What is Haemophilus influenzae, a bacterium that affects children under 5 and individuals with compromised immune systems, such as those with Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) or undergoing chemotherapy?

What is Haemophilus influenzae?

Haemophilus influenzae is a gram-negative bacterial pathogen that colonizes the human respiratory tract and causes both invasive diseases (meningitis, bacteremia, epiglottitis) and localized respiratory infections (otitis media, sinusitis, pneumonia), with children under 5 years and immunocompromised individuals at highest risk. 1

Bacterial Characteristics

• H. influenzae is a small, pleomorphic, facultatively anaerobic gram-negative coccobacillus that requires both hemin (X factor) and NAD (V factor) for growth 1, 2
• The bacterium exists in two forms: encapsulated (typeable, with six serotypes designated a through f) and unencapsulated (nontypeable) strains 1, 2
• It is a strict human parasite found principally in the upper respiratory tract, spreading person-to-person through airborne droplets or direct contact with respiratory secretions 2

Clinical Disease Patterns

H. influenzae produces two distinct patterns of disease:

Invasive Infections (Primarily Type b)

• Type b strains cause more than 95% of systemic infections, including meningitis, septic arthritis, epiglottitis, pneumonia, and cellulitis, with bacteremia as a prominent feature 2
• These invasive diseases occur predominantly in young children under 5 years of age, particularly those under 2 years 3
• Before the Hib vaccine introduction in 1987, invasive H. influenzae type b disease occurred at a rate of 34 cases per 100,000 children under 5 years; this decreased 99% to 0.4 cases per 100,000 by 1995 3

Localized Respiratory Infections (Primarily Nontypeable)

• Nontypeable strains cause contiguous spread within the respiratory tract, resulting in otitis media, sinusitis, bronchitis, and the conjunctivitis-otitis syndrome 4, 5
• These infections are numerically more common but less serious than invasive disease 2, 4
• Nontypeable H. influenzae is a primary pathogen in acute otitis media, particularly associated with older age and recurrent disease 5

High-Risk Populations

Children

• Children under 5 years, especially those under 2 years, are at highest risk for invasive disease 3
• The highest hospitalization rates occur in children under 6 months of age 3
• In developing countries, nontypeable strains cause many cases of pediatric pneumonia 4

Immunocompromised Patients

• More than 50% of patients with multiple myeloma lack protective anti-Haemophilus influenzae antibodies, and 70% lack serum bactericidal activity against Hib 3
• Patients with HIV/AIDS, those undergoing chemotherapy, and transplant recipients on immunosuppressive therapy are at increased risk 3
• Patients with asplenia, complement deficiencies, and chronic medical conditions require special vaccination considerations 3

Virulence Mechanisms

• The capsular polysaccharide (particularly type b, composed of ribosyl-ribitol phosphate) is the most important virulence factor for invasive disease 2, 6
• H. influenzae produces factors that inhibit ciliary activity of respiratory epithelial cells, including lipopolysaccharide and a heat-stable glycopeptide 2
• Additional virulence factors include adhesion proteins, pili, outer membrane proteins, IgA1 protease, and lipooligosaccharide 6

Antibiotic Resistance

• Approximately 30-40% of H. influenzae strains produce beta-lactamase, conferring resistance to ampicillin and amoxicillin 1, 4
• Beta-lactamase production is the primary mechanism of resistance to penicillins 1, 6
• H. influenzae has intrinsically poor susceptibility to macrolides and azalides due to efflux pumps 1
• Essentially all isolates, including beta-lactamase-producing strains, remain susceptible to high-dose amoxicillin-clavulanate 1

Diagnosis

• Laboratory confirmation requires isolation from normally sterile sites (blood, cerebrospinal fluid, joint fluid, pleural fluid, pericardial fluid) 1
• Gram stain of specimens shows small gram-negative coccobacilli 2
• Detection of capsular antigen in serum, CSF, or concentrated urine using latex agglutination or immunoassay can diagnose up to 90% of culture-proven meningitis cases 2

Treatment Considerations

• For susceptible (beta-lactamase-negative) strains, high-dose amoxicillin (80-90 mg/kg/day in 2 divided doses) is first-line treatment 1, 7
• Third-generation cephalosporins (cefotaxime or ceftriaxone) are used for life-threatening infections when H. influenzae is known or suspected 8, 2
• For respiratory infections where H. influenzae is suspected, empiric therapy should cover both H. influenzae and S. pneumoniae 1

Prevention

• Haemophilus influenzae type b (Hib) vaccine has dramatically reduced invasive type b disease 1, 3
• Vaccination is recommended for all children following standard schedules, with catch-up vaccination for those who start late 3
• Patients with hydrocephalus and shunts, asplenia, or immunocompromising conditions should receive Hib vaccine due to higher risk of invasive bacterial infections 3, 9
• In the post-vaccine era, nontypeable strains have become increasingly important causes of disease 6, 5