***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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    ***EXAMPLES*** 
    Input: BACKGROUND Adherence to antimalarial drug regimens is improved by simple dosing . If the fixed antimalarial drug combination artemether-lumefantrine ( AL ) could be given once daily , this should improve adherence and thus effectiveness and lower the risk of selecting for resistance . METHODS In an open r and omized study , 43 patients with uncomplicated falciparum malaria were given equivalent doses of AL with 200 ml flavoured milk either as the conventional twice-daily regimen or as a single daily dose for 3 days . The primary end point was a comparison of the areas under the plasma lumefantrine concentration-time curves ( AUC ) . Secondary end points were the day 42 polymerase chain reaction (PCR)-adjusted cure rates and the tolerability profiles . RESULTS Lumefantrine pharmacokinetic profiles were obtained for 36 patients . The AUC((0 - ->infinity ) ) of the once-daily regimen was 30 % lower than that in the conventional regimen ( P = 0.011 ) with a median ( range ) value of 306 ( 114 - 5781 ) microg/ml h , compared with 432 ( 308 - 992 ) microg/ml h. There was no significant difference in the peak plasma concentrations reached . PCR-adjusted cure rate estimates at day 42 of follow-up were 94 % ( 95 % CI : 84 - 100 ) in the six-dose arm and 85 % ( 70 - 100 ) in the three-dose arm ( P = 0.3 ) . CONCLUSION Artemether-lumefantrine  efficacy is reduced by once-daily dosing , because absorption of lumefantrine is dose limited . At currently recommended doses , this antimalarial should be given twice daily in a 3-day regimen , with food containing fat BACKGROUND Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease . There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border , historically a site of emerging antimalarial-drug resistance . METHODS In two open-label , r and omized trials , we compared the efficacies of two treatments for uncomplicated falciparum malaria in Pailin , western Cambodia , and Wang Pha , northwestern Thail and : oral artesunate given at a dose of 2 mg per kilogram of body weight per day , for 7 days , and artesunate given at a dose of 4 mg per kilogram per day , for 3 days , followed by mefloquine at two doses totaling 25 mg per kilogram . We assessed in vitro and in vivo Plasmodium falciparum susceptibility , artesunate pharmacokinetics , and molecular markers of resistance . RESULTS We studied 40 patients in each of the two locations . The overall median parasite clearance times were 84 hours ( interquartile range , 60 to 96 ) in Pailin and 48 hours ( interquartile range , 36 to 66 ) in Wang Pha ( P<0.001 ) . Recrudescence confirmed by means of polymerase-chain-reaction assay occurred in 6 of 20 patients ( 30 % ) receiving artesunate monotherapy and 1 of 20 ( 5 % ) receiving artesunate-mefloquine therapy in Pailin , as compared with 2 of 20 ( 10 % ) and 1 of 20 ( 5 % ) , respectively , in Wang Pha ( P=0.31 ) . These markedly different parasitologic responses were not explained by differences in age , artesunate or dihydroartemisinin pharmacokinetics , results of isotopic in vitro sensitivity tests , or putative molecular correlates of P. falciparum drug resistance ( mutations or amplifications of the gene encoding a multidrug resistance protein [ PfMDR1 ] or mutations in the gene encoding sarco-endoplasmic reticulum calcium ATPase6 [ PfSERCA ] ) . Adverse events were mild and did not differ significantly between the two treatment groups . CONCLUSIONS P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thail and . Resistance is characterized by slow parasite clearance in vivo without corresponding reductions on conventional in vitro susceptibility testing . Containment measures are urgently needed . ( Clinical Trials.gov number , NCT00493363 , and Current Controlled Trials number , IS RCT N64835265 . Background The use of antimalarial drug combinations with artemisinin derivatives is recommended to overcome drug resistance in Plasmodium falciparum . The fixed combination of oral artemether-lumefantrine , an artemisinin combination therapy ( ACT ) is highly effective and well tolerated . It is the only registered fixed combination containing an artemisinin . The trial presented here was conducted to monitor the efficacy of the six-dose regimen of artemether-lumefantrine ( ALN ) in an area of multi-drug resistance , along the Thai-Myanmar border . Methods The trial was an open-label , two-arm , r and omized study comparing artemether-lumefantrine and mefloquine-artesunate for the treatment of uncomplicated falciparum malaria with 42 days of follow up . Parasite genotyping by polymerase chain reaction ( PCR ) was used to distinguish recrudescent from newly acquired P. falciparum infections . The PCR adjusted cure rates were evaluated by survival analysis . Results In 2001–2002 a total of 490 patients with slide confirmed uncomplicated P. falciparum malaria were r and omly assigned to receive artemether-lumefantrine ( n = 245 ) or artesunate and mefloquine ( n = 245 ) and were followed for 42 days . All patients had rapid initial clinical and parasitological responses . In both groups , the PCR adjusted cure rates by day 42 were high : 98.8 % ( 95 % CI 96.4 , 99.6 % ) for artemether-lumefantrine and 96.3 % ( 95 % CI 93.1 , 98.0 % ) for artesunate-mefloquine . Both regimens were very well tolerated with no serious adverse events observed attributable to either combination . Conclusion Overall , this study confirms that these two artemisinin-based combinations remain highly effective and result in equivalent therapeutic responses in the treatment of highly drug-resistant falciparum malaria BACKGROUND Combination treatments , preferably containing an artemisinin derivative , are recommended to improve efficacy and prevent Plasmodium falciparum drug resistance . Our aim was to show non-inferiority of a new dispersible formulation of artemether-lumefantrine to the conventional crushed tablet in the treatment of young children with uncomplicated malaria . METHODS We did a r and omised non-inferiority study on children weighing 5 - 35 kg with uncomplicated P falciparum malaria in Benin , Kenya , Mali , Mozambique , and Tanzania . The primary outcome measure was PCR-corrected 28-day parasitological cure rate . We aim ed to show non-inferiority ( with a margin of -5 % ) of dispersible versus crushed tablet . We constructed an asymptotic one-sided 97.5 % CI on the difference in cure rates . A computer-generated r and omisation list was kept central ly and investigators were unaware of the study medication administered . We used a modified intention-to-treat analysis . This trial is registered with Clinical Trials.gov , number NCT00386763 . FINDINGS 899 children aged 12 years or younger were r and omly assigned to either dispersible ( n=447 ) or crushed tablets ( n=452 ) . More than 85 % of patients in each treatment group completed the study . 812 children qualified for the modified intention-to-treat analysis ( n=403 vs n=409 ) . The PCR-corrected day-28 cure rate was 97.8 % ( 95 % CI 96.3 - 99.2 ) in the group on dispersible formulation and 98.5 % ( 97.4 - 99.7 ) in the group on crushed formulation . The lower bound of the one-sided 97.5 % CI was -2.7 % . The most common drug-related adverse event was vomiting ( n=33 [ 7 % ] and n=42 [ 9 % ] , respectively ) . No signs of ototoxicity or relevant cardiotoxicity were seen . INTERPRETATION A six-dose regimen of artemether-lumefantrine with the new dispersible formulation is as efficacious as the currently used crushed tablet in infants and children , and has a similar safety profile In India , treatment of acute , uncomplicated Plasmodium falciparum malaria is becoming increasingly difficult due to resistance to chloroquine , thus there is a need for new antimalarial drugs . CGP 56697 ( co-artemether ) , a new drug , is a combination of artemether and lumefantrine in a single oral formulation ( one tablet = 20 mg of artemether plus 120 mg of lumefantrine ) . In a double-blind study , 179 patients with acute uncomplicated P. falciparum malaria were r and omly assigned to receive either CGP ( n = 89 ) given as a short course of 4 x 4 tablets over a 48-hr period or chloroquine ( n = 90 ) given as four tablets ( one tablet = 150 mg of chloroquine base ) initially , followed by two tablets each at 6 - 8 , 24 , and 48 hr . Due to a death in the chloroquine group and a decrease in the chloroquine cure rate to < 50 % ( based on the blinded overall cure rate at that time ) , recruitment was terminated prematurely . CGP 56697 showed a superior 28-day cure rate ( 95.4 % versus 19.7 % ; P < 0.001 ) , time to parasite clearance ( median = 36 versus 60 hr ; P < 0.001 ) , and resolution of fever ( median = 18 versus 27 hr ; P = 0.0456 ) . This drug provides a safe , effective , and rapid therapy for the treatment of acute uncomplicated P. falciparum malaria One hundred and two Chinese out- patients with naturally acquired , previously untreated , falciparum malaria were selected to evaluate the efficacy of a new combination anti-malaria therapy , CGP 56697 ( artemether plus benflumetol ) . In this open non-comparative trial each patient received a combination of 80 mg artemether and 480 mg benflumetol given orally at 0 , 8 , 24 and 48 hours ( total : 320 mg artemether , 1,920 mg benflumetol ) . Patients were kept for 28 days in a transmission-free hospital in an area with chloroquine resistant falciparum malaria to prevent reinfection and to aid diagnosis of recrudescence . Progress and possible adverse effects were monitored by blood film parasitology , blood biochemistry assays , urinalysis , ECG and X-ray .  Ninety-eight of the 102 patients were shown to be free of infection at 28 days , a 96.1 % cure rate . Parasite reduction at 24 hours was 99.4 % . Time to effect complete parasite clearance ranged from 24 to 54 hours ( median 30 hours ) . Time for fever clearance ranged from 6 to 78 hours ( median 18 hours ) . Recrudescence was low ( 3.9 % ) . No significant adverse side-effects were encountered . It is concluded that CGP 56697 , a combination anti-malaria therapy of artemether with benflumetol , offered a rapid and highly effective treatment for acute uncomplicated falciparum malaria in an area of chloroquine-resistant malaria in China ABSTRACT The objective of this study was to conduct a prospect i ve population pharmacokinetic and pharmacodynamic evaluation of lumefantrine during blinded comparisons of artemether-lumefantrine treatment regimens in uncomplicated multidrug-resistant falciparum malaria . Three combination regimens containing an average adult lumefantrine dose of 1,920 mg over 3 days ( four doses ) ( regimen A ) or 2,780 mg over 3 or 5 days ( six doses ) ( regimen B or C , respectively ) were given to 266 Thai patients . Detailed observations were obtained for 51 hospitalized adults , and sparse data were collected for 215 patients of all ages in a community setting . The population absorption half-life of lumefantrine was 4.5 h. The model-based median ( 5th and 95th percentiles ) peak plasma lumefantrine concentrations were 6.2 ( 0.25 and 14.8 ) μg/ml after regimen A , 9.0 ( 1.1 and 19.8 ) μg/ml after regimen B , and 8 ( 1.4 and 17.4 ) μg/ml after regimen C. During acute malaria , there was marked variability in the fraction of drug absorbed by patients ( coefficient of variation , 150 % ) . The fraction increased considerably and 
    Output:
    
INTERPRETATION The recommended dose of artemether-lumefantrine provides reliable efficacy in most patients with uncomplicated malaria .