Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Paediatrics and Adolescent Medicine, Hans Christian Andersen Children's Hospital, Odense, Denmark.
Lancet Child Adolesc Health. 2024 Feb;8(2):112-121. doi: 10.1016/S2352-4642(23)00295-X. Epub 2023 Dec 13.
A historic increase in paediatric invasive group A streptococcal (iGAS) infections was reported globally in 2022. iGAS infections can lead to severe manifestations (eg, pleural empyema, necrotising fasciitis, toxic shock syndrome, osteomyelitis, septic arthritis, and meningitis). We aimed to compare the incidence and severity of iGAS infections overall, for distinct clinical phenotypes, and for GAS emm variants in Denmark in 2022-23 with reference to the previous six seasons (ie, 2016-17, 2017-18, 2018-19, 2019-20, 2020-21, and 2021-22).
In this nationwide, multicentre, population-based cohort study, we included all children and adolescents in Denmark aged 0-17 years with a positive culture of GAS or GAS confirmed through PCR-based methods from otherwise sterile sites in 2022-23 and the previous six seasons from 2016-17 to 2021-22. For all seven seasons, data were obtained from week 21 to week 20 of the next year. Patients at all 18 paediatric hospital departments in Denmark were identified through the Danish Microbiology Database, in which iGAS isolates from sterile sites are prospectively registered, including emm typing. We obtained electronic medical health records for each patient admitted with a diagnosis of iGAS. We calculated the incidence of iGAS per 1 000 000 inhabitants aged 0-17 years in each season from week 21 to week 20 of the next year and the risk ratios (RRs) for incidence of iGAS, distinct disease manifestations, and emm variants in 2022-23 versus the three pre-COVID-19 seasons in 2016-17, 2017-18, and 2018-19 using Fisher's exact test and Pearson's χ test.
Among the Danish population of 1 152 000 children and adolescents aged 0-17 years, 174 with iGAS disease were included. 76 children and adolescents with iGAS during 2022-23 were identified; 31 (41%) of 76 were female and 45 (59%) were male. 98 children and adolescents with iGAS during 2016-17 to 2021-22 were identified; 41 (42%) of 98 were female and 57 (58%) were male. There was an increase in incidence of iGAS from mean 22·6 (95% CI 14·7-33·1) per 1 000 000 children and adolescents during 2016-17 to 2018-19 to 66·0 (52·0-82·6) per 1 000 000 during 2023-23 (RR 2·9, 95% CI 1·9-4·6; p<0·0001). During the COVID-19 pandemic in 2019-20, 2020-21, and 2021-22, the mean incidence of iGAS was 6·1 (95% CI 2·4-12·5) per 1 000 000 children and adolescents. In 2022-23, there was a 9·5-fold increase in emm-12 (95% CI 2·2-40·8; p=0·0002) and a 2·7-fold increase in emm-1 (1·3-5·5; p=0·0037). The most common clinical manifestations of iGAS in 2022-23 were soft-tissue infections, which increased by 4·5-fold (1·9-10·9; p=0·0003), and complicated pneumonia with parapneumonic effusion, which increased by 4·0-fold (1·4-11·4; p=0·0059), both compared with the three pre-COVID-19 seasons. Overall, there was no increased severity of iGAS in 2022-23 compared with the previous six seasons as measured by median duration of hospital stay (8 days, IQR 4-14 vs 9 days, 5-15; p=0·39), paediatric intensive care unit (PICU) admission (17 [22%] of 76 vs 17 [17%] of 98; p=0·53), duration of stay in PICU (4 days, IQR 2-10 vs 4 days, 2-11; p=0·84), or mortality (three [4%] of 76 vs three [3%] of 98; p=1·00). In 2022-23, there was a 3·6-fold (95% CI 1·8-7·3; p=0·0001) increase in children with a preceding upper respiratory tract infection and a 4·6-fold (1·5-14·1; p=0·0034) increase in children with a preceding varicella-zoster infection, both compared with the three pre-COVID-19 seasons.
In Denmark, the incidence of paediatric iGAS increased in 2022-23 compared with the three pre-COVID-19 seasons of 2016-17, 2017-18, and 2018-19. However, the course of iGAS disease in children and adolescents in 2022-23 was not more severe than in previous seasons. The high morbidity across all seasons highlights iGAS as a major invasive bacterial infection in children and adolescents.
