Evaluating the Impact of the BioFire FilmArray in Childhood Meningitis: An Observational Cohort Study.

BACKGROUND: Multiplex polymerase chain reaction assays have the potential to reduce antibiotic use and shorten length of inpatient stay in children with suspected central nervous system infection by obtaining an early microbiological diagnosis. The clinical impact of the implementation of the BioFire FilmArray Meningitis/Encephalitis Panel on the management of childhood meningitis was evaluated at the John Radcliffe Hospital in Oxford and Children's Health Ireland at Temple Street in Dublin. METHODS: Children who had lumbar punctures performed as part of a septic screen were identified retrospectively through clinical discharge coding and microbiology databases from April 2017 to December 2018. Anonymized clinical and laboratory data were collected. Comparison of antibiotic use, length of stay and outcome at discharge was made with a historical cohort in Oxford (2012-2016), presenting before implementation of the FilmArray. RESULTS: The study included 460 children who had a lumbar puncture as part of an evaluation for suspected central nervous system infection. Twelve bacterial cases were identified on the FilmArray that were not detected by conventional bacterial culture. Bacterial culture identified one additional case of bacterial meningitis, caused by Escherichia coli , which had not been identified on the FilmArray. Duration of antibiotics was shorter in children when FilmArray was used than before its implementation; enterovirus meningitis (median: 4 vs. 5 days), human parechovirus meningitis (median: 4 vs. 4.5 days) and culture/FilmArray-negative cerebrospinal fluid (median: 4 vs. 6 days). CONCLUSIONS: The use of a FilmArray can identify additional bacterial cases of meningitis in children that had been negative by traditional culture methods. Children with viral meningitis and culture-negative meningitis received shorter courses of antibiotics and had shorter hospital stays when FilmArray was used. Large studies to evaluate the clinical impact and cost effectiveness of incorporating the FilmArray into routine testing are warranted.

The epidemiology of aseptic meningitis in New Zealand children from 1991 to 2020.

AIM: Aseptic meningitis, including culture negative and viral meningitis, contributes a significant health-care burden, including unnecessary antibiotic use and hospitalisation to treat possible bacterial meningitis. This study analysed aseptic meningitis hospitalisations in New Zealand (NZ) children over 29 years. METHODS: In this population-based study, aseptic meningitis hospitalisations in NZ children <15 years old were analysed from 1991 to 2020. Incident rate ratios were calculated using Poisson regression models. Variations in hospitalisations by age, year, sex, ethnicity, geographical region and socio-economic deprivation were analysed. RESULTS: There were 5142 paediatric aseptic meningitis hospitalisations from 1991 to 2020. Most were unspecified viral meningitis (64%), followed by enterovirus (29%). Hospitalisation rates varied annually with a median of 18.4/100 000 children including a peak in 2001 of 56.4/100 000 (51.7-61.6). From 2002 to 2019, rates increased by 8.4%/year (7.2-9.5%) in infants <90 days old but decreased in all other age groups. In 2020, a reduction in hospitalisations to 9.6/100 000 (7.9-11.8) occurred, and in infants <90 days old were 0.37 times expected. Hospitalisations were 1.50 times (1.49-1.68) higher in males than females; higher in children of Maori (P < 0.001) and Pacific (P < 0.001) versus European ethnicity; and higher for children living in the most (2.44 times, (2.16-2.75)) versus least deprived households; and in northern versus southern NZ. CONCLUSIONS: Aseptic meningitis hospitalisations increased in young infants during 29 years of surveillance, apart from 2020 when admissions reduced during the COVID-19 pandemic. In contrast, hospitalisations decreased in children aged >1 year. Further investigation into reasons for higher admissions by ethnic group, geographical location and increased deprivation are required.

Adherence to the New Zealand Pediatric Guideline for the Assessment and Diagnosis of Inflammatory Bowel Disease.

