DESCRIPTION (provided by applicant): The World Health Organization (WHO) is coordinating an aggressive effort to contain artemisinin resistant Plasmodium falciparum malaria in Southeast Asia before it spreads from its recent site of emergence in Western Cambodia. This containment effort is hampered by the lack of surveillance tools to track the extent and direction of the spread of resistance from its focus of origin. Molecular resistance markers such as those used to detect resistance to chloroquine and other antimalarial drugs are not yet available for artemisinin resistance. Without such markers, the only means of mapping artemisinin resistance is to perform clinical trials of artesunate monotherapy, limiting the comprehensiveness and timeliness of resistance data needed to guide containment efforts. A molecular marker of artemisinin resistance would therefore be valuable for surveillance of resistance in Myanmar (formerly known as Burma), the country with the most malaria of any in the region. We propose to work with scientists in Myanmar to conduct a pilot study of P. falciparum population structure and gene flow in preparation for subsequent studies to validate candidate artemisinin resistance markers. We will collect and analyze filter paper blood samples from P. falciparum-infected individuals at several sites across Myanmar. Sources of samples will include archived samples from completed and separately funded antimalarial drug efficacy studies, and an observational cross-sectional survey. DNA extracted from these samples will be subjected to parasite population genetics analyses to measure the extent of population structure and gene flow, information that will be useful in guiding resistance containment efforts. We will also analyze samples for the presence of molecular markers of resistance to artemisinin-based combination therapy (ACT) partner drugs and, as they become available, emerging candidate markers of artemisinin resistance. This pilot study will generate useful data on the extent and prevalence of known resistance markers, and lay the groundwork to help to validate new candidate markers as predictors of clinical resistance. Moreover this project will build a foundation for subsequent research collaboration between the U.S. and Myanmar aimed at validating artemisinin resistance markers with support from future R01 and other grants. To our knowledge this will be the first NIH grant awarded to work directly inside Myanmar, a country of major importance to malaria control and drug resistance containment efforts in Asia. The project will be conducted in collaboration with molecular and clinical investigators at the WHO Collaborating Center for Research and Training on Malaria in the Department of Medical Research, Lower Myanmar. This work is expected to contribute to the development of robust surveillance tools that can be used to track and contain artemisinin resistance in Southeast Asia and elsewhere.

Newly emerging drug-resistant malaria may have spread to the Southeast Asian country of Myanmar, the country with the most malaria of any in the region. This pilot project aims to collect preliminary data on the genetic population structure of Plasmodium falciparum malaria in Myanmar, providing information that will help to guide malaria control and target drug resistance containment efforts. We will also begin to validate candidate molecular markers for resistance to artemisinins and other antimalarial drugs, providing a foundation for subsequent, more comprehensive studies.