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Herpes simplex CNS infection is a rare but important cause of neurological disability. Long term outcomes after HSV CNS infection in Australia have not yet been fully described. We sought to provide a comprehensive review of HSV CNS infection in children using a retrospective 13-year evaluation of statewide laboratory and clinical records and a parent survey conducted at least one year after the initial infection.All positive PCR HSV 1 and 2 results from cerebrospinal fluid (CSF) or brain tissue were obtained from Queensland pathology providers for children aged 0-16 years between 1 January 2005 and 31 December 2017. Clinical data were obtained from patient records and longer-term outcomes via parent survey at least 1 year after initial infection.Forty-three children were identified over the 13-year period, 17 (39.5%) neonates and 26 (60.4%) non-neonates. The annual incidence for HSV CNS infection in Queensland children aged ≤16 years was 0.3/100 000 (95% confidence intervals (CIs): 0.2-0.4) with neonates at highest risk (incidence 2.5/100 000 live births, 95% CI: 1.5-3.9). HSV 1 was the predominant serotype in both neonates and non-neonates (9/17, 52.9% neonates and 19/26, 73.1% non-neonates). Seven (16.3%) children died, five (5/17, 29.4% neonates), directly attributable to HSV CNS infection (all neonates). Twenty-five (58.1%) had neurological morbidity at discharge (9/17 neonates (52.9%) vs. 16/26 (61.5%) non-neonates) and 20/27 (74.1%) reported long-term neurological morbidity at follow-up (5/9 neonates (55.6%) vs. 15/18 non-neonates (83.3%)). Seven children (two neonates and four non-neonates) with long-term neurological sequelae had no neurological morbidity identified at discharge.Significant long-term neurologic sequelae were seen in children with HSV CNS infection even in children with no neurological disability identified at discharge from hospital. Careful neurodevelopmental follow-up of all children is recommended.

Human parechovirus (HPeV) is an increasingly recognised cause of severe illness and central nervous system infection in infants. Medium- to long-term neurodevelopmental outcomes post-HPeV infection remain unknown. This study aims to assess neurodevelopmental outcomes for children hospitalised as infants with HPeV infection in their second and third years of life.This prospective cohort study followed children hospitalised with HPeV in Brisbane, Queensland during the 2017/2018 outbreak. Serial application of Ages and Stages Questionnaire (ASQ) was used to assess developmental progress in the second and third years of life. Data from clinical follow-up, audiology and neuroradiology were included.In the second year of life, 63% (n = 29) of children showed some or significant concerns for developmental delay. This had largely been ameliorated by the third year of life when only 30% (n = 14) reported developmental concerns. Prematurity and apnoeas were associated with developmental concerns at 27-36 months of age. Communication was the most common domain of concern.The majority of infants hospitalised with HPeV infection in 2017-2018 showed normalisation of developmental progress by 27-36 months of age. Further investigation into more subtle neurological impairments in later childhood is required. These results can help guide clinicians in counselling parents during the acute illness and in planning appropriate follow-up.

AimThe Australian 'There is no place like home' project is implementing a paediatric low-risk febrile neutropenia (FN) programme across eight paediatric hospitals. We sought to identify the impact of the coronavirus disease 2019 (COVID-19) pandemic on programme implementation.MethodsPaediatric oncology, infectious diseases and emergency medicine health-care workers and parent/carers were surveyed to explore the impact of the COVID-19 pandemic on home-based FN care. Online surveys were distributed nationally to health-care workers involved in care of children with FN and to parents or carers of children with cancer.ResultsSurveys were completed by 78 health-care workers and 32 parents/carers. Overall, 95% of health-care workers had confidence in the safety of home-based FN care, with 35% reporting changes at their own hospitals in response to the pandemic that made them more comfortable with this model. Compared to pre-pandemic, >50% of parent/carers were now more worried about attending the hospital with their child and >80% were interested in receiving home-based FN care. Among both groups, increased telehealth access and acceptance of home-based care, improved patient quality of life and reduced risk of nosocomial infection were identified as programme enablers, while re-direction of resources due to COVID-19 and challenges in implementing change during a crisis were potential barriers.ConclusionThere is strong clinician and parent/carer support for home-based management of low-risk FN across Australia. Changes made to the delivery of cancer care in response to the pandemic have generally increased acceptance for home-based treatments and opportunities exist to leverage these to refine the low-risk FN programme.

Background: National neonatal surveillance for herpes simplex virus (HSV) disease suggests that the incidence of HSV disease may be higher in Queensland (QLD) than in other Australian States. We sought to investigate the incidence via a retrospective 13-year evaluation of statewide laboratory data, autopsy data and linked clinical records of infants with laboratory confirmed infection. Methods: All positive polymerase chain reaction HSV 1 and 2 results were obtained for infants 0-3 months of age from January 1, 2005 to December 31, 2017. Clinical data were obtained from patient records and parent questionnaires were used to evaluate long-term sequelae. Results: One hundred seventy-two infants with HSV positive polymerase chain reaction results: 121 (70.3%) with HSV 1. Of 104 (60.5%) infants with signs of HSV disease, 76 (73.1%) were neonates (≤28 days of age) [incidence 9.6 (95% confidence interval, 7.0-11.5) per 100,000 live births] and 28 (26.9%) were young infants (29-90 days of age) [3.6 (95% confidence interval, 2.4-5.4) per 100,000 live births]. The annual incidence of neonatal HSV disease increased significantly in Queensland over the study period (P < 0.01). Of the 76 neonates with HSV disease, 58 (76.3%) presented with the skin, eye, mouth (SEM) disease, 17 (22.4%) with HSV encephalitis and 11 (14.5%) had disseminated disease. Young infants presented with HSV skin, eye, mouth disease (21, 75.0%) or HSV encephalitis (6, 21.4%). Death occurred in 12/104 (11.5%) infants (all neonates) with 10 attributable to HSV disease. Conclusion: The incidence of neonatal HSV disease in QLD is almost 3 times the national reported incidence. Further research is being undertaken to explore reasons for this change and implications for practice.

