Using Amplicon Deep Sequencing to Detect Genetic Signatures of Plasmodium vivax Relapse
Program in Bioinformatics and Integrative Biology
Cambodia; DNA, Protozoan; Gene Expression Regulation; Genetic Variation; Haplotypes; Humans; Malaria, Vivax; Merozoite Surface Protein 1; Microsatellite Repeats; Phylogeny; Plasmodium vivax; Recurrence
Bioinformatics | Computational Biology | Genetics | Genomics | Immunology of Infectious Disease | Parasitology | Population Biology
Plasmodium vivax infections often recur due to relapse of hypnozoites from the liver. In malaria-endemic areas, tools to distinguish relapse from reinfection are needed. We applied amplicon deep sequencing to P. vivax isolates from 78 Cambodian volunteers, nearly one-third of whom suffered recurrence at a median of 68 days. Deep sequencing at a highly variable region of the P. vivax merozoite surface protein 1 gene revealed impressive diversity-generating 67 unique haplotypes and detecting on average 3.6 cocirculating parasite clones within individuals, compared to 2.1 clones detected by a combination of 3 microsatellite markers. This diversity enabled a scheme to classify over half of recurrences as probable relapses based on the low probability of reinfection by multiple recurring variants. In areas of high P. vivax diversity, targeted deep sequencing can help detect genetic signatures of relapse, key to evaluating antivivax interventions and achieving a better understanding of relapse-reinfection epidemiology.
Plasmodium vivax, amplicon sequencing, deep sequencing, genetic diversity, hypnozoite, malaria, microsatellite, multiplicity of infection, pvmsp1, relapse
DOI of Published Version
J Infect Dis. 2015 Sep 15;212(6):999-1008. doi: 10.1093/infdis/jiv142. Epub 2015 Mar 6. Link to article on publisher's site
The Journal of infectious diseases
Lin, Jessica T.; Hathaway, Nicholas J.; Saunders, David L.; Lon, Chanthap; Balasubramanian, Sujata; Kharabora, Oksana; Gosi, Panita; Sriwichai, Sabaithip; Kartchner, Laurel; Chuor, Char Meng; Satharath, Prom; Lanteri, Charlotte; Bailey, Jeffrey A.; and Juliano, Jonathan J., "Using Amplicon Deep Sequencing to Detect Genetic Signatures of Plasmodium vivax Relapse" (2015). Program in Bioinformatics and Integrative Biology Publications and Presentations. 73.