Imported falciparum Malaria Among Adults in the ICU
Imported falciparum Malaria Among Adults in the ICU
This is the first review of imported falciparum malaria among adults who were sufficiently unwell to require admission to ICU. The review supports four important conclusions. First, hyperparasitaemia, however this is defined, is not a feature in almost 50% of patients; second, up to 40% of these patients were originally from or still resident in a malaria-endemic region and may therefore be assumed to have at least partial immunity to the disease; third, co-infection with community-acquired gram-negative bacteraemia is uncommon among adults; and, finally, the case fatality rate for severe imported malaria in ICU is in the region of 10%.
AKI, ARDS and cerebral malaria were all common. Invasive ventilation was required in 22% and renal replacement therapy was required in approximately 22%. Hyperparasitaemia, which is often used as a proxy for severe falciparum, was seen in only 57% of subjects when a cut-off of ≥2% was used. When using a definition of ≥5% parasitaemia, which the WHO recommends as the criterion for severe disease in endemic areas, this proportion fell to 44%. Clinicians would be well advised not to rely on parasite count as the only indicator of severe disease.
Gram-negative bacteraemia, classically with non-typhoidal Salmonellae, is a well recognized complication of malaria in children, occurring in up to 20%. Recent studies have suggested that dysfunctional granulocyte mobilization may be responsible for this. While 8% of patients had a presumed community-acquired bacterial co-infection, usually pneumonia, at admission, only 25 (3%) had culture-positive, gram-negative bacteraemia. Previous prescription of antibiotics may have caused some bias and a lower yield but it is possible that this reflects a difference in the pathophysiology of severe malaria in adults compared to children.
The overall case-fatality rate was 9% although one study reported a rate as high as 29%. Quinine was the most commonly used anti-malarial agent in all 13 studies. Artesunate has been shown to significantly reduce case fatality from severe malaria in both Southeast Asia and Africa. Only one of these studies included patients treated with artemisinins, but as these drugs become more widely available the case fatality from severe imported malaria may decline.
This review has several weaknesses. A number of studies that were not published in English were excluded and it is possible that this may have had an effect. Most of the included studies were from Europe and the conclusions may not be relevant to other settings where imported malaria is seen. In particular, indications for ICU admission are likely to have varied both between the study sites and over the period that the studies were conducted, which may partially explain the spectrum of disease severity and outcomes seen. Individual patient data were often unavailable, which meant paediatric cases could not reliably be excluded, although there were only 15 of these. For the same reasons, it was not possible to analyse temporal trends in case fatality rates or perform a detailed meta-analysis of risk factors associated with mortality. However, the review includes all series of more than ten patients published in English over more than 40 years and provides important insights into the management of this relatively uncommon disease.
It is noteworthy that no case series from North America were included in the current paper. In 2011 the United States reported 1,925 cases of America of which 183 were reported to have severe disease. Given the significantly larger population of the United States, compared to the other countries represented in this paper, it is possible that no American centre sees a sufficiently large enough number of cases to inform a study of severe malaria in the USA.
The overall case fatality rate of 9% may not reflect modern practice. Management of ARDS has improved considerably in recent years and newer strategies for fluid resuscitation, in particular, may reduce the incidence of both multi-organ failure and long-term disability. Similarly, optimizing fluid management for patients with ARDS may reduce pulmonary capillary leak and subsequently the length of time that patients require on ICU. Greater awareness of what constitutes AKI may also result in a better outcome. Each of these factors, as well as improved antimicrobial protocols, management of shock and acidosis and increasing use of artemisinins, may further reduce the case fatality associated with severe imported malaria in the future.
Conclusions
This is the first review of imported falciparum malaria among adults who were sufficiently unwell to require admission to ICU. The review supports four important conclusions. First, hyperparasitaemia, however this is defined, is not a feature in almost 50% of patients; second, up to 40% of these patients were originally from or still resident in a malaria-endemic region and may therefore be assumed to have at least partial immunity to the disease; third, co-infection with community-acquired gram-negative bacteraemia is uncommon among adults; and, finally, the case fatality rate for severe imported malaria in ICU is in the region of 10%.
AKI, ARDS and cerebral malaria were all common. Invasive ventilation was required in 22% and renal replacement therapy was required in approximately 22%. Hyperparasitaemia, which is often used as a proxy for severe falciparum, was seen in only 57% of subjects when a cut-off of ≥2% was used. When using a definition of ≥5% parasitaemia, which the WHO recommends as the criterion for severe disease in endemic areas, this proportion fell to 44%. Clinicians would be well advised not to rely on parasite count as the only indicator of severe disease.
Gram-negative bacteraemia, classically with non-typhoidal Salmonellae, is a well recognized complication of malaria in children, occurring in up to 20%. Recent studies have suggested that dysfunctional granulocyte mobilization may be responsible for this. While 8% of patients had a presumed community-acquired bacterial co-infection, usually pneumonia, at admission, only 25 (3%) had culture-positive, gram-negative bacteraemia. Previous prescription of antibiotics may have caused some bias and a lower yield but it is possible that this reflects a difference in the pathophysiology of severe malaria in adults compared to children.
The overall case-fatality rate was 9% although one study reported a rate as high as 29%. Quinine was the most commonly used anti-malarial agent in all 13 studies. Artesunate has been shown to significantly reduce case fatality from severe malaria in both Southeast Asia and Africa. Only one of these studies included patients treated with artemisinins, but as these drugs become more widely available the case fatality from severe imported malaria may decline.
This review has several weaknesses. A number of studies that were not published in English were excluded and it is possible that this may have had an effect. Most of the included studies were from Europe and the conclusions may not be relevant to other settings where imported malaria is seen. In particular, indications for ICU admission are likely to have varied both between the study sites and over the period that the studies were conducted, which may partially explain the spectrum of disease severity and outcomes seen. Individual patient data were often unavailable, which meant paediatric cases could not reliably be excluded, although there were only 15 of these. For the same reasons, it was not possible to analyse temporal trends in case fatality rates or perform a detailed meta-analysis of risk factors associated with mortality. However, the review includes all series of more than ten patients published in English over more than 40 years and provides important insights into the management of this relatively uncommon disease.
It is noteworthy that no case series from North America were included in the current paper. In 2011 the United States reported 1,925 cases of America of which 183 were reported to have severe disease. Given the significantly larger population of the United States, compared to the other countries represented in this paper, it is possible that no American centre sees a sufficiently large enough number of cases to inform a study of severe malaria in the USA.
The overall case fatality rate of 9% may not reflect modern practice. Management of ARDS has improved considerably in recent years and newer strategies for fluid resuscitation, in particular, may reduce the incidence of both multi-organ failure and long-term disability. Similarly, optimizing fluid management for patients with ARDS may reduce pulmonary capillary leak and subsequently the length of time that patients require on ICU. Greater awareness of what constitutes AKI may also result in a better outcome. Each of these factors, as well as improved antimicrobial protocols, management of shock and acidosis and increasing use of artemisinins, may further reduce the case fatality associated with severe imported malaria in the future.