Recent advances in genetic testing technologies have revolutionised the identification of genetic abnormalities in early onset developmental and epileptic encephalopathies (DEEs). In this Review, we provide an update on the expanding landscape of genetic factors contributing to DEEs, encompassing over 800 reported genes. We focus on the cellular and molecular mechanisms driving epileptogenesis, with an emphasis on emerging therapeutic strategies and effective treatment options. We explore noteworthy, novel genes linked to DEE phenotypes, such as gBRAT-1 and GNAO1, and gene families such as GRIN and HCN. Understanding the network-level effects of gene variants will pave the way for potential gene therapy applications. Given the diverse comorbidities associated with DEEs, a multidisciplinary team approach is essential. Despite ongoing efforts and improved genetic testing, DEEs lack a cure, and treatment complexities persist. This Review underscores the necessity for larger international prospective studies focusing on both seizure outcomes and developmental trajectories.
基因检测技术的最新进展彻底改变了对早发性发育性和癫痫性脑病（DEEs）基因异常的鉴定。在本综述中，我们将介绍导致 DEEs 的遗传因素不断扩展的最新情况，包括已报道的 800 多个基因。我们将重点放在驱动癫痫发生的细胞和分子机制上，同时强调新出现的治疗策略和有效的治疗方案。我们探讨了与 DEE 表型相关的值得注意的新基因，如 gBRAT-1 和 GNAO1，以及基因家族，如 GRIN 和 HCN。了解基因变异的网络级效应将为潜在的基因治疗应用铺平道路。鉴于与 DEE 相关的合并症多种多样，因此必须采用多学科团队方法。尽管我们一直在努力改进基因检测，但 DEE 仍无法治愈，治疗的复杂性依然存在。本综述强调，有必要开展更大规模的国际前瞻性研究，重点关注癫痫发作结果和发育轨迹。
{"title":"The expanding field of genetic developmental and epileptic encephalopathies: current understanding and future perspectives","authors":"Nicola Specchio MD , Marina Trivisano MD , Prof Eleonora Aronica MD , Simona Balestrini MD , Prof Alexis Arzimanoglou MD , Gaia Colasante PhD , Prof J Helen Cross MD , Sergiusz Jozwiak MD , Prof Jo M Wilmshurst MD , Federico Vigevano MD , Prof Stéphane Auvin MD , Prof Rima Nabbout MD , Prof Paolo Curatolo MD","doi":"10.1016/S2352-4642(24)00196-2","DOIUrl":"10.1016/S2352-4642(24)00196-2","url":null,"abstract":"<div><div>Recent advances in genetic testing technologies have revolutionised the identification of genetic abnormalities in early onset developmental and epileptic encephalopathies (DEEs). In this Review, we provide an update on the expanding landscape of genetic factors contributing to DEEs, encompassing over 800 reported genes. We focus on the cellular and molecular mechanisms driving epileptogenesis, with an emphasis on emerging therapeutic strategies and effective treatment options. We explore noteworthy, novel genes linked to DEE phenotypes, such as <em>gBRAT-1</em> and <em>GNAO1</em>, and gene families such as <em>GRIN</em> and <em>HCN</em>. Understanding the network-level effects of gene variants will pave the way for potential gene therapy applications. Given the diverse comorbidities associated with DEEs, a multidisciplinary team approach is essential. Despite ongoing efforts and improved genetic testing, DEEs lack a cure, and treatment complexities persist. This Review underscores the necessity for larger international prospective studies focusing on both seizure outcomes and developmental trajectories.</div></div>","PeriodicalId":54238,"journal":{"name":"Lancet Child & Adolescent Health","volume":"8 11","pages":"Pages 821-834"},"PeriodicalIF":19.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142437895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 10.1016/S2352-4642(24)00229-3
Hannah M M Thomas PhD , Stephanie L Enkel MPH , Marianne Mullane BSc , Tracy McRae PhD , Timothy C Barnett PhD , Prof Jonathan R Carapetis PhD , Raymond Christophers , Prof Julianne Coffin PhD , Rebecca Famlonga MAH , John Jacky , Mark Jones MBiostat , Julie Marsh PhD , Kelli McIntosh , Vicki O'Donnell , Edward Pan BA , Glenn Pearson BA , Slade Sibosado , Bec Smith MC-HHS , Prof Thomas Snelling PhD , Prof Andrew Steer PhD , Edie Wright
Background
Skin infections affect physical health and, through stigma, social-emotional health. When untreated, they can cause life-threatening conditions. We aimed to assess the effect of a holistic, co-designed, region-wide skin control programme on the prevalence of impetigo.
