Meningococcemia pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Pathophysiology

• Meningococcal disease is caused by the bacterium Neisseria meningitidis, also called meningococcus.
• About 10% of people have this type of bacteria in the back of their nose and throat with no signs or symptoms of disease, called being 'a carrier'. But sometimes Neisseria meningitidis bacteria can invade the body causing certain illnesses, which are known as meningococcal disease.

Transmission

• Neisseria meningitidis bacteria are spread through the exchange of respiratory and throat secretions like spit (e.g., by living in close quarters, kissing). Fortunately, these bacteria are not as contagious as germs that cause the common cold or the flu. The bacteria are not spread by casual contact or by simply breathing the air where a person with meningococcal disease has been.
• Sometimes Neisseria meningitidis bacteria spread to people who have had close or lengthy contact with a patient with meningococcal disease. People in the same household, roommates, or anyone with direct contact with a patient's oral secretions, meaning saliva or spit, (such as a boyfriend or girlfriend) would be considered at increased risk of getting the infection.
• People who qualify as close contacts of a person with meningococcal disease should receive antibiotics to prevent them from getting the disease. This is known as prophylaxis (pro-fuh-lak-sis). The health department investigates each case of meningococcal disease to make sure all close contacts are identified and receive prophylaxis. This does not mean that the contacts have the disease; it is to prevent it.

Progression

• Shock is due to lipooligosaccharide which is a potent toxin. This toxin initiates release of inflammatory cytokines, reactive oxygen radicals, prostaglandins, arachidonic acid, complement activated products, platelet aggregating factor, and perhaps nitric oxide.
• The bacteria attach to and multiply on the mucosal cells of the nasopharynx.
• In a small proportion (less than 1%) of colonized persons, the organism penetrates the mucosal cells and enters the bloodstream.
• The bacteria spread by way of the blood to many organs. In about 50% of bacteremic persons, the organism crosses the blood–brain barrier into the cerebrospinal fluid and causes purulent meningitis. An antecedent upper respiratory infection may be a contributing factor.
• The bacteria attach to and multiply on the mucosal cells of the nasopharynx.
• In a small proportion (less than 1%) of colonized persons, the organism penetrates the mucosal cells and enters the bloodstream.
• The bacteria spread by way of the blood to many organs. In about 50% of bacteremic persons, the organism crosses the blood–brain barrier into the cerebrospinal fluid and causes purulent meningitis.
• An antecedent upper respiratory infection may be a contributing factor.

Molecular Pathophysiology of Meningococcemia

• The toll like receptor system (TLR) protects the body from invasive pathogens and also causes destruction of host in fulminent infections.
• The cell wall of Neisseria meningitidis has molecules that activate the TLR system in a dose dependent manner. This causes the release inflammatory mediators which can cause organ dysfunction and meningococcemia.
• The lipopolysacchrides in the outer membrane is another factor that illicits immune response.
• Peptidoglycan, bacterial lipoprotein and genetic polymorphism are factors that help contribute to broaden the inflammatory response.
• There is a close association between the load of meningococci,[ alive or dead in CSF (cerebrospinal fluid)] and plasma and magnitude of inflammatory response to the patient.

Classification of Clinical Presentations

• They present with a wide range of clinical conditions from transient bacteremia to rapidly progressing septicemia.
• Most of them develop meningitis as meningococci invade the meninges.
• Meningococcal infections are classified into four different clinical groups based on the following conditions.

• Presence or absence of signs of septic shock.
• Presence or absence of clinical symptoms and laboratory signs of distinct meningitis.

Clinical group	Characteristic feature	Case fatality
Fulminent meningocccal septicemia	Severe persistent septic shock lasting for >24 hours or until death and minimal pleocytosis or lack of clinical signs of meningitis.	25-55%
Distinct meningitis	Marked pleocytosis or distinct clinical signs of meningitis.	10-25%
Distinct meningitis and persistent septic shock.	Marked pleocytosis or distinct signs of meningitis and severe persistent septic shock.	<5%
Mild systemic meningococcal infection	Mild meningococcemia without developing persistent septic shock or distinct meningitis.	0%

Infection

• The meningococci after getting attached, gets endocytosed by parasite directed endocytosis across epithelium.
• The alteration in the gene expression induce a specific structural change which causes endocytosis.

Distribution

• Meningococci once it enters the circulation survives and multiplies in it causing systemic circulation.

Neisseria meningitidis IgA1 Protease

• Neisseria secretes IgA1 protease which splits IgA1 at the hinge region.

Systemic Infection

Meningococci after entering the systemic circulaion get seeded to different parts of the body mainly meninges and skin. Sites like eyes, joints, pericardiucan also be seeded by the organism. When the breeding bacteria reaches a threshold it produces systemic symptoms like musche ache, fever and malaise. The TLR4 and TLR2 from the preoptic area of anterior hypothalamus are expressed which produces the fever causing cytokines like interleukin 1 and interleukin 6 and tumor necrosis factor alpha. They activate the cycloxygenase system which produces prostaglandin E2 and activates the hypothalamic prostaglandin E2 and the hypothalamic thermoregulation center raises the body temperature, increases muscle work and alter skin perfusion.

Proliferation Markers

• Meeningococcal lipopolysachride in plasma
• Meningococcal lipopolysacchride in CSF.
• Meningococcal DNA copies.

Patients who were diagnosed to have massive disseminated intravascular coagulation or disseminated septic shock had almost 1000 fold higher amount of LPS in plasma and CSF and copies of DNA of meningococcus than those with only meningitis with the same incubation period.

References

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