Residual Plasmodium falciparum parasitemia in Kenyan children after artemisinin-combination therapy is associated with increased transmission to mosquitoes and parasite recurrence

J Infect Dis. 2013 Dec 15;208(12):2017-24. doi: 10.1093/infdis/jit431. Epub 2013 Aug 14.

Abstract

Background: Parasite clearance time after artemisinin-based combination therapy (ACT) may be increasing in Asian and African settings. The association between parasite clearance following ACT and transmissibility is currently unknown.

Methods: We determined parasite clearance dynamics by duplex quantitative polymerase chain reaction (qPCR) in samples collected in the first 3 days after treatment of uncomplicated malaria with ACT. Gametocyte carriage was determined by Pfs25 quantitative nucleic acid sequence-based amplification assays; infectiousness to mosquitoes by membrane-feeding assays on day 7 after treatment.

Results: Residual parasitemia was detected by qPCR in 31.8% (95% confidence interval [CI], 24.6-39.8) of the children on day 3 after initiation of treatment. Residual parasitemia was associated with a 2-fold longer duration of gametocyte carriage (P = .0007), a higher likelihood of infecting mosquitoes (relative risk, 1.95; 95% CI, 1.17-3.24; P = .015), and a higher parasite burden in mosquitoes (incidence rate ratio, 2.92; 95% CI, 1.61-5.31; P < .001). Children with residual parasitemia were also significantly more likely to experience microscopically detectable parasitemia during follow-up (relative risk, 11.25; 95% CI, 4.08-31.01; P < .001).

Conclusions: Residual submicroscopic parasitemia is common after ACT and is associated with a higher transmission potential. Residual parasitemia may also have consequences for individual patients because of its higher risk of recurrent parasitemia.

Keywords: PCR; anopheles; artemisinin; infectivity; resistance; submicroscopic; transmission.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / therapeutic use*
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins / therapeutic use*
  • Chi-Square Distribution
  • Child
  • Child, Preschool
  • DNA, Protozoan / blood
  • Drug Combinations
  • Drug Resistance
  • Ethanolamines / therapeutic use*
  • Fluorenes / therapeutic use*
  • Humans
  • Infant
  • Kenya / epidemiology
  • Malaria, Falciparum / drug therapy*
  • Malaria, Falciparum / epidemiology
  • Malaria, Falciparum / parasitology*
  • Malaria, Falciparum / transmission
  • Parasitemia / parasitology
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / isolation & purification*
  • Plasmodium falciparum / pathogenicity
  • Polymerase Chain Reaction
  • Quinolines / therapeutic use
  • Recurrence

Substances

  • Antimalarials
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins
  • DNA, Protozoan
  • Drug Combinations
  • Ethanolamines
  • Fluorenes
  • Quinolines
  • artenimol
  • piperaquine