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Malaria is still a major global health problem, killing more than one million
people every year. Almost all of these deaths are caused by Plasmodium
falciparum, one of the four species of malaria parasites infecting humans.
This high burden of mortality falls heavily on sub-Saharan Africa, where
over 90% of these deaths are thought to occur, and 5% of children die before
the age of 5 years. The death toll from malaria is still growing, with malariaspecificmortality
in youngAfrican children estimated to have doubled during
the last 20 years. This increase has been associated with drug resistance of
the parasite, spread of insecticide-resistant mosquitoes, poverty, social and
political upheaval, and lack of effective vaccines.
Failure of the host to control a malaria infection is in part related to the
complexity of the parasite and the interaction with the immune system of
the host. Although there is now considerably more investment in malaria
research, and there are encouraging signs in vaccine development, we are a
long way from understanding the nature and control of protective immunity
or the pathological consequences of the host’s response to Plasmodium.With
themajor advances in knowledge in basicimmunology, inflammation, and the
genomic information on the host, vector and parasite, we are nowin a position
to elucidate the key unknowns in the immune response to malaria. What
initiates the immune response? How is it regulated?What are the mechanisms
of immune evasion employed by the parasite? What are the key molecules of
the parasite that induce protective immune responses?
The early interaction of the parasite with the host is important in determining
the nature of the subsequent acquired response and the pathology
associated with the severe complications of malaria such as cerebral malaria,
severe anemia, and hypoglycemia. Thus the manner inwhich the malaria parasite
activates the innate immune system and the cytokines and chemokines
inducedwill all influence the magnitude of the inflammatory response and the
types of T and B cell responses elicited. An understanding of these processes
might enable us to determine the level at which host responses contribute
to malarial disease, or might allow us to dissect out protective from pathological
processes, and thus lead to some immunologically based intervention
strategies. |
