***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 To compare the effectiveness and safety of quinine sulfate and artesunate with mefloquine for treating second trimester pregnancy in women who suffered from Plasmodium falciparum malaria . The prospect i ve study was done in Srisangwal Hospital , Mae Hong Son , Thail and . Sixty , second to third trimester pregnant patients with P. falciparum infection , were recruited at r and om . They received either quinine sulfate 10 mg/kg/day for at least 7 days , 29 women ( group I ) , or oral artesunate 2 mg/kg as the first dose , 1 mg/kg every 12 hours orally for at least 5 days together with split doses of mefloquine , 15 mg/kg and 6 hours later 10 mg/kg orally 1 day after artesunate was stopped , 28 women ( group II ) . Three cases ( 5 % ) were lost to follow-up before delivery , one case in group I and two cases in group II . After treatment , the mean hematocrit of group I was significantly less than group II ( p = 0.000 ) . The PCT ( parasite clearance time ) and FCT ( fever clearance time ) of group II were significantly shorter than group I ( p = 0.000 ) . None of the patients in both groups had recrudescences within 28 days . Group I had more adverse effects than group II . No adverse neurological effects in pregnancy were found in both groups . The calcification of placenta and IUGR ( Intrauterine growth retard ) were not different between the two groups ( p = 0.964 , 0.363 respectively ) . The PCT was not different between the calcified placenta group and normal placenta group ( p = 0.058 ) , but the TTPP ( Total time of parasite presentation ) was ( p = 0.000 ) . TTPP related to low birth weight and low apgar score at 1 minute might be the cause ( p = 0.000 , 0.000 F = 5.261 , 21.627 respectively ) . TTPP and PCT related to neonatal blood pH and caused low neonatal blood pH ( p = 0.000 , 0.001 F = 24.351 , 11.162 respectively ) . The physical and neurological development of the babies at 2 , 4 , 6 and 12 months follow-up , were normal and there were no congenital abnormalities in either group . TTPP relating to fetal outcome , the longer the TTPP , the worse the fetal outcome , so we should diagnose early and treat P. falciparum malaria in pregnancy to prevent fetal jeopardy . Artesunate with mefloquine could shorten the PCT more than quinine sulfate in pregnancy , so the fetal outcome was better than that of quinine sulfate . In cases of prolonged infection before treatment , artesunate might be the alternative treatment of P. falciparum malaria in pregnancy . However , its safety should be carefully studied further with a larger sample size ABSTRACT The activities of primaquine in combination with quinine or artesunate against asexual- and sexual-stage parasites were assessed in 176 adult Thai patients with uncomplicated Plasmodium falciparum malaria . Patients were r and omized to one of the six following 7-day oral treatment regimens : ( i ) quinine alone , ( ii ) quinine with tetracycline , ( iii ) quinine with primaquine at 15 mg/day , ( iv ) quinine with primaquine at 30 mg/day , ( v ) artesunate alone , or ( vi ) artesunate with primaquine .  Clinical recovery occurred in all patients . There were no significant differences in fever clearance times , rates of P. falciparum reappearance , or recurrent vivax malaria between the six treatment groups . Patients treated with artesunate alone or in combination with primaquine had significantly shorter parasite clearance times ( mean ± st and ard deviation = 65± 18 versus 79 ± 21 h ) and lower gametocyte carriage rates ( 40 versus 62.7 % ) than those treated with quinine ( P ≤ 0.007 ) . Primaquine did not affect the therapeutic response ( P > 0.2 ) . Gametocytemia was detected in 98 patients ( 56 % [ 22 % before treatment and 34 % after treatment ] ) . Artesunate reduced the appearance of gametocytemia ( relative risk [ 95 % confidence interval ] = 0.34 [ 0.17 to 0.70 ] ) , whereas combinations containing primaquine result ed in shorter gametocyte clearance times ( medians of 66 versus 271 h for quinine groups and 73 versus 137 h for artesunate groups ; P≤ 0.038 ) . These results suggest that artesunate predominantly inhibits gametocyte development whereas primaquine accelerates gametocyte clearance in P. falciparum malaria AIMS The antimalarial efficacy/pharmacodynamics and pharmacokinetics of intramuscular ( i.m . ) artemotil in Thai patients with acute uncomplicated falciparum malaria were studied to determine effective dose regimens and to compare these with the st and ard dose regimen of artemether . METHODS In part I of the study three different artemotil dose regimens were explored in three groups of 6 - 9 patients for dose finding : 3.2 mg kg-1 on day 0 and 1.6 mg kg-1 on days 1 - 4 ( treatment A ) , 1.6 mg kg-1 on day 0 and 0.8 mg kg-1 on days 1 - 4 ( treatment B ) , 3.2 mg kg-1 on day 0 and 0.8 mg kg-1 on days 1 - 4 ( treatment C ) . In part II of the study , artemotil treatments A and C were compared in three groups of 20 - 22 patients with st and ard i.m . artemether treatment : 3.2 mg kg-1 on day 0 and 0.8 mg kg-1 on days 1 - 4 ( treatment R ) . RESULTS Full parasite clearance was achieved in all patients in Part I , but parasite clearance time ( PCT ) and fever clearance time ( FCT ) tended to be longer in treatment B. Also the incidence of recrudescence before day 28 ( RI ) tended to be higher for treatment B. In part II , the mean PCT for each of the two artemotil treatments ( 52 and 55 h , respectively ) was significantly longer than for artemether ( 43 h ) . The 95 % CI for the difference A vs R was 0 , 16 h ( P=0.0408 ) and for difference C vs R it was 2 , 19 h ( P=0.0140 ) . FCT was similar for the three treatments . The incidence of RI ranged from 5 out of 19 for treatment C to 3 out of 20 for treatment R. Plasma concentration-time profiles of artemotil indicated an irregular and variable rate of absorption after i.m . injection . A late onset of parasite clearance was associated with delayed absorption and /or very low initial artemotil plasma concentrations . Pharmacokinetic-pharmacodynamic evaluations supported a relationship between the rate of parasite clearance and exposure to artemotil during approximately the first 2 days of treatment , and suggested that artemotil has a slower rate of absorption than artemether . Safety assessment , including neurological and audiometric examinations showed no clinical ly relevant findings . Adverse events before and during treatment included headache , dizziness , nausea , vomiting and abdominal pain . These are characteristic of acute malaria infections and resolved during treatment . CONCLUSIONS The optimum dose regimen for artemotil in this study was identical to the st and ard dose regimen of artemether . The findings that artemotil is more slowly absorbed from the i.m . injection site than artemether , and that early systemic availability may be insufficient for an immediate onset of parasite clearance contributed to the decision to choose a higher loading dose of artemotil ( divided over two injection sites ) and to omit the fifth dose in later studies . With this optimized dosing schedule , the more pronounced depot characteristics of i.m . artemotil can be an advantage , since it may allow shorter hospitalization Sixty-six children presenting to Singa hospital , Sudan with different manifestations of severe Plasmodium falciparum malaria were r and omly divided into two well-matched groups ( 33 in each arm ) to receive either intravenous artesunate 2·4 mg/kg at 0 , 12 , and 24 hours , then daily , or intravenous quinine 20mg/kg initially then 10mg/kg three times a day . There was no significant difference in the fever , parasite clearance , and coma resolution times . Three patients died , one in the artesunate and two in the quinine groups . One patient developed hypoglycaemia following quinine infusion . Thus , artesunate can be used for the treatment of severe falciparum malaria 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(-1 ) . Following i.m . ARTS , Cmax was 2.3 microm ( 3.7 mg l(-1 ) ) , the apparent t1/2 = 41 min , CL = 2.9 l h(-1 ) kg(-1 ) and V = 2.6 l kg(-1 ) . The relative bioavailability of DHA was 88 % , Cmax was 4.1 microm ( 1.16 mg l(-1 ) ) and t1/2 = 64 min . In the rectal DHA study , relative bioavailability of DHA was 16 % . CONCLUSIONS For patients with uncomplicated falciparum malaria i.m . ARTS is a suitable alternative to i.v . ARTS , at equal doses . To achieve plasma  DHA concentrations equivalent to parenteral administration of ARTS , rectal DHA should be given at approximately four-fold higher milligram doses . Further studies are needed to determine whether these recommendations can be applied to patients with severe malaria The emergence and spread of multidrug-resistant Plasmodium falciparum compromises the treatment of malaria , especially during pregnancy , where the choice of antimalarials is already limited . Artesunate ( n=528 ) or artemether ( n=11 ) was used to treat 539 episodes of acute P. falciparum malaria in 461 pregnant women , including 44 first-trimester episodes . Most patients ( 310 [ 57.5 % ] ) received re-treatments after earlier treatment with quinine or mefloquine . By use of survival analysis , the cumulative artemisinin failure rate for primary infections was 6.6 
    Output:
    
MAIN RESULTS Eight trials enrolling 1664 adults and 5765 children are included in this review .Treatment with artesunate significantly reduced the risk of death both in adults ( RR 0.61 , 95 % Confidence Interval ( CI ) 0.50 to 0.75 ; 1664 participants , five trials ) and children ( RR 0.76 , 95 % CI 0.65 to 0.90 ; 5765 participants , four trials)In children , treatment with artesunate increased the incidence of neurological sequelae at the time of hospital discharge .
The majority of these sequelae were transient and no significant difference between treatments was seen at later follow up .
The evidence clearly supports the superiority of parenteral artesunate over quinine for the treatment of severe malaria in both adults and children and in different regions of the world