Baked egg food challenges - clinical utility of skin test to baked egg and ovomucoid in children with egg allergy.

BACKGROUND: Many children with IgE-mediated egg allergy can tolerate products containing extensively heated (baked) egg. Aside from food challenge, there are no tests which reliably predict tolerance to baked egg in egg-allergic individuals. OBJECTIVES: To determine if skin prick test (SPT) to baked egg (muffin) and ovomucoid can predict the outcome of baked egg challenges in egg allergic patients. METHODS: In this prospective study, children with a recent history of immediate allergic reactions to egg [and corroborative positive SPT or serum-specific IgE (ssIgE) to egg] or those with SPT/ssIgE > 95% PPV for egg allergy were invited to undergo an open standardized baked egg (muffin) challenge. SPT to egg white, ovomucoid, and fresh muffin were performed immediately prior to challenge. RESULTS: One hundred and forty-three egg allergic children underwent baked egg challenge and of these, 90 (63%) tolerated 1 g of egg protein in a baked muffin. Of the 53 positive challenges, eight (15%) had respiratory and/or cardiovascular symptoms. The median SPT diameters in positive challenges compared with negative challenges were baked muffin - 6.0 mm/4.0 mm and ovomucoid 7.5 mm/5.0 mm respectively. Receiver operating characteristic (ROC) curves were generated for SPT to baked egg and ovomucoid. The area under the curve was 0.68 for baked egg, and 0.67 for ovomucoid. A muffin SPT of < 2 mm had a negative predictive value of 88% and an ovomucoid SPT ≥ 11 mm had a positive predictive value of 100%. CONCLUSIONS AND CLINICAL RELEVANCE: A SPT of < 2 mm to muffin had a high negative predictive value to baked egg challenge. Ovomucoid SPT ≥ 11 mm was very likely to predict a reaction to baked egg. In these children, deferring the challenge would be appropriate.

Is Roifman syndrome an X-linked ciliopathy with humoral immunodeficiency? Evidence from 2 new cases.

Roifman syndrome is a rare syndrome of bone dysplasia, growth retardation, retinal dystrophy and humeral immunodeficiency. Six cases have been reported to date, all of whom are male. We report a boy with clinical features of Roifman syndrome, whose older sister has skewed X-inactivation and a milder phenotype of the same disorder, supporting the hypothesis that this is an X-linked recessive condition. Both children had previously had a provisional diagnosis of Jeune dysplasia, and the boy had neonatal hip X-rays which demonstrated 'acetabular spurs' which are seen in a number of diseases thought to be caused by dysfunction of nonmotile cilia, including Jeune asphyxiating thoracic dystrophy. This finding in combination with other features such as retinal dystrophy, hepatic and renal disease suggests that the gene which is affected in Roifman syndrome may be involved with the function of nonmotile cilia and that Roifman syndrome may be the first example of a ciliopathy with associated immunodeficiency.

Guidelines for the prevention of sepsis in asplenic and hyposplenic patients.

Asplenic or hyposplenic patients are at risk of fulminant sepsis. This entity has a mortality of up to 50%. The spectrum of causative organisms is evolving as are recommended preventive strategies, which include education, prophylactic and standby antibiotics, preventive immunizations, optimal antimalarial advice when visiting endemic countries and early management of animal bites. However, there is evidence that adherence to these strategies is poor. Consensus-updated guidelines have been developed to help Australian and New Zealand clinicians and patients in the prevention of sepsis in asplenic and hyposplenic patients.

Radioimmunoassay for the detection of active-site specific thrombin inhibitors in biological fluids. I. Assay characteristics and quantitation of recombinant hirudin.

A sensitive radioimmunoassay (RIA) for the quantitation of recombinant (r) hirudin in biological fluids is described. Taking advantage of the highly specific hirudin-thrombin interaction, a monoclonal antibody to human alpha-thrombin was used to capture hirudin-thrombin complexes in a competitive binding assay. Quantitation of r.hirudin in buffer, plasma or urine at concentrations ranging from 0.17 to 20 ng/ml (1.7 x 10(-3) to 2 x 10(-2) antithrombin units/ml) was achieved. In the absence of competing unlabelled r.hirudin the assay also measured alpha-thrombin (from 2 x 10(-4) to 1 x 10(-2) NIH units/ml) in citrated or defibrinated human plasma. A series of peptides corresponding to the carboxyl-terminal region of hirudin and with varying anticoagulant activities did not displace 125I-r.hirudin in the RIA described, confirming published data that these hirudin fragments bind to a site distant to the catalytic site of thrombin. The assay was used to test hirudin clearance after bolus i.v. injections of 0.1 mg r.hirudin [Val1-Val2] into human volunteers. The plasma concentrations and elimination kinetics of r.hirudin were in good agreement with published data and a close correlation between hirudin plasma concentration and prolonged clotting time was observed.

