Meningitis
Prof
Prof. Abeer Sheneef
By the end of the lecture we should be able to:
Define meningitis.
List infectious causes of meningitis.
Differentiate the morphological characteristics and identify the
mode of infection of some pathogens.
Demonstrate pathogenesis and explain the main clinical
presentations of these pathogens.
Describe prevention of these pathogens.
Describe laboratory diagnosis of a case of meningitis
Definition
Meningitis is acute inflammation
of the protective membranes
covering the brain and spinal cord
(the meninges) due to infective
(bacterial, viral, or fungal) or non-
infective causes.
Classification of Meningitis
1- Septic meningitis (bacterial)
N. meningitidis, H. influenzae (the commonest cause in children aged
2-5 years) and Pneumococci are the commonest cause of pyogenic
meningitis.
Staphylococci, streptococci, pneumococci, E. coli, klebsiella, proteus,
pseudomonas or anaerobes may be the cause, after trauma or surgery.
Spirochetes; syphilis and leptospirosis are rare causes.
Neonatal meningitis is caused by group B haemolytic streptococci
(Str. agalactia), E. coli and other intestinal flora e.g. klebsiella and
proteus. Listeria monocytogenes is a less common cause.
the organisms most commonly responsible for
community-acquired bacterial meningitis are
Streptococcus pneumoniae (50%), N. meningitidis
(25%), group B streptococci (15%) and H.
influenzae (10%).
P. aeruginosa is the most common organism
responsible for hospital-acquired meningitis.
Mortality rate in bacterial meningitis is about 25%
in adults.
2- Aseptic meningitis
M. tuberculosis meningitis.
Viral meningitis: is more common but self-limiting,
mortality rate <1%. A number of viruses can cause
meningitis:
• Enteroviruses: are the most common viral cause; Echovirus
and Coxsackievirus.
• Herpes simplex virus (HSV): HSV-1and HSV-2.
• Varicella-zoster virus (VZV).
• Mumps virus.
Fungal meningitis: Cryptococcus neoformans and
candida.
Neisseria meningitides
(Meningococci)
Neisseria meningitidis was identified in 1887.
.
* Morphology:
Gram negative cocci arranged in pairs with the adjacent sides
flattened; "kidney shaped appearance". In pathological
specimens, N. meningitidis occurs intracellularly in pus cells as
well as extracellularly. N. meningitides is capsulated
(polysaccharide capsule).
* Cultural characters
N. meningitidis is aerobe and requires for
growth enriched media containing heated
blood e.g. chocolate agar or the selective
Modified Thayer-Martin (MTM) medium.
Cultures are incubated in a humid
atmosphere containing 5-10% CO2 at 35-
37°C.
Colonies are convex, glistening, non
hemolytic and non pigmented.
* Biochemical Activities
Oxidase test: All Neisseria species give positive oxidase reaction.
Sugar fermentation with acid production: can be used for differentiation
of the pathogenic and commensal Neisseria.
Glucose Maltose Sucrose
N. meningitides + + -
N. gonorrhoeae + - -
N. flavescens - - -
N. sicca + + +
N.meningitidis
Antigenic composition and virulence factors
1- Capsular polysaccharide antigens; according to which
the meningococci are classified into 13 serogroups. The
most important serogroups associated with disease in man
are A, B, C, Y and W-135. Serotype A is the leading cause of
epidemic meningitis worldwide.
2- Pili mediate attachment to the nasopharyngeal mucosa.
3- Outer membrane proteins play a role in attachment.
4- Lipooligosaccharide (LOS or endotoxin) is responsible
for the septic shock due to septicaemia associated with
meningococcal diseases.
5- IgA1 protease hydrolyzes secretory IgA1, and helps the
attachment of the organism to the mucous membrane
(colonization).
Pathogenesis & Epidemiology
Pathogenesis & Epidemiology
Humans are the only natural hosts for meningococci.
The organisms are transmitted by airborne droplets;
they colonize the membranes of the nasopharynx and
become part of the transient flora of the upper respiratory
tract. Carriers are usually asymptomatic.
From the nasopharynx, the organism can enter the
bloodstream and spread to specific sites, such as the
meninges or joints, or be disseminated throughout the
body (meningococcemia).).
Clinical Findings
The two most important manifestations of disease are
meningococcemia and meningitis.
The most severe form of meningococcemia is the life-
threatening Waterhouse–Friderichsen syndrome, which is
characterized by high fever, shock, widespread purpura,
disseminated intravascular coagulation, thrombocytopenia,
and adrenal insufficiency.
