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S. Anderson2, S. Walters1, B. Williams2, A. Williams2, A. Gordon1, N. Martinez‐Alier1, B. Kampmann1. 1Imperial College, London, UK; 2Northwick Park NHS Trust, London, UK
BackgroundMany believe that the tuberculin‐skin‐test (TST) is a blunt tool for diagnosing MTB infection in children. The new NICE Guidelines for tuberculosis recommend the use of IFNGRA in TST positive children. However, there is no guidance on which assay to use and there is a paucity of data regarding the performance of these assays in children. No direct comparison between all 3 available tests for the diagnosis of childhood Tb (active or latent) in UK cohorts has been published.
AimsTo assess the performance of TST and IFNGRA in a UK paediatric cohort.
MethodsSide‐by‐side comparison of the two commercially available IFNGRA (T‐SpotTB and Quantiferon Gold QFG) and the TST in children referred to our paediatric TB clinics in London, plus assessment of a control group (n=30).
ResultsThis study is ongoing. Data in 74 children with presumed active (n=32) or latent TB (n=42) show that both IFNGRA were highly concordant but differed significantly from the TST read‐out. A significantly higher number of patients were treated for both active and latent TB than would have been indicated, if IFNGRA results had guided the decision making process, as summarised in the table.
ConclusionThe concordance between IFNGRA is good, but clinical management of patients should only change once more information about their performance in children is available. Paediatricians who use IFNGRA should strive to combine data from their cohorts to gain a better understanding of the validity of these novel assays for use in paediatric practice, as we may be overtreating assumed MTB infection in UK children.
S. Ladhani1, P. Heath2, M. Ramsay1, P. Thompson2, M. Sharland2, M. Slack1. 1Centre for Infections, Health Protection Agency, London, UK; 2St George's, University of London, London, UK
ObjectivesTo determine trends in antibiotic resistance rates for invasive Haemophilus influenzae isolates over the last 20 years and their association with antibiotic use in primary care.
MethodsMicrobiology laboratories throughout England and Wales are encouraged to routinely submit all invasive H influenzae isolates to the Health Protection Agency for serotyping and antimicrobial susceptibility testing. Antimicrobial resistance was defined using British Society for Antimicrobial Chemotherapy criteria (http://bsac.org.uk). Data for antibiotic prescribing in primary care were obtained from the Prescribing Analysis and Cost Tool (PACT) system and from the General Practice Research Database.
ResultsBetween 1985 and 2004, 3398 H influenzae isolates from blood (n=2076, 61.1%) and CSF (n=1322, 38.9%) were obtained from children under 16 years of age. Overall, resistance to ampicillin/amoxycillin was highest at 16.0%, followed by trimethoprim (6.9%), tetracycline (1.7%) and chloramphenicol (1.1%). All isolates were sensitive to cefotaxime and rifampicin. When analysing trends, ampicillin/amoxycillin resistance rates fell from 20% in the mid‐1990s to their lowest at 10.2% in 2004. Resistance rates for trimethoprim initially fell from 10.0% in 1985 to 1.9% in 1989 and then rose consistently to 13.2% in 2004. This increase was observed for both blood and CSF isolates, and among all serogroups. The recent fall in ampicillin/amoxycillin resistance rates was associated with a marked decline in primary care prescription rates for this group of antiobiotics. On the other hand, trimethoprim use in primary care has remained constant while resistance among H influenzae isolates has increased significantly.
ConclusionsRifampicin and cefotaxime remain highly effective against all H influenzae serotypes. A marked reduction of ampicillin/amoxycillin use in primary care in recent years was associated with a fall in resistance, while extensive use of trimethoprim for chemoprophylaxis of vesico‐ureteric reflux may be driving the increasing trimethoprim resistance rates in H influenzae.
S. Moss1, A. Fenton1, J. Toomey2, A. Grainger2, J. Smith1, A. Gennery2. 1RVI, Newcastle upon Tyne, UK; 2Newcastle University, Newcastle upon Tyne, UK
AimsTo examine the response of preterm infants to 7VCPnc when immunised at 2, 3 and 4 months of age with other vaccines in the UK primary immunisation schedule.
BackgroundWe have previously reported a diminished response to serotype 6B in healthy term infants following administration of 7VCPnc at 2, 3 and 4 months of age. Preterm infants have been demonstrated to have a diminished response to Hib conjugate vaccines. There is a paucity of data examining the response of preterm infants to 7VCPnc, especially when co‐administered with other vaccines in the UK primary immunisation schedule.
Methods133 preterm and 54 term infants were immunised at 2, 3 and 4 months of age with 7VCPnc, a meningitis C conjugate vaccine and diphtheria, tetanus, pertussis, polio and Hib vaccines. Pneumococcal serotype specific IgG was measured by ELISA. Geometric mean concentrations (GMCs) and the proportion of infants achieving putatively protective levels (anti‐pneumococcal IgG 0.35 μg/ml) were calculated for each serotype. Term and preterm responses were compared using linear and logistic regression.
ResultsPre‐immunisation GMCs were lower in the preterm infants (median gestation 28 weeks, median birth weight 1062 g) for all 7 serotypes (p<0.02). Post‐immunisation GMC for serotype 23F was also lower in the preterm group (p<0.01), whilst the degree of prematurity adversely affected post‐immunisation GMCs for serotypes 4, 6B and 23F (p<0.04). Results for the remaining serotypes were comparable between groups. Preterm infants were as likely to have achieved putatively protective levels as term infants against all serotypes except 23F (p<0.01). However, only 37% of term infants and 39% of preterm infants had protective levels against serotype 6B. The proportion of infants that were protected against all 7 serotypes was similar in both groups.
ConclusionsThis is the largest study examining the immunogenicity of preterm infants to 7VCPnc. Both term and preterm infants responded poorly to serotype 6B. Although prematurity adversely affected the post‐immunisation GMCs of 3 of the 7 vaccine serotypes preterm infants are as likely to achieve protective levels as term infants to all serotypes except serotype 23F.
