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Impaired fitness of drug-resistant malaria parasites: evidence and implication on drug-deployment policies

Babiker, H. A., Hastings, Ian and Swedberg, G. (2009) 'Impaired fitness of drug-resistant malaria parasites: evidence and implication on drug-deployment policies'. Expert Review of Anti-Infective Therapy, Vol 7, Issue 5, pp. 581-593.

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Abstract

Malaria, a leading parasitic disease, inflicts an enormous toll on human lives and is caused by protozoal parasites belonging to the genus Plasmodium. Antimalarial drugs targeting essential biochemical processes in the parasite are the primary resources for management and control. However, the parasite has established mutations, substantially reducing the efficacy of these drugs. First-line therapy is faced the with the consistent evolution of drug-resistant genotypes carrying these mutations. However, drug-resistant genotypes are likely to be less fit than the wild-type, suggesting that they might disappear by reducing the volume of drug pressure. A substantial body of epidemiological evidence confirmed that the frequency of resistant genotypes wanes when active drug selection declines. Drug selection on the parasite genome that removes genetic variation in the vicinity of drug-resistant genes (hitch-hiking) is common among resistant parasites in the field. This can further disadvantage drug-resistant strains and limit their variability in the face of a mounting immune response. Attempts to provide unequivocal evidence for the fitness cost of drug resistance have monitored the outcomes of laboratory competition experiments of deliberate mixtures of sensitive and resistant strains, in the absence of drug pressure, using isogenic clones produced either by drug selection or gene manipulation. Some of these experiments provided inconclusive results, but they all suggested reduced fitness of drug-resistant clones in the absence of drug pressure. In addition, biochemical analyses provided clearer information demonstrating that the mutation of some anti malarial-targeted enzymes lowers their activity compared with the wild-type enzyme. Here, we review current evidences for the disadvantage of drug-resistance mutations, and discuss some strategies of drug deployment to maximize the cost of resistance and limit its spread.

Item Type: Article
Additional Information: chloroquine drug-resistant genotype fitness cost Plasmodium chabaudi Plasmodium falciparum pyrimethamine sulfadoxine
Subjects: WC Communicable Diseases > Tropical and Parasitic Diseases > WC 680 Tropical diseases (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors
WB Practice of Medicine > Medical Climatology > WB 710 Diseases of geographic areas
QX Parasitology > Protozoa > QX 50 Protozoa
QW Microbiology and Immunology > QW 4 General works. Classify here works on microbiology as a whole.
QX Parasitology > Protozoa > QX 135 Plasmodia
QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified.
QX Parasitology > Insects. Other Parasites > QX 510 Mosquitoes
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 695 Parasitic diseases (General)
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1586/eri.09.29
Depositing User: Mary Creegan
Date Deposited: 29 Mar 2010 11:27
Last Modified: 06 Feb 2018 12:59
URI: http://archive.lstmed.ac.uk/id/eprint/227

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