The Impact of Pneumococcal Conjugate Vaccines on Invasive Pneumococcal Disease

The UK introduced the 7-valent pneumococcal conjugate vaccine (PCV7) into the national childhood immunisation programme in 2006, which was replaced with the 13-valent PCV (PCV13) in 2010. The published articles presented in this thesis assessed the impact of PCVs on invasive pneumococcal disease (IPD) especially in children and those with underlying comorbidities, particularly sickle cell disease (SCD). The systematic review of PCV failures found a low incidence of vaccine failures irrespective of the PCV used in the national immunisation programme. After PCV7 introduction, serotypes 19F and 6B were responsible for more than two-thirds of vaccine failure cases. In keeping with published studies, these serotypes were also responsible for most cases of vaccine failure in the national surveillance of PCV failures in England and wales before the introduction of PCV13. After PCV7 was replaced with PCV13, serotypes 3 and 19A were over-represented among the vaccine failure cases. Overall case fatality rate (CFR) in children with PCV failure was low, with only six of 161 children (4%) dying, including five (83%) who had significant underlying comorbidities. A review of IPD in children with SCD however identified continued increased risk of IPD in children with SCD. The overall CFR among published cases was 11.5%. More than half of the serotypes associated with IPD were not included in the PCV13, of which more than half were due to serogroup 15. Similarly, in the enhanced national surveillance of IPD in children with SCD, in England, it was identified that there were 881 IPD cases, including eleven children homozygote for haemoglobin S (HbSS) and one double heterozygote for haemoglobin S and C (HbSC). Children with SCD remained 49 times more likely to develop IPD and 5 times more likely to die of their infection compared to their healthy peers. Most IPD cases in SCD were also due to serotypes that were not covered by PCV13, particularly serogroup 15, and this finding was found to be consistent with published literatures. Research was also carried out to determine the epidemiology of pneumococcal meningitis following the introduction of PCV in England and Wales. The incidence of pneumococcal meningitis did not change after PCV7 introduction, but declined by 48% after the vaccine was replaced with PCV13 in keeping with large reductions in cases due to the additional PCV13 serotypes 7F and 19A. Currently, meningitis due to PCV13 serotypes is rare and the 6 non-PCV13 serotypes 8 and 12F are the predominant causes of pneumococcal meningitis. Additionally, while the incidence of pneumococcal meningitis has declined, the CFR has remained high at 17.5%. However, childhood CFR for IPD remained low at 4.8%, with more than half (59%) of deaths occurring in infants, mainly in those aged <3 months who accounted for 28% of all fatal cases. Overall, 35% of children who died had underlying risk factors for IPD while meningitis was responsible for 47% of IPD-related deaths. In summary, this thesis has demonstrated that the rate of PCV failure, irrespective of the vaccine used or schedule, was very low, as was CFR in children with PCV failure. Most children with PCV13 failure were healthy, developed LRTI, and survived their infection without long-term complications. The continuing low prevalence of PCV7 failures after PCV13 introduction is reassuring and it is likely that PCV13 failure will also decline in the coming years. However, children with SCD remained at risk of IPD and death despite these measures of daily penicillin prophylaxis as well as pneumococcal vaccination. The majority of serotypes causing IPD in SCD are no longer vaccine preventable, therefore every effort should be made to ensure that these children adhere to penicillin prophylaxis and pneumococcal vaccines. Thus, in conclusion, PCVs are highly effective in preventing IPD due to the respective vaccine serotypes. The childhood pneumococcal vaccination programme has led to a significant reduction in the incidence of IPD, including meningitis. However, compared to other clinical presentations, there was a lower than expected impact on pneumococcal meningitis, with case fatality rates due to meningitis remaining relatively unchanged across the age groups. Given that most IPD cases, including meningitis are now due to non-PCV13 serotypes, including most fatal IPD cases, additional strategies need to be introduced to reduce childhood pneumococcal deaths in countries with established pneumococcal vaccination programmes

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. 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

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 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

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 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-T

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

Risk of Transverse Myelitis Following Dengue Infection: A Systematic Review of the Literature

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&ndash;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

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

Significantly lower infection fatality rates associated with SARS-CoV-2 Omicron (B.1.1.529) infection in children and young people: Active, prospective national surveillance, January-March 2022, England.

Funder: UK Health Security Agenc

The changing epidemiology of PIMS-TS across COVID-19 waves: prospective national surveillance, January 2021 to July 2022, England

No abstract available