Methods
The SToP (See, Treat, and Prevent Skin Sores and Scabies) trial is a pragmatic, open-cohort, stepped-wedge cluster randomised trial involving participants aged 0–18 years in nine remote communities of the Kimberley, Western Australia. The trial involves programmatic interventions in three domains: See (skin checks and skin infection recognition training), Treat (skin infection treatment training, sulfamethoxazole–trimethoprim for impetigo, and ivermectin for scabies), and Prevent (co-designed health promotion and environmental health). Four clusters, defined as pragmatic aggregations of communities, were randomised in two steps to progressively receive the activities during ten visits. The primary outcome was the proportion of school-aged children (aged 5–9 years) with impetigo. We adopted an intention-to-treat analysis and compared the intervention with the control (usual care before the start of intervention) states to derive a time and cluster averaged effect using Bayesian modelling. This study is registered with Australian New Zealand Clinical Trials Registry, ACTRN12618000520235.
Findings
Between Sept 19, 2018, and Nov 22, 2022, 915 children were consented and 777 (85%) had skin checks performed on at least one of ten possible visits between May 5, 2019, and Nov 22, 2022. Of the participants, 448 (58%) of 777 were aged 5–9 years at one or more of the visit timepoints and were eligible for primary outcome assessment. A decline in impetigo occurred across all clusters, with the greatest decline during the observational period of baseline skin checks before commencement of the interventional trial activities activities. The mean (95% credible interval) for the conditional posterior odds ratio for observing impetigo in the intervention compared with the control period was 1·13 (0·71–1·70). The probability that the intervention reduced the odds of observing impetigo was 0·33.
Interpretation
A decreased prevalence of impetigo during the observational period before the commencement of trial activities was sustained across the trial, attributable to the trimodal skin health initiative. Although the prevalence of impetigo reduced, there is no direct evidence to attribute this to the individual effects of the trial activities. The wholistic approach inclusive of skin checks collectively contributed to the sustained reduction in impetigo.
Funding
Western Australia Department of Health, Australian National Health and Medical Research Council, and Healthway.
{"title":"Trimodal skin health programme for childhood impetigo control in remote Western Australia (SToP): a cluster randomised, stepped-wedge trial","authors":"Hannah M M Thomas PhD , Stephanie L Enkel MPH , Marianne Mullane BSc , Tracy McRae PhD , Timothy C Barnett PhD , Prof Jonathan R Carapetis PhD , Raymond Christophers , Prof Julianne Coffin PhD , Rebecca Famlonga MAH , John Jacky , Mark Jones MBiostat , Julie Marsh PhD , Kelli McIntosh , Vicki O'Donnell , Edward Pan BA , Glenn Pearson BA , Slade Sibosado , Bec Smith MC-HHS , Prof Thomas Snelling PhD , Prof Andrew Steer PhD , Edie Wright","doi":"10.1016/S2352-4642(24)00229-3","DOIUrl":"10.1016/S2352-4642(24)00229-3","url":null,"abstract":"<div><h3>Background</h3><div>Skin infections affect physical health and, through stigma, social-emotional health. When untreated, they can cause life-threatening conditions. We aimed to assess the effect of a holistic, co-designed, region-wide skin control programme on the prevalence of impetigo.