H influenzae invasive infections after 3 decades of Hib conjugate vaccine

Haemophilus influenzae serotype b (Hib) used to be the commonest cause of bacterial meningitis in children in children aged less than 5 years, with most cases occurring in children aged 3 months to 3 years. In high income countries the case fatality ratio of Hib meningitis was ~ 5 to 10%, and 15% to 30% of survivors had significant long-term sequelae, including sensorineural deafness, intellectual impairment, epilepsy, cerebral palsy or hydrocephalus.

The major virulence factor of Hib is the polyribosyl ribitol (PRP) polysaccharide capsule. In the 1980s, PRP- protein conjugate Hib vaccines were developed and are now included in almost all national immunization programmes, achieving a sustained decline in invasive Hib meningitis. However, invasive Hib infections have not yet been eliminated in countries with low vaccine coverage and sporadic outbreaks of Hib infection still occur occasionally in countries with high vaccine coverage.

Over the past two decades, other capsulated serotypes have been recognised increasingly as causing invasive infections. Hib meningitis is now uncommon, but meningitis caused by other capsulated serotypes of H.influenzae and non-typeable strains (NTHi) should be considered. H.influenzae serotype a (Hia) has emerged as a significant cause of meningitis in Indigenous children in North America, and this may necessitate an Hia conjugate vaccine. Cases of Hie, Hif and NTHi meningitis are predominantly seen in young children and less commonly in older age groups with underlying predisposing conditions, and other vulnerable patients. The changing epidemiology of H.influenzae meningitis emphasises the importance of on-going surveillance. Epidemiological and microbiological surveillance should be comprehensive, covering all ages and all types of H.influenzae, documenting clinical presentation, underlying risk factors and outcome together with accurate typing of strains by molecular methods.

In 2020, the World Health Organisation (WHO) published the document “Defeating meningitis by 2030: a global road map”. The aims of the road map included reducing deaths from vaccine-preventable meningitis; introduction of new vaccines; increasing vaccine coverage; and improving surveillance and advocacy. In this presentation the current epidemiology of H.influenzae meningitis will be reviewed to assess the progress made to date in achieving the goals set out in the road map.

Professor Slack is an Independent Consultant Medical Microbiologist. She was formerly employed by Public Health England (PHE) as Head of the Haemophilus Reference Unit in the Respiratory & Vaccine Preventable Bacteria Reference Unit, Colindale, London, United Kingdom. She coordinated the laboratory aspects of enhanced population-based surveillance on invasive Haemophilus influenzae and Streptococcus pneumoniae disease in England and Wales. From 1975 to 2003 she was the University Lecturer (Honorary Consultant) in Bacteriology at the University of Oxford, responsible for clinical microbiology teaching to Oxford Clinical Medical Students. She is currently a Professor in the School of Medicine, Griffith University, Queensland, Australia.

She was formerly Head of the WHO Collaborating Centre for Haemophilus influenzae and Streptococcus pneumoniae; Head of the Global Reference Laboratory for Haemophilus influenzae in the WHO Global Vaccine-Preventable Invasive Bacterial Disease (VP-IBD) Surveillance Network.

She has worked extensively in developing countries- assisting WHO, PATH, IVI, the Hib Initiative and the PneumoADIP by providing technical support, advice and training for sentinel site surveillance of paediatric bacterial meningitis, pneumonia and sepsis.

Her principal research interests include aspects of infections caused by H. influenzae and S. pneumoniae, specifically the epidemiology of invasive haemophilus and pneumococcal infections, the impact of Hib and pneumococcal conjugate vaccines, mechanisms of antimicrobial resistance in H. influenzae, the role of vaccines in combatting antimicrobial resistance and community acquired pneumonia.