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Antimicrobial stewardship (AMS) is central to the World Health Organisation Global Action Plan against antimicrobial resistance (AMR). If antibiotics are used without restraint, morbidity and mortality from AMR will continue to increase. In resource-rich settings, AMS can safely reduce antibiotic consumption. However, for children in low- and middle-income countries (LMIC), the impact of different AMS interventions is unknown.To determine the impact of different AMS interventions on antibiotic use and clinical and microbiologic outcomes in children in LMIC.MEDLINE, Embase and PubMed were searched for studies of AMS interventions in pediatric population in LMIC settings. Controlled trials, controlled before-and-after studies and interrupted time series studies were included. Outcomes assessed were antibiotic use, multidrug-resistant organism (MDRO) rates, clinical outcomes and cost.Of 1462 studies, 34 met inclusion criteria including a total population of5,000,000 in 17 countries. Twenty were in inpatients, 2 in ED, 10 in OPD and 2 in both. Seven studies were randomized controlled trials. All types of interventions reported a positive impact on antibiotic prescribing. AMS bundles with education, and clinical decision tools appeared more effective than guidelines alone. AMS interventions resulted in significantly decreased clinical infections (4/4 studies) and clinical failure (2/2) and reduced MDRO colonization rate (4/4). There was no concomitant increase in mortality (4/4 studies) or length of stay (2/2).Multiple effective strategies exist to reduce antibiotic consumption in LMIC. However, marked heterogeneity limit conclusions regarding the most effective approach, particularly regarding clinical outcomes. Overall, AMS strategies are important tools in the reduction of MDRO-related morbidity in children in LMIC.

IntroductionDespite recommendation that all women receive an ultrasound in pregnancy prior to 24 weeks', this remains unavailable to many women in low-income countries where trained practitioners are scarce. Although many programmes have demonstrated efficacy, few have achieved longterm sustainability, with a lack of information about how best to implement such programmes. This mixed-methods study aimed to evaluate the implementation of a novel education package to teach ultrasound-naive midwives in Malawi basic obstetric ultrasound, assessing its impact in the context of the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework.MethodsThe study ran across six sites in Malawi between October 2020 and June 2021, encompassing three phases; pre-implementation, implementation and post-implementation. Twenty nine midwives underwent a bespoke education package with matched pre and post course surveys assessed their knowledge, attitudes and confidence and “hands on” assessments evaluating practical skills. Training evaluation forms and in-depth interviews explored their satisfaction with the package, with repeat assessment and remote image review evaluating maintenance of skills.Results28/29 midwives completed the training, with significant increases in knowledge, confidence and practical skills. Adherence to the education package varied, however many changes to the proposed methodology were adaptive and appeared to facilitate the efficacy of the programme. Unfortunately, despite reporting approval regarding the training itself, satisfaction regarding supervision and follow up was mixed, reflecting the difficulties encountered with providing ongoing in-person and remote support.ConclusionThis programme was successful in improving trainees' knowledge, confidence and skill in performing basic obstetric ultrasound, largely on account of an adaptive approach to implementation. The maintenance of ongoing support was challenging, reflected by trainee dissatisfaction. By evaluating the success of this education package based on its implementation and not just its efficacy, we have generated new insights into the barriers to sustainable upscale, specifically those surrounding maintenance.

The use of ultrasound to determine gestational age is fundamental to the optimum management of pregnancy and is recommended for all women by the World Health Organization. However, this modality remains unavailable to many women in low-income countries where trained practitioners are scarce. Although previous initiatives have demonstrated efficacy in training midwives and technicians to perform antenatal ultrasound, these programs have often been too long and too complex to be realistic within the specific constraints of this context, highlighting the need for a novel and pragmatic approach. We describe the development and piloting of a bespoke course to teach midwives 3 fundamental components of early antenatal ultrasound scanning: (1) to identify the number of fetuses, (2) to confirm fetal viability, and (3) to determine gestational age. Having established that 5 days is insufficient, we propose that the minimum duration required to train ultrasound-naive midwives to competency is 10 days. Our completed program therefore consists of one and one-half days of didactic teaching, followed by 8 and one-half days of supervised hands-on practical training in which trainees are assessed on their skills. This package has subsequently been successfully implemented across 6 sites in Malawi, where 28 midwives have achieved competency. By describing the processes involved in our cross-continental collaboration, we explain how unexpected challenges helped shape and improve our program, demonstrating the value of preimplementation piloting and a pragmatic and adaptive approach.