Aim: To identify barriers to influenza vaccination of children hospitalised for acute respiratory illness in Australia. Methods: A total of 595 parents of children hospitalised with acute respiratory illness across five tertiary hospitals in 2019 participated in an online survey. Multivariate logistic regression identified factors most strongly associated with influenza vaccination barriers. Results: Odds of influenza vaccination were lower with lack of health-care provider (HCP) recommendation (adjusted odds ratio (aOR) 0.18; 95% confidence interval (CI): 0.08–0.38); if parents had difficulties (aOR 0.19; 95% CI: 0.08–0.47) or were ‘neutral’ (aOR 0.23; 95% CI: 0.06–0.82) in remembering to make an appointment; and if parents had difficulties (aOR 0.21; 95% CI: 0.07–0.62) or were ‘neutral’ (aOR 0.24; 95% CI: 0.07–0.79) regarding getting an appointment for vaccination. Odds were also lower if parents did not believe (aOR 0.27; 95% CI: 0.08–0.90) or were ‘neutral’ (aOR 0.15; 95% CI: 0.04–0.49) regarding whether the people most important to them would have their child/ren vaccinated against influenza. Children had lower odds of vaccination if parents did not support (aOR 0.09; 95% CI: 0.01–0.82) or were ambivalent (aOR 0.09; 95% CI: 0.01–0.56) in their support for influenza vaccination. Finally, lack of history of influenza vaccination of child (aOR 0.38; 95% CI: 0.18–0.81) and respondent (aOR 0.25; 95% CI: 0.11–0.56) were associated with lack of receipt of influenza vaccine before admission for acute respiratory infection. Conclusions: Assisting parents in remembering and accessing influenza vaccination and encouraging health-care providers to recommend vaccination may increase uptake.

Children with severe needle phobia find vaccination extremely distressing and can remain unvaccinated, which puts them at an increased risk of contracting and transmitting vaccine preventable disease. Referral to a specialist or hospital service may occur when they cannot be safely vaccinated in the community, but engagement of allied health services can be inconsistent. The aim of the study was to assess the impact of a multidisciplinary, consumer-oriented model of care on vaccinations for needle phobic children.Needle phobic children aged between 6 and 16 years attended multidisciplinary consultation, as part of a care package, to assess previous experiences and determine the level of intervention that was required to support vaccination. A multidisciplinary case meeting followed this appointment and an individualised plan formulated for each patient. The main outcome of the project was rate of successful vaccination.The care package resulted in a successful vaccination rate of 83% (n = 20) with 69 vaccines administered across three clinics. Of those successful, 90% required multiple injections per visit. The majority of patients indicated moderate to high level of anxiety. Supportive care was escalated and de-escalated as tolerated.Results demonstrate the diversity of patients presenting with needle phobia and indicate an individualised, collaborative approach is preferable to a 'one size fits all' model of care. The study highlights a need for the development of guidelines that streamline the assessment and individualisation of procedural anxiety plans to meet patient needs and embed these processes into standard care.

Background Invasive fungal disease (IFD) is a common and important complication in children with acute myeloid leukaemia (AML). We describe the epidemiology of IFD in a large multicentre cohort of children with AML. Methods As part of the retrospective multicentre cohort TERIFIC (The Epidemiology and Risk factors for Invasive Fungal Infections in immunocompromised Children) study, proven/probable/possible IFD episodes occurring in children with primary or relapsed/refractory AML from 2003 to 2014 were analysed. Crude IFD prevalence, clinical characteristics, microbiology and treatment were assessed. Kaplan-Meier survival analysis was used to estimate 6-month survival. Results There were 66 IFD episodes diagnosed in 63 children with AML. The majority (75.8%) of episodes occurred in the context of primary AML therapy. During primary AML therapy, the overall prevalence was 20.7% (95% CI 15.7%-26.5%) for proven/probable/possible IFD and 10.3% (95% CI 6.7%-15.0%) for proven/probable IFD. Of primary AML patients, 8.2% had IFD diagnosed during the first cycle of chemotherapy. Amongst pathogens implicated in proven/probable IFD episodes, 74.4% were moulds, over a third (37.9%) of which were non-Aspergillus spp. Antifungal prophylaxis preceded 89.4% of IFD episodes, most commonly using fluconazole (50% of IFD episodes). All-cause mortality at 6 months from IFD diagnosis was 16.7% with IFD-related mortality of 7.6% (all in cases of proven IFD). Conclusions IFD is a common and serious complication during paediatric AML therapy. Mould infections, including non-Aspergillus spp. predominated in this cohort. A systematic approach to the identification of patients at risk, and a targeted prevention strategy for IFD is needed.

Mycobacterium abscessus complex pulmonary disease (M. abscessus PD) in cystic fibrosis (CF) is challenging to treat. Current guideline therapeutic regimens involving an intensive phase of intravenous (IV) antibiotics followed by a consolidation phase of inhaled and oral antibiotics are not evidence-based. The objectives of this study were to characterize the clinical outcomes and clearance of Mycobacterium abscessus complex (M. abscessus) from respiratory cultures in children with CF M. abscessus PD.This retrospective longitudinal cohort analysis evaluated the first course of treatment for M. abscessus PD in 33 children in Queensland, Australia between 2001 and 2015. Spirometry and nutritional outcomes 2 years pretreatment and 1 year posttreatment were compared with clearance or relapse/persistence of Mycobacterium abscessus complex from respiratory cultures.Nine of 18 children who completed therapy, cleared infection. Three of 7 children who completed only intensive therapy cleared sputum compared with 0/8 children who did not. The trajectory of the percent predicted forced expiratory volume in 1 s and age standardized body mass index significantly improved posttreatment in those that cleared sputum (P0.0001).These results suggest that current treatment recommendations for M. abscessus PD are associated with some success in clearing infection in children with CF and improvement in lung function and body mass index. Clinical trials are required to determine the best treatment approaches.

