Comparison of msp genotyping and a 24 SNP molecular assay for differentiating Plasmodium falciparum recrudescence from reinfection.
Antigens, Protozoan
/ genetics
Child, Preschool
Clinical Trials as Topic
Female
Genotype
Genotyping Techniques
/ methods
Humans
Infant
Malaria, Falciparum
/ diagnosis
Malawi
Male
Merozoite Surface Protein 1
/ genetics
Plasmodium falciparum
/ classification
Polymorphism, Single Nucleotide
Protozoan Proteins
/ genetics
Recurrence
Sensitivity and Specificity
Time Factors
24 SNP genotyping
Malaria
Plasmodium falciparum
Recrudescence
Reinfection
msp genotyping
Journal
Malaria journal
ISSN: 1475-2875
Titre abrégé: Malar J
Pays: England
ID NLM: 101139802
Informations de publication
Date de publication:
18 Mar 2019
18 Mar 2019
Historique:
received:
31
08
2018
accepted:
01
03
2019
entrez:
20
3
2019
pubmed:
20
3
2019
medline:
23
4
2019
Statut:
epublish
Résumé
Current World Health Organization guidelines for conducting anti-malarial drug efficacy clinical trials recommend genotyping Plasmodium falciparum genes msp1 and msp2 to distinguish recrudescence from reinfection. A more recently developed potential alternative to this method is a molecular genotyping assay based on a panel of 24 single nucleotide polymorphism (SNP) markers. Performance parameters of these two genotyping methods were compared using data from two recently completed drug efficacy trials. Blood samples from two anti-malarial therapeutic trials were analysed by both msp genotyping and the 24 SNP assay. Additionally, to conserve time and resources, the statistical program R was used to select the most informative SNPs for a set of unrelated Malawian samples to develop a truncated SNP-based assay for the region surrounding Blantyre, Malawi. The ability of this truncated assay to distinguish reinfection from recrudescence when compared to the full 24 SNP assay was then analysed using data from the therapeutic trials. A total of 360 samples were analysed; 66 for concordance of msp and SNP barcoding methodologies, and 294 for assessing the most informative of the 24 SNP markers. SNP genotyping performed comparably to msp genotyping, with only one case of disagreement among the 50 interpretable results, where the SNP assay identified the sample as reinfection and the msp typing as recrudescence. Furthermore, SNP typing was more robust; only 6% of samples were uninterpretable by SNP typing, compared to 19.7% when msp genotyping was used. For discriminating reinfection from recrudescence, a truncated 6 SNP assay was found to perform at 95.1% the accuracy of the full 24 SNP bar code. The use of SNP analysis has similar sensitivity to the standard msp genotyping in determining recrudescence from reinfection. Although more expensive, SNP typing is faster and less work intensive. Limiting the assay to those SNPs most informative in the geographical region of interest may further decrease the workload and the cost, making this technique a feasible and affordable alternative in drug efficacy trials.
Sections du résumé
BACKGROUND
BACKGROUND
Current World Health Organization guidelines for conducting anti-malarial drug efficacy clinical trials recommend genotyping Plasmodium falciparum genes msp1 and msp2 to distinguish recrudescence from reinfection. A more recently developed potential alternative to this method is a molecular genotyping assay based on a panel of 24 single nucleotide polymorphism (SNP) markers.
METHODS
METHODS
Performance parameters of these two genotyping methods were compared using data from two recently completed drug efficacy trials. Blood samples from two anti-malarial therapeutic trials were analysed by both msp genotyping and the 24 SNP assay. Additionally, to conserve time and resources, the statistical program R was used to select the most informative SNPs for a set of unrelated Malawian samples to develop a truncated SNP-based assay for the region surrounding Blantyre, Malawi. The ability of this truncated assay to distinguish reinfection from recrudescence when compared to the full 24 SNP assay was then analysed using data from the therapeutic trials.
RESULTS
RESULTS
A total of 360 samples were analysed; 66 for concordance of msp and SNP barcoding methodologies, and 294 for assessing the most informative of the 24 SNP markers. SNP genotyping performed comparably to msp genotyping, with only one case of disagreement among the 50 interpretable results, where the SNP assay identified the sample as reinfection and the msp typing as recrudescence. Furthermore, SNP typing was more robust; only 6% of samples were uninterpretable by SNP typing, compared to 19.7% when msp genotyping was used. For discriminating reinfection from recrudescence, a truncated 6 SNP assay was found to perform at 95.1% the accuracy of the full 24 SNP bar code.
CONCLUSIONS
CONCLUSIONS
The use of SNP analysis has similar sensitivity to the standard msp genotyping in determining recrudescence from reinfection. Although more expensive, SNP typing is faster and less work intensive. Limiting the assay to those SNPs most informative in the geographical region of interest may further decrease the workload and the cost, making this technique a feasible and affordable alternative in drug efficacy trials.
Identifiants
pubmed: 30885193
doi: 10.1186/s12936-019-2695-0
pii: 10.1186/s12936-019-2695-0
pmc: PMC6423793
doi:
Substances chimiques
Antigens, Protozoan
0
Merozoite Surface Protein 1
0
Protozoan Proteins
0
merozoite surface protein 2, Plasmodium
0
Types de publication
Comparative Study
Evaluation Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
84Subventions
Organisme : NIAID NIH HHS
ID : R01 AI034969
Pays : United States
Organisme : NCPDCID CDC HHS
ID : U01 CI000189
Pays : United States
Organisme : National Institutes of Health
ID : RO1AI34969
Organisme : Center for Global Health
ID : 5 U01 CI000189
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