Repeated prevalence surveys of paediatric hospital-acquired infection.

Hospital-acquired infection (HAI) results in an enormous burden of excess morbidity, mortality and cost in both adults and children. Monitoring HAI is difficult, especially with limited resources, but it is vital if infection control measures are to be appropriately implemented and assessed. Cross-sectional prevalence surveys, repeated every six months, have been used effectively to monitor HAI in adults, but this technique has not been previously employed in the paediatric population. We performed prevalence surveys of HAI on a single day once every six months for five years, using a standardized questionnaire. Of the 1623 inpatients surveyed, 125 (7.7%) had HAI and 352 (21%) had community-acquired infection. In those with HAI, central-line infections, pneumonia, and wound infections predominated. A hospital stay of greater than seven days was associated with a sixfold increase in the risk of HAI. In addition, admission to a paediatric or neonatal intensive care unit, the presence of a urinary or vascular catheter, the presence of an endotracheal tube, immunosuppression and recent surgery were all associated with a significantly increased risk of HAI. In contrast to other studies, younger children were not at increased risk of HAI; admission to the neonatal unit, rather than age per se, was associated with increased risk. We conclude that repeated prevalence surveys enable simple and cost-effective assessment of HAI, facilitating appropriate infection control interventions. They should be used more widely in the paediatric setting.

Rice: a common and severe cause of food protein-induced enterocolitis syndrome.

OBJECTIVE: To examine and compare the characteristics of food protein-induced enterocolitis syndrome (FPIES) caused by rice and cow's milk/soy. DESIGN: Retrospective study of children presenting with FPIES to the Children's Hospital at Westmead, NSW, Australia, over a 16-year period. RESULTS: There were 14 children with 26 episodes of rice FPIES compared with 17 children with 30 episodes of cow's milk (n = 10) or soy (n = 7) FPIES. Children with rice FPIES were more likely to have FPIES caused by other foods (36%) than children with FPIES caused by cow's milk/soy (0%). Rice caused more episodes of FPIES before a correct diagnosis was made (median 4 (range 1-4) vs median 2 (range 1-4)) and triggered more severe reactions with higher rates of intravenous fluid resuscitation (42% vs 17%) than reactions caused by cow's milk/soy. CONCLUSIONS: This study highlights the emerging importance of rice, a food commonly thought to be "hypoallergenic", as a significant trigger of FPIES. Paediatricians should be aware that rice not only has the potential to cause FPIES, but that such reactions tend be more severe than those caused by cow's milk/soy.

Asthma prevention: breast is best?

Whilst breastfeeding has been considered to exert a preventative effect on the development of allergic disease, several recent publications have challenged this view, particularly with respect to the long-term outcomes for asthma. There are many other beneficial effects of breastfeeding apart from the possibility of allergy prevention. The suggestion that breastfeeding may increase the development of allergic disease raises concerns about the appropriate steps to take for primary prevention of allergy. It is concluded that breastfeeding can still be recommended for the beneficial effects in reducing atopic disease in childhood in addition to the other demonstrated benefits, and that there are unresolved questions concerning the few studies that suggest the possibility of increased allergic disease in later life.

Effect of locally administered heparins on delayed-type hypersensitivity reactions.

Inflammatory reactions involved in delayed-type hypersensitivity (DTH) are associated with extravascular coagulation and fibrin deposition. Heparin and other anticoagulants administered systemically inhibit DTH reactions but the direct effect of intradermally injected heparin on the development of DTH skin responses has not been reported. The effects of heparin on the DTH reaction elicited by ovalbumin (OVA) in guinea pigs 1-3 weeks after sensitization were examined. Unfractionated heparin, low affinity heparin (LAH; non-anticoagulant) and high affinity heparin (HAH; anticoagulant) were injected together with suboptimal amounts of OVA. Heparin and LAH enhanced skin induration, LAH (0.5 micrograms) by an average of 50% above that due to OVA alone at 24 h (p less than 0.01). In contrast, HAH (0.5 micrograms) significantly reduced skin induration at 24 h. Heparin and LAH also significantly increased cellular infiltration with LAH having the greater effect. At 4 h the infiltrate consisted mainly of neutrophils whereas at 24 h mononuclear cells predominated. Fibrin deposition, assessed both by immunohistology and quantitation of radioactive fibrin extracted from skin test sites, was increased by 30% when OVA was tested in the presence of LAH. Mast cell heparin released locally at sites of DTH has the potential to modulate these reactions in either a pro- or anti-inflammatory manner. This study is the first to demonstrate differences in the capacities of LAH and HAH to modulate cell-mediated inflammation.