Objectives: Reduction of nosocomial infections represents an increasingly recognized aspect of PICU benchmarking. We investigated the prevalence and outcomes of viral respiratory infections acquired during admission to PICU.Design: Multicenter, statewide retrospective linkage study.Setting: Tertiary PICU.Patients: All children less than 16 years requiring PICU admission for greater than 48 hours from January 1, 2008, until December 31, 2013.Intervention: Testing was performed in symptomatic patients using an extended panel polymerase chain reaction capturing nine respiratory viruses. Duration of intubation and total duration of respiratory support were primary outcomes.Measurements and Main Results: Of 3,607 patients admitted to PICU for greater than 48 hours, 102 (2.8%) were diagnosed with a PICU-associated viral infection out of 702 patients (19.4%) undergoing viral testing, reflecting a rate of 2.8 PICU-associated viral infections per 1,000 PICU patient days. Compared with negative/untested patients, those with PICU-associated viral infections had greater intubation duration (median 164 vs 67; p < 0.001), longer respiratory support (204 vs 68 hr; p < 0.001), were more likely to require extracorporeal life support (odds ratio, 5.3; 2.7-10.3; p < 0.001), high-frequency oscillatory ventilation (odds ratio, 3.0; 1.7-5.4; p < 0.001), and inhaled nitric oxide (odds ratio, 2.7; 1.5-5.0; p = 0.001). When comparing patients with PICU-associated viral infection with patients who tested negative for respiratory viruses, no substantial difference in these outcomes was found.Conclusions: The acquisition of viral infections during PICU admission is less frequent compared with previous reports on bacterial and fungal hospital-acquired infections. We did not observe worse patient-centered outcomes when comparing virus positive versus tested but negative patients. Our findings challenge the clinical value of performing viral respiratory diagnostics in PICU patients evaluated for infection.

Viral infections are common in children, but there is a lack of data on severe viral infections in critically ill children. We investigated testing for viral infections in children requiring PICU admission and describe the epidemiology and outcomes.Multicenter retrospective study. Results of viral testing for nine respiratory viruses using polymerase chain reaction were collected.Children less than 16 years old nonelectively admitted to PICU over a 6-year period.Two tertiary PICUs in Queensland, Australia.None.Primary outcome was PICU length of stay. Secondary outcomes included need for and duration of intubation and mortality in PICU. Univariate and multivariate regression analyses were performed, adjusting for age, indigenous status, comorbidities, and severity of illness.Of 6,426 nonelective admissions, 2,956 (46%) were polymerase chain reaction tested for a virus of which 1,353 (46%) were virus positive. Respiratory syncytial virus was the most common pathogen identified (n = 518, 33%), followed by rhinovirus/enterovirus and adenovirus. Across all patients who underwent polymerase chain reaction testing, identification of a respiratory virus was not significantly associated with longer overall length of stay (multivariate odds ratio, 1.08; 95% CI, 0.99-1.17; p = 0.068) or longer intubation (p = 0.181), whereas the adjusted odds for intubation and mortality were significantly lower (p0.01). Subgroup analyses restricted to patients with acute respiratory infections (n = 1,241), bronchiolitis (n = 761), pneumonia (n = 311), confirmed bacterial infection (n = 345), and malignancy (n = 95) showed that patients positive for a virus on testing had significantly longer PICU length of stay (multivariate p0.05). In children with pneumonia, identification of a respiratory virus was associated with significantly increased duration of ventilation (p = 0.003). No association between positive test results for multiple viruses and outcomes was observed.Viral infections are common in critically ill children. Viral infections were associated with lower intubation and mortality rates compared with all children testing negative for viral infections. In several subgroups studied, identification of viral pathogens was associated with longer PICU length of stay while mortality was comparable. Prospective studies are required to determine the benefit of routine testing for respiratory viruses at the time of PICU admission.

Anti-N-Methyl-D-Aspartate-receptor encephalitis is the most common antibody-mediated autoimmune encephalopathy. A HIV-infected African boy presented with subacute psychosis as manifestation of anti-N-Methyl-D-Aspartate-receptor encephalitis. Intravenous immunoglobulin and corticosteroids induced complete remission. Although this is the first pediatric case described, 5 adult cases have been reported. The role of HIV in the etiology of this autoimmune condition requires further exploration.

OBJECTIVES: To describe the features and frequency of RSV-associated severe acute neurologic disease in children. STUDY DESIGN: We performed a systematic review of the literature to identify reports of severe acute neurologic complications associated with acute respiratory syncytial virus (RSV) infection in children aged

Influenza-associated encephalitis/encephalopathy (IAE) is an important cause of acute encephalitis syndrome in children. IAE includes a series of clinicoradiologic syndromes or acute encephalopathy syndromes that have been infrequently reported outside East Asia. We aimed to describe cases of IAE identified by the Australian Childhood Encephalitis study.Children ≤ 14 years of age with suspected encephalitis were prospectively identified in 5 hospitals in Australia. Demographic, clinical, laboratory, imaging, and outcome at discharge data were reviewed by an expert panel and cases were categorized by using predetermined case definitions. We extracted cases associated with laboratory identification of influenza virus for this analysis; among these cases, specific IAE syndromes were identified where clinical and radiologic features were consistent with descriptions in the published literature.We identified 13 cases of IAE during 3 southern hemisphere influenza seasons at 5 tertiary children's hospitals in Australia; 8 children with specific acute encephalopathy syndromes including: acute necrotizing encephalopathy, acute encephalopathy with biphasic seizures and late diffusion restriction, mild encephalopathy with reversible splenial lesion, and hemiconvulsion-hemiplegia syndrome. Use of influenza-specific antiviral therapy and prior influenza vaccination were infrequent. In contrast, death or significant neurologic morbidity occurred in 7 of the 13 children (54%).The conditions comprising IAE are heterogeneous with varied clinical features, magnetic resonance imaging changes, and outcomes. Overall, outcome of IAE is poor emphasizing the need for optimized prevention, early recognition, and empiric management.

This study describes a successful, targeted intervention in central venous access device routine care to decrease central line-associated bloodstream infection. Taurolidine-citrate locks significantly reduced the rate of central line-associated bloodstream infection, particularly Gram-negative organisms without adverse events.

