Artemisinin-based combination therapies (ACTs) play an essential 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 active ingredients are life-threatening, while substandard drugs encourage resistance development. The scale of this 'lethal problem'is particularly 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 nations. For this purpose, fast and reliable methods of artemisinin detection and quantitation 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 sensitive and variable. Based on our recent success of developing a highly sensitive and reliable enzyme-linked immunosorbent assay (ELISA) using a specific monoclonal antibody 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 dipstick assay for rapid, semi-quantitative analysis of artemisinins in antimalarial drugs, 3) perform systematic field surveys of the drug quality of artemisinin-based antimalarial 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 quantification of artemisinins and rapid detection of counterfeit and substandard artemisinin derivative drugs, contributing to antimalarial 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-quantitative analysis of artemisinins in antimalarial drugs under field conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI089672-05
Application #
8691669
Study Section
Special Emphasis Panel (ZAI1-AWA-M)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
5
Fiscal Year
2014
Total Cost
$103,778
Indirect Cost
$12,233
Name
Pennsylvania State University
Department
Type
DUNS #
003403953
City
University Park
State
PA
Country
United States
Zip Code
16802
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