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Journal of Clinical Microbiology, March 2007, p. 752-761, Vol. 45, No. 3
0095-1137/07/$08.00+0     doi:10.1128/JCM.01683-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

A Multiplex Ligase Detection Reaction-Fluorescent Microsphere Assay for Simultaneous Detection of Single Nucleotide Polymorphisms Associated with Plasmodium falciparum Drug Resistance{triangledown}

Eric P. Carnevale,1 Drew Kouri,1 Jeana T. DaRe,1 David T. McNamara,1 Ivo Mueller,2 and Peter A. Zimmerman1*

The Center for Global Health and Diseases, Case Western Reserve University, Wolstein Research Building, Room 4-125, 2103 Cornell Road, Cleveland, Ohio 44106-7286,1 Papua New Guinea Institute of Medical Research, P.O. Box 60, Goroka, EHP 441, Papua New Guinea2

Received 15 August 2006/ Returned for modification 29 September 2006/ Accepted 15 November 2006

Incomplete malaria control efforts have resulted in a worldwide increase in resistance to drugs used to treat the disease. A complex array of mutations underlying antimalarial drug resistance complicates efficient monitoring of parasite populations and limits the success of malaria control efforts in regions of endemicity. To improve the surveillance of Plasmodium falciparum drug resistance, we developed a multiplex ligase detection reaction-fluorescent-microsphere-based assay (LDR-FMA) that identifies single nucleotide polymorphisms (SNPs) in the P. falciparum dhfr (9 alleles), dhps (10 alleles), and pfcrt (3 alleles) genes associated with resistance to Fansidar and chloroquine. We evaluated 1,121 blood samples from study participants in the Wosera region of Papua New Guinea, where malaria is endemic. Results showed that 468 samples were P. falciparum negative and 453 samples were P. falciparum positive by a Plasmodium species assay and all three gene assays (concordance, 82.2%). For P. falciparum infections where the assay for each gene was positive, 2 samples carried resistance alleles for all three genes, 299 carried resistance alleles for dhfr and pfcrt, 131 carried resistance alleles for only one gene (dhfr [n = 40], dhps [n = 1], or pfcrt [n = 90]), and 21 carried only sensitive alleles at all three genes. Mixed-strain infections characterized 100 samples. Overall, 95.4% (432/453) of P. falciparum-infected samples carried at least one allele associated with resistance to Fansidar or chloroquine. In view of the fact that 86.3% (391/453) of P. falciparum-infected samples carried pfcrt mutations, chloroquine is largely ineffective against P. falciparum in Papua New Guinea. Surveillance of additional dhfr and dhps polymorphisms in order to monitor the continued effectiveness of Fansidar is recommended.

* Corresponding author. Mailing address: The Center for Global Health and Diseases, Case Western Reserve University, Wolstein Research Building, Room 4-125, 2103 Cornell Rd., Cleveland, OH 44106-7286. Phone: (216) 368-0508. Fax: (216) 368-4825. E-mail: paz{at}case.edu.

{triangledown} Published ahead of print on 22 November 2006.

Journal of Clinical Microbiology, March 2007, p. 752-761, Vol. 45, No. 3
0095-1137/07/$08.00+0     doi:10.1128/JCM.01683-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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