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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.

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 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

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.

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

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.

Aims The incidence of paediatric empyema has been rising in the UK. The UK-ESPE study aims to monitor the changing epidemiology of paediatric empyema and to compare empyema management across the UK. Methods Demographic, clinical and microbiological data on children with empyema undergoing pleural drainage were obtained from 19 paediatric respiratory centres from September 2006 until March 2011. Culture negative samples of pleural fluid were investigated using pneumococcal PCR. Pneumococcal PCR positive samples then underwent non-culture serotyping using an assay capable of detecting 14 serotypes/groups. Robust multivariate survival models were used to analyse length of stay (LOS). Chi-squared, Kruskal-Wallis and Fisher9s test were used for other analyses. Results Data on 635 children were obtained (56% male, median age 4.3 years). Where a microbiological cause was identified (n=287), Streptococcus pneumoniae accounted for 68%, Streptococcus pyogenes 14% and Staphylococcus aureus 4%. A pneumococcal serotype was detected in 125 patients; of these serotype 1 accounted for 46% and other prominent serotypes were 3 (22%), 7 (12%) and 19A (9%). Serotypes covered by the 7 valent conjugate vaccine (PCV-7) accounted for 48% of serotypes detected in 2006/07 but had disappeared by 2010/11. Non-PCV-7 serotypes increased over the same period. When comparing severity between serotypes, 19A was associated with severe disease and the only reported death. Median tertiary LOS was 8 days (range 3-33) and median total hospital stay (THS) 11 days (range 5-43). Surgical methods (open thoracotomy or video-assisted thoracoscopy) were associated with a decrease in tertiary LOS of 41% (95% Confidence intervals 7-88%, p=0.015) and THS of 43% (95% CI 7-92%, p=0.015) when compared to non-surgical methods (thoracocentesis +/- fibrinolysis). This effect did not achieve significance when each treatment group was analysed separately. Antibiotic choice in the tertiary centre did not significantly change either LOS measure. Conclusions Pneumococcus was the most commonly identified cause of paediatric empyema in the UK. The incidence of causative serotypes has evolved over time. Continuing surveillance is required to monitor changes following the introduction of the 13 valent vaccine in 2010. Primary surgical strategies were associated with reduced hospital stay in this cohort but this needs further investigation.

Background An important obstacle when undertaking clinical research in children is the consent procedure. Understanding the factors influencing this process is vital in improving children9s involvement in clinical research. Objective To report the rates and causes for recruitment refusal into two studies of childhood pneumonia and empyema and investigate the underlying factors contributing to refusal. Methods Two paediatric respiratory studies investigating childhood pneumonia and empyema and requiring informed consent were carried out at the same site. During the period from April 2010 to March 2011, the number of eligible children who gave or refused consent for each study was documented. Each research team included a paediatric research nurse and paediatric research registrar (doctor). Information was collected prospectively on each consent refusal. Rates of refusal by role of person taking consent, severity of illness and reason for refusal were then analysed. Results A total of 116 children were eligible for enrolment into pneumonia study and 28 into empyema study, giving 144 consent procedures. Ten (7%) parents refused the consent. The rate of refusal did not differ between medical and nursing staff. Eighty percent of the children who were not enrolled had severe disease. Refusals were linked with not wanting the child to undergo further investigations, research delaying discharge, and anxiety regarding written consent and length of information sheets. Conclusion Consent refusal was not related to the role of the person seeking consent. Severity of child9s illness appears to determine parent9s decision regarding participation in clinical research.

