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Catatonia commonly refers to a cluster of movement abnormalities, behaviour, volition and speech that has long been associated with psychiatric disorders in adults. Recent evidence suggests increasing prevalence in adolescents and older children with autistic spectrum disorder (ASD), but its occurrence in younger children is rare. Here we describe a 6-year-old boy presenting with catatonic autism, highlighting the diagnostic challenge and demonstrating the importance of timely assessment and management.

Background: Norovirus is the commonest cause of acute viral gastroenteritis with significant morbidity. Extra intestinal manifestation following norovirus infection is rare and the mechanism is unknown. Methods: We undertook a review of the English literature published from January 1967 to April 2019 to evaluate the risk of acute viral hepatitis due to norovirus gastroenteritis. Data sources included MEDLINE, EMBASE, Cochrane library, and references within identified articles. Results: We identified 126 potential studies and included 5 publications involving 17 cases of norovirus induced hepatitis, and all had elevated ALT (31.7–458IU/l) and AST levels (45.6–1150IU/l). Majority of the cases were below the age of 18 (88%, n = 15) and almost two-third (64.7%, n = 11) had supportive treatment, mainly intravenous fluid administration. In cases reporting sex, there were more females than males (62.5%, 5/8 vs. 37.5%, 3/8). The duration of illness was longer, on average 10 days, compared to 3 days in those without elevated transaminitis and it took an average of 22.5 days for liver enzymes to settle. All patients recovered fully with no progression to chronic liver disease. Conclusion: Norovirus gastroenteritis is a self-limiting illness with majority not requiring hospitalisation and invasive investigations. We recommend that clinicians should be aware of norovirus induced transaminitis, and to suspect this especially in children who are likely to have protracted illness and require hospitalisation due to norovirus acute hepatitis.

Background Coronavirus Disease 2019 (COVID-19) deaths are rare in children and young people (CYP). The high rates of asymptomatic and mild infections complicate assessment of cause of death in CYP. We assessed the cause of death in all CYP with a positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test since the start of the pandemic in England. Methods and findings CYP aged There were 185 deaths during the 22-month follow-up and 81 (43.8%) were due to COVID-19. Compared to non-COVID-19 deaths in CYP with a positive SARS-CoV-2 test, death due to COVID-19 was independently associated with older age (aOR 1.06 95% confidence interval (CI) 1.01 to 1.11, p = 0.02) and underlying comorbidities (aOR 2.52 95% CI 1.27 to 5.01, p = 0.008), after adjusting for age, sex, ethnicity group, and underlying conditions, with a shorter interval between SARS-CoV-2 testing and death. Half the COVID-19 deaths (41/81, 50.6%) occurred within 7 days of confirmation of SARS-CoV-2 infection and 91% (74/81) within 30 days. Of the COVID-19 deaths, 61 (75.3%) had an underlying condition, especially severe neurodisability (n = 27) and immunocompromising conditions (n = 12). Over the 22-month surveillance period, SARS-CoV-2 was responsible for 1.2% (81/6,790) of all deaths in CYP aged Conclusions COVID-19 deaths remain extremely rare in CYP, with most fatalities occurring within 30 days of infection and in children with specific underlying conditions.

Background: The Pharmacy Minor Ailment Service (PMAS) was introduced in the UK over 15 years ago for use in treating minor ailments and has been shown to be effective and acceptable by the public in reducing the burden on high-cost healthcare settings (such as general practice and emergency departments). This paper aims to review the use of a PMAS in the paediatric population. Methods: PMAS was established in a London Borough in 2013. Data were collected from 33 pharmacists and 38 GPs on demographics, service utilization and costs. Results: In total, 6974 face-to-face consultations by 4174 patients were provided by pharmacies as part of the PMAS over a 12-month period. Moreover, 57% of patients were children with fever, hay fever and sore throat, accounting for 58% of consultations. Only 2% were signposted to other services. Sixty-nine percent of patients reported being seen within 5 min and 96% of patients were seen within 10 min with high levels of satisfaction. Cost savings of over GBP 192,000 were made during the scheme. Conclusions: PMAS is a highly cost effective, accessible and acceptable service for children with minor illnesses.

Background: Granuloma annulare (GA) is a benign inflammatory dermatosis of unknown cause, of which generalised granuloma annulare (GGA) is a subtype that tends to be resistant to treatment. Various antibiotics have been used to treat GGA, the most recent being combination therapy with rifampicin, ofloxacin and minocycline (ROM). This study aims to explore the efficacy of antibiotics in treating GGA, and whether antibiotics may be useful in children with GGA. Materials and Methods: A systematic review of literature published from 1947 to 2017 was undertaken in order to evaluate the use of antibiotics in treating GGA. Data on characteristics of children with GGA were extracted and eligible studies were then qualitatively analysed. Results: Seven hundred and ninety (790) potential studies were identified, of which 16 were eligible for inclusion in the final analysis. Of these 16 studies, majority were case studies (n=9, 56.3%), with 2 case series (12.5%), 2 retrospective studies (12.5%) and 3 open-label prospective studies (18.8%). Main antibiotic treatments reported were either monthly combination therapy of rifampicin, ofloxacin and minocycline (ROM), or monotherapy with dapsone or doxycycline. Out of a total of 158 patients with GA, 72 patients (45.6%) were treated with antibiotics. Of the 72, 48.6% (n=35) of these patients had GGA while 4 were children; two with GA (2 with GGA), all of whom were treated with dapsone. Conclusion: There is paucity of evidence to support the use of antibiotics in the treatment of GGA in children. Although ROM has shown promising results in adults, more studies are needed to validate these findings in children. Keywords: granuloma annulare; generalised granuloma annulare; antibiotics; children; outcome

