How long should we treat this infection for?

Infection accounts for approximately half of all paediatric admissions to hospital and an even greater proportion of primary care. Guidelines on duration of antibiotic therapy exist, but antibiotic therapy for children needs to be individualised. If a child is not improving the clinical condition and treatment should be reviewed and/or discussed with an expert. However, slavishly completing the recommended course of antibiotics in a child who is well, may not be appropriate. Recent studies on treatment duration advocate shortened courses with certain caveats, but guidelines and clinical practice do not always follow the evidence from the few randomised trials of treatment duration of infection.

Medical pediatric inpatients and outpatients are at risk of influenza and pneumococcal disease.

Influenza and pneumococcal vaccines are recommended for certain risk groups. All children admitted to the Children's wards or attending Children's Outpatients were studied for these risk factors. Risk factors for influenza were present in 78 (41%) of 193 admissions and 93 (27%) of 348 outpatients. Risk factors for pneumococcal infection were present in 22 (11.5%) admissions and 42 (12%) outpatients. Only 29 of these children had been given influenza (n = 19) or pneumococcal (n = 10) vaccines. Pediatricians could improve the coverage of influenza and pneumococcal vaccines by identifying children with risk factors in hospital discharge summaries and outpatient clinic letters.

Imported malaria in children: a review of clinical studies.

Imported malaria is a preventable disease, yet it is responsible for several thousand cases and a substantial number of deaths every year. There has been a pronounced rise in the incidence of imported malaria in most developed countries over the past three decades and, more concerning, Plasmodium falciparum, which is responsible for almost all cases of severe malaria, is now the most prevalent species. Children account for around 15-20% of all imported malaria cases and must be considered separately from adults because they have different risk factors for developing malaria and a higher risk of developing severe disease since they are more likely to be non-immune to malaria. We did a thorough review of the literature since 1980 to identify and critically assess clinical case series on children with imported malaria with respect to travel destination, reason for travel, the use of antimalarial prophylaxis, clinical presentation, delay in diagnosis, laboratory features, complications, management, and outcome. Children living in non-endemic countries and travelling during school holidays to visit family and relatives in their parents' country of origin currently account for the largest proportion of cases in many European countries. This group of travellers deserves special attention because they often do not take antimalarial prophylaxis or other preventive measures. There is a need for standardised recommendations on management and prevention of imported malaria in children, which should be supported by large multicentre clinical trials. A prospective national surveillance study on imported malaria in children was launched in the UK and Ireland through the British Paediatric Surveillance Unit in 2006, which may provide answers to some of the questions raised in this Review.

Bacterial meningitis: the impact of vaccination.

Acute bacterial meningitis remains an important cause of morbidity and mortality in children. Children <2 years of age are particularly susceptible to infection with encapsulated bacteria due to their immature response to polysaccharide antigens. Conjugate vaccines, which induce T cell memory, can provide immunological protection for these children. The Haemophilus influenzae type b (Hib) conjugate vaccine was the first such vaccine to become available. The efficacy of the vaccine has been quoted as being 98%. Its introduction was followed by a dramatic decrease in the incidence of all invasive Hib disease, including meningitis. This reduction was in part due to the ability of these vaccines to reduce nasopharyngeal carriage of the organism and thereby induce herd immunity. Different Hib vaccines use a variety of protein carriers and differ in their immunogenicity and efficacy. The most suitable vaccine needs to be determined according to the local epidemiology of Hib disease. Commercial combination vaccines may lead to lower antibody levels. A recent increase in the incidence of Hib disease in the UK highlights the importance of continued surveillance and the need for booster vaccinations to ensure continued protection. Conjugate vaccines to Streptococcus pneumoniae and Neisseria meningitidis have been developed. The introduction of a pneumococcal conjugate vaccine in the US has led to a decrease in the rate of infection by nearly 60% in children <5 years of age. A reduction in pneumococcal carriage may also modify disease epidemiology. The UK introduced the conjugate meningococcal C vaccine into its infant schedule with a corresponding reduction in N. meningitidis group C disease. A recent decrease in the effectiveness of the vaccine, however, suggests a booster may be necessary in the future. Our present understanding of the immunology of conjugate vaccines is far from complete. Developed countries have introduced conjugate vaccines into their immunisation schedules to prevent bacterial meningitis; however, their high cost precludes their use in many developing countries. Progress needs to be made in order to get these highly effective vaccines to those areas that need them.

"Random" gentamicin concentrations do not predict trough levels in neonates receiving once daily fixed dose regimens.

