Abstract：
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.
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.
摘要：
背景：侵袭性流感嗜血杆菌血清型（Hia）疾病很少见，报告的大多数病例来自北美的土著居民。在英国,自2016-17流行病学年以来,实验室确诊的侵袭性Hia病增加,国家监测得到加强.这项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。
方法：英格兰的医院实验室常规向英国卫生安全局提交侵袭性流感嗜血杆菌分离株进行确认和血清分型。在这项前瞻性国家监测研究中，我们联系了2008-09年至2021-22年流行病学年度所有实验室确诊的侵袭性Hia患者的全科医生和临床医生，以完成关于人口统计学的临床问卷。潜在条件，临床表现,并发症,结果，以及患者的旅行史。来自英格兰居民的所有Hia侵入性分离株都包括在研究中；非侵入性分离株被排除。多位点序列分型(MLST),全基因组单核苷酸多态性，在Illumina全基因组测序(WGS)之后进行细菌分离物的基于k聚体的分析。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。
结果：从2008-09到2021-22流行病学年，英国有52例流感嗜血杆菌血清型a的侵袭性感染(女性患者25例[48%],男性患者27例[52%]).在2015-16年之前，每年有零至两例Hia病例（占血清型流感嗜血杆菌分离株的<0·5％），此后，英格兰的病例在2021-22年增加到19例（每100000例发病率为0·03例），当Hia占484株血清分型的流感嗜血杆菌中的19株（4％）时，100例包囊病例中有19例（19%），在2008-09年至2021-22年期间，所有流感嗜血杆菌病例中有37%（52例中的19例）。最近病例增加的大部分发生在65岁及以上的个人(52人中有17人[33%]),通常出现细菌性肺炎（17人中有13人[76%]），1岁以下的婴儿，发病率最高，更有可能出现脑膜炎（十分之五[50%]）。总病死率为7·7%（95%CI2·1-19·7；52例患者中有4例）。WGS发现密切相关的MLST序列类型ST1511（51个中的20[39%]），ST23（51个中的13个[25%]），ST56（51个中的7个[14%]）占大多数病例，没有血清型b菌株将胶囊转换为Hia的证据。重复的胶囊操纵子，与更严重的疾病相关，存在于40种这些序列类型中的32种（80％）中。对核心和辅助基因组含量的分析将大多数分离株分为单个菌株。
结论：英格兰和所有年龄段的侵袭性Hia病例持续增加表明传播广泛，与其他欧洲国家的报道一致，需要密切监测.
背景：英国卫生安全局。
方法：英格兰的医院实验室常规向英国卫生安全局提交侵袭性流感嗜血杆菌分离株进行确认和血清分型。在这项前瞻性国家监测研究中，我们联系了2008-09年至2021-22年流行病学年度所有实验室确诊的侵袭性Hia患者的全科医生和临床医生，以完成关于人口统计学的临床问卷。潜在条件，临床表现,并发症,结果，以及患者的旅行史。来自英格兰居民的所有Hia侵入性分离株都包括在研究中；非侵入性分离株被排除。多位点序列分型(MLST),全基因组单核苷酸多态性，在Illumina全基因组测序(WGS)之后进行细菌分离物的基于k聚体的分析。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。
结果：从2008-09到2021-22流行病学年，英国有52例流感嗜血杆菌血清型a的侵袭性感染(女性患者25例[48%],男性患者27例[52%]).在2015-16年之前，每年有零至两例Hia病例（占血清型流感嗜血杆菌分离株的<0·5％），此后，英格兰的病例在2021-22年增加到19例（每100000例发病率为0·03例），当Hia占484株血清分型的流感嗜血杆菌中的19株（4％）时，100例包囊病例中有19例（19%），在2008-09年至2021-22年期间，所有流感嗜血杆菌病例中有37%（52例中的19例）。最近病例增加的大部分发生在65岁及以上的个人(52人中有17人[33%]),通常出现细菌性肺炎（17人中有13人[76%]），1岁以下的婴儿，发病率最高，更有可能出现脑膜炎（十分之五[50%]）。总病死率为7·7%（95%CI2·1-19·7；52例患者中有4例）。WGS发现密切相关的MLST序列类型ST1511（51个中的20[39%]），ST23（51个中的13个[25%]），ST56（51个中的7个[14%]）占大多数病例，没有血清型b菌株将胶囊转换为Hia的证据。重复的胶囊操纵子，与更严重的疾病相关，存在于40种这些序列类型中的32种（80％）中。对核心和辅助基因组含量的分析将大多数分离株分为单个菌株。
结论：英格兰和所有年龄段的侵袭性Hia病例持续增加表明传播广泛，与其他欧洲国家的报道一致，需要密切监测.
背景：英国卫生安全局。
