Anthony Harnden

British Thoracic Society guidelines for the management of community acquired pneumonia in children: update 2011

The British Thoracic Society first published management guidelines for community acquired pneumonia in children in 2002 and covered available evidence to early 2000. These updated guidelines represent a review of new evidence since then and consensus clinical opinion where evidence was not found. This document incorporates material from the 2002 guidelines and supersedes the previous guideline document.

Clinical recognition of meningococcal disease in children and adolescents

BACKGROUND Meningococcal disease is a rapidly progressive childhood infection of global importance. To our knowledge, no systematic quantitative research exists into the occurrence of symptoms before admission to hospital. METHODS Data were obtained from questionnaires answered by parents and from primary-care records for the course of illness before admission to hospital in 448 children (103 fatal, 345 non-fatal), aged 16 years or younger, with meningococcal disease. In 373 cases, diagnosis was confirmed with microbiological techniques. The rest of the children were included because they had a purpuric rash, and either meningitis or evidence of septicaemic shock. Results were standardised to UK case-fatality rates. FINDINGS The time-window for clinical diagnosis was narrow. Most children had only non-specific symptoms in the first 4-6 h, but were close to death by 24 h. Only 165 (51%) children were sent to hospital after the first consultation. The classic features of haemorrhagic rash, meningism, and impaired consciousness developed late (median onset 13-22 h). By contrast, 72% of children had early symptoms of sepsis (leg pains, cold hands and feet, abnormal skin colour) that first developed at a median time of 8 h, much earlier than the median time to hospital admission of 19 h. INTERPRETATION Classic clinical features of meningococcal disease appear late in the illness. Recognising early symptoms of sepsis could increase the proportion of children identified by primary-care clinicians and shorten the time to hospital admission. The framework within which meningococcal disease is diagnosed should be changed to emphasise identification of these early symptoms by parents and clinicians.

Assessment of the efficacy and effectiveness of influenza vaccines in healthy children: systematic review

BACKGROUND We aimed to assess evidence of efficacy and effectiveness of live attenuated and inactivated influenza vaccines in children up to 16 years of age. METHODS We searched the Cochrane Library, MEDLINE, EMBASE Biological Abstracts, and Science Citation Index to June, 2004, in any language, and contacted vaccine manufacturers and authors of relevant studies to identify additional data. We included randomised, cohort, and case-control studies comparing efficacy of vaccines against influenza (reduction in laboratory-confirmed cases), effectiveness of vaccines against influenza-like illness (reduction in symptomatic cases), or both, with placebo or no intervention. We analysed the following outcomes: influenza, influenza-like illness, admissions, school absences, complications, and secondary transmission. FINDINGS We included 14 randomised controlled trials, eight cohort studies, one case-control study, and one randomised controlled trial of intraepidemic use of the vaccines. Live attenuated influenza vaccines had 79% efficacy and 38% effectiveness in children older than 2 years compared with placebo or no immunisation. Inactivated vaccines had lower efficacy (65%) than live attenuated vaccines, and in children aged 2 years or younger they had similar effects to placebo. Effectiveness of inactivated vaccines was about 28% in children older than 2 years. Vaccines were effective in reducing long school absences (relative risk 0.14 [95% CI 0.07-0.27]). Studies assessing the effects of vaccines against secondary cases, lower-respiratory tract disease, acute otitis media, and hospital stay suggested no difference with placebo or standard care, but lacked statistical power. INTERPRETATION Influenza vaccines (especially two-dose live attenuated vaccines) are efficacious in children older than 2 years. Efficacy and effectiveness of the vaccines differed strikingly. Only two small studies assessed the effects of influenza vaccines on hospital admissions and no studies assessed reductions in mortality, serious complications, and community transmission of influenza. If influenza immunisation in children is to be recommended as public-health policy, large-scale studies assessing such important outcomes and undertaking direct comparisons of vaccines are urgently needed.

Neuraminidase inhibitors for treatment and prophylaxis of influenza in children: systematic review and meta-analysis of randomised controlled trials.

