Timing of routine infant vaccinations and risk of food allergy and eczema at one year of age.

BACKGROUND: Epidemiological evidence suggests that routine vaccinations can have nontargeted effects on susceptibility to infections and allergic disease. Such effects may depend on age at vaccination, and a delay in pertussis vaccination has been linked to reduced risk of allergic disease. We aimed to test the hypothesis that delay in vaccines containing diphtheria-tetanus-acellular pertussis (DTaP) is associated with reduced risk of food allergy and other allergic diseases. METHODS: HealthNuts is a population-based cohort in Melbourne, Australia. Twelve-month-old infants were skin prick-tested to common food allergens, and sensitized infants were offered oral food challenges to determine food allergy status. In this data linkage study, vaccination data for children in the HealthNuts cohort were obtained from the Australian Childhood Immunisation Register. Associations were examined between age at the first dose of DTaP and allergic disease. RESULTS: Of 4433 children, 109 (2.5%) received the first dose of DTaP one month late (delayed DTaP). Overall, delayed DTaP was not associated with primary outcomes of food allergy (adjusted odds ratio (aOR) 0.77; 95% CI: 0.36-1.62, P = 0.49) or atopic sensitization (aOR: 0.66; 95% CI: 0.35-1.24, P = 0.19). Amongst secondary outcomes, delayed DTaP was associated with reduced eczema (aOR: 0.57; 95% CI: 0.34-0.97, P = 0.04) and reduced use of eczema medication (aOR: 0.45; 95% CI: 0.24-0.83, P = 0.01). CONCLUSIONS: There was no overall association between delayed DTaP and food allergy; however, children with delayed DTaP had less eczema and less use of eczema medication. Timing of routine infant immunizations may affect susceptibility to allergic disease.

Neonatal vitamin A supplementation associated with increased atopy in girls.

BACKGROUND: Neonatal vitamin A supplementation (NVAS) is currently being considered as policy in countries at risk of deficiency. A previous study suggested that NVAS may be associated with increased atopy. We examined the effect of NVAS on atopy by conducting long-term follow-up of a previous randomized controlled trial in Guinea-Bissau. METHODS: In 2002-2004, we randomized 4345 normal birthweight neonates to NVAS (50 000 IU retinyl palmitate) or placebo together with their Bacillus Calmette-Guérin vaccination. In 2013, we visited the 1692 (39%) children now aged 8-10 years who were still living in the study area, and 1478 (87%) were found at home. Provided consent, a skin prick test was performed, and history of allergic symptoms was recorded. Associations of NVAS and atopy (defined as skin prick test reaction of ≥3 mm) were analysed using binomial regression. RESULTS: Of the 1430 children with a valid skin prick test, 228 (16%) were positive (more boys (20%) than girls (12%), P-value < 0.0001). NVAS did not increase the overall risk of atopy (RR 1.10 [95% CI 0.87-1.40]). However, NVAS was associated with significantly increased risk among females (RR 1.78 [1.17-2.72]) but not among males (0.86 [0.64-1.15], P-value for interaction between NVAS and gender = 0.005). Furthermore, NVAS was associated with increased risk of wheezing among females (RR 1.80 [1.03-3.17], but not among males, P-value for interaction = 0.05). CONCLUSION: The study corroborated previous observations; NVAS was associated with increased risk of atopy and wheezing, in this study only among females. Further studies on NVAS and atopy are warranted.

Vitamin A supplementation and BCG vaccination at birth may affect atopy in childhood: long-term follow-up of a randomized controlled trial.

BACKGROUND: Recent evidence suggests that immunogenic interventions such as vaccines and micronutrients may affect atopic sensitization and atopic disease. We aimed to determine whether neonatal BCG vaccination, vitamin A supplementation and other vaccinations affect atopy in childhood. METHODS: In Guinea-Bissau, low-birthweight infants were randomized to early (intervention) or delayed (usual policy) BCG. A subgroup was also randomly assigned vitamin A supplementation or placebo in a two-by-two factorial design. Participants were followed up at age 3-9 years. The main outcome was atopy defined as skin prick test reaction ≥3 mm. Secondary outcomes were symptoms of eczema, asthma and food allergy. RESULTS: Two hundred eighty-one children had valid skin prick tests performed, and 14% (39/281) were atopic. There was no significant difference in atopy between the early and delayed BCG groups (OR, 0.71; 95% CI, 0.34-1.47). Atopy was significantly reduced in children who had responded to BCG with a scar (OR, 0.42; 0.19-0.94). Vitamin A supplementation was associated with increased atopy (OR, 2.88; 1.26-6.58), especially in those who received simultaneous BCG (5.99; 1.99-18.1, P = 0.09 for interaction between vitamin A supplementation and BCG). Early vs delayed BCG was not associated with symptoms of atopic disease, but vitamin A supplementation increased odds of wheeze within the past 12 months (OR, 2.45; 1.20-4.96). CONCLUSIONS: There were no statistically significant effects of early vs delayed BCG on atopy or symptoms of atopic disease. Having a BCG scar was associated with reduced atopy, whereas neonatal vitamin A supplementation was associated with increased atopy. STUDY REGISTRATION: Clinicaltrials.gov NCT 01420705.