Interferon-gamma levels in nasopharyngeal secretions of infants with respiratory syncytial virus and other respiratory viral infections.

Respiratory syncytial virus (RSV) infection, one of the most common causes of hospitalization of children in developed countries, has been implicated as a cause of asthma. We aimed to characterize the cytokine profile in nasopharyngeal aspirates (NPAs) taken from infants during upper respiratory tract infection to investigate whether RSV induced a unique immune response as compared with other viruses. Additionally, we sought to determine whether this profile was influenced by the infants' atopic status. A prospective birth cohort of babies at high risk of atopy was recruited. Ratios of a T-helper 1 (Th1) cytokine, interferon gamma (IFN-gamma) and a T-helper 2 (Th2)-like cytokine, interleukin-10 (IL-10), in NPAs were determined during episodes of respiratory tract infections in the first year. The viral aetiology of the respiratory tract infections was determined using polymerase chain reaction (PCR), culture and immunofluorescence. Atopic status was ascertained at 1 year of age using skin prick tests. Participants were recruited antenatally and subsequently followed in the community. Sixty babies with one or both parents atopic were enrolled into the study. IFN-gamma : IL-10 ratios in NPAs during upper respiratory tract infections and their correlation with viral aetiology and atopic status were the main outcome measures. The mean IFN-gamma : IL-10 ratio was significantly lower (due to lower IFN-gamma) during RSV infections than during infections with other viruses (P = 0.035). The cytokine ratio, however, did not differ between infants with or without wheeze during URTIs (P = 0.44), or between infants who were atopic or non-atopic (P = 0.49). This study suggests that RSV is associated with lower IFN-gamma production in young babies, regardless of their atopic status, compared to upper respiratory tract infections where either another virus is detected or where no viral identification is made.

A comparison of IL-2 levels in nasopharyngeal and endotracheal aspirates of babies with respiratory syncytial viral bronchiolitis.

BACKGROUND: Cytokines such as IL-2 are thought to be important in the pathogenesis of respiratory tract inflammation. Cytokine levels in nasopharyngeal aspirates (NPAs) have been used as a measure of respiratory inflammation in children with viral infections, but it is unclear whether they reflect levels in the lower respiratory tract. OBJECTIVE: We sought to assess the correlation between IL-2 levels in the nasopharyngeal and endotracheal secretions of children intubated with respiratory syncytial virus (RSV)-positive bronchiolitis. METHODS: NPA and endotracheal aspirates were collected concurrently from intubated infants with RSV-positive bronchiolitis. IL-2 levels were assayed by ELISA, and the results were compared according to collection site. RESULTS: Nine paired specimens were collected. IL-2 levels ranged from 31 pg/mL to 8040 pg/mL. No significant difference was found in the geometric mean IL-2 values from the 2 collection sites. The intraclass correlation coefficient between NPA IL-2 levels and endotracheal aspirate IL-2 levels was 0.83. CONCLUSION: IL-2 levels in NPAs are comparable with those in the lower respiratory tracts of infants with RSV-positive bronchiolitis. NPA cytokine levels provide a simple and useful means of assessing respiratory tract inflammation.

Investigation of suspected deficient Fas-mediated apoptosis in a father and son.

BACKGROUND: A 2-year-old boy presented with symptoms consistent with a diagnosis of autoimmune lymphoproliferative syndrome (ALPS). His father had been splenectomized at age 12 with similar symptoms. ALPS is a rare hereditary syndrome that may result from a functional defect in Fas-mediated apoptosis. METHODS: Peripheral blood lymphocytes (PBL) and splenic lymphocytes from the patient and PBL from his father and a normal control were analyzed for surface Fas expression. They were then stimulated with an anti-Fas monoclonal antibody (DX2). Apoptosis was assayed by flow cytometry at 0, 20, 28, and 34 h. RESULTS: There was no significant difference in expression of Fas (CD95) in the PBL of the patient, his father, or the normal control, or the splenic lymphocytes. Compared with the normal control, the PBL of the patient and his father failed to progress to apoptosis. They also contained a markedly elevated proportion of CD3+CD4-CD8- "double-negative" cells. CONCLUSIONS: PBL from both the patient and his father expressed CD95, but failed to proceed to apoptosis after stimulation, suggesting a functional defect. These results and the clinical presentation are consistent with published descriptions of ALPS.