M. Fadaee‐Shohada, R. A. Hirst, A. Rutman, C. O' Callaghan, P. W. Andrew. University of Leicester, Leicester, UK
IntroductionCiliated ependymal cells line the cerebral ventricles and aqueducts separating the CSF from the brain parenchyma. Little is known of the interaction between the ependyma and L monocytogenes during meningitis. In this study we demonstrate, using cultured rat brain ependymal cells, that a strain of L monocytogenes reduced the ciliary beat frequency (CBF) and all strains significantly reduced the ciliary beat amplitude (CBA) compared to control. The presence of the ependyma induced aggregation of the bacteria in an extra cellular matrix (agglutination).
AimTo use a series of L monocytogenes strains deficient in known virulence genes to improve our understanding of the patho‐physiology of listeria‐meningitis.
MethodsAfter 14 days in culture ciliated cells were incubated with 108 colony‐forming units (cfu) of bacteria for 4 h and CBF, CBA and the % of tissue covered with bacterial aggregates were determined.
ResultsThe table shows the effect of three wild type strains of listeria (10403S, EGDe and C52) and two mutants deficient in the pfrA gene (10403SΔprfA and EGDΔprfA). Their effect on CBF, % mean ciliary amplitude compared to control and the % of tissue covered with aggregates of bacteria in an extracellular matrix are shown.
ConclusionOur results show that reduction in ciliary beat frequency is dependent on the infecting strain of listeria. However, ciliary amplitude was reduced following infection by all strains. Aggregation of the bacteria in an extra cellular matrix was a prfA dependent phenomenon.
K. Doerholt1, A. Judd6, M. Sharland1, P. Tookey7, A. Riordan5, E. Menson4, V. Novelli3, J. Masters7, H. Lyall2, G. Tudor‐Williams2, T. Duong6, D. Gibb6. 1St George's Hospital, London, UK; 2St Mary's Hospital, London, UK; 3Great Ormond Street Hospital, London, UK; 4Evelina's Children's Hospital, London, UK; 5Royal Liverpool Children's Hospital, London, UK; 6MRC Clinical Trials Unit, London, UK; 7Institute of Child Health, London, UK
AimTo describe changes over time in perinatally HIV‐infected children and adolescents in the UK and Ireland.
MethodsAnalysis of prospective cohort data reported to the National Study of HIV in Pregnancy and Childhood (NSHPC) and the Collaborative HIV Paediatric Study (CHIPS).
ResultsBy 30 June 2006, 1441 children had been reported to NSHPC, of whom 44% were aged 10 years at last follow‐up, and 48% were receiving care outside London. The number of newly diagnosed children has increased over time. The proportion born abroad also increased (24% of 212 newly diagnosed in 1994/6, 64% of 366 in 2003/6). The overall proportion of time on 3 or 4 drug antiretroviral therapy (ART) increased from 36% in 1997/9 to 63% in 2003/6. Among 629 children starting ART for the first time, the proportion achieving HIV‐1 RNA viral load <400 copies/ml after 12 months increased from 54% to 81% over the same time. In multivariate analysis, only calendar time predicted virological response, whereas both younger age and lower CD4% at ART initiation predicted CD4% increases of >10%. AIDS/death rates per 100 child‐years (cy) declined from 13.3 before 1996 to 3.1 in 2000/2, and 2.5 in 2003/6; hospital admissions also declined (4.3/100 cy in 1996 to 1.0 in 2000/2 and 0.7 in 2003/6).
ConclusionsMorbidity and mortality among HIV‐infected children has continued to decline and is now very low. As these children are increasingly dispersed outside London, specialist care is now provided in a national network. Transition pathways to adolescent and adult services and long‐term follow‐up to monitor the effects of prolonged exposure to both HIV and ART are required.
C. Townsend, J. Masters, C. Peckham, P. Tookey. UCL Institute of Child Health, London, UK
AimTo describe cases of vertically acquired HIV infection in children born from 2000 to 2005 and reported in the British Isles (UK and Ireland).
BackgroundHigh uptake of routine antenatal HIV testing (>90% of infected women are now diagnosed before delivery) means that most infected women can take advantage of interventions to reduce the risk of vertical transmission.
MethodsSurveillance of obstetric and paediatric HIV is carried out by the National Study of HIV in Pregnancy and Childhood (NSHPC), through active reporting schemes run in collaboration with the Royal College of Obstetricians and Gynaecologists and the British Paediatric Surveillance Unit. Infants born 2000–5 with HIV infection confirmed by September 2006 are described here.
Results4309 infants born in the British Isles to diagnosed HIV‐infected women were reported. Only 53 (1.2%) of the 3961 for whom infection status was available were confirmed as infected. Factors associated with transmission included late diagnosis and premature delivery before initiation of anti‐retroviral therapy (ART). 12 women had no ART antenatally and 10 had less than 14 days of treatment. However, 31 infants were born to women who were reported to have received at least 14 days of ART antenatally, including 13 who were delivered by elective caesarean section (CS) at 37 weeks. Anecdotally, management of several pregnancies was complicated by late booking for antenatal care, drug adherence issues, or high HIV RNA viral load despite ART. An audit of vertically infected infants born in England (2002–5) was established to explore possible contributory factors more closely. In addition to infants born to diagnosed women, another 142 infected infants have already been reported who were born in the British Isles during this period to the small proportion (~10–15%) of women who were undiagnosed at delivery; these women were mostly from sub‐Saharan Africa (75%, 106/142). Another 87 infected infants born within the period outside the British Isles have also been reported.
ConclusionMost paediatric HIV infection in the British Isles in recent years occurs in infants born to undiagnosed women or born abroad. Only 53 infected infants born to diagnosed women in the British Isles were reported over this 6‐year period; of these women, only a quarter received at least two weeks of antenatal ART and delivered by elective CS.
J. E. Harrop, J. Gardner, L. J. Michaelis, E. G. Weinberg. St Mary's Hospital, London, UK
AimsDrug allergies are commonly suspected in paediatric patients. Children labelled as “allergic”, are denied further treatment often on poor evidence of causality. There is little consensus on investigating and diagnosing drug allergies. We have studied the outcome of 33 drug challenges in children suspected of being allergic carried out over a 12‐month period in a specialist paediatric allergy department.
