Figure 1. Simulated Plots of Weekly Incidence Rates and Cumulative Proportions for Recrudescent Primary Infections and Re-Infections Following Treatment of Uncomplicated P. falciparum Malaria with a Slowly Eliminated (Partner) Drug (Half-Life of ~1 Week).

The solid line represents recrudescent infections with a cumulative failure rate of 5% by day 42. Dashed lines represent different rates of re-infections corresponding to entomological inoculation rates of two (yellow), four (orange), and six (red) infective mosquito bites/year, respectively. Trailing plasma drug concentrations delay both detectable recrudescent primary and secondary blood stage infections—however, both effects are fading until day 42. Figure 1A illustrates that most recrudescent primary infections are captured by day 42. Extension of follow-up beyond day 28 results in increased ratios of new versus recrudescent infections and hence, elevated risk of outcome misclassifications due to intrinsic limitations of current molecular techniques used to discriminate between primary and secondary infections. The assessment of the total number of recurrent infections as a composite outcome (often denoted the PCR “uncorrected cure rate”) requires some time limits as re-infection occurs eventually in almost everyone after blood concentrations of the drug(s) fall below the MIC (Figure 1B).