Background: Bacille Calmette-Guérin (BCG) vaccine could play a role in counteracting the rising prevalence of atopic diseases, through its beneficial off-target effects. We aimed to determine whether neonatal BCG vaccination reduces the incidence of eczema in infants.Methods: Randomized controlled trial with 1272 infants allocated to receive BCG-Denmark or no BCG at birth. The primary outcome was the 12-month incidence of eczema based on 3-monthly questionnaires. Eczema was also assessed at a 12-month clinic visit. ClinicalTrial.gov: NCT01906853.Results: The 12-month eczema incidence was 32.2% in the BCG group compared with 36.6% in the control group (adjusted risk difference (aRD) -4.3%, 95% CI -9.9% to 1.3%, multiple imputation model). In addition, comparing infants in the BCG group with the control group, 15.7% vs. 19.2% had eczema lesions at the 12-month visit (aRD -3.5%, 95% CI -8.0% to 1.0%); 35.7% vs. 39.0% reported using topical steroids (aRD -3.3, 95% CI -9.2 to 2.7); and 7.3% vs. 10.2% had severe eczema scores (aRD -3.0%, 95% CI -8.8% to 2.7%). In 344 high-risk infants (two atopic parents), the 12-month eczema incidence was 35.3% in the BCG group compared with 46.8% in the control group (aRD -11.5%, 95% CI -21.9% to -1.2%; number needed to treat 8.7, 95% CI 4.6 to 83.3).Conclusion: There is insufficient evidence to recommend neonatal BCG vaccination in all infants for the prevention of eczema in the first year of life; however, a modest beneficial effect was observed among high-risk infants. A single dose of BCG-Denmark soon after birth could reduce the incidence of eczema in infants with two atopic parents.

Background Bacille Calmette-Guérin (BCG) vaccination has beneficial off-target effects that may include protecting against non-mycobacterial infectious diseases. We aimed to determine whether neonatal BCG vaccination reduces lower respiratory tract infections (LRTI) in infants in the Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR) trial. Methods In this investigator-blinded trial, neonates in Australia were randomized to receive BCG-Denmark vaccination or no BCG at birth. Episodes of LRTI were determined by symptoms reported in parent-completed, 3-month questionnaires over the first year of life. Data were analyzed by intention-to-treat using binary regression. Results A total of 1272 neonates were randomized to the BCG vaccination (n = 637) or control (n = 635) group. The proportion of participants with an episode of LRTI in the first year of life among BCG-vaccinated infants was 54.8% compared to 58.0% in the control group, resulting in a risk difference of −3.2 (95% confidence interval, −9.0 to 2.6) after multiple imputation. There was no interaction observed between the primary outcome and sex, maternal BCG, or the other prespecified effect modifiers. Conclusions Based on the findings of this trial, there is insufficient evidence to support the use of neonatal BCG vaccination to prevent LRTI in the first year of life in high-income settings.