Objective To assess the effects of the neuraminidase inhibitors oseltamivir and zanamivir in treatment of children with seasonal influenza and prevention of transmission to children in households. Design Systematic review and meta-analysis of data from published and unpublished randomised controlled trials. Data sources Medline and Embase to June 2009, trial registries, and manufacturers and authors of relevant studies. Review methods Eligible studies were randomised controlled trials of neuraminidase inhibitors in children aged ≤12 in the community (that is, not admitted to hospital) with confirmed or clinically suspected influenza. Primary outcome measures were time to resolution of illness and incidence of influenza in children living in households with index cases of influenza. Results We identified four randomised trials of treatment of influenza (two with oseltamivir, two with zanamivir) involving 1766 children (1243 with confirmed influenza, of whom 55-69% had influenza A), and three randomised trials for postexposure prophylaxis (one with oseltamivir, two with zanamivir) involving 863 children; none of these trials tested efficacy with the current pandemic strain. Treatment trials showed reductions in median time to resolution of symptoms or return to normal activities, or both, of 0.5-1.5 days, which were significant in only two trials. A 10 day course of postexposure prophylaxis with zanamivir or oseltamivir resulted in an 8% (95% confidence interval 5% to 12%) decrease in the incidence of symptomatic influenza. Based on only one trial, oseltamivir did not reduce asthma exacerbations or improve peak flow in children with asthma. Treatment was not associated with reduction in overall use of antibiotics (risk difference −0.30, −0.13 to 0.01). Zanamivir was well tolerated, but oseltamivir was associated with an increased risk of vomiting (0.05, 0.02 to 0.09, number needed to harm=20). Conclusions Neuraminidase inhibitors provide a small benefit by shortening the duration of illness in children with seasonal influenza and reducing household transmission. They have little effect on asthma exacerbations or the use of antibiotics. Their effects on the incidence of serious complications, and on the current A/H1N1 influenza strain remain to be determined.

Kawasaki disease: What is the epidemiology telling us about the etiology?

Summary Kawasaki disease (KD) is an important and common inflammatory vasculitis of early childhood with a striking predilection for the coronary arteries. It is the predominant cause of paediatric acquired heart disease in developed countries. Despite 40 years of research, the aetiology of KD remains unknown and consequently there is no diagnostic test and treatment is non-specific and sub-optimal. The consensus is that KD is due to one or more widely distributed infectious agent(s), which evoke an abnormal immunological response in genetically susceptible individuals. The epidemiology of KD has been extensively investigated in many populations and provides much of the supporting evidence for the consensus regarding etiology. These epidemiological data are reviewed here, in the context of the etiopathogenesis. It is suggested that these data provide additional clues regarding the cause of KD and may account for some of the continuing controversies in the field.

Effect of antibiotic prescribing on antibiotic resistance in individual children in primary care: prospective cohort study

Objective To assess the effect of community prescribing of an antibiotic for acute respiratory infection on the prevalence of antibiotic resistant bacteria in an individual child. Study design Observational cohort study with follow-up at two and 12 weeks. Setting General practices in Oxfordshire. Participants 119 children with acute respiratory tract infection, of whom 71 received a β lactam antibiotic. Main outcome measures Antibiotic resistance was assessed by the geometric mean minimum inhibitory concentration (MIC) for ampicillin and presence of the ICEHin1056 resistance element in up to four isolates of Haemophilus species recovered from throat swabs at recruitment, two weeks, and 12 weeks. Results Prescribing amoxicillin to a child in general practice more than triples the mean minimum inhibitory concentration for ampicillin (9.2 �g/ml v 2.7 �g/ml, P=0.005) and doubles the risk of isolation of Haemophilus isolates possessing homologues of ICEHin1056 (67% v 36%; relative risk 1.9, 95% confidence interval 1.2 to 2.9) two weeks later. Although this increase is transient (by 12 weeks ampicillin resistance had fallen close to baseline), it is in the context of recovery of the element from 35% of children with Haemophilus isolates at recruitment and from 83% (76% to 89%) at some point in the study. Conclusion The short term effect of amoxicillin prescribed in primary care is transitory in the individual child but sufficient to sustain a high level of antibiotic resistance in the population.

Chloramphenicol treatment for acute infective conjunctivitis in children in primary care: a randomised double-blind placebo-controlled trial

BACKGROUND One in eight schoolchildren have an episode of acute infective conjunctivitis every year. Standard clinical practice is to prescribe a topical antibiotic, although the evidence to support this practice is scarce. We undertook a randomised double-blind trial to compare the effectiveness of chloramphenicol eye drops with placebo in children with infective conjunctivitis in primary care. METHODS Our study included 326 children aged 6 months to 12 years with a clinical diagnosis of conjunctivitis who were recruited from 12 general medical practices in the UK. We assigned 163 children to receive chloramphenicol eye drops and 163 to receive placebo eye drops. Eye swabs were taken for bacterial and viral analysis. The primary outcome was clinical cure at day 7, which was assessed from diaries completed by parents. All children were followed up for 6 weeks to identify relapse. Survival statistics were used for comparison, and analysis was by intention to treat. FINDINGS Nine children were lost to follow-up (one in chloramphenicol group; eight in placebo group). Clinical cure by day 7 occurred in 128 (83%) of 155 children with placebo compared with 140 (86%) of 162 with chloramphenicol (risk difference 3.8%, 95% CI -4.1% to 11.8%). Seven (4%) children with chloramphenicol and five (3%) with placebo had further conjunctivitis episodes within 6 weeks (1.2%, -2.9% to 5.3%). Adverse events were rare and evenly distributed between each group. INTERPRETATION Most children presenting with acute infective conjunctivitis in primary care will get better by themselves and do not need treatment with an antibiotic.

