The clinical manifestations of severe malaria are several and occur in different anatomical sites. Both parasite- and host-related factors contribute to the pathogenicity of the severe forms of the disease. Cytoadherence of infected red blood cells to the vascular endothelium of different organs and rosetting are unique features of malaria parasites which are likely to contribute to the vascular damage and the consequent excessive inflammatory/immune response of the host. In addition to cerebral malaria or severe anaemia, which are quite common manifestation of severe malaria, clinical evidences of thrombocytopenia, acute respiratory distress syndrome (ARDS), liver and kidney disease, are reported. In primigravidae from endemic areas, life threatening placental malaria may also be present.In the following pages, some of the pathogenetic aspects will be briefly reviewed and then data on selected and less frequent manifestation of severe malaria, such as liver or renal failure or ARDS will be discussed.

Malaria infection is still to be considered a major public health problem in those 106 countries where the risk of contracting the infection with one or more of the Plasmodium species exists. According to estimates from the World Health Organization, over 200 million cases and about 655.000 deaths have occurred in 2010. Estimating the real health and social burden of the disease is a difficult task, because many of the malaria endemic countries have limited diagnostic resources, especially in rural settings where conditions with similar clinical picture may coexist in the same geographical areas. Moreover, asymptomatic parasitaemia may occur in high transmission areas after childhood, when anti-malaria semi-immunity occurs. Malaria endemicity and control activities are very complex issues, that are influenced by factors related to the host, to the parasite, to the vector, to the environment and to the health system capacity to fully implement available anti-malaria weapons such as rapid diagnostic tests, artemisinin-based combination treatment, impregnated bed-nets and insecticide residual spraying while waiting for an effective vaccine to be made available.

The flow of international travellers to and from malaria-endemic areas, especially Africa, has increased in recent years. Apart from the very high morbidity and mortality burden imposed on malaria-endemic areas, imported malaria is the main cause of fever possibly causing severe disease and death in travellers coming from tropical and subtropical areas, particularly Sub-Saharan Africa. The importance of behavioural preventive measures (bed nets, repellents, etc.), adequate chemoprophylaxis and, in selected circumstances, stand-by emergency treatment may not be overemphasized. However, no prophylactic regimen may offer complete protection. Expert advice is needed to tailor prophylactic advice according to traveller (age, baseline clinical conditions, etc.) and travel (destination, season, etc.) characteristics in order to reduce malaria risk.