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

NCT04969185 | Completed

• 1 other identifier: 21-33890
• Study Type: observational
• Target: 310
• Locations: 1 country
• Sites: 2

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.

Conditions

Malaria,Falciparum

Keywords

seasonal malaria chemoprevention; sulfadoxine-pyrimethamine; amodiaquine; antimalarial resistance; pharmacokinetics; falciparum malaria; malnutrition

Outcome Measures

Primary Outcomes (3)

• Risk of parasitemia

  Detected by blood smear microscopy

  during the seasonal SMC campaign period over three years

• Prevalence of antimalarial resistance markers associated with SP

  Prevalence of pfdhfr and pfdhps mutations

  during the seasonal SMC campaign period over three years

• Prevalence of antimalarial resistance markers associated with AQ

  Prevalence of pfcrt and pfmdr1 mutations

  during the seasonal SMC campaign period over three years

Study Arms (3)

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

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

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

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.

Eligibility Criteria

• Age: 6 Months - 10 Years
• Sex: all
• Age Groups: Child (0-17)
• 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.

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• Institut de Recherche en Sciences de la Sante, Burkina Faso: collaborator

Study Sites (2)

Colsama Health Facility

Bobo-Dioulasso, Burkina Faso

Location

Sakaby Health Facility

Bobo-Dioulasso, Burkina Faso

Location

Related Publications (1)

• 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.

  PMID: 37221018 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples will be used to determine: (1) the levels of exposure to SDX, PYR, and AQ; (2) presence of malaria parasitemia; and (3) characterize markers of antimalarial drug resistance

MeSH Terms

Conditions

Malaria, Falciparum; Malnutrition

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Nutrition Disorders; Nutritional and Metabolic Diseases

Study Officials

• Philip Rosenthal, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Jean-Bosco Ouédraogo, MD PhD

  Institut de Recherche en Sciences de la Santé, Burkina Faso

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2021
• First Posted: July 20, 2021
• Study Start: August 16, 2021
• Primary Completion: November 30, 2021
• Study Completion: May 23, 2023
• Last Updated: August 14, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

BU (2)