Genomic Meningococcal Load in the Nasopharynx of Children with Meningococcal Disease.

This study demonstrates the feasibility of using quantitative real time PCR to measure genomic bacterial load in the nasopharynx of children with invasive meningococcal disease and shows that these loads are exceptionally high (median 6.6 × 10(5) (range 1.2 × 10(5)-1.1 × 10(8)) genome copies of Neisseria meningitidis per swab).

Optimising the management of bronchiolitis in infants.

Bronchiolitis shows a seasonal pattern with peak incidence occurring in the winter. Around 2-3% of children require admission to hospital. Admission rates are highest in infants less than three months old and those with underlying comorbidities. It typically affects children in the first year of life peaking between three and six months of age. Infants will have a coryzal prodrome lasting one to three days before developing a persistent cough. Fever and reduced feeding are common and very young infants may present with apnoeic episodes. Symptoms normally peak between days three to five of the illness. There will be evidence of increased work of breathing such as tachypnoea, in drawing/recession, head bobbing, grunting, nasal flaring or tracheal tug. Auscultation typically reveals wheeze and/or crepitations throughout both lung fields. Most children with bronchiolitis do not need to be referred to secondary care and can be managed safely at home. Immediate referral to hospital should be arranged if there is: apnoea (observed or reported), the child looks seriously unwell, severe respiratory distress, marked chest recession or a respiratory rate >70 breaths/minute, central cyanosis or persistent oxygen saturation < 92% when breathing room air.

Susceptibility to invasive meningococcal disease: polymorphism of complement system genes and Neisseria meningitidis factor H binding protein.

BACKGROUND: Neisseria meningitidis can cause severe infection in humans. Polymorphism of Complement Factor H (CFH) is associated with altered risk of invasive meningococcal disease (IMD). We aimed to find whether polymorphism of other complement genes altered risk and whether variation of N. meningitidis factor H binding protein (fHBP) affected the risk association. METHODS: We undertook a case-control study with 309 European cases and 5,200 1958 Birth Cohort and National Blood Service cohort controls. We used additive model logistic regression, accepting P<0.05 as significant after correction for multiple testing. The effects of fHBP subfamily on the age at infection and severity of disease was tested using the independent samples median test and Student's T test. The effect of CFH polymorphism on the N. meningitidis fHBP subfamily was investigated by logistic regression and Chi squared test. RESULTS: Rs12085435 A in C8B was associated with odds ratio (OR) of IMD (0.35 [95% CI 0.19-0.67]; P = 0.03 after correction). A CFH haplotype tagged by rs3753396 G was associated with IMD (OR 0.56 [95% CI 0.42-0.76], P = 1.6x10⁻4). There was no bacterial load (CtrA cycle threshold) difference associated with carriage of this haplotype. Host CFH haplotype and meningococcal fHBP subfamily were not associated. Individuals infected with meningococci expressing subfamily A fHBP were younger than those with subfamily B fHBP meningococci (median 1 vs 2 years; P = 0.025). DISCUSSION: The protective CFH haplotype alters odds of IMD without affecting bacterial load for affected heterozygotes. CFH haplotype did not affect the likelihood of infecting meningococci having either fHBP subfamily. The association between C8B rs12085435 and IMD requires independent replication. The CFH association is of interest because it is independent of known functional polymorphisms in CFH. As fHBP-containing vaccines are now in use, relationships between CFH polymorphism and vaccine effectiveness and side-effects may become important.

Diagnostic accuracy of loop-mediated isothermal amplification as a near-patient test for meningococcal disease in children: an observational cohort study.

BACKGROUND: Diagnosis of meningococcal disease relies on recognition of clinical signs and symptoms that are notoriously non-specific, variable, and often absent in the early stages of the disease. Loop-mediated isothermal amplification (LAMP) has previously been shown to be fast and effective for the molecular detection of meningococcal DNA in clinical specimens. We aimed to assess the diagnostic accuracy of meningococcal LAMP as a near-patient test in the emergency department. METHODS: For this observational cohort study of diagnostic accuracy, children aged 0-13 years presenting to the emergency department of the Royal Belfast Hospital for Sick Children (Belfast, UK) with suspected meningococcal disease were eligible for inclusion. Patients underwent a standard meningococcal pack of investigations testing for meningococcal disease. Respiratory (nasopharyngeal swab) and blood specimens were collected from patients and tested with near-patient meningococcal LAMP and the results were compared with those obtained by reference laboratory tests (culture and PCR of blood and cerebrospinal fluid). FINDINGS: Between Nov 1, 2009, and Jan 31, 2012, 161 eligible children presenting at the hospital underwent the meningococcal pack of investigations and were tested for meningococcal disease, of whom 148 consented and were enrolled in the study. Combined testing of respiratory and blood specimens with use of LAMP was accurate (sensitivity 89% [95% CI 72-96], specificity 100% [97-100], positive predictive value 100% [85-100]; negative predictive value 98% [93-99]) and diagnostically useful (positive likelihood ratio 213 [95% CI 13-infinity] and negative likelihood ratio 0·11 [0·04-0·32]). The median time required for near-patient testing from sample to result was 1 h 26 min (IQR 1 h 20 min-1 h 32 min). INTERPRETATION: Meningococcal LAMP is straightforward enough for use in any hospital with basic laboratory facilities, and near-patient testing with this method is both feasible and effective. By contrast with existing UK National Institute of Health and Care Excellence guidelines, we showed that molecular testing of non-invasive respiratory specimens from children is diagnostically accurate and clinically useful. FUNDING: Health and Social Care Research and Development, Public Health Agency, Northern Ireland.

Are APLS formulae for estimating weight appropriate for use in children admitted to PICU?

AIM: To determine if the revised APLS UK formulae for estimating weight are appropriate for use in the paediatric intensive care population in the United Kingdom. METHODS: A retrospective observational study involving 10,081 children (5622 male, 4459 female) between the age of term corrected and 15 years, who were admitted to Paediatric Intensive Care Units in the United Kingdom over a five year period between 2006 and 2010. Mean weight was calculated using retrospective data supplied by the 'Paediatric Intensive Care Audit Network' and this was compared to the estimated weight generated using age appropriate APLS UK formulae. RESULTS: The formula 'Weight=(0.5×age in months)+4' significantly overestimates the mean weight of children under 1 year admitted to PICU by between 10% and 25.4%. While the formula 'Weight=(2×age in years)+8' provides an accurate estimate for 1-year-olds, it significantly underestimates the mean weight of 2-5 year olds by between 2.8% and 4.9%. The formula 'Weight=(3×age in years)+7' significantly overestimates the mean weight of 6-11 year olds by between 8.6% and 20.7%. Simple linear regression was used to produce novel formulae for the prediction of the mean weight specifically for the PICU population. CONCLUSIONS: The APLS UK formulae are not appropriate for estimating the weight of children admitted to PICU in the United Kingdom. Relying on mean weight alone will result in significant error as the standard deviation for all age groups are wide.