Immunisation Department, UK Health Security Agency, London, UK.
Respiratory and Vaccine Preventable Bacteria Reference Unit, UK Health Security Agency, London, UK.
Lancet Infect Dis. 2023 Oct;23(10):1197-1206. doi: 10.1016/S1473-3099(23)00188-3. Epub 2023 Jun 22.
Invasive Haemophilus influenzae serotype a (Hia) disease is rare, with most cases reported among Indigenous populations in North America. In England, national surveillance was enhanced following an increase in laboratory-confirmed invasive Hia disease since the 2016-17 epidemiological year. This study aimed to describe the epidemiological trends, clinical characteristics of cases, and assess potential genomic drivers.
Hospital laboratories in England routinely submit invasive H influenzae isolates to the UK Health Security Agency for confirmation and serotyping. In this prospective national surveillance study we contacted the general practitioners and clinicians of all patients with laboratory-confirmed invasive Hia from the 2008-09 to the 2021-22 epidemiological year to complete a clinical questionnaire on demographics, underlying conditions, clinical presentation, complications, outcomes, and travel history of the patient. All Hia invasive isolates from residents in England were included in the study; non-invasive isolates were excluded. Multilocus sequence typing (MLST), whole genome single-nucleotide polymorphism, and k-mer-based analysis of bacterial isolates were performed following Illumina whole-genome sequencing (WGS). Outcomes included epidemiological trends, clinical characteristics of confirmed Hia cases, and genomic analyses.
From the 2008-09 to the 2021-22 epidemiological years, there were 52 cases of invasive infection with H influenzae serotype a in England (25 [48%] in female patients and 27 [52%] in male patients). There were zero to two annual Hia cases (accounting for <0·5% of serotyped H influenzae isolates) until 2015-16, after which cases increased across England to 19 cases in 2021-22 (incidence 0·03 cases per 100 000), when Hia accounted for 19 (4%) of 484 serotyped H influenzae isolates, 19 (19%) of 100 capsulated cases, and 37% (19 of 52) of all H influenzae cases between 2008-09 and 2021-22. Most of the recent increase in cases occurred among individuals aged 65 years and older (17 [33%] of 52), who typically presented with bacteraemic pneumonia (13 [76%] of 17), and infants younger than 1 year, who had the highest incidence and were more likely to present with meningitis (five [50%] of ten). Overall case fatality rate was 7·7% (95% CI 2·1-19·7; four of 52 patients). WGS found that closely related MLST sequence types ST1511 (20 [39%] of 51), ST23 (13 [25%] of 51), and ST56 (seven [14%] of 51) accounted for most cases, with no evidence of serotype b strains switching capsule to Hia. Duplication of the capsule operon, associated with more severe disease, was present in 32 (80%) of 40 of these sequence types. Analysis of the core and accessory genome content grouped most isolates into a single strain.
The persistent increase in invasive Hia cases across England and across all age groups suggests widespread transmission, consistent with reports from other European countries, and will require close monitoring.
UK Health Security Agency.
侵袭性乙型流感嗜血杆菌血清型 a（Hia）疾病较为罕见，大多数病例发生在北美原住民人群中。在英格兰，自 2016-17 流行病学年以来，实验室确诊的侵袭性 Hia 疾病增加后，加强了国家监测。本研究旨在描述流行病学趋势、病例的临床特征，并评估潜在的基因组驱动因素。
英格兰的医院实验室常规将侵袭性流感嗜血杆菌分离株提交给英国卫生安全局进行确认和血清分型。在这项前瞻性全国性监测研究中，我们联系了所有 2008-09 至 2021-22 流行病学年期间实验室确诊的侵袭性 Hia 患者的全科医生和临床医生，以完成一份关于患者人口统计学、潜在疾病、临床表现、并发症、结局和旅行史的临床问卷。英格兰居民的所有侵袭性 Hia 分离株均纳入研究；排除非侵袭性分离株。采用 Illumina 全基因组测序（WGS）对所有 Hia 侵袭性分离株进行多位点序列分型（MLST）、全基因组单核苷酸多态性和基于 k-mer 的细菌分离株分析。结果包括流行病学趋势、确诊 Hia 病例的临床特征和基因组分析。
在 2008-09 至 2021-22 流行病学年期间，英格兰有 52 例侵袭性感染乙型流感嗜血杆菌血清型 a（25 例[48%]为女性患者，27 例[52%]为男性患者）。直到 2015-16 年，每年 Hia 病例数为零至两例（占血清型乙型流感嗜血杆菌分离株的<0.5%），此后英格兰的病例数增加到 2021-22 年的 19 例（发病率为每 100000 人 0.03 例），当时 Hia 占 484 例血清型乙型流感嗜血杆菌分离株的 19（4%），100 例有荚膜病例的 19（19%），以及 2008-09 至 2021-22 年所有乙型流感嗜血杆菌病例的 37%（52 例中的 19 例）。最近病例的增加主要发生在 65 岁及以上的人群（17 例[33%]，52 例），他们通常表现为菌血症性肺炎（17 例中的 13 例[76%]），以及 1 岁以下的婴儿，他们的发病率最高，更有可能出现脑膜炎（10 例中的 5 例[50%]）。总病死率为 7.7%（95%CI 2.1-19.7；52 例患者中有 4 例）。WGS 发现，密切相关的 MLST 序列类型 ST1511（51 例中的 20 例[39%]）、ST23（51 例中的 13 例[25%]）和 ST56（51 例中的 7 例[14%]）占大多数病例，没有证据表明血清型 b 菌株将荚膜切换到 Hia。与更严重疾病相关的荚膜操纵子的重复在这些序列类型中的 40 例（80%）中存在。核心和辅助基因组内容分析将大多数分离株分为单一菌株。
英格兰侵袭性 Hia 病例的持续增加以及所有年龄组的病例增加表明存在广泛传播，这与其他欧洲国家的报告一致，需要密切监测。
英国卫生安全局。