BACKGROUND: Monitoring plasma gentamicin concentrations in neonates 24 hours after a once daily dose (4 mg/kg) often necessitates additional blood sampling. In adults a nomogram has been developed enabling evaluation of gentamicin doses by sampling concentrations with other blood tests, 4-16 hours after administration. We attempted to develop a similar nomogram for neonates. METHODS: In addition to standard 24 hour sampling to monitor trough concentrations, one additional "random" gentamicin concentration was measured in each of 50 neonates < 4 days of age (median gestation 33 weeks [28-41]), when other blood samples were clinically necessary, 4-20 hours after gentamicin administration. 24 hour concentrations of > 1 mg/L were considered high, and an indication to extend the dosing interval. RESULTS: Highest correlation (r2 = 0.51) of plasma gentamicin concentration against time (4 to 20 hours) was with logarithmic regression. A line drawn 0.5 mg/L below the true regression line resulted in all babies with 24 hr gentamicin concentrations > 1 mg/L having the additional "random" test result above that line, i.e. 100% sensitivity for 24 hour concentrations > 1 mg/L, though only 58% specificity. Having created the nomogram, 39 further babies (median gestation 34 weeks [28-41]), were studied and results tested against the nomogram. In this validation group, sensitivity of the nomogram for 24 hr concentrations > 1 mg/L was 92%; specificity 14%, positive predictive value 66%, and negative predictive value 50%. Prematurity (< or = 37 weeks) was a more sensitive (94%) and specific (61%) indicator of high 24-hour concentrations. 62 (87%) of 71 preterm babies had high 24-hour concentrations. CONCLUSION: It was not possible to construct a nomogram to predict gentamicin concentrations at 24 hours in neonates with a variety of gestational ages. Dosage tailored to gestation with monitoring of trough concentrations remains management of choice.

Validation of two algorithms for managing children with a non-blanching rash.

BACKGROUND: Paediatricians are concerned that children who present with a non-blanching rash (NBR) may have meningococcal disease (MCD). Two algorithms have been devised to help identify which children with an NBR have MCD. AIM: To evaluate the NBR algorithms' ability to identify children with MCD. METHODS: The Newcastle-Birmingham-Liverpool (NBL) algorithm was applied retrospectively to three cohorts of children who had presented with NBRs. This algorithm was also piloted in four hospitals, and then used prospectively for 12 months in one hospital. The National Institute for Health and Care Excellence (NICE) algorithm was validated retrospectively using data from all cohorts. RESULTS: The cohorts included 625 children, 145 (23%) of whom had confirmed or probable MCD. Paediatricians empirically treated 324 (52%) children with antibiotics. The NBL algorithm identified all children with MCD and suggested treatment for a further 86 children (sensitivity 100%, specificity 82%). One child with MCD did not receive immediate antibiotic treatment, despite this being suggested by the algorithm. The NICE algorithm suggested 382 children (61%) who should be treated with antibiotics. This included 141 of the 145 children with MCD (sensitivity 97%, specificity 50%). CONCLUSIONS: These algorithms may help paediatricians identify children with MCD who present with NBRs. The NBL algorithm may be more specific than the NICE algorithm as it includes fewer features suggesting MCD. The only significant delay in treatment of MCD occurred when the algorithms were not followed.

Estimating hospital admissions due to rotavirus gastroenteritis from hospital episode statistics.

OBJECTIVES: To determine the proportion of hospital admissions, in children < 5 years old, coded for intestinal infectious disease or non-infectious gastroenteritis, using ICD-10 codes, that were due to rotavirus infection. To assess how many children admitted with rotavirus gastroenteritis were given the specific ICD-10 code (A080) for this disease. METHODS: Sixteen-month prospective, observational study of children < 5 years old, admitted to district general hospital with: acute gastroenteritis (> or =3 loose stools/day), proven rotavirus infection and those coded as intestinal infectious disease or non-infectious gastroenteritis. RESULTS: Four hundred and twenty children < 5 years old were admitted with acute gastroenteritis. Rotavirus was detected in 170 children's stools. Acute rotavirus gastroenteritis accounted for 81/397 (20%) children coded as having non-infectious gastroenteritis and 32/81 (40%) coded for intestinal infectious disease. Only 18 children were coded for rotavirus gastroenteritis. Potentially preventable rotavirus gastroenteritis occurred in 122 children; 78 coded as non-infectious gastroenteritis (20%) and 26 coded for intestinal infectious disease (34%). CONCLUSIONS: The proportion of children coded with diarrhoeal diseases and found to have rotavirus is less than previously estimated. Using the specific code for rotavirus infection to estimate hospital admissions would be a gross underestimate. Hospital episode statistics cannot reliably estimate the burden of disease due to rotavirus.

