Hib strains cause systemic disease by invasion and systemic spread from the respiratory tract to distant sites (e.g., meninges, bones, joints). In contrast, NTHi strains cause disease by spread from the nasopharynx to contiguous sites (e.g., middle ear, lower respiratory tract).

• The polysaccharide capsule of encapsulated strains is critical for the organism's avoidance of opsonization.
• Levels of maternally derived antibodies to the capsular polysaccharide decline from birth to ~6 months of age and—in the absence of vaccination—remain low until ~2-3 years of age.