Haemophilus influenzae used to be the leading cause of meningitis in young children, but the use of the highly effective “conjugate” vaccine has greatly reduced the incidence of meningitis caused by this organism. It is still an important cause of upper respiratory tract infections (otitis media, sinusitis, conjunctivitis, and epiglottitis) and sepsis in children. It also causes pneumonia in adults, particularly in those with chronic obstructive lung disease. Haemophilus ducreyi, the agent of chancroid, is discussed in Chapter 27.
Haemophilus influenzae is a small, pleomorphic gram-negative rod (coccobacillary rod) with a polysaccharide capsule (Figure 19–1). It is one of the three important encapsulated pyogens, along with the pneumococcus and the meningococcus. Serologic typing is based on the antigenicity of the capsular polysaccharide. Of the six serotypes (a–f), type b is the most important. Type b used to cause most of the severe, invasive diseases, such as meningitis and sepsis, but the widespread use of the vaccine containing the type b capsular polysaccharide as the immunogen has greatly reduced the incidence of invasive disease caused by this type. The type b capsule is composed of polyribitol phosphate.
Haemophilus influenzae—Gram stain. Arrows point to two small “coccobacillary” gram-negative rods. (Used with permission from Professor Shirley Lowe, University of California, San Francisco School of Medicine.)
Unencapsulated strains can also cause disease, especially mucosal diseases of the upper respiratory tract such as sinusitis and otitis media, but are usually noninvasive. Growth of the organism on laboratory media requires the addition of two components, heme (factor X) and NAD (factor V), for adequate energy production.
Pathogenesis & Epidemiology
Haemophilus influenzae infects only humans; there is no animal reservoir. It enters the body by the inhalation of airborne droplets into the respiratory tract, resulting in either asymptomatic colonization or infections such as otitis media, sinusitis, or pneumonia. The organism produces an IgA protease that degrades secretory IgA, thus facilitating attachment to the respiratory mucosa. After becoming established in the upper respiratory tract, the organism can enter the bloodstream (bacteremia) and spread to the meninges. Meningitis is caused primarily by the encapsulated strains, but nonencapsulated strains are frequently involved in otitis media, sinusitis, and pneumonia. Note that the incidence of meningitis caused by capsular type b has been greatly reduced because the vaccine contains the type b polysaccharide as the immunogen. Pathogenesis of H. influenzae involves its antiphagocytic capsule and endotoxin; no exotoxin is produced.
Most infections occur in children between the ages of 6 months and 6 years, with a peak in the age group from 6 months to 1 year. This age distribution is attributed to a decline in maternal IgG in the child coupled with the inability of the child to generate sufficient antibody against the polysaccharide capsular antigen until the age of approximately 2 years.
Meningitis caused by H. influenzae cannot be distinguished on clinical grounds from that caused by other bacterial pathogens (e.g., pneumococci or meningococci). The rapid onset of fever, headache, and stiff neck, along with drowsiness, is typical. Sinusitis and otitis media cause pain in the affected area, opacification of the infected sinus, and redness with bulging of the tympanic membrane. Haemophilus influenzae is second only to the pneumococcus as a cause of these two infections.
Other serious infections caused by this organism include septic arthritis, cellulitis, and sepsis, the latter occurring especially in splenectomized patients. Rarely, epiglottitis, which can obstruct the airway, occurs. A swollen “cherry-red” epiglottis is seen. This life-threatening disease of young children is caused almost exclusively by H. influenzae. Pneumonia in elderly adults, especially those with chronic respiratory disease, can be caused by untypeable strains of H. influenzae.
Laboratory diagnosis depends on isolation of the organism on heated-blood (“chocolate”) agar enriched with two growth factors required for bacterial respiration, namely, factor X (a heme compound) and factor V (NAD). The blood used in chocolate agar is heated to inactivate nonspecific inhibitors of H. influenzae growth.
An organism that grows only in the presence of both growth factors is presumptively identified as H. influenzae; other species of Haemophilus, such as Haemophilus parainfluenzae, do not require both factors. Definitive identification can be made with either biochemical tests or the capsular swelling (quellung) reaction. Additional means of identifying encapsulated strains include fluorescent antibody staining of the organism and counterimmunoelectrophoresis or latex agglutination tests, which detect the capsular polysaccharide.
The treatment of choice for meningitis or other serious systemic infections caused by H. influenzae is ceftriaxone. From 20−30% of H. influenzae type b isolates produce a β-lactamase that degrades penicillinase-sensitive β-lactams such as ampicillin but not ceftriaxone. It is important to institute antibiotic treatment promptly, because the incidence of neurologic sequelae (e.g., subdural empyema) is high. Untreated H. influenzae meningitis has a fatality rate of approximately 90%. H. influenzae upper respiratory tract infections, such as otitis media and sinusitis, are treated with either amoxicillin-clavulanate or trimethoprim-sulfamethoxazole.
The vaccine contains the capsular polysaccharide of H. influenzae type b conjugated to diphtheria toxoid or other carrier protein. Depending on the carrier protein, it is given some time between the ages of 2 and 15 months. This vaccine is much more effective in young children than the unconjugated vaccine and has reduced the incidence of meningitis caused by this organism by approximately 90% in immunized children. Meningitis in close contacts of the patient can be prevented by rifampin. Rifampin is used because it is secreted in the saliva to a greater extent than ampicillin. Rifampin decreases respiratory carriage of the organism, thereby reducing transmission.