This involves the assessment of clinical and parasitological outcomes of treatment over a certain period following the start of treatment, to check for the reappearance of parasites in the blood. Reappearance indicates reduced parasite sensitivity to the treatment drug. As a significant proportion of treatment failures do not appear until after day 14, shorter observation periods lead to a considerable overestimation of the efficacy of the tested drug. This is a particular problem at low levels of resistance and with low failure rates. The current recommended duration of follow-up is ≥28 days in areas of high as well as low to moderate transmission. Assessment over only 14 days, the period previously recommended in areas of high transmission, is no longer considered sufficient. Antimalarial treatment should also be assessed on the basis of parasitological cure rates. Where possible, blood or plasma levels of the antimalarial should also be measured in prospective assessments so that drug resistance can be distinguished from treatment failures due to pharmacokinetic reasons.
In high-transmission settings reinfection is inevitable, but cure of malaria (i.e. prevention of recrudescences) is important as it benefits both the patient, by reducing anaemia, and the community, by slowing the emergence and spread of resistance. In the past, "clinical" and "parasitological" cure rates were regarded separately, but with increasing appreciation of the adverse effects of treatment failure, the two are now considered together. Persistence of parasitaemia without fever following treatment has previously not been regarded seriously in high-transmission situations. This still represents a treatment failure and is associated with anaemia. Slowly eliminated antimalarials provide the additional benefit of suppressing malaria infections that are newly acquired during the period in which residual antimalarial drug levels persist in the body. On the other hand, these residual drug levels do provide a selection pressure for resistance. In these treatment recommendations, the curative efficacy of the antimalarials has taken precedence over these considerations.