title: Estimating true antimalarial efficacy by heteroduplex tracking assay in patients with complex Plasmodium falciparum infections.
abstract: Heteroduplex tracking assays (HTAs) of Plasmodium falciparum merozoite surface protein 1 block-2 were used to assess complexity of infection and treatment efficacy in a trial of three antimalarial treatments in 141 Malawian pregnant women. An elevated complexity of infection (COI) was associated with anemia, parasite burden, and human immunodeficiency virus infection but was not associated with age or gravidity. Comparisons of HTA patterns before and after treatment allowed the classification of 20 of 30 (66%) recurrent episodes as either definite treatment failures or reinfections. An elevated COI was strongly associated with treatment failure (P=0.003). An algorithm was developed to assign a probability of failure for the 10 indeterminate participants, some of whose infections shared a single variant of high prevalence (>10%). By summing these probabilities, treatment efficacy was estimated.
authors.affiliation: University of North Carolina at Chapel Hill School of Public Health, Department of Epidemiology, CB# 7435, Chapel Hill, NC 27599-7435, USA. kwiek@unc.edu
authors.forename: Jesse J
authors.initials: JJ
authors.lastname: Kwiek
authors.forename: Alisa P
authors.initials: AP
authors.lastname: Alker
authors.forename: Emily C
authors.initials: EC
authors.lastname: Wenink
authors.forename: Marjorie
authors.initials: M
authors.lastname: Chaponda
authors.forename: Linda V
authors.initials: LV
authors.lastname: Kalilani
authors.forename: Steven R
authors.initials: SR
authors.lastname: Meshnick
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000032:analysis / Q000235:genetics; D000962:Antimalarials / Q000627:therapeutic use*; D001483:Base Sequence; D001681:Biological Assay; D016054:DNA, Protozoan / Q000032:analysis / Q000235:genetics; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000188:drug therapy* / Q000469:parasitology*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000188:drug therapy / Q000469:parasitology; D015800:Protozoan Proteins / Q000032:analysis / Q000235:genetics; D012680:Sensitivity and Specificity; D016415:Sequence Alignment; D016896:Treatment Outcome
chemical_list: D000953:Antigens, Protozoan; D000962:Antimalarials; D016054:DNA, Protozoan; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium