英格兰和威尔士儿童侵袭性不可分型流感嗜血杆菌疾病的临床与分子流行病学
Clinical and Molecular Epidemiology of Childhood Invasive Nontypeable Haemophilus influenzae Disease in England and Wales.
作者信息
Collins Sarah, Vickers Anna, Ladhani Shamez N, Flynn Sally, Platt Steven, Ramsay Mary E, Litt David J, Slack Mary P E
机构信息
From the *Immunisation, Hepatitis and Blood Safety Department (IHBSD), †Respiratory and Vaccine Preventable Bacterial Reference Unit (RVPBRU), §Infectious Disease Informatics, Public Health England, London, United Kingdom; ‡Paediatric Infectious Diseases Research Group, St. George's University of London, London, United Kingdom; ¶Institute for Hygiene and Microbiology, University of Wuerzburg, Wuerzburg, Germany; and ‖School of Medicine, Griffith University Gold Coast Campus, Queensland, Australia.
出版信息
Pediatr Infect Dis J. 2016 Mar;35(3):e76-84. doi: 10.1097/INF.0000000000000996.
INTRODUCTION
In countries with established Haemophilus influenzae type b (Hib) immunization programs, nontypeable H. influenzae (NTHi) is now responsible for nearly all invasive H. influenzae cases across all age groups.
METHODS
Public Health England (PHE) conducts enhanced national surveillance of invasive H. influenzae disease in England and Wales. Invasive NTHi isolates submitted to Public Health England from children of ages 1 month to 10 years during 2003-2010 were characterized by multilocus sequence typing (MLST). Detailed clinical information was obtained for all laboratory-confirmed cases of invasive NTHi disease in children during 2009-2013.
RESULTS
In England and Wales, there were 7797 cases of invasive H. influenzae disease diagnosed during 2000-2013 and 1585 (20%) occurred in children aged 1 month to 10 years, where NTHi was responsible for 31-51 cases (incidence, 0.53-0.92/100,000) annually. Detailed clinical follow-up of 214 confirmed NTHi cases diagnosed in this age-group during 2009-2013 revealed that 52% (n = 111) occurred in <2-year-old and 52% (n=110) had comorbidity. Bacteremic pneumonia was the most common clinical presentation (n = 99, 46%), 16% (n = 34) required intensive care and 11% (n = 23) died. Characterization by biotyping and MLST of 316 NTHi strains from children with invasive disease during 2003-2010 revealed a genetically heterogeneous population (155 MLSTs) with diverse biotypes and no association with comorbidity status, clinical disease or outcome.
CONCLUSIONS
The high level of genetic diversity in invasive NTHi strains highlights the difficulties in developing an effective vaccine against this pathogen.
引言
在已实施b型流感嗜血杆菌（Hib）免疫规划的国家，目前所有年龄组的几乎所有侵袭性流感嗜血杆菌病例均由非b型流感嗜血杆菌（NTHi）引起。
方法
英国公共卫生署（PHE）在英格兰和威尔士对侵袭性流感嗜血杆菌病开展强化的全国监测。2003年至2010年期间，提交给英国公共卫生署的1个月至10岁儿童的侵袭性NTHi分离株通过多位点序列分型（MLST）进行特征分析。获取了2009年至2013年期间所有实验室确诊的儿童侵袭性NTHi病病例的详细临床信息。
结果
在英格兰和威尔士，2000年至2013年期间共诊断出7797例侵袭性流感嗜血杆菌病病例，其中1585例（20%）发生在1个月至10岁的儿童中，NTHi每年导致31至51例病例（发病率为0.53至0.92/10万）。对2009年至2013年期间在该年龄组确诊的214例NTHi病例进行的详细临床随访显示，52%（n = 111）发生在2岁以下儿童中，52%（n = 110）有合并症。菌血症性肺炎是最常见的临床表现（n = 99，46%），16%（n = 34）需要重症监护，11%（n = 23）死亡。对2003年至2010年期间侵袭性疾病儿童的316株NTHi菌株进行生物分型和MLST特征分析，发现其为基因异质性群体（155种MLST型），生物型多样，且与合并症状态、临床疾病或结局无关。
结论
侵袭性NTHi菌株的高度遗传多样性凸显了研发针对该病原体的有效疫苗的困难。
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