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Antimicrobial Agents and Chemotherapy, February 2007, p. 521-527, Vol. 51, No. 2
0066-4804/07/$08.00+0     doi:10.1128/AAC.00902-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Estimating True Antimalarial Efficacy by Heteroduplex Tracking Assay in Patients with Complex Plasmodium falciparum Infections{triangledown}

Jesse J. Kwiek,* Alisa P. Alker, Emily C. Wenink, Marjorie Chaponda, Linda V. Kalilani, and Steven R. Meshnick

Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina

Received 21 July 2006/ Returned for modification 25 September 2006/ Accepted 7 November 2006

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.

* Corresponding author. Mailing address: University of North Carolina at Chapel Hill School of Public Health, Department of Epidemiology, CB# 7435, Chapel Hill, NC 27599-7435. Phone: (919) 843-4384. Fax: (919) 966-2089. E-mail: kwiek{at}unc.edu.

{triangledown} Published ahead of print on 20 November 2006.

Antimicrobial Agents and Chemotherapy, February 2007, p. 521-527, Vol. 51, No. 2
0066-4804/07/$08.00+0     doi:10.1128/AAC.00902-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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  • Juliano, J. J., Bacon, D. J., Mu, J., Wang, X., Meshnick, S. R. (2009). Novel dhps and pfcrt Polymorphisms in Plasmodium falciparum Detected by Heteroduplex Tracking Assay. Am J Trop Med Hyg 80: 734-736 [Abstract] [Full Text]  
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  • Greenhouse, B., Dokomajilar, C., Hubbard, A., Rosenthal, P. J., Dorsey, G. (2007). Impact of Transmission Intensity on the Accuracy of Genotyping To Distinguish Recrudescence from New Infection in Antimalarial Clinical Trials. Antimicrob. Agents Chemother. 51: 3096-3103 [Abstract] [Full Text]  


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