Using Amplicon Deep Sequencing to Detect Genetic Signatures of Plasmodium vivax Relapse.
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.
Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill.
Jessica T
JT
Lin
Program in Bioinformatics and Integrative Biology, University of Massachusetts, Worcester.
Nicholas J
NJ
Hathaway
US Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
David L
DL
Saunders
US Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Chanthap
C
Lon
Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill.
Sujata
S
Balasubramanian
Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill.
Oksana
O
Kharabora
US Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Panita
P
Gosi
US Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Sabaithip
S
Sriwichai
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill.
Laurel
L
Kartchner
National Center for Parasitology, Entomology and Malaria Control.
Char Meng
CM
Chuor
Royal Cambodian Armed Forces, Phnom Penh, Cambodia.
Prom
P
Satharath
US Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Charlotte
C
Lanteri
Program in Bioinformatics and Integrative Biology, University of Massachusetts, Worcester Division of Transfusion Medicine, University of Massachusetts Medical School, Worcester.
Jeffrey A
JA
Bailey
Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill.
Jonathan J
JJ
Juliano
D002160:Cambodia / Q000453:epidemiology; D016054:DNA, Protozoan / Q000235:genetics*; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D016780:Malaria, Vivax / Q000453:epidemiology / Q000469:parasitology*; D020066:Merozoite Surface Protein 1 / Q000235:genetics / Q000378:metabolism; D018895:Microsatellite Repeats / Q000235:genetics; D010802:Phylogeny; D010966:Plasmodium vivax / Q000235:genetics*; D012008:Recurrence
D016054:DNA, Protozoan; D020066:Merozoite Surface Protein 1
Plasmodium vivax; amplicon sequencing; deep sequencing; genetic diversity; hypnozoite; malaria; microsatellite; multiplicity of infection; pvmsp1; relapse