</div></div><div><h3>Methods</h3><div>The SToP (See, Treat, and Prevent Skin Sores and Scabies) trial is a pragmatic, open-cohort, stepped-wedge cluster randomised trial involving participants aged 0–18 years in nine remote communities of the Kimberley, Western Australia. The trial involves programmatic interventions in three domains: See (skin checks and skin infection recognition training), Treat (skin infection treatment training, sulfamethoxazole–trimethoprim for impetigo, and ivermectin for scabies), and Prevent (co-designed health promotion and environmental health). Four clusters, defined as pragmatic aggregations of communities, were randomised in two steps to progressively receive the activities during ten visits. The primary outcome was the proportion of school-aged children (aged 5–9 years) with impetigo. We adopted an intention-to-treat analysis and compared the intervention with the control (usual care before the start of intervention) states to derive a time and cluster averaged effect using Bayesian modelling. This study is registered with Australian New Zealand Clinical Trials Registry, ACTRN12618000520235.</div></div><div><h3>Findings</h3><div>Between Sept 19, 2018, and Nov 22, 2022, 915 children were consented and 777 (85%) had skin checks performed on at least one of ten possible visits between May 5, 2019, and Nov 22, 2022. Of the participants, 448 (58%) of 777 were aged 5–9 years at one or more of the visit timepoints and were eligible for primary outcome assessment. A decline in impetigo occurred across all clusters, with the greatest decline during the observational period of baseline skin checks before commencement of the interventional trial activities activities. The mean (95% credible interval) for the conditional posterior odds ratio for observing impetigo in the intervention compared with the control period was 1·13 (0·71–1·70). The probability that the intervention reduced the odds of observing impetigo was 0·33.</div></div><div><h3>Interpretation</h3><div>A decreased prevalence of impetigo during the observational period before the commencement of trial activities was sustained across the trial, attributable to the trimodal skin health initiative. Although the prevalence of impetigo reduced, there is no direct evidence to attribute this to the individual effects of the trial activities. The wholistic approach inclusive of skin checks collectively contributed to the sustained reduction in impetigo.</div></div><div><h3>Funding</h3><div>Western Australia Department of Health, Australian National Health and Medical Research Council, and Healthway.</div></div>","PeriodicalId":54238,"journal":{"name":"Lancet Child & Adolescent Health","volume":"8 11","pages":"Pages 809-820"},"PeriodicalIF":19.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-24DOI: 10.1016/S2352-4642(24)00231-1
Tsige Ketema , Quique Bassat
{"title":"Primaquine for children, once and for all","authors":"Tsige Ketema , Quique Bassat","doi":"10.1016/S2352-4642(24)00231-1","DOIUrl":"10.1016/S2352-4642(24)00231-1","url":null,"abstract":"","PeriodicalId":54238,"journal":{"name":"Lancet Child & Adolescent Health","volume":"8 11","pages":"Pages 775-777"},"PeriodicalIF":19.9,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-24DOI: 10.1016/S2352-4642(24)00210-4
Robert J Commons FRACP , Megha Rajasekhar PhD , Elizabeth N Allen PhD , Prof Daniel Yilma MD , Palang Chotsiri PhD , Tesfay Abreha MPH , Prof Ishag Adam PhD , Ghulam Rahim Awab PhD , Bridget E Barber PhD , Larissa W Brasil PhD , Cindy S Chu MD , Prof Liwang Cui PhD , Peta Edler MBiostat , Margarete do Socorro M Gomes PhD , Lilia Gonzalez‑Ceron PhD , Matthew J Grigg PhD , Muzamil Mahdi Abdel Hamid PhD , Jimee Hwang MD , Harin Karunajeewa PhD , Prof Marcus V G Lacerda PhD , Adugna Woyessa
