Pathogenic Neisseriae: Gonorrhea, Neonatal Ophthalmia and Meningococcal Meningitis (page 6)
(This chapter has 7 pages)
© 2008 Kenneth Todar, PhD
Clinical manifestations of N. meningitidis
infection
The onset of meningococcal meningitis may be abrupt or insidious.
Infants
with meningococcal meningitis rarely display signs of meningeal
irritation.
Irritability and refusal to take food are typical; vomiting occurs
early
in the disease and may lead to dehydration. Fever is typically absent
in
children younger than 2 months of age. Hypothermia is more common in
neonates.
As the disease progresses, apnea, seizures, disturbances in motor tone,
and coma may develop.
In older children and adults, specific symptoms and signs are
usually
present, with fever and altered mental status the most consistent
findings.
Headache is an early, prominent complaint and is usually very severe.
Nausea,
vomiting, and photophobia are also common symptoms.
Neurologic signs are common; approximately one-third of patients
have
convulsions or coma when first seen by a physician. Signs of meningeal
irritation such as spinal rigidity, hamstring spasms and exaggerated
reflexes
are common.
Petechiae (minute hemorrhagic spots in the skin) or purpura
(hemorrhages
into the skin) occurs from the first to the third day of illness in 30
to 60% of patients with meningococcal disease, with or without
meningitis.
The lesions may be more prominent in areas of the skin subjected to
pressure,
such as the axillary folds, the belt line, or the back.
Fulminant meningococcemia occurs in 5 to 15% of patients with
meningococcal
disease and has a high mortality rate. It begins abruptly with sudden
high
fever, chills, myalgias, weakness, nausea, vomiting, and headache.
Apprehension,
restlessness, and delirium occur within the next few hours. Widespread
purpuric and ecchymotic skin lesions appear suddenly. Typically, no
signs
of meningitis are present. Pulmonary insufficiency develops within a
few
hours, and many patients die within 24 hours of being hospitalized
despite
appropriate antibiotic therapy and intensive care.
Figure 4. The characteristic
skin rash (purpura) of meningococcal septicemia, caused by Neisseria
meningitidis
Virulence Factors
For a time, the virulence of Neisseria meningitidis was
attributed
to the production of an "exotoxin" that could be recovered from culture
filtrates of the organism. But when studies revealed that antitoxin
reacted
equally well with washed cells as culture filtrate, it was realized
that
the bacteria underwent autolysis during growth and released parts of
their
cell walls in a soluble form. Hence, the major toxin of N.
meningitidis
is its lipooligosaccharide,LOS, and its mechanism is endotoxic.
The other important determinant of virulence of N. meningitidis
is its antiphagocytic polysaccharide capsule.
The human nasopharynx is the only known reservoir of N.
meningitidis.
Meningococci are spread via respiratory droplets, and transmission
requires
aspiration of infective particles. Meningococci attach to the
nonciliated
columnar epithelial cells of the nasopharynx. Attachment is mediated by
fimbriae
and possibly by other outer membrane components. Invasion of the
mucosal
cells occurs by a mechanism similar to that observed with gonococci.
Events
involved after bloodstream invasion are unclear and how the
meningococcus
enters the central nervous system is not known.
Purified meningococcal LOS is highly toxic and is as lethal for mice
as the LOS from E. coli or Salmonella typhimurium;
however,
meningococcal LOS is 5 to 10 times more effective than enteric LPS in
eliciting
a dermal Shwartzman phenomenon (a characteristic type of inflammatory
reaction)
in rabbits. Meningococcal LOS has been shown to suppress leukotriene B4
synthesis in human polymorphonuclear leukocytes. The loss of
leukotriene
B4 deprives the leukocytes of a strong chemokinetic and chemotactic
factor.
