Malaria is unusual among the systemic infections of humans in that the number of organisms causing the disease may be quantitated with reasonable precision. This applies particularly to those causing benign human malarias, ie, Plasmodium vivax, P. malariae, and P. ovale, as these parasites are not sequestered in the microcirculation (13). The assessment of parasite burden for the sequestering, potentially lethal parasite P. falciparum is more difficult, but there are some clues which allow a rough estimation of the proportion of parasites circulating in the bloodstream (65). If the number of organisms causing an infection is known, then the pharmacodynamic properties required of an anti-infective drug to produce a cure can be defined. The assessment of the treatment response in malaria rests on the clinical outcome (mortality, speed of recovery from coma, fever clearance, etc.) and the parasitological outcome—the subject of this discussion. Although a great deal remains to be learned about the pharmacodynamic properties of antimalarial drugs in vivo, sufficient information is already available to construct simple models which predict for how long antimalarial treatment should be given and the chances of treatment failure (ie, recrudescence of the infection). In the management of individual patients, the ratio of the parasitemia at the time of treatment to the count 48 h later (the parasite reduction ratio [PRR]), representing the fractional reduction per asexual life cycle, may be a simple but useful predictive index.

General principles. Parasitological recovery from malaria is assessed conventionally by the clearance of parasites from peripheral blood smears (68). In highly drug-resistant infections, parasites do not disappear from the peripheral blood or may increase following the administration of antimalarial drugs. Parasites with lower grades of resistance disappear from the peripheral blood (in fact, the concentration falls below the level of microscopic detection) but recur at a later time, usually in association with a return of symptoms. The efficacy of antimalarial drug treatment is assessed in terms of the speed at which symptoms and signs resolve and parasitemia declines (usually recorded as the parasite clearance time [PCT]) and the proportion of patients in whom infections recur within a defined period (71).