Haemophilus influenzae and Hib Meningitis (page 3)
(This chapter has 4 pages)
© 2008 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.
chapter continued
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