Background and aims A UK-wide study of Toxic Shock Syndrome (TSS) cases in UK children under 16 years of age was undertaken beginning November 2008 until the end of November 2009. Little data regarding incidence, management and outcomes has been published about children with TSS. Previous literature suggested staphylococcal TSS to have a significantly greater incidence than streptococcal TSS. Methods Consultants from paediatric and burns units notified the British Paediatric Surveillance Unit of cases. Questionnaires requesting detailed information on case presentation and progression were sent to notifying consultants. TSS cases were identified as staphylococcal or streptococcal if they met the established criteria used by the US Centre for Disease Control and American Academy of Paediatrics respectively. Results 50 confirmed and probable cases were identified. 15 were confirmed and 5 probable staphylococcal cases; 18 were confirmed and 12 probable streptococcal cases. There were nine deaths, all from the confirmed or probable streptococcal groups. Mortality was 18% overall but 30% of the streptococcal cases. Four were reported to have residual morbidity. 78% (n=39) received treatment in paediatric intensive care facilities. 70% (n=35) required invasive ventilatory support, 68% (n=34) inotropic support and12% (n=6) haemofiltration. All patients received antibiotics, with two thirds (n=33) receiving clindamycin and only two receiving linezolid. 20% (n=10) received immunoglobulin and 40% (n=20) fresh frozen plasma. Conclusions This study demonstrates streptococcal TSS to have a higher incidence than staphylococcal TSS, in contrast to previous literature. This finding is in keeping with the increasing incidence of other types of invasive streptococcal disease. A significantly higher mortality was seen with streptococcal TSS indicating it may be a more virulent disease than staphylococcal TSS. Intensive care support facilities were required in three-fourth of patients. It was noted that proven antitoxin therapies which have been shown to reduce toxin production, such as clindamycin and linezolid, appeared to be underused. This study highlights the need for education on patho-aetiology and management of TSS.

We enrolled 43 children admitted with an unequivocal clinical diagnosis of meningococcal sepsis into a study to determine whether cefotaxime eradicated nasopharyngeal carriage of Neisseria meningitidis . In 28 cases (70%) the diagnosis was confirmed by positive culture from blood, nose, throat, or skin scraping, detection of meningococcal DNA in blood by polymerase chain reaction, or convalescent meningococcal serology. All children were treated with intravenous cefotaxime for seven days. …

Editor,—We were interested to read Brogan and Raffles' audit of the management of fever and petechiae.1This is an important audit for many general paediatricians in the UK. In Newcastle 36% of children with petechiae were treated with antibiotics, and only 10% had meningococcal disease (MCD). Brogan and Raffles correctly state that more studies are required to validate their proposed guideline. We offer two such studies: (1) The ILL criteria (irritability, lethargy, low capillary refill) were applied retrospectively to a cohort of children presenting with petechiae who were part of a multicentre prospective study of MCD from Merseyside, UK.2 The ILL criteria would have identified all except two of 66 children with MCD and petechiae. Both those not identified presented with seizures, one had meningism, the other a maculopapular rash. However, the ILL criteria were also present in 62 of 65 children with petechiae initially thought to have MCD, whose final diagnosis was a viral illness. In this cohort the features that suggested MCD were tachypnoea or signs of meningitis or septicaemia.3 The ILL criteria are therefore of limited use in children already suspected of having MCD. Local paediatricians in training asked for an algorithm to help assess children with fever and petechiae. We therefore designed an algorithm which includes risk factors from previous studies (recently reviewed),4 the ILL criteria, the criteria from the above Merseyside study, and a period of observation. We introduced this algorithm into routine use in our hospitals this year. We are prospectively validating its use. (2) During the first three months, 49 children presented with petechiae. Only one child had meningococcal disease. The algorithm was correctly followed in 34 (68%) children; this included prompt treatment for the child with MCD. For 15 children the algorithm was not followed; 7 … Dr Mukherjee. Samudra.Surangama{at}ukgateway.net Malcolm Jones, Department of Community Child Health, St George's Hospital, Blackshaw Road, London SW17 0QT. malcolmjones{at}doctors.net.uk Malcolm Jones, Department of Community Child Health, St George's Hospital, Blackshaw Road, London SW17 0QT. malcolmjones{at}doctors.net.uk