Pneumococcal conjugate vaccines (PCVs) are highly effective in preventing invasive pneumococcal diseases (IPD) in children, including those with sickle cell disease (SCD). A systematic review of the English literature published between 2000 and 2017 was undertaken to evaluate the serotype distribution, clinical presentation and outcomes of IPD in children with SCD in PCV programmes. We identified 475 potential studies and included 16 publications, involving 9438 children up to 22 years of age with SCD and 182 IPD episodes (prevalence, 1·9%. 95% confidence interval [CI], 1·7-2·2%). Septicaemia was the most prevalent clinical presentation (84/137; 61%) followed by lower respiratory tract infection (39/137; 29%) and meningitis (12/137, 9%). More than half the serotypes associated with IPD (88/148; 59·5%) were not included in the 13-valent PCV; of these, 54% (44/82) were due to serogroup 15. The crude case fatality rate was 11·5% (21/182 cases; 95% CI, 7·3-17·1%). Most cases of IPD in children with SCD were due to serotypes that are not included in any of the licensed PCVs. IPD in children with SCD remains associated with high morbidity and mortality, highlighting the importance of strict adherence to daily penicillin prophylaxis. Until a serotype-independent pneumococcal vaccine becomes available, higher-valent PCVs should include serogroup 15 to protect this highly vulnerable group of children.

Background: Paediatric Multisystem Inflammatory Syndrome temporally associated with SARS-CoV-2 (PIMS-TS), first identified in April 2020, shares features of both Kawasaki disease (KD) and toxic shock syndrome (TSS). The surveillance describes the epidemiology and clinical characteristics of PIMS-TS in the United Kingdom and Ireland. Methods: Public Health England initiated prospective national surveillance of PIMS-TS through the British Paediatric Surveillance Unit. Paediatricians were contacted monthly to report PIMS-TS, KD and TSS cases electronically and complete a detailed clinical questionnaire. Cases with symptom onset between 01 March and 15 June 2020 were included. Findings: there were 216 cases with features of PIMS-TS alone, 13 with features of both PIMS-TS and KD, 28 with features of PIMS-TS and TSS and 11 with features of PIMS-TS, KD and TSS, with differences in age, ethnicity, clinical presentation and disease severity between the phenotypic groups. There was a strong geographical and temporal association between SARS-CoV-2 infection rates and PIMS-TS cases. Of those tested, 14.8% (39/264) children had a positive SARS-CoV-2 RT-PCR, and 63.6% (75/118) were positive for SARS-CoV-2 serology. In total 44·0% (118/268) required intensive care, which was more common in cases with a TSS phenotype. Three of five children with cardiac arrest had TSS phenotype. Three children (1·1%) died. Interpretation: the strong association between SARS-CoV-2 infection and PIMS-TS emphasises the importance of maintaining low community infection rates to reduce the risk of this rare but severe complication in children and adolescents. Close follow-up will be important to monitor long-term complications in children with PIMS-TS. Funding: PHE

Background: Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS), first identified in April 2020, shares features of both Kawasaki disease (KD) and toxic shock syndrome (TSS). Methods: Public Health England initiated prospective national surveillance of PIMS-TS through the British Paediatric Surveillance Unit. Paediatricians were contacted monthly to report PIMS-TS, KD and TSS cases electronically and complete a detailed clinical questionnaire. Cases with symptom onset between 01 March and 15 June 2020 were included. Findings: There were 216 cases with features of PIMS-TS alone, 13 with features of both PIMS-TS and KD, 28 with features of PIMS-TS and TSS and 11 with features of PIMS-TS, KD and TSS, with differences in age, ethnicity, clinical presentation and disease severity between the three phenotypic groups. There was a strong geographical and temporal association between SARS-CoV-2 infection rates and PIMS-TS cases. Of those tested, 14·8% (39/264) children had a positive SARS-CoV-2 RT-PCR, and 63·6% (75/118) were positive for SARS-CoV-2 serology. In total 118 children (44·0%) required intensive care, which was more common in cases with a TSS phenotype: 89/216 (41·2%) with PIMS-TS only vs. 19/28 (67·9%) with PIMS-TS/TSS and 6/11 (54·5%) with PIMS-TS/KD/TSS. Three of five children with cardiac arrest had PIMS-TS/TSS phenotype. Three children (1·1%) died. Interpretation: The strong association between SARS-CoV-2 infection and PIMS-TS emphasises the importance of maintaining low community infection rates to reduce the risk of this rare but severe complication in children and adolescents. Close follow-up will be important to monitor long-term complications in children with PIMS-TS. Funding: PHE Declaration of Interests: None to declare. Ethics Approval Statement: PHE has legal permission under Regulation 3 of The Health Service (Control of Patient Information) Regulations 2002, to conduct national surveillance of communicable diseases in England and, as such, individual patient consent is not required. Public Health Wales, through the established order legislation, is required to conduct surveillance of communicable diseases in Wales and, as such, individual patient consent is not required. The surveillance protocol was approved by the Public Benefit and Privacy Panel for Health and Social Care in Scotland (Ref: 2021-0041, 19th May 2020).

Background: In December 2019, the infection caused by 2019 novel coronavirus (COVID-19) led to an outbreak in Wuhan, situated in the Hubei Province of China. Following this, there has been a rapid increase in the number of cases. On 12th March 2020, there were over 100,000 confirmed cases and almost 4,300 deaths worldwide. The clinical profile of children with COVID-19 is unknown due to the few number of cases reported. Currently, available data suggest they may have a milder form of illness. Methods: A review of the literature published from June 2019 to March 2020 was undertaken to evaluate the clinical presentation, management and outcomes of COVID-19 in in children. Data sources included EMBASE, MEDLINE, Cochrane library, ISI Web of Knowledge and references within identified articles. Results: We identified 303 potential studies, and 295 were excluded for reasons including duplicates, experimental studies and case reports. Eight studies were eligible for inclusion, including a total of 820 paediatric cases of COVID-19. Asymptomatic cases represented 14.3% (n = 117) of the total number of cases identified, and thus the remaining 85.7% (n = 703) experienced symptoms. Fever was the commonest symptom in 53.9% (n = 48) of cases, followed by cough in 39.3% (n = 35) of cases, and rhinorrhoea or pharyngeal congestion in 13.5% (n = 12) of cases. Diarrhoea and sore throats were less common symptoms, 7.9% (n = 7) and 9.0% (n = 8) respectively. Other symptoms, including fatigue, headache and dizziness were rare. Conclusion: Children are disproportionately affected by COVID-19 and are more likely to run a milder cause of illness following this infection compared to adults. This outbreak only started 3 months ago, therefore, further population wide studies are needed to validate these findings.