Background Invasive fungal infections (IFI) are an important complication of acute lymphoblastic leukaemia (ALL) treatment. Our study describes the prevalence and outcomes of IFI in children with ALL. Methods IFI episodes in children with primary or relapsed ALL, identified for The Epidemiology and Risk Factors for Invasive Fungal Infections in Immunocompromised Children study, were analysed. IFI were classified according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group criteria with a 'modified-possible' category included. Results A total of 123 IFI episodes in 119 patients with ALL were included. A proven, probable, possible and modified-possible IFI was diagnosed in 56 (45.5%), 22 (17.9%), 39 (31.7%) and six (4.9%) episodes, respectively. The prevalence was 9.7% (95% confidence interval [CI] 8-11.4%) overall and 23.5% (95% CI 14.5-32.5%) for relapsed/refractory ALL. For non-relapsed ALL, the IFI prevalence was significantly higher for children with high-risk compared to standard-risk ALL (14.5% vs 7.3%, P = .009), and IFI were more common during induction, consolidation and delayed intensification phases. Mould infections occurred more frequently than non-mould infections. Thirteen children (10.9%) died within 6 months of IFI diagnosis with five deaths (4.2%) attributable to an IFI. Conclusions IFI is more common in children with high-risk ALL and in relapsed disease. Overall survival was encouraging, with IFI contributing to very few deaths.

The aim of the present study was to review the potential impacts and barriers to upscaling a pilot congenital Cytomegalovirus (cCMV) screening program into a state-wide permanent universal newborn hearing screening (UNHS) program.This study reviewed the outcomes of the cCMV screening program pilot operating at three maternity hospitals to standard state-wide laboratory notifications in Queensland, Australia between August 2014 to April 2018. Stakeholder interviews were also conducted to inform state-wide program implementation.Of the 485 infants tested for CMV on a saliva swab at the pilot sites, 4 (0.8%) returned a positive result. Review of the state-wide laboratory infant CMV PCR notifications for the same time-period revealed more than half of infants with cCMV (63.7%) would not have been detected under a state-wide targeted screening program as they either passed newborn hearing screening, were deceased, symptomatic, or were born34 weeks gestational age. Barriers to state-wide program implementation included program-level factors (timing of the cCMV screen, funding, cross-agency communication, workforce and training) and community-level factors (low public cCMV awareness and prevalence).Although cCMV screening alongside UNHS is achievable, a number of barriers need to be addressed prior to state-wide program implementation.

AIM The human parechovirus (HPeV) has emerged as a pathogen causing sepsis-like presentations in young infants, but there is a lack of data on HPeV presentations requiring intensive care support. We aimed to characterise the clinical presentation, disease severity, management and outcome of a population-based cohort of children with microbiologically confirmed HPeV infection requiring admission to paediatric intensive care units (PICUs) in Queensland, Australia during a recent outbreak. METHODS This was a multicentre retrospective study of children admitted to PICU between 1 January 2015 and 31 December 2016 with confirmed HPeV infection. RESULTS Thirty infants (median age 20 days) with HPeV genotype 3 were admitted to PICU, representing 16% of all children with HPeV admitted to hospital and 6.4% of non-elective PICU admissions in children

Aim: Targeted screening by a salivary cytomegalovirus (CMV) polymerase chain reaction (PCR) of infants who ‘refer’ on their newborn hearing screen has been suggested as an easy, reliable and cost-effective approach to identify and treat babies with congenital CMV (cCMV) to improve hearing outcomes. This study aimed to investigate the feasibility and cost-effectiveness of introducing targeted salivary cCMV testing into a newborn hearing screening programme. Methods: The study included three tertiary maternity hospitals in Queensland, Australia between August 2014 and April 2016. Infants who ‘referred’ on the newborn hearing screen were offered a salivary swab for CMV PCR at the point of referral to audiology. Swabs were routinely processed and tested for CMV DNA by real-time quantitative PCR. Parents of babies with a positive CMV PCR were notified, and the babies were medically assessed and, where appropriate, were offered treatment (oral valganciclovir). Results: Of eligible infants, the parents of 83.0% (234/283) consented to the cCMV screen. Of these, 96.6% returned a negative result (226/234), and 3.4% (8/234) returned a positive result (three true positive; five false positive). The prevalence of cCMV for infants with confirmed hearing loss was 3.64% (P = 2/55; confidence interval = 0.44–12.53%). The cost comparison suggests the cost implementation of cCMV screening (and subsequent potential treatment benefits and management over time), compared to non-screening (and subsequent management), to be negligible. Conclusion: Incorporating cCMV testing into Universal Newborn Hearing Screening within Queensland is realistic and achievable, both practically and financially.

To investigate the proportion of children with moderate to profound hearing loss who have congenital cytomegalovirus (cCMV) infection. Retrospective analysis of CMV dried blood spot (DBS) polymerase chain reaction (PCR) in children with moderate to profound hearing impairment referred to tertiary referral centres in Queensland. Participants were under 18 years old with no readily identified cause of hearing impairment, between 2008 and 2011. The primary outcome measure was DBS CMV PCR. Other outcome measures for cases referred to the Childhood Hearing Clinic (CHC) at the Mater Children's Hospital were level of hearing impairment and the neonatal hearing screen result. Of DBS CMV PCR testing for 106 children at the CHC for 2008 to 2011 inclusive, nine (8.5%) were positive (five with bilateral hearing impairment, four with unilateral hearing impairment). The prevalence of cCMV infection in children with moderate to profound hearing impairment was 8.4%, consistent with the statewide rate of 9.4% for 2008 to mid-2011. cCMV is a significant cause of hearing impairment in Queensland children. Investigation for cCMV by retrospective DBS CMV PCR should be part of the routine investigation of all babies and young children with hearing impairment. However early diagnosis is preferable and could be achieved by routine early screening of all newborns with hearing impairment for CMV before 3 weeks of age. The healthy hearing screening programme is a routine part of neonatal care. Enhancing the integration of screening for cCMV may reduce the current delays in diagnosis and should be evaluated.