<div><h3>Background</h3><div>Primaquine, the only widely available treatment to prevent relapsing <em>Plasmodium vivax</em> malaria, is produced as 15 mg tablets, and new paediatric formulations are being developed. To inform the optimal primaquine dosing regimen for children, we aimed to determine the efficacy and safety of different primaquine dose strategies in children younger than 15 years.</div></div><div><h3>Methods</h3><div>We undertook a systematic review (Jan 1, 2000–July 26, 2024) for <em>P vivax</em> efficacy studies with at least one treatment group that was administered primaquine over multiple days, that enrolled children younger than 15 years, that followed up patients for at least 28 days, and that had data available for inclusion by June 30, 2022. Patients were excluded if they were aged 15 years or older, presented with severe malaria, received adjunctive antimalarials within 14 days of diagnosis, commenced primaquine more than 7 days after starting schizontocidal treatment, had a protocol violation in the original study, or were missing data on age, sex, or primaquine dose. Available individual patient data were collated and standardised. To evaluate efficacy, the risk of recurrent <em>P vivax</em> parasitaemia between days 7 and 180 was assessed by time-to-event analysis for different total mg/kg primaquine doses (low total dose of ∼3·5 mg/kg and high total dose of ∼7 mg/kg). To evaluate tolerability and safety, the following were assessed by daily mg/kg primaquine dose (low daily dose of ∼0·25 mg/kg, intermediate daily dose of ∼0·5 mg/kg, and high daily dose of ∼1 mg/kg): gastrointestinal symptoms (vomiting, anorexia, or diarrhoea) on days 5–7, haemoglobin decrease of at least 25% to less than 7g/dL (severe haemolysis), absolute change in haemoglobin from day 0 to days 2–3 or days 5–7, and any serious adverse events within 28 days. This study is registered with PROSPERO, CRD42021278085.</div></div><div><h3>Findings</h3><div>In total, 3514 children from 27 studies and 15 countries were included. The cumulative incidence of recurrence by day 180 was 51·4% (95% CI 47·0–55·9) following treatment without primaquine, 16·0% (12·4–20·3) following a low total dose of primaquine, and 10·2% (8·4–12·3) following a high total dose of primaquine. The hazard of recurrent <em>P vivax</em> parasitaemia in children younger than 15 years was reduced following primaquine at low total doses (adjusted hazard ratio [HR] 0·17, 95% CI 0·11–0·25) and high total doses (0·09, 0·07–0·12), compared with no primaquine. In 525 children younger than 5 years, the relative rates of recurrence were also reduced, with an adjusted HR of 0·33 (95% CI 0·18–0·59) for a low total dose and 0·13 (0·08–0·21) for a high total dose of primaquine compared with no primaquine. The rate of recurrence following a high total dose was reduced compared with a low dose in children younger than 15 years (adjusted HR 0·54, 95% CI 0·35–0·85) and children younger than 5 years (0·41,
{"title":"Primaquine for uncomplicated Plasmodium vivax malaria in children younger than 15 years: a systematic review and individual patient data meta-analysis","authors":"Robert J Commons FRACP , Megha Rajasekhar PhD , Elizabeth N Allen PhD , Prof Daniel Yilma MD , Palang Chotsiri PhD , Tesfay Abreha MPH , Prof Ishag Adam PhD , Ghulam Rahim Awab PhD , Bridget E Barber PhD , Larissa W Brasil PhD , Cindy S Chu MD , Prof Liwang Cui PhD , Peta Edler MBiostat , Margarete do Socorro M Gomes PhD , Lilia Gonzalez‑Ceron PhD , Matthew J Grigg PhD , Muzamil Mahdi Abdel Hamid PhD , Jimee Hwang MD , Harin Karunajeewa PhD , Prof Marcus V G Lacerda PhD , Adugna Woyessa","doi":"10.1016/S2352-4642(24)00210-4","DOIUrl":"10.1016/S2352-4642(24)00210-4","url":null,"abstract":"<div><h3>Background</h3><div>Primaquine, the only widely available treatment to prevent relapsing <em>Plasmodium vivax</em> malaria, is produced as 15 mg tablets, and new paediatric formulations are being developed. To inform the optimal primaquine dosing regimen for children, we aimed to determine the efficacy and safety of different primaquine dose strategies in children younger than 15 years.