ObjectiveTo estimate the overall and infection-related neonatal mortality rate and the pathogens responsible using electronic death registrations.DesignRetrospective analysis of national electronic death registrations data.SettingEngland and Wales.PatientsNeonates aged Main outcome measuresOverall and infection-related mortality rate per 1000 live births in term, preterm (28–36 weeks) and extremely preterm (ResultsThe neonatal mortality rate during 2013–2015 (2.4/1000 live births; 5095 deaths) was 31% lower than in 2003–2005 (3.5/1000; 6700 deaths). Infection-related neonatal mortality rate in 2013–2015 (0.32/1000; n=669) was 20% lower compared with 2003–2015 (0.40/1000; n=768), respectively. Infections were responsible for 13.1% (669/5095) of neonatal deaths during 2013–2015 and 11.5% (768/6700) during 2003–2005. Of the infection-related deaths, 44.2% (296/669) were in term, 19.9% (133/669) preterm and 35.9% (240/669) extremely preterm neonates. Compared with term infants (0.15/1000 live births), infection-related mortality rate was 5.9-fold (95% CI 4.7 to 7.2) higher in preterm (0.90/1000) and 188-fold (95% CI 157 to 223) higher in extremely preterm infants (28.7/1000) during 2013–2015. A pathogen was recorded in 448 (67%) registrations: 400 (89.3%) were bacterial, 37 (8.3%) viral and 11 (2.4%) fungal. Group B streptococcus (GBS) was reported in 30.4% (49/161) of records that specified a bacterial infection and 7.3% (49/669) of infection-related deaths.ConclusionsOverall and infection-related neonatal mortality rates have declined, but the contribution of infection and of specific pathogens has not changed. Further preventive measures, including antenatal GBS vaccine may be required to prevent the single most common cause of infection-related deaths in neonates.

Background Pneumococcal conjugate vaccines (PCVs) are highly effective in preventing invasive pneumococcal disease (IPD), but deaths due to IPD still occur. We aimed to describe children who died of IPD since PCV introduction in England and Wales. Methods Public Health England conducts enhanced IPD surveillance in England and Wales. IPD cases in PCV-eligible children aged

ObjectiveTo estimate the contribution of infections to childhood deaths in England and Wales over a 3-year period.DesignRetrospective analysis of national electronic death registration data.SettingEngland and Wales.PatientsChildren aged 28 days to 15 years who died during 2013–15.Main outcome measuresThe proportion of children who died of infection compared with total deaths over 3 years; the main pathogens responsible for infection-related deaths in different age groups; comparison with similar data from 2003 to 2005.ResultsThere were 5088 death registrations recorded in children aged 28 days to ConclusionsBeyond the neonatal period, all-cause and infection-related childhood mortality rates have declined by 26% and 31%, respectively, over the past decade. However, infection continues to contribute to one in five childhood deaths.

Streptococcus pneumoniae is one of the commonest bacteria that cause morbidity and mortality in children and the elderly. The two extremes of age and individuals with underlying disease are particularly at risk of developing pneumococcal disease. The pneumococcus is responsible for a wide range of infectious diseases, ranging from mild, non-invasive infections such as otitis media and sinusitis, to more severe infections including pneumonia, septicemia, and meningitis. Despite the licensure of highly effective pneumococcal conjugate vaccines, the control of pneumococcal disease is still challenging. Here we describe the critical role of Streptococcus pneumoniae in public health.

Invasive infections caused by Streptococcus pneumoniae, such as pneumonia, meningitis, and bacteremia, are a major cause of morbidity and mortality in young children and older adults worldwide. The introduction of pneumococcal conjugate vaccines into national childhood immunization programs has led to large and sustained reductions in the incidence of invasive pneumococcal disease across all age groups. Here we describe the epidemiology and biostatistics of pneumococcal disease as well as the impact of vaccination on the burden of pneumococcal disease globally.

We describe a case of cerebrospinal fluid pleocytosis in a previously well infant after his first immunisation with the multicomponent meningococcal serogroup B and advice clinicians to be cautious with the interpretation of CSF findings in children post Meningococcal B vaccination until clearer guidelines are available Keywords: meningococcal B vaccine - cerebrospinal fluid pleocytosis - inflammatory response - infant.

Streptococcus pneumoniae is one of the commonest bacteria that cause morbidity and mortality in children and the elderly. The two extremes of age and individuals with underlying disease are particularly at risk of developing pneumococcal disease. The pneumococcus is responsible for a wide range of infectious diseases, ranging from mild, non-invasive infections such as otitis media and sinusitis, to more severe infections including pneumonia, septicemia, and meningitis. Despite the licensure of highly effective pneumococcal conjugate vaccines, the control of pneumococcal disease is still challenging. Here we describe the critical role of Streptococcus pneumoniae in public health.

Invasive infections caused by Streptococcus pneumoniae, such as pneumonia, meningitis, and bacteremia, are a major cause of morbidity and mortality in young children and older adults worldwide. The introduction of pneumococcal conjugate vaccines into national childhood immunization programs has led to large and sustained reductions in the incidence of invasive pneumococcal disease across all age groups. Here we describe the epidemiology and biostatistics of pneumococcal disease as well as the impact of vaccination on the burden of pneumococcal disease globally.

Teicoplanin is now increasingly used as a first-line prophylactic therapy for major surgical procedures, treatment of methicillin-resistant Staphylococcus aureus infections and for those with reported penicillin allergy. Teicoplanin is rarely associated with anaphylaxis and there is limited information on the prevalence of teicoplanin-induced perioperative anaphylaxis. Here, we describe a case of a 12-year-old child with teicoplanin-induced anaphylaxis peri-operatively.

