Neisseria meningitidis – causes, symptoms, diagnosis, treatment, pathology

Learning medicine is hard work! Osmosis makes it easy. It takes your lectures and notes to create
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much more. Try it free today! Neisseria meningitidis, also called N. meningitidis
or just meningococcus, is a gram-negative round bacterium that causes meningitis in
humans, as well as life-threatening conditions like sepsis and disseminated intravascular
coagulation. Now, N. meningitidis has a thin peptidoglycan
layer, so it doesn’t retain the crystal violet dye during Gram staining. Instead, like any other Gram-negative bacteria,
it stains pink with safranin dye. N. meningitidis typically live in pairs called
diplococci, stacked side to side, so the pair looks like a coffee bean. They are also non-motile, non-spore forming,
and obligate aerobes, which means that they absolutely need oxygen to grow. Finally, they’re catalase and oxidase positive
– which means they produce both these enzymes. N. meningitidis grows on a special chocolate
medium called Thayer-Martin agar, which mainly consists of sheep’s blood… err, yum? Some antimicrobials, like vancomycin and nystatin
are usually added to the Thayer-Martin agar, to inhibit the possible growth of undesired
bacteria or fungi, and maximize the growth of Neisseria species. However, other Neisseria species, like N gonorrhoeae,
also share these properties. So the maltose fermentation test is done to
differentiate the two. The gist of it is that N. meningitidis can
ferment maltose, whereas N. gonorrhoeae cannot. To check for this, a pure sample from the
culture is transferred to a sterile tube containing a mix of phenol red and maltose, which is
then incubated at 36 degrees Celsius for 24 hours. N. meningitidis causes acidic fermentation
of maltose, and the resulting byproducts make the solution turn yellow. With N. gonorrhoeae, the solution stays red. Now, N. meningitidis has a number of virulence
factors, that are like assault weaponry that help it attack and destroy the host cells,
and evade the immune system. First, N. meningitidis is encapsulated – meaning
it’s covered by a polysaccharide layer called a capsule. The capsule has pili, which are hair-like
extensions that help the bacteria attach to host cells. Underneath the capsule, there’s the outer
cell membrane, which has two opacity proteins, called Opa and Opc, that also help N. meningitidis
attach to host cells. Additionally, N. meningitidis produces toxins
– and the most important one is is IgA protease, a toxic protein that this bacterium uses to
destroy Immunoglobulin A – IgA. IgA is an immune system protein found in the
nasopharyngeal mucosa secretions that normally osponizes invading bacteria – meaning it tags
them so neutrophils can recognize and destroy them. So IgA protease neutralizes the first line
of mucosal defense! However, not all IgA molecules get neutralized,
so some N meningitidis bacteria are still opsonized, and they get attacked by the neutrophils. Within a neutrophil, N meningitidis gets wrapped
in a phagosome, which is like a bubble inside which reactive oxygen species, such as H2O2,
are released to kill it. However, N. meningitidis releases catalase,
which breaks down H2O2. Unfortunately, this translates as a win for
N. meningitidis, which now takes over the neutrophil and uses its energetic resources
to multiply. The neutrophil eventually becomes too full,
bursting open, and releasing N. meningitidis in the bloodstream, what’s known as meningococcemia. Inside the bloodstream, N. meningitidis uses
another toxin called factor H binding protein, which disables factor H, a protein involved
in the alternate complement pathway, which plays a role in anti-bacterial immunity. This allows N. meningitidis to spread, multiply
and produce toxins in the bloodstream, causing destruction of the capillary endothelial cells,
which result into leaky capillaries. N. meningitidis also has a cell wall antigen
called Lipooligosaccharide, or LOS, which can trigger a widespread immune reaction that
results in sepsis – meaning blood vessels dilate, so blood pressure drops, and vital
organs don’t get enough blood. Yikes! Finally, meningococcal sepsis can lead to
disseminated intravascular coagulation, or DIC. That’s because the damaged endothelial cells
release procoagulant-like tissue factor, which makes clots form inside the blood vessels,
and that depletes platelets and clotting factors. Unfortunately, this leads to severe bleeding
throughout the body. If a lot of blood pools within the adrenal
gland, local pressure increases, which makes the adrenal blood vessels pinch shut. This results in ischemia and eventually, necrosis
of the various hormone-producing cells in the adrenal gland, a condition known as Waterhouse-Friderichsen
syndrome. Insufficient production of adrenal hormones,
especially aldosterone and cortisol, can further worsen the shock. Now, the good news is that meningococcus can
actually colonize the nasal and pharyngeal mucosa of many people, where it doesn’t
do any harm so long as the immune system keeps them in check, restricting their growth and
preventing them from getting into the bloodstream. Problems arise in individuals with weaker
immune systems, like infants and the elderly. Other immune-weakening conditions include
an HIV infection, diabetes, malignancy, or alcohol abuse. Additionally, since the spleen plays an important
role in immunity against encapsulated bacteria, N. meningitidis infections are more common
in people who’ve had a splenectomy, meaning their spleen was surgically removed, or in
those with sickle cell disease who have functional asplenia. Most commonly, meningococcemia results in
meningitis. N. meningitidis is actually the only bacteria
known to cause meningitis epidemically, most likely in people living in close quarters
like soldiers in a camp, or among larger communities that share the same source of freshwater. Meningitis happens when the bacteria move
within the bloodstream up in the brain, and use its toxins to break through the endothelial
cells that make up the blood-brain barrier. This way, it gets into the cerebrospinal fluid
or CSF, resulting in meningitis. People with meningitis typically present with
headache, fever, and neck stiffness. Symptoms of meningococcemia include a petechial
rash, which are small, red or purple, spots that often appear on the trunk and lower extremities,
and with sepsis, there may be signs of shock, like hypotension and tachycardia. Diagnosis requires blood cultures to look
for N meningitidis in the blood, as well as a lumbar puncture for CSF analysis and culture. Treatment relies on prompt administration
of ceftriaxone. Following the results of the antibiogram,
treatment can be switched to penicillin G. Additionally, prophylactic ceftriaxone, rifampin,
or ciprofloxacin should be given to close contacts of the affected individual. Finally, it is recommended that people who
are at risk of a meningococcal infection get vaccinated, and these include babies, children
and teens, adults with spleen issues, or those who travel in places where N. meningitidis
is endemic. Currently, there’s two kinds of vaccines
against N. meningitidis. One is the meningococcal conjugate vaccine
typically given to children and teens. The other is is the meningococcal recombinant
vaccine, and it’s the one typically given to adults. Alright, as a quick recap, Neisseria meningitidis
is a Gram-negative diplococcus, that grows on Thayer-Martin agar. It is non-motile, non-spore forming, oxidase
positive, catalase positive, and it can ferment maltose. Its virulence factors include the capsule,
the pili, and proteins like Opa, Opc, IgA protease and LOS. Meningococcemia mainly causes meningitis,
but it can also result in other severe conditions such as sepsis, disseminated intravascular
coagulation, and Waterhouse-Friderichsen syndrome. Treatment with intravenous ceftriaxone, and
it’s rapidly started upon clinical suspicion, the treatment can then be adjusted afterwards,
as soon as the CSF culture and antibiogram are available.

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  1. I can't imagine studying without you guys. Thank you Osmosis chanel for making everything much more understandable and easy to remember. 😊👌

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