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.
Phase:
N/A
Details
Lead Sponsor:
Centers for Disease Control and Prevention
Collaborator:
Malaria Research and Training Center, Bamako, Mali
Treatments:
Amodiaquine Amodiaquine, artesunate drug combination Antimalarials Artemether Artemether-lumefantrine combination Artemether, Lumefantrine Drug Combination Artemisinins Artesunate Chloroquine Fanasil, pyrimethamine drug combination Lumefantrine Mefloquine Pyrimethamine Sulfadoxine