***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 New antimalarials are needed for P. vivax and P. falciparum malaria . This study compared the efficacy and safety of pyronaridine-artesunate with that of chloroquine for the treatment of uncomplicated P. vivax malaria . Methods and Findings This phase III r and omized , double-blind , non-inferiority trial included five centers across Cambodia , Thail and , India , and Indonesia . In a double-dummy design , patients ( aged > 3–≤60 years ) with microscopically confirmed P. vivax mono-infection were r and omized ( 1∶1 ) to receive pyronaridine-artesunate ( target dose 7.2∶2.4 mg/kg to 13.8∶4.6 mg/kg ) or chloroquine ( st and ard dose ) once daily for three days . Each treatment group included 228 r and omized patients . Outcomes for the primary endpoint , Day-14 cure rate in the per- protocol population , were 99.5 % , ( 217/218 ; 95%CI 97.5 , 100 ) with pyronaridine-artesunate and 100 % ( 209/209 ; 95%CI 98.3 , 100 ) with chloroquine . Pyronaridine was non-inferior to chloroquine : treatment difference −0.5 % ( 95%CI −2.6 , 1.4 ) , i.e. , the lower limit of the 2-sided 95%CI for the treatment difference was greater than −10  % . Pyronaridine-artesunate cure rates were non-inferior to chloroquine for Days 21 , 28 , 35 and 42 . Parasite clearance time was shorter with pyronaridine-artesunate ( median 23.0 h ) versus chloroquine ( 32.0 h ; p<0.0001 ) , as was fever clearance time ( median 15.9 h and 23.8 h , respectively ; p = 0.0017 ) . Kaplan-Meier estimates of post-baseline P. falciparum infection incidence until Day 42 were 2.5 % with pyronaridine-artesunate , 6.1 % with chloroquine ( p = 0.048 , log-rank test ) . Post-baseline P. vivax or P. falciparum infection incidence until Day 42 was 6.8 % and 12.4 % , respectively ( p = 0.022 , log rank test ) . There were no deaths . Adverse events occurred in 92/228 ( 40.4 % ) patients with pyronaridine-artesunate and 72/228 ( 31.6 % ) with chloroquine . Mild and transient increases in hepatic enzymes were observed for pyronaridine-artesunate . Conclusion Pyronaridine-artesunate efficacy in acute uncomplicated P. vivax malaria was at least that of chloroquine . As pyronaridine-artesunate is also efficacious against P. falciparum malaria , this combination has potential utility as a global antimalarial drug . Trial registration Clinical trials.gov Background Pyronaridine-artesunate ( PA ) is indicated for the treatment of acute uncomplicated Plasmodium falciparum and Plasmodium vivax malaria . Methods Individual patient data on safety outcomes were integrated from six r and omized clinical trials conducted in Africa and Asia in patients with microscopically confirmed P. falciparum ( five studies ) or P. vivax ( one study ) malaria . Efficacy against P. falciparum was evaluated across three Phase III clinical trials . Results The safety population included 2,815 patients r and omized to PA , 1,254 to comparators : mefloquine + artesunate ( MQ + AS ) , artemether-lumefantrine ( AL ) , or chloroquine . All treatments were generally well tolerated . Adverse events occurred in 57.2 % ( 1,611/2,815 ) of patients with PA versus 51.5 % ( 646/1,254 ) for comparators , most commonly ( PA ; comparators ) : headache ( 10.6 % ; 9.9 % ) , cough ( 5.9 % ; 5.6 % ) and anaemia ( 4.5 % ; 2.9 % ) . Serious averse events were uncommon for all treatments ( 0–0.7 % ) . Transient increases in alanine aminotransferase and aspartate aminotransferase were observed with PA but did not lead to any clinical sequelae . For P. falciparum malaria , day-28 PCR-corrected adequate clinical and parasitological response with PA was 93.6 % ( [ 1,921/2,052 ] 95 % CI 92.6 , 94.7 ) in the intent-to-treat population and 98.5 % ( [ 1,852/1,880 ] 95 % CI 98.0 , 99.1 ) in the per- protocol population . Median parasite