MethodsRetrospective case note review of all children referred for drug challenge during a one‐year period. Data were collected about the drugs being tested, the results of the challenges as well as the initial presentation of the “allergy” and the person making the referral.
ResultsOnly 15% of the drug challenges carried out were positive, and in 80% of these the reaction was delayed hypersensitivity in response to continuing the medication for 5 days after initial exposure. Of the drugs tested, over half were penicillins (55%), with the rest being made up of other antibiotics (24%), NSAIDs (6%), local anaesthetics (12%) and vaccines (3%). Of the 5 positive challenges, 2 were to penicillin, 1 to cephalosporin, one to erythromycin and one to local anaesthetic. “Rash” was the commonest presentation (58%), followed by “swelling of the lips/tongue” (32%), with only 5% having documented respiratory symptoms. Of the children with a positive drug challenge, as many presented with an isolated rash as with swelling of the lips/tongue. Most of the children were referred by their GP (40%), with 27% being referred by a general paediatrician and 33% by a paediatric subspecialist.
ConclusionDiagnosis of drug allergies in children is not straightforward. Of 33 children with a strong clinical suspicion of allergy, only 15% were positive on re‐challenge. The presenting symptoms (rash v swelling of tongue/lips) were a poor predictor of those who were allergic. Most of the positive challenges were to commonly used antibiotics. The importance of giving a “course” of the suspected drug allergen is highlighted.
J. Thachil, R. Salim, A. Field, R. Moots, P. B. Maggs. Royal Liverpool University Hospital, Liverpool, UK
AimTo demonstrate the possible link between a karyotypic abnormality and an immunological disorder by an observational report.
MethodA 14‐year‐old female first presented with a history of recurrent, severe mouth ulcers she had since the age of 10. Full blood count revealed anaemia and neutropaenia. Bone marrow studies confirmed a diagnosis of Myelodysplastic syndrome (MDS) with the presence of trisomy 8. She was begun on thalidomide (100 mg daily) for the mouth ulcers with regular monitoring of her blood counts. The treatment with thalidomide was continued for 6 years with good symptomatic control but her mouth ulcers reoccurred once off the drug. Further detailed questioning at this time revealed recurring symptoms from genital ulceration and nasal discharge. The possibility of Behçet's syndrome was considered especially with a positive pathergy test (skin hypersensitivity to sterile needle puncture). Along with the history of recurrent oral and genital ulcers, these observations led to a formal diagnosis of Behçet's disease. Meanwhile, MDS has not progressed for nearly 10 years with annual surveillance bone marrows, consistently showing trisomy 8.
ResultsThe report demonstrates the occurrence of a bone marrow disorder with dysfunction of the immune system. MDS has also been associated rarely with rheumatological conditions other than Behçet disease. including leukocytoclastic vasculitis, polyarthritis, pleuropericarditis, Raynaud syndrome, and relapsing polychondritis. The underlying pathophysiology may be the generation of high levels of reactive oxygen species (ROS), resulting in endothelial tissue damage. It is possible that the increased ROS production by activated neutrophils will play a role in some of the disease manifestations in immunological disorders.
ConclusionThe report should stimulate more work to identify and correlate karyotypic abnormalities to dysfunction in the immune system.
MCastroDLConnDWPSuet al Rheumatic manifestations in myelodysplastic syndromes. J Rheumatol199118 pp 721-7 YNiwaSMiyakeTSakaneet al Auto oxidative damage in Behcet's disease—Endothelial cell damage following the elevated oxygen radicals generated by stimulated neutrophils. Clin Exp Immunol198249 pp 247-55
N. Qayyum, A. Sie, M. Lilley, R. Hague. Royal Hospital for Sick Children, Glasgow, UK
AimsTo evaluate Epipen carriage and usage among patients and carers attending an allergy clinic.
MethodsSubjects were assessed and followed annually in the allergy clinic after an initial referral by their GP/other Hospital Specialist. We assessed 1. Epipen carriage 2. Parental recognition and management of both allergic/anaphylactic reactions 3. Usage of Epipen.
Results208 parents were enrolled into the study. The mean patient age was 8 years (1–16). 35 patients (16.8%) were seen at their initial visit to the allergy clinic of which 22 had been prescribed an Epipen by their GP. 173 (83.2%) were seen at their annual review, of which 19 were the first following allergy clinic prescription of an Epipen. The mean number of previous annual reviews was 3.1 (0– >7). 52% (n=110) of the Epipens had originally been prescribed by the allergy clinic. There was no link between the number of previous reviews and current carriage of an Epipen (p=0.453). Length of attendance at allergy clinic was associated with greater awareness of indications for epipen use (p=0.014) and correct usage of an Epipen (p=0.002). Allergy clinic prescription did not increase parental knowledge or Epipen carriage and usage at first review compared to those prescribed by their GP (p=0.3–0.71).
ConclusionsThese findings highlight the importance of regular review and education of all patients prescribed an Epipen if it is to be used as part of an anaphylaxis management plan. Repeated clinic visits are necessary before adequate proficiency is demonstrated. GPs also need to play a role in providing ongoing education and support in Epipen use.
S. R. West, L. Michaelis, S. Choo, H. Cox, J. Warner. St Mary's Hospital NHS Trust, London, UK
Aims/MethodSpecific IgE (sIgE) tests are commonly requested to identify suspected allergies. We retrospectively gathered all test results obtained by a hospital with a tertiary allergy service over a three month period and compared the cost effectiveness of testing individual sIgEs against mixes of sIgEs.
ResultsData comprised of 379 patients and 3378 sIgE results. 77% of results were for children, the majority 2–5 years of age. 53% of requests were made by tertiary specialists and 9% by GPs. 103 specific allergens were tested. Peanut was the most commonly requested allergen (6%). 36% of all tests were positive with similar proportions of positive results from tertiary specialists, GPs and other departments. With nuts the most commonly requested group of allergens, we compared hypothetical testing strategies for 2 panels and 2 mixes of nuts. We identified potentially useful panels based on the 4 most frequently tested nuts (peanut, hazelnut, cashew and almond) and pistachio. There are also 2 commercially available nut mixes: M1 (peanut, hazelnut, almond, brazil nut and coconut), m2 (pecan, cashew, pistachio and walnut). As the data consisted of single allergen results, a mix test was assumed to be positive if one or more tests in the mix was positive. We classified a mix test as a failure if the result was negative for the mix but positive for any other nut. Costs were calculated on the basis that a positive mix result would require further testing for the individual component sIgEs. Similar cost analyses were performed for the following allergen groups: seafood/fish, legumes, mixed food groups, aeroallergens and drugs.
