1. K05-08
Neisseria meningitidis
SPC Daniel S Kim

2. N. meningitidis
CASE
A 3⅟₂-year-old male presented to an outside
emergency room with fever and lethargy
since the previous evening and a petechial
rash first noted on the day of evaluation.
On physical examination the patient was
listless and had a temperature of 39°C, blood
pressure of 104/52mmHg, and heart rate of
148 beats/min.

3. N. meningitidis
CASE (Cont.)
Examination of the skin revealed a petechial
rash as well as two purpuric lesions. Blood
cultures were obtained, and he was given
intravenous antibiotics and transferred to this
hospital. On arrival here, he underwent a
lumbar puncture, which was notable for
cerebrospinal fluid with 190 white blood
cells/mm³, with 94% neutrophils, consistent

4. N. meningitidis
CASE (Cont.)
with bacterial meningitis.
NO organisms were seen on Gram stain of
the cerebrospinal fluid. Blood cultures from
the outside hospital were subsequently
positive for an oxidase-positive, gram-
negative diplococcus.

5. N. meningitidis
Background
THE NEISSERIAE
The neisseriae are a group of gram-negative
diplococci 0.6-1.5 µm in diameter. Two species
of Neisseria, N. gonorrhoeae and N. meningitidis,
are considered as true human pathogens. Both
of these organisms possess pili and adhesions
for adherence to host cells, produce endotoxins,
and resist destruction within phagocytes. N.
meningitidis also produces a capsule to resist
phagocytic engulfment.

6. N. meningitidis
Background
The gonococcus may also cause extragenital
infections such as pharyngitis (from oral-genital
sex), ophthalmia (from inoculation of the eyes
with contaminated fingers), and proctitis (from
anal sex). In 1% - 3% of infected women and a
lower percentage of infected males, the
organism invades the blood and disseminates,
causing a rash, septic arthritis, endocarditis,
and/or meningitis.

7. N. meningitidis
Background
Dissemination occurs more frequently in
females. Congenital gonorrhea is known as
ophthalmia neonatorum and occurs as a result
of the eyes of newborns becoming infected as
the baby passes through the birth canal.
Neisseria meningitidis (the meningococcus) is
the causative organism of meningococcal
(epidemic) meningitis.

8. N. meningitidis
Background
There are between 2000 and 3000 cases of
meningococcal meningitis per year in the U.S.
Approximately 50% of the cases occur in
children between 1 and 4 years old. N.
meningitidis infects the nasopharynx of
humans causing a usually mild or subclinical
upper respiratory infection. Colonization of
the nasopharynx may persist for months.

9. N. meningitidis
Background
However, in about 15% of these individuals, the
organism invades the blood and disseminates,
leading septicemia and from the there may cross
the blood-brain barrier causing meningitis. A
petechial skin rash, caused by endotoxin in the
blood, appears in about 75 percent of the septic
cases and fatality rates for meningococcal
septicemia are as high as 30 percent as a result
of the shock cascade.

10. N. meningitidis
Background
A fulminating form of the disease, called
Waterhouse-Frederichsen syndrome, can be
fatal within several hours due to massive
intravascular coagulation and resulting shock,
probably a result of massive endotoxin
release. N. meningitidis is especially
dangerous in young children.

11. N. meningitidis
Isolation and Identification
• Gram stain
A presumptive diagnosis of meningococcal
meningitisis often made by doing a gram stain of
cerebrospinal fluid or petichial skin lesions and
looking for gram-negative diplococci seen both
inside and outside of polymorphonuclear
leukocytes. This can be followed by serologic
tests, nucleic acid probes, or culturing.

12. N. meningitidis
Isolation and Identification
• Serologic identification
There are at least 12 different serological groups
of N. meningitidis based on their capsular
polysaccharides, but over 90 percent of
meningococcal meningitis cases are caused by
five serologic groups: A, B, C, Y, and W135.
Serogroups A and C usually causes the epidemic
form of meningitis. Serogroup C is is the most
common serogroup in North America whereas B
is the most common in Europe and Latin
America.

13. N. meningitidis
Isolation and Identification
Serogroup Y has been increasing in the U.S.,
Israel, and Sweden. Direct serologic testing to
detect meningococcal capsular
polysaccharides can be performed on
cerebrospinal fluid or on organisms from skin
lesions for rapid identification.

14. N. meningitidis
Isolation and Identification
• Nucleic acid identification
A polymerase chain reaction test to amplify
meningococcal DNA can also be used to
detect N. meningitidis in cerebrospinal fluid
or blood.

