Abstract
BackgroundSevere falciparum malaria can be compounded by bacterial sepsis, necessitating antibiotics in addition to anti-malarial treatment. The objective of this analysis was to develop a prognostic model to identify patients admitted with severe malaria at higher risk of developing bacterial sepsis.MethodsA retrospective data analysis using trial data from the South East Asian Quinine Artesunate Malaria Trial. Variables correlating with development of clinically defined sepsis were identified by univariable analysis, and subsequently included into a multivariable logistic regression model. Internal validation was performed by bootstrapping. Discrimination and goodness-of-fit were assessed using the area under the curve (AUC) and a calibration plot, respectively.ResultsOf the 1187 adults with severe malaria, 86 (7.3%) developed clinical sepsis during admission. Predictors for developing sepsis were: female sex, high blood urea nitrogen, high plasma anion gap, respiratory distress, shock on admission, high parasitaemia, coma and jaundice. The AUC of the model was 0.789, signifying modest differentiation for identifying patients developing sepsis. The model was well-calibrated (Hosmer–Lemeshow Chi squared = 1.02). The 25th percentile of the distribution of risk scores among those who developed sepsis could identify a high-risk group with a sensitivity and specificity of 70.0 and 69.4%, respectively.ConclusionsThe proposed model identifies patients with severe malaria at risk of developing clinical sepsis, potentially benefiting from antibiotic treatment in addition to anti-malarials. The model will need further evaluation with more strictly defined bacterial sepsis as outcome measure.
Highlights
Severe falciparum malaria can be compounded by bacterial sepsis, necessitating antibiotics in addition to anti-malarial treatment
Hypotension is much less common in severe malaria compared to bacterial sepsis [9], other clinical features of severe malaria and severe sepsis with organ failure overlap, hampering the diagnosis of concomitant sepsis
Study population and sampling The study was a retrospective analysis of the South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT), a large randomized controlled trial (RCT) comparing intravenous artesunate with quinine as antimalarial treatment
Summary
Severe falciparum malaria can be compounded by bacterial sepsis, necessitating antibiotics in addition to anti-malarial treatment. In paediatric severe malaria, where concomitant bacterial sepsis is common, treatment guidelines recommend routine co-administration of antibiotics to anti-malarial treatment [11, 12]. Routine antibiotics it not recommended for adult patients with severe malaria. In this group it is important to identify patients at risk for concomitant bacterial sepsis, since these would require life-saving antibiotic treatment in addition to antimalarial treatment. Antibiotics can be withheld in patients identified at low risk for bacterial sepsis, saving costs and reducing antibiotic drug pressure driving antimicrobial drug resistance [13]
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