ConclusionCurrently, tests on sIgEs are performed as requested or on 7 individual nuts if “nuts” is requested. The use of mixes or panels of specific allergens could reduce the number of inappropriate tests. However the costs and sensitivities of these testing strategies need further evaluation.
F. A. Riordan1, D. Dean1, E. Carrol2, T. Hart2. 1Royal Liverpool Children's Hospital, Liverpool, UK; 2University of Liverpool, Liverpool, UK
AimsExtended‐spectrum beta‐lactamases (ESBL) are produced by gram‐ negative bacteria and confer resistance to all penicillins and cephalosporins. ESBL infections are of concern because they may not be detected by standard methods of antibiotic sensitivity testing, thereby causing delays in starting appropriate antibiotic therapy. We aimed to investigate the prevalence and types of ESBL infection and examine the risk factors, and clinical outcomes at a large children's hospital.
MethodsFrom September 2005 all gram negative bacilli isolated at our hospital from blood cultures, swabs or respiratory samples were screened for ESBL production. Routine weekly surveillance swabs were taken from all children on intensive care (PICU), oncology wards and long‐term parenteral nutrition (TPN).
ResultsBetween September 2005 and August 2006 there were 733 positive isolates for ESBL‐producing bacteria in our hospital, isolated from 114 children. 61 children had ESBL isolated on more than 2 occasions. The commonest source of isolation was surveillance swabs; 376 (52%) rectal and 148 (20%) throat swabs. The commonest ESBL‐producing organisms were Klebsiella pneumoniae (62%), Enterobacter cloacae (28%), Citrobacter freundi (4%) and Escherichia coli (3%). 38 (5%) children had more than one ESBL‐producing organism isolated at any time. There were 38 positive blood cultures (K pneumoniae: 30 (79%), E cloacae: 4 (10.5%), E coli: 2, C freundi: 1, K oxytoca: 1), from 22 episodes of ESBL bacteraemia, which occurred in 16 children (median age 14 months, range 2 months–16 years). All ESBL bacteraemias occurred in children with chronic diseases (TPN 10, oncology 4, post‐op on PICU 2). 21/22 episodes were associated with central venous catheters (CVCs), 20 episodes had ESBL organisms on surveillance swabs before bacteraemia. All children with ESBL bacteraemia survived.
ConclusionsESBL‐producing organisms should be looked for in high‐risk hospitalised children. ESBL carriers should not be treated empirically with penicillins or cephalosporins if they become systemically unwell.
B. Padmakumar1, V. Deshpande2. 1Royal Oldham Hospital, Oldham, Manchester, UK; 2Booth Hall Children's Hospital, Manchester, UK
AimsTo review two cases of neonatal submandibular sialadenits with respect to their clinical presentation, management and outcome.
PatientsWe present two cases of neonatal suppurative submandibular siladenitis in term infants with no risk factors. Both of them presented with rapid swelling in the submandibular region with pus from the Wharton's duct growing Staph aureus. Our patients responded to treatment with Cefotaxime and Flucloxacillin over a period of seven days with complete resolution of swelling.
DiscussionNeonatal suppurative submandibular sialadenitis is a rare but important cause for swelling in the submandibular region in the neonatal period. Prematurity has been described as a major risk factor due to lack of salivary stimulation secondary to tube feeding and increased risk of dehydration. In total there are 17 previous cases described in the English literature (none from UK), 4 in term infants with no risk factors (6 including ours). The most pathogen described is Staphylococcus aureus identified from culture of pus from the Wharton's duct in 17/19 cases (89%), including our cases. There was 1 case where Pseudomonas aeroginosa was isolated. None of the patients described had a positive blood culture. The age of presentation varied from (6–60) days in these 19 patients (median age 12 days). 33% (6/19) of the cases went on to develop abscess needing surgical drainage. From the previous case reports abscess formation seemed to develop more when antibiotics were administered orally or when intravenous antibiotics were changed to oral too early.[1, 3, 4]
ConclusionNeonatal suppurative submandibular sialadenitis is a relatively rare but important condition in neonates. Prompt recognition and appropriate treatment will prevent abscess formation.
B. Williams, A. Williams, S. Anderson. Northwick Park Hospital, Harrow, London, UK
AimsEpidemiological data link vitamin D deficiency with increased tuberculosis (TB) rates in adults, but there is no published research in children. We aimed to: assess the burden of vitamin D deficiency in a London paediatric TB clinic assess the effects of gender, age, ethnicity, season of presentation and type of presenting disease, active versus latent tuberculosis infection (LTBI) on vitamin D levels. determine whether a raised serum alkaline phosphatase level is a surrogate marker of vitamin D deficiency.
MethodsRetrospective review over a 24‐month period to June 2006 of all patients attending the paediatric TB clinic with a diagnosis of either active TB or LTBI. Vitamin D and alkaline phosphatase levels measured at the time of diagnosis, and prior to commencing TB treatment, were retrieved from pathology reports.
ResultsSixty seven patients presented to the clinic during the study period of whom 64 had vitamin D measurements completed and were therefore included in the study. 26 (41%) were treated for active TB and 38 (59%) were treated for LTBI. Of these 33 (52%) were of south Asian origin and 23 (36%) black African in origin. Overall, 75% of children were vitamin D deficient (<12.5 nmol/l) or insufficient (12.5–50 nmol/l). There was no significant difference in vitamin D results between children with active TB and those with LTBI. However, age had a significant effect on vitamin D level with children >10 years having lower vitamin D levels than younger children (p<0.01). There was no effect of gender on vitamin D level and no difference in level between the two main ethnic groups. However, although the numbers were too small for statistical analysis, all Caucasian and Chinese children (n=3 (5%)) were vitamin D replete. Children with active TB presenting between November and April were significantly more likely to be vitamin D deficient than those presenting between May and October; mean 21.5 nmol/l and 41.7 nmol/l respectively (p=0.02) However, there was no influence of season on vitamin D levels for those with LTBI. There was no correlation between alkaline phosphatase result and vitamin D (r=0.18) with just one patient having a raised alkaline phosphatase level.