clearance time was 24.1 h with PA , 31.9 h with MQ + AS , and 24.0 h with AL . Median fever clearance time was 15.5 h with PA , 15.8 h with MQ + AS , and 14.0 h with AL . By day 42 , P. falciparum gametocytes had declined to near zero for all treatments . Conclusions Pyronaridine-artesunate was well tolerated with no safety concerns with the exception of mostly mild transient rises in transaminases . Efficacy was high and met the requirements for use as first-line therapy . Pyronaridine-artesunate should be considered for inclusion in malaria treatment programmes . Trial registration Clinical trials.gov : NCT00331136 ; NCT00403260 ; NCT00422084 ; NCT00440999 ; NCT00541385 ; BACKGROUND Pyronaridine-artesunate is an artemisinin-based combination therapy under evaluation for the treatment of Plasmodium falciparum and P. vivax malaria . METHODS We conducted a phase 3 , open-label , multicenter , noninferiority trial that included 1271 patients between 3 and 60 years of age from Asia ( 81.3 % ) or Africa ( 18.7 % ) with microscopically confirmed , uncomplicated P. falciparum malaria . Patients underwent r and omization for treatment with a fixed-dose combination of 180 mg of pyronaridine and 60 mg of artesunate or with 250 mg of mefloquine plus 100 mg of artesunate . Doses were calculated according to body weight and administered once daily for 3 days . RESULTS Pyronaridine-artesunate was noninferior to mefloquine plus artesunate for the primary outcome : adequate clinical and parasitologic response in the per- protocol population on day 28 , corrected for reinfection with the use of polymerase-chain-reaction ( PCR ) genotyping . For this outcome , efficacy in the group receiving pyronaridine-artesunate was 99.2 % ( 743 of 749 patients ; 95 % confidence interval [ CI ] , 98.3 to 99.7 ) and that in the group receiving mefloquine plus artesunate was 97.8 % ( 360 of 368 patients ; 95 % CI , 95.8 to 99.1 ) , with a treatment difference of 1.4 percentage points ( 95 % CI , 0.0 to 3.5 ; P=0.05 ) . In the intention-to-treat population , efficacy on day 42 in the group receiving pyronaridine-artesunate was 83.1 % ( 705 of 848 patients ; 95 % CI , 80.4 to 85.6 ) and that in the group receiving mefloquine plus artesunate was 83.9 % ( 355 of 423 patients ; 95 % CI , 80.1 to 87.3 ) . In Cambodia , where there were 211 study patients , the median parasite clearance time was prolonged for both treatments : 64 hours versus 16.0 to 38.9 hours in other countries ( P<0.001 , on the basis of Kaplan-Meier estimates ) . Kaplan-Meier estimates of the recrudescence rate in the intention-to-treat population in Cambodia until day 42 were higher with pyronaridine-artesunate than with mefloquine plus artesunate ( 10.2 % [ 95 % CI , 5.4 to 18.6 ] vs. 0 % ; P=0.04 as calculated with the log-rank test ) , but similar for the other countries combined ( 4.7 % [ 95 % CI , 3.3 to 6.7 ] and 2.8 % [ 95 % CI , 1.5 to 5.3 ] , respectively ; P=0.24 ) . Elevated levels of aminotransferases were observed in those receiving pyronaridine-artesunate . Two patients receiving mefloquine plus artesunate had seizures . CONCLUSIONS Fixed-dose pyronaridine-artesunate was efficacious in the treatment of uncomplicated P. falciparum malaria . In Cambodia , extended parasite clearance times were suggestive of in vivo resistance to artemisinin . ( Funded by Shin Poong Pharmaceutical Company and the Medicines for Malaria Venture ; Clinical Trials.gov number , NCT00403260 . ) Background Children are most vulnerable to malaria . A pyronaridine-artesunate pediatric granule formulation is being developed for the treatment of uncomplicated Plasmodium falciparum malaria . Methods This phase III , multi-center , comparative , open-label , parallel-group , controlled clinical trial included patients aged ≤12 years , bodyweight ≥5 to < 25 