***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 Safety surveillance of widely used artemisinin-based combination therapy ( ACT ) is essential , but tolerability data in the over five years age group are largely anecdotal . Methods Two open-label , r and omized trials were conducted in Nimba County , Liberia : i ) the main tolerability trial with 1,000 Plasmodium falciparum malaria patients aged over five years ( Study -T ) , and , ii ) an efficacy trial with a secondary objective of collecting tolerability data among 300 children age six to 59 months ( Study -E ) . In both studies patients were r and omized to fixed-dose artesunate-amodiaquine ( ASAQ Winthrop ® ) or artemether-lumefantrine ( AL , Coartem ® ) , respectively . Clinical - and laboratory-adverse events ( AEs ) were recorded until day 28 . Results Study -T : most patients experienced at least one AE . Severe AEs were few , primarily asymptomatic blood system disorders or increased liver enzyme values . No treatment or study discontinuation occurred . Mild or moderate fatigue ( 39.8 % vs 16.3 % , p < 0.001 ) , vomiting ( 7.1 % vs 1.6 % , p < 0.001 ) , nausea ( 3.2 % vs 1.0 % , p = 0.01 ) , and anaemia ( 14.9 % vs 9.8 % , p = 0.01 ) were more frequently recorded in the ASAQ versus AL arm . Study -E : mild or moderate AEs were common , including anaemia , fatigue , vomiting or diarrhoea . The few severe events were asymptomatic blood system disorders and four clinical events ( pneumonia , malaria , vomiting and stomatitis ) . Conclusion Both ASAQ and AL were well tolerated in patients of all age groups . No unexpected AEs occurred . Certain mild or moderate AEs were more frequent in the ASAQ arm . St and ardised safety surveillance should continue for all forms of ACT.Trial registration The protocol s were registered with Current Controlled Trials , under the identifier numbers IS RCT N40020296 , IS RCT N51688713 , ( http://www.controlled-trials.com ) Background Malaria is a very important cause of anaemia in tropical countries . Anaemia is assessed either by measurement of the haematocrit or the haemoglobin concentration . For comparisons across studies , it is often necessary to derive one measure from the other . Methods Data on patients with slide-confirmed uncomplicated falciparum malaria were pooled from 85 antimalarial drug trials conducted in 25 different countries , to assess the haemoglobin/haematocrit relationship at different time points in malaria . Using a linear r and om effects model , a conversion equation for haematocrit was derived based on 3,254 measurements from various time points ( ranging from day 0 to day 63 ) from 1,810 patients with simultaneous measurements of both parameters . Haemoglobin was also estimated from haematocrit with the commonly used threefold conversion . Results A good fit was obtained using Haematocrit = 5.62 + 2.60 * Haemoglobin . On average , haematocrit/3 levels were slightly higher than haemoglobin measurements with a mean difference ( ± SD ) of -0.69 ( ± 1.3 ) for children under the age of 5 ( n = 1,440 measurements from 449 patients ) . Conclusion Based on this large data set , an accurate and robust conversion factor both in acute malaria and in convalescence was obtained . The commonly used threefold conversion is also valid Background Home-management of malaria ( HMM ) strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa . However , limited data are available on the effectiveness of using artemisinin-based combination therapy ( ACT ) within the HMM strategy . The aim of this study was to assess the effectiveness of artemether-lumefantrine ( AL ) , presently the most favoured ACT in Africa , in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania , when provided by community health workers ( CHWs ) and administered unsupervised by parents or guardians at home . Methods An open label , single arm prospect i ve study was conducted in two rural villages with high malaria transmission in Kibaha District , Tanzania . Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test ( RDT ) were provisionally enrolled and provided AL for unsupervised treatment at home . Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and review ed weekly by the CHWs during 42 days . Primary outcome measure was PCR corrected parasitological cure rate by day 42 , as estimated by Kaplan-Meier survival analysis . This trial is registered with Clinical Trials.gov , number NCT00454961 . Results A total of 244 febrile children were enrolled between March-August 2007 . Two patients were lost to follow up on day 14 , and one patient withdrew consent on day 21 . Some 141/241 ( 58.5 % ) patients had recurrent infection during follow-up , of whom 14 had recrudescence . The PCR corrected cure rate by day 42 was 93.0 % ( 95 % CI 88.3%-95.9 % ) . The median lumefantrine concentration was statistically significantly lower in patients with recrudescence ( 97 ng/mL [ IQR 0 - 234 ] ; n = 10 ) compared with reinfections ( 205 ng/mL [ 114 - 390 ] ; n = 92 ) , or no parasite reappearance ( 217 [ 121 - 374 ] ng/mL ; n = 70 ; p ≤ 0.046 ) . Conclusions Provision of AL by CHWs for unsupervised malaria treatment at home was highly effective , which provides evidence base for scaling-up implementation of HMM with AL in Tanzania 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 Objectives Co-administration of artemether/lumefantrine with antiretroviral therapy has potential for pharmacokinetic drug interactions . We investigated drug – drug interactions between artemether/lumefantrine and efavirenz or nevirapine . Methods We performed a cross-over study in which HIV-infected adults received st and ard  six-dose artemether/lumefantrine 80/480 mg before and at efavirenz or nevirapine steady state . Artemether , dihydroartemisinin , lumefantrine , efavirenz and nevirapine plasma concentrations were measured and compared . Results Efavirenz significantly reduced artemether maximum concentration ( Cmax ) and plasma AUC ( median 29 versus 12 ng/mL , P < 0.01 , and 119 versus 25 ng · h/mL , P < 0.01 ) , dihydroartemisinin Cmax and AUC ( median 120 versus 26 ng/mL , P < 0.01 , and 341 versus 84 ng · h/mL , P < 0.01 ) , and lumefantrine Cmax and AUC ( median 8737 versus 6331 ng/mL , P = 0.03 , and 280 370 versus 124 381 ng · h/mL ,  P < 0.01 ) . Nevirapine significantly reduced artemether Cmax and AUC ( median 28 versus 11 ng/mL , P < 0.01 , and 123 versus 34 ng · h/mL , P < 0.01 ) and dihydroartemisinin Cmax and AUC ( median 107 versus 59 ng/mL , P < 0.01 , and 364 versus 228 ng · h/mL , P < 0.01 ) . Lumefantrine Cmax and AUC were non-significantly reduced by nevirapine . Artemether/lumefantrine reduced nevirapine Cmax and AUC ( median 8620 versus 4958 ng/mL , P < 0.01 , and 66 329 versus 35 728 ng · h/mL , P < 0.01 ) , but did not affect efavirenz exposure . Conclusions Co-administration of artemether/lumefantrine with efavirenz or nevirapine result ed in a reduction in artemether , dihydroartemisinin , lumefantrine and nevirapine exposure . These drug interactions may increase the risk of malaria treatment failure and development of resistance to artemether/lumefantrine and nevirapine . Clinical data from population pharmacokinetic and pharmacodynamic trials evaluating the impact of these drug interactions are urgently needed 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 To date no comparative trials have been done , to our knowledge , of fixed-dose artemisinin combination therapies ( ACTs ) for the treatment of Plasmodium 
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The highest risk of recrudescence was observed in areas of emerging artemisinin resistance and very low transmission intensity .
Current artemether-lumefantrine dosing recommendations achieve day 7 lumefantrine concentrations ≥200 ng/ml and high cure rates in most uncomplicated malaria patients .