Meningococcal disease presenting as bronchiolitis.

Meningococcal disease is the leading infective cause of mortality in children. Bronchiolitis and meningococcal disease share some common features. Both are seasonal diseases with epidemics in winter. A preceding history of upper respiratory tract infection is commonly present in both. We report two cases of meningococcal disease in infants whose initial presentation was suggestive of bronchiolitis. We draw attention to tachypnoea as an important but overlooked early sign of meningococcal septicaemia.

Meningococcal disease in children in Merseyside, England: a 31 year descriptive study.

Meningococcal disease (MCD) is the leading infectious cause of death in early childhood in the United Kingdom, making it a public health priority. MCD most commonly presents as meningococcal meningitis (MM), septicaemia (MS), or as a combination of the two syndromes (MM/MS). We describe the changing epidemiology and clinical presentation of MCD, and explore associations with socioeconomic status and other risk factors. A hospital-based study of children admitted to a tertiary children's centre, Alder Hey Children's Foundation Trust, with MCD, was undertaken between 1977 to 2007 (n = 1157). Demographics, clinical presentations, microbiological confirmation and measures of deprivation were described. The majority of cases occurred in the 1-4 year age group and there was a dramatic fall in serogroup C cases observed with the introduction of the meningococcal C conjugate (MCC) vaccine. The proportion of MS cases increased over the study period, from 11% in the first quarter to 35% in the final quarter. Presentation with MS (compared to MM) and serogroup C disease (compared to serogroup B) were demonstrated to be independent risk factors for mortality, with odds ratios of 3.5 (95% CI 1.18 to 10.08) and 2.18 (95% CI 1.26 to 3.80) respectively. Cases admitted to Alder Hey were from a relatively more deprived population (mean Townsend score 1.25, 95% CI 1.09 to 1.41) than the Merseyside reference population. Our findings represent one of the largest single-centre studies of MCD. The presentation of MS is confirmed to be a risk factor of mortality from MCD. Our study supports the association between social deprivation and MCD.

Novel strategies in the use of lopinavir/ritonavir for the treatment of HIV infection in children.

Lopinavir/ritonavir (LPV/r) is considered by many as the first choice protease inhibitor (PI) for children. This co-formulation avoids the need for children to take ritonavir separately to "boost" the levels of lopinavir. LPV/r has high virologic potency, an excellent toxicity profile and a high barrier to the development of viral resistance. However, LPV/r has poor tolerability of the oral suspension (due to the poor taste of ritonavir), difficult dosing requirements and metabolic side effects, especially hyperlipidemia. The new tablet low-dose formulation (100/25 mg) may allow more convenient antiretroviral treatment in children. Novel strategies of LPV/r in childhood could maximize its advantages. For example, infants infected with HIV despite single dose Nevirapine after birth need effective combination antiretroviral treatment. This can be given using a higher dose of LPV/r with therapeutic drug monitoring. Other novel uses include once daily LPV/r regimens in older children and adolescents and lower doses of LPV/r in certain populations, which may decrease hyperlipidemia. Heavily pre-treated children might benefit from a double PI/r regimen which includes LPV/r. The high potency of LPV/r needs to be balanced with convenient regimens, to enhance adherence and decrease toxicity whenever possible. The aim of this review is to discuss the rationale behind these novel strategies of LPV/r use in pediatric antiretroviral treatment as well as their results and limitations.

Referrals for MMR immunisation in hospital.

Concern exists about measles, mumps and rubella (MMR) vaccine in egg-allergic children, although this has been shown to be safe. Guidelines from the Royal College of Paediatrics and Child Health (RCPCH) and British Society of Allergy and Clinical Immunology (BSACI) suggesting which children should be referred to hospital for MMR, were published in 2000. We audited referrals to hospital for MMR against these guidelines. One hundred and ten children were referred for MMR to Birmingham Heartlands Hospital (2002-2004) and Alder Hey Children's Hospital (2006-2009). Eighty-two (75%) children did not meet the published criteria. Only 13 children (12%) had severe egg allergy. The first dose of MMR vaccine was delayed by >30 days in 81% of children. All children were given MMR, none had a significant reaction. Children with egg allergy do not need to be given MMR in hospital, but MMR is often delayed by unnecessary hospital referral. New BSACI guidelines encouraging MMR vaccination of egg-allergic children in primary care need to be disseminated.