Congenital cytomegalovirus (cCMV) is the most common non-genetic cause of sensorineural hearing loss (SNHL) in children. Ganciclovir has been shown to prevent the continued deterioration in hearing of children with symptomatic cCMV, but some children with cCMV-related SNHL are unidentified in the neonatal treatment period. Neonatal cCMV screening provides an opportunity to identify infants with cCMV-related SNHL who might benefit from early treatment.To assess the feasibility (ability to take samples before 3 weeks of age and clinical assessment by 30 days of age) and acceptability (maternal anxiety) of targeted CMV testing of infants who are 'referred' for further audiological testing after routine newborn hearing screening programme (NHSP).Parents of infants who have 'no clear responses' on routine NHSP before 22 days of life in London and North East England were approached. Salivary and urine samples were tested by CMV PCR. At recruitment and 3 months, the short form Spielberger State-Trait Anxiety Inventory measured maternal anxiety.411 infants were recruited. 99% (407/411) returned a sample; 98% (404/411) successfully yielded a CMV result, 6 had cCMV, all diagnosed on salivary samples taken22 days of age (1.5%; 95% CI 0.6% to 3.2%). Only 50% returned urine samples compared with 99% returning salivary samples (p0.001). Using saliva swabs 98% were successfully screened for CMV within 3 weeks. All positive screening CMV results were known by day 23, and 5/6 infants with cCMV were assessed within 31 days. Anxiety was not increased in mothers of infants screened for cCMV.Targeted salivary screening for cCMV within the NHSP is feasible, acceptable and detects infants with cCMV-related SNHL who could benefit from early treatment.

Wet cough is a common feature of many disease processes affecting children. Our aim was to examine the relationships between cough nature, lower airway infection (bacterial, viral, and viral-bacterial) and severity of neutrophilic airway inflammation. We hypothesized that viral-bacterial co-infection of the lower airway would be associated with wet cough and heightened neutrophilic airway inflammation. We prospectively recruited 232 children undergoing elective flexible bronchoscopy. Participants were grouped using a cough nature symptom-based approach, into wet, dry or no cough groups. Broncho-alveolar lavage (BAL) and clinical data, including presence, nature, and duration of cough and key demographic factors, were collected. Children with wet cough (n = 143) were more likely to have lower airway bacterial infection (OR 2.6, P = 0.001), viral infection (OR 2.04, P = 0.045) and viral-bacterial co-infection (OR 2.65, P = 0.042) compared to those without wet cough. Wet cough was associated with heightened airway neutrophilia (median 19%) as compared to dry or no cough. Viral-bacterial co-infection was associated with the highest median %neutrophils (33.5%) compared to bacteria only, virus/es only and no infection (20%, 18%, and 6%, respectively, P

Background A thorough understanding of local and contemporary invasive fungal infection (IFI) epidemiology in immunocompromised children is required to provide a rationale for targeted prevention and treatment strategies. Methods Retrospective data over 10 years from four tertiary pediatric oncology and hematopoietic stem cell transplant (HSCT) units across Australia were analyzed to report demographic, clinical, and mycological characteristics of IFI episodes, and crude IFI prevalence in select oncology/HSCT groups. Kaplan-Meier survival analyses were used to calculate 180-day overall survival. Results A total of 337 IFI episodes occurred in 320 children, of which 149 (44.2%), 51 (15.1%), and 110 (32.6%) met a modified European Organization for Research and Treatment of Cancer (mEORTC) criteria for proven, probable, and possible IFI, respectively. There were a further 27 (8.0%) that met a "modified possible IFI" criteria. Median age at IFI diagnosis was 8.4 years. Crude mEORTC IFI prevalence in acute lymphoblastic leukemia, acute myeloid leukemia, solid tumor, and allogeneic HSCT cohorts was 10.6%, 28.2%, 4.4%, and 11.7%, respectively. Non-Aspergillus species represented 48/102 (47.1%) molds identified, and non-albicans Candida represented 66/93 (71.0%) yeasts identified. There were 56 deaths among 297 children who met mEORTC criteria, with 180-day overall survival for proven, probable, and possible IFIs of 79.7%, 76.2%, and 84.4%, respectively. Conclusion Non-Aspergillus molds and non-albicans Candida contributed substantially to pediatric IFI in our study, with high IFI prevalence in leukemia and allogeneic HSCT cohorts. Inclusion of IFIs outside of European Organization for Research and Treatment of Cancer criteria revealed an IFI burden that would go otherwise unrecognized in published reports.

Although antenatal care and diagnosis have improved and many abnormalities are now anticipated infants are still born that pose diagnostic conundrums. We present one such scenario with complex diagnostic and management challenges. Emily was born at 35+6 weeks. This was the first pregnancy for her 19-year-old mum who had no significant medical or obstetric history. She was known to fetal medicine because of fetal growth retardation, with an estimated fetal weight at 33+4 weeks below the third percentile. Following a 3-week period of static growth labour was induced for fetal wellbeing. Shortly after induction following fetal bradycardia Emily was delivered by caesarean section. Emily weighed 1.58 kg (

Background The value of interferon-γ release assays (IGRA) to diagnose active tuberculosis (TB) in children is not established, but these assays are being widely used for this purpose. The authors examined the sensitivity of commercially available IGRA to diagnose active TB in children in the UK compared with the tuberculin skin test (TST). Methods The authors established a paediatric tuberculosis network and conducted a retrospective analysis of data from children investigated for active TB at six large UK paediatric centres. All centres had used TST and at least one of the commercially available IGRA (T-Spot.TB or Quantiferon-Gold in Tube) in the diagnostic work-up for active TB. Data were available from 333 children aged 2 months to 16 years. The authors measured the sensitivity of TST and IGRA in definite (culture confirmed) and probable TB in children, agreement between TST and either IGRA, and their combined sensitivity. Results Of 333 children, 49 fulfilled the criteria of definite TB, and 146 had probable TB. Within the definite cohort, TST had a sensitivity of 82%, Quantiferon-Gold in tube (QFT-IT) had a sensitivity of 78% and T-Spot.TB of 66%. Neither IGRA performed significantly better than a TST with a cut-off of 15 mm. Combining the results of TST and IGRA increased the sensitivity to 96% for TST plus T-Spot.TB and 91% for TST plus QFG-IT in the definite TB cohort. Conclusions A negative IGRA does not exclude active TB disease, but a combination of TST and IGRA increases the sensitivity for identifying children with active TB.

