Neisseria species, a bacteria.
Neisseria, are gram-negative diplococci which appear on
gram-stain like kidney beans
facing each other such as you see on this picture here.
This picture shows neisseria meningitidis.
This one shows neisseria gonorrhoeae, another important form
Both, however, appear to be facing kidney beans.
Neisseria meningitidis which we'll spend our time talking
about in this section,
are typically known by their serogroup positivity.
This slide demonstrates the typical outer
structure of Neisseria Meningitidis,
including pilots structures, capsular
membrane proteins and lipid oligosaccharides
in the outer membrane which contains the
lipid A which functions as a lipid based
Neisseria Meningitidis usually is classified
into various groups, however, based on its
The most common types being A, B, C, X, Y,
W135 and L.
The most important testable facts.
So the thing to remember for these variants
is that the polysaccharide capsule of
Serogroup B has a very poor immune response
a that has made it a difficult target for vaccine discovery,
but also that vaccine
for meningococcal type B targets membrane
proteins as opposed to the
As noted before, Neisseria meningitidis are gram-negative
and you can see a beautiful picture on this slide, looking
almost like owl's eyes,
not the classic pathologic definition, but looking like
two-kidney shapes facing each other.
On culture, the organism itself is non-motile, it does not
Diplococci or paired cells are typically how the organism is
It would be rare to see individual gram-negative cocci by
The organism is pretty much everything-positive: maltose,
oxidase, and catalase.
create endotoxin activity mostly
which create this endotoxin activity mostly
by precipitating a proinflammatory cytokine reaction.
The organism itself ferments both maltose and glucose as
and in the growth, it is especially able to grow on a
chocolate-based agar, typically the Thayer-Martin agar.
Neiserria meningitidis is incredibly contagious.
Unfortunately, it can be presented and acquired through
as well as occasionally via large droplets which is come to
rest on a horizontal surface.
Patients who are most at risk of developing disease
from Neisseria meningitidis are those with terminal
complement deficiencies, C5 to C9.
However, anybody can get disease with Neisseria meningitidis
especially including those who are the very young, children
less than five,
and those who are a little bit older.
There's a specific at-risk patient population
that are those young adults attending college in the first
one or two years.
Exactly why is not known and that specific age association
has not been definitely proven by evidence-based medicine.
However, factors that are important may be close proximity,
i.e., going out for drinks after school, smoking cigarettes
which compromises respiratory cilia as in, defense
mechanism, and fatigue,
being up at all hours studying, I'm sure, no partying
involved in young college students.
Put all those factors together, may precipitate that
On this slide,
we see a graph of the so-called meningitis
belt, including areas at high
epidemic risk in sub-Saharan Africa.
The dark shaded band across the middle
of the sub-Saharan part of Africa
demonstrates areas at high epidemic risk.
The lighter shade of gray
for those countries shows areas
with increased risk for meningitis
due to meningococcal disease.
How does the disease occur?
How does neisseria meningitidis do what it does?
The first step is to enter the respiratory tract
then it invades the mucosal membranes and ultimately enters
So, a several step process which requires there to be
which enters into the bloodstream for it to actually cause
Once entering the bloodstream, an organism proliferation
then Neisseria meningitidis starts to release endotoxin,
and it is that endotoxin along with the proinflammatory
to its polysaccharide capsule, which creates the sepsis:
fever, increased vascular permeability, followed by leakage
of fluids, shock,
and then localized bleeding causing petechiae.
The antiphagocytic capsule, as mentioned,
is also important not only in inducing proinflammatory
but also in avoiding detection by and ingestion by
So, several mechanisms of virulence occur in the setting of
Diseases that it causes: perhaps the most fearsome is
an easy one to remember because it's in the name.
Typical meningitis is, as you would anticipate, an acute
onset of fever,
followed by a severe headache and a stiff neck.
Importantly, some patients, especially children,
are unable to report or even demonstrate on physical exam
evidence of a stiff neck
so instead, one sees evidence of extreme irritability.
Along with meningitis, patients may have what's called acute
This simply means by its name, presence of the organism,
Neisseria meningitidis organism, within the bloodstream,
creating its endotoxin and its capsular virulence.
Patients with meningococcemia will have septicemia or septic
They may or they may not have active meningitis.
Patients with the -- the disease process will present with
acute onset fever
but rapidly progress into shock, generalized hemorrhage
such as you see on the picture of the baby to the right,
along with diffused purpura lesions,
and discrete petechiae, and they will also have multi-organ
The only way to survive meningococcemia is to have it be
promptly recognized and treated empirically.