Prospective, national clinical and epidemiologic study on imported childhood malaria in the United Kingdom and the Republic of Ireland.

BACKGROUND: Current knowledge of clinical features of imported childhood malaria is largely limited to small, retrospective, and/or single-center case series. This prospective, population-based study describes the epidemiology and clinical features of imported childhood malaria in children <16 years in the United Kingdom and Republic of Ireland. METHODS: Active prospective national surveillance with clinical data collection was performed between January 1, 2006 and January 31, 2007 through the British Pediatric Surveillance Unit and capture-recapture analysis using cases reported independently to respective national surveillance centers. RESULTS: There were 290 cases, including 186 reported through the British Pediatric Surveillance Unit with clinical details. Capture-recapture analysis estimated the burden of imported childhood malaria to be 2.8/100,000 per year for the United Kingdom and 4.6/100,000 per year for Ireland. Black-African children born in the United Kingdom and Ireland and traveling to West Africa during school holidays without antimalarial prophylaxis accounted for the majority of cases. Thirty of 117 children (26%) who had traveled to a malaria-endemic country had previously been diagnosed with malaria, reflecting missed opportunities to educate families on malaria prevention. A third of children (46/148) with Plasmodium falciparum malaria fulfilled World Health Organization criteria for severe or potentially complicated malaria, although only 11/46 (24%) required intensive care. The choice of antimalarials varied considerably among hospitals and within the same hospital. However, recrudescence occurred in only 1 child and none died. CONCLUSIONS: Interventions to prevent imported childhood malaria should focus on Black-African families traveling to West Africa, while pediatricians should be offered clearer guidance on the treatment of childhood malaria.

Intensive care admissions for children with imported malaria in the United kingdom.

This study describes 977 children with imported malaria in England and Wales between 2004 and 2008, focusing on 29 (3.0%) patients admitted to intensive care, of whom 10 had cerebral malaria, 4 required inotropes, and 1 had concurrent septicemia. The remaining 14 were admitted for monitoring only. None died, but 1 child developed cerebellar infarction.

Staphylococcus aureus bacteraemia in children and neonates: a 10 year retrospective review.

UNLABELLED: Rates of Staphylococcus aureus bacteraemia (SAB) are published performance indicators for hospital-acquired infection. In adults SAB is often associated with central venous catheters (CVC), mortality is high and up to 40% are MRSA. However, there is little data on SAB in neonates and children in the UK. AIM: To describe the presentation, management and outcome of SAB on a neonatal and paediatric unit in a District General Hospital (DGH) over a 10 year period. METHOD: Case notes of children<16 years with SAB between May 1993 and April 2003 were studied. SAB which developed >48 h after admission was defined as hospital-acquired. Contamination was probable if the clinical picture was unsupportive of infection, or if repeat culture was negative and no treatment was given. RESULTS: Neonatal unit: Thirty-three of 40 episodes were reviewed (median gestation 32 weeks, median age 21 days). Three of 33 (9%) were contaminants. All SAB were hospital acquired. Twenty-six of 30 (87%) had non-specific presentation, but 15 developed a focus of infection (skin 12, chest 3). Seventeen (57%) infants had CVCs. Eight (27%) infants had MRSA bacteraemia, seven with CVCs. Three (10%) infants died. Paediatric unit: Sixty-four of 70 episodes were reviewed (median age 2 years). Thirteen of 64 (20%) were contaminants. Ten of 51 (20%) were hospital acquired. Presentations were with skin infection 18, bone/joint infection 13, non-specific 13, respiratory 8. Only two had MRSA, one with CVC. One (2%) child died, from an unrelated cause. CONCLUSION: SAB on a paediatric unit shows a very different pattern compared to SAB in adults. The pattern on a neonatal unit is more similar to that in adults. Both children and neonates have a lower mortality and a lower incidence of MRSA, whilst paediatric SAB has a weaker association with CVC. The proportion of SAB which is hospital acquired is low on a paediatric unit, making SAB an unreliable performance indicator. Most SA in blood cultures are not due to contamination. Prospective studies are needed to determine appropriate investigation and treatment.

Acute bacterial meningitis in children presenting to the Royal Liverpool Children's Hospital, Liverpool, UK and the Queen Elizabeth Central Hospital in Blantyre, Malawi: a world of difference.

