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Table 1 Resistance associated factors

From: A framework for assessing the risk of resistance for anti-malarials in development

Factor

Level of action

Variables

Drug mode-of-action

Parasite

Target nature (cellular process, protein, other).

Target gene localization (nuclear or mitochondrial genome).

Drug subcellular localization (vacuole, organelle, cytoplasm).

Resistance mode-of-action

Parasite

Target mutation rate.

Nature of mutations required for resistance (single nt, in/del, copy number).

Number of mutations required for resistance (causal and compensating).

Fitness

Human host

Growth rate of resistant parasite (within host competition)

Effect of drug on gametocytogenesis and gametocyte viability.

Effect of resistance mutations on gametocytogenesis and gametocyte viability.

Drug pharmacokinetic

Human host

Clinical parasite reduction ratio

Drug half-life

Drug dosage

Drug deployment

Human population

Drug pressure

Drug combination

Parasite transmission intensity

  

Human population immunity