***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    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 Cerebral malaria remains a major cause of childhood morbidity . Quinine is the drug of choice for which resistance is now emerging . A total of 77 children admitted to Khartoum Children Emergency Hospital who conform to WHO criteria of cerebral malaria were r and omly allocated to receive either artemether ( 1.6 mg/kg body wt . , repeated after 12 hrs and then daily for four days ) or quinine ( 10 mg/kg body wt in 10 ml/kg body wt of 5 % dextrose in 0.9 % saline intravenously . Repeated every 8 hrs and changed to oral administration when the child was able to drink to finish seven days ) . Response to therapy was evaluated using fever clearance time ( FCT ) , time of regaining consciousness ( TRC ) and parasite clearance time ( PCT ) . The FCT ( mean+SD ) , TRC and PCT for the artemether-treated group were 32 ( + 13 ) hrs , 21 ( + 11 ) hrs and 36 ( + 18 ) hrs , respectively , while for the quinine-treated group the respective figures were 36 ( + 18 ) , 26 ( + 15 ) hrs and 41 ( + 12 ) hrs . The response to artemether was slightly better than that of quinine , but the differences between the two groups were not statistically significant . The outcome in terms of cure rate , neurological sequalae and case fatality was also comparable 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 ABSTRACT We present the first population pharmacokinetic analysis of quinine in patients with Plasmodium falciparum malaria . Ghanaian children ( n = 120 ; aged 12 months to 10 years ) with severe malaria received an intramuscular loading dose of quinine dihydrochloride ( 20 mg/kg of body weight ) . A two-compartment model with first-order absorption and elimination gave post hoc estimates for pharmacokinetic parameters that were consistent with those derived from non- population pharmacokinetic studies ( clearance [ CL ] = 0.05 liter/h/kg of body weight ; volume of distribution in the central compartment [ V1 ] = 0.65 liter/kg ; volume of distribution at steady state = 1.41 liter/kg ; half-life at β phase = 19.9 h ) . There were no covariates ( including age , gender , acidemia , anemia , coma , parasitemia , or anticonvulsant use ) that explained interpatient variability in weight-normalized CL and V1 . Intramuscular quinine was associated with minor , local toxicity in some patients ( 13 of 108 ; 12 % ) , and 11 patients ( 10 % ) experienced one or more episodes of postadmission hypoglycemia . A loading dose of intramuscular quinine results in predictable population pharmacokinetic profiles in children with severe malaria and may be preferred to the intravenous route of administration in some circumstances OBJECTIVES To compare the efficacy of intramuscular artemether and intravenous quinine in the treatment of severe falciparum malaria . DESIGN An open r and omized controlled clinical trial . SETTING New Halfa Teaching Hospital , Eastern Sudan , in the period November 2001-January 2002 . SUBJECTS Forty one male and female children ; 21 on artemether and 20 on quinine .  MAIN OUTCOME MEASURES Fever clearance time , parasite clearance time , coma resolution time and side effects of the two drugs . RESULTS The two groups ( artemether and quinine ) were well matched in the admission variable . The mean + /- ( SD ) fever clearance time was 30.5 + /- ( 20.9 ) hours in the artemether group , while it was 18.0 + /- ( 8.1 ) hours in the quinine group ; the difference was highly significant ( P=0.02 ) . The mean parasite clearance time was shorter in the artemether group than in the quinine group , but it was not statistically significant , ( 16.0 vs. 22.4 hours ; p>0.05 ) . In comatose patients ( three in the artemether group , three in the quinine group ) the time of recovery from coma was significantly shorter in artemether group than in quinine group ( 12.5 vs. 20.16 hours ; P<0.05 ) . Recrudescence of P. falciparum ( confirmed by polymerase chain reaction ) occurred in one out of fifteen patients ( 6.6 % ) in the quinine group seen on day 28 , which was successfully treated by sulphadoxine-pyrimethamine . In the quinine group , one patient died and one patient developed hypoglycaemia . CONCLUSION Artemether caused faster parasite clearance than quinine , but quinine lowered the temperature in shorter time than artemether . The results obtained show that artemether can be used as safe and effective alternative drug for the treatment of severe falciparum malaria in the wake of the growing resistance to quinine in Sudan 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 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. 
    Output:
    
There was no statistically significant difference between the two groups in parasite clearance time , fever clearance time , incidence of neurological sequelae and 28th day cure rate .
Conclusion There was no evidence that treatment of children with severe malaria with parenteral artemisinin derivatives was associated with lower mortality or long-term morbidity compared to parenteral quinine .