>>The evolution of drug resistance and the curious orthodoxy of aggressive chemotherapy
Andrew F. Reada,b,1, Troy Dayc, and Silvie Huijbena
+ Author Affiliations
aCenter for Infectious Disease Dynamics, Departments of Biology and Entomology, Pennsylvania State University, University Park, PA 16802;
bFogarty International Center, National Institutes of Health, Bethesda, MD 20892; and
cDepartments of Mathematics, Statistics, and Biology, Queen's University, Kingston, ON, Canada K7L 3N6
Edited by John C. Avise, University of California, Irvine, CA, and approved April 13, 2011 (received for review February 13, 2011)
Abstract
The evolution of drug-resistant pathogens is a major challenge for 21st century medicine. Drug use practices vigorously advocated as resistance management tools by professional bodies, public health agencies, and medical schools represent some of humankind's largest attempts to manage evolution. It is our contention that these practices have poor theoretical and empirical justification for a broad spectrum of diseases. For instance, rapid elimination of pathogens can reduce the probability that de novo resistance mutations occur. This idea often motivates the medical orthodoxy that patients should complete drug courses even when they no longer feel sick. Yet “radical pathogen cure” maximizes the evolutionary advantage of any resistant pathogens that are present. It could promote the very evolution it is intended to retard. The guiding principle should be to impose no more selection than is absolutely necessary. We illustrate these arguments in the context of malaria; they likely apply to a wide range of infections as well as cancer and public health insecticides. Intuition is unreliable even in simple evolutionary contexts; in a social milieu where in-host competition can radically alter the fitness costs and benefits of resistance, expert opinion will be insufficient. An evidence-based approach to resistance management is required.<<
Full text freebie here:
pnas.org
Controversial paper; see Derek Lowe's blog and comments:
pipeline.corante.com
Is that our Rick at comment #18? Sure looks like his writing style.
Cheers, Tuck |