</div></div><div><h3>Methods</h3><div>We undertook a systematic review (Jan 1, 2000–July 26, 2024) for <em>P vivax</em> efficacy studies with at least one treatment group that was administered primaquine over multiple days, that enrolled children younger than 15 years, that followed up patients for at least 28 days, and that had data available for inclusion by June 30, 2022. Patients were excluded if they were aged 15 years or older, presented with severe malaria, received adjunctive antimalarials within 14 days of diagnosis, commenced primaquine more than 7 days after starting schizontocidal treatment, had a protocol violation in the original study, or were missing data on age, sex, or primaquine dose. Available individual patient data were collated and standardised. To evaluate efficacy, the risk of recurrent <em>P vivax</em> parasitaemia between days 7 and 180 was assessed by time-to-event analysis for different total mg/kg primaquine doses (low total dose of ∼3·5 mg/kg and high total dose of ∼7 mg/kg). To evaluate tolerability and safety, the following were assessed by daily mg/kg primaquine dose (low daily dose of ∼0·25 mg/kg, intermediate daily dose of ∼0·5 mg/kg, and high daily dose of ∼1 mg/kg): gastrointestinal symptoms (vomiting, anorexia, or diarrhoea) on days 5–7, haemoglobin decrease of at least 25% to less than 7g/dL (severe haemolysis), absolute change in haemoglobin from day 0 to days 2–3 or days 5–7, and any serious adverse events within 28 days. This study is registered with PROSPERO, CRD42021278085.</div></div><div><h3>Findings</h3><div>In total, 3514 children from 27 studies and 15 countries were included. The cumulative incidence of recurrence by day 180 was 51·4% (95% CI 47·0–55·9) following treatment without primaquine, 16·0% (12·4–20·3) following a low total dose of primaquine, and 10·2% (8·4–12·3) following a high total dose of primaquine. The hazard of recurrent <em>P vivax</em> parasitaemia in children younger than 15 years was reduced following primaquine at low total doses (adjusted hazard ratio [HR] 0·17, 95% CI 0·11–0·25) and high total doses (0·09, 0·07–0·12), compared with no primaquine. In 525 children younger than 5 years, the relative rates of recurrence were also reduced, with an adjusted HR of 0·33 (95% CI 0·18–0·59) for a low total dose and 0·13 (0·08–0·21) for a high total dose of primaquine compared with no primaquine. The rate of recurrence following a high total dose was reduced compared with a low dose in children younger than 15 years (adjusted HR 0·54, 95% CI 0·35–0·85) and children younger than 5 years (0·41, ","PeriodicalId":54238,"journal":{"name":"Lancet Child & Adolescent Health","volume":"8 11","pages":"Pages 798-808"},"PeriodicalIF":19.9,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-24DOI: 10.1016/S2352-4642(24)00193-7
Fariyo Abdullahi MSc , Marta Bertran MSc , Joshua C D'Aeth PhD , Seyi Eletu PhD , Yung-Wai Chan MSc , Nick J Andrews PhD , David J Litt PhD , Prof Mary E Ramsay FFPH , Prof Shamez N Ladhani PhD
Background
On Jan 1, 2020, the UK transitioned from a 2+1 to a 1+1 national infant immunisation schedule with the 13-valent pneumococcal conjugate vaccine (PCV13). We assessed whether the 1+1 PCV13 schedule had any impact on incidence, disease characteristics, or outcomes after invasive pneumococcal disease (IPD) in eligible children aged 0–3 years.
Methods
The UK Health Security Agency conducts IPD surveillance and serotyping of invasive pneumococcal isolates via whole-genome sequencing in England. IPD was defined as identification of Streptococcus pneumoniae in a sterile site. We compared IPD incidence, demographics, clinical presentation, comorbidity prevalence, serotype distribution, and case-fatality rates (CFRs) in children from a single birth cohort eligible for the 1+1 schedule (born between Jan 1, 2020, and Dec 31, 2022) who developed IPD in the 2022–23 financial year (April to March) with children from three equivalent historical birth cohorts (born between Jan 1, 2015, and Dec 31, 2019) eligible for the 2+1 schedule who developed IPD during three respective pre-pandemic financial years: 2017–18, 2018–19, and 2019–20.
