title: Plasmodium falciparum gametocyte carriage is associated with subsequent Plasmodium vivax relapse after treatment.
abstract: Mixed P. falciparum/P. vivax infections are common in southeast Asia. When patients with P. falciparum malaria are treated and followed for several weeks, a significant proportion will develop P. vivax malaria. In a combined analysis of 243 patients recruited to two malaria treatment trials in western Cambodia, 20/43 (47%) of those with P. falciparum gametocytes on admission developed P. vivax malaria by Day 28 of follow-up. The presence of Pf gametocytes on an initial blood smear was associated with a 3.5-fold greater rate of vivax parasitemia post-treatment (IRR = 3.5, 95% CI 2.0-6.0, p<0.001). The increased rate of post-treatment P. vivax infection persisted when correlates of exposure and immunity such as a history of malaria, male gender, and age were controlled for (IRR = 3.0, 95% CI 1.9-4.7, p<0.001). Polymerase chain reaction (PCR) confirmed that only a low proportion of subjects (5/55 or 9.1%) who developed vivax during follow-up had detectable Pv parasites in the peripheral blood at baseline. Molecular detection of falciparum gametocytes by reverse transcriptase PCR in a subset of patients strengthened the observed association, while PCR detection of Pv parasitemia at follow-up was similar to microscopy results. These findings suggest that the majority of vivax infections arising after treatment of falciparum malaria originate from relapsing liver-stage parasites. In settings such as western Cambodia, the presence of both sexual and asexual forms of P. falciparum on blood smear at presentation with acute falciparum malaria serves as a marker for possible occult P. vivax coinfection and subsequent relapse. These patients may benefit from empiric treatment with an 8-aminoquinolone such as primaquine.
authors.affiliation: Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. jesstlin@gmail.com
authors.forename: Jessica T
authors.initials: JT
authors.lastname: Lin
authors.forename: Delia
authors.initials: D
authors.lastname: Bethell
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Tyner
authors.forename: Chanthap
authors.initials: C
authors.lastname: Lon
authors.forename: Naman K
authors.initials: NK
authors.lastname: Shah
authors.forename: David L
authors.initials: DL
authors.lastname: Saunders
authors.forename: Sabaithip
authors.initials: S
authors.lastname: Sriwichai
authors.forename: Phisit
authors.initials: P
authors.lastname: Khemawoot
authors.forename: Worachet
authors.initials: W
authors.lastname: Kuntawunggin
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Smith
authors.forename: Harald
authors.initials: H
authors.lastname: Noedl
authors.forename: Kurt
authors.initials: K
authors.lastname: Schaecher
authors.forename: Duong
authors.initials: D
authors.lastname: Socheat
authors.forename: Youry
authors.initials: Y
authors.lastname: Se
authors.forename: Steven R
authors.initials: SR
authors.lastname: Meshnick
authors.forename: Mark M
authors.initials: MM
authors.lastname: Fukuda
mesh_terms: D000328:Adult; D000962:Antimalarials / Q000627:therapeutic use*; D002160:Cambodia; D005260:Female; D006801:Humans; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology / Q000503:physiopathology*; D008297:Male; D010963:Plasmodium falciparum / Q000302:isolation & purification*; D010966:Plasmodium vivax / Q000302:isolation & purification*; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D000962:Antimalarials