Aims: To describe the clinical features, diagnosis and management of children with tuberculosis in the United Kingdom and Republic of Ireland. Methods: Cases of culture-confirmed and clinically diagnosed tuberculosis were reported to the British Paediatric Surveillance Unit from December 2003 to January 2005. Results: 385 eligible cases were reported. Pulmonary disease was present in 154 (40%) children. Just over half (197, 51%) of children presented clinically and most of the remainder (166, 43%) at contact tracing. A probable source case was identified for 73/197 (36%) of the children presenting clinically. The majority (253, 66%) of children had a microbiological and/or histological investigation, and culture results were available for 240 (62%), of whom 102 (26%) were culture positive. Drug resistance was reported in 15 (0.4%) cases. 44% (128/292) of non-white children did not receive the recommended quadruple drug therapy. Seven children died. Only 57% (217) of children were managed by a paediatric subspecialist in respiratory or infectious diseases or a general paediatrician with a special interest in one of these areas. Fewer than five cases were reported from 119/143 (83%) respondents and 72 of 96 (75%) centres. Conclusions: Many paediatricians and centres see few children with tuberculosis. This may affect adherence to national guidelines. Managed clinical networks for children with tuberculosis may improve management and should be the standard of care.

Repeated episodes of infection are required for the development of a competent immune system and, therefore, are an expected norm in early childhood. Although most children with recurrent infection have normal immunity and do not have serious underlying disease, early and accurate detection of immunodeficient children is essential for delivery of optimised care. This review aims to provide a framework for rational investigation.

To evaluate the impact of an antimicrobial stewardship (AMS) intervention, involving introduction of new guidelines on the treatment of febrile neutropenia (FN), on improving the use of gentamicin in paediatric oncology patients.Updated guidelines for gentamicin usage in paediatrics with FN were implemented at a tertiary children's teaching hospital, in Brisbane, Australia. Data on gentamicin usage before and after the guideline change were collected retrospectively from children with cancer admitted to hospital with FN between January 2012 and December 2013. Gentamicin use, duration of gentamicin therapy and therapeutic monitoring practice were compared against bacterial culture status for admissions before and after the guideline change to assess the impact on practice.Data were collected from 227 children corresponding to 453 separate admissions, 195 preguideline and 257 post-guideline change. Following guideline change, the proportion of admissions in which gentamicin was administered reduced from 79.0 to 20.9% (P-value 0.001) and administrations not associated with a cultured Gram-negative organism dropped from 87.2 to 58.2% (P-value 0.001), indicating a change in practice according to the new guideline. Following guideline change, admissions in which gentamicin was used for 48 hr despite the absence of a confirmed Gram-negative infection decreased from 85.6 to 46.9% (P-value 0.001).Guideline changes driven through an AMS initiative involving paediatric oncology patients significantly improved targeted- and nontargeted-antimicrobial use potentially reducing the risk of emergence of resistance against gentamicin in this cohort.

Over recent years non-culture techniques such as specific viral and bacterial nucleic acid amplification, serology and antigen detection have considerably developed and been applied within research studies to clinical samples, significantly increasing pathogen detection in pneumonia. There are promising signs of improved diagnostic yields for pneumococcal pneumonia when using molecular techniques to detect pneumococcal gene sequences in blood or by combining serum biomarkers with rapid pneumococcal urinary antigen testing. Pathogens have traditionally been difficult to detect in pneumonia and treatment is usually successful with empiric antibiotics. However, directed antibiotic treatment has significant benefits in terms of antibiotic stewardship and these new technologies make this goal a possibility, though not yet a reality.

Background Congenital cytomegalovirus (cCMV) is an important cause of childhood deafness, which is modifiable if diagnosed within the first month of life. Targeted screening of infants who do not pass their newborn hearing screening tests in England is a feasible approach to identify and treat cases to improve hearing outcome. Aims To conduct a cost analysis of targeted screening and subsequent treatment for cCMV-related sensorineural hearing loss (SNHL) in an, otherwise, asymptomatic infant, from the perspective of the UK National Health Service (NHS). Methods Using data from the newborn hearing screening programme (NHSP) in England and a recent study of targeted screening for cCMV using salivary swabs within the NHSP, we estimate the cost (in UK pounds (£)) to the NHS. The cost of screening (time, swabs and PCR), assessing, treating and following up cases is calculated. The cost per case of preventing hearing deterioration secondary to cCMV with targeted screening is calculated. Results The cost of identifying, assessing and treating a case of cCMV-related SNHL through targeted cCMV screening is estimated to be £6683. The cost of improving hearing outcome for an infant with cCMV-related SNHL through targeted screening and treatment is estimated at £14 202. Conclusions The costs of targeted screening for cCMV using salivary swabs integrated within NHSP resulted in an estimate of cost per case that compares favourably with other screening programmes. This could be used in future studies to estimate the full economic value in terms of incremental costs and incremental health benefits.

BACKGROUND Toxic shock syndrome (TSS) is an acute toxin-mediated illness caused by toxin-producing strains of Staphylococcus aureus and Streptococcus pyogenes. There is no recent data regarding incidence, management and mortality of TSS in UK children. METHODS Consultants from paediatric and burns units in the UK and Ireland, reported cases of TSS seen between November 2008 and December 2009, via the British Paediatric Surveillance Unit. Respondents were sent questionnaires requesting detailed information about TSS cases. Established criteria were used to divide cases into staphylococcal or streptococcal TSS. RESULTS Forty-nine cases were identified overall; 29 cases of streptococcal TSS (18 confirmed and 11 probable) and 20 cases of staphylococcal TSS (15 confirmed and 5 probable). The incidence of TSS children in the UK & the Republic of Ireland was calculated to be 0.38 per 100 000 children. Children with staphylococcal TSS were older than those with streptococcal TSS (9.5 vs 3.8 years; p

Tuberculosis (TB) is a serious disease of global importance, with a rising incidence in the developed world in recent years. Tuberculous lymphadenitis, tuberculous meningitis, osteoarticular tuberculosis and miliary tuberculosis are some of the more well-recognised manifestations of non-pulmonary TB in childhood. The diagnosis of non-pulmonary TB poses a particular challenge for clinicians because of the protean ways in which the disease presents. The omission of tuberculosis from the differential diagnosis of patients with obscure illnesses and the relatively insensitive bacteriological methods for detecting Mycobacterium tuberculosis add to the complexity of the problem. A high index of suspicion is required in order to avoid delays in diagnosis which may influence treatment outcome. The advent of DNA amplification techniques such as the polymerase chain reaction may herald a promising new era in the prompt and accurate management of extrapulmonary tuberculosis.

