Malaria in the Greater Mekong Subregion (GMS) of Southeast Asia remains an important public health problem. There is immense spatial heterogeneity in malaria distribution, with Myanmar having the highest regional malaria burden. Highly mobile populations crossing porous international borders are a major contributor to parasite introduction and continued transmission. The recent emergence of resistance to the artemisinin (ART) family of drugs as well as to their partner drugs raised global concerns. The vectorial system is highly diverse, and increased outdoor biting and development of insecticide resistance have rendered the two core vector control interventions ? insecticide-treated nets and indoor residue spray less effective. Furthermore, falsified and substandard ART-based combination therapies (ACTs) have become a global crisis. Therefore, the central goal of this program is to improve our understanding of how mobile human populations, parasite drug resistance, and mosquito biology contribute to continuous malaria transmission at international borders so that innovative control strategies can be developed to propel the course of regional malaria elimination. To achieve this overarching objective, we have selected study sites in the international border regions of three GMS countries, Myanmar, China, and Thailand, with drastically different malaria epidemiology to conduct comprehensive research on humans, vectors, and parasites in four interrelated projects. In Project 1, the foundation of the whole program, we will conduct malaria surveillance, monitor human migration and its impact on parasite introduction, and evaluate the effectiveness of the current treatment of the predominant P. vivax malaria. Project 2 will study how environmental changes affect mosquito community structures and malaria transmission, identify whether behavioral changes of major vectors are genetically determined, and determine the extent and mechanisms of insecticide resistance in malaria vectors. In Project 3, we will address the emerging problem of resistance of P. falciparum to both the ART family of drugs and partner drugs through molecular studies of resistance mechanisms and by tracking resistance spread in the GMS. Finally, we want to develop monoclonal antibody-based immunoassays to detect both active ingredients in an ACT, and use our newly developed point-of-care dipstick assays for large-scale assessment of the extent of problem of the falsified and substandard ACTs in the GMS countries using a stratified random sampling approach. This program, built on the scientific achievements of the current ICEMR program and the strong network of international collaborators, aims to dissect the complex interactions between migrant human populations, diverse mosquito vectors, MDR parasites, and falsified and substandard ACTs, which are responsible for continued malaria transmission along international borders. These scientific questions are not only pertinent to the GMS nations, but are also applicable to other malaria regions. Therefore, findings from these studies will bear far-reaching impacts on global malaria elimination.

Public Health Relevance

Program Narrative Malaria is a significant public health problem and impediment to socioeconomic development in the Greater Mekong Subregion (GMS) of Southeast Asia. As all GMS nations are moving toward malaria elimination, they face a daunting array of technical challenges, including persistent transmission of malaria along international borders, a complex and changing vectorial system that renders conventional vector control measures less effective, emerging resistance of the malaria parasite Plasmodium falciparum to artemisinins and the partner drugs of artemisinin-based combination therapies (ACTs), and circulation of falsified and substandard ACTs. This interdisciplinary program aims to address these urgent problems through comprehensive research along international borders of three select GMS countries, Myanmar, China, and Thailand, using a series of innovative technologies and approaches. Altogether, the proposed four projects of this center will elucidate the factors and underlying mechanisms contributing to continuous malaria transmission in the border regions. This knowledge will be deemed essential for developing innovative malaria control strategies to achieve regional malaria elimination.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI089672-12
Application #
9915839
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Rao, Malla R
Project Start
2010-07-01
Project End
2024-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
12
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of South Florida
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
069687242
City
Tampa
State
FL
Country
United States
Zip Code
33617
Deng, Zeshuai; Li, Qing; Yi, Haoan et al. (2018) Hemoglobin E protects against acute Plasmodium vivax infections in a Kachin population at the China-Myanmar border. J Infect 77:435-439
Zhong, Daibin; Koepfli, Cristian; Cui, Liwang et al. (2018) Molecular approaches to determine the multiplicity of Plasmodium infections. Malar J 17:172
Bunditvorapoom, Duangkamon; Kochakarn, Theerarat; Kotanan, Namfon et al. (2018) Fitness Loss under Amino Acid Starvation in Artemisinin-Resistant Plasmodium falciparum Isolates from Cambodia. Sci Rep 8:12622
Siddiqui, Faiza A; Cabrera, Mynthia; Wang, Meilian et al. (2018) Plasmodium falciparum Falcipain-2a Polymorphisms in Southeast Asia and Their Association With Artemisinin Resistance. J Infect Dis 218:434-442
Yang, Henglin; Wang, Jingyan; Liu, Hui et al. (2018) Randomized, Double-Blind, Placebo-Controlled Studies to Assess Safety and Prophylactic Efficacy of Naphthoquine-Azithromycin Combination for Malaria Prophylaxis in Southeast Asia. Antimicrob Agents Chemother 62:
Chaverra-Rodriguez, Duverney; Macias, Vanessa M; Hughes, Grant L et al. (2018) Targeted delivery of CRISPR-Cas9 ribonucleoprotein into arthropod ovaries for heritable germline gene editing. Nat Commun 9:3008
Mbenda, Huguette Gaelle Ngassa; Zeng, Weilin; Bai, Yao et al. (2018) Genetic diversity of the Plasmodium vivax phosphatidylinositol 3-kinase gene in two regions of the China-Myanmar border. Infect Genet Evol 61:45-52
Bai, Yao; Zhang, Jiaqi; Geng, Jinting et al. (2018) Longitudinal surveillance of drug resistance in Plasmodium falciparum isolates from the China-Myanmar border reveals persistent circulation of multidrug resistant parasites. Int J Parasitol Drugs Drug Resist 8:320-328
Zhao, Yan; Zeng, Jie; Zhao, Yonghong et al. (2018) Risk factors for asymptomatic malaria infections from seasonal cross-sectional surveys along the China-Myanmar border. Malar J 17:247
Miao, Jun; Chen, Zhao; Wang, Zenglei et al. (2017) Sex-Specific Biology of the Human Malaria Parasite Revealed from the Proteomes of Mature Male and Female Gametocytes. Mol Cell Proteomics 16:537-551

Showing the most recent 10 out of 115 publications