There is no standardized definition for infant eczema, and various tools have been used across studies, precluding direct comparison.The aim of the study was to assess and to compare the accuracy of diagnostic tools for infant eczema using the extensive data collected in Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR), an eczema prevention trial.Eczema incidence was assessed by 3 questionnaire-based measures: modified UK diagnostic tool, parent-reported medically diagnosed eczema, and parent-reported use of topical corticosteroids. Agreement between the definitions was quantified using κ coefficient. Eczema severity was assessed by 3-monthly Patient-Oriented Eczema Measure (POEM) scores and a SCORing Atopic Dermatitis (SCORAD) clinical assessment at a 12-month visit (ClinicalTrial.gov: NCT01906853).Among the 538 participants fulfilling at least 1 of the 3 questionnaire-based eczema definitions, only 197 participants (37%) met all 3 definitions. Agreement between the definitions was poor with κ coefficients ranging from -0.11 to 0.62. The most frequently reported symptoms were generally dry skin (483/538, 90%) and pruritus (400/538, 74%). The face (352/538, 65%) and the trunk (306/538, 57%) were more frequently affected than the creases (257/538, 48%). Participants fulfilling all 3 questionnaire-based definitions of eczema were more likely to have higher severity scores and earlier onset of symptoms.There is poor agreement between currently available tools for assessing infant eczema.

BackgroundThis study aims to describe the use of a paediatric advice line (PAL) provided to parents whose infants were recruited to a large randomised controlled trial (RCT), including the number and types of medical concerns addressed, seasonal variability and call outcomes. Additionally, sociodemographic characteristics of the parents and children of those parents who used the PAL are compared with those who did not.MethodsProspective cohort of 1246 children nested in the Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR) RCT. All MIS BAIR participants were offered access to the PAL. Data were collected over the initial 2 years of a 5-year follow-up. Data were analysed using χ2tests, and ORs were calculated using multiple logistic regression.ResultsThe PAL was used by 230 (18.5%) participants, who made a total of 586 calls during the 2-year study period. The reasons for calling the PAL were dermatological (24%); gastrointestinal (18%); disturbances in feeding, sleeping and crying (14%); respiratory (7%); and developmental/neurological (6%). Analysis revealed that those who used the PAL were more likely to be first-time parents (OR 1.4, 95% CI 1.1 to 1.9) and mothers who hold a university degree (OR 3.3, 95% CI 1.3 to 8.4). PAL costs were minimal and comprised 15 clinicians with paediatric experience.ConclusionsA cost-effective PAL service for clinical trial participants was used appropriately by parents for relatively minor concerns and may have a role in trials to promote participant engagement and reduce demand for other health services.

Bacille Calmette-Guérin (BCG) and hepatitis B (HBV) vaccines are frequently given concomitantly at birth. Neonatal BCG vaccination induces off-target immunological effects. Whether HBV vaccine has immunomodulatory effects is unknown. As off-target effects might vary when vaccines are given simultaneously, this randomised controlled trial aimed to evaluate the influence of neonatal vaccination with BCG and/or HBV on heterologous immune responses.A total of 185 neonates in Australia were randomised to receive either neonatal BCG-Denmark vaccine, HBV vaccine, both (BCG + HBV group), or none (No vaccine group). In-vitro responses to heterologous stimulants were assessed 7 days after vaccination. The influence of (i) randomisation group and (ii) sex on interferon-gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP-1), and tumour necrosis factor-alpha (TNF-α) responses was analysed using linear regression.Overall, BCG vaccination alone or with HBV co-administration reduced IFN-γ and MCP-1 responses to heterologous stimulants. HBV vaccination alone did not alter heterologous cytokine responses. In general, males produced more IFN-γ and TNF-α than females. We observed a sex-differential effect in relation to the influence of HBV co-administration on the effect of BCG on heterologous responses. Compared with males in the No vaccine group, males in the BCG + HBV group had lower IFN-γ and MCP-1 responses. In contrast, compared with females in the No vaccine group, females in the BCG group had higher IFN-γ response and lower MCP-1 responses.Neonatal BCG vaccination resulted in lower cytokine responses to unrelated pathogens. HBV co-administration did not have a significant impact on responses overall but influenced the heterologous effects of neonatal BCG vaccination in a sex-differential manner.