BACKGROUND There are few data on paediatric community acquired pneumonia (PCAP) in the UK. AIMS To investigate the aetiology and most useful diagnostic tests for PCAP in the north east of England. METHODS A prospective study of hospital admissions with a diagnosis of PCAP. RESULTS A pathogen was isolated from 60% (81/136) of cases, and considered a definite or probable cause of their pneumonia in 51% (70/136). Fifty (37%) had a virus implicated (65% respiratory syncytial virus) and 19 (14%) a bacterium (7% group A streptococcus, 4% Streptococcus pneumoniae ), with one mixed infection. Of a subgroup (51 patients) in whom serum antipneumolysin antibody testing was performed, 6% had evidence of pneumococcal infection, and all were under 2 years old. The best diagnostic yield was from paired serology (34%, 31/87), followed by viral immunofluorescence (33%, 32/98). CONCLUSION Viral infection accounted for 71% of the cases diagnosed. Group A streptococcus was the most common bacterial infective agent, with a low incidence of both Mycoplasma pneumoniae and S pneumoniae . Pneumococcal pneumonia was the most common bacterial cause of pneumonia in children under 2 years but not in older children. Inflammatory markers and chest x ray features did not differentiate viral from bacterial pneumonia; serology and viral immunofluorescence were the most useful diagnostic tests.

Pediatric pleural empyema has increased substantially over the past 20 years and reasons for this rise remain not fully explained. We investigated potential risk factors for the development of empyema in children by examining a cohort of patients with community-acquired pneumonia. Demographic, clinical, and socioeconomic characteristics, use of Ibuprofen prior to presentation and selected potential epidemiological risk factors were analyzed. Data were collected from a prospective etiological study of radiologically confirmed pneumonia in hospitalized children aged ≤16 years. One hundred sixty children were enrolled; 56% were male and 69% aged

Objective To determine the role of viral infections in causing fetal and infant death. Study design We assessed a well-validated population database of fetal (≥20 weeks gestation) and infant death for infective deaths and deaths from viruses over a 21-year period (1988-2008). We analyzed by specific viral cause, timing (late fetal loss [20-23 weeks], stillbirth [≥24 weeks], neonatal death [0-27 days], and post-neonatal infant death [28-364 days]) and across time. Results Of the 989 total infective deaths, 108 were attributable to viral causes (6.5% of late fetal losses, 14.5% of stillbirths, 6.5% of neonatal deaths, and 19.4% of postneonatal infant deaths). Global loss (combined fetal and infant losses per 100 000 registerable births) was 139.6 (95% CI, 130.9-148.3) for any infective cause and 15.2 (95% CI, 12.3-18.1) for viral infections. More than one-third (37%) of viral-attributed deaths were before live birth, from parvovirus (63%) or cytomegalovirus (33%). Parvovirus accounted for 26% (28 of 108) of all viral deaths. Cytomegalovirus was associated with a global loss rate of 3.1 (95% CI, 1.8-4.4) and an infant mortality rate of 1.3 (95% CI, 0.4-2.1) per 100 000 live births; 91% of cases were congenital infections. Herpes simplex virus caused death only after live births (infant mortality rate, 1.4; 95% CI, 0.5-2.3). No changes in rates were seen over time. Conclusion We have identified a substantial contribution of viral infections to global fetal and infant losses. More than one-third of these losses occurred before live births. Considering our methodology, our estimates represent the minimum contribution of viral illness. Strategies to reduce this burden are needed.

Brain abscess (BA) and subdural empyema (SDE) are uncommon but clinically important conditions in childhood. Treatment involves surgery and prolonged courses of antibiotics. There is no consensus on the optimal approach. The objective was to review management and outcome of BA and SDE in a single UK center.This retrospective case notes review of children with brain abscess or subdural empyema admitted to a tertiary pediatric infectious diseases and neurosurgical center from 2001 to 2009.Forty-two children were included in the study; 17 children were with BA, 23 with SDE, and two both with BA and SDE. The causative factors found in 88 % of the patients were most commonly sinusitis and meningitis with congenital heart disease and immunocompromise unusual. Streptococcus anginosus group organisms were most common; 10 % of the children had a resistant pathogen and 86 % had surgical intervention. Fifteen patients with BA underwent surgery; nine of these patients underwent burrhole aspiration, three had craniotomy, two had stereotactic surgery, and one had endoscopic aspiration. Remaining 19 patients with SDE underwent surgery: seven had burrhole aspiration, 11 underwent craniotomy, and one had aspiration via the anterior fontanel. The most common antibiotic regime was cefotaxime, metronidazole, and amoxicillin. Mean duration of treatment was 14.4 weeks. Mean time until normalization of C reactive protein was 23 days. Survival was 95 % and 20 % had ongoing neurological sequelae.BA and SDE remain important childhood infections in the UK. Antibiotics are essential in the management of these cases. Empiric antibiotic choices require knowledge of likely pathogens and local resistance. Selected infections can be treated without surgical intervention. Long courses of antibiotics were administered. Outcome is good, and neurological sequelae were less common than found in previous series.

A single-center experience of catheter-related blood stream infections in children undergoing hematopoietic stem cell transplant for primary immunodeficiency is described. The rate of definite central venous catheter infections was 5.31/1000 line days. Staphylococcus epidermidis was the most commonly identified organism. Teicoplanin resistance occurred in 17% of S. epidermidis infections. The central catheter was removed in 21% of infections.

