Invasive Haemophilus influenzae Infections after 3 Decades of Hib Protein Conjugate Vaccine Use

Abstract

Haemophilus influenzae serotype b (Hib) was previously the most common cause of bacterial meningitis and an important etiologic agent of pneumonia in children aged <5 years. Its major virulence factor is the polyribosyl ribitol phosphate (PRP) polysaccharide capsule. In the 1980s, PRP-protein conjugate Hib vaccines were developed and are now included in almost all national immunization programs, achieving a sustained decline in invasive Hib infections. However, invasive Hib disease has 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 2 decades, other capsulated serotypes have been recognized increasingly as causing invasive infections. H. influenzae serotype a (Hia) is now a major cause of invasive infection in Indigenous communities of North America, prompting a possible requirement for an Hia conjugate vaccine. H. influenzae serotypes e and f are now more common than serotype b in Europe. Significant year-to-year increases in nontypeable H. influenzae invasive infections have occurred in many regions of the world. Invasive H. influenzae infections are now seen predominantly in patients at the extremes of life and those with underlying comorbidities. This review provides a comprehensive and critical overview of the current global epidemiology of invasive H. influenzae infections in different geographic regions of the world. It discusses those now at risk of invasive Hib disease, describes the emergence of other severe invasive H. influenzae infections, and emphasizes the importance of long-term, comprehensive, clinical and microbiologic surveillance to monitor a vaccine's impact.

Keywords: Haemophilus influenzae; Hib; conjugate vaccine; epidemiology; immunization; nontypeable H. influenzae.

FIG 1

Posteroanterior chest radiograph of an 11-month-old infant showing right-sided pneumonia caused by H. influenzae type b (copyright 2020 Grant Mackenzie).

FIG 2

Cartoon illustrating Hib conjugate vaccine. Polyribosyl ribitol phosphate (PRP) [composed of repeating units of 5-d-ribitol-(1→1)-β-d-ribose-3-phosphate] covalently linked to a carrier protein (chemical structure kindly provided by Neni Nurainy, Biofarma, Indonesia).

FIG 3

The six designated World Health Organization regions.

FIG 4

Number of cases of invasive Haemophilus influenzae infections in England, 1990 to 2018, by serotype (unpublished data from Public Health England, with permission from Shamez Ladhani).

FIG 5

Number of cases of invasive Haemophilus influenzae infection, by serotype, reported to National Institute of Communicable Diseases (NICD), South Africa, 2006 to 2018 (from GERMS-SA Annual Reports, 2006 to 2018, with permission from Anne von Gottberg, NICD, Johannesburg, South Africa) (139, 227–237).