New Zealand (NZ) guidelines for the approach to diagnosis and management of inflammatory bowel disease (IBD) in children were developed in 2014. Objectives: This study aimed to assess the application of the guidelines in a group of children diagnosed with IBD in regards to baseline investigations. Methods: This retrospective observational study analyzed the application of recommended baseline investigations included in the NZ guidelines in a group of children aged <16 years diagnosed consecutively with IBD at the 2 NZ tertiary pediatric gastroenterology centers. Results: Fifty children were included from each center. Seventy-two were diagnosed with Crohn's disease (CD), 15 with ulcerative colitis (UC), and 13 were with IBD unclassified. The children with CD had a mean Pediatric Crohn's Disease Activity Index score of 31 and almost half had ileocolonic involvement (47%). The 15 children with UC had a mean PUCAI score of 42, and 13 had pancolonic involvement. All 100 children underwent upper and lower gastrointestinal endoscopy with biopsies, and 92% had magnetic resonance enterography at diagnosis. Iron studies, folate, and vitamin B12 were measured in >70 children. Serum zinc, magnesium, and phosphate were infrequently measured. Current anthropometry was recorded in all children but historical growth data were variably recorded. Vaccination status was also inconsistently recorded. Conclusion: Most of this group of children diagnosed with IBD in 2 NZ centers underwent key recommended investigations at diagnosis including gastrointestinal endoscopy and small bowel imaging. Other baseline assessments, including measurement of micronutrient levels, were completed variably. Measures to enhance consistent baseline assessments are required.

Three-year outcomes of childhood inflammatory bowel disease in New Zealand: A population-based cohort study.

BACKGROUND AND AIM: High rates of inflammatory bowel disease (IBD) have been documented in New Zealand (NZ) children. The objectives of this study were to describe the outcomes and disease course of childhood IBD in the first 3 years following diagnosis. METHODS: All children diagnosed with IBD in 2015 in NZ were included. Clinical data obtained during routine care for 3 years following diagnosis were analyzed. Growth parameters, disease activity scores, and blood parameters were compared at diagnosis and follow up. RESULTS: Three-year outcome data were available for 48 of 51 children. At follow up, median age was 15.1 years, and 34 had Crohn's disease (CD), 11 had ulcerative colitis (UC), and three had IBD-unclassified (IBDU). Although disease progression including development of perianal disease occurred in 13 (38%) of 34 children with CD, the majority (n = 30) had inflammatory disease at follow up. Disease extension occurred in 25% (2/8) of children initially diagnosed with UC. Of all IBD patients, the mean body mass index z-score increased from -0.40 to +0.10 (P = 0.01). Disease activity scores reduced from diagnosis to follow up in both CD (mean pediatric Crohn's disease activity index 35-6, P < 0.001) and UC (mean pediatric ulcerative colitis activity index 44-6, P < 0.001). Overall, 56% of children received steroids, 44% of children with CD received biologic therapy, and four children with CD or UC had intestinal surgery. CONCLUSIONS: Most children with IBD were in remission with improved growth 3 years after diagnosis. Biologic therapies were commonly prescribed. This is the first NZ study assessing disease course in pediatric IBD. Ongoing follow up will continue to inform outcomes.

Outcomes beyond hospital discharge in infants and children with viral meningitis: A systematic review.

Viruses are the commonest cause of childhood meningitis, but outcomes beyond hospital discharge are poorly described. We undertook a systematic literature review of long-term outcomes following paediatric viral meningitis. A search was carried out using MEDLINE, Embase, and Cochrane Review for studies from 1 January 1990 to 31 December 2018. Studies were included where specific outcome measures were available beyond hospital discharge for children <16 years old with viral meningitis. In total, 3588 papers were identified of which 14 were eligible for inclusion. Four studies reported outcomes in children with nonenterovirus 71 meningitis. A US study of 16 cases demonstrated subtle language difficulties at 3-year follow-up in infants in contrast to an Australian study, which revealed no impairment in language. A Fijian study showed that two out of eight cases had sensorineural hearing loss compared with none in a UK cohort of 668 infants. Three studies evaluated outcomes of enterovirus 71 meningitis in China and Taiwan, two showed cases recovered without sequelae, while one demonstrated an increased risk of attention deficit hyperactivity disorder. Two studies including 141 cases of human parechovirus revealed no evidence of neurodevelopmental sequelae. Conversely, an Australian study demonstrated neurodevelopmental sequelae in 11 out of 77 infants with parechovirus meningitis. Most studies identified in this review demonstrated a high proportion of good clinical outcomes following viral meningitis. However, the data are limited, so robustly conducted neurodevelopmental studies are warranted to inform the evidence-based management of viral meningitis beyond hospital discharge.

Single high-dose oral vitamin D3 treatment in New Zealand children with inflammatory bowel disease.

