Combination Antimalarials in Uncomplicated Malaria

Primary Outcome Measures:

• Therapeutic efficacy defined as:
  
• Adequate Clinical and Parasitological Response (ACPR), Early Treatment Failure (ETF), Late Treatment Failure (LTF), defined as Late Clinical Failure (LCF) and Late Parasitological Failure (LPF);
  
• Sensitive or parasitological failure (RI, early and late, RII, RIII)
  
• Parasitological failures will be classified as recrudescence or re-infection (or indeterminate) using GLURP and MSP I & II markers;
  
• Parasite clearance time;
  
• Fever clearance time.
  

Secondary Outcome Measures:

• Association between study treatment and gametocyte carriage
  
• Pharmacokinetics by measurement of whole blood levels of Sulfadoxine and Pyrimethamine, and lumefantrine should a reliable assay become available
  
• Correlation of frequency of DHFR and DHPS mutations with parasitological outcome
  
• Tolerability by describing adverse events and changes in haematological parameters
  
• Capacity by describing the training and development of study teams and their subsequent skills attained
  

The resistance of Plasmodium falciparum to anti-malarial drugs is a serious impediment to the control of malaria. In the South East African Combination Anti-malarial Therapy (SEACAT) evaluation, there will be a comprehensive evaluation of phased introduction of combination anti-malarials (CAT) in Mozambique, Swaziland and South Africa. In order to facilitate formulation of an effective regional drug policy and provide a database for decision-making on the implementation of combination therapy, it is essential that the in vivo response to CAT in all three countries be investigated. An SP therapeutic efficacy study will be conducted according to this modified WHO protocol to guide the selection of CAT. After CAT is introduced an in vivo CAT efficacy study will then be conducted to evaluate the efficacy of artesunate plus SP (or artemether-lumefantrine in KwaZulu Natal and Limpopo). In areas of low intensity malaria transmission the CAT in vivo study results will be compared across sites and with those found at baseline with monotherapy, for each site.