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

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Hastings, Ian ORCID: https://orcid.org/0000-0002-1332-742X, Nsanzabana, Christian and Smith, Tom 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, Issue 3, pp. 489-95.

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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 < or = 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.

Item Type: Article
Subjects: QV Pharmacology > QV 38 Drug action.
QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified.
QX Parasitology > QX 45 Host-parasite relations
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.4269/ajtmh.2010.10-0072
Depositing User: Mary Creegan
Date Deposited: 07 Jun 2011 15:44
Last Modified: 28 Sep 2018 15:34
URI: https://archive.lstmed.ac.uk/id/eprint/2036

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