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare idiopathic inflammatory disease that affects mainly children and young adults, resulting in significant morbidity especially if not diagnosed early. The clinical signs and symptoms are nonspecific, with a consequential delay in diagnosis. Radiological and histopathological criteria are important for its definition. Two cases of CRMO are reported, highlighting the diagnostic challenge and demonstrating the importance of timely investigations.

Introduction Transverse myelitis (TM) is a neurological disorder causing acute cord injury as a result of acute inflammation, and it is often associated with infectious or autoimmune disease. 20% of all cases of TM occur in children. Since 2015, an outbreak of Zika Virus infection (ZiKV) has been reported in over 30 countries. Emerging evidence suggest ZikV causes a spectrum of neurologic diseases. However, its association with TM, especially in children, is not well described. Methods We undertook a systematic review of the English literature published from 1947 to August 2017 to evaluate the risk factors, distribution, pathogenesis, clinical presentation, management and outcomes of TM following Zika virus infection. Data sources included MEDLINE, EMBASE, Cochrane library, and references within identified articles. We also searched the papers using the ISI web of knowledge, to identify relevant articles and conference proceedings. Results We identified 102 potential studies, of which 9 were duplicates and 89 were excluded on the basis of title and abstracts. Of the 4 eligible studies [5–8], there were 6275 with suspected ZiKV in all age groups. 695 cases were confirmed ZiKV either by RT-PCR in plasma, CSF and urine, ELIZA or MRI while excluding other aetiologies. There were 11 (1.6%) cases of TM. Among 3 studies reporting clinical characteristics and outcome, the mean age was 23 years (Range 15–43) and 63% (n=5/8) of cases were male. 40% (n=4/10) required admission to the ITU, with no reported case fatality. Conclusions and clinical implications Complications from ZiKV, although uncommon, may be severe. With international spread, clinicians need to be aware that ZiKV may be associated with TM. As only 10% of cases were children, standardising the collection and reporting for individual cases across regions and countries would further allow meaningful analysis of the data collected, enabling monitoring of trends over time.

Introduction Hypoglycaemia is a common reason for admission for term and near term infants to neonatal units (NICU). Early recognition and management of neonatal hypoglycaemia has important clinical and economic consequences. In our hospital neonatal blood sugar is measured using both a standard ‘blood gas analyser’ and a branded hand-held glucose measurement device (HHGMD), and there is tendency to trust the HHGMD result in preference to blood gas result. Aim We aimed to compare the blood glucose results of both the blood gas analyser and HHGMD on same blood sample at same time to ensure no significant difference was detected. Methods Blood sugar results in individual neonates were recorded using both the HHGMD and blood gas analyser. We obtained basic demographics and route of sample for all babies. A quality control measure for the HHGMD was carried out most days by the biochemist and a calibration of the blood gas machine was done daily. Data are mainly descriptive; categorical variables are described as percentages with binomial 95% confidence intervals (95% CI). Wilcoxan Matched-Pairs Signed Ranks Test was used to test for statistical significance. Results There were 118 separate paired blood gas and HHGMD results logged from 32patients in the 8 week period of this study, of which 53% (n=17/32) were term and 47% (n=15/32) were preterm babies. One third (67%, n=79/118) of these samples were preterm. Only 0.3% (n=4/118) samples were taken from babies not currently admitted to NICU. 3% (n=4) of cases both HHGMD/blood gas results were same while in 6% (n=7) of cases HHGMD result was lower than the blood gas result. However in 107 cases HHGMD result was higher than blood gas result with a mean difference of 1.07 mmol (95% CI 0.94–1.15, p Conclusions A mean difference of approximately 1 mmol/L glucose between both measurement devices on the same blood sample has potential clinical and economic significance particularly in our population where hypoglycaemia and subsequent neonatal unit admission is common. A more robust way of standardising glucose measurement is required in this cohort of babies.

Introduction Climate change refers to long-term shifts in weather conditions and patterns of extreme weather events, with recent earthquakes, natural disasters, there is epidemic and increase in many paediatric infectious diseases (PID) worldwide, including some newly-circulating ones, such as Zika virus and arbo-viruses in North America and the Caribbean, Ebola and Cholera outbreak in Africa, SIRS in middle east e.t.c. This reflects the combined impacts of rapid demographic, environmental, social, technological and other changes in our ways of living. Aims We reviewed the available scientific evidences of the impact of recent climate change on PID and also examines the observed and predicted impacts of changes in major climate variables on pathogen, host, and transmission of PID in order to estimate the future burden of infectious diseases on children. Methods We reviewed published and unpublished literature on climate change and PID. The data were mainly descriptive and we used predictive analytical modelling to assess the future burden. Findings We observed evidence of associations between climatic conditions and PID in children with different modality of transmission. The responsible agents identified were viruses, bacteria, protozoa and parasites, with various adaptations in the host. Increasing temperature was the most important contributing factor when compared with other natural disasters. There is a global resurgence of hitherto controlled diseases and the emergence of new ones with redistribution of existing infectious diseases due to an unstable climate. Many of the most common infectious diseases, and particularly those transmitted by vectors, are highly sensitive to climate variation. New and resurgent vector-borne communicable diseases, including arbo-viruses, such as dengue, Zika and Ebola, and malaria are evident widely. Other infectious diseases, such cholera have shown increased outbreaks due to elevated temperature and flooding with the resultant displacement of affected people. Conclusions Changes in infectious disease transmission patterns are a likely major consequence of climate change. There is need for a better understanding of the causal relationships, in order to predict the future impacts of this on children’s health. In addition, paediatrician are likely to see an increasing number of cases due to adverse effects of climate change. An international collaborative effort with an integrated model of care is therefore required.