Bacteremia can result in the seeding of many organs,
especially the meninges (meningitis).
Meningitis usually begins suddenly, with the classical clinical
triad severe headache, fever, and neck stiffness. It may
progress to coma within few hours.
Clinical Findings
Meningitic symptoms:
Severe frontal/occipital headache
Stiff neck
Photophobia
Meningitic signs:
Kernig's sign
Brudzinski's sign
Diagnosis
The principal laboratory procedures are smear and
culture of blood and spinal fluid samples.
Throat swabs are collected for detection of carrier state.
CSF is withdrawn by lumbar puncture (LP) under
complete aseptic conditions.
• Physical examination:
In septic meningitis, the CSF is under tension and turbid due
to the large number of pus cells; 20000/cmm.
• Chemical examination:
The proteins are elevated and glucose is reduced.
b. Diagnosis
• Bacteriological examination:
a. The CSF is centrifuged and the deposit is examined
microscopically after staining with gram. The presence of
intracellular capsulated gram negative diplococci in pus
cells is diagnostic..
b. Detection of meningococcal polysaccharide antigens in
CSF by Latex agglutination kits (used for the detection of
antigens in the CSF, for the most important 3 causes of
meningitis i.e. meningococci, pneumococci, and H.
influenzae type b, are very useful for rapid diagnosis).
Diagnosis
Since meningitis is a serious condition; the
detection of intracellular gram negative diplococci
in CSF smears, as well as, direct detection of
meningococcal antigens should be immediately
reported to the treating physician, who should
start treatment immediately.
Diagnosis
c. The deposit is cultured on chocolate agar and incubated
at 35-37°C in a humid atmosphere containing 5-10% CO2.
Colonies appear in 2-3 days and are identified by:
Morphology as gram negative diplococci.
Biochemical reactions; oxidase positive and acid production from
glucose and maltose.
Agglutination with anti-meningococcal serum.
2- Blood cultures commonly give positive results.
3- PCR test has been developed for the detection of
meningococccal DNA in blood or CSF.
Diagnosis of N. meningitidis carriers
Commensal neisseriae e.g. N. sicca and N. flavescens are
normal inhabitants of the throat and nasopharynx and very
rarely cause disease.
For diagnosis of meningococcal carriers nasopharyngeal
swabs are cultured on enriched selective media (MTM).
Isolated gram negative cocci should be differentiated from
commensal neisseria by the difference in their cultural
characters, biochemical reactions and serologic
identification with specific anti-meningococcal serum.
Treatment
Either ceftriaxone or penicillin G is the
drug of choice for meningococcal
infections.
Prevention
Chemoprophylaxis and immunization are
both used to prevent meningococcal disease.
Chemoprophylaxis: Rifampicin, 600 mg
orally twice daily for 2 days or oral
ciprofloxacin are used for contacts.
Immunization
Two meningococcal vaccines are available. A
meningococcal polysaccharide vaccine (MPSV4)
and a meningococcal conjugate vaccine (MCV4),
both are tetravalent and immunize against types
A, C, Y and W-135.
Both vaccines are protective, reduce the carrier
rate and are effective in preventing epidemics.
Recommended for adolescents and adults 11-55
years who are at increased risk for infection i.e.
military recruits, travelers to crowded areas (e.g.
Hajj) and asplenic patients .
Haemophilus influenzae
Haemophilus influenzae used to be the leading cause of
meningitis in young children.
Morphology: small, pleomorphic gram-negative cocco-bacilli
with a polysaccharide capsule.
Cultural characters: Facultative anaerobes require heated
blood containing media for their growth. They grow on
chocolate agar which provides X factor (haematin) and V
factor (NAD) that are essential for their growth.
Satellitism: around S. aureus colonies, the colonies of H.
influenzae are much larger and denser, since staphylococci
produce V factor.
* Serological characters
Smooth capsulated strains can be classified into 6 types (a-f),
depending on the capsular polysaccharide. H. influenzae type b
(Hib) is the most pathogenic.
* Pathogenesis, virulence factors and diseases:
The organism enters the upper respiratory tract by inhalation or
droplets. The polysaccharide capsule is the major virulence
factor that facilitates invasion. Other factors include fimbriae
and IgA protease that degrades secretory IgA and facilitates
attachment to respiratory mucosa, resulting in colonization.
Outer membrane proteins and lipopolysaccharide contribute to
invasion.
Diagnosis
• Specimen: CSF