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C H A P T E R
5
Antigenic variation in African
trypanosomes and malaria
George A.M. Cross
Laboratory of Molecular Parasitology, The Rockefeller University,
New York, NY, USA
INTRODUCTION
Two important human diseases, malaria and
African trypanosomiasis (African sleeping sickness),
have evolved sophisticated molecular
mechanisms to evade the immune responses
of their mammalian hosts, creating persistent
infections that may or may not be ultimately
lethal. It is not in the interests of a parasite to
kill its host. Parasites that are too virulent will
themselves die, if their hosts do not survive
long enough for the infection to be transmitted.
For both trypanosomes and malaria parasites,
antigenic variation is the major but
probably not the sole mechanism for persistence.
Antigenic variation in trypanosomes has
been long recognized, as exemplified in the following
quotation (translated from the German)
from a 1905 paper by E. Franke, working in
Paul Ehrlich’s institute, just 10 years after trypanosomes
were implicated as the cause of
the ‘tsetse fly disease’, by Surgeon-Captain
David Bruce of the British Army Medical
Service: ‘The trypanosomes must have acquired
other biological characteristics during their
stay in the semi-immune body that rendered
them resistant to the defensive substances.’
This explanation was consistent with previous
experiments in which the transfer of immune
serum prolonged the life of infected animals
but did not cure them, and with the relapsing
nature of the parasitemia in humans. So, why
do we not yet understand a phenomenon
described 100 years ago?
Antigenic variation in trypanosomes is the
best studied and probably the most highly
developed example of an infectious microbe
evolving a mechanism for countering the host’s
immune-diversity generator with a diversity
generator of its own. Antigenic variation in the
African trypanosomes appears to have arisen
solely for the purpose of evading the host
immune responses, although other roles for
these cell-surface variations may have evaded
Molecular Medical Parasitology
ISBN 0–12–473346–8
89
Copyright © 2003 Elsevier Science Ltd.
All rights of reproduction in any form reserved.