Artemisinin-based combination therapies (ACTs) as the frontline treatment of uncomplicated Plasmodium falciparum malaria have played an indispensable role in reducing the global malaria burden. Thus, the circulation of falsified and substandard ACTs has become an emerging global crisis, which greatly threatens the gain made in malaria control. Yet, the extent of this problem is not known and there is a pressing need for systematic surveillance efforts of falsified ACTs. Since traditional methods for quality control of ACTs mostly require expensive instruments and substantial technical support, the development of a point-of-care (POC) test for the detection of the active ingredients in ACTs under endemic settings is highly desired. In addition, as many malaria-endemic nations are moving towards malaria elimination, mass drug administration (MDA) and seasonal malaria chemoprevention (SMC) programs are being increasingly deployed. A cheap and higher- throughput assay that could be used to measure the serum levels of the long-lasting ACT partner drugs will allow cost-effective assessment of the coverage and compliance rates in the MDA and SMC programs. To address these needs, we developed highly sensitive and reliable enzyme-linked immunosorbent assays (ELISAs) for accurate quantitation of artemisinin and its derivatives. We further developed an antibody-based dipstick assay as a POC test for qualitative and semi-quantitative evaluation of ART and its derivatives in ACT drugs, which have been pilot-tested to be fast, convenient, and easy to perform in endemic sites. Based on these recent successes, we propose to 1) use the new POC diagnostic tools to systematically investigate the extent of falsified artemisinin drugs in the Greater Mekong Subregion, where the problem had been most serious, 2) to develop a series of specific monoclonal antibodies for three ACT partner drugs using an innovative design of immunogens, and 3) develop and optimize ELISAs and dipsticks for quantification and detection of ACT partner drugs in both commercial drugs and human plasma. We anticipate that the ELISAs will provide highly convenient tools for accurate quantification of active pharmaceutical ingredients in ACTs in the laboratory, while the combination dipsticks offer POC devices for quality control of ACTs in remote endemic settings.
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