The SARS-CoV-2 pandemic has challenged health systems and healthcare workers worldwide. Access to personal protective equipment (PPE) is essential to mitigate the risk of excess mortality in healthcare providers. In Malawi, the cost of PPE represents an additional drain on available resources. In the event of repeated waves of disease over several years, the development of sustainable systems of PPE is essential. We describe the development, early implementation and rapid scale up of a reusable gown service at a tertiary-level hospital in Blantyre, Malawi. Challenges included healthcare worker perceptions around the potential of reduced efficacy of cotton gowns, the need to plan for surge capacity and the need for ongoing training of laundry staff in safety and hygiene procedures. Benefits of the system included increased coverage, decreased cost and reduced waste disposal. The implementation of a reusable cotton gown service is feasible, acceptable and cost-effective in tertiary centres providing specialist COVID-19 care at the height of the pandemic. This innovation could be expanded beyond low-income settings.

The COVID-19 pandemic curve in Africa has lagged behind that of Europe. The first case of SARS-CoV-2 in Malawi was confirmed on 2 April.1 Malawi closed schools and airports, but no ‘lockdown’ was enforced in recognition of the risk to a population vulnerable to economic and health service disruption.2 Although overall ascertainment was low, detection of cases nationwide confirmed community transmission by July. Nonetheless, the number of acute cases presenting to hospital remained less than expected. The current total number of confirmed COVID-19 cases nationwide is just over 60001 with Blantyre district contributing one-third of the nationwide total.3 Queen Elizabeth Central Hospital (QECH) in Blantyre is the tertiary referral hospital for the Southern Region of Malawi. The pandemic heightened existing challenges related to limited human and material resources. Public fear and healthcare worker (HCW) sit-ins associated with concerns around inadequate personal protective equipment (PPE) disrupted services and contributed to delayed patient presentation. We established a multidisciplinary COVID-19 task force to work with hospital, district and national leaders in the coordination of activities aimed at mitigating the direct and indirect risks of the COVID-19 pandemic on staff and paediatric patients. We now reflect and share our initial lessons in pandemic preparedness in the Department of Paediatrics at QECH. In the early months of the pandemic, there was mounting evidence that the risk of nosocomial transmission and occupational exposure was high.4 5 In response, the Ministry of Health of Malawi developed COVID-19 treatment centres separate from central hospitals. This policy was challenging for paediatrics as the WHO clinical case definition used for isolation overlaps with the majority of in-patient paediatric diagnoses. Limited diagnostics led to a risk of inappropriate isolation, unnecessary exposure of high-risk children and guardians to COVID-19 and a reduced level of specialty care for …

Iron is essential for growth and haematopoiesis but iron overload can have detrimental effects. The aim of this study is to correlate iron indices at 1 month of age in very low birth weight infants undergoing intensive care prior to additional iron supplementation and correlate results with clinical measures and 2 year corrected neurodevelopmental outcomes.A prospective observational cohort study was undertaken of very low birth weight infants at a tertiary neonatal intensive care unit. In 45 eligible infants, iron overload existed in 14 (31%) who had significantly decreased: mean (SD) gestational age at birth [26(2) v 28(2) weeks], birth weight [814(231)g v 1011(238)g], weight on assessment [1180(369)g v 1502(423)g], haemoglobin level at birth [13.8(3.1)g/dL v 16.1(2.5)g/dL] and mean corpuscular volume at assessment [85(4)fL v 90(6)fL] with increased number of red cell transfusions [4(2.5-5) v 1(0-2)] and volume of transfusions [65 (38)mL v 27 (23)mL]. Regression analysis determined the number of transfusions had the strongest correlation with iron status on testing. Neurodevelopmental outcomes at 2 years were not significantly different.Conclusion: Very low birth weight infants at risk of iron overload (≥2 red cell transfusions) may benefit from the measurement of iron indices prior to oral iron supplementation.

