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Tolerance is the key to understanding antimalarial drug resistance

Ian M Hastings1, William M Watkins

  • 1Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK. hastings@liverpool.ac.uk

Trends in Parasitology
|January 13, 2006
PubMed

Insights

Antimalarial drug resistance is more complex than a simple sensitive or resistant state. A crucial intermediate stage of drug tolerance allows parasites to spread, impacting malaria evolution.

Area of Science:

  • Malariology
  • Parasitology
  • Evolutionary Biology

Background:

  • Antimalarial drug resistance is typically viewed as a binary process (sensitive vs. resistant).
  • This overlooks the critical intermediate stage of drug tolerance in malaria parasites.
  • Drug tolerance presents unique challenges for malaria control strategies.

Purpose of the Study:

  • To highlight the significance of drug tolerance in the evolution of antimalarial drug resistance.
  • To explain the mechanism by which drug-tolerant malaria parasites can persist and spread.
  • To underscore the implications of this intermediate stage for malaria treatment and eradication.

Main Methods:

  • Conceptual analysis of parasite resistance evolution.
  • Review of pharmacokinetic and pharmacodynamic principles of antimalarial drugs.
  • Modeling parasite population dynamics under drug pressure.

Main Results:

  • Drug-tolerant malaria parasites survive sub-curative drug concentrations present post-treatment.
  • These tolerant parasites can infect new hosts, facilitating their propagation.
  • The persistence of residual drug levels enables the spread of tolerant strains.

Conclusions:

  • Drug tolerance represents a crucial, often underestimated, phase in the development of full antimalarial drug resistance.
  • Understanding and addressing drug tolerance is vital for preventing the emergence and spread of resistant malaria.
  • This intermediate stage has significant implications for global malaria eradication efforts.

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