• 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
  

• Association between study treatment and gametocyte carriage
  
• Pharmacokinetics by measurement of whole blood levels of Sulfadoxine and Pyrimethamine
  
• 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
  

Resistance of Plasmodium falciparum to anti-malarial drugs is a serious impediment to malaria control. In the South East African Combination Anti-malarial Therapy (SEACAT) evaluation, there is an evaluation of the phased introduction of combination anti-malarial therapy (CAT) in Mozambique, Swaziland and South Africa. In order to facilitate formulation of effective regional drug policy and provide a database for decision-making on the implementation of CAT, it is essential that the in vivo response to CAT be investigated. This will be achieved through the SEACAT 01 protocol which is a component of the SEACAT evaluation described in another file on this website. However, in selected Mozambique sites where the intensity of malaria transmission is high, a direct parallel group comparison of monotherapy (SP) with CAT (artesunate, AS, plus SP) will be conducted according to a specific amendment (Amendment 4) to the SEACAT 01 protocol. Amendment 4 is presented in this separate file on the website for clarity.

Inclusion Criteria:

• Male or female, older than 12 months.
• Weight > 10 kg.
• Diagnoses of uncomplicated acute P. falciparum malaria parasitaemia of up to 500 000 asexual parasite/mcl blood with axillary temperature of greater than and equal to 37.50C or history of fever.
• Documented informed consent.
• Lives close enough to the health centre for reliable follow up.

Exclusion Criteria:

• Has received anti-malarial treatment in the past 7 days.
• Is infected with other malarial species (such subjects will be excluded retrospectively).
• Severely ill (based on WHO Criteria for severe malaria ) or if patient is considered, in the opinion of the investigator or designee, to have moderately severe malaria (e.g. prostrate, repeated vomiting, dehydrated).
• Has received cotrimoxazole or chloramphenicol in the past 7 days.
• History of G6PD deficiency.
• Is pregnant.
• Has a history of allergy to any sulphonamide (for SP) or artemisinin derivative (for artesunate and co-artemether).