Antimalarial Drug Resistance in Mali

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

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

Criteria

Inclusion Criteria:

• Aged 6-59 months

• Absence of severe malnutrition (defined as a child whose weight-for-height is below 3 standard deviations of less than 70% of the median of World Health Organization (WHO) reference values, or who has symmetrical edema involving at least the feet)

• A slide-confirmed infection with P. falciparum only (i.e. no mixed infections)

• Initial parasite density between 2,000 and 200,000 asexual parasites per microliter.

• Absence of general danger signs among children < 5 years (inability to drink or breastfeed; vomiting everything; recent history of convulsions; lethargy or unconsciousness; inability to sit or stand up) or other signs of severe and complicated falciparum malaria according to WHO definitions

• Measured axillary temperature ≥ 37.5 °C

• Ability to attend stipulated follow-up visits

• Informed consent provided by parent/guardian

• Absence of history of hypersensitivity reactions to any of the drugs being evaluated

Exclusion Criteria:

• Aged < 6 or >59 months

• Severe malnutrition (defined as a child whose weight-for-height is below 3 standard deviations of less than 70% of the median of WHO reference values, or who has symmetrical edema involving at least the feet)

• No slide confirmed infection with P. falciparum or a mixed infection that includes a non P. falciparum species

• Initial parasite density < 2,000 or > 200,000 asexual parasites per microliter.

• Presence of general danger signs among children < 5 years (inability to drink or breastfeed; vomiting everything; recent history of convulsions; lethargy or unconsciousness; inability to sit or stand up) or other signs of severe and complicated falciparum malaria according to WHO definitions

• Measured axillary temperature <37.5 °C

• Inability to attend stipulated follow-up visits

• Unwilling to provide informed consent provided by parent/guardian

• History of hypersensitivity reactions to any of the drugs being evaluated