Whooping cough in school age children with persistent cough: prospective cohort study in primary care

Abstract Objective To estimate the proportion of school age children with a persistent cough who have evidence of a recent Bordetella pertussis infection. Design Prospective cohort study (October 2001 to March 2005). Setting General practices in Oxfordshire, England. Participants 172 children aged 5-16 years who presented to their general practitioner with a cough lasting 14 days or more who consented to have a blood test. Main outcome measures Serological evidence of a recent Bordetella pertussis infection; symptoms at presentation; duration and severity of cough; sleep disturbance (parents and child). Results 64 (37.2%, 95% confidence interval 30.0% to 44.4%) children had serological evidence of a recent Bordetella pertussis infection; 55 (85.9%) of these children had been fully immunised. At presentation, children with whooping cough were more likely than others to have whooping (odds ratio 2.85, 95% confidence interval 1.39 to 5.82), vomiting (4.35, 2.04 to 9.25), and sputum production (2.39, 1.14 to 5.02). Children with whooping cough were also more likely to still be coughing two months after the start of their illness (85% v 48%; P = 0.001), continue to have more than five coughing episodes a day (P = 0.049), and cause sleep disturbance for their parents (P = 0.003). Conclusions For school age children presenting to primary care with a cough lasting two weeks or more, a diagnosis of whooping cough should be considered even if the child has been immunised. Making a secure diagnosis of whooping cough may prevent inappropriate investigations and treatment.

How well do vital signs identify children with serious infections in paediatric emergency care

Objectives: To determine whether vital signs identify children with serious infections, and to compare their diagnostic value with that of the Manchester triage score (MTS) and National Institute for Health and Clinical Excellence (NICE) traffic light system of clinical risk factors. Design: Prospective cohort of children presenting with suspected acute infection. We recorded vital signs, level of consciousness, activity level, respiratory distress, hydration and MTS category. Setting: Paediatric assessment unit at a teaching hospital in England. Participants: 700 children (median age 3 years), of whom 357 (51.0%) were referred from primary care, 198 (28.3%) self-referrals and 116 (16.6%) emergency ambulance transfers. Just over half (383 or 54.7%) were admitted. Main outcome measures: Severity of infection categorised as serious, intermediate, minor or not infection. Results: Children with serious or intermediate infections (n = 313) were significantly more likely than those with minor or no infection (n = 387) to have a temperature ⩾39°C, tachycardia, saturations ⩽94% or capillary refill time (CRT) >2 seconds. Having one or more of temperature ⩾39°C, saturations ⩽94%, tachycardia and tachypnoea was 80% (95% CI 75% to 85%) sensitive and 39% (95% CI 34% to 44%) specific for serious or intermediate infection. This was comparable to the MTS score (84% sensitive, 38% specific), and the NICE traffic light system (85% sensitive, 29% specific). Conclusions: A combination of vital signs can be used to differentiate children with serious infections from those with less serious infections in a paediatric assessment unit and has comparable sensitivity to more complicated triage systems. The diagnostic value of combined vital signs and the NICE traffic light system remains to be determined in populations where the prevalence of severe illness is much lower.

Kawasaki disease in England: ethnicity, deprivation, and respiratory pathogens.

Background: Kawasaki disease is now the commonest cause of acquired heart disease in children in the United Kingdom. Its incidence has increased in recent years. Epidemiologic analyses have provided insights into the possible etiology, but European data are scarce. Methods: We analyzed linked England-wide hospital admission data for Kawasaki disease in people younger than 18 years of age, during a 5-year period (1998–2003), relating incidence to geographic location, urbanization, deprivation, ethnicity, and to laboratory reports of respiratory virus infection. Results: There were 2432 admissions with Kawasaki disease in the study period for 1704 individuals. One thousand twenty-eight (60%) of the 1704 were male and 1228 (72%) were younger than 5 years of age. The annual age-specific incidence rate in those younger than 5 years was 8.39/100,000. Incidence rates in different areas of residence were significantly and independently related to both the degree of deprivation of the area and the proportion of the population in each area who were Chinese. After adjusting for the winter peaks in both the incidence of Kawasaki disease and respiratory virus infections, there was no correlation between Kawasaki disease and specific viruses. Interpretation: The previously reported increase in Kawasaki disease incidence in England has reached a plateau. These data support the concept of an infectious trigger in a genetically susceptible population, but known respiratory viral pathogens are unlikely to be the specific etiologic agents.