AIM To (i) determine the appropriateness of antimicrobial prescribing in the neonatal intensive care unit (NICU) and (ii) assess the impact of a collaborative antimicrobial stewardship (AMS) intervention on prescribing practices. METHODS The intervention was a weekly AMS audit-feedback joint ward round (6-month period) of Neonatology and Infectious Diseases clinicians in a tertiary neonatal intensive care unit in Melbourne, Australia. Antibiotic prescriptions were audited and recommendations delivered in real time. The proportion of recommendations implemented was used to assess acceptability of the intervention. RESULTS During the study period, there were 23 AMS rounds, during which 249 patients were reviewed at 627 separate episodes. Of these, 233 (37%) episodes were for patients receiving antimicrobials. Of these, 147 (63%) received empirical antimicrobial treatment, 43 (18%) targeted antimicrobial treatment and 43 (18%) antimicrobial prophylaxis. There were 58 (25%) of 233 episodes of inappropriate antibiotic use, and 62 recommendations for improvement. Most common recommendations were to narrow (33/62, 53%) or stop (12/62, 19%) antimicrobials. The majority (45, 73%) of recommendations were accepted, resulting in significant improvement in the proportion of the 233 episodes that had completely appropriate antibiotic prescribing: 175 (75%) to 217 (93%) (relative risk 1.2, 95% confidence intervals 1.1-1.3, P

Background BCG vaccination has beneficial nonspecific (heterologous) effects that protect against nonmycobacterial infections. We have previously reported that BCG vaccination at birth alters in vitro cytokine responses to heterologous stimulants in the neonatal period. This study investigated heterologous responses in 167 infants in the same trial 7 months after randomization. Methods A whole-blood assay was used to interrogate in vitro cytokine responses to heterologous stimulants (killed pathogens) and Toll-like receptor (TLR) ligands. Results Compared to BCG-naive infants, BCG-vaccinated infants had increased production of interferon gamma (IFN-γ) and monokine induced by gamma interferon (MIG) (CXCL9) in response to mycobacterial stimulation and decreased production of IFN-γ in response to heterologous stimulation and TLR ligands. Reduced IFN-γ responses were attributable to a decrease in the proportion of infants who mounted a detectable IFN-γ response. BCG-vaccinated infants also had increased production of MIG (CXCL9) and interleukin-8 (IL-8), and decreased production of IL-10, macrophage inflammatory protein-1α (MIP-1α), and MIP-1β, the pattern of which varied by stimulant. IL-1Ra responses following TLR1/2 (Pam3CYSK4) stimulation were increased in BCG-vaccinated infants. Both sex and maternal BCG vaccination status influenced the effect of neonatal BCG vaccination. Conclusions BCG vaccination leads to changes in IFN-γ responsiveness to heterologous stimulation. BCG-induced changes in other cytokine responses to heterologous stimulation vary by pathogen., Neonatal BCG vaccination results in a decreased proportion of infants mounting an IFN-γ response to heterologous stimulation at 7 months of age. Both sex and maternal BCG vaccination status influenced the effect of BCG vaccination on heterologous cytokine responses.

The WHO Special Advisory Group of Experts (SAGE) review of the available epidemiological and trial evidence in humans concluded that bacillus Calmette-Guérin (BCG) vaccination leads to beneficial heterologous ('non-specific') effects, specifically on all-cause mortality. Randomized controlled trials showing this beneficial effect suggest improved survival is the result of enhanced protection against infection. This paper reviews the available evidence for the attenuating effects of BCG vaccine on experimental infections in animal models, including protection from bacteria, viruses, parasites and fungi. The reviewed studies suggest that BCG activates multiple immune pathways and that the basis for BCG-associated heterologous immunity may vary by pathogen. Modern immunological and molecular methods, exemplified by 'vaccinomics', are well placed to further investigate the basis of BCG's heterologous effects using a systems biology approach.

