Haemophilus influenzae and Hib Meningitis (page 2)
(This chapter has 4 pages)
© Kenneth Todar, PhD
Naturally-acquired disease caused by H. influenzae seems to
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,
and joint infections. Nontypable H. influenzae causes
infections (otitis media) and sinusitis in children, and
is associated with respiratory tract infections (pneumonia) in
children and adults.
Seven serotypes of the bacterium have been identified on the basis
capsular polysaccharides. H.
influenzae type b is the most important serotype involved in
Disease caused by H. influenzae usually begins in the upper
tract as nasopharyngitis and may be followed by sinusitis and otitis,
leading to pneumonia. In severe cases, bacteremia may occur, which
results in joint infections or meningitis.
Infection with Haemophilus
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
although the presence of the type b polysaccharide capsule is
to be the major factor in virulence. Encapsulated organisms can
the epithelium of the nasopharynx and invade the blood capillaries
Their capsule allows them to resist phagocytosis and
lysis in the nonimmune host. Nontypable (non encapsulated) strains
are less invasive, but they are apparently able to induce an
response that causes disease. Outbreaks of H. influenzae type
infection may occur in nurseries and child care centers, and
administration of antibiotics is warranted. Vaccination with type b
(in the form of Hib conjugate vaccines) is effective in
infection, and several vaccines are now available for routine use.
Figure 3. Tissues infected
b and nontypable strains of Haemophilus influenzae.
H. influenzae does not produce any demonstrable exotoxins The
role of endotoxin in meningitis or bacteremia is unclear,
the Gram-negative bacterium's outer membrane lipooligosaccharide
is thought to play a role in inflammation associated with otitis media.
All virulent strains produce neuraminidase and an IgA
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
antigen, as defined in red blood cells, appears to be the receptor.
Virulence, at least in the case of bacteremia and meningitis, is
related to capsule formation. Virtually all of these infections are
by the type b serotype, and its capsular polysaccharide, containing
ribitol and phosphate, is the proven determinant of virulence. The
material is antiphagocytic, and it is ineffective in inducing the
complement pathway, so that the bacterium can invade the blood or
fluid without attracting phagocytes or provoking an inflammatory
and complement-mediated bacteriolysis. For this reason, anticapsular
which promotes both phagocytosis and lysis of bacteria, is the main
in immune defense against H. influenzae infections.
The polyribosyl ribitol phosphate (PRP) capsule is the most
virulence factor because it renders type b H. influenzae
to phagocytosis by polymorphonuclear leukocytes in the absence of
anticapsular antibody, and it reduces the bacterum's susceptibility to
the bactericidal effect of serum. However, susceptibility to the
effect of serum depends on the presence of antibodies to a number of
antigenic sites, including the lipooligosaccharide and outer
membrane proteins designated as P1 and P2. (See
Type b H. influenzae is plainly the most virulent of the Haemophilus
species; 95 percent of bloodstream and meningeal Haemophilus
in children are due to this bacterium. In contrast, in adults,
strains of H. influenzae are the most common cause of Haemophilus
infection, presumably because most adults have naturally acquired