Using Amplicon Deep Sequencing to Detect Genetic Signatures of Plasmodium vivax Relapse

Jessica T. Lin*, Nicholas J. Hathaway, David L. Saunders, Chanthap Lon, Sujata Balasubramanian, Oksana Kharabora, Panita Gosi, Sabaithip Sriwichai, Laurel Kartchner, Char Meng Chuor, Prom Satharath, Charlotte Lanteri, Jeffrey A. Bailey, Jonathan J. Juliano

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)999-1008
Number of pages10
JournalJournal of Infectious Diseases
Volume212
Issue number6
DOIs
StatePublished - 15 Sep 2015
Externally publishedYes

Keywords

  • Plasmodium vivax
  • amplicon sequencing
  • deep sequencing
  • genetic diversity
  • hypnozoite
  • malaria
  • microsatellite
  • multiplicity of infection
  • pvmsp1
  • relapse

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