Introduction The introduction of pneumococcal conjugate vaccines (PCV) was associated with reduction in incidence of invasive pneumococcal disease (IPD) especially IPD caused by the vaccine serotypes. Its impact on meningitis in the United Kingdom has not been assessed. Methods Public Health England conducts enhanced surveillance for IPD and provides a national reference service for serotyping pneumococcal isolates in England and Wales. Data were extracted for isolates from confirmed IPD cases between 1 st July 2000 and 30th June 2016, covering the 2000/01 to 2015/16 epidemiological years. Incidence rate ratio (IRR) and case fatality rate (CFR) were calculated. Multivariable logistic regression was used to calculate the odds of meningitis and assessed its association with death. Results There were 80 313 laboratory-confirmed IPD cases over the 16 year surveillance period, including 4160 cases (4.9%) with meningitis. Of the 4108 with reported age, 1611 (39.2%) cases were reported in children aged PCV7 introduction in September 2006 had no impact on the overall incidence of pneumococcal meningitis (0.55/100,00 during 2000/01–2005/06 vs 0.56/100,000 during 2008/09–2009/10) because of serotype replacement disease. PCV7 replacement with PCV13 in April 2010, however, led to a 48% (95% CI: 38%–62%) reduction in pneumococcal meningitis incidence by 2015/16, whilst meningitis cases due to non-PCV13 serotypes remained static. The overall CFR was 17.5% (631/3,611, increasing from 10.7% (150/1408) in Conclusions The impact of PCV on pneumococcal meningitis has been less prominent than for other IPD presentations and case fatality remains high; a different strategy is, therefore, required to reduce the burden and outcomes of pneumococcal meningitis.

Introduction Invasive pneumococcal disease (IPD) is the leading cause of morbidity and mortality in children with sickle cell disease (SCD). 7-valent pneumococcal conjugate vaccine (PCV7) was first introduced in 2000 in US and at various times in other countries. It was replaced by 13-valent pneumococcal conjugate vaccines (PCV13) in 2010. This PCV are highly effective in preventing IPD in children with SCD. The risk of IPD has not been systematically assessed in children with SCD since the introduction of PCV. Methods We undertook a systematic review of the English literature published from 2000 to October 2017 to evaluate the risk factors, serotype distribution, clinical presentation and outcomes of IPD in children with sickle cell disease. Data sources included MEDLINE, EMBASE Cochrane library, and references within identified articles. Results We identified 475 potential studies, of which 66 were duplicates. A further 299 were excluded on the basis of title and abstracts and another 94 studies did not meet eligibility criteria on full-text screening. We included 16 publications involving 11 383 children less than 21 years-olds with SCD. A total of 161 (1.4%) IPD was identified: 147 homozygote for haemoglobin S (HbSS), 10 double heterozygote for haemoglobin S and C (HbSC) and 4 others. Among the nine studies reporting clinical presentation, septicaemia was the commonest (n=69/108; 63.8%) followed by pneumonia (n=20/108; 18.5%). The serotypes associated with IPD in SCD were mainly non-PCV13 (n=117/133; 88%), of which more than a quarter was due to serogroup 15A/B/C (n=34/117; 29%,). Serotype 23 F (n=6/16, 37.5%) and 7 F (n=4/16; 25%) were the main vaccine serotypes. Majority were sensitive to penicillin and ceftriaxone. The crude case fatality rate was 11.2% (n=18/161). Conclusions and clinical implications This report demonstrates the effectiveness of conjugate vaccines to reduce the rate of IPD in children with SCD. However, these children remain at increased risk and are also more likely to die of their infection compared to their peers without SCD. Most IPD cases are now due to serotypes not covered by PCV13. Therefore better prevention strategies are needed to reduce the overall burden IPD in children with SCD.

Background There are well established gender, ethnicity and socio-economic differences in the incidence and prevalence of epilepsy, autism and allergy sensitisation. 1,2,3,4 Less is known about these differences within an ED setting. Simons et al. noted a gender disparity with more boys presenting to ED with sickness, head injury and falls than girls, 5 but this was not statistically significant. Aim To establish the role of gender, ethnicity, and social deprivation as factors associated with presentation to ED in children under 5. Methods Study design: A retrospective study was conducted on a routine operational data set of basic demographic data collected from a large district general hospital. Sample: Paediatric ED data 01/04/2015–31/03/2016 for children below 5 years. Levels of deprivation: 2015 Index of Multiple Deprivation. 6 Office for National Statistics (ONS) mid-year data used for denominator. Analysis: Descriptive analysis. Rate ratios were calculated for each age. Deciles were obtained for each postcode using 2015 Index of Multiple Deprivation data. Results Of the 19 267 under 16 year-olds paediatric attendances, 10 925 (56.7%) were less than 5 years of age. Of these, 6227 (57%) were male; M:F ratio in ED 1.33 cf. 1.05 local population. The proportion of the population attending ED decreased with age. Presentation rate was consistently higher in males than in females, but the gender gap decreased with age. Ethnicity was recorded for 89.9% of attendances. The gender difference in presentations was greatest for the black population (622 males vs 392 females, M:F ratio 1.59 cf. 1.01 population). At extremes of IMD, the rates of presentation were lowest (4.8% decile 1, 7.3% decile 10) and gender gap is least pronounced (male:female rate ratio 1.13 decile 1, 1.26 decile 10, greatest 1.39 decile 4. Conclusions and clinical implications More males attend ED than females in all ages and ethnic groups, with greatest gender disparity in the black population. In addition, it appears that the least and most deprived are least likely to present to ED. This study emphasises the utility of operational data for epidemiological research at local level and supports the need to further explore clinical and sociological reasons for differences in gender related attendances. References . Levine R, Kilbourne B, Rust G, Langston M, Husaini B, Gittner L, Sanderson M, Hennekens C. Social determinants and the classification of disease: Descriptive epiidemiology of selected socially mediated disease constellations. PLoS One 2014;9(11). . Retico AG Alessia, Tancredi R, Cosenza A, Apicella F, Narzisi A, Biagi L, Tosetti M, Muratori F, Calderoni S. The effect of gender on the neuroanatomy of children with autism spectrum disorders: A support vector machine case-control study. Mol Autism2016;7(5). . Pickrell W, Lacey A, Bodger O, Demmler J, Thomas R, Lyons R, Smith P, Rees M, Kerr M. Epilepsy and deprivation, a data linkage study. Epilepsia2015;56(4):585–91. . Joseph C, Zoratti E, Ownby D, Havstad D, Nicholas C, Nageotte C, Misiak R Enbeg, Ezell R, Johnson C. Exploring racial differences in IgE- mediated food allergy in the WHEALS birth cohort. Ann Allergy Asthma Immunol2016;116(3):219- 224. . Simons J. Young children in AE24(7). . Department for Communities and Local Government. The English indices of deprivation 2015;2015.

