In areas of the Sahel sub-region of Africa with intense seasonal malaria transmission, seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SP+AQ) has become the standard-of-care for the prevention of malaria in children. Despite the scale-up of SMC across West Africa, the malaria burden remains high. Reasons for this are not well understood, however, it is hypothesized that children eligible for SMC who get malaria may be underdosed or may have not received SP+AQ. Moreover, there are major concerns that the continued use of the SMC strategy may increase selection of AQ and/or SP-resistant Plasmodium falciparum parasites. The overall objective of this observational study are to understand the factors driving malaria among children eligible to receive SMC and whether circulating levels of sulfadoxine (SDX), pyrimethamine (PYR), and AQ are associated with risks of malaria and antimalarial drug resistance.

In areas of the Sahel sub-region of Africa with intense seasonal malaria transmission, seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SP+AQ) has become the standard-of-care for the prevention of malaria in children. Despite the scale-up of SMC across West Africa, the malaria burden remains high. Reasons for this are not well understood, however, it is hypothesized that children eligible for SMC who get malaria may be underdosed or may have not received SP+AQ. Moreover, there are major concerns that the continued use of the SMC strategy may increase selection of AQ and/or SP-resistant Plasmodium falciparum parasites. The overall objective of this observational study are to understand the factors driving malaria among children eligible to receive SMC and whether circulating levels of sulfadoxine (SDX), pyrimethamine (PYR), and AQ are associated with risks of malaria and antimalarial drug resistance. The specific objectives of this study are as follows:

1. To determine associations between the levels of exposure to the components of SP+AQ (SDX, PYR, and AQ) and malaria risk.
2. To determine associations between levels of exposure to the components of SP+AQ and the prevalence of P. falciparum genetic polymorphisms associated with drug resistance.
3. To compare the prevalence of genetic polymorphisms associated with SP+AQ resistance between parasites infecting children eligible to receive SMC and those infecting older children ineligible to receive SMC.
4. To assess whether the prevalence of genetic polymorphisms associated with SP+AQ resistance changes over time.

The inclusion criteria will differ for each group enrolled into the study:

Inclusion criteria for Group 1 (Children 6-59 months of age diagnosed with uncomplicated P. falciparum malaria):

• Aged 6-59 months
• Resident of health facility catchment area
• Provision of parental consent
• Fever (temperature of ≥37.5°C) or history of fever in the past 24 hours
• Confirmed P. falciparum parasitemia by RDT and/or microscopy

Inclusion criteria for Group 2 (Children 6-59 months of age without malaria):

• Aged 6-59 months
• Resident of health facility catchment area
• Provision of parental consent
• Negative for P. falciparum parasitemia by RDT and/or microscopy

Inclusion criteria for Group 3 (Children 5-10 years of age diagnosed with uncomplicated P. falciparum malaria):

• Aged 5-10 years
• Resident of health facility catchment area
• Provision of parental consent
• Fever (temperature of ≥37.5°C) or history of fever in the past 24 hours
• Confirmed P. falciparum parasitemia by RDT and/or microscopy

The exclusion criteria for all children are as follows:

• Refusal to participate
• Residence outside of health facility catchment areas
• Known treatment of malaria (not SMC) in the past 14 days
• Danger signs (lethargy, unable to drink or breast feed, repeated vomiting, unable to stand or sit due to weakness)
• Signs of severe malaria, including altered conscious, respiratory distress (rapid breathing), severe anemia (<5 g/dL), or other signs of organ dysfunction.
• Non-malarial illness that is severe or prevents necessary study procedures

The target population will be children residing in the catchment areas of study health facilities within Bobo-Dioulasso, Burkina Faso.