Randomized controlled trials indicate that bacille Calmette-Guerin (BCG) has beneficial heterologous ('non-specific') effects on mortality in high mortality settings. These findings have stimulated interest in understanding the immunological mechanisms underlying these effects in the hope of harnessing them to reduce all-cause mortality. This line of investigation is especially important in light of BCG being discontinued in some countries as the prevalence of TB falls. Stopping routine BCG in this situation may have the unintended consequence of depriving children of the beneficial immune modulating effects of this vaccine. BCG has been recognized as a potent immunomodulator for decades. This review details experimental studies involving BCG and any heterologous antigen that aimed to interrogate potential immunological mechanisms. To provide a historical perspective, the evidence is presented chronologically. The lines of immunological enquiry can be seen to mirror the evolution of our understanding of cell-mediated immunity and its components. As new clinical trials to investigate the heterologous effects of BCG are undertaken, an understanding of the history of BCG-induced immunity against heterologous antigens may provide information on immunological pathways worthy of further interrogation using modern immunological methods.

Background.BCG vaccination is associated with a reduction in all-cause infant mortality in high-mortality settings. The under-lying mechanisms remain uncertain, but long-term modulation of the innate immune response (trained immunity) may be involved.Methods.Whole-blood specimens, collected 7 days after randomization from 212 neonates enrolled in a randomized trial of neo-natal BCG vaccination, were stimulated with killed pathogens and Toll-like receptor (TLR) ligands to interrogate cytokine responses.Results.BCG-vaccinated infants had increased production of interleukin 6 (IL-6) in unstimulated samples and decreased pro-duction of interleukin 1 receptor antagonist, IL-6, and IL-10 and the chemokines macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and monocyte chemoattractant protein 1 (MCP-1) following stimulation with peptidoglycan (TLR2) and R848 (TLR7/8). BCG-vaccinated infants also had decreased MCP-1 responses following stimulation with heterologous pathogens. Sex and maternal BCG vaccination status interacted with neonatal BCG vaccination.Conclusions.Neonatal BCG vaccination influences cytokine responses to TLR ligands and heterologous pathogens. This effect is characterized by decreased antiinflammatory cytokine and chemokine responses in the context of higher levels of IL-6 in unstim-ulated samples. This supports the hypothesis that BCG vaccination modulates the innate immune system. Further research is war-ranted to determine whether there is an association between these findings and the beneficial nonspecific (heterologous) effects of BCG vaccine on all-cause mortality.

Mycobacterium gordonae is a slow growing, pigmented, nontuberculous mycobacterium. It is commonly associated with environmental contamination of clinical specimens, but it is also a recognized pathogen in immunocompromised hosts. We describe an immunocompetent child with a spontaneously occurring skin ulcer on the face caused by M. gordonae infection.

IntroductionBCG vaccination reduces all-cause infant mortality in high-mortality settings by more than can be attributed to protection against tuberculosis. This is proposed to result from non-specific protection against non-vaccine targeted (‘off-target’) infections. There is also evidence that BCG protects against allergic diseases.Methods and analysisThe Melbourne Infant Study: BCG for Allergy and Infection Reduction is a phase III multicentre, single-blinded, randomised controlled trial. A total of 1438 healthy neonates will be randomised to receive either BCG vaccination or no BCG vaccination in the first 10 days of life. Measures of allergy, eczema, infection and asthma will be obtained from parent-completed questionnaires 3 monthly in the first year and 6 monthly from 1 to 5 years of age, and clinical assessments at 1 and 5 years of age. Biological samples will also be collected for future immunological studies.Analysis primary outcomeThe proportion of participants with measures of allergy and infection (atopic sensitisation, eczema, lower respiratory tract infection) at 1 and 5 years of age, and asthma at 5 years of age. Secondary outcomes: (1) the proportion of participants with additional measures of allergy, eczema, asthma and infections; (2) medication use for eczema and asthma; (3) the severity and age of onset of eczema and asthma; (4) the number of episodes of infection; (5) hospitalisations for infections and (6) laboratory measures of immune responses.Ethics and disseminationThis trial has ethical and governance approval from Mercy Health Human Research Ethics Committee (HREC, No. R12-28) and Royal Children’s Hospital HREC (No. 33025) with additional governance approval from Barwon Health and St John of God, Geelong, Victoria. Results of this trial will be published in peer-reviewed journals and presented at scientific conferences.Trial registration numberNCT01906853