ICU staffing: identification and survey of staff involved in providing technical support services to Australian and New Zealand intensive care units.

We conducted a survey of all (200) Australian and New Zealand intensive care units to determine the presence and nature of staff employed in a technical support role. Specifically, we attempted to identify staff who are formally employed in a role where they are directly responsible for the equipment used in intensive care. Of 130 returned surveys, 80 units (62%) reported not having any personnel in this role. In these units technical tasks were most commonly performed by registered nurses (79%) but were also performed by a variety of other personnel. Fifty units (38%), consisting of approximately 105 individuals providing a total of 84.3 EFTs and most commonly in public (84%) or metropolitan (70%) hospitals or level 3 (64%) intensive care units, did have one or more staff acting in a formal technical support role. The most common groups filling the technical support role were nurses (42%), technicians (24%), biomedical engineers (10%) and technologists (6%). The most common duties performed were equipment troubleshooting (92%), training (80%), equipment evaluation (80%), ordering supplies (77%), consumable evaluation (75%), equipment cleaning (73%), delivery of supplies (70%), handling product recalls (65%), equipment maintenance (65%) and sitting on hospital committees (52%). This is the first attempt to identify and understand the technical support role in Australian and New Zealand intensive care units. Numerous issues remain and future work will hopefully add to our findings, with the possibility of formal recognition of the role, training and/or accreditation and its extension into other hospital departments.

Facilitation of spike-wave discharge activity by lipopolysaccharides in Wistar Albino Glaxo/Rijswijk rats.

In normal rats the proinflammatory cytokines like interleukin-1beta, interleukin-6, which are induced by bacterial lipopolysaccharides, are able to control thalamo-cortical excitability by exerting strong effects on physiological synchronization such as sleep and on pathological synchronization like that in epileptic discharges. To investigate whether proinflammatory cytokines or lipopolysaccharides could modulate absence seizures resulting from a very different generator mechanism than the already investigated bicuculline-, kindling- and kainate-induced seizures, we used a genetically epileptic Wistar Albino Glaxo/Rijswijk rat strain, which is spontaneously generating high voltage spike-wave discharges. Wistar Albino Glaxo/Rijswijk rats responded with an increase of the number of spike-wave discharges to lipopolysaccharide injection (from 10 microg/kg to 350 microg/kg). Repetitive administration of 350 microg/kg lipopolysaccharides daily for 5 days increased the number of spike-wave discharges on the first, second and third days but the number of spike-wave discharges returned to the control value on day 5, at the 5th injection of lipopolysaccharides, showing a tolerance to lipopolysaccharides. The lipopolysaccharide-induced increase in spike-wave discharges was not directly correlated with the elevation of the core body temperature, as it is in febrile seizures, although lipopolysaccharide induced prostaglandin and is clearly pyrogenic at the doses used. Indomethacin, the prostaglandin synthesis inhibitor, efficiently blocked lipopolysaccharide-induced enhancement of spike-wave discharge genesis suggesting that the spike-wave discharge facilitating effect of lipopolysaccharides involves induction of cyclooxygenase 2 and subsequent synthesis and actions of prostaglandin E2. Low dose (40 mg/kg, i.p.) of competitive N-methyl-d-aspartate receptor antagonist 2-amino-5-phosphonopentanoic acid, and low dose of lipopolysaccharide (20 microg/kg) showed a synergistic interaction to increase the number of spike-wave discharges, whereas at supramaximal doses of lipopolysaccharide and the N-methyl-D-aspartate antagonist no synergy was present. The data reveal a functional connection between absence epileptic activity and lipopolysaccharide induction of prostaglandin synthesis and prostaglandin action and suggest some common cellular targets in epilepsy and lipopolysaccharide-induced inflammation.