Findings
There were a total of 702 IPD episodes in 697 children, including 158 (incidence 8·99 per 100 000 person-years) in the single 1+1 birth cohort and 544 (incidence 9·39 per 100 000 person-years) in the 2+1 birth cohorts, with no significant difference in the incidence of overall IPD (incidence rate ratio 0·96, 95% CI 0·80–1·14, p=0·63), PCV13-type IPD (1·21, 0·71–2·00, p=0·45), or pneumococcal meningitis (0·97, 0·66–1·40, p=0·88). Comorbidity prevalence, clinical presentation, and CFRs were also similar between the two cohorts, as was the percentage of cases in infants too young to be vaccinated (<2 months old) and infants aged 5–11 months who received one or two PCV13 priming doses, in the 1+1 and 2+1 cohorts respectively.
Interpretation
After 3 years, the 1+1 schedule continues to provide direct and indirect protection against PCV13-type IPD in children, with no significant change in overall IPD incidence, serotype distribution, clinical presentation, or CFRs in children eligible for the 1+1 compared with the 2+1 schedule. Ongoing surveillance will be important to assess longer-term direct and indirect population protection.
{"title":"Characteristics of children with invasive pneumococcal disease eligible for the 1+1 compared with the 2+1 PCV13 infant immunisation schedule in England: a prospective national observational surveillance study","authors":"Fariyo Abdullahi MSc , Marta Bertran MSc , Joshua C D'Aeth PhD , Seyi Eletu PhD , Yung-Wai Chan MSc , Nick J Andrews PhD , David J Litt PhD , Prof Mary E Ramsay FFPH , Prof Shamez N Ladhani PhD","doi":"10.1016/S2352-4642(24)00193-7","DOIUrl":"10.1016/S2352-4642(24)00193-7","url":null,"abstract":"<div><h3>Background</h3><div>On Jan 1, 2020, the UK transitioned from a 2+1 to a 1+1 national infant immunisation schedule with the 13-valent pneumococcal conjugate vaccine (PCV13). We assessed whether the 1+1 PCV13 schedule had any impact on incidence, disease characteristics, or outcomes after invasive pneumococcal disease (IPD) in eligible children aged 0–3 years.</div></div><div><h3>Methods</h3><div>The UK Health Security Agency conducts IPD surveillance and serotyping of invasive pneumococcal isolates via whole-genome sequencing in England. IPD was defined as identification of <em>Streptococcus pneumoniae</em> in a sterile site. We compared IPD incidence, demographics, clinical presentation, comorbidity prevalence, serotype distribution, and case-fatality rates (CFRs) in children from a single birth cohort eligible for the 1+1 schedule (born between Jan 1, 2020, and Dec 31, 2022) who developed IPD in the 2022–23 financial year (April to March) with children from three equivalent historical birth cohorts (born between Jan 1, 2015, and Dec 31, 2019) eligible for the 2+1 schedule who developed IPD during three respective pre-pandemic financial years: 2017–18, 2018–19, and 2019–20.</div></div><div><h3>Findings</h3><div>There were a total of 702 IPD episodes in 697 children, including 158 (incidence 8·99 per 100 000 person-years) in the single 1+1 birth cohort and 544 (incidence 9·39 per 100 000 person-years) in the 2+1 birth cohorts, with no significant difference in the incidence of overall IPD (incidence rate ratio 0·96, 95% CI 0·80–1·14, p=0·63), PCV13-type IPD (1·21, 0·71–2·00, p=0·45), or pneumococcal meningitis (0·97, 0·66–1·40, p=0·88). Comorbidity prevalence, clinical presentation, and CFRs were also similar between the two cohorts, as was the percentage of cases in infants too young to be vaccinated (<2 months old) and infants aged 5–11 months who received one or two PCV13 priming doses, in the 1+1 and 2+1 cohorts respectively.</div></div><div><h3>Interpretation</h3><div>After 3 years, the 1+1 schedule continues to provide direct and indirect protection against PCV13-type IPD in children, with no significant change in overall IPD incidence, serotype distribution, clinical presentation, or CFRs in children eligible for the 1+1 compared with the 2+1 schedule. Ongoing surveillance will be important to assess longer-term direct and indirect population protection.</div></div><div><h3>Funding</h3><div>None.</div></div>","PeriodicalId":54238,"journal":{"name":"Lancet Child & Adolescent Health","volume":"8 11","pages":"Pages 788-797"},"PeriodicalIF":19.9,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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