Daniel Brasseur

ENTEROPATHOGENIC AGENTS IN CHILDREN WITH DIARRHOEA IN RURAL ZAIRE

A systematic study of enteropathogenic agents in the stools of children was carried out in a rural area of Kivu Province in Zaire in June, 1979. 84 inpatients and 271 outpatients with diarrhoea were investigated together with 117 inpatient and 203 outpatient controls without diarrhoea. Campylobacter jejuni was the most frequently recovered pathogen in both inpatients (24%) and outpatients (13.7%). Enterotoxigenic Escherichia coli was the next most common among children presenting as outpatients with diarrhoea (10.3%). Yersinia enterocolitica was isolated for the first time in this region. Rotaviruses were found only in outpatients with diarrhoea, and usually in children under two years of age. C. jejuni and Vibrio cholerae could also be isolated from the faeces of domestic animals living in close contact with these village families. Analysis of the clinical features did not lead to the recognition of a pattern typical of any particular pathogen. Salmonella, Shigella, and enteropathogenic E. coli did not play a significant role in the cases studied.

Copper deficiency in infants with active celiac disease.

Celiac disease was diagnosed in two unrelated infants aged 7 and 7.5 months with severe malnutrition. They showed typical clinical, biological, and histological signs of the disease. Moreover, accompanying copper deficiency was suggested by severe hypocupremia and persistent neutropenia; bone radiographs were also compatible with this diagnosis. Rapid and complete correction of these anomalies could only be obtained after addition of oral copper sulfate to the gluten-free diet. Mechanisms possibly involved in the development of copper deficiency in young infants with celiac disease are: chronic malabsorption; high copper needs in rapidly growing infants; and possibly increased biliary and digestive losses. It is therefore suggested that young children with severe celiac disease should be monitored for their copper status.

Lessons learnt from pandemic A(H1N1) 2009 influenza vaccination. Highlights of a European workshop in Brussels (22 March 2010).

This European workshop identified a number of lessons learnt in the field of vaccine licensure, prioritization of target groups, communication on pandemic vaccines, implementation of vaccination and safety monitoring. The mild severity of the pandemic A(H1N1) 2009 influenza virus influenced the perception of pandemic vaccines, as previous pandemic preparedness had anticipated a more virulent virus. This vaccination experience provides an important opportunity for research on the long-term immunogenicity and safety of pandemic vaccines in pregnant women and children, as well as on the long-term safety of adjuvants. Preparedness for future pandemics could involve improved decision-making on target groups and increased communication on vaccine safety.

Safe oral rehydration of hypertonic dehydration.

Summary: Eighteen infants with severe hypernatremic dehydration secondary to acute gastroenteritis were rehydrated during the 1st day with an oral glucose electrolyte solution containing 60 mmol sodium/L at a mean rate of 120 ml/kg/24 h. These 18 children were safely treated with oral therapy alone. No convulsions were observed during treatment. The mean decrease in natremia was 0.32 mmol/L/h, which compared favorably with the mean fall in natremia of 26 other infants in similar initial conditions who were treated intravenously. The present study lends additional support to the opinion that a slow decrease in plasma sodium (<0.5 mmol/L/h) helps to avoid seizures during treatment. As no other untoward effects were observed, this study also confirms that oral solutions given at a slow rate can effectively replace intravenous fluids in the majority of such children.

Tick-borne relapsing fever in a premature infant

Relapsing fever is caused by the Borrelia species of spirochetes. Louse-born epidemics of the disease may occur but the endemic disease is usually transmitted to humans by the bite of an infected tick (Ornithodorus). Transplacental infection was suggested more than 75 years ago (1) but has been rarely documented (2). We describe a case of neonatal relapsing fever where maternal infection was the probable cause of the premature delivery and infection in the infant.

A Belgian consensus-statement on growing-up milks for children 12-36 months old

Growing-up milks (GUM) are milk-based drinks with low protein and added minerals and vitamins intended for children 12–36 months. Since the advantages of GUM are heavily debated, we reviewed the literature. A literature search was done using the classic databases (Pubmed, Embase, Cochrane) on the use of GUM in 12- to 36-month-old young children. Only limited data are available. GUM have a highly variable composition as their marketing is not regulated. Nevertheless, all papers conclude that GUM help to cover nutritional requirements of 12- to 36-month-old infants. Conclusion: Appropriate intakes of macro- and micronutrients in 1- to 3-year-old children have long-term health benefits. Present diets offered to toddlers do in general not meet the requirements. Supplemented foods are therefore helpful, of which GUM is a possibility.

