Pediatr. Rep., Volume 3, Issue 2 (April 2011) – 8 articles

Cancer remains a major death cause in children, though outcomes have considerably improved over the past decades (1-3). Outcomes for children diagnosed with cancer have changed since ’70 from 80% mortality to 80% survival (2); while children with solid tumors 5-year survival has been reported as 67%, cure rates for childhood leukemia now approach 90% [4-5). Moreover, hematopoietic stem cell transplantation (HSCT) indications are still expanding for both malignant and non-malignant diseases. Full article

In Malta, the health system is hybrid, with similarities to both UK system and the US system, where the National Health Service is supplemented by private practice. This is widely performed either as a primary job or as a supplement to a government salary. This article reviews unfavourable secular trends in Maltese fertility, births, marriages, separations, single parenthood and loans incurred after marriage, and relates them to (equally unfavourable in terms of private practice) escalating numbers of paediatricians working in private practice. Overall, future prospects appear bleak for private practice in this branch of medicine, with a dwindling patient pool being shared by an ever-increasing number of paediatricians. The only identifiable factor that may mitigate is the potential for more private health insurance uptake. This must be coupled with a movement to improve the perception of a substantial proportion of the public that facilities are poorer in the private health sector than in the NHS service. Since Malta is a developed, EU country, these results may (cautiously) be extrapolated to other, larger developed countries. Full article

Recent increases in the dosages of the essential antituberculosis agents isoniazid (INH), rifampicin and pyrazinamide for use in children recommended by World Health Organization have raised concerns regarding the risk of hepatotoxicity. Published data relating to the incidence and pathogenesis of antituberculosis drug-induced hepatotoxicity (ADIH), particularly in children, is reviewed. Amongst 12,708 children receiving chemoprophylaxis, mainly with INH, but also other combinations of INH, rifampicin and pyrazinamide only 1 case (0.06%) of jaundice was recorded and abnormal liver functions documented in 110 (8%) of the 1225 children studied. Excluding tuberculous meningitis (TBM) 8984 were children treated for tuberculosis disease and jaundice documented in 75 (0.83%) and abnormal liver function tests in 380 (9.9%) of the 3855 children evaluated. Amongst 717 children treated for TBM, however, jaundice occurred in 72 (10.8%) and abnormal LFT were recorded in 174 (52.9%) of those studied. Case reports document the occurrence of ADIH in at least 63 children. Signs and symptoms of ADIH were frequently ignored in the recorded cases. Conclusion: ADIH is less common in children than adults, but can occur in children at any dosage of INH, RMP or PZA, but its incidence is considerably lower than in adults. Children with disseminated forms of disease are at greater risk of ADIH. Full article

Invasive fungal disease is a significant cause of morbidity and mortality in the neonate. The current study aims to assess the 1, 3-βD-Glucan (BG) assay in a prospective analysis in neonates with suspected fungaemia. A multicentre, prospective cohort study was conducted in Johannesburg, South Africa. The study included 72 neonates with clinically suspected late onset sepsis who were at high risk of fungaemia. A BG assay was performed on each patient and correlated with a sepsis classification based on the full blood count, C-reactive protein and blood culture results as no fungaemia, possible fungaemia, probable fungaemia or definite fungaemia. Sensitivity and specificity of the BG assay at levels of 60pg/ml are 73.2% and 71.0% respectively and at levels of 80pg/ml are 70.7% and 77.4% respectively. Positive and negative predictive values at 60pg/ml are 76.9% and 66.7% respectively and at 80pg/ml are 80.6% and 66.7% respectively. The area under the receiver operating curve is 0.753. The BG assay is a useful adjunct to the diagnosis of invasive fungal disease in neonates. It does, however, need to be considered in the context of the clinical picture and supplementary laboratory investigations. Full article