15. N. meningitidis
Isolation and Identification
•Isolation of N.meningitidis
To isolate N. meningitidis, cultures are taken
from the nasopharynx, blood, cerebrospinal fluid,
and skin lesions. Typically cultures are done on
an enriched, non-selective medium such as
blood agar or chocolate agar grown in 3-7%
carbon dioxide. MTM Chocolate agar is also
sometimes used for isolation. Medium to large,
blue-gray, mucoid, convex, colonies form in 48
hours at 35-37°C.

16. N. meningitidis
Isolation and Identification
• Identification of N.meningitidis
Once isolated, N. meningitidis is identified by
the oxidase test, gram staining, and
carbohydrate utilization reactions. N.
meningitidis, like all neisseriae, is oxidase-
positive and appears in a gram stain as gram-
negative diplococci.

17. N. meningitidis
Isolation and Identification
In carbohydrate utilization tubes, N.
meningitidis produces acid from both glucose
and maltose, but not from lactose and
sucrose . The acid end products turn the
phenol red pH indicator from red to yellow. N.
meningitidis also produces gamma-
glutamylaminopeptidase, an enzyme that can
be detected by biochemical testing.

18. N. meningitidis
CASE STUDY
Q1. Which bacterium was causing this
patient’s illness? Is the finding of meningitis
a positive or negative prognostic sign?

19. N. meningitidis
CASE STUDY
A1. The clinical presentation, the finding of
meningitis (190 white blood cells/mm³,
primarily neutrophils, in the CSF), and the
finding of oxidase-positive, gram-negative
diplococci growing in the blood strongly
indicated that the etiologic agent of this
infection was Neisseria meningitidis.

20. N. meningitidis
CASE STUDY
Q2. Is this organism ever part of the normal
oropharyngeal flora?

21. N. meningitidis
CASE STUDY
A2. N. meningitidis is usually considered to
be part of the oropharyngeal flora and can be
found in 20 to 40% of healthy young adults.
During epidemics of meningococcal disease
in institutionalized populations such as the
military, colonization rate may approach 90%.

22. N. meningitidis
CASE STUDY
Q3. which immunologic abnormalities
predispose individuals to infection with this
organism?

23. N. meningitidis
CASE STUDY
A3. Most people who are colonized with this
organism mount a humoral response to it.
These individuals produce bactericidal
antibodies, which appear to be protective.
The very small percentage of patients who do
not make bactericidal antibodies in response
to colonization by this organism are high risk
for development of invasive disease.

24. N. meningitidis
CASE STUDY
Q4. Which serogroup(s) causes illness? The
serogroup is based on antigen from which
part of the bacterium?

25. N. meningitidis
CASE STUDY
A4. The serogruops most commonly
associated with meningitis in the United
States are types A,C,Y,W135, and B. The two
most frequently isolated serogroups are
B(50%) and C(20%). Typically groups A and C
are thought of as epidemic strains because of
their association with epidemics, whereas
group B isolates are most likely to cause
sporadic cases.

26. N. meningitidis
CASE STUDY
Cases due to group B are most frequent
because of the rarity of epidemics of
N.meningiditis disease in the United States.
The serogroups are based on the biochemical
structure of the capsular polysaccharide that
surrounds the organism. Nonencapsulated
isolates rarely cause invasive disease,
indicating that encapsulation is critical to the
pathogenicity of the organism.

27. N. meningitidis
CASE STUDY
Q5. Which prophylactic strategies are useful
for large populations?

28. N. meningitidis
CASE STUDY
A5. Vaccination is the mainstay of
prophylactic strategies for large populations.
Vaccines derived from capsular
polysaccharide are highly protective against
groups A and C in adults and children over 2
years of age.

29. N. meningitidis
CASE STUDY
Q6. Which prophylactic strategies can be
used for exposed individuals?

30. N. meningitidis
CASE STUDY
A6. Both vaccination and chemoprophylaxis
may be in order for exposed individuals,
especially health care workers who come in
close contact with respiratory secretions of
infected individuals. Rifampin is the drug of
choice for antimicrobial prophylaxis. It
penetrates well into respiratory secretions
and is well tolerated.

31. N. meningitidis
CASE STUDY
Q7. What are purpuric lesions and a
petechial rash, and which virulence factor
plays a central role responsible for their
appearance?

32. N. meningitidis
CASE STUDY
A7. Petechial rash and purpuric lesions can
be manifestation of disseminated
intravascular coagulation (DIC). Petechial
lesions are pinpoint, purplish red lesions that
are caused by hemorrhage in the intradermal
vascular bed. Purpuric lesions are similar to
petechial lesions but are largerm probably
representing coalescence of number of
petechial lesions.

33. N. meningitidis

34. N. meningitidis

35. Petechial rash

36. Lumbar puncture

37. Purpura

38. Diplococcus

39. N. meningitidis

40. WF syndrome

41. symptom

42. symptom

43. nasopharynx

44. PCR