Malaria remains one of the biggest health problems in large parts of the world.
In sub-Saharan Africa alone, it is currently estimated that there are more than
150 million clinical cases annually, and that about 2 million people die from
the disease every year. The bulk of malaria-related morbidity and mortality
in an endemic setting (malaria is regularly found) is concentrated in children
below the age of five years, and the increasing resistance to infection and
disease with age is conventionally thought to reflect a slow and gradual acquisition
of protective immunity. Many recent and comprehensive reviews of malarial immunity
exist; rather than attempting to add another, this review summarises some of
the recent evidence on how protective immunity is acquired in humans and what
precipitates clinical disease, specifically as it relates to populations living
in areas where the disease is endemic. It is becoming increasingly clear that
naturally acquired protective immunity depends largely on responses directed
against highly variable parasite antigens. This implies that a successful blood-stage
vaccine against this disease must be able to either induce protective responses
against many of these variants, or artificially initiate protective immune responses
that do not normally occur following natural exposure to the parasites. Such
protective immune responses might either rely on a different immunological mechanism,
or be directed against other antigens, other than those seen in naturally acquired
protective immunity. It remains to be seen whether it will be possible to induce
protective responses such as these by ‘artificially’ immunising humans.