Introduction Granuloma anulare (GA) is a benign inflammatory dermatosis of unknown cause. The Generalised granuloma annulare (GGA) is a subtype of which tends to be resistant to treatment. Various antibiotics have been proposed as a potential therapy for GGA, the most recent being combination therapy with Rifampicin, Ofloxacin and Minocycline (ROM). Aims This study aim to explore the efficacy of antibiotics in treating GGA, and whether antibiotics may be useful in Children. Methods We undertook a systematic review of English literature published from August 1947 to July 2017 to evaluate the efficacy of antibiotics in treating GGA and extract relevant data in children less than 18 years. Data sources included MEDLINE, EMBASE, Cochrane library, and references of identified articles. Results We identified 790 potential studies, of which 229 were duplicates. 541 were excluded on the basis of title and abstracts. Of the 20 eligible studies included in the final analysis. Studies were from USA (40%, n=8), Europe (35%, n=7), Asia (25%, n=5). Majority were case studies (65%, n=13), case series (10%, n=2), cohort studies (10%, n=2) and Open label prospective studies (15%, n=3; 2 on ROM therapy and 1 of dapsone). There were 113 treated patients, 60% (n=68) were female. Children constitute 14% (n=16/113), with age range 2–18 years, treated with antibiotics, of which 3 were GGA and 13 Non-GGA (i.e 8 Localised GA, 2 perforating GA, and 3 subcutaneous GA). Main antibiotic treatments reported were either the monthly combination therapy given as ROM, or single therapy of dapsone or doxycycline/Minocycline. There was a good response in Non-GGA in Children with only 15% recurrence rate while only 33% achieve remission in the GGA. Unlike adults, no side effects reported in Children. Strength and limitations Our results highlight the strengths of combining outcomes of rare events. The lack randomised controlled trials, however, was a significant limitation. In addition, none of the literature looking at ROM combination therapy were in Children. Conclusion There is paucity of evidence to support the use of antibiotics in the treatment of GGA in children. Although, recently ROM as shown promising results in adults, more studies are needed to validate this findings. References . Garg S, Baveja S. Monthly rifampicin, ofloxacin, and minocycline therapy for generalised and localised granuloma annulare. Indian J Dermatol Venereol Leprol2015;81(1):35–39. . Simpson B, Foster S, Ku JH, Simpson EL, Ehst BD. Triple antibiotic combination therapy may improve but not resolve granuloma annulare. Dermatologic Therapy2014;27(6):343–347. . Mahmood T, Mansouri B, Menter A. Successful treatment of generalised granuloma annulare with adalimumab. Clin Exp Dermatol2015;40(5):537–539. . Garg S, Baveja S. Generalised granuloma annulare treated with monthly rifampicin, ofloxacin, and minocycline combination therapy. Indian J Dermatol2013;58(3):197–199. . Successful treatment of recalcitrant disseminated granuloma annulare with minocycline, ofloxacin, and rifampin combination therapy. Journal of the American Academy of Dermatology2013;68(4):AB64. http://dx.doi.org/10.1016/j.jaad.2012.12.268 Accessed 8/20/2017 3:18:52 PM. . Marcus DV, Mahmoud BH, Hamzavi IH. Granuloma annulare treated with rifampin, ofloxacin, and minocycline combination therapy. Arch Dermatol2009;145(7):787–789. . Steiner A, Pehamberger H, Wolff K. Sulfone treatment of granuloma annulare. Journal of the American Academy of Dermatology1985;13(6):1004–1008. http://dx.doi.org/10.1016/S0190-9622(85)70253-8 [Accessed: 8/19/2017, 11:06:43 AM] . Boyd AS. Granuloma annulare responsive to oral calcitriol. Int J Dermatol2012;51(1):120–122. . Martin-Saez E, Fernandez-Guarino M, Carrillo-Gijon R, Munoz-Zato E, Jaen-Olasolo P. Efficacy of dapsone in disseminated granuloma annulare: A case report and review of the literature. Actas Dermo-Sifiliograficas (English ed.) 2008;99(1):64–68. http://dx.doi.org/10.1016/S1578-2190(08)70196-3 [Accessed: 8/16/2017 1:20:39 PM]. . Gualco F, Zaccaria E, Drago F, Rebora A. Interstitial granuloma annulare and borreliosis: A new case. Journal of the European Academy of Dermatology and Venereology 2007;21(8):1117–1118. . Kiremitci U, Karagulle S, Topcu E, et al.Generalised granuloma annulare resolving to anetoderma. Dermatol Online J 2006;12(7):16. . Altomare GF, Frigerio E, Capella GL. Disseminated granuloma annulare: Effectiveness of sulphone treatment. G Ital Dermatol Venereol 2003;138(5):419–424. . Saied N, Schwartz RA, Estes SA. Treatment of generalised granuloma annulare with dapsone. Arch Dermatol 1980;116(12):1345–1346. . Cheng Y, Tsai W, Chuang F, et al. A retrospective analysis of 44 patients with granuloma annulare during an 11-year period from a tertiary medical centre in south Taiwan. Dermatologica Sinica 2016;34(3):121–125. Accessed 8/20/2017 3:19:30 PM. doi: http://dx.doi.org/10.1016/j.dsi.2015.11.002. . Yun JH, Lee JY, Kim MK, et al. Clinical and pathological features of generalised granuloma annulare with their correlation: A retrospective multicenter study in Korea. Ann Dermatol 2009;21(2):113–119. . Kozic H, Webster GF. Treatment of widespread granuloma annulare with adalimumab: A case report. J Clin Aesthet Dermatol 2011;4(11):42–43. . Duarte A, Mota A, Pereira M, Baudrier T, Azevedo F. Generalised granuloma annulare: Response to doxycycline. Journal of the European Academy of Dermatology and Venereology 2009;23(1):84–85. . Kovich O, Burgin S. Generalised granuloma annulare. Dermatology Online Journal 2005;11(4). . Ashida M, Katayama I, Kamo T. Oral minocycline improved generalised granuloma annulare possibly triggered by spider-bite (arachnidism). Nishi Nihon Hifuka 2004;66(3):246–250. . Successful treatment of generalised granuloma annulare with amoxicillin/clavulanic acid. J Am Acad Dermatol 74(5):AB73.

