A Study by the Tracking Resistance to Artemisinin Collaboration (TRAC) (TRACII)

• PCR corrected efficacy defined as adequate clinical and parasitological response (ACPR) [ Time Frame: 42 days ]
  

• Parasite clearance half-life [ Time Frame: 42 days ]
  Parasite clearance half-life assessed by microscopy as primary parameter to de-termine parasite clearance
  
  
• Parasite reduction rates and ratios at 24 and 48 hours assessed by microscopy [ Time Frame: at 24 and 48 hours ]
  
• Time for parasite count to fall to 50% of initial parasite density [ Time Frame: 42 days ]
  
• Time for parasite count to fall to 90% of initial parasite density [ Time Frame: 42 days ]
  
• Time for parasite count to fall to 99% of initial parasite density [ Time Frame: 42 days ]
  
• Fever clearance time [ Time Frame: 42 days ]
  
• Incidence of adverse events and serious adverse events [ Time Frame: 42 days ]
  
• Incidence of adverse events concerning markers of hepatic toxicity [ Time Frame: 42 days ]
  Total billirubin, ALT, AST and Alkaline Phosphatase will be measured
  
  
• Incidence of adverse events concerning markersof renal toxicity [ Time Frame: 42 days ]
  Creatinine will be measured
  
  
• Incidence of prolongation of the QTc-interval [ Time Frame: 3 days ]
  Incidence of prolongation of the Qtc-interval above 500 ms or > 60ms above baseline values
  
  
• Change in hemoglobin/hematocrit [ Time Frame: 42 days ]
  Change in hemoglobin/hematocrit on day 1 to 7, 14, 21, 28, 35 and 42 according to geographical location and study arm, stratified for G6PD status
  
  
• Proportion of patients that reports completing a full course of observed TACT or ACT without withdrawal of consent or exclusion from study [ Time Frame: 42 days ]
  
• Prevalence of Kelch13 mutations of known functional significance [ Time Frame: 42 days ]
  
• Prevalence/incidence of other genetic markers of antimalarial drug resistance [ Time Frame: 42 days ]
  
• Genome wide association with in vivo/in vitro sensitivity parasite phenotype [ Time Frame: 42 days ]
  
• Correlation between SNPs measured in dry blood spots and whole genome sequencing in leukocyte depleted blood samples [ Time Frame: 42 days ]
  
• Transcriptomic patterns at t=0 and t=6h comparing sensitive and resistant parasites [ Time Frame: 6hrs after start of treatment ]
  
• Correlation between qPCR based versus microscopy based assessments of parasite clearance dynamics [ Time Frame: 14 days ]
  
• Proportion of patients with gametocytemia before,after treatment with Primaquine [ Time Frame: assessed at admission, up to day 14 ]
  
• Levels of RNA transcription coding for male or female specific gametocytes [ Time Frame: at admission up to day 14 ]
  
• In vitro sensitivity (expressed in IC50 values among others) of P. falciparum to artemisinins and partner drugs [ Time Frame: 42 days ]
  
• • Pharmacokinetic profiles and interactions of artemisinin-derivatives and partner drugs (half-life, Cmax, AUC, Tmax) in 20 ACT treated and 20 TACT treated patients of both study arms [ Time Frame: 42 days ]
  
• Day 7 drug levels of partner drugs in association with treatment efficacy and treatment arm [ Time Frame: Day 7 ]
  

In Laos, Myanmar, Bangladesh, India and DRC, the following two combinations will be used:

1. Artemether-lumefantrine combined with amodiaquine (TACT arm) or
2. Artemether-lumefantrine (ACT arm)

In Cambodia, Myanmar, Vietnam and Thailand, the following two combinations will be used:

1. Dihydroartemisinin-piperaquine combined with mefloquine (TACT arm) or
2. Dihydroartemisinin-piperaquine (ACT arm)