Bacterial Meningitis

Common causes of bacterial meningitis by age group:

Meningitis due to Neisseria meningitidis (pathogenesis will be similar for Haemophilus influenzae type B):

Neisseria are gram negative cocci associated with purulent infections

N. gonorrhoeae - localized inflammation of the genitourinary tract. Rarely causes septicemia and meningitis.

N. meningitidis - usually asymptomatic, but can cause severe, life-threatening infections

acute meningitis

sepsis - meningococcemia

Organism:

Gram negative diplococci that resemble paired kidney beans

Major surface antigens:

1. Pili - responsible for attachment

2. Polysaccharide capsule - antiphagocytic, protective antibody directed against capsule

13 serologic groups based on the capsules. Most important are A, B, C< Y and W-135

Types A and C are associated with epidemics

Type B - sporadic cases, most common serotype seen in the U. S. where epidemics are rare

Capsule is shed into the blood and CSF during active disease - can be detected, diagnostic

Capsule is the vaccine antigen

3. Outer membrane proteins- also important in colonization, 20 esrotypes

4. LOS - lipooligosaccharide, similar to LPS but lack the repeating O-antigen polysaccharides,

considerable antigenic variation among meningococci

potent endotoxin, can cause adrenal cortical necrosis associated with fulminant meningococcemia (Waterhouse-Friderichsen syndrome)

target antigen for bactericidal antibody

 

Epidemiology

Distribution:

1. Endemic meningococcal disease - worldwide

2. Epidemic disease

Seen most often in developing countries

U.S. - associated withclosed populations such as military, prison, dorms

3. Higher incidence of endemic and epidemic disease in the "meninigitis best" of sub-Saharan Africa

Endemic rate: 10-25 per 100,000

Epidemics more frequent than elsewhere

Reservoir - strictly human

Carriage

1. Asymptomatic carriage in the nasopharynx ranges from 1 - 40 %

2. Carriage rates highest in school-age children

3. During epidemics of diesease, carriage rates increase dramatically - carrier epidemic

4. Carriage is temporary - clearance after development of specific antibodies

Transmission

person-to-person via aerosols

Risk

1. Highest incidence in children <5 yrs old. Infants are protected by maternal antibodies.

2. Close contacts are at higher risk.

3. Late complement deficiencies (C5 - C9) increase risk.

Molecular epidemiology

1. Sporadic cases are caused by a variety of different strain

2. Epidemics are usually clonal, i.e. descendents of a single strain or clone cause disease

3. Changes in disease grequency and severity are associated with clonal replacement - the introduction of a new virulent clone into an immunologically naive population. Analogous to effect of antigenic shift in influenza epidemics.

4. Clones can be detected by subtyping strains within a serogroup using DNA sequence analysis or enzyme electrophoresis

Clinical syndromes

1. Meningitis

a. Sudden onset - headache, fever, stiff neck, vomiting may progress to coma within a few hours, can cause death or permanet neurological sequelae

b. Meninges are acutely inflamed with thrombosis of blood vessels and thick purulent exudate

c. CSF - increase leukocytes, low glucose, high protein

2. Meningococcemia

a. Sepsis may occur with or without meningitis

b. fever and a petechial, purpuric or maculopapular rash

Hemorrhoagic rashes - caused by effects of endotoxin

3. Fulminant meningococcemia - Waterhouse-Friderichsen syndrome

Fever, extensive rash, hypotension, circulatory collapse and shock, disseminated intravascular coagulation (DIC), bleeding into the brain and adrenal glands

Sequence of events:

Septicemia

Bacteria lyse, releasing LOS

LOS binds to LPS binding protein which in turn binds to macrophages

Macrophages release mediators: IL-1, IL-6, IL-8, TNF, platelet activating factor etc. Mediators stimulate the production of vasoactive compounds, complement cascade and coagulation cascade

Activation of these systems leads to damage to the endothelial cells.

Can elad to multiple organ system failure.

4. Other syndromes include septic arthritis and pneumonia

Pathogenesis

1. Colonization of the nasopharynx.

Specific attachment by pili and Opc outer membrane protein to the micovilli of the non-ciliated columnar epithelium

Survival on the mucosal sruface is promoted by the productin of secretory IgA protease

Progression to bacteremia is favored if:

there is no bactericidal antibody - IgM or IgG to activate complement through the classical pathway

the meningococci coat their surface with blocking IgA antibodies

the patient has a comlement deficiency

2. Mucosal penetration and invasion into the bloodstream

Following attachment, the bacteria invade the epithelial cell, cross to the submucosa and enter the bloodstream. Survival is enhanced by the polysaccharide capsule which inhibits phagocytosis.

3. Invasion of the meninges - the bacteria may invade across the choroid plexus into the subarachnoid space

Immunity

Associated with the presence of specific, complement-dependent, bactericidal antibodies in serum. Antibodies usually develop after subclinical infections and are group specific (directed against the capsule) and type specific (directed against the outer membrane protein) or both.

Diagnosis

1. Presumptive diagnosis is based on clinical examination

2. Definitive diagnossis is based on obtaining blood or CSF sample and showing the presence of the organisms or their capsular polysaccharide.

Treatment

Penicillin can be used for treatment but contacts are treated with rifampin to eliminate carriage and progression to disease.

Prevention

Both vaccination and chemopryophylaxis (rifampin) can be used.

Vaccine contains capsular polycassharide of serogroups A, C, Y, and W135. B is not included because this capsular polysaccharide is not immunogenic. The vaccine is protective in adults and children >2 yrs olf.