A previously healthy 10-year-old girl became acutely unwell with headache, nausea and vomiting, all exacerbated by movement. She also had an episode of altered consciousness with subsequent retrograde amnesia and was incontinent of urine. She presented to her local hospital and was found to be afebrile with no focal neurological signs. She was discharged with a diagnosis of first-episode absence seizure. Over …

The pathogenesis of Kawasaki disease (KD) remains unknown and there is accumulating evidence for the importance of the innate immune system in initiating and mediating the host inflammatory response. We compared innate immune responses in KD and toxic shock syndrome (TSS) participants more than two years after their acute illness with control participants to investigate differences in their immune phenotype. Toxic shock syndrome shares many clinical features with KD; by including both disease groups we endeavoured to explore changes in innate immune responses following acute inflammatory illnesses more broadly. We measured the in vitro production of interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-1 receptor antagonist (IL-1ra), and IL-10 following whole blood stimulation with toll-like receptor and inflammasome ligands in 52 KD, 20 TSS, and 53 control participants in a case-control study. Analyses were adjusted for age, sex, and unstimulated cytokine concentrations. Compared to controls, KD participants have reduced IL-1ra production in response to stimulation with double stranded RNA (geometric mean ratio (GMR) 0.37, 95% CI 0.15, 0.89, p = 0.03) and increased IL-6 production in response to incubation with Lyovec™ (GMR 5.48, 95% CI 1.77, 16.98, p = 0.004). Compared to controls, TSS participants have increased IFN-γ production in response to peptidoglycan (GMR 4.07, 95% CI 1.82, 9.11, p = 0.001), increased IL-1β production to lipopolysaccharide (GMR 1.64, 95% CI 1.13, 2.38, p = 0.01) and peptidoglycan (GMR 1.61, 95% CI 1.11, 2.33, p = 0.01), and increased IL-6 production to peptidoglycan (GMR 1.45, 95% CI 1.10, 1.92, p = 0.01). Years following the acute illness, individuals with previous KD or TSS exhibit a pro-inflammatory innate immune phenotype suggesting a possible underlying immunological susceptibility or innate immune memory.

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.

You are working on the postnatal ward of a busy maternity hospital. While doing a routine discharge check of a newborn baby, the mother asks you about the availability of BCG vaccination. Her two older children have severe eczema, asthma and food allergies, and she has read on the internet that BCG may reduce the risk of allergic disease. In a newborn infant (patient), does BCG vaccination (intervention) prevent the development of allergic disease in later life (outcome)? Medline and Embase were searched (1946 to current date) using the keywords ((bacille Calmette-Guerin) OR (BCG)) AND (allergy OR asthma). Restrictions were human subjects, randomised controlled trials, systematic reviews and meta-analyses. This search yielded 64 articles. A search of the Cochrane Library revealed a further five articles. Of these 69 articles, one randomised controlled trial and four systematic reviews (three with meta-analyses) of observational studies were relevant and selected for full text review. Excluded articles included 10 randomised controlled trials of BCG as an immune therapy for asthma and allergic rhinitis in childhood as they did not relate to the question of prevention. The hygiene hypothesis proposes that diminished microbial exposure in early life prevents the switch from the T helper 2 (Th2) immune response that predominates in neonates to a T helper 1 (Th1) response.1 A persistent …

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.