Introduction Since 2015, an outbreak of Zika Virus infection (ZiKV) has been reported in over 30 countries. Emerging evidence suggest ZikV causes a spectrum of neurologic diseases both directly and by secondary autoimmunity. In pregnancy, ZiKV is a well-known cause of congenital brain abnormalities, including microcephally, and has been linked with Guillain-Barre syndrome. However, its association with seizures in children is not well described. Methods We undertook a systematic review of the English literature published from 1947 to August 2017 to evaluate the risk factors, epidemiology, clinical presentation, management and outcomes of seizure following Zika virus infection in children less than 18 years. Data sources included MEDLINE, EMBASE, Cochrane library, and references within identified articles. We also searched the papers using the ISI web of knowledge, to identify relevant articles and conference proceedings. Results We identified 140 potential studies, of which 8 were duplicate and 122 were excluded on the basis of title and abstracts. A further 2 additional studies did not meet eligibility criteria. Of the 8 eligible studies [3–10], there were 215 with confirmed ZiKV in children less than 18 years by either RT-PCR in plasma, CSF and urine, EEG and MRI while excluding other etiologies. 20% (n=44) cases of had seizure. Among 5 studies reporting clinical characteristics and outcome, the mean age was 5 months (Range 1–8 months) and 75% (n=12/16) of cases were female. All had abnormal neuroimaging (n=44) and responded to anti-convulsant therapy, with no reported mortality. Conclusions and clinical implications Complications from ZiKV, although uncommon, may be severe. With international spread, clinicians need to be aware that ZiKV may be associated with seizures in children. Therefore, standardising the collection and reporting for individual cases across regions and countries would further allow meaningful analysis of the data collected, enabling monitoring of trends over time.

Introduction Since 2015, an outbreak of Zika Virus infection (ZiKV) has been reported in over 30 countries. Emerging evidence suggest ZikV causes a spectrum of neurologic diseases both directly and by secondary autoimmunity. In pregnancy, ZiKV is a well-known cause of congenital brain abnormalities, including microcephaly.1 It has also been linked with Guillain-Barre syndrome.2 However, its association with meningoencephalitis is not well described, especially in children. Methods We undertook a systematic review of the English literature published from 1947 to August 2017 to evaluate the risk factors, distribution, pathogenesis, clinical presentation, management and outcomes of encephalitis following Zika virus infection. Data sources included MEDLINE, EMBASE, Cochrane library, and references within identified articles. We also searched the papers using the ISI web of knowledge, to identify relevant articles and conference proceedings. Results We identified 167 potential studies, of which 16 were duplicates and 140 were excluded on the basis of title and abstracts (figure 1). There were 9784 with suspected ZiKV in all age groups. 1411 cases were confirmed ZiKV either by RT-PCR in plasma, CSF and urine, ELIZA or MRI. There were 26 (1.8%) cases of meningoencephalitis. Among eight studies reporting clinical characteristics and outcomes of 16 cases, the mean age was 43 years (Range 19–81) and 75% (n=12) of cases were male. 63% (n=10) of the cases required admission to ITU, with a crude case fatality rate of 12% (n=2). Conclusions and clinical implications Complications from ZiKV, although uncommon, may be severe. With international spread, clinicians need to be aware that ZiKV may be associated with meningoencephalitis. Although our review found a paucity of evidence of Zika virus associated meningoencephalitis in children, standardising the collection and reporting for individual cases across regions and countries would further allow meaningful analysis of the data collected, enabling monitoring of trends over time.

Background Pneumococcal conjugate vaccines (PCV) are highly effective in preventing invasive pneumococcal disease (IPD) but deaths due to IPD still occur. We aimed to describe children who died of IPD since PCV introduction in England and Wales. Methods Public Health England conducts enhanced IPD surveillance in England and Wales. IPD cases in PCV-eligible children aged Results During the 8 year period, there were 3146 IPD cases and 150 IPD-related deaths (case fatality rate, 4.8%). Overall, 132 isolates from fatal cases were serotyped (88%) and 35 distinct serotypes were identified, with no serotype predominance. Most deaths occurred in Conclusions Most fatal IPD cases are currently not vaccine-preventable. Additional strategies will be required to reduce childhood pneumococcal deaths in countries with established pneumococcal vaccination programmes.

