This report shows that patients with severe malaria requiring admission to ICU who are managed at a specialist centre have a good outcome, with a mortality rate of only 4%. Consistent with previous reports, acute kidney injury, ARDS, and cerebral malaria were the most common complications. This report demonstrates that ARDS occurs later and at lower parasitaemia and emphasises the need for vigilance even after patients appear to be responding to treatment. The data reinforce the idea that there is a complex inter-relationship between ethnicity, “immunity” and the response to malaria. There were no significant differences between those individuals who had grown up in an endemic region and those patients who were malaria-naive. Co-infection with HIV was common, especially in patients who were African in origin. Finally, this report adds to the limited number of series reporting the efficacy and safety of parenteral artemisinins in severe malaria in a non-endemic setting [18–20]. The introduction of these agents has been associated with a dramatic reduction in the need for exchange transfusion.
In this series, the case-fatality rate was 4%. In contrast, a paper from Kilifi  showed that African children who had evidence of cerebral malaria, acidosis and severe anaemia had a 35% risk of death. In the SEAQUAMAT trial , among young Asian adults, the group treated with quinine had a mortality of 22%. In Africa, most deaths occur within the first 24 hours and children who survive beyond three days are much less likely to die. In this series, only one death occurred at a time when there was evidence of active malarial infection and the other four resulted from complications associated with intensive care, such as cardiac arrhythmia or nosocomial infection. Previous studies have reported a mortality rate between seven and 25% [5–11]. Recent data from the Malaria Reference Laboratory have shown a marked geographical variation in mortality from imported malaria from different parts of the UK . It is possible that the lower mortality in various specialist centres may be a reflection of wider experience in the management of severe malaria.
Most patients were young, Caucasian travellers to Africa but the second largest group were Africans visiting friends and relatives. For both groups, adherence to chemoprophylaxis was poor. The UK Health Protection Agency have previously reported an increased risk of acquiring malaria in individuals travelling to visit friends and relatives . Between 1994 and 2010, HTD treated 1451 patients for falciparum malaria who did not require admission to ICU. Among all these patients, Africans were significantly less likely than Caucasians to require ICU admission (OR: 0.26 95% CI: 0.18-0.38) which is in keeping with earlier reports . However, among those who did require intensive care, Africans were no less sick. There were no differences in the number of WHO markers of severity between Africans and other ethnicities, suggesting that Africans admitted to ICU had no appreciable immunity to the disease. These findings highlight the inherent problems in using ethnicity as a proxy for “immunity” to malaria.
Cerebral involvement and/or AKI tended to be present on admission or develop within the first 48 hours. ARDS tended to develop later, often when there was little or no evidence of persisting malaria. Those caring for patients with severe malaria need to be aware that an initial response to treatment, manifest by a reduction in parasitaemia, does not necessarily mean a successful outcome.
Before the introduction of artesunate, this hospital recommended a six-unit exchange transfusion for patients with a parasitaemia greater than 20% or those with a parasitaemia greater than 10% but with evidence of end-organ dysfunction. In total, 33 (26%) patients had an exchange transfusion, including three of the five who died. Since switching to parenteral artemisinins, we have seen evidence of a rapid and dramatic decline in parasitaemia compared to the response to treatment with quinine. As a result, we have not performed an exchange transfusion since 2008 and, in agreement with other UK specialist centres such as the Liverpool School of Tropical Medicine (D Lalloo, personal communication), we no longer recommend this as a modality of treatment.
Children presenting to African hospitals with malaria often have positive cultures for gram-negative organisms, particularly non-typhoidal salmonellae. The rate of blood culture positivity can be as high as 12% [25, 26]. Co-existing bacteraemia has been inconsistently reported in other series of imported malaria, with rates between 2.5 and 5% [5, 6]; in this series, only two (1.6%) patients had positive blood cultures at admission, neither of which were salmonellae.
The extent of the interaction between HIV and falciparum malaria remains open to debate, but in sub-Saharan Africa, HIV positive pregnant women in particular appear to be at an increased risk of developing severe disease . In this series, three patients were already known to be living with HIV/AIDS before they developed malaria; a further five were found to have HIV during admission, four of whom were African. A minimum of 17% of Africans therefore were positive for HIV, which will be an underestimate as not all were tested. These findings and the shared epidemiological risk factors for both diseases suggest that all patients presenting with severe malaria should be tested for HIV.
This study shows that both a CAM score <2 and an MSA <5 identified patients who would survive. However, these scores had limited ability to predict mortality and it remains unclear what role, if any, they may play in clinical practice in areas of the world where malaria is not endemic. No clinical factor was associated with a poor outcome but given the low case fatality rate, the study was under-powered to detect such a difference.
The main limitation of this study was its retrospective nature; as a result some data were missing or incomplete. Despite this, data capture was high, in particular data relating to ICU care, which were recorded systematically. Although the possibility of referral bias can not be excluded it is likely that our data are applicable to all patients with imported malaria requiring admission to ICU.