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