Severe malaria

Abstract

Severe malaria is a medical emergency. It is a major cause of preventable childhood death in tropical countries. Severe malaria justifies considerable global investment in malaria control and elimination yet, increasingly, international agencies, funders and policy makers are unfamiliar with it, and so it is overlooked. In sub-Saharan Africa, severe malaria is overdiagnosed in clinical practice. Approximately one third of children diagnosed with severe malaria have another condition, usually sepsis, as the cause of their severe illness. But these children have a high mortality, contributing substantially to the number of deaths attributed to 'severe malaria'. Simple well-established tests, such as examination of the thin blood smear and the full blood count, improve the specificity of diagnosis and provide prognostic information in severe malaria. They should be performed more widely. Early administration of artesunate and broad-spectrum antibiotics to all children with suspected severe malaria would reduce global malaria mortality.

Fig. 1

Relationship between peripheral blood parasite density and outcome in patients with acute falciparum malaria studied by Field and colleagues in Kuala Lumpur over 70 years ago [31]

Fig. 2

Overlap of clinical syndromes and mortalities in adults and children with severe falciparum malaria. These proportions are derived from prospective studies in SouthEast Asia and Africa of adults and children with severe falciparum malaria conducted or coordinated by the Mahidol Oxford Research Unit over the past 40 years [26]

Fig. 3

Approximate age relationships for the major clinical manifestations of severe falciparum malaria in relation to the intensity of transmission [53]. Holoendemic in this illustration approximates to a sustained entomological inoculation rate > 10 per year or a parasite rate (prevalence) in children of 0.5, and hypoendemic refers to an average entomological inoculation rate ≤ 1 year

Fig. 4

Proposed algorithm for managing suspected/confirmed severe anaemia in African children aged from 2 months to 12 years [58]

Fig. 5

Brain smear from fatal cerebral malaria. The vessels (A, C and D) are packed with red cells containing P. falciparum schizonts (many of which are disrupted) and malaria pigment (haemozoin). Vessel segment B, by contrast, contains mainly unparasitized erythrocytes

Fig. 6

Misdiagnosis of severe falciparum malaria in African children -approximate relationships. [108, 109]

Fig. 7

Relationship between estimated parasite biomass and mortality [4, 110] in the large randomized controlled trial which compared artesunate and quinine in African children with severe malaria (AQUAMAT) [19]. The upper panel divides the patients into tertiles by treatment effect (reduction in mortality by artesunate). The mortality reduction in the preceding randomized controlled trial (SEAQUAMAT) which compared artesunate and quinine in Southeast Asia (where the diagnosis of severe malaria is more specific) is shown for comparison [18] (upper green dashed line). There was no treatment benefit from artesunate in patients in the lowest tertile of parasite biomass (red), likely corresponding to patients with another cause of severe illness (probably sepsis) and incidental parasitaemia [108, 109]. The lower panel shows the corresponding relationship between mortality in the AQUAMAT study and the estimated total parasite numbers in the body derived from the admission plasma PfHRP2 concentration [110]