Invasive Pneumococcal Disease in UK Children &lt;1 Year of Age in the Post–13-Valent Pneumococcal Conjugate Vaccine Era: What Are the Risks Now?

Kent, Alison; Makwana, Ashley; Sheppard, Carmen; Collins, Sarah; Fry, Norman K.; Heath, Paul T; Ramsay, Mary; Ladhani, Shamez

doi:10.1093/cid/ciy842

Cited by 21 publications

(16 citation statements)

References 26 publications

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“…Incidence of IPD has subsequently reduced dramatically, with an incidence of IPD in infants of 19/100.000 in the period 2013 to 2016. 20 The mortality in our IPD cohort was 6%, which is comparable to other reports. 21…”

Section: Discussionsupporting

confidence: 89%

Screening for Immunodeficiencies in Children With Invasive Pneumococcal Disease: Six-year Experience From a UK Children’s Hospital

Bijker

Bateman

Trück

et al. 2022

Pediatric Infectious Disease Journal

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Background: A previous study showed that investigation of children with invasive pneumococcal disease (IPD) revealed an immunodeficiency in up to 10% of cases. Following this report, we implemented a protocol to investigate children with IPD, to assess the proportion with an immunodeficiency in our setting. Methods: We retrospectively identified patients who presented with IPD from January 2015 to November 2020 and collected data from medical records. Immunological investigations included complement C3 and C4 levels, classical and alternative pathway complement function, IgG, IgA and IgM levels, specific IgG levels (H. influenza B, tetanus and pneumococcal serotypes), peripheral blood film, lymphocyte subsets, and CD62L-shedding upon activation with Toll-like receptor-agonists in selected cases. Results: We identified a total of 68 children with IPD, with a mortality of 6%. Immunological investigations were performed in 51 children. Four children (8%) had abnormal findings that were deemed of clinical significance. Two children had complement deficiencies (Factor I and C2 deficiency), one child had specific antibody deficiency, and another child had low IgM, low NK-cells and poor persistence of serotype-specific anti-pneumococcal IgG concentrations. Of the 17 children with IPD who were not tested for immunodeficiencies, 4 died and four had possible explanations for the infection. Conclusions: We identified clinically relevant abnormal immunological findings in 4/51 (8%) of children with IPD. Our results support the recommendation to perform immunological investigations in children with IPD, since this might reveal underlying immunodeficiencies, allowing for necessary preventive measures and close follow-up.

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Section: Discussionsupporting

confidence: 89%

Screening for Immunodeficiencies in Children With Invasive Pneumococcal Disease: Six-year Experience From a UK Children’s Hospital

Bijker

Bateman

Trück

et al. 2022

Pediatric Infectious Disease Journal

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“…In our study, meningitis was the most common IPD manifestation across all age groups, with a similar IR of 1.48 (95% CI 1.22–1.78) across the study period in children aged 0–17 years. Also, using surveillance data from England, Kent A., et al, in infants aged < 1 year in 2013–2016, reported an IPD incidence of 19 cases per 100,000 infants, which was not dissimilar to our study estimate of 15.52 (95% CI 12.64–18.86) per 100,000 PY in children 0–1 year old in 2003–2019 [ 31 ].…”

Section: Discussionsupporting

confidence: 58%

Incidence of pneumococcal disease from 2003 to 2019 in children ≤17 years in England

