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Tag words: Haemophilus, Haemophilus influenzae, H influenzae, H flu, Hib vaccine, meningitis, Hib meningitis.

Haemophilus influenzae

Kingdom: Bacteria
Phylum: Proteobacteria
Class: Gamma Proteobacteria
Order: Pasteurellales
Family: Pasteurellaceae
Genus: Haemophilus
Species: H. influenzae








Kenneth Todar currently teaches Microbiology 100 at the University of Wisconsin-Madison.  His main teaching interests include general microbiology, bacterial diversity, microbial ecology and pathogenic bacteriology.

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Haemophilus influenzae and Hib Meningitis (page 3)

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© Kenneth Todar, PhD

Immunity

The age incidence of H. influenzae meningitis is inversely proportional to the titer of bactericidal antibody in the blood, whether passively acquired from the mother or actively formed (see Figure 4 below). Without artificial immunization, in children aged 2 months to 3 years, antibody levels are minimal; thereafter antibody levels increase and the disease becomes much less common. From this curve, it is obvious that artificial active immunization should begin at 2 months of age, when nearly all passive immunity has waned, and the child enters a vulnerable non immune period of life.

Figure 4. Relation of the age incidence of bacterial meningitis caused by Haemophilus influenzae to bactericidal antibody titers in the blood (data pre 1985).

H. influenzae is susceptible to lysis by antibody and complement. Furthermore, anticapsular antibodies promote phagocytosis, as well as bacteriolysis. Thus, serum antibody, complement, lysozyme and phagocytes can work in concert during a bacteremia. During meningitis, phagocytosis is probably the main host defense mechanism since complement rarely occurs in the cerebrospinal fluid.

For many years it was believed that bactericidal antibody directed against PRP capsule of H. influenzae type b was entirely responsible for host resistance to infection. However, some recent studies have stressed a role for antibody to somatic (cell wall) antigens as well. For example, antibody to PRP can often be detected in the sera of children on admission to the hospital with sepsis due to H. influenzae type b. Adsorption of immune serum with PRP alone does not remove its protective capabilities, whereas adsorption with whole organisms does. Separation of the outer membrane of type b H. influenzae into its many protein constituents reveals several individual membrane proteins that may be associated with immunity. Bactericidal antibodies that react with individual outer membrane proteins (e.g. P1, P2) or with lipooligosaccharide constituents have been identified. These findings support indicate the potential importance of antibody to noncapsular antigens in adaptive immunity to H. influenzae type b infection. In addition, opsonizing antibodies, which also play a role in protection, may be directed against PRP, as well as somatic constituents (Figure 5).


Figure 5. Phagocytic engulfment of H. influenzae bacterium opsonized by antibodies specific for the capsule and somatic (cell wall) antigens.

Recent studies of nontypable H. influenzae have shown that bactericidal antibody to outer membrane proteins develops in infants in response to otitis media caused by the organism. Normal adults generally have both bactericidal and opsonizing antibodies directed against nontypable H. influenzae.

Treatment

Virtually all patients treated early in the course of H. influenzae meningitis are cured. The mortality rate of treated infections is less than 10 percent, but nearly 30 percent of the children who recover have residual neurologic effects. Ampicillin has been the drug of choice, but presently over 20 percent of all strains of H. influenzae are resistant to ampicillin because of plasmid-mediated ß-lactamase production.

The recommended treatment for H. influenzae meningitis is ampicillin for strains of the bacterium that do not produce ß-lactamase, and a third-generation cephalosporin or chloramphenicol for strains that do. Amoxicillin, together with a substance such as clavulanic acid, that blocks the activity of ß-lactamase, has been unreliable in treatment of meningitis, although it is effective in treatment of sinusitis, otitis media and respiratory infections.  Chloramphenicol was long considered the drug of choice for meningitis caused by penicillin-resistant H. influenzae, and it is still highly effective, but not without potential toxic side effects. Third-generation cephalosporins, such as ceftriaxone or cefotaxime, are effective against H. influenzae and penetrate the meninges well. Tetracyclines and sulfa drugs remain effective in treating sinusitis or respiratory infection caused by nontypable H. influenzae. Amoxicillin plus clavulanic acid (Augmentin) is effective against non type b ß-lactamase producing strains. Erythromycin is ineffective in treatment of H. influenzae infections.


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Kenneth Todar is an emeritus lecturer at University of Wisconsin-Madison. He has taught microbiology to undergraduate students at The University of Texas, University of Alaska and University of Wisconsin since 1969.

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