The mortality or the death rate is at least 25% and
untreated, it approaches 100%.
There is a less severe form of disease caused by neisseria
which is called chronic meningococcemia.
Unfortunately, that name, meningococcemia,
strikes fear in the hearts of clinicians because it is so
overtly associated with bad outcomes.
But chronic meningococcemia is not severe and is not
Typically, these patients have circulating bacteremia,
circulating Neisseria meningitidis for several weeks at a
And then, they may develop low-grade fevers sometimes
with arthritis or even just arthralglas, painful joints.
And then as the fevers subside for a week or so,
they may develop petechial skin lesions
such as you see on the legs of one of my patients on the
picture to the right. This is a mild illness.
It is not known to progress to severe disease,
except in rare instances when the patient develops
And then, they may enter full fledged acute meningococcemia
with all the attendant morbidity and mortality that we just
So, a mild febrile disease.
Also, in addition to chronic meningococcemia, patients can
develop a transient, short-lived pharyngitis illness,
which may also be associated with other evidence of
So, the serosa, the pleura lining various organs such as the
lungs, the joints,
the urethra, can become inflamed and these are patients
who are acutely ill as you might be with the flu for several
and then spontaneously improve.
A horrible complication of meningococcemia
is known as the Waterhouse-Friderichsen Syndrome.
And in this case, there is an addition to the already-severe
with acute meningococcemia, there is an overwhelming
to the polysaccharide capsule, which is associated
with disseminated intervascular coagulation disease or DIC
with bilateral hemorrhagic adrenal infarcs,
septic shock, acute hypotension, all of the above, along
with cardiac dysfunction,
tachyarrhythmia, etc., and so forth.
And these patients, in addition to having purpuric disease,
will also have petechial disease.
This is a process which, even if recognized, is very
difficult to reverse
and extremely fatal to those who suffer from it.
So, prevention. Well, the best prevention of course is to
avoid exposure in the first place.
Although, that may not be necessary, so it may not be
However, creating an immunologic prevention is the next best
Exclusive breastfeeding, transfer of maternal immunity
for the first six months of life is always a good idea.
Although, the mother may not herself have been exposed to
she may have been low-level exposed from other people
and thus have some partial immunity to transfer to her baby.
For those who don't have the benefit of that exposure,
there is now an immunization or a vaccine product
which is conjugated to a protein to induce an exaggerated
and effective seroprotective response.
Several products are on the market.
All of them are licensed and in use for children ages two
years of age and older.
However, they are effective down to two months of life
However, they are effective down to two months of life
The quadrivalent meningococcal
which can be meningococcal
ACWY are indicated for eligible groups.
These include all pediatric patients ages
11 to 18 years of life,
as well as children ages
two months to ten years of life or through
ten years of life who have an increased
risk for meningococcal disease.
The high risk categories
include those with persistent
deficiencies taking a complement inhibitor
such as Soliris, those with anatomic
or functional asplenieas
such as sickle cell disease,
traumatic splenic etc.
Those with active HIV infection
regardless of treatment,
and those who reside in a hyper endemic
or epidemic region,
especially if they'll have prolonged
contact with the local population.
For those patients who are exposed to Neisseria
because it is so highly contagious and because it is so
robustly associated with various severe disease,
those are patients who do deserve antibiotic prophylaxis.
Most commonly, the drug rifampin is used.
Although, quinolones such as ciprofloxacin or sulfonamides
are also used to prevent that disease process.
And so Neisseria meningitidis is associated with most often
very severe disease,
highly contagious, occuring at those who are most at risk,
it can also cause a more chronic form, but regardless of the
When one sees gram-negative diplococci or kidney bean faced
or gram-negative rods facing each other,
one should be very worried and start treatment right away
for the possibility of meningococcemia.
And so, treatment. Historically, penicillin was the
treatment of choice for all of the Neisseria species:
meningitidis, gonorrhoeae, etc.
Unfortunately worldwide, many reports now exist of
And so the alternatives: broad-spectrum cephalosporins,
most especially the drug ceftriaxone, as well as, in parts
of the world that have access to this,
chloramphenicol and sulfonamides are the treatment of
While empiric treatment is not something in terms of
that we wish to indulge in too frequently, in the case of
where the outcomes are so uniformly horrible and the onset
and progression disease is so rapid, empiric treatment is
indicated in this specific circumstance.