ConclusionOur data suggest that vitamin D deficiency is common in children attending our paediatric TB clinic and is likely to be significantly underestimated if alkaline phosphatase level is used as a marker for deficiency. Further population studies amongst healthy children of the same and different ethnic background need to be completed.
J. M. Cohen1, E. Whittaker1, S. Walters1, H. Lyall1, G. Tudor‐Williams2, B. Kampmann2. 1St Mary's Hospital NHS Trust, London, UK; 2Imperial College, London, UK
BackgroundTuberculosis (TB) has emerged as a significant co‐infection for children infected with HIV, but diagnosis and management are challenging.
AimsTo characterise TB/HIV co‐infection in our paediatric population.
MethodsRetrospective case note review of patients seen in a tertiary HIV referral centre who had been treated for TB in the last 15 years.
ResultsOf 328 patients seen with HIV infection, notes were available on 14 who had been treated for TB. Only 6/14 children were known to be HIV‐infected prior to TB diagnosis, 3 were receiving ART at the time. Presentation with TB prompted HIV‐investigation in 6 further patients. Clinical signs and symptoms were similar to HIV uninfected children. Of 12 patients diagnosed with pulmonary TB (PTB), specimens for microbiological culture were only obtained from 8, all of which were negative. One case was confirmed by PCR of bronchoalveolar lavage. Two cases of extrapulmonary TB (EPTB) were confirmed microbiologically. Immunological status at TB diagnosis did not predict EPTB. Overall mean CD4 T‐cell count at TB presentation was 340×109/ml (15%), range 0–790 (0–34%). Of the 12 patients treated for PTB, 10 received 6 months anti‐TB therapy (ATT) and 2 received 12 months. 10/12 patients had a full clinical response to ATT. The 2 patients with residual symptoms had the lowest CD4 counts. Two patients with EPTB received ATT for 12 months. ART was suspended in 1 patient on starting ATT. In 2 patients ART was deferred until ATT was complete. Of 5 concurrently treated patients, 4 started ART 2 months into ATT. Therapeutic drug monitoring of nevirapine, efavirenz and lopinavir plasma levels guided management in these 5 patients. No immune reconstitution disease occurred in any patient.
ConclusionsDespite limitations to this retrospective study, a number of conclusions can be drawn: (1) HIV was only diagnosed after presentation with TB in 8/14 patients. An HIV test should be considered in all children diagnosed with TB, especially if there are epidemiological risk factors. (2) Therapeutic drug monitoring should guide concurrent ART‐ATT. (3) A comprehensive diagnostic effort is required to confirm TB in these children, including new interferon‐gamma release assays. (4) Diagnosis and management of TB/HIV co‐infection is a challenge and a prospective multicentre study is required to better characterise this problem in the UK.
S. Ladhani, M. Slack, M. Heys, J. White, M. Ramsay. Centre for Infections, Health Protection Agency, London, UK
ObjectiveTo assess the coverage of and impact on invasive Haemophilus influenzae serotype b (Hib) disease from the 2003 Hib vaccination booster campaign.
DesignNational surveillance of invasive Hib disease between January 1991 and December 2005.
PopulationAdults and Children in England and Wales.
ResultsSeventy one per cent (190457/266618) of 6–12 month olds and 63% (1020294/1617957) of 13–48 months old children received the Hib booster between May and September 2003. In 2004, a dramatic reduction was observed in invasive Hib cases within the age groups targeted, with a smaller decline among older children and adults. During 2005, there was a slight increase in the number of cases reported among 1–4 year olds (13 cases in 2004 v 26 cases in 2005). Cases in adults continued to decline slightly, but levels of disease remain substantially higher than any year in the decade following the introduction of the vaccine.
ConclusionsThe Hib booster campaign has been successful at improving Hib control. The slight increase in toddlers during 2005 suggests that routine boosting for Hib will be required. A Hib booster dose is to be added to the childhood immunisation programme at 12 months of age.
A. Turkova, R. Ahmad, E. Brown, U. Varma, W. Faulknell, H. Issler. Queen Elizabeth Hospital, Woolwich, London, UK
BackgroundThe risk of developing active TB in HIV infected individuals is high. It is recommended by national guidelines to give BCG vaccine to HIV‐negative children born to HIV‐positive mothers. Universal BCG cannot be offered to these children until their HIV status has been established. In 1997 an audit done in the local area showed that only 14% of eligible children had received BCG immunisation.
Aims(1) To determine whether arranging BCG vaccination in a hospital setting has improved uptake. (2) To investigate possible reasons for patients not attending the clinic.
MethodsA retrospective study of hospital and CHD electronic records was undertaken, exploring the uptake of BCG vaccination in HIV‐negative babies of HIV‐positive women born in 2004–5. Data after the introduction of a special BCG immunisation clinic for these children were analysed. Possible reasons for non‐attendance to the clinic were investigated.
ResultsAll 54 cases were analysed. The introduction of BCG vaccination in a hospital setting in early 2004 resulted in a substantial increase in BCG uptake to over 63%. One of the commonest reasons for non‐attendance was that a significant proportion of patients were “lost in the system”, with neither GPs nor CHD having any records for them. Other reasons included population migration and receiving BCG vaccination in the community.
ConclusionsHospital based BCG vaccination significantly increases the uptake of the vaccine. The health surveillance of HIV‐negative children born to HIV‐positive mothers by a paediatrician is warranted to address numerous issues including vaccinations.
M. Gaffari, M. Quinibi, D. Johnston. Scarborough General Hospital, Scarborough, UK
BackgroundPasturella multocida, a gram negative cocco bacillus, is a commensal in upper respiratory tract of many domestic pet species like dogs and cats. Skeletal infection due to Pasturella multocida has been rarely documented but virtually all cases have resulted from direct inoculation of organism or contiguous spread of local infection following animal bites or scratches.
