Microbiology

H. influenzae is a small, gram-negative, pleomorphic coccobacillus that grows both aerobically and anaerobically.

• Six major serotypes (designated a-f) have been identified on the basis of antigenically distinct polysaccharide capsules.
• Unencapsulated strains are referred to as nontypable (NTHi).

Epidemiology

H. influenzae, an exclusively human pathogen, is spread by airborne droplets or through direct contact with secretions or fomites.

• Type b (Hib) strains are most important clinically, causing systemic invasive disease, primarily in infants and children <6 years of age.
• Of the 194 World Health Organization member countries, 99% have introduced Hib conjugate vaccination, but a large number of children worldwide remain unimmunized.
• Both typable and nontypable strains can asymptomatically colonize the nasopharynx.

Pathogenesis

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.

Clinical Manifestations

• Hib infection: The most serious Hib infections are associated with meningitis or epiglottitis.
  • - Meningitis: primarily affects children <2 years old and presents similarly to meningitis due to other bacterial pathogens
    • Mortality rates are ∼5%.
    • Morbidity rates are high: 6% of pts have sensorineural hearing loss; one-fourth have some significant handicap; and one-half have some neurologic sequelae.
  • Epiglottitis: occurs in children 2-7 years old and occasionally in adults. It involves cellulitis of the epiglottis and supraglottic tissues that begins with a sore throat and fever and progresses rapidly to dysphagia, drooling, and airway obstruction.
  • Other infections: include cellulitis, pneumonia, osteomyelitis, septic arthritis, and bacteremia without an identifiable focus
• NTHi infection: NTHi is a common cause of lower respiratory tract disease in adults, particularly those with chronic obstructive pulmonary disease (COPD).
  • - COPD exacerbations: characterized by increased cough, sputum production, and shortness of breath
  • - Pneumonia: presents similarly to other bacterial pneumonias, including pneumococcal pneumonia
  • - Other infections: NTHi is one of the three most common causes of childhood otitis media and is an important cause of sinusitis (in adults and children) and neonatal bacteremia. It is a less common cause of invasive infections in adults.

Diagnosis

Recovery of the organism in culture is the most reliable method for diagnosis.

• The presence of gram-negative coccobacilli in gram-stained CSF provides strong evidence for meningitis due to H. influenzae.
• Detection of polyribitol ribose phosphate (PRP)-polymers of which form the type b capsule-in CSF allows rapid diagnosis of Hib meningitis before culture results are available.

Prevention

Hib vaccine is recommended for all children worldwide; the immunization series should be started at ∼2 months of age.

• Secondary attack rates are high among household contacts of pts with Hib disease. All children and adults (except pregnant women) in households with a case of Hib disease and at least one incompletely immunized contact <4 years of age should receive prophylaxis with oral rifampin.
• A vaccine that combines NTHi and pneumococcal antigens is used in many countries outside the United States and has shown partial efficacy in preventing H. influenzae otitis media.