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Clinical and Molecular Epidemiology of Childhood Invasive Nontypeable Haemophilus influenzae Disease in England and Wales

Collins, Sarah MPH; Vickers, Anna PhD; Ladhani, Shamez N. MRCPCH, PhD; Flynn, Sally FIBMS; Platt, Steven PhD; Ramsay, Mary E. FFPHM; Litt, David J. PhD; Slack, Mary P. E. FRCPath

The Pediatric Infectious Disease Journal: March 2016 - Volume 35 - Issue 3 - p e76–e84
doi: 10.1097/INF.0000000000000996
Original Studies

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.

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.

Accepted for publication November 10, 2015.

Both S.C. and A.V. contributed equally to this work.

This work was supported by an investigator-initiated research grant from GlaxoSmithKline Biologicals SA (GSK study identifier: 114996). The sponsor of the study had no role in study design, data collection, data analysis, data interpretation, writing the report or the final decision to submit the article for publication. GlaxoSmithKline Biologicals SA was provided the opportunity to review a preliminary version of this manuscript for factual accuracy, but the authors are solely responsible for final content and interpretation. The authors received no financial support or other form of compensation related to the development of the manuscript. All authors had full access to all the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. S.N.L. has performed contract research on behalf of St. George’s University of London but has not received any personal remuneration. M.P.E.S. and S.N.L. have received assistance for attending conferences from vaccine manufacturers. S.C., S.N.L. and M.E.R. have provided vaccine manufactures with post-marketing surveillance reports, which the companies are required to submit to the U.K. Licensing authority in compliance with their Risk Management Strategy. In accordance with Public Health England policy a cost recovery charge is made for these reports payable to the Immunisation Department. Public Health England has received payment for lectures given by M.P.E.S. and S.L. from GSK, Baxter, SPMSD and Novartis. Public Health England has received grants from GSK in payment for research carried out by the authors, including A.V.’s salary.

Address for correspondence: Shamez N. Ladhani, MRCPCH, PhD, Health Protection Services; Immunisation, Hepatitis, and Blood Safety Department; Public Health England, 61 Colindale Avenue, London NW9 5EQ, United Kingdom. E-mail:

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