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The Trager Lectures
A Symposium to Honor a Lifetime of Contributions by Dr. William Trager to the Study of Malaria
Saturday, June 18, 2005 - Lillie Auditorium, 2:00 PM.
Investigations into the molecular basis of chloroquine resistance in the malaria parasite Plasmodium falciparum
David Fidock, Ph.D., Associate Professor, Department of Microbiology and Immunology, Albert Einstein College of Medicine of Yeshiva University
Lecture Abstract:
Of all the infectious diseases afflicting children, malaria has the deadliest impact, with over 1 million children in Africa estimated to die from Plasmodium falciparum malaria each year. Earlier efforts to control and treat malaria were largely founded on the use of chloroquine, a cheap, safe and rapidly effective antimalarial. Yet resistance to this drug appeared in Asia and South America and has since spread around the globe. In Africa, the dissemination of CQ-resistant P. falciparum has been associated with significant increases in malaria mortality and morbidity.
The analysis of a genetic cross has recently led to the identification of the primary gene responsible for CQ resistance (CQR). This gene, termed pfcrt (Plasmodium falciparum chloroquine resistance transporter), encodes multiple mutations that cluster into geographically distinct origins, consistent with the appearance of CQR in a handful of locations around the world. Genetic transformation studies have now definitively proven that mutant pfcrt can confer CQR to CQ-sensitive P. falciparum. Recent studies now demonstrate that CQR is entirely dependent on the pfcrt K76T mutation, which is conserved in all laboratory-adapted CQ-resistant isolates studied to date. This K76T marker has become an invaluable marker to rapidly assess the extent of CQR in endemic areas and predict the degree of CQ efficacy. This mutation appears to control CQ access to its heme receptor, inside the acidic digestive vacuole of the intra-erythrocytic parasite. Ongoing genetic, functional and clinical studies are revealing the molecular basis of CQR and are helping elaborate new strategies to more efficiently detect and treat drug-resistant P. falciparum infections.
David A. Fidock is an Associate Professor in the department of Microbiology and Immunology at the Albert Einstein College of Medicine. He received a B.Sc. in Genetics and Computer Science from Adelaide University, South Australia in 1985 and a Ph.D. in Microbiology from the Pasteur Institute in Paris in 1994. Dr. Fidock was a post-doctoral fellow in the laboratory of Dr. Anthony James at the University of California, Irvine from 1995 to 1996 and a post-doctoral fellow in the laboratory of Dr. Thomas Wellems at the National Institute of Allergy and Infectious Diseases from 1996 to 1999. In 2000, after completing his post-doctoral fellowships, Dr. Fidock joined the faculty of the Albert Einstein College of Medicine. He has received several honors, scholarships, and awards including the Speaker’s Fund in Biomedical Research from the New York Academy of Medicine and a New Scholar award in Global Infectious Diseases from the Ellison Medical Foundation. In 2003 he was designated an Investigator in Pathogenesis of Infectious Disease from the Burroughs Wellcome Fund.
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