title: Stage-dependent production and release of histidine-rich protein 2 by Plasmodium falciparum.
abstract: Because of their sequestration in the microcirculation, the pathogenic late stages of Plasmodium falciparum are under-represented in peripheral blood samples from patients with falciparum malaria. Excreted products of the parasite might help to estimate this sequestered biomass. We quantified the stage-dependent production and release per parasite of P. falciparum histidine-rich protein 2 (PfHRP2) with the objective of measuring the sequestered biomass. A simple method to relate parasite stage to parasite age was developed to facilitate this. In four isolates of P. falciparum, the median (range) PfHRP2 content was 2.0fg (0.5-4.3fg) for a young ring stage infected erythrocyte, and 5.4fg (2.1-10.2fg) for the schizont stage. The amount of PfHRP2 in the parasitized erythrocyte increased most during development to the mature trophozoite stage. The median (range) amount of PfHRP2 secreted per parasite per entire erythrocytic cycle was 5.2fg (1.1-13.0fg). A median of 89% of the total PfHRP2 was excreted at the moment of schizont rupture. This assessment of the stage-dependent release of PfHRP2 is an essential prerequisite for future studies aimed at estimating the total patient parasite mass from the peripheral blood PfHRP2 concentration.
authors.affiliation: Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand.
authors.forename: Varunee
authors.initials: V
authors.lastname: Desakorn
authors.forename: Arjen M
authors.initials: AM
authors.lastname: Dondorp
authors.forename: Kamolrat
authors.initials: K
authors.lastname: Silamut
authors.forename: Wirichada
authors.initials: W
authors.lastname: Pongtavornpinyo
authors.forename: Duangjai
authors.initials: D
authors.lastname: Sahassananda
authors.forename: Kesinee
authors.initials: K
authors.lastname: Chotivanich
authors.forename: Punnee
authors.initials: P
authors.lastname: Pitisuttithum
authors.forename: A M
authors.initials: AM
authors.lastname: Smithyman
authors.forename: Nicholas P J
authors.initials: NP
authors.lastname: Day
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
mesh_terms: D000818:Animals; D018533:Biomass; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004912:Erythrocytes / Q000469:parasitology; D008018:Life Cycle Stages; D016778:Malaria, Falciparum / Q000469:parasitology; D010963:Plasmodium falciparum / Q000254:growth & development / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D000099053:Histidine-Rich Glycoprotein
chemical_list: D011506:Proteins; D000099053:Histidine-Rich Glycoprotein