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The types of infectious diseases caused by Haemophilus influenzae have changed considerably in recent years as a result of the widespread implementation of routine childhood immunization against type b organisms, but the organism remains an important pathogen. There are 2 major categories of disease caused by H influenzae: infections caused by unencapsulated strains (nontypeable [NTHi]) and disease induced by encapsulated strains (typeable). The unencapsulated strains are responsible chiefly for infections at mucosal surfaces, including conjunctivitis, otitis media, sinusitis, and bronchitis. In contrast, encapsulated strains are associated with invasive disease. Of the 6 encapsulated strains, type b in particular is associated with septicemia, meningitis, cellulitis, septic arthritis, epiglottitis, and pneumonia. Prior to the availability of an effective vaccine, H influenzae type b (Hib) was the most common cause of pediatric bacterial meningitis in the United States.


H influenzae is a small gram-negative coccobacillus that shows considerable microscopic pleomorphism, necessitating careful and cautious interpretation of Gram stains of clinical specimens (Fig. 258-1). Biochemical identification of H influenzae has classically been based on the demonstration that growth on rich media (blood agar) is dependent on supplements, factors X (hemin) and V (β-nicotinamide adenine dinucleotide [NAD]), as found in chocolate agar. Although both factors are present in erythrocytes, the V factor must be released from the cell in order to sustain replication, and hence, standard blood agar is an unsatisfactory media for growth of H influenzae. The V factor may be exogenously provided or derived from lysed red blood cells; heated blood agar (chocolate agar) provides both factors. The growth of H influenzae is fastidious, and the viability of the organism is lost rapidly, necessitating expeditious handling of clinical specimens.

Figure 258-1

Gram stain of Haemophilus influenzae. Arrows point to 2 small “cocco-bacillary” gram-negative rods. (Used with permission from Professor Shirley Lowe, University of California, San Francisco School of Medicine.)

The polysaccharide capsule of H influenzae has a central role in the virulence of the organism and plays a role in the pathogenesis of invasive disease. Six antigenically and biochemically distinct capsular polysaccharide subtypes (a–f) have been identified. All isolates associated with invasive infection should be serotyped, either through slide agglutination serotyping or genotyping by polymerase chain reaction. Although type b encapsulated strains have historically been of primary clinical and immunologic importance (because of the association with invasive infection, including meningitis), the other encapsulated strains also are capable of producing invasive disease. Lipopolysaccharide (LPS) is another important component of the H influenzae cell wall that contributes to pathogenesis. Although chemically different from the LPS of the Enterobacteriaceae, the biological activity of Hib LPS is similar to that of other gram-negative endotoxins. Multiple adhesins target specific cells of the airway and provide redundancy for adherence to respiratory tissues. H influenzae encodes 3 distinct immunoglobulin ...

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