INTRODUCTION
Haemophilus influenzae are facultative, anaerobic, Gram-negative
coccobacilli requiring two accessory growth factors, X (hemin) and V
(nicotinamide adenine dinucleotide, NAD). They are restricted human
pathogens comprising both encapsulated (a–f) and unencapsulated or
non-typeable (non-typeable H. influenzae [NTHi ])
strains. Encapsulated serotypes cause invasive disease, whileNTHi strains are genetically diverse and have adapted to colonize
the nasopharynx and cause local mucosal infections. NTHi are
acquired by either person-to-person transmission from respiratory
droplets or from direct contact with respiratory secretions.
Nasopharyngeal colonization by NTHi begins during infancy, where
one-third are colonized by 1-year of age and nearly one-half by age
2-years.Colonization rates are higher in Indigenous children, those with
older siblings, amongst childcare attendees, and during viral
respiratory infectionNTHi carriage is dynamic, with frequent
strain turnover; the same child can acquire a new strain with loss of
the old ones or carry multiple strains simultaneously, some of which are
shared with primary caregivers, suggesting that transmission is
occurring between them.
In children, NTHi colonizing the nasopharynx can cause otitis
media, sinusitis, and conjunctivitis, while in preterm and young
infants, and those with serious underlying comorbidities, they may
occasionally invade leading to sepsis and bacteremic pneumonia. As an
upper airway colonizer, NTHi can also access the lungs by
inhalation or via micro-aspiration episodes and direct mucosal
dispersion. In healthy children, these incursions are transient, as
microbes are removed by mucociliary clearance (MCC) and innate immune
defenses. However, NTHi are able to colonize the lower airways of
children with chronic suppurative lung disease (CSLD) where impaired
MCC, airway wall injury, and regional microenvironments favor microbial
growth. This review describes the lower airway defenses, and howNTHi evades these defenses to establish infection. In so doing,NTHi contributes to the pathogenesis of CSLD, an umbrella term
used here to encompass protracted bacterial bronchitis (PBB),
bronchiectasis, cystic fibrosis (CF) and primary ciliary dyskinesia
(PCD). The role of NTHi in asthma is beyond the scope of this
review and is discussed elsewhere.17