Recommendations for the management of severe malaria and severe dengue in resource-limited settings

Abstract

Sepsis in resource-limited settings will often have different aetiologies to those in western settings, including severe malaria, severe dengue, viral haemorrhagic fevers, mellioidosis, typhus, and leptospirosis. The Surviving Sepsis Campaign (SSC) guidelines [1] are mainly based on evidence from studies on bacterial sepsis. These guidelines are widely applicable, but there are also exceptions. We focus here on disease-specific recommendations for the management of severe falciparum malaria and severe dengue. An international team with extensive practical experience in resource-limited intensive care units (ICUs) identified key questions concerning the SSC’s management recommendations on these diseases. Pertinent evidence from resource-limited settings was evaluated using the grading of recommendations assessment, development and evaluation (GRADE) tools. Recommendations for the management of severe malaria and severe dengue in resource-limited settings Severe falciparum malaria Severe falciparum malaria is a multi-organ disease caused by Plasmodium falciparum transmitted by Anopheles mosquitoes. The highest transmission and disease burden is in sub-Saharan Africa, where severe malaria is largely a paediatric disease, as older children and adults become partly immune. In Asia and South America, all age groups may be affected. Independent of age, the presenting symptoms with the strongest prognostic significance are coma (cerebral malaria), metabolic (lactic) acidosis and renal dysfunction. Hypotension occurs infrequently (~12% of cases). One of the main pathophysiologic differences of severe falciparum malaria compared to bacterial sepsis is microcirculatory impairment caused by sequestration of parasite-infected erythrocytes, red cell rigidity and red cell clumping. Management requires rapid parasitological diagnosis by microscopy or rapid diagnostic testing (RDT) and prompt initiation of parenteral artesunate [2]. The SSC recommends that, in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia, with either hypotension or hyperlactatemia, an initial fluid challenge of at least 30 ml/kg of crystalloids be administered, of which a portion may be albumin equivalent [1]. Both paediatric and adult patients with severe malaria and tissue hypoperfusion are volume depleted intravascularly. A large trial on fluid bolus therapy in 3138 African children with severe infections and compensated shock, 57% of whom had falciparum malaria, showed an overall 40% increase in mortality with fluid bolus therapy (20 or 40 ml/kg with either saline or 5% albumin). In the 1793 children with severe P. falciparum malaria, mortality in the bolus groups was 51% higher [RR 1.51 (1.17–1.95)] [3]. In Asian studies of adult severe malaria, rapid fluid resuscitation did not improve metabolic acidosis [4, 5] and transpulmonary thermodilution-guided rapid fluid resuscitation resulted in pulmonary oedema in 8/28 (29%) patients [5]. One observational study from Myanmar showed no deterioration in renal function or plasma lactate with maintenance fluid therapy between 1.3 and 2.2 ml/kg/h [6]. We recommend against the use of fluid bolus therapy in normotensive patients with severe falciparum malaria (1A). In normotensive patients, we suggest initial (24 h) crystalloid fluid therapy of 2–4 ml/kg/h, which may subsequently be reduced to 1 ml/kg/h in patients receiving additional fluids, e.g. through enteral tube feeding (2D). We suggest fluid bolus therapy (30 ml/kg) with an isotonic crystalloid in patients with hypotensive shock and, if available, early initiation of vasopressor support (ungraded) (Table 1). Table 1 Recommendations and suggestions for the management of patients with severe malaria and severe dengue in resource-limited settings (with grading)