BACKGROUND: High-dose oral vitamin D (stoss) is a novel treatment in children with inflammatory bowel disease (IBD). Vitamin D supplementation may have benefits in IBD beyond bone health including reduced disease activity and improvements in inflammatory markers. The aim of this study was to retrospectively assess the efficacy, safety and impact on disease activity of single oral high-dose vitamin D3 therapy in New Zealand (NZ) children with IBD and vitamin D deficiency. METHODS: In this retrospective chart review, children with IBD and vitamin D deficiency [serum 25-OH vitamin D level (25-OHD) <50 nmol/L] in Christchurch, NZ, who were managed with single high-dose vitamin D3 therapy were identified. Measurements of serum 25-OHD, calcium and standard serum inflammatory markers prior to and up to 6 months following stoss therapy were extracted from patient records. Disease activity was also defined using the Pediatric Crohn's Disease (CD) Activity Index (PCDAI) at time points before and 3 months following stoss. RESULTS: Twenty-eight doses of stoss were given to 23 children, aged 3-16 years. Mean 25-OHD levels increased after stoss therapy from 39 nmol/L (95% CI: 37-42 nmol/L) at baseline to 189 nmol/L (148-231 nmol/L) at 1-2 months (P<0.001). All children with 1 month levels measured achieved 25-OHD >75 nmol/L. One child had a serum calcium of 2.7 (normal range, 2.2 to 2.6 mmol/L) 2 weeks after treatment, which normalized on repeat testing 10 days later. PCDAI scores, mean platelet count, erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) all reduced significantly from baseline to 3 months following stoss therapy. CONCLUSIONS: Single high-dose oral vitamin D therapy was used successfully and safely to manage vitamin D deficiency in these children with IBD. An improvement in inflammatory markers and disease activity scores also occurred following stoss therapy.

Intravenous immunoglobulin for the treatment of childhood encephalitis.

BACKGROUND: Encephalitis is a syndrome of neurological dysfunction due to inflammation of the brain parenchyma, caused by an infection or an exaggerated host immune response, or both. Attenuation of brain inflammation through modulation of the immune response could improve patient outcomes. Biological agents such as immunoglobulin that have both anti-inflammatory and immunomodulatory properties may therefore be useful as adjunctive therapies for people with encephalitis. OBJECTIVES: To assess the efficacy and safety of intravenous immunoglobulin (IVIG) as add-on treatment for children with encephalitis. SEARCH METHODS: The Cochrane Multiple Sclerosis and Rare Diseases of the CNS group's Information Specialist searched the following databases up to 30 September 2016: CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, and the WHO ICTRP Search Portal. In addition, two review authors searched Science Citation Index Expanded (SCI-EXPANDED) & Conference Proceedings Citation Index - Science (CPCI-S) (Web of Science Core Collection, Thomson Reuters) (1945 to January 2016), Global Health Library (Virtual Health Library), and Database of Abstracts of Reviews of Effects (DARE). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing IVIG in addition to standard care versus standard care alone or placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently selected articles for inclusion, extracted relevant data, and assessed quality of trials. We resolved disagreements by discussion among the review authors. Where possible, we contacted authors of included studies for additional information. We presented results as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI). MAIN RESULTS: The search identified three RCTs with 138 participants. All three trials included only children with viral encephalitis, one of these included only children with Japanese encephalitis, a specific form of viral encephalitis. Only the trial of Japanese encephalitis (22 children) contributed to the primary outcome of this review and follow-up in that study was for three to six months after hospital discharge. There was no follow-up of participants in the other two studies. We identified one ongoing trial.For the primary outcomes, the results showed no significant difference between IVIG and placebo when used in the treatment of children with Japanese encephalitis: significant disability (RR 0.75, 95% CI 0.22 to 2.60; P = 0.65) and serious adverse events (RR 1.00, 95% CI 0.07 to 14.05; P = 1.00).For the secondary outcomes, the study of Japanese encephalitis showed no significant difference between IVIG and placebo when assessing significant disability at hospital discharge (RR 1.00, 95% CI 0.60 to 1.67). There was no significant difference (P = 0.53) in Glasgow Coma Score at discharge between IVIG (median score 14; range 3 to 15) and placebo (median 14 score; range 7 to 15) in the Japanese encephalitis study. The median length of hospital stay in the Japanese encephalitis study was similar for IVIG-treated (median 13 days; range 9 to 21) and placebo-treated (median 12 days; range 6 to 18) children (P = 0.59).Pooled analysis of the results of the other two studies resulted in a significantly lower mean length of hospital stay (MD -4.54 days, 95% CI -7.47 to -1.61; P = 0.002), time to resolution of fever (MD -0.97 days, 95% CI -1.25 to -0.69; P < 0.00001), time to stop spasms (MD -1.49 days, 95% CI -1.97 to -1.01; P < 0.00001), time to regain consciousness (MD -1.10 days, 95% CI -1.48 to -0.72; P < 0.00001), and time to resolution of neuropathic symptoms (MD -3.20 days, 95% CI -3.34 to -3.06; P < 0.00001) in favour of IVIG when compared with standard care.None of the included studies reported other outcomes of interest in this review including need for invasive ventilation, duration of invasive ventilation, cognitive impairment, poor adaptive functioning, quality of life, number of seizures, and new diagnosis of epilepsy.The quality of evidence was very low for all outcomes of this review. AUTHORS' CONCLUSIONS: The findings suggest a clinical benefit of adjunctive IVIG treatment for children with viral encephalitis for some clinical measures (i.e. mean length of hospital stay, time (days) to stop spasms, time to regain consciousness, and time to resolution of neuropathic symptoms and fever. For children with Japanese encephalitis, IVIG had a similar effect to placebo when assessing significant disability and serious adverse events.Despite these findings, the risk of bias in the included studies and quality of the evidence make it impossible to reach any firm conclusions on the efficacy and safety of IVIG as add-on treatment for children with encephalitis. Furthermore, the included studies involved only children with viral encephalitis, therefore findings of this review cannot be generalised to all forms of encephalitis. Future well-designed RCTs are needed to assess the efficacy and safety of IVIG in the management of children with all forms of encephalitis. There is a need for internationally agreed core outcome measures for clinical trials in childhood encephalitis.

