Graduation Year

2009

Document Type

Thesis

Degree

M.S.P.H.

Degree Granting Department

Global Health

Major Professor

Dennis Kyle, Ph.D.

Keywords

SYBR green, Plasmodium falciparum, Resistance, ACTs, Artemisinin

Abstract

Plasmodium falciparum, one of the parasites that cause clinical malaria, is a continuous public health concern, especially in Asia and Africa. Unfortunately, the parasite has developed resistance to many drugs created to treat and prevent the disease. Artemisinin and its derivatives are the new gold standard for treatment of malaria, yet treatment failures in clinical studies are starting to be reported. Clearly, artemisinin resistance needs to be characterized and dealt with accordingly. In support of the Gates Foundation Artemisinin Consortium, we conducted a blinded study to elucidate the phenotypic response of artemisinin derivatives of parasites derived from patient blood samples from Cambodia and Thailand. Blood samples containing Plasmodium falciparum were cultured and then assayed using SYBR green as an indicator to obtain drug IC50s. The data suggested that many isolates are not demonstrating resistance to artemisinin. However, a select few are showing some resistant characteristics in the form of elevated IC 50s, especially to some of the drugs already identified in previous studies as drugs having resistant characteristics. Compared to studies conducted within the past ten years, no significant changes in parasite susceptibility to the artemisinin drugs have been observed. Additional analysis of clinical outcomes, therapeutic drug levels, and molecular markers needs to be completed before it can be assumed that artemisinin resistance has emerged.

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