Background Researchers advise caution with use of new health apps as they may not incorporate robust scientific evidence or support behavioural change. A recent review (1) notes increased use of Vitamin D purchased supplements, with suggestion that a specific app be designed to help consumers decide on need for supplementation, followed by appropriate dose and product purchase advice, with decision further facilitated by discussion with health professionals. With possibly a national level role for Public Health, the NHS and even governments to support development of such informed electronic systems. Aim To identify and evaluate Vitamin D apps currently available for public use. Methods Vitamin D apps identified on iOS and Android mobile smart-phones systems were categorised based on proposed aims of app. An adapted mobile applications rating scale, MARS (2), was then used to score the apps (subset category relevant to health care provision) for validated information quality criteria. Results 51 and 21 apps identified on the I-phone iOS and Android smart-phones respectively, available as a free or chargeable resource. Categories included: safe sun exposure (n=13; 6 respectively), nutritional advice and support (n=19; 7), Vitamin D levels testing, tracking and for discussion with doctor (n=6; 2). Some designed for USA leisure industry (safe sun exposure, exercise, relaxation treatments) (n=6; 1), for commercial use (n=3; 1), with three iOS apps for educational utility (eg. chemistry, architecture). One iOS app was designed by a research institute targeting improvement in child health. Of the total 9 apps evaluated, MARS Information Quality scores ranged between 8 – 26. With the app for use exclusively by clinicians providing osteoporosis care scoring 26; and the child health app assigned score of 22. The remaining apps (n=7) focused mainly on advice to improve dietary intake. One commercial app available on both iOS and Android systems (MARS 20, 22 respectively) targeted consumers with chronic conditions and on Vitamin D. Conclusion There were no high quality Vitamin D apps identified for use by consumers to help decision on routine Vitamin D nutritional supplementation.

Background Pneumococcal conjugate vaccines (PCVs) are highly effective in preventing pneumococcal invasive disease (IPD) due to serotypes included in the vaccines. The risk of vaccine-type IPD in immunised children (i.e. vaccine failure) has not been systematically assessed in countries with established PCV programmes. Methods We undertook a systematic review of the English literature published from January 2000 to April 2016 to evaluate the vaccine schedule, risk factors, serotype distribution, clinical presentation and outcomes of vaccine failure in children vaccinated with the 7-valent (PCV7), 10-valent (PCV10), and 13-valent (PCV13) vaccines. Data sources included MEDLINE, EMBASE, Cochrane library, and references within identified articles. Results We identified 1742 potential studies and included 20 publications involving 7584 participants in children aged ⩽5 year-olds: 5202 received 2 doses followed by a booster in 10 studies, (68.6%), 64 (0.8%) received 3 doses without a booster in 2 studies, and 2318 received a 3 + 1 schedule (30.6%) in 8 studies. A total of 159 vaccine failure cases were identified, representing 2.1% [95% CI: 1.8–2.4%] of the reported IPD cases. Most studies did not report clinical characteristics or outcomes. Among eight studies reporting comorbidities, 33/77 patients (42.9%) had an underlying condition. The main serotypes associated with vaccine failure were 19F (51/128 cases with known serotype; 39.8%), 6B (33/128; 25.8%), and 4 (10/128; 7.8%). Only five studies reported patient outcomes, with a crude case fatality rate of 2.4% (2/85; 95%CI: 0.3–8.5%). Conclusion Pneumococcal conjugate vaccines have been implemented in national immunisation programmes for more than a decade, yet there are only a few studies reporting vaccine failure. PCV failure is rare, irrespective of vaccine or schedule. Co-morbidity prevalence was high amongst vaccine failure cases but case fatality rate was relatively low. There is a need for more systematic reporting vaccine failure cases in countries with established pneumococcal vaccination programmes.

Introduction: Dengue virus (DENV) is one of the most common arbovirus diseases, with a wide spectrum of presentation. Spinal cord involvement in dengue infection (DF) is rare. However, the risk of transverse myelitis (TM) following Dengue has not been systematically assessed. Methods: We undertook a systematic review of published English literature from January 1974 to December 2017 to assess risk of TM and outcomes following DF. Data sources included EMBASE, MEDLINE, Cochrane library, ISI web of knowledge, conference proceedings and references within identified articles. Results: We identified 242 potential studies, 62 were duplicates. A further 136 were excluded on the basis of title and abstract and 19 studies did not meet the eligibility criteria on full text screening. We included 25 publications involving 2672 cases of DF. A small proportion (10.8%, (289/2672)) had neurological complications, of which 2.3% (61/2672) was TM. For articles reporting epidemiological data, the neurological complication was twice in males compared to female 67.7% (130/192) vs. 32.7% (62/192) and 1.5-fold increase TM for males 59.3% (32/54) vs 40.7% (22/54). The mean age at presentation was 33.1years (range 0.75–61), with onset at 11.7days. The method of diagnosing TM due to DF was mainly IgM seropositivity 92% (n = 23/25) and the commonest treatment modality was steroid 78.3% (n = 18/23). Only half had full recovery 50.8% (n = 31/61). There was no mortality following dengue, however, the crude case fatality rate following TM was 3.3% (n = 2/61). Conclusion: This review highlights the risk of TM following dengue. Although neurological complications are rare, especially TM, once set in, it is associated with a significant morbidity.

Background: The 7-valent and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13, respectively) are highly effective in preventing invasive pneumococcal disease (IPD) caused by vaccine serotypes. Vaccine failure (vaccine-type IPD after age-appropriate immunization) is rare. Little is known about the risk, clinical characteristics, or outcomes of PCV13 compared to PCV7 vaccine failure. Methods: Public Health England conducts IPD surveillance and provides a national reference service for serotyping pneumococcal isolates in England and Wales. We compared the epidemiology, rates, risk factors, serotype distribution, clinical characteristics, and outcomes of IPD in children with PCV13 and PCV7 vaccine failure. Results: A total of 163 episodes of PCV failure were confirmed in 161 children over 8 years (4 September 2006 to 3 September 2014) in 10 birth cohorts. After 3 vaccine doses, PCV7 and PCV13 failure rates were 0.19/100000 (95% confidence interval [CI],.10-.33 [57 cases]) and 0.66/100000 (95% CI,.44-.95 [104 cases]) vaccinated person-years, respectively. Children with PCV13 failure were more likely to be healthy (87/105 [82.9%] vs 37/56 [66.1%]; P =.02), present with bacteremic lower respiratory tract infection (LRTI) (61/105 [58.1%] vs 11/56 [19.6%]; P