Pertussis antibody levels in infants immunized with an acellular pertussis component vaccine, measured using whole-cell pertussis ELISA.

A commercially available whole-cell pertussis IgG ELISA was used to test the response of 137 2-month-old infants to immunization with a trivalent acellular pertussis vaccine. The pre-immunization geometric mean (GM) IgG index was 6.96 (95% confidence interval (CI) 5.88-8.04) and the postimmunization GM index was 13.16 (95% CI 12. 20-14.11), P < 0.001. Eighty percent of subjects (110/137) had a significant 1.5-fold increase of pertussis IgG index (97/137, 71%) or a postimmunization IgG index > 10 (93/137, 68%). In single antigen ELISA, 83% showed at least a fourfold increase in pertussis toxin-specific IgG (PT-IgG) and 91% showed an increase in IgG specific for filamentous haemagglutinin (FHA-IgG). Four percent had high pre- immunization antibody levels (index > 20), likely to reflect recent maternal exposure to pertussis. This correlated with a smaller increase in pertussis IgG index. A decline in pertussis IgG index postimmunization occurred in 17/24 infants (71%) whose pre-immunization IgG index was > 10. This postimmunization pertussis IgG index was not significantly different to that of infants with a low pre-immunization index. A similar trend was noted with PT-IgG and FHA-IgG results. The whole-cell ELISA can detect a response to acellular pertussis vaccination in most infants if both antibody index and degree of seroconversion are calculated and at least one criterion is satisfied.

The emergence of resistant pneumococcal meningitis--implications for empiric therapy.

BACKGROUND: Following the emergence of penicillin and cephalosporin resistant pneumococcal meningitis in the United States, inclusion of vancomycin in empiric therapy for all suspected bacterial meningitis was recommended by the American Academy of Pediatrics. Few data are available to evaluate this policy. AIMS: To examine the management and clinical course in relation to antibiotic therapy of a large unselected cohort of children with pneumococcal meningitis in a geographic area where antibiotic resistance has recently increased. METHODS: Retrospective review of all cases of pneumococcal meningitis in a defined population (Sydney, Australia), 1994-99. RESULTS: A total of 104 cases without predisposing illnesses were identified; timing of lumbar puncture (LP) was known in 103. Resistance to penicillin increased from 0 to 20% over the study period. Only 57 (55%) had an early LP (prior to parenteral antibiotics); 55 (96%) had organisms on Gram stain. Severe disease (intensive care admission or death) increased significantly from 57 cases with early LP (28%) to 33 with delayed LP (42%) to 13 with no LP (62%). Evidence of pneumococcal infection was available within 24 hours in 85% of those with delayed or no LP. Outcome was not related to empiric vancomycin use, which increased from 5% prior to 1998 to 48% in 1999. CONCLUSION: LP is frequently delayed in pneumococcal meningitis. Based on disease severity, empiric vancomycin is most justified when LP is deferred. If an early LP is done, vancomycin can be withheld if Gram positive diplococci are not seen.

Optimal age for measles and mumps vaccination in Australia.

Trivalent measles-mumps-rubella vaccine has recently replaced measles-mumps vaccine in Australia and is recommended as a single dose at the age of 12 to 15 months, with the exception of Aboriginal children in central Australia who are vaccinated at 9 months. The timing of measles vaccination has been controversial not only in Australia but also in the United States, where measles outbreaks continue to occur. This study aimed to determine seroconversion rates for measles-mumps vaccine in children aged 12 to 18 months and to make a recommendation for the timing of vaccination based on seroconversion rates and attack rates. The parents of 425 children aged 12 to 18 months gave consent for their children to have serum collected at the time of measles-mumps vaccination and three months later. The mean age at vaccination of the children who had two serum samples for measles and mumps antibody estimations was 13.9 months (mode, 13.1). The seroconversion rate for measles was 95% (314/329) (95% confidence interval (CI), 92.5% to 97.3%) and for mumps 97% (309/320) (95% CI, 93.8% to 98.1%). There were no statistically significant differences in the rates of seroconversion for measles or mumps related to age in months at the time of vaccination or in post-vaccination measles antibody titres related to age at vaccination. Post-vaccination mumps antibody titres tended to be lower in older vaccinees. None of the children who presented for vaccination had serological evidence of prior measles infection but five had evidence suggestive of prior mumps. As the seroconversion rates for measles and mumps vaccines were very high in these children it was concluded that no advantage resulted from delaying vaccination until 15 months and that the current National Health and Medical Research Council recommendations for vaccination at age 12 to 15 months should remain.