Background. Serious bacterial illness (SBI) presents a diagnostic challenge in febrile infants. History, clinical signs, and laboratory information combined with experiential knowledge affects decisions to admit and treat. Aim. To assess the utility of serum procalcitonin and the Acute Infantile Observation Score (AIOS) performed at emergency department presentation in predicting (a) confirmed serious bacterial illness and (b) illness severity. Methods. Sensitivity, specificity, and likelihood ratios were calculated for C-reactive protein, white cell count, serum procalcitonin, and AIOS. Results. Forty-six infants were recruited. Seven had a diagnosis of SBI, 28 were moderately ill with length of stay >24 hours, and 12 were severely ill with length of stay >96 hours. The positive likelihood ratios for confirmed SBI were C-reactive protein = 5.3, procalcitonin = 0.43, white cell count = 1.9, and AIOS = 1.5. Conclusion. Procalcitonin and the AIOS do not modify the diagnostic uncertainty of the ED physician assessing the febrile infant with respect to admission or antibiotic treatment above standard laboratory investigations.

Figure 1. Occipital skull defect and a small cerebellar abscess (11 9 12 mm). A previously healthy 3-year-old girl presented with a 4-week history of subcutaneous midline occipital swelling, which subsequently became fluctuant with spontaneous discharge of pus (Figure 1). Surgical drainage revealed a sinus tract extending into the occipital periosteum. Intraoperative magnetic resonance imaging identified an occipital skull defect and a small cerebellar abscess (11 9 12 mm) (Figure 2; available at www. jpeds.com). Posterior fossa craniectomy, abscess drainage, and sinus tract excision were performed. Histopathology of the midline lesion confirmed a dermoid cyst, and culture from the pus grew Staphylococcus lugdunensis (sensitive to flucloxacillin, vancomycin, and teicoplanin). To account for the possibility of polymicrobial infection, combined therapy with intravenous teicoplanin and ceftriaxone was initiated. Six weeks of therapy resulted in full clinical recovery. S lugdunensis is one of a group of Gram-positive, coagulase-negative staphylococci (CoNS) that is unique in its virulence compared with other CoNS. It has been associated with invasive infections of skin, soft tissue, and prosthetic devices, in particular with ventriculoperitoneal shunt infections, where brain abscess formation has been reported as well. Furthermore, it is the second most common CoNS (after Staphylococcus epidermidis), causing infective endocarditis of native/prosthetic valves and associated with destructive valvular disease. The clinical significance of the organism in pediatric patients may be lower than that reported in adult studies. To reflect its enhanced pathogenicity, the European Committee on Antimicrobial Susceptibility Testing/Clinical and Laboratory Standards Institute breakpoints for oxacillin are the same as those for Staphylococcus aureus (multiplicity of infection >2.0), in contrast to those for other CoNS (0.25). b-lactams are appropriate only in cases where antimicrobial susceptibility testing results are known, given that resistance to all b-lactams conferred by altered penicillin-binding proteins is common. Thus, a glycopeptide antibiotic is usually used empirically for known CoNS infection. In this case, ceftriaxone was added to teicoplanin to provide enhanced cerebrospinal fluid penetration and to cover the possibility of polymicrobial infection. n

Adequate iron isessential for growth and haematpoiesis. Oral iron supplementation is the standard of care in VLBW infants. Post mortem evidence has confirmed significant iron overload. Excessive free iron has been associated with free radical formation and brain injury in term infants. Iron indices were measured in VLBW infants (weight 300microg/L was considered elevated. Data was analysed using SPSS Version 14.0. Associations were assessed using Mann Whitney U tests for non-parametric variables and p< 0.05. Ferritin levels were elevated in 31% (n=14). The mean ferritin level was 270microgms/L. The mean total Iron was within normal limits at 16.64umol (11-34umol). However mean Transferrin and TIBC levels were below normal at 1.75g/dl (2-3g/dl) and 42.35umol (50-85umol) respectively. 19 MRIs had been conducted at term. Of 6 MRIs conducted in the high ferritin group, 3 were abnormal and 3 were normal. In the low ferritin group 13 MRIS were conducted at term, 10 were normal and 3 were abnormal. In this group of healthy VLBW infants there was a 31% of iron overload at time of starting routine iron supplementation. ELBW and lower gestational age were risk factors for developing iron overload which seems to be associated with number of transfusions required. VLBW infants with high ferritin longer on both NCPAP and 02.