BACKGROUND: Bacterial meningitis is a serious childhood illness worldwide. Children can now be immunised against meningitis with conjugate vaccines. The outcome of bacterial meningitis in British and Malawian children before the introduction of these vaccines was compared. METHODS: All children with culture-positive bacterial meningitis treated in the Royal Liverpool Children's Hospital (RLCH), UK during 1984-1991 (n=197) and in the Children's Unit, Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi during 1996-1997 (n=175) were studied. RESULTS: Children at QECH presented later and were more often comatose and malnourished. Mortality was 7% in RLCH compared with 41% in QECH. Three organisms caused most cases of meningitis: N. meningitidis 56% vs 4%, H. influenzae b 27% vs 25%, and S. pneumoniae 11% vs 35% in RLCH and QECH, respectively. Mortality was lower in RLCH for each organism: N. meningitidis 10% vs 28%, H. influenzae b 6% vs 43%, S. pneumoniae 0% vs 46%. CONCLUSIONS: Mortality from bacterial meningitis in Malawian children is much higher than in British children, even when infected with the same organisms. This might be owing to delay in presentation, malnutrition and HIV infection. Immunisation of Malawian children with conjugate vaccines should continue to develop since their risk of dying from meningitis is five times greater than that of British children.

Underdosing of antiretrovirals in UK and Irish children with HIV as an example of problems in prescribing medicines to children, 1997-2005: cohort study.

OBJECTIVE: To measure the extent of underdosing of antiretroviral drugs in children. DESIGN: Multicentre cohort study. SETTING: Clinical centres in hospitals in the United Kingdom and Ireland in the collaborative HIV paediatric study (CHIPS). PARTICIPANTS: 615 HIV infected children aged 2-12 years receiving antiretrovirals. MAIN OUTCOME MEASURES: Doses relative to weight and height compared with current recommended doses in 2004 European guidelines. RESULTS: The CHIPS cohort of 934 children comprises 80% of diagnosed HIV infected children in the UK and Ireland between January 1997 and March 2005, of which 66% (615) aged 2-12 years were prescribed antiretrovirals. Actual doses standardised to weight or surface area varied widely across individual drugs, antiretroviral class, and calendar time, with children underdosed (prescribed less than 90% of current recommended doses) from 6-62% child time at risk. Three serious issues in prescribing antiretrovirals, which may also be relevant to paediatric prescribing in general, were identified. Firstly, dosing was inadequate before incorrect recommendations at licensing were later revised when important pharmacokinetic results emerged. Secondly, guidelines stating dosage alternatives (by weight/surface area) for the same drug led to different and inconsistent doses. And, thirdly, ongoing growth was not adjusted for. CONCLUSIONS: Largely inadvertently, HIV infected children in the United Kingdom and Ireland have been underdosed with antiretrovirals, highlighting problems applicable throughout paediatric prescribing.

Prospective validation of the Glasgow Meningococcal Septicaemia Prognostic Score. Comparison with other scoring methods.

UNLABELLED: A prospective observational study was done to derive performance characteristics for the Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS) and compare it with nine other severity scores (Stokland, Stiehm and Damrosch, Ansari, Niklasson, Leclerc, Kahn and Blum, Lewis, Istanbul and Bjark) and laboratory markers of disease severity. In the paediatric departments of six hospitals in Merseyside, UK, 278 children with confirmed or probable meningococcal disease were admitted between November 1988 and August 1990 ( n=152) and between September 1992 and April 1994 ( n=126); 26 of whom died. GMSPS was recorded on admission and again if there was clinical deterioration. Laboratory markers of disease severity (including endotoxin and cytokine levels) were measured on admission. The nine other scores were recorded on the first cohort. "Maximum" GMSPS (before referral to the paediatric intensive care unit) was achieved within 12 h of arrival in 97% of children. A GMSPS > or =8 had sensitivity 100%, specificity 75% and positive predictive value for death of 29%, GMSPS > or =10 had 100%, 88% and 46% respectively. All 26 who died scored >10, before referral to the paediatric intensive care unit. GMSPSs calculated by other medical staff had similar characteristics to those calculated by research fellows. All scores correlated significantly with white cell count, coagulopathy, endotoxin and cytokine levels. However, the predominantly clinical scores were the most robust. GMSPS had amongst the best performance characteristics of all scores and was more sensitive than laboratory markers. CONCLUSION: the Glasgow Meningococcal Septicaemia Prognostic Score is an easily performed, repeatable, clinical score that can rapidly identify children with fulminant meningococcal disease. When performed prospectively, a score > or =8 had a positive predictive value for death of 29%. This score can identify those children who should be offered intensive care and can select those who may benefit from novel therapies.