Application of Pharmacogenomics to Malaria: A Holistic Approach for Successful Chemotherapy

Abstract

Drug resistance in malaria jeopardizes the most elementary objectives of malaria control – reducing suffering and eliminating mortality. An important, and so far the only known, mechanism of drug resistance appears to be polymorphisms in the malaria parasite genes. Efforts to circumvent antimalarial drug resistance now range from the use of combination therapies with existing agents to genomics-based studies directed toward discovering novel targets and agents. However, the potential contribution of host genetic/molecular factors, particularly those associated with antimalarial drug metabolism, remains largely unexplored. Our knowledge concerning the basic mechanisms involved in the pharmacokinetics of antimalarial drugs is fragmentary. In addition, the link between antimalarial drug pharmacokinetics and treatment outcomes is generally unclear. The purpose of this article is to provide general background information on antimalarial drug resistance and associated parasite genetic factors, and subsequently highlight the aforementioned unexplored and unclear areas, with a view to stimulate much needed further research.

KEYWORDS::

• antimalarial drug metabolism
• antimalarial drug resistance
• antimalarial drugs
• artemisinin drugs
• CYP2B6
• malaria
• UGT2B7

Financial & competing interests disclosure

This work was supported mainly by a grant from the National Institutes of Health (AI-52312) to PAZ. RKM was supported, in part, by another grant from the National Institutes of Health (AI-36478 to James Kazura). We are grateful to Carolyn Myers, Dave McNamara, Brian Grimberg, Laurie Gray, Jeana DaRe and Rebekah Benish for their critical comments, which have enriched this manuscript. RKM is thankful to Tim Anderson for his helpful suggestions during the early developmental stages of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported mainly by a grant from the National Institutes of Health (AI-52312) to PAZ. RKM was supported, in part, by another grant from the National Institutes of Health (AI-36478 to James Kazura). We are grateful to Carolyn Myers, Dave McNamara, Brian Grimberg, Laurie Gray, Jeana DaRe and Rebekah Benish for their critical comments, which have enriched this manuscript. RKM is thankful to Tim Anderson for his helpful suggestions during the early developmental stages of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.