Assessment of therapeutic responses to gametocytocidal drugs in Plasmodium falciparum malaria.

Indirect clinical measures assessing anti-malarial drug transmission-blocking activity in falciparum malaria include measurement of the duration of gametocytaemia, the rate of gametocyte clearance or the area under the gametocytaemia-time curve (AUC). These may provide useful comparative information, but they underestimate dose-response relationships for transmission-blocking activity. Following 8-aminoquinoline administration P. falciparum gametocytes are sterilized within hours, whereas clearance from blood takes days. Gametocytaemia AUC and clearance times are determined predominantly by the more numerous female gametocytes, which are generally less drug sensitive than the minority male gametocytes, whereas transmission-blocking activity and thus infectivity is determined by the more sensitive male forms. In choosing doses of transmission-blocking drugs there is no substitute yet for mosquito-feeding studies.

In Vivo Assessments to Detect Antimalarial Resistance.

In vivo drug clinical trials are the gold standard for assessing the therapeutic efficacy of antimalarials. They must be conducted in a rigorous and standardized manner so that the resistance of antimalarial drugs can be compared both in time and in space. This chapter presents the methodology for conducting such clinical studies of antimalarials for the treatment of uncomplicated malaria and describes the logistical difficulties and limitations of this methodology. Finally it highlights the importance of such knowledge in preventing resistance, in prolonging the utility of existing antimalarial drugs, and in ensuring that all individuals and populations suffering from malaria get the right malaria treatment at the right time.