Use of area under the curve to characterize transmission potential after antimalarial treatment.
To evaluate transmission potential of Plasmodium falciparum, we use the area under the curve (AUC) of gametocyte levels after treatment as an approach to combine their duration and magnitude. Analysis of determinants of AUC was based on two main exposures: parasite clearance time (PCT) and presence of dihydrofolate reductase and dihydropteroate synthase mutations associated with sulfadoxine-pyrimethamine (SP) resistance in vitro. Exposures were determined based on the first three days after treatment with SP of 96 individuals who had malaria, cleared parasitemia by days 1-3, and were followed-up for 21 days. Using regression methods, we characterized both the heterogeneity of the presence of gametocytes (AUC > 0) and the magnitude of the AUC among those with an AUC > 0. A PCT of two or three days was associated with a substantial and highly significant odds ratio for presence of gametocytes. Among those who developed gametocytes, if their clearance time was 3 days or if they had any mutations (1 or 2) the magnitude of gametocytemia was > or = 3-fold. Methods presented are applicable to both observational studies and clinical trials assessing the effect of therapies on transmission potential.
Méndez
Fabián
F
Escuela de Salud Pública, Universidad del Valle, Cali, Colombia. famendez@univalle.edu.co
Muñoz
Alvaro
A
Plowe
Christopher V
CV
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D004094:Dihydropteroate Synthase / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology / Q000635:transmission*; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D017354:Point Mutation; D011739:Pyrimethamine / Q000494:pharmacology* / Q000627:therapeutic use; D013413:Sulfadoxine / Q000494:pharmacology* / Q000627:therapeutic use; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine