COVID-19 deaths in children and young people in England, March 2020 to December 2021: An active prospective national surveillance study.

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 <20 years who died within 100 days of laboratory-confirmed SARS-CoV-2 infection between 01 March 2020 and 31 December 2021 in England were followed up in detail, using national databases, surveillance questionnaires, post-mortem reports, and clinician interviews. 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 <20 years, with an infection fatality rate of 0.70/100,000 SARS-CoV-2 infections in this age group estimated through real-time, nowcasting modelling, and a mortality rate of 0.61/100,000. Limitations include possible under-ascertainment of deaths in CYP who were not tested for SARS-CoV-2 and lack of direct access to clinical data for hospitalised CYP. 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.

Effect of Pneumococcal Conjugate Vaccines on Pneumococcal Meningitis, England and Wales, July 1, 2000-June 30, 2016.

We describe the effects of the 7-valent (PCV7) and 13-valent (PCV13) pneumococcal conjugate vaccines on pneumococcal meningitis in England and Wales during July 1, 2000-June 30, 2016. Overall, 84,473 laboratory-confirmed invasive pneumococcal disease cases, including 4,160 (4.9%) cases with meningitis, occurred. PCV7 implementation in 2006 did not lower overall pneumococcal meningitis incidence because of replacement with non-PCV7-type meningitis incidence. Replacement with PCV13 in 2010, however, led to a 48% reduction in pneumococcal meningitis incidence by 2015-16. The overall case-fatality rate was 17.5%: 10.7% among patients <5 years of age, 17.3% among patients 5-64 years of age, and 31.9% among patients >65 years of age. Serotype 8 was associated with increased odds of death (adjusted odds ratio 2.9, 95% CI 1.8-4.7). In England and Wales, an effect on pneumococcal meningitis was observed only after PCV13 implementation. Further studies are needed to assess pneumococcal meningitis caused by the replacing serotypes.

Risk of invasive pneumococcal disease in children with sickle cell disease in the era of conjugate vaccines: a systematic review of the literature.

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.

Cerebrospinal Fluid Pleocytosis following Meningococcal B vaccination in an Infant.

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.

Childhood Deaths Attributable to Invasive Pneumococcal Disease in England and Wales, 2006-2014.

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 <5 years (born since 4 September 2004 and diagnosed between 4 September 2006 and 3 September 2014) were actively followed up by postal questionnaires and, for fatal cases, detailed information was requested prospectively from multiple sources. 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 children aged <1 year (88/150 [59%]) and 1-year-olds (36/150 [24%]). One-third (53/150 [35%]) had a known risk factor for IPD. Clinical presentation varied with age but not by serotypes in the different conjugate vaccines. Meningitis was diagnosed in nearly half the fatal cases (71/150 [47%]). The IPD-related mortality rate declined after 7-valent PCV introduction from 1.25/100000 children in 2006-2007 to 0.60/100000 in 2009-2010, with a further reduction following 13-valent PCV introduction from April 2010 to 0.39/100000 in 2013-2014 (14 deaths; incidence rate ratio, 0.31 [95% confidence interval, .16-.61]; P = .0003), when most deaths were due to nonvaccine serotypes or in neonates. 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 programs.

Characteristics and Serotype Distribution of Childhood Cases of Invasive Pneumococcal Disease Following Pneumococcal Conjugate Vaccination in England and Wales, 2006-2014.

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 < .001), and develop empyema (41/61 [67.2%] vs 1/11 [9.1%]; P < .001) compared to PCV7 failures. Serotypes 3 (n = 38 [36.2%]) and 19A (n = 30 [28.6%]) were responsible for most PCV13 failures. Six children died (4% [95% CI, 1%-8%]), including 5 with comorbidities. Conclusions: PCV failure is rare and, compared to PCV7 serotypes, the additional PCV13 serotypes are more likely to cause bacteremic LRTI and empyema in healthy vaccinated children.

