Artemisinin-based combination therapies (ACTs) play an essenfial role in the current malaria control and elimination campaign. However, the circulation of counterfeit and substandard artemisinins greatly threatens the malaria control efforts. Fake artemisinins containing no or little acfive ingredients are life-threatening, while substandard drugs encourage resistance development. The scale of this 'lethal problem'is particulariy huge in some Southeast Asian countries, where as much as 64% of the artesunate sold on the market was fake. To prolong the life span of artemisinin drugs for treating malaria, strict drug quality control needs to be implemented in these nafions. For this purpose, fast and reliable methods of artemisinin detection and quanfitation are needed. Traditional methods for quantitation of artemisinins often require expensive instruments and substantial technical support, whereas the rapid qualitative method for screening of fake artemisinin derivatives is less sensifive and variable. Based on our recent success of developing a highly sensifive and reliable enzyme-linked immunosorbent assay (ELISA) using a specific monoclonal anfibody against artemisinins, we propose to 1) develop a series of monoclonal antibodies with specificities for the major artemisinin derivatives (dihydroartemisinin, artemether, arteether, and artesunate) using an innovative design of immunogens, 2) develop and optimize an ELISA for accurate quantification of artemisinins, and a lateral flow dipsfick assay for rapid, semi-quanfitafive analysis of artemisinins in anfimalarial drugs, 3) perform systematic field surveys of the drug quality of artemisinin-based anfimalarial medicines in three Southeast Asian countries using these new tools, and 4) optimize the ELISA conditions so that it can be used as an alternative tool for quantification of artemisinins and its derivatives in pharmacokinetic studies. These immunoassays will offer convenient tools for both accurate quanfificafion of artemisinins and rapid detecfion of counterfeit and substandard artemisinin derivative drugs, contribufing to anfimalarial drug quality control.

Public Health Relevance

The prevalence of counterfeit and substandard artemisinin drugs is a big threat to the success of the malaria control campaign. In response to this escalating problem, we want to design two convenient, monoclonal antibody-based immunoassays for accurate quantification of artemisinin derivatives in laboratories and rapid, semi-quanfitative analysis of artemisinins in antimalarial drugs under field condifions.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Pennsylvania State University
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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
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
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

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