Hospital admissions for viral meningitis in children in England over five decades: a population-based observational study.

BACKGROUND: A substantial reduction in bacterial meningitis has occurred in the UK following successful implementation of immunisation programmes. Most childhood meningitis in developed countries is now caused by viruses. Long-term trends in paediatric viral meningitis in England have not previously been reported. The objective of this study is to report on epidemiological trends over time in childhood viral meningitis in England. METHODS: In this population-based observational study, we used routinely collected hospital discharge records from English National Health Service hospitals from 1968-2011 to analyse annual age-specific admission rates for viral meningitis, including specific viral aetiologies, in children younger than 15 years. FINDINGS: We analysed hospital discharge records from Jan 1, 1968, to Dec 31, 2011. Hospital admission rates for viral meningitis from Jan 1, 1968, to Dec 31, 1985, varied annually, with a mean of 13·5 admissions per 100 000 children aged less than 15 years, per year (95% CI 13·0-14·0). Admission rates declined during the late 1980s, and the mean number of admissions from 1989-2011 was 5·2 per 100 000 per year (5·1-5·3). This decrease was entirely in children aged 1-14 years. Admission rates for infants aged less than 1 year increased since 2005, to 70·0 per 100 000 (63·7-76·2) in 2011, which was driven by an increase in admission of infants aged 90 days or less. In 1968-85, the majority of cases in children were in those aged 1-14 years (22 150 [89%] of 24 920 admissions). In 2007-11, 1716 (72%) of 2382 cases were in infants. Admissions for mumps-related meningitis almost disappeared following introduction of the measles-mumps-rubella (MMR) vaccine in 1988. Admissions with a specified viral aetiology have increased since 2000. INTERPRETATION: Trends in viral meningitis admissions have changed substantially over the past 50 years, and probably reflect the impact of the MMR vaccine programme and the use of more sensitive diagnostic techniques. FUNDING: None.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis In A Young Child With Histological Evidence On Brain Biopsy Of Coexistent Herpes Simplex Virus Type 1 Infection.

We report a 3-year-old boy with anti-N-methyl-D-aspartate receptor encephalitis with a typical syndrome of movement disorder and encephalopathy and evidence of herpes simplex virus (HSV) type 1 infection on brain biopsy. HSV type 1 infection and anti-N-methyl-D-aspartate receptor encephalitis are temporally linked in some cases: this case suggests that prodromal HSV type-1 infection may be clinically subtle and easily missed.

Childhood meningitis in the conjugate vaccine era: a prospective cohort study.

