Background: Few recent descriptions of severe childhood malaria have been published from high-transmission regions. In the current study, the clinical epidemiology of severe malaria in Mbale, Eastern Uganda, is described, where the entomological inoculation rate exceeds 100 infective bites per year. Methods: A prospective descriptive study was conducted to determine the prevalence, clinical spectrum and outcome of severe Plasmodium falciparum malaria at Mbale Regional Referral Hospital in Eastern Uganda. All children aged 2 months-12 years who presented on Mondays to Fridays between 8.00 am and 5.00 pm from 5th May 2011 until 30th April 2012 were screened for parasitaemia. Clinical and laboratory data were then collected from all P. falciparum positive children with features of WHO-defined severe malaria by use of a standardized proforma. Results: A total of 10 208 children were screened of which 6582 (64%) had a positive blood film. Of these children, 662 (10%) had clinical features of severe malaria and were consented for the current study. Respiratory distress was the most common severity feature (554; 83.7%), while 365/585 (62.4%) had hyperparasitaemia, 177/662 (26.7%) had clinical jaundice, 169 (25.5%) had severe anaemia, 134/660 (20.2%) had hyperlactataemia (lactate ≥ 5 mmol/L), 93 (14.0%) had passed dark red or black urine, 52 (7.9%) had impaired consciousness and 49/662 (7.4%) had hypoxaemia (oxygen saturations < 90%). In-hospital mortality was 63/662 (9.5%) overall but was higher in children with either cerebral malaria (33.3%) or severe anaemia (19.5%). Factors that were independently associated with mortality on multivariate analysis included severe anaemia [odds ratio (OR) 5.36; 2.16-1.32; P = 0.0002], hyperlactataemia (OR 3.66; 1.72-7.80; P = 0.001), hypoxaemia (OR) 3.64 (95% CI 1.39-9.52; P = 0.008), and hepatomegaly (OR 2.29; 1.29-4.06; P = 0.004). No independent association was found between mortality and either coma or hyperparasitaemia. Conclusions: Severe childhood malaria remains common in Eastern Uganda where it continues to be associated with high mortality. An unusually high proportion of children with severe malaria had jaundice or gave a history of having recently passed dark red or black urine, an issue worthy of further investigation.

BackgroundSevere anemia (SA, hemoglobin <6 g/dl) is a leading cause of pediatric hospital admission in Africa, with significant in-hospital mortality. The underlying etiology is often infectious, but specific pathogens are rarely identified. Guidelines developed to encourage rational blood use recommend a standard volume of whole blood (20 ml/kg) for transfusion, but this is commonly associated with a frequent need for repeat transfusion and poor outcome. Evidence is lacking on what hemoglobin threshold criteria for intervention and volume are associated with the optimal survival outcomes.MethodsWe evaluated the safety and efficacy of a higher volume of whole blood (30 ml/kg; Tx30: n = 78) against the standard volume (20 ml/kg; Tx20: n = 82) in Ugandan children (median age 36 months (interquartile range (IQR) 13 to 53)) for 24-hour anemia correction (hemoglobin >6 g/dl: primary outcome) and 28-day survival.ResultsMedian admission hemoglobin was 4.2 g/dl (IQR 3.1 to 4.9). Initial volume received followed the randomization strategy in 155 (97%) patients. By 24-hours, 70 (90%) children in the Tx30 arm had corrected SA compared to 61 (74%) in the Tx20 arm; cause-specific hazard ratio = 1.54 (95% confidence interval 1.09 to 2.18, P = 0.01). From admission to day 28 there was a greater hemoglobin increase from enrollment in Tx30 (global P <0.0001). Serious adverse events included one non-fatal allergic reaction and one death in the Tx30 arm. There were six deaths in the Tx20 arm (P = 0.12); three deaths were adjudicated as possibly related to transfusion, but none secondary to volume overload.ConclusionA higher initial transfusion volume prescribed at hospital admission was safe and resulted in an accelerated hematological recovery in Ugandan children with SA. Future testing in a large, pragmatic clinical trial to establish the effect on short and longer-term survival is warranted.Trial registrationClinicalTrials.Gov identifier: NCT01461590 registered 26 October 2011.Please see related commentary article http://www.biomedcentral.com/1741-7015/12/68/abstract.

Highlights d Inpatient feeding with standard or legume-based feeds resulted in similar weight gain d Legume feeds limited antibiotic-mediated decrease in gut microbiota richness at day 7 d Microbial fermentation was preserved, which has implications for gut health and integrity d Further testing of legume-enriched feeds in severe acute malnutrition is warranted

This study was approved by the Mbale Research Ethics committee (Reference: 2013-050). Transfusion and Treatment of severe Anaemia in African Children: a randomized controlled Trial (TRACT) registration: ISRCTN84086586.

Background: Changes in intestinal mucosal integrity and gut microbial balance occur in severe acute malnutrition (SAM), resulting in treatment failure and adverse clinical outcomes (gram-negative sepsis, diarrhoea and high case-fatality). Transient lactose intolerance, due to loss of intestinal brush border lactase, also complicates SAM, thus milk based feeds may not be optimal for nutritional rehabilitation. Since the gut epithelial barrier can be supported by short chain fatty acids, derived from microbiota fermentation by particular fermentable carbohydrates, we postulated that an energy-dense nutritional feed comprising of legume-based fermentable carbohydrates, incorporated with lactose-free versions of standard World Health Organization (WHO) F75/F100 nutritional feeds will enhance epithelial barrier function in malnourished children, reduce and promote resolution of diarrhoea and improve overall outcome. Methods: We will investigate in an open-label trial in 160 Ugandan children with SAM, defined by mid-upper arm circumference <11.5cm and/or presence of kwashiorkor. Children will be randomised to a lactose-free, chickpea-enriched feed containing 2 kcal/ml, provided in quantities to match usual energy provision (experimental) or WHO standard treatment F75 (0.75 kcal/ml) and F100 (1 kcal/ml) feeds on a 1:1 basis, conducted at Mbale Regional Referral Hospital nutritional rehabilitation unit. The primary outcomes are change in MUAC at day 90 and survival to day 90. Secondary outcomes include: i) moderate to good weight gain (>5 g/kg/day), ii) de novo development of diarrhoea (>3 loose stools/day), iii) time to diarrhoea resolution (if >3 loose stools/day), and iv) time to oedema resolution (if kwashiorkor) and change in intestinal biomarkers (faecal calprotectin). Discussion: We hypothesize that, if introduced early in the management of malnutrition, such lactose-free, fermentable carbohydrate-based feeds, could safely and cheaply improve global outcome by reducing lactose intolerance-related diarrhoea, improving mucosal integrity and enhancing immunity, and limiting the risk of systemic infection and associated broad-spectrum antibiotic resistance. Registration: ISRCTN 10309022.