AimWe report an unusual case of Osteomyelitis due to Pasturella multocida in a 10 month old immuno‐competent female infant without any history of animal bite or trauma, to help in better understanding of the disease.
Case ReportA 10‐month‐old infant presented with a 2‐day history of not using her left upper limb following a trivial fall (from 2 feet high bed while asleep). She was noticed to be hot on the day of presentation but was otherwise systemically well. There was no past history of note and the child was fully immunised. The family had a pet dog at home and she had been in close contact with it. On examination she was febrile and was indeed reluctant to use her left arm and attempted passive movement led to distress. There were no bruises or breaks in the overlying skin nor localised rise of temperature over joints. Examination of other systems was unremarkable.
Investigationsx Ray of her left upper limb including shoulder joint showed no fracture or joint abnormality. Her blood results showed raised white cell count with neutrophilia, raised CRP (160 on admission and 220 on 3rd day after admission). Ultrasound of the left upper limb joints was normal. A clinical diagnosis of Osteomyelitis was made and she was commenced on intra venous Cefotaxime and Flucloxacillin. Blood cultures came back positive after 2 days and both aerobic and anaerobic bottles isolated Pasturella multocida, sensitive to Amoxicillin, Ceftriaxone and Penicillin and antibiotics were changed accordingly.
ConclusionDrug of choice appears to be Penicillin or Coamoxiclav, which has effect in vitro and also has shown to have therapeutic effect in reported cases. In our case, there was initial deterioration while baby was on Flucloxacillin and Cefotaxime. Subsequent clinical improvement after commencing Amoxicillin would support the efficacy of Penicillins in Pasturella infections.
M. Sawal1, M. Cohen2, A. Petros6, J. Irazuzta4, M. Brundler5, C. Kirton2, A. Azaz3, R. Kumar3, P. Raffeeq1, P. Fenton3, J. A. Wilson3, C. Evans2, H. Klonin3. 1North Staffordshire University Hospital, Stoke‐on‐Trent, UK; 2Sheffield Children Hospital, Sheffield, UK; 3Hull Royal infirmary, Hull, UK; 4University of Florida, Jacksonville, USA; 5Birmingham Children Hospital, Birmingham, UK; 6Great Ormond Street, London, UK
AimsBordatella pertussis carries a high risk of mortality, especially in very young infants. The mechanism of refractory cardiorespiratory failure is complex and may be multifactorial. The objective of the study was to describe the clinicopathological features of fatal cases.
MethodsReview of the clinical records and postmortem findings of six patients with fatal Bordetella pertussis infection.
ResultsThe 6 patients were less than 8 weeks of age and presented with cough and coryzal symptoms. They later required ventilation for worsening respiratory symptoms and inotropic support for severe haemodynamic compromise. All had increased leukocyte counts, ranging from 55×109/l to 132×109/l, with prominent neutrophilia. The six patients succumbed, despite intensive care. In all cases, postmortem demonstrated necrotising bronchitis bronchiolitis and pneumonia with extensive areas of necrosis of the alveolar epithelium and sloughing of the pneumocytes into the air space. Hyaline membranes were present in those cases with viral co‐infection. In 5/5 cases where the thymus and the spleen were evaluated they were depleted. The lymph nodes also had lymphocyte depletion in 4 cases where they were examined. The blood vessels were filled with leukocytes but there was no organised thrombi or associated pulmonary infarction. 3/6 had co‐infection with Parainfluenza type 3, 1/6 with RSV, 1/6 with coliform and 1/6 with MRSA Staphylococcus aureus.
ConclusionsSevere hypoxemia and intractable cardiac failure may be due to necrotising bronchiolitis, extensive damage to the alveolar epithelium, tenacious secretions and possibly increased leucocytes in the lumen of blood vessels, leading to pulmonary hypertension. We have not found well‐organised thrombi in the pulmonary blood vessels with associated pulmonary infarction. The thymus and lymph node depletion may have caused the patients to be secondarily immunocompromised and susceptible to further infection with Para influenza or RSV viruses. This may have further damaged the lungs. The different modalities of treatment have supportive role but the mortality remains high in this age group.
M. Erlewyn‐Lajeunesse1, J. Haining2, A. Lovering4, S. Dymond1, A. MacGowan2, M. Fletcher3. 1Bristol Royal Hospital for Children, Bristol, UK; 2University of Bristol, Bristol, UK; 3University of the West of England, Bristol, UK; 4North Bristol NHS Trust, Bristol, UK
IntroductionThe administration of out of hospital parenteral benzyl penicillin is current best practice for children presenting with suspected meningococcal disease (MCD). However, data from case control studies suggest that there is a significant excess mortality when the sickest children are treated in this way. We need to understand the effects of this treatment, but despite its routine use no pharmacokinetic studies have been conducted.
AimsTo study the feasibility of measuring blood penicillin concentrations in this acute context.
MethodsThis was a retrospective analysis, from a study of invasive infection in children, who had either received benzyl penicillin or had a confirmed diagnosis of MCD. An EDTA whole blood sample was collected during the acute admission and stored at −80°C. We measured benzyl penicillin and its metabolite (penicilloic acid) using high performance liquid chromatography (HPLC) with a cut‐off of 2 mg/l for detection, and compared this to clinical and prognostic data.
ResultsPenicillin was measured in samples from 33 children, of whom penicillin was detected in 6 of the 17 (35%) who received benzyl penicillin. We were only able to detect penicillin within a day of admission in keeping with its short half life of 20 minutes. We detected BP in 2/3 children who died. Children with detectable penicillin were sicker with a Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS) of median 12 (95% CI 3–12; cf 5 (CI 4–9); Mann–Whitney U p=0.29). Penicillin was also found in 4/13 children admitted to PICU and 2/4 who were not. Overall, those receiving benzyl penicillin were older at 3.1 years (CI 1.3–5.0) compared to 1.5 (0.8–2.2; p=0.01), sicker (GMSPS 5 (CI 4–12) cf. 3 (CI 2–9)), and were more likely to be admitted to the Paediatric Intensive Care Unit 13/22 cf. 4/11.