Bacterial conjugate vaccines have dramatically changed the epidemiology of childhood meningitis; viral causes are increasingly predominant, but the current UK epidemiology is unknown. This prospective study recruited children under 16 years of age admitted to 3 UK hospitals with suspected meningitis. 70/388 children had meningitis-13 bacterial, 26 viral and 29 with no pathogen identified. Group B Streptococcus was the most common bacterial pathogen. Infants under 3 months of age with bacterial meningitis were more likely to have a reduced Glasgow Coma Score and respiratory distress than those with viral meningitis or other infections. There were no discriminatory clinical features in older children. Cerebrospinal fluid (CSF) white blood cell count and plasma C-reactive protein at all ages, and CSF protein in infants <3 months of age, distinguished between bacterial meningitis and viral meningitis or other infections. Improved diagnosis of non-bacterial meningitis is urgently needed to reduce antibiotic use and hospital stay.

Hospital admission rates for meningitis and septicaemia caused by Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae in children in England over five decades: a population-based observational study.

BACKGROUND: Infection with Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae causes substantial mortality and long-term morbidity in children. We know of no study to assess the long-term trends in hospital admission rates for meningitis and septicaemia caused by these pathogens in children in England. We aimed to do such a study using routinely reported data in England. METHODS: In this population-based observational study, we used datasets that include routinely collected administrative statistics for hospital care: the Hospital In-Patient Enquiry (data for England from 1968 to 1985), the Hospital Episode Statistics dataset (data for England from 1989 onwards), and the Oxford record linkage study (data for Oxfordshire and surrounding areas from 1963 to 2011). We analysed annual age-specific and age-standardised admission rates in children younger than 15 years with H influenzae, meningococcal and pneumococcal meningitis, and septicaemia. FINDINGS: We saw a reduction in hospital admission rates for childhood invasive bacterial disease after the introduction of conjugate vaccines against H influenzae, N meningitidis, and S pneumoniae in England. Annual incidence of H influenzae meningitis per 100,000 children decreased from 6·72 admissions (95% CI 6·18-7·26) in 1992 to 0·39 admissions (0·26-0·52) in 1994, after the introduction of routine H influenzae type b vaccination. We saw a small rise in admissions in the early 2000s, peaking at 1·24 admissions per 100,000 children (0·99-1·48) in 2003, which decreased to 0·28 per 100,000 children (0·17-0·39) by 2008 after the introduction of catch-up (2003) and routine (2006) booster programmes for young children. Meningococcal disease increased during the 1990s, reaching a peak in 1999, with 34·54 admissions (33·30-35·78) per 100,000 children. Hospital admissions decreased after the meningococcal serogroup C vaccine was introduced in 1999 and was 12·40 admissions (11·68-13·12) per 100,000 in 2011. Admissions for invasive pneumococcal disease increased from the 1990s reaching a peak in 2006 at 4·45 admissions for meningitis (95% CI 4·0-4·9) per 100,000 children and 2·81 admissions for septicaemia (2·45-3·17) per 100,000 children. A reduction in admissions occurred after the introduction of the pneumococcal conjugate vaccine in 2006: hospital admission rates in 2011 were 2·03 per 100,000 children for meningitis and 1·12 per 100,000 children for septicaemia. INTERPRETATION: Vaccine-preventable invasive bacterial disease in children has decreased substantially in England in the past five decades, most notably with the advent of effective conjugate vaccines since the 1990s. Ongoing disease surveillance and continued development and implementation of vaccines against additional pneumococcal serotypes and serogroup B meningococcal disease are important. FUNDING: None.

A multicomponent serogroup B meningococcal vaccine is licensed for use in Europe: what do we know, and what are we yet to learn?

The first meningococcal vaccine with the potential to provide broad coverage against serogroup B disease has recently been approved for use in Europe. This vaccine, multi-component serogroup B vaccine (4CMenB), contains recombinant proteins and outer membrane vesicles, and has been extensively studied in clinical trials involving over 7500 adults, children and infants. As well as demonstrating immunogenicity against a range of serogroup B meningococcal strains, these trials have also demonstrated relatively high rates of fever following infant immunization. This article will summarize the vaccine composition, clinical trials and suggested schedules of this vaccine, with specific attention to immunogenicity, reactogenicity, safety, potential coverage and optimal implementation of this vaccine.