BackgroundThe degree of volume depletion in severe malaria is currently unknown, although knowledge of fluid compartment volumes can guide therapy. To assist management of severely ill children, and to test the hypothesis that volume changes in fluid compartments reflect disease severity, we measured body compartment volumes in Gabonese children with malaria.Methods and FindingsTotal body water volume (TBW) and extracellular water volume (ECW) were estimated in children with severe or moderate malaria and in convalescence by tracer dilution with heavy water and bromide, respectively. Intracellular water volume (ICW) was derived from these parameters. Bioelectrical impedance analysis estimates of TBW and ECW were calibrated against dilution methods, and bioelectrical impedance analysis measurements were taken daily until discharge. Sixteen children had severe and 19 moderate malaria. Severe childhood malaria was associated with depletion of TBW (mean [SD] of 37 [33] ml/kg, or 6.7% [6.0%]) relative to measurement at discharge. This is defined as mild dehydration in other conditions. ECW measurements were normal on admission in children with severe malaria and did not rise in the first few days of admission. Volumes in different compartments (TBW, ECW, and ICW) were not related to hyperlactataemia or other clinical and laboratory markers of disease severity. Moderate malaria was not associated with a depletion of TBW.ConclusionsSignificant hypovolaemia does not exacerbate complications of severe or moderate malaria. As rapid rehydration of children with malaria may have risks, we suggest that fluid replacement regimens should aim to correct fluid losses over 12–24 h.

In severe malaria, there was a positive correlation between plasma glutamine and lactate levels (p=0.009, r=0.281). This correlation may reflect impaired gluconeogenesis. Glutamine supplementation is probably not justified in severe P. falciparum infection.

Understanding blood volume changes in children with malaria is important for managing fluid status. Traditionally, blood/red cell volume measurements have used radioactive chromium isotopes. We applied an alternative approach, using non-radioactive chromium-53 labelling and mass spectrometry to investigate red cell volume (RCV) in Gabonese children with malaria. Nineteen children with malaria participated (10 severe, 9 moderately severe; ages 15 months to 7 years). Blood labelled with 53 Cr-chromate ex vivo was re-injected, then sampled 30 min later. Pre-and post-injection 53 Cr content were measured by gas chromatography/electron ionisation mass spectrometry of the chromium-trifluoroacetylacetone (TFA) chelate, calibrated against 50 Cr standards. Blood and red cell volumes were calculated from isotopic dilution in 15 of 19 children (in four, insufficient signal mitigated analysis). In this small pilot study, there were no significant differences between moderate and severe cases. Including all subjects, the mean RCV was reduced compared with predicted values (184 vs. 269 mL; p ¼ 0.016) but blood volume, 71 W 33 mL/kg (normalised for weight), was close to predicted, $77 mL/kg, commensurate with reduced haematocrit. Blood lactate concentration correlated negatively with RCV/weight (r ¼ À0.56, p ¼ 0.028), consistent with anaemia. In one case, sequential samples over 42 days gave an estimated rate of 53 Cr disappearance of 1.4%/day (equivalent half-life: 70 days). 53 Cr-labelling of red cells may be used to estimate blood and red cell volumes and can be used as an investigative tool in situations such as childhood diseases and resource-constrained settings. Although the red cell mass is depleted in malaria, the blood volume appears relatively well preserved.