The influence of neonatal BCG vaccination on in vitro cytokine responses to Plasmodium falciparum.

BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccination has off-target protective effects against infections unrelated to tuberculosis. Among these, murine and human studies suggest that BCG vaccination may protect against malaria. We investigated whether BCG vaccination influences neonatal in vitro cytokine responses to Plasmodium falciparum. Blood samples were collected from 108 participants in the Melbourne Infant Study BCG for Allergy and Infection Reduction (MIS BAIR) randomised controlled trial (Clinical trials registration NCT01906853, registered July 2013), seven days after randomisation to neonatal BCG (n = 66) or no BCG vaccination (BCG-naïve, n = 42). In vitro cytokine responses were measured following stimulation with P. falciparum-infected erythrocytes (PfIE) or E. coli. RESULTS: No difference in the measured cytokines were observed between BCG-vaccinated and BCG-naïve neonates following stimulation with PfIE or E. coli. However, age at which blood was sampled was independently associated with altered cytokine responses to PfIE. Being male was also independently associated with increased TNF-a responses to both PfIE and E. coli. CONCLUSION: These findings do not support a role for BCG vaccination in influencing in vitro neonatal cytokine responses to P. falciparum. Older neonates are more likely to develop P. falciparum-induced IFN-γ and IFN-γ-inducible chemokine responses implicated in early protection against malaria and malaria pathogenesis.

A Case Report of Immunosuppressant Medication‒Associated Polyarticular Tophaceous Gout Successfully Treated Using the Polyethylene Glycol‒Conjugated Uricase Enzyme Pegloticase.

This case describes a female patient with polyarticular tophaceous gout who was given transplant immunosuppressant medications. The 36-year-old was treated for Wilms tumor at 3 years of age by operative removal of 1 kidney, chemotherapy, and radiotherapy. At age 19, the patient was diagnosed with cardiomyopathy attributed to prior chemotherapy and radiotherapy. She underwent a heart transplant at age 22 and has received prednisone, mycophenolate mofetil, and cyclosporine to prevent rejection since the transplant. The patient presented with numerous gouty tophi and elevated serum uric acid, likely precipitated by her immunosuppressant medications, and underwent a 38-week course of pegloticase infusions at 2-week intervals. After the first infusion, her serum uric acid decreased to <89 µmol/L (<1.5 mg/dL) and remained at this level throughout treatment. Her proximal tophi, and subsequently distal tophi, resolved over the course of treatment; she did not report any gout flares. The patient reported improved mobility, pain, and quality of life on completion of therapy. Immunosuppressant medications necessary for transplant viability potentially reduced her immunologic response to pegloticase therapy by inhibiting the development of anti-pegloticase antibodies.

Epidemiology of high falls from windows in children.

Falls from a height result in significant morbidity and mortality worldwide. Targeted prevention strategies in the US combined data collection, publicity campaigns and building regulation and reduced high falls in New York by 93%. This retrospective cohort study describes children who fell from a height presenting or referred to Children's University Hospital Temple St. over a 2 year period. Case ascertainment was through the Emergency Department Symphony registration system and the Trauma Area Research Network (TARN) database. Forty five falls were identified, 33 falls (73.3%) were in children less than 5 with boys being three times more likely to fall. Forty four falls were from windows, 31 from < 12 feet and 7 were witnessed. Injury severity Scores (ISS) correlated to height of fall; both deaths fells from > 24ft. A publicity campaign is warranted to highlight the frequency of injury following falls from windows. Building legislation is required to safeguard high windows and balconies. A post fall questionnaire would enable the collection of unbiased forensic data.

Perinatal Treponema pallidum: evidence based guidelines to reduce mother to child transmission.

Universal antenatal screening for T. pallidum is standard in Irish maternity units. The prevalence of adult syphilis has increased in Ireland. We audited the neonatal management of infants exposed to T. pallidum in utero. A cross sectional retrospective analysis of all pregnancies with confirmed positive serology for T. pallidum from January 2005 to December 2010 was conducted at the National Maternity Hospital, Holles St. Data were analysed using SPSS 14.0. Ethical approval was obtained. There were 55,058 live births during the study period. Fifty-eight women had positive serology and 41 met inclusion criteria. Infant evaluation and follow up was decided by allocation to an evidence based algorithm. Twenty-one infants (51%) were accurately allocated and assessed, 5 (12%) had a partial assessment and the algorithm was incorrectly applied in 15 (36%) of cases. Failure to adhere to evidence based neonatal guidelines is common and undermines efficacy of the screening program.

Influenza in hospitalized children in Ireland in the pandemic period and the 2010/2011 season: risk factors for paediatric intensive-care-unit admission.

Influenza causes significant morbidity and mortality in children. This study's objectives were to describe influenza A(H1N1)pdm09 during the pandemic, to compare it with circulating influenza in 2010/2011, and to identify risk factors for severe influenza defined as requiring admission to a paediatric intensive care unit (PICU). Children hospitalized with influenza during the pandemic were older, and more likely to have received antiviral therapy than children hospitalized during the 2010/2011 season. In 2010/2011, only one child admitted to a PICU with underlying medical conditions had been vaccinated. The risk of severe illness in the pandemic was higher in females and those with underlying conditions. In 2010/2011, infection with influenza A(H1N1)pdm09 compared to other influenza viruses was a significant risk factor for severe disease. An incremental relationship was found between the number of underlying conditions and PICU admission. These findings highlight the importance of improving low vaccination uptake and increasing the use of antivirals in vulnerable children.

Higher specialist training in paediatrics 2005-2010, the graduates' reflections.

This study of paediatric trainees, who were awarded their CSCST from 2005 to 2010, evaluated their training experience and assessed whether the curriculum goals were achieved. From an incomplete database 23 (57.7%) graduates based in Ireland and 3 (19%) based abroad responded. Twenty one (81%) of respondents were currently working in Ireland as consultants, 20 (80%) had a post membership qualification and 23 (92%) had travelled abroad for fellowships. Positive experiences included clinical training (44%), positive role models (44%), quality of the training days (52%).Negative experiences included lack of protected time for research (52%), excessive clinical service (28%), and poor monitoring of trainers (20%). Mean Likert scores for curriculum competencies were clinical care 4.9, clinical knowledge 5, application of evidence 3.7, academic supervisor skills3.3, knowledge of public health 3.2, health economics 2.2, and healthcare systems modification 2.3. The curriculum deficiencies can be addressed through the diploma in Leadership and Quality in Healthcare which has been developed by the Health Service Executive and the College of Physicians but an adequate database of graduates needs to be maintained.