Acute kidney injury is common in severe malaria and associated with short- and long-term mortality developing in 50% of cases after admission. Cystatin C and BUN are associated with the severity of AKI, are elevated at admission and predict mortality.

BackgroundSevere malaria remains a major cause of childhood mortality globally. Decreased endothelial nitric oxide is associated with severe and fatal malaria. The hypothesis was that adjunctive inhaled nitric oxide (iNO) would improve outcomes in African children with severe malaria.MethodsA randomized, blinded, placebo-controlled trial of iNO at 80 ppm by non-rebreather mask versus room air placebo as adjunctive treatment to artesunate in children with severe malaria was conducted. The primary outcome was the longitudinal course of angiopoietin-2 (Ang-2), an endothelial biomarker of malaria severity and clinical outcome.ResultsOne hundred and eighty children were enrolled; 88 were assigned to iNO and 92 to placebo (all received IV artesunate). Ang-2 levels measured over the first 72 h of hospitalization were not significantly different between groups. The mortality at 48 h was similar between groups [6/87 (6.9 %) in the iNO group vs 8/92 (8.7 %) in the placebo group; OR 0.78, 95 % CI 0.26–2.3; p = 0.65]. Clinical recovery times and parasite clearance kinetics were similar (p > 0.05). Methaemoglobinaemia >7 % occurred in 25 % of patients receiving iNO and resolved without sequelae. The incidence of neurologic deficits (<14 days), acute kidney injury, hypoglycaemia, anaemia, and haemoglobinuria was similar between groups (p > 0.05).ConclusionsiNO at 80 ppm administered by non-rebreather mask was safe but did not affect circulating levels of Ang-2. Alternative methods of enhancing endothelial NO bioavailability may be necessary to achieve a biological effect and improve clinical outcome.Trial Registration: ClinicalTrials.gov NCT01255215Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0946-2) contains supplementary material, which is available to authorized users.

Plasmodium falciparum resistance to artemisinin derivatives is emerging in Asia. We examined molecular markers of resistance in 78 children in Uganda who had severe malaria and were treated with intravenous artesunate. We observed in the K13-propeller domain, A578S, a low-frequency (3/78), nonsynonymous, single-nucleotide polymorphism associated with prolonged parasite clearance.

IntroductionThe development of simple clinical tools to identify children at risk of death would enable rapid and rational implementation of lifesaving measures to reduce childhood mortality globally.MethodsWe evaluated the ability of three clinical scoring systems to predict in-hospital mortality in a prospective observational study of Ugandan children with fever. We computed the Lambaréné Organ Dysfunction Score (LODS), Signs of Inflammation in Children that Kill (SICK), and the Pediatric Early Death Index for Africa (PEDIA). Model discrimination was evaluated by comparing areas under receiver operating characteristic curves (AUCs) and calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. Sub-analyses were performed in malaria versus non-malaria febrile illness (NMFI), and in early (≤48 hours) versus late (>48 hours) deaths.ResultsIn total, 2089 children with known outcomes were included in the study (99 deaths, 4.7% mortality). All three scoring systems yielded good discrimination (AUCs, 95% confidence interval (CI): LODS, 0.90, 0.88 to 0.91; SICK, 0.85, 0.83 to 0.86; PEDIA, 0.90, 0.88 to 0.91). Using the Youden index to identify the best cut-offs, LODS had the highest positive likelihood ratio (+LR, 95% CI: LODS, 6.5, 5.6 to 7.6; SICK, 4.4, 3.9 to 5.0; PEDIA, 4.4, 3.9 to 5.0), whereas PEDIA had the lowest negative likelihood ratio (−LR, 95% CI: LODS, 0.21, 0.1 to 0.3; SICK, 0.22, 0.1 to 0.3; PEDIA, 0.16, 0.1 to 0.3), LODS and PEDIA were well calibrated (P = 0.79 and P = 0.21 respectively), and had higher AUCs than SICK in discriminating between survivors and non-survivors in malaria (AUCs, 95% CI: LODS, 0.92, 0.90 to 0.93; SICK, 0.86, 0.84 to 0.87; PEDIA, 0.92, 0.90 to 0.93), but comparable AUCs in NMFI (AUCs, 95% CI: LODS, 0.86, 0.83 to 0.89; SICK, 0.82, 0.79 to 0.86; PEDIA, 0.87, 0.83 to 0.893). The majority of deaths in the study occurred early (n = 85, 85.9%) where LODS and PEDIA had good discrimination.ConclusionsAll three scoring systems predicted outcome, but LODS holds the most promise as a clinical prognostic score based on its simplicity to compute, requirement for no equipment, and good discrimination.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0773-4) contains supplementary material, which is available to authorized users.

Abstract. Severe malaria is frequently managed without access to laboratory testing. We report on the performance of point-of-care tests used to guide the management of a cohort of 179 children with severe malaria in a resource-limited Ugandan hospital. Correlation coefficients between paired measurements for glucose (i-STAT and One Touch Ultra), lactate (i-STAT and Lactate Scout), and hemoglobin (Hb; laboratory and i-STAT) were 0.86, 0.85, and 0.73, respectively. The OneTouch Ultra glucometer readings deviated systematically from the i-STAT values by +1.7 mmol/L. Lactate Scout values were systematically higher than i-STAT by +0.86 mmol/L. Lactate measurements from either device predicted subsequent mortality. Hb estimation by the i-STAT instrument was unbiased, with upper and lower limits of agreement of −34 and +34 g/L, and it was 91% sensitive and 89% specific for the diagnosis of severe anemia (Hb 50 g/L). New commercially available bedside diagnostic tools, although imperfect, may expedite clinical decision-making in the management of critically ill children in resource-constrained settings.