Malaria is caused by infection of red blood cells with protozoan parasites of the genus Plasmodium. The parasites are inoculated into the human host by a feeding female anopheline mosquito. The four Plasmodium species that infect humans are P. falciparum, P. vivax, P. ovale and P. malariae. Occasional infections with monkey malaria parasites, such as P. knowlesi, also occur.
The first symptoms of malaria are nonspecific and similar to the symptoms of a minor systemic viral illness. They comprise: headache, lassitude, fatigue, abdominal discomfort and muscle and joint aches, followed by fever, chills, perspiration, anorexia, vomiting and worsening malaise. This is the typical picture of uncomplicated malaria. Residents of endemic areas are often familiar with this combination of symptoms, and frequently self-diagnose.
Malaria is therefore frequently overdiagnosed on the basis of symptoms alone. Infection with P. vivax and P. ovale , more than with other species, can be associated with well-defined malarial paroxysms, in which fever spikes, chills and rigors occur at regular intervals. At this stage, with no evidence of vital organ dysfunction, the case-fatality rate is low (circa 0.1% for P. falciparum infections - the other human malarias are rarely fatal) provided prompt and effective treatment is given. But if ineffective drugs are given or treatment is delayed in falciparum malaria, the parasite burden continues to increase and severe malaria may ensue. A patient may progress from having minor symptoms to having severe disease within a few hours. This usually manifests with one or more of the following: coma (cerebral malaria), metabolic acidosis, severe anaemia, hypoglycaemia and, in adults, acute renal failure or acute pulmonary oedema. By this stage, mortality in people receiving treatment has risen to 15-20%. If untreated, severe malaria is almost always fatal.
The nature of the clinical disease depends very much on the pattern and intensity of malaria transmission in the area of residence, which determines the degree of protective immunity acquired and, in turn, the clinical disease profile. Where malaria transmission is "stable" - meaning where populations are continuously exposed to a fairly constant rate of malarial inoculations - and if the inoculation rates are high - entomological inoculation rate (EIR) >10/year -, then partial immunity to the clinical disease and to its severe manifestations 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 almost always confined to young children who suffer high parasite densities and acute clinical disease. If untreated, this can progress very rapidly to severe malaria. In stable and high-transmission areas, adolescents and adults are partially immune and rarely suffer clinical disease, although they continue to harbour low blood-parasite densities. Immunity is reduced in pregnancy, and can be lost when individuals move out of the transmission zone.
In areas of unstable malaria, the situation prevailing 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. EIRs are usually <5/year and often <1/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. Epidemics manifest as a very high incidence of malaria in all age groups and can overwhelm health services. Severe malaria is common if effective treatment is not made widely available.
Thus in areas of high transmission, it is children who are at risk of severe malaria and death, whereas in areas of low or unstable transmission, all age groups are at risk.