Innovation Fund Denmark.
2022 年，全球报告了儿童侵袭性 A 组链球菌（iGAS）感染的历史性增加。iGAS 感染可导致严重表现（例如，脓胸、坏死性筋膜炎、中毒性休克综合征、骨髓炎、化脓性关节炎和脑膜炎）。我们旨在比较丹麦 2022-23 年所有 iGAS 感染的发生率和严重程度、不同临床表型以及 GASemm 变异体与前六个季节（即 2016-17 年、2017-18 年、2018-19 年、2019-20 年、2020-21 年和 2021-22 年）的参考情况。
在这项全国性、多中心、基于人群的队列研究中，我们纳入了 2022-23 年所有年龄在 0-17 岁之间、来自丹麦的经培养或 PCR 方法从其他无菌部位检测到 GAS 阳性的儿童和青少年。前六个季节的数据从 2016-17 年到 2021-22 年每周 21 日到下一年每周 20 日获得。丹麦微生物数据库中确定了丹麦所有 18 个儿科医院部门的患者，该数据库中前瞻性登记了来自无菌部位的 iGAS 分离株，包括 emm 型鉴定。我们为每例诊断为 iGAS 并住院的患者获得了电子病历。我们计算了每个季节每周 21 日至下周 20 日每 100 万 0-17 岁居民中 iGAS 的发病率以及 2022-23 年 iGAS、不同疾病表现和 emm 变异体的发病率与 2016-17 年、2017-18 年和 2018-19 年三个 COVID-19 前季节的风险比（RR）使用 Fisher 精确检验和 Pearson χ 检验。
在丹麦 115.2 万 0-17 岁儿童和青少年人群中，有 174 例 iGAS 疾病患者入选。在 2022-23 年期间，有 76 名儿童和青少年患有 iGAS，其中 31 名（41%）为女性，45 名（59%）为男性。在 2016-17 年至 2021-22 年期间，有 98 名儿童和青少年患有 iGAS，其中 41 名（42%）为女性，57 名（58%）为男性。iGAS 的发病率从 2016-17 年至 2018-19 年的平均 22.6（95%CI，14.7-33.1）/100 万儿童和青少年增加到 2023-23 年的 66.0（52.0-82.6）/100 万（RR，2.9，95%CI，1.9-4.6；p<0.0001）。在 2019-20 年、2020-21 年和 2021-22 年 COVID-19 大流行期间，iGAS 的平均发病率为 6.1（95%CI，2.4-12.5）/100 万儿童和青少年。在 2022-23 年，emm-12 的发病率增加了 9.5 倍（95%CI，2.2-40.8；p=0.0002），emm-1 的发病率增加了 2.7 倍（1.3-5.5；p=0.0037）。2022-23 年最常见的 iGAS 临床表型为软组织感染，增加了 4.5 倍（1.9-10.9；p=0.0003），伴有肺炎并伴有脓胸的复杂性肺炎增加了 4.0 倍（1.4-11.4；p=0.0059）与前三个 COVID-19 季节相比。与前六个季节相比，2022-23 年 iGAS 的严重程度没有增加，这一点从住院时间中位数（8 天，四分位距 4-14 与 9 天，5-15；p=0.39）、儿科重症监护病房（PICU）入院率（17 [22%] 例 76 与 17 [17%] 例 98；p=0.53）、PICU 住院时间中位数（4 天，四分位距 2-10 与 4 天，2-11；p=0.84）或死亡率（3 [4%] 例 76 与 3 [3%] 例 98；p=1.00）均可以看出。与前三个 COVID-19 季节相比，2022-23 年有 3.6 倍（95%CI，1.8-7.3；p=0.0001）患有上呼吸道感染的儿童和 4.6 倍（1.5-14.1；p=0.0034）患有带状疱疹感染的儿童发生 iGAS 的风险增加。
在丹麦，2022-23 年儿童侵袭性 iGAS 的发病率与 2016-17 年、2017-18 年和 2018-19 年三个 COVID-19 前季节相比有所增加。然而，儿童和青少年 iGAS 疾病的病程并不比前几个季节更严重。所有季节的高发病率都突显了 iGAS 是儿童和青少年的主要侵袭性细菌性感染。
丹麦创新基金会。
