Estimating the window of selection of antimalarial drugs using field data

Excerpt

Drug resistance spreads through a population because (i) parasites can survive direct treatment and/or (ii) survive “residual” drug levels persisting from previous treatment. High levels of drug use and long drug half-lives mean a high proportion of the population may have residual drug levels selecting for resistance. Field studies can quantify this second force of resistance by estimating a window of selection (WoS); a period of time during which drug levels have declined sufficiently to allow new infections with drug resistant parasites while still able to prevent infections by drug sensitive parasites. Typically this is estimated by comparing how early different genotypes become detectable after treatment. These WoS estimates are widely cited and we refer to them as ‘apparent’ WoS to denote their origin in clinical observations. In fact the ‘true’ WoS is the period in which infections bearing the mutation can emerge from the liver and survive to produce a patent infection while sensitive parasites are killed by residual drug concentrations. Unfortunately, it is impossible to observe this emergence because parasites (assuming 105 emerge) are below the microscopic limit of detection (assumed to be 10⁸) and so we are forced to rely on ‘apparent’ WoS i.e., the time at which they have grown to patency. …