Objective: Assays based on interferon γ (IFNγ) are an exciting new development for screening for latent tuberculosis infection (LTBI) in adults, but there are limited data on their effectiveness in children. Nevertheless new National Institute for Health and Clinical Excellence (NICE) guidelines recommend their use when screening paediatric tuberculosis (TB) contacts. We evaluated the potential effect of the new NICE guidelines on current paediatric practice. Design: Children screened for TB who had had an IFNγ assay performed (QuantiFERON-TB Gold (QFG)) were included. Actual outcomes from existing guidelines were compared with those that would have been obtained using NICE guidelines. Results: QFG assays were performed on 120 children, 103 as part of TB contact tracing. Six of the 120 (5%) were QFG positive, and seven of the 120 (6%) were indeterminate. Where both Mantoux and QFG results were available, these agreed in 62/104 (60%) of cases. QFG tests were more likely to correlate with a negative Mantoux (98% agreement) than with a positive Mantoux (11% agreement). Management outcomes differed for 23/ 103 children seen as part of TB contact tracing. Only one (1%) of these had an indeterminate QFG result. 17 (85%) fewer children would have been given LTBI treatment (chemoprophylaxis) and two (2%) children with possible TB would not have been identified using NICE guidelines. Conclusion: New NICE guidelines for the use of IFNγ-based tests for TB screening will reduce the number of children treated for presumed LTBI. Long-term prospective studies are needed to determine the number of children with positive Mantoux tests but negative IFNγ results who are not given LTBI treatment yet later develop TB.

Objective: To describe the spectrum of clinical features and management of community acquired pneumonia in the UK. Design: Prospectively recorded clinical details for all children with possible pneumonia and chest x ray (CXR) changes in 13 hospitals in the North of England between 2001 and 2002. Results: 89% of 711 children presenting to hospital with pneumonia were admitted; 96% received antibiotics, 70% intravenously. 20% had lobar CXR changes, 3% empyema and 4% required intensive care. Respiratory rate (RR), hypoxia and dyspnoea all correlated with each other and prompted appropriate interventions. Admission in children, not infants, was independently associated with RR, oxygen saturation, lobar CXR changes and pyrexia. Neither C-reactive protein, lobar CXR changes or pyrexia were associated with severity. Children over 1 year old with perihilar CXR changes more often had severe disease (p = 0.001). Initial intravenous antibiotics were associated with lobar CXR changes in infants and children and with dyspnoea, pyrexia and pleural effusion in children. The presence of pleural effusion increased duration of antibiotic treatment (p

Summary The spectrum of morbidity seen in NTM lymphadenopathy varies widely, from complete cure after surgical resection, to continuing induration, erythema and sinus formation. Lesions close to important structures like the facial nerve, making resection almost impossible together with resistance to many drugs makes this a fascinating and challenging condition to treat. Correct initial diagnosis and treatment will prevent months of distress, and complicated drug therapy.

Background and aims: The incidence of complement abnormalities in the UK is not known. It is suggested in at least three major paediatric textbooks to test for abnormalities of the complement system following meningococcal disease (MCD). Methods: Over a four year period, surviving children with a diagnosis of MCD had complement activity assessed. A total of 297 children, aged 2 months to 16 years were screened. Results: All children except one had disease caused by B or C serogroups. One child, with group B meningococcal septicaemia (complicated by disseminated intravascular coagulation and who required ventilation and inotropic support) was complement deficient. C2 deficiency was subsequently diagnosed. She had other major pointers towards an immunological abnormality prior to her MCD. Conclusion: It is unnecessary to screen all children routinely following MCD if caused by group B or C infection. However, it is important to assess the previous health of the child and to investigate appropriately if there have been previous suspicious infections, abnormal course of infective illnesses, or if this is a repeated episode of neisserial infection.

Background Infection is a major cause of perinatal, neonatal and infant deaths, but the viral contribution to these deaths is poorly described. Objective To describe the contribution of viruses to perinatal, neonatal and infant deaths in one Region of the UK (1985–2008). Methods Using Regional Perinatal Mortality Survey – a population based database of fetal deaths ≥20 weeks gestation and in live-born individuals within the first year. Deaths from viral infection were identified, verified and specified. Results From 819 890 live births and 4478 stillbirths (>24 weeks) 1123 deaths were infectious: 585 bacterial, 102 viral. Of viral deaths 29% were parvovirus (mostly stillbirths); 23% were cytomegalovirus (CMV) (mostly stillbirths). 92% of CMV cases were congenital (cCMV). 23 infant deaths were due to respiratory viruses (table 1). Conclusions Viruses caused 9% of all infective deaths: 6% of fetal losses 24 weeks, 5% of neonatal deaths and 15% of non-neonatal infant deaths. In this population viral deaths occur in ∼7:100 000 live-births and 6:1000 stillbirths ≥24 weeks, most commonly from parvovirus or CMV. By comparison 13% of these deaths were attributed to GBS infection. Morbidity from cCMV is more common than mortality: this population has considerable burden from cCMV.

We report an unusual case of toxic shock syndrome in a 4-day-old baby, with mucosal isolates of Staphylococcus aureus (SEC, G, and I) and group G streptococcus. Treatment involved intravenous immunoglobulin and antibiotics. This case highlights the difficulties associated with the diagnosis and treatment of this condition in neonates.

The surgical and antimicrobial treatment of non-tuberculous mycobacterial lymphadenopathy in 17 children was reviewed. Node excision was curative, but most nodes were still incised leaving discharging lesions. Standard antituberculous treatment was unhelpful, but a new macrolide/quinolone combination appeared to be effective in three cases.

Background Congenital CMV (cCMV) causes up to 15% sensorineural hearing loss (SNHL) in the UK, however hearing outcomes may improve with ganciclovir treatment commencing in the first month of life. Targeted screening of infants who are ‘referred’ for further audiological testing after ‘no clear responses’ are found on their newborn hearing screen for CMV might identify these babies early enough to offer treatment. Aims We present initial feasibility and acceptability data of targeted cCMV screening. Methods Eligible infants from Northumbria and South-West London, (those9 referred9 for further hearing testing after their newborn hearing screening and Results Of 14,373 newborns 351 were9 referred9 for further hearing testing after their initial hearing screening and 248 families were approached with 152 (62%) agreeing to cCMV screening. Three newborns were found positive, all detected in time to allow assessment for treatment within 28 days. Salivary samples were easier to acquire with 95% (145) returning salivary samples and 41% (63) urine samples. Anxiety scores in study mothers were not significantly different to reference mothers. Conclusions Targeted cCMV screening using saliva is feasible and acceptable to parents. Extending the National screening programme to include cCMV testing in all infants without clear early hearing responses may improve hearing outcomes. Economic analysis and mechanistic processes require further evaluation.