Epidemiology of invasive pneumococcal disease in urban New South Wales, 1997-1999.

OBJECTIVES: To describe the serotypes, incidence and morbidity of invasive pneumococcal disease in urban New South Wales. DESIGN: Prospective laboratory surveillance. SETTING: Microbiology laboratories and hospitals in the Sydney, Hunter and Illawarra Statistical Divisions of NSW, June 1997 to May 1999. RESULTS: 1270 cases were identified in two years. Incidence of disease was highest in those aged < 2 years (96.4 per 100,000; 95% CI, 83.7-107.9) and > or = 85 years (100.1 per 100,000; 95% CI, 81.8-121.3). Incidence of disease increased significantly from the age of 60 years, compared with low rates in those aged 5-59 years. Underlying diseases predisposing to pneumococcal infection increased with age, from 4% (< 2 years) to 60% (> or = 65 years). A seven-valent conjugate vaccine would have covered 84.8% of serotypes in those aged 0-14 years, falling to 69% in those > or = 15 years. Penicillin resistance was significantly higher in the < 5 years group (19.0%) than in older people (14.6%). CONCLUSIONS: Incidence of invasive pneumococcal disease was higher in this study using active surveillance than in previous Australian studies. An effective sevenvalent conjugate pneumococcal vaccine could prevent more than 80% of cases in children aged < 5 years.

Acyclovir for the prevention and treatment of varicella zoster in children, adolescents and pregnancy.

Varicella causes a mild, self-limiting childhood disease that may reactivate years later as shingles. In immunocompromised patients with altered cell mediated immunity, and rarely in healthy individuals, varicella results in a life-threatening infection. The antiviral drug, acyclovir, substantially reduces the mortality and risk of severe disease in these groups of patients. Early commencement of acyclovir is recommended for children with both varicella and altered cell mediated immunity, newborns during the first 2 weeks of life, preterm infants in the neonatal nursery, and severe varicella or shingles (including ocular zoster) in any patient, as well as during pregnancy. Acyclovir may be considered in children with serious cardiopulmonary disease or chronic skin disorders where varicella may exacerbate the underlying disease or increase the risk of secondary bacterial sepsis. Acyclovir, however, is not recommended for healthy individuals without severe disease, as a prophylactic agent against varicella, for asthmatics receiving aerosolized or low-dose oral steroids and/or as treatment of the post-varicella syndromes. When acyclovir is prescribed it should be given intravenously to those with severe disease, those at risk of dissemination and in children younger than 2 years of age.

"On the spot' vaccination: does it work?

OBJECTIVE: To trial and evaluate a system of "on the spot' vaccination for children up to the age of 15 years in the Early Childhood Centres of the Central Sydney Area Health Service, at the Royal Alexandra Hospital for Children and in a number of general practices in the area. METHODOLOGY: A brief questionnaire was used to collect data from parents and health care professionals about the child's vaccination status and vaccines given "on the spot'. RESULTS: Over an 8 week period in August-September 1993, 5162 questionnaires were completed; 71% of children were up to date with their vaccination. If Haemophilus influenzae type b vaccine, which had been introduced only 2 months before commencement of the study, was excluded, 84% of the children were up to date. A total of 441 children were given 663 vaccinations "on the spot'. Very few children were too ill to be vaccinated (6%). However, only 30% of those who needed vaccination "on the spot' actually received it (441 of 1480), and only 41% (24 of 58) of a subset of those who were not vaccinated were known to have complied 1 month later. Children attending Early Childhood Centres were younger than children attending general practices or the hospital. CONCLUSIONS: A high proportion of children who attended for routine or acute health care had vaccinations overdue (30%). If this scheme could be continued and expanded it would have an important impact on vaccination coverage, and hence on the incidence of vaccine-preventable diseases.