ConclusionsWe have demonstrated that it is possible to detect penicillin in children receiving parenteral benzyl penicillin for MCD. This makes it possible to conduct more detailed pharmacokinetic studies. In keeping with the literature, penicillin was given to the sickest children in our study. It is intriguing that penicillin was detected only in the sickest of these. This suggests that abnormal pharmacokinetics, including delayed intramuscular absorption or renal excretion, may prolong the half‐life of penicillin in this group.
S. Orwa, K. Connolly, J. Gilvarry, R. Mahon, N. Arthur, D. McCarthy. The Irish Medicines Board, Earlsfort Court Dublin, Mullingar, Dublin, Ballinasloe, Ireland
AimThis presentation details the adverse reactions reported, and discusses possible reasons for the increase in reporting of suspected adverse reactions.
MethodsData detailing suspected adverse drug reactions (ADRs) following BCG vaccination, spontaneously reported to the Irish Medicines Board from August 2002–August 2004 were analysed. Information regarding the age at administration, batch numbers, dose and route of administration, type of reaction, management, was collected. Subsequently, questionnaires were sent to reporters in order to obtain supplementary information. Cases were classified according to the clinically most significant reaction reported. The total number of doses of BCG administered in the two‐year period was estimated by birth cohorts from the National Statistics Office.
ResultsIn the two‐year period, approximately 85000 doses of BCG were administered to neonates in Ireland. 121 adverse reports were received (0.14%). A breakdown based on clinical evaluation of ADRs is shown below. There were 59 cases of regional lymphadenopathy, 58 cases of local exceeding 10 mm in diameter and 4 cases of generalised rash. Use of incorrect dose (0.1 ml instead of 0.05 ml) was reported in 4 infants and incorrect route of administration (sc or im) was reported in 6 cases. 21 babies required surgical intervention.
ConclusionsThere has been a significant increase in the notification of suspected ADRs following introduction of the Danish 1331 BCG strain. However, the overall reporting rate remains within the frequency of ADRs reported for the project. The findings of this retrospective review has implications in deciding whether or not to continue with the universal Irish BCG immunisation.
A. Cunnington, W. Leith. Whittington Hospital NHS Trust, London, UK
BackgroundIn 2005 the British HIV Association published guidelines for the management of HIV in pregnancy. We developed a simplified local guideline for the management of infants born to HIV infected mothers. We audited the implementation of the guideline over the next 11 months.
MethodsPatients were identified from three sources (antenatal clinic, postnatal ward and paediatric clinic) to ensure full ascertainment. We collected demographic, clinical and laboratory data and assessed adherence to the guideline.
ResultsFourteen mothers were identified, with 12 live infants delivered. In only 5 cases (36%) was the mother's general practitioner aware of her diagnosis. In 7 cases (50%) significant social problems were identified. 11 infants received zidovudine monotherapy and one received zidovudine, lamivudine and nevirapine. No infants had positive HIV DNA PCR at any stage. We identified two areas of weakness in practice: diagnostic testing and explanation about medication. Only 3 (25%) of the initial infant blood samples were tested in parallel with a maternal sample. In 2 cases incorrect blood samples were sent. Despite correct prescriptions for take‐home medication, 1 infant went home without any medication, one infant received double the usual dose of zidovudine, and one infant received 6 (rather than 4) weeks of zidovudine.
ConclusionsWe have identified a need to improve practice. We believe many of these problems could be remedied with better communication and documentation. We are amending our guidelines to take this into account.
R. Kumar1, L. Yeung2, P. Tomlin2. 1Royal Manchester Children's Hospital, Manchester, UK; 2Royal Preston Hospital, Preston, Lancashire, UK
AimsTo identify the clinical features of children who received intravenous aciclovir treatment for suspected encephalitis; the reasons for stopping aciclovir treatment; and the eventual diagnosis of the children at discharge.
MethodsProspective audit in a district general hospital paediatric ward over a 10‐month period from October 2004 to August 2005. Inclusion criteria: children in the age range 8 weeks to 16 years old; combination of fever and other neurological symptoms OR clinical concern of central nervous system infection by the admitting staff.
Results5890 admissions were screened in the 10‐month period. 24 children were suspected of having a central nervous system infection. Intravenous aciclovir was started in 11 of these children. All except one of these 11 children were also started on intravenous antibiotics. Seizure was the main presenting complaint in 10 children, being focal in 5 and prolonged in 6. One child had transverse myelopathy. Seizures were a presenting feature in only 1 child who received antibiotics alone without aciclovir. Seven of the 11 children had CSF HSV PCR requested—all were negative. CSF cell count and biochemistry were normal in all children. Nine children had urgent neuroimaging (3 had MRI) which revealed a subdural haemorrhage in 1 infant. Two children had urgent EEG, which showed diffuse slow activity in both. Two children received a 10‐day course of aciclovir despite negative CSF HSVPCR due to persistent signs. In 8 children, the aciclovir was stopped prior to CSF HSV PCR becoming available. The reason for stopping aciclovir early was clearly documented in only 1 child, who had venous access problems. The discharge diagnoses were: acute transverse myelitis (1 child), febrile seizure syndrome (5), epilepsy syndrome (3), accidental subdural haemorrhage (1), lost to follow‐up (1). None of the children had a viral encephalitis.
ConclusionsIn children suspected of having a central nervous system infection, intravenous aciclovir was started along with antibiotics when seizure was the main presenting complaint. Problems with venous access may limit optimum treatment. Clearer criteria are needed to define which children should be started on aciclovir, and indications for stopping treatment if CSF HSV PCR is not available.
J. Heraghty3, T. McHugh1, C. Ling1, S. Davidson1, H. Caulfield1, A. Sutcliffe2. 1Royal Free NHS Trust, London, UK; 2University College Hospital NHS Trust, London, UK; 3University Hospital for Wales, Cardiff, UK
AimThe aim of this study was to look for evidence of an association between Chlamydia pneumoniae carriage in children who have normal sized tonsils and those who have enlarged tonsils and/or adenoids.
