Antimalarial Drug Resistance in Mali

Summary

Resistance of Plasmodium falciparum (malaria) to current antimalarial drugs and the continuing development of resistance to new antimalarial formulations is one of the major obstacles to effective malaria control and case management. Efficient, comprehensive and validated methods for monitoring drug resistance in advance of the development of resistance to the antimalarial drugs that are in use are urgently needed. Molecular markers of genetic polymorphisms that give rise to resistant P. falciparum parasites and methods in population genetics for evaluating the data can be valuable tools for monitoring drug resistance in the field. This study aims to:

1. Prospectively measure the in vivo response of P. falciparum malaria in Mali to several different antimalarial drugs and drug combinations: chloroquine (CQ), sulfadoxine-pyrimethamine (SP), amodiaquine (AQ), sulfadoxine-pyrimethamine in combination with amodiaquine (SP/AQ), amodiaquine in combination with artesunate (AQ/AS), sulfadoxine-pyrimethamine in combination with artesunate (SP/AS), and artemether-lumefantrine (Co-artem). In one site with preliminary data showing a high rate of P. falciparum resistance to mefloquine (MQ), this drug will also be tested.
2. Measure the frequencies of molecular markers for antimalarial drug resistance, and examine how those results relate to the efficacy of these drugs in treating clinical malaria
3. Measure drug levels at 3 days and correlate with efficacy results.
4. Examine early clinical, parasitologic, and clinical predictors of late treatment failure.
5. Use the knowledge gained in Aims 1-3 to develop a molecular tool for a countrywide resistance surveillance system for antimalarial drugs.

Conditions

• Malaria

Interventions

DRUG

chloroquine

DRUG

sulfadoxine-pyrimethamine

DRUG

amodiaquine

DRUG

amodiaquine+artesunate

DRUG

amodiaquine+sulfadoxine-pyrimethamine

DRUG

sulfadoxine-pyrimethamine+artesunate

DRUG

artemether-lumefantrine

DRUG

mefloquine

Sponsors & Collaborators

• Malaria Research and Training Center, Bamako, Mali

  collaborator OTHER

• Centers for Disease Control and Prevention

  lead FED

Principal Investigators

• Robert D. Newman, MD, MPH · Centers for Disease Control and Prevention

• Kassoum Kayentao, MD, MSPH · Malaria Research and Training Center, Bamako, Mali

• John Barnwell, PhD, MPH · Centers for Disease Control and Prevention

• Ogobara Doumbo, MD, PhD · Malaria Research and Training Center, Bamako, Mali

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

6 Months

Max Age

59 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2005-07-31

Countries

• Mali

Study Locations