et al. 2023

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Background Pneumococcal disease is a leading cause of communicable disease morbidity and mortality globally. We aimed to estimate invasive pneumococcal disease (IPD), pneumococcal pneumonia (PP) and all-cause pneumonia (ACP) incidence rates (IRs) in children aged 0–17 years in England from 2003 to 2019. Methods A retrospective study in children ≤17 years old from 2003 to 2019 using the Clinical Practice Research Datalink (CPRD) Gold and Hospital Episodes Statistics Admitted Patient Care (HES APC) databases. IPD episodes were identified in hospital records (HES APC). PP (caused by Streptococcus pneumoniae only) and ACP episodes (caused by any pathogen) were identified in primary care (CPRD) and in hospital records (HES APC). Annual IRs by age-group were calculated as the number of episodes/person-years (PY) at risk, with 95% confidence intervals (95% CI). Interrupted time series analyses were conducted to assess changes in IRs across the post-PCV7 (2007–2009), early post-PCV13 (2011–2014) and late post-PCV13 (2015–2019) periods compared to the pre-PCV7 period (2003–2005) using generalized linear models. Results 170 IPD episodes, 769 PP episodes and 12,142 ACP episodes were identified in 1,500,686 children in 2003–2019. The overall IPD, PP and ACP IRs (per 100,000 PY) were 2.29 (95% CI 1.96–2.66), 10.34 (95% CI 9.62–11.10) and 163.37 (95% CI 160.47–166.30), respectively. The highest IPD, PP and ACP IRs were observed in children aged < 2 years compared to older children (2–4 and 5–17 years). IPD IRs decreased between the pre-PCV7 period and the late post-PCV13 period from 3.28 (95% CI 2.42–4.33) to 1.41 (95% CI 0.80–2.29), IRR 0.28 (95% CI 0.09–0.90), p-value 0.033. PP IRs declined between the pre-PCV7 period and the late post-PCV13 period from 14.65 (95% CI 12.77–16.72) to 3.87 (95% CI 2.81–5.20), IRR 0.19 (95% CI 0.09–0.38), p-value < 0.001. ACP IRs declined between the pre-PCV7 period and the late post-PCV13 period from 167.28 (95% CI 160.78–173.96) to 124.96 (95% CI 118.54–131.63), IRR 0.77 (95% CI 0.66–0.88), p-value < 0.001. Conclusions The clinical burden of IPD, PP and ACP declined in children in England aged 0–17 years between 2003 and 2019, especially in the late post-PCV13 period. This study highlights the importance of PCV vaccination in reducing the burden of PD and ACP in children in England.

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“…Globally, an estimated 14.9 million infants are born preterm, i.e., before 37 weeks of pregnancy. The risk of infection in preterm (PT) infants increases nine-fold when compared to their full term (FT) counterparts (2)(3)(4)(5) and correlates inversely with gestational age (6); furthermore, PT infants face an increased risk of VPDs emphasizing importance of vaccination (7,8). It is generally recommended that the preterm infants should be vaccinated using the same schedules as those usually recommended for full-term infants with the only exception of birth dose of hepatitis B vaccine, to be administered to babies weighing > 2000 g (9,10).…”

Section: Introductionmentioning

confidence: 99%

Immune Response of Indian Preterm Infants to Pentavalent Vaccine Varies With Component Antigens and Gestational Age

et al. 2021

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Childhood vaccination plays critical role in protecting infants from several dreaded diseases. Of the global 15 million preterm (PT) infants with compromised immune system born annually, India contributes to >3.5 million. Generation of adequate vaccine-induced immune response needs to be ensured of their protection. Immune response of Indian PT (n = 113) and full-term (FT, n = 80) infants to pentavalent vaccine administered as per the national recommendation was studied. Antibody titers against component antigens of pentavalent vaccine, immune cells profiling (T and B cells, monocytes and dendritic cells) and plasma cytokines were determined pre- and post-vaccination. Additionally, cell-mediated recall immune responses to pentavalent antigens were evaluated after short time antigenic exposure to infant PBMCs. Irrespective of gestational age (GA), all the infants developed adequate antibody response against tetanus, diphtheria, and protective but lower antibody levels for Haemophilus influenzae type-b and hepatitis B in preterm infants. Lower (~74%) protective antibody response to pertussis was independent of gestational age. PT-infants exhibited lower frequencies of CD4 T cells/dendritic cells/monocytes, increased plasma IL-10 levels and lower proliferation of central and effector memory T cells than in term-infants. Proliferative central memory response of FT-infants without anti-pertussis antibodies suggests protection from subsequent infection. Responder/non-responder PT-infants lacked immunological memory and could be infected with Bordetella. For hepatitis B, the recall response was gestational age-dependent and antibody status-independent. Humoral/cellular immune responses of PT-infants were dependent on the type of the immunogen. Preterm infants born before 32 weeks of gestation may need an extra dose of pentavalent vaccine for long lived robust immune response.

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Invasive Pneumococcal Disease in UK Children <1 Year of Age in the Post–13-Valent Pneumococcal Conjugate Vaccine Era: What Are the Risks Now?

Abstract: Whilst the incidence of invasive pneumococcal disease (IPD) in infants in England remains low, the risk of IPD is significantly higher in premature infants compared to term infants. Changes to the infant pneumococcal immunisation schedule may disproportionally affect premature infants.

Cited by 21 publications

References 26 publications

Screening for Immunodeficiencies in Children With Invasive Pneumococcal Disease: Six-year Experience From a UK Children’s Hospital

Screening for Immunodeficiencies in Children With Invasive Pneumococcal Disease: Six-year Experience From a UK Children’s Hospital

Incidence of pneumococcal disease from 2003 to 2019 in children ≤17 years in England

Immune Response of Indian Preterm Infants to Pentavalent Vaccine Varies With Component Antigens and Gestational Age

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