Community Pharmacy Minor Ailment Service (PMAS): An Untapped Resource for Children and Their Carers.

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.

Retrospective analysis of neonatal deaths secondary to infections in England and Wales, 2013-2015.

OBJECTIVE: To estimate the overall and infection-related neonatal mortality rate and the pathogens responsible using electronic death registrations. DESIGN: Retrospective analysis of national electronic death registrations data. SETTING: England and Wales. PATIENTS: Neonates aged <28 days. MAIN OUTCOME MEASURES: Overall and infection-related mortality rate per 1000 live births in term, preterm (28-36 weeks) and extremely preterm (<28 weeks) neonates; the contribution of infections and specific pathogens; comparison with mortality rates in 2003-2005. RESULTS: The 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. CONCLUSIONS: Overall 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.

Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS): Prospective, national surveillance, United Kingdom and Ireland, 2020.

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 antibodies. 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.

A Rare Case of Juvenile Idiopathic Arthritis following a Ruptured Baker's Cyst in a Toddler.

A Baker's cyst is usually an incidental finding in adults being investigated for a joint arthropathy, and its rupture preceding the diagnosis of juvenile idiopathic arthritis (JIA) is rare in children. Here, we describe a case of a 4-year-old girl who presented to the Emergency Department with right calf pain, swelling, and no preceding history of trauma. MRI confirmed a ruptured Baker's cyst with inflammatory arthropathy alongside an extensive synovial proliferation throughout the knee joint with large joint effusions and associated soft tissue oedema tracking superiorly and inferiorly along the medial head of gastrocnemius and anteriorly along the tibia. Further investigations revealed bilateral uveitis consistent with a diagnosis of juvenile idiopathic arthritis.

The Dilemma of Chronic Recurrent Multifocal Osteomyelitis.

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.

Catatonia as a presentation of autism in a child: a case report.

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.

Infection is associated with one in five childhood deaths in England and Wales: analysis of national death registrations data, 2013-15.

OBJECTIVE: To estimate the contribution of infections to childhood deaths in England and Wales over a 3-year period. DESIGN: Retrospective analysis of national electronic death registration data. SETTING: England and Wales. PATIENTS: Children aged 28 days to 15 years who died during 2013-15. MAIN OUTCOME MEASURES: The 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. RESULTS: There were 5088 death registrations recorded in children aged 28 days to <15 years in England and Wales during the three calendar years, 2013-2015 (17.6 deaths/100 000 children annually) compared with 6897 (23.9/100 000) during 2003-05 (incidence rate ratios (IRR) 0.74, 95% CI 0.71 to 0.77). During 2013-15, there were 951 (18.7%, 951/5088) infection-related deaths compared with 1368 (19.8%, 1368/6897) during 2003-05, equivalent to an infection-related mortality rate of 3.3/100 000 compared with 4.8/100 000 during the two periods (IRR 0.69, 95% CI 0.64 to 0.75), respectively. An underlying comorbidity was recorded in 55.0% (523/951) of death registrations during 2013-15 and increased with age. Where recorded, respiratory tract infection was the most commonly reported presentation (374/876, 42.7%) during 2013-15. Central nervous system infections accounted for only 4.8% (42/876). Overall, 63.1% (378/599) of infection-related deaths were associated with a bacterial, 34.2% (205/599) with a viral and 2.5% (15/599) with a fungal infection. CONCLUSIONS: Beyond 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.

Does norovirus induce acute hepatitis?

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.

Clinical Characteristics of Children with COVID-19.

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.

Rare and Imported Infections: Are We Prepared?

The world's population is rapidly expanding [...].

ARE ANTIBIOTICS OF ANY USE IN THE MANAGEMENT OF GRANULOMA ANNULARE IN CHILDREN?

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.

The Pneumococcus and Its Critical Role in Public Health.

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.

The Epidemiology and Biostatistics of Pneumococcus.

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-Induced Anaphylactic Reaction in Children: A Case Report.

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.