Haemophilus influenzae and Hib Meningitis (page 2)
(This chapter has 4 pages)
© Kenneth Todar, PhD
Pathogenesis
Naturally-acquired disease caused by H. influenzae seems to
occur
in humans only. In infants and young children (under 5 years of age), H.
influenzae type b causes bacteremia and acute bacterial meningitis.
Occasionally, it causes epiglottitis (obstructive laryngitis), cellulitis,
osteomyelitis,
and joint infections. Nontypable H. influenzae causes
ear
infections (otitis media) and sinusitis in children, and
is associated with respiratory tract infections (pneumonia) in
infants,
children and adults.
Seven serotypes of the bacterium have been identified on the basis
of
capsular polysaccharides. H.
influenzae type b is the most important serotype involved in
meningitis.
Disease caused by H. influenzae usually begins in the upper
respiratory
tract as nasopharyngitis and may be followed by sinusitis and otitis,
possibly
leading to pneumonia. In severe cases, bacteremia may occur, which
frequently
results in joint infections or meningitis.
Infection with Haemophilus
influenzae
type b (Hib) can result in meningitis and other severe infections
(e.g., pneumonia, bacteremia, cellulitis, septic arthritis, and
epiglottitis) primarily among infants and children <5 years of age.
Hib disease is uncommon in individuals 5 years of age or older. Hib
meningitis has a case-fatality ratio of 5-10% in the United States even
with initiation of early antimicrobial therapy. As a result of the
widespread use of Hib conjugate
vaccines, the disease is now uncommon
in the U.S. and is seen primarily in infants too young to be
vaccinated and unvaccinated children. According to the CDC, in 2004,
the estimated annual
incidence of Hib was 0.15 cases per 100,000 in children younger than 5
years of age.
The pathogenesis of H. influenzae infections is not completely
understood,
although the presence of the type b polysaccharide capsule is
known
to be the major factor in virulence. Encapsulated organisms can
penetrate
the epithelium of the nasopharynx and invade the blood capillaries
directly.
Their capsule allows them to resist phagocytosis and
complement-mediated
lysis in the nonimmune host. Nontypable (non encapsulated) strains
are less invasive, but they are apparently able to induce an
inflammatory
response that causes disease. Outbreaks of H. influenzae type
b
infection may occur in nurseries and child care centers, and
prophylactic
administration of antibiotics is warranted. Vaccination with type b
polysaccharide
(in the form of Hib conjugate vaccines) is effective in
preventing
infection, and several vaccines are now available for routine use.
Figure 3. Tissues infected
by
type
b and nontypable strains of Haemophilus influenzae.
Virulence
H. influenzae does not produce any demonstrable exotoxins The
direct
role of endotoxin in meningitis or bacteremia is unclear,
although
the Gram-negative bacterium's outer membrane lipooligosaccharide
(LOS)
is thought to play a role in inflammation associated with otitis media.
All virulent strains produce neuraminidase and an IgA
protease,
but the role of these extracellular enzymes in invasion is unproven. Fimbriae
increase the adherence of bacteria to human mucosal cells in vitro, and
they are required for successful colonization of the nasopharynx. The
Anton
antigen, as defined in red blood cells, appears to be the receptor.
Virulence, at least in the case of bacteremia and meningitis, is
directly
related to capsule formation. Virtually all of these infections are
caused
by the type b serotype, and its capsular polysaccharide, containing
ribose,
ribitol and phosphate, is the proven determinant of virulence. The
capsule
material is antiphagocytic, and it is ineffective in inducing the
alternative
complement pathway, so that the bacterium can invade the blood or
cerebrospinal
fluid without attracting phagocytes or provoking an inflammatory
response
and complement-mediated bacteriolysis. For this reason, anticapsular
antibody,
which promotes both phagocytosis and lysis of bacteria, is the main
factor
in immune defense against H. influenzae infections.
The polyribosyl ribitol phosphate (PRP) capsule is the most
important
virulence factor because it renders type b H. influenzae
resistant
to phagocytosis by polymorphonuclear leukocytes in the absence of
specific
anticapsular antibody, and it reduces the bacterum's susceptibility to
the bactericidal effect of serum. However, susceptibility to the
bactericidal
effect of serum depends on the presence of antibodies to a number of
other
antigenic sites, including the lipooligosaccharide and outer
membrane proteins designated as P1 and P2. (See
Immunity, below.)
Type b H. influenzae is plainly the most virulent of the Haemophilus
species; 95 percent of bloodstream and meningeal Haemophilus
infections
in children are due to this bacterium. In contrast, in adults,
nontypable
strains of H. influenzae are the most common cause of Haemophilus
infection, presumably because most adults have naturally acquired
antibody
to PRP.
chapter continued
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