Association Between Drug Levels, Malaria, and Antimalarial Resistance in the Setting of Seasonal Malaria Chemoprevention (DRUMARS)

University of California San Francisco (UCSF)

Status: Completed

Conditions: Malaria,Falciparum

Study type: Observational

Funder types: Other

Identifiers

NCT04969185

21-33890

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 310 patients

Sex: All

Ages: 6 months to 10 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

310 participants in 3 patient groups

Group 1: Children eligible to receive SMC diagnosed with uncomplicated Plasmodium falciparum malaria

Description:

Children eligible to receive SMC (6-59 months of age) who were diagnosed with uncomplicated P. falciparum malaria at the health facility.

Group 2: Children eligible to receive SMC presenting at health facility without malaria parasitemia

Description:

Group 2 will be defined as children eligible to receive SMC (6-59 months of age) who presented at the health facility and tested negative for malaria parasitemia.This group will serve as the control group to Group 1 Cases to compare the SP-AQ drug levels between children who did and did not get malaria.

Group 3: Children 5-10 years of age diagnosed with uncomplicated Plasmodium falciparum malaria

Description:

Group 3 will be defined as children ineligible to receive SMC (5-10 years of age) who were diagnosed with uncomplicated P. falciparum malaria at the health facility. This group will serve as the control group to Group 1 Cases to compare the prevalence of SP and AQ resistance markers.