Characterization of Novel Molecular Tools for the Epidemiological Surveillance of Antimalarial Drug Resistance in Mali

NCT00127998 NA COMPLETED

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.

Details

Lead sponsor	Centers for Disease Control and Prevention
Phase	NA
Status	COMPLETED
Enrolment	1011
Start date	2005-07

Conditions

• Malaria

Interventions

• chloroquine
• sulfadoxine-pyrimethamine
• amodiaquine
• amodiaquine+artesunate
• amodiaquine+sulfadoxine-pyrimethamine
• sulfadoxine-pyrimethamine+artesunate
• artemether-lumefantrine
• mefloquine

Primary outcomes

• Early Treatment Failure (ETF, defined as: Development of danger signs or severe malaria on Day 1, 2, or 3, in the presence of parasitemia
• Parasitemia on Day 2 higher than Day 0 count irrespective of axillary temperature
• Parasitemia on Day 3 with axillary temperature ≥37.5°C
• Parasitemia on Day 3 ≥ 25% of count on Day 0
• Late Clinical Failure (LCF), defined as: Development of danger signs or severe malaria from Day 4 to Day 28 in the presence of parasitemia, without previously meeting any of the criteria of ETF
• Presence of parasitemia and axillary temperature ≥37.5° C on any day from Day 4 to Day 28, without previously meeting any of the criteria of ETF

Countries

Mali