MethodChildren who were having planned removal of enlarged tonsils and/or adenoids for any indication were recruited. Any child with a respiratory condition or any respiratory symptoms, such as a cough were excluded. The child then had a nasopharyngeal aspirate (NPA) taken during their surgical procedure. The NPA was sent for Chlamydia pneumoniae PCR testing. A control group of 33 children had a NPA taken for Chlamydia testing while they were undergoing general anaesthetic for gastroenterological endoscopy.
ResultsOf the children undergoing adenotonsillectomy 27% (5/18) had a positive PCR result. In the control group there were 12% (4/33) who had a positive result for Chlamydia pneumoniae. This suggests an association with Chlamydia pneumoniae but is not statistically significant (p=0.154).
ConclusionThis study has high Chlamydia pneumoniae rates in the group of children with enlarged tonsils and adenoids but a larger cohort is required to confirm this trend.
DiscussionChlamydia pneumoniae is epidemic and varies between seasons; rates can range between 5.6% in healthy controls to 45% in children with respiratory tract infections. High rates of Chlamydia carriage have been shown on throat swab PCRs and serology in children undergoing adenoidectomy, but previous studies have not had a control group to assess the background rates during the study. The low recruitment of patients to this study indicates that it is too early to exclude or confirm an association between children with enlarged tonsils and adenoids and Chlamydia pneumoniae carriage.
P. Thompson1, R. Gilbert2, P. Long1, M. Sharland3, I. Wong1. 1Centre for Paediatric Pharmacy Research, London, UK; 2Institute of Child Health, London, UK; 3St George's Hospital, London, UK
AimsWhat are antibiotics being prescribed to children for and how has this changed over time?
MethodsOral antibiotic (BNF Header 5.1) prescribing data for the main indications (as identified by a study of 100 random patients from the General Practice Research Database (GPRD)) were extracted from the GPRD for children aged 0–18 years, between 1 January 1990 and 31 December 2005. The GPRD contains anonymised primary care records for approximately 5% of the UK population.
ResultsWe have previously noted a decrease in paediatric antibiotic prescribing between 1990 and 2005. However, prescribing by diagnoses has remained relatively stable over this 15 year study period (table). The most notable differences lie within the “upper respiratory tract infection/cough” (4% increase), “respiratory tract infection/lower respiratory tract infection' (3% increase) and “other” (8% decrease) categories (further work is necessary in order to determine the “other” indications). There are still a lot of prescriptions for upper respiratory tract infections, thus indicating that it is probably possible to reduce antibiotic prescribing even further.
ConclusionPaediatric antibiotic prescribing has decreased over the past 15 years. Prescriptions by diagnoses have remained relatively stable. A further reduction in antibiotic prescribing may be possible.
S. Didier, S. Jayasooriya, T. Fenton, N. Wright, A. Raghavan. Sheffield Children's Hospital, Sheffield, UK
IntroductionLemierre's syndrome (LS) is an infection related syndrome which although rare is thought to be increasing in prevalence in the paediatric population. It is a clinical condition characterised by septicaemia arising from oropharyngeal foci, complicated by a septic thrombophlebitis of the ipsilateral internal jugular vein. Embolisation occurs to various sites, classically the lungs.
AimTo increase the awareness of paediatricians to the importance of making this diagnosis to enable prompt treatment and avoidance of life threatening complications.
CaseA 12‐year‐old male presented with a four week history of right ear discharge and otalgia. Despite a course of oral Clarithromycin, Sofradex and Gentamicin ear drops prior to presentation he remained symptomatic with a discharging right ear. At presentation he had a five‐day history of fever, rigors, lethargy, vomiting, diarrhoea and jaundice. The examination was remarkable for pyrexia, jaundice and moderate dehydration. Mild right mastoid tenderness was present with a purulent right ear discharge. Abdominal examination revealed mild tender hepatomegaly with no spleen palpable. There was no meningism or neurological deficit. Initial investigations showed thrombocytopenia and raised white cell count. He had a raised C reactive protein of 155, moderate hyponatremia, conjugated hyperbilirubinaemia and evidence of renal impairment. Broad‐spectrum antibiotics and supportive therapy were implemented. Blood cultures taken at the time of admission subsequently grew Fusobacterium necrophorum. He developed left‐sided pleuritic chest pain, continued to have vague right‐sided neck pain and high spiking temperatures. Chest radiograph showed changes consistent with pulmonary emboli. High resolution CT of the head and neck showed an extensive thrombus in the right sigmoid and transverse sinus extending proximally into the internal jugular vein consistent with Lemierre's syndrome. He commenced anticoagulation with warfarin to prevent clot progression. Four weeks post discharge he is well, has restarted school and remains on anticoagulation. He will have a repeat CT scan in 4 months. Further tests should include investigations for a hereditary predisposition to thrombosis.
NAGoldenburgRKnapp-ClevengerTHayset al Lemierre's and Lemierre's‐like syndromes in children. Survival and thromboembolic outcomes. Pediatrics2005116 pp e543-8
A. Macken, M. McAleer, D. Devaney, D. Gill, B. O'Donnell. The Children's University Hospital, Temple Street, Dublin, Ireland
AimsPyoderma gangrenosum (PG) is an uncommon, ulcerative disorder of unknown aetiology. Presentation in infancy is extremely rare. Because of its rarity, diagnosis is difficult and management strategies are not established for this age group. We aim to describe the clinical features, course and management of PG in an 8‐month‐old boy.
MethodsA case description with contemporaneous clinical photography of an 8‐month‐old infant who presented with PG, detailing investigations, clinical course response to therapeutic interventions.
ResultsAn 8‐month‐old boy presented with a large ulcer on his left thigh which was excised. He subsequently developed extensive inflammation and ulceration at the wound site with further lesions occurring at sites of trauma (pathergy). He initially responded to high dose steroid therapy (prednisolone 3 mg/kg) but subsequently relapsed with further ulceration. Disease control was achieved following the addition of cyclosporin. His lesions have healed and he was discharged 3 months after presentation.
ConclusionOnly 13 cases of PG in infancy have been reported previously. The majority of these cases were controlled with steroid therapy. In this case we report the first instance of healing of PG in an infant after the introduction of cyclosporin where steroid therapy had failed.