How selection forces dictate the variant surface antigens used by malaria parasites
Authored by Hans Heesterbeek, Maite Severins, Don Klinkenberg
Date Published: 2012
DOI: 10.1098/rsif.2011.0239
Sponsors:
No sponsors listed
Platforms:
C++
Model Documentation:
Other Narrative
Mathematical description
Model Code URLs:
Model code not found
Abstract
Red blood cells infected by the malaria parasite Plasmodium falciparum
express variant surface antigens (VSAs) that evade host immunity and
allow the parasites to persist in the human population. There exist many
different VSAs and the differential expression of these VSAs is
associated with the virulence (damage to the host) of the parasites. The
aim of this study is to unravel the differences in the effect key
selection forces have on parasites expressing different VSAs such that
we can better understand how VSAs enable the parasites to adapt to
changes in their environment (like control measures) and how this may
impact the virulence of the circulating parasites. To this end, we have
built an individual-based model that captures the main selective forces
on malaria parasites, namely parasite competition, host immunity, host
death and mosquito abundance at both the within-and between-host levels.
VSAs are defined by the net growth rates they infer to the parasites and
the model keeps track of the expression of, and antibody build-up
against, each VSA in all hosts. Our results show an ordered acquisition
of VSA-specific antibodies with host age, which causes a dichotomy
between the more virulent VSAs that reach high parasitaemias but are
restricted to young relatively non-immune hosts, and less virulent VSAs
that do not reach such high parasitaemias but can infect a wider range
of hosts. The outcome of a change in the parasite's environment in terms
of parasite virulence depends on the exact balance between the selection
forces, which sets the limiting factor for parasite survival. Parasites
will evolve towards expressing more virulent VSAs when the limiting
factor for parasite survival is the within-host parasite growth and the
parasites are able to minimize this limitation by expressing more
virulent VSAs.
Tags
Within-host
Erythrocyte-membrane protein-1
Plasmodium-falciparum gametocytes
Mutually exclusive expression
Frequent recombination events
Naturally
acquired-immunity
Infected erythrocytes
Var genes
Retrospective examination
Differential expression