Lars Hviid — Page 3 | PubMed Health

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Acute P. falciparum malaria induces a loss of CD28- T IFN-gamma producing cells.

P. falciparum malaria is associated with increased activation among peripheral lymphocytes. In the present study, we investigated markers of susceptibility to apoptosis and expression of IFN-gamma and IL-4 by CD28-and CD28+T cells in West African children with acute P. falciparum malaria. The study showed increased susceptibility to apoptosis and cytokine production among T lymphocytes during acute malaria but also that T cells, in particular IFN-gamma producing CD28-T cells, were substantially reduced. These results are in line with previous studies suggesting that certain T cell subsets are sequestered away from the peripheral blood during P. falciparum malaria.

Acute Disease↗

PubMedDate not supplied

In vitro selection of Plasmodium falciparum 3D7 for expression of variant surface antigens associated with severe malaria in African children.

P. falciparum-infected red blood cells (IRBC) can adhere to endothelial host receptors through parasite-encoded, clonally variant surface antigens (VSA). The VSA-mediated IRBC adhesion and the acquired VSA-specific antibody response have both been linked to IRBC organ tropism and disease severity. Parasites isolated from young children with severe malaria (SM) tend to express a limited and conserved set of VSA (VSASM) that are both stronger and more commonly recognized by IgG in the plasma of malaria-exposed individuals than VSA (VSAUM) expressed by parasites causing uncomplicated malaria (UM) in older semi-immune children. Establishment of the genetic mechanism underlying changes in VSA expression in response to in vitro selective pressure is now possible because of the availability of the entire genomic sequence of the P. falciparum clone 3D7. As a first step towards direct molecular identification of VSASM-encoding genes in 3D7, we report here a method of enforcing expression of VSASM-like antigens in this parasite clone by a novel selection method using plasma from semi-immune children with low VSAUM-specific, but high VSASM-specific, IgG reactivity. In addition to the resulting increase in VSA-specific IgG recognition, VSASM-expressing 3D7(3D7-Dodowa1) showed reduced adhesion to CD36. Finally, levels of IgG specific for the VSA expressed by 3D7-Dodowa1 were uniformly higher than those of IgG with specificity for VSA expressed by the unselected 3D7 in plasma samples from geographically and epidemiologically diverse areas of endemic parasite transmission. The described selection method appears a useful tool in the identification of genes encoding VSA involved in severe and life-threatening P. falciparum malaria.

Adolescent↗