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2. Clinical disease and epidemiology

usually manifests with one or more of the following: coma (cerebral malaria), metabolic
acidosis, severe anaemia, hypoglycaemia, acute renal failure or acute pulmonary oedema.
By this stage of the disease, the case fatality in people receiving treatment is typically
10–20%. However, if left untreated, severe malaria is fatal in the majority of cases.
The nature of malaria clinical disease depends greatly on the background level of the
acquired protective immunity, a factor which is the outcome of the pattern and intensity
of malaria transmission in the area of residence.

Where the transmission of malaria is “stable”, meaning where populations are continuously
exposed to a fairly constant, high rate of malarial inoculations (entomological inoculation
rate [EIR] >10 per year), partial immunity to the clinical disease and to its severe
manifestation is acquired early in childhood. In such situations, which prevail in much
of sub-Saharan Africa and parts of Oceania, the acute clinical disease described above is
mostly confined to young children, who suffer high parasite densities and acute clinical
disease. If untreated, this can progress very rapidly to severe malaria; adolescents and
adults are partially immune and seldom suffer clinical disease, although they may
continue to harbour low blood-parasite densities. Immunity is, however, modified in
pregnancy, and it is often gradually lost, at least partially, when individuals move out of
the endemic areas for long durations (usually many years).
In areas of unstable malaria, which prevails in much of Asia and Latin America, and
the remaining parts of the world where malaria is endemic, the rates of inoculation
fluctuate greatly over seasons and years. Entomological inoculation rates are usually
< 5 per year and often < 1 per year. This retards the acquisition of immunity and results
in people of all ages, adults and children alike, suffering acute clinical malaria, with a
high risk of progression to severe malaria if untreated. Epidemics may occur in areas
of unstable malaria when inoculation rates increase rapidly due to a sudden increase
in mosquito vector densities. Epidemics manifest as a very high incidence of malaria in
all age groups and can overwhelm health services. Severe malaria is common if prompt
effective treatment is not made widely available. Non-immune travellers to a malaria
endemic area are at a high risk of acquiring malaria, unless protective measures are
taken, and of the disease progressing to fatal severe malaria if infections are not treated
promptly and effectively.

With effective malaria control (as with a population-wide coverage with effective vector
control and large-scale deployment of ACTs), the number of malaria inoculations can be
greatly reduced; this will be followed in time by a corresponding change in the clinical
epidemiological profile in the area and a risk of epidemics, if control measures are not
sustained.

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