Clinical trial NCT04969185: Association Between Drug Levels, Malaria, and Antimalarial Resistance in the Setting of Seasonal Malaria Chemoprevention
Official title: Associations Between Drug Levels and the Risk of Malaria and Drug Resistance in the Setting of Seasonal Malaria Chemoprevention in Bobo-Dioulasso, Burkina Faso
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Malaria,Falciparum
Keywords: seasonal malaria chemoprevention
sulfadoxine-pyrimethamine
amodiaquine
antimalarial resistance
pharmacokinetics
falciparum malaria
malnutrition
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Institut de Recherche en Sciences de la Sante, Burkina Faso
First posted: 2021-07-20
Enrollment: 310
Sex: ALL
Minimum age (years): 6
Maximum age (years): 10
Standard ages: CHILD
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The target population will be children residing in the catchment areas of study health facilities within Bobo-Dioulasso, Burkina Faso.

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Risk of parasitemia
timeFrame: during the seasonal SMC campaign period over three years
measure: Prevalence of antimalarial resistance markers associated with SP
timeFrame: during the seasonal SMC campaign period over three years
measure: Prevalence of antimalarial resistance markers associated with AQ
timeFrame: during the seasonal SMC campaign period over three years
Secondary outcomes:
Other outcomes:
Locations:
city: Bobo-Dioulasso
country: Burkina Faso
facility: Colsama Health Facility
city: Bobo-Dioulasso
country: Burkina Faso
facility: Sakaby Health Facility
Study officials:
affiliation: University of California, San Francisco
name: Philip Rosenthal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut de Recherche en Sciences de la Santé, Burkina Faso
name: Jean-Bosco Ouédraogo, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Roh ME, Zongo I, Haro A, Huang L, Some AF, Yerbanga RS, Conrad MD, Wallender E, Legac J, Aweeka F, Ouedraogo JB, Rosenthal PJ. Seasonal Malaria Chemoprevention Drug Levels and Drug Resistance Markers in Children With or Without Malaria in Burkina Faso: A Case-Control Study. J Infect Dis. 2023 Oct 3;228(7):926-935. doi: 10.1093/infdis/jiad172.