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

August 9, 2023 updated by: University of California, San Francisco

Associations Between Drug Levels and the Risk of Malaria and Drug Resistance in the Setting of Seasonal Malaria Chemoprevention in Bobo-Dioulasso, Burkina Faso

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.

Study Overview

Status

Completed

Conditions

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.

Study Type

Observational

Enrollment (Actual)

310

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Burkina Faso
      • Bobo-Dioulasso, Burkina Faso
        • Colsama Health Facility
      • Bobo-Dioulasso, Burkina Faso
        • Sakaby Health Facility

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 10 years (Child)

Accepts Healthy Volunteers

N/A

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Risk of parasitemia
Time Frame: during the seasonal SMC campaign period over three years
Detected by blood smear microscopy
during the seasonal SMC campaign period over three years
Prevalence of antimalarial resistance markers associated with SP
Time Frame: during the seasonal SMC campaign period over three years
Prevalence of pfdhfr and pfdhps mutations
during the seasonal SMC campaign period over three years
Prevalence of antimalarial resistance markers associated with AQ
Time Frame: during the seasonal SMC campaign period over three years
Prevalence of pfcrt and pfmdr1 mutations
during the seasonal SMC campaign period over three years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

Institut de Recherche en Sciences de la Sante, Burkina Faso

Investigators

  • Principal Investigator: Philip Rosenthal, MD, University of California, San Francisco
  • Principal Investigator: Jean-Bosco Ouédraogo, MD PhD, Institut de Recherche en Sciences de la Sante, Burkina Faso

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 16, 2021

Primary Completion (Actual)

November 30, 2021

Study Completion (Actual)

May 23, 2023

Study Registration Dates

First Submitted

July 9, 2021

First Submitted That Met QC Criteria

July 9, 2021

First Posted (Actual)

July 20, 2021

Study Record Updates

Last Update Posted (Actual)

August 14, 2023

Last Update Submitted That Met QC Criteria

August 9, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 21-33890

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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