β-thalassemias, a group of autosomal recessive disorders resulting from reduced or absent production of β-globin chains from the β-globin locus, are very heterogeneous at the molecular level (for review see Weatherall & Clegg, 2001 and Cao & Galanello).1-2 More than 200 disease-causing mutations have been described to date. The large majority of mutations are simple nucleotide substitutions or deletions or insertions of oligonucleotides leading to frameshift. Rarely the β-thalassemias are the result of gross gene deletions. Homozygosity for β-thalassemia usually leads to the severe transfusion-dependent phenotype of thalassemia major. Treatment with a regular transfusion program and chelation therapy, aimed at reducing the transfusion iron-overload allows for normal growth and development and extends the life expectancy into the third to fifth decade. Bone marrow or cord blood transplantation (BMT) from an HLA-identical sib represent an alternative to traditional transfusion and chelation therapy. More rarely the homozygous state for β-thalassemia leads to the phenotype of thalassemia intermedia. Individuals with thalassemia intermedia present later, and have milder anemia and only rarely require transfusion. However also patients with thalassemia intermedia are at risk to develop iron overload secondary to increased intestinal iron absorption because of ineffective erythropoiesis. In the last few years there has been a dramatic advancement in the field of chelation therapy, genetic factors ameliorating the clinical phenotype, hemoglobin switching, gene therapy with lentiviral vectors and development of embryonic-like stem cells obtained by transfection and reprogramming differentiated somatic cells with key regulatory factors. All these developments, which are the topics of this review, may lead in the long term to advances in the traditional and in the gene and stem-cell-based therapy. Full article

Evans Syndrome is a rare autoimmune disease consisting of hemolytic anemia, thrombocytopenia and/or neutropenia. It may be associated with other autoimmune or lymphoproliferative diseases. Its course can be extremely serious and, rarely, even life-threatening; thus it represents a excellent treatment challenge for the pediatric hematologist. First line treatment consists of steroids and/or immunoglobulin; further therapy with rituximab, vincristine, cyclophosphamide and other immunosuppressive drugs can be considered in unresponsive patients. We describe a baby with refractory Evans Syndrome that was cured by prolonged administration of mycophenolate mofetil and remained disease-free for 4 years after the discontinuation of treatment. Full article

Because the development of healthy bodies during the years of growth has life-long health consequences, it is important to understand the early influences of diet and physical activity (PA). One way to generate hypotheses concerning such influences is to conduct cross-sectional studies of how diet and PA are related to different components of body composition. The subjects were 660 black and white adolescents. Total body bone mineral content (BMC) was measured with dual-energy X-ray absorptiometry; free-living diet and PA were assessed with 4-7 separate 24-h recalls. The main dietary variables investigated were: total energy intake, macronutrient distribution (%), dairy servings, vitamin D, and calcium. The main PA variables were hours of moderate PA (3-6 METs) and vigorous PA (>6 METs). BMC was higher in blacks than in whites (P<0.01) and it increased more in boys than in girls (age by sex interaction) as age increased (P<0.01). After adjustment for age, race and sex, higher levels of BMC were associated with higher levels of energy intake, dairy servings, calcium, vitamin D, and vigorous PA (all P 's<0.05). In the multivariable model, significant and independent proportions of the variance in BMC were explained by race, the age by sex interaction, calcium, and vigorous PA (all P 's<0.01). When height was used as the outcome variable, similar diet results were obtained; however, there was a sex by vigorous PA interaction, such that vigorous PA was associated with height only in the girls. These data are consistent with the hypothesis that the bone mass and height of growing youths are positively influenced by higher dietary intake of energy and dairy foods, along with sufficient amounts of vigorous PA. This hypothesis needs to be tested in randomized controlled trials. Full article

Neurobrucellosis manifesting as optic neuritis is a rare disease in childhood. We report a case of neurobrucellosis in a 11 year old girl leading to visual impairment and headache. Physical examination revealed mild oedema of right tibiotarsic joint and optic neuritis. Investigations showed CSF pleocytosis and a Brucella serum agglutination titer of 1/640. Complete reversal of the symptoms was observed after appropriate antibiotic treatment. To our knowledge only four cases of neurobrucellosis manifesting with visual impairment in childhood are previously reported in literature. Full article