malaria . Mortality rate is directly proportional to the number of coexisting manifestations of severe malaria One hundred and two children aged 0 - 10 years with cerebral malaria ( Blantyre coma score of 2 or less ) were r and omly treated either with intramuscular arteether ( 3.2 mg/kg on Day 0 , followed by 1.6 mg/kg on Days 1 to 4 ) or intravenous ( i.v . ) quinine dihydrochloride ( 20 mg of the salt/kg , followed by 10 mg of the salt/kg every 8 hr up to Day 6 ) . Treatment with oral quinine sulfate ( 10 mg/kg every 8 hr ) was substituted for i.v . quinine when the patient was able to take oral medicine . All patients were followed up in the hospital for 7 days ; thereafter , they were treated as out patients on Days 14 , 21 , and 28 . Mortality rate , the main efficacy parameter , was 11.8 % lower in the arteether treatment group than in the quinine group ( 15.7 % versus 27.4 % ) ; however , the difference was not significant ( P = 0.25 ) . Means for fever clearance time , coma resolution time , and parasite clearance time were similar in the 2 treatment groups ( 42.2 + /- 34.9 hr ; 34.8 + /- 18.8 hr , and 46.3 + /- 28.5 hr , respectively for arteether , versus 45.0 + /- 26.7 hr ; 30.3 + /- 18.9 hr , and 40.7 + /- 18.9 hr , respectively , for quinine ) . At 28 days , the cure rates were 73.2 % and 64.9 % for the arteether and quinine treatment groups , respectively . Arteether is safe and therapeutically at least as effective as quinine for the treatment of cerebral malaria in children in Cameroon . Because of its ease of administration , arteether appears to be suited for use in the rural zones where 
    Output:
    
The WHO ’s 2010 Guideline ( 1 ) strongly recommends aresunate in adults with severe malaria , positioning quinine only as an alternative ; however , it cites lack of evidence to frame a similar recommendation for children