Significance of very low retinol levels during severe protein-energy malnutrition

In developing countries, severe vitamin A deficiency is associated with increased child mortality. In Kivu, Zaïre, child mortality rate is approximately 50 per 1000 per year and protein calorie malnutrition is endemic. To evaluate vitamin A status in this population, we measured plasma retinol levels in 28 severely malnourished hospitalized children (plasma albumin level below 3 g/dl), and in 153 outpatients (mean plasma albumin level: 3.19 +/- 0.7 g/dl) as controls. Sixty percent of inpatients and 37 percent of out-patients had retinol levels below 10 micrograms/dl (P = 0.02) suggesting a high prevalence of severe vitamin A deficiency in this population. We found that plasma retinol levels were correlated with low retinol binding protein plasma levels (r = 0.77). We conclude that although vitamin A deficiency probably exists in this malnourished population, low retinol levels could at least partly be related to decreased levels of its carrier protein.

Shigella and Shigellaemia

Two cases of bacteraemia with Shigella flexneri 2a in children are described. They illustrate the wide variety of clinical manifestations of shigellosis, ranging from benign gastroenteritis to septicaemia associated with severe extra-intestinal manifestations.

Biological risk factors for fatal protein energy malnutrition in hospitalized children in Zaire.

SummaryBiological markers were used in an attempt to predict mortality in children admitted to the hospital in Kivu, Zaire, for protein energy malnutrition. Data for 39 children who died (16.4%) showed significantly lower levels of albumin (1.61 vs. 2.53 g/dl; p < 0.001), transferrin (82.1 vs. 167.7 mg/dl; p < 0.001), and transthyretin (6.49 vs. 9.87 mg/dl; p < 0.001), but not of retinol-binding protein, than for the 199 survivors. Since albumin and transferrin were correlated, a Cox model was used to see whether albumin or transferrin has a significant predictive value independent of transthyretin. The relative risk predicted by each indicator was of the same order of magnitude, ∼4. We conclude that specific biological markers help to discriminate among hospitalized subjects at risk and to identify those in need of more intensive nutritional support to prevent early death.

Improvement of Pediatric Drug Development: Regulatory and Practical Frameworks.

PURPOSE A dearth in pediatric drug development often leaves pediatricians with no alternative but to prescribe unlicensed or off-label drugs with a resultant increased risk of adverse events. We present the current status of pediatric drug development and, based on our data analysis, clarify the problems in this area. Further action is proposed to improve the drug development that has pediatric therapeutic orphan status. METHODS We analyzed all Phase II/III and Phase III trials in ClinicalTrials.gov that only included pediatric participants (<18 years old) between 2006 and 2014. Performance index, an indicator of pediatric drug development, was calculated by dividing the annual number of pediatric clinical trials by million pediatric populations acquired from Census.gov. Effects of the 2 Japanese premiums introduced in 2010, for the enhancement of pediatric drug development, were analyzed by comparing mean performance index prepremiums (2006-2009) and postpremiums (2010-2014) among Japan, the European Union, and the United States. The European Union Clinical Trials Register and published reports from the European Medicines Agency were also surveyed to investigate the Paediatric Committee effect on pediatric clinical trials in the European Union. FINDINGS Mean difference of the performance index in prepremiums and postpremiums between Japan and the European Union were 0.296 (P < 0.001) and 0.066 (P = 0.498), respectively. Those between Japan and the United States were 0.560 (P < 0.001) and 0.281 (P = 0.002), indicating that pediatric drug development in Japan was more active after the introduction of these premiums, even reaching the level of the European Union. The Pediatric Regulation and the Paediatric Committee promoted pediatric drug development in the European Union. The registered number of clinical trials that includes at least 1 participants <18 years old in the European Union Clinical Trials Register increased by 247 trials (from 672) in the 1000 days after regulation. The ratio of pediatric clinical trials with an approved Paediatric Investigation Plan increased to >15% after 2008. IMPLICATIONS Recruitment and ethical obstacles make conducting pediatric clinical trials challenging. An improved operational framework for conducting clinical trials should mirror the ever-improving regulatory framework that incentivizes investment in pediatric clinical trials. Technological approaches, enhancements in electronic medical record systems, and community approaches that actively incorporate input from physicians, researchers, and patients could offer a sustainable solution to recruitment of pediatric study participants. The key therefore is to improve pediatric pharmacotherapy collaboration among industry, government, academia, and community. Expanding the regulatory steps taken in the European Union, United States, and Japan and using innovative clinical trial tools can move pediatric pharmacotherapy out of its current therapeutic orphan state.