Initiation of gametocytogenesis at very low parasite density in Plasmodium falciparum infection

J Infect Dis. 2017 Apr 1;215(7):1167-1174. doi: 10.1093/infdis/jix035.

Abstract

The recent focus on the elimination of malaria has led to an increased interest in the role of sexual stages in its transmission. We introduce Plasmodium falciparum gametocyte exported protein-5 (PfGEXP5) transcript analysis as an important tool for evaluating the earliest (ring) stage sexual gametocytes in the blood of infected individuals. We show that gametocyte rings are detected in the peripheral blood immediately following establishment of asexual infections-without the need for triggers such as high-density asexual parasitemia or drug treatment. Committed gametocytes are refractory to the commonly used drug piperaquine, and mature gametocytes reappear in the bloodstream 10 days after the initial appearance of gametocyte rings. A further wave of commitment is observed following recrudescent asexual parasitemia, and these gametocytes are again refractory to piperaquine treatment. This work has implications for monitoring gametocyte and transmission dynamics and responses to drug treatment.

Keywords: Gametocyte EXported Protein-5; Plasmodium; early gametocyte marker; experimentally induced blood stage malaria; piperaquine..

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antimalarials / administration & dosage
  • Australia
  • Biomarkers / blood
  • Carrier Proteins / genetics
  • Female
  • Humans
  • Life Cycle Stages
  • Linear Models
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / parasitology*
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Parasite Load*
  • Plasmodium falciparum / cytology*
  • Plasmodium falciparum / genetics
  • Protozoan Proteins / genetics*
  • Quinolines / administration & dosage
  • Young Adult

Substances

  • Antimalarials
  • Biomarkers
  • Carrier Proteins
  • Membrane Proteins
  • Pfs25 protein, Plasmodium falciparum
  • Pfsbp1 protein, Plasmodium falciparum
  • Protozoan Proteins
  • Quinolines
  • piperaquine