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A comparison of methods to detect and quantify the markers of antimalarial drug resistance

Hastings, I. M. and Nsanzabana, C. and Smith, T. A.. (2010) A comparison of methods to detect and quantify the markers of antimalarial drug resistance. American journal of tropical medicine and hygiene, Vol. 83, H. 3. S. 489-495.

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Official URL: http://edoc.unibas.ch/dok/A5842787

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Abstract

We compare, contrast, and evaluate methods to quantify genetic markers of antimalarial drug resistance. Frequency estimates should be reported along with crude prevalence. There are four main potential methods to estimate frequencies in blood samples: simple counting of single nucleotide polymorphisms (SNPs) and haplotypes in samples with multiplicity of infection (MOI) = 1; SNP counting in samples with MOI >/= 2; SNP and haplotypes counting in samples with unambiguous genotypes; statistical inference using SNP and MOI data from all samples. Large differences between the methods became apparent when analyzing field data with high MOI. Simple counting dramatically reduced sample size and estimate precision, and we show that analysis of unambiguous samples is biased, leaving maximum likelihood or similar statistical inference as the only practical option. It is essential to account for genotyping missing minor clones; ignoring this phenomenon resulted in a 2-fold underestimation of SNPs and haplotypes present at low frequencies
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Health Systems Research and Dynamic Modelling > Dynamical Modelling (Smith)
UniBasel Contributors:Smith, Thomas A.
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:Williams and Wilkins
ISSN:0002-9637
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:14 Sep 2012 07:19
Deposited On:14 Sep 2012 06:49

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