kg , with a reported history of fever at inclusion or in the previous 24 h and microscopically-confirmed uncomplicated P. falciparum malaria . Patients were r and omized ( 2:1 ) to pyronaridine-artesunate granules ( 60/20 mg ) once daily or artemether-lumefantrine crushed tablets  ( 20/120 mg ) twice daily , both dosed by bodyweight , orally ( liquid suspension ) for three days . Results Of 535 patients r and omized , 355 received pyronaridine-artesunate and 180 received artemether-lumefantrine . Day-28 adequate clinical and parasitological response ( ACPR ) , corrected for re-infection using polymerase chain reaction ( PCR ) genotyping ( per- protocol population ) was 97.1 % ( 329/339 ; 95 % CI 94.6 , 98.6 ) for pyronaridine-artesunate ; 98.8 % ( 165/167 ; 95 % CI 95.7 , 99.9 ) for artemether-lumefantrine . The primary endpoint was achieved : pyronaridine-artesunate PCR-corrected day-28 ACPR was statistically significantly > 90 % ( P < .0001 ) . Pyronaridine-artesunate was non-inferior to artemether-lumefantrine : treatment difference -1.8 % ( 95 % CI -4.3 to 1.6 ) . The incidence of drug-related adverse events was 37.2 % ( 132/355 ) with pyronaridine-artesunate , 44.4 % ( 80/180 ) with artemether-lumefantrine . Clinical biochemistry results showed similar mean changes versus baseline in the two treatment groups . From day 3 until study completion , one patient in each treatment group had peak alanine aminotransferase ( ALT ) > 3 times the upper limit of normal ( ULN ) and peak total bilirubin > 2xULN ( i.e. within the Hy ’s law definition ) . Conclusions The pyronaridine-artesunate pediatric granule formulation was efficacious and was non-inferior to artemether-lumefantrine . The adverse event profile was similar for the two comparators . Pyronaridine-artesunate should be considered for inclusion in paediatric malaria treatment programmes . Trial registration Clinical Trials.gov : identifier Pyronaridine is a new antimalarial agent developed in China . In this r and omized , unblinded study , the safety , tolerance , and clinical efficacy of pyronaridine ( n = 44 ) were evaluated and compared with those of chloroquine ( n = 44 ) , the st and ard first-line antimalarial drug in most of Africa , in 88 Cameroonian children with acute uncomplicated falciparum malaria . The target sample size was determined to detect a 35 % difference in in vivo resistance between the two treatment groups , with 95 % power . Clinical and parasitological responses were monitored for 14 days on an outpatient basis . Seven children ( 3 treated with pyronaridine and 4 treated with chloroquine ) were lost to 
    Output:
    
Plain Language summary Artesunate plus pyronaridine for treating uncomplicated Plasmodium falciparum malaria What is uncomplicated malaria and how might artesunate-pyronaridine work Uncomplicated malaria is the milder form of malaria which usually causes fever , with or without headache , tiredness , muscle pains , abdominal pains , nausea , and vomiting .
If left untreated , uncomplicated malaria can rapidly develop into severe malaria with kidney failure , fitting , unconsciousness , and eventually death .
Plasmodium falciparum is the most common parasite causing malaria in sub-Saharan Africa and causes most of the severe malaria worldwide .
Serious adverse events were rare in people treated with either artesunate-pyronaridine or other ACTs .
However , short-lasting liver toxicity was more frequent in people treated with artesunate-pyronaridine than with the other antimalarials ( moderate quality evidence ) .
Authors ' conclusions Artesunate-pyronaridine performed well compared to the other two ACT with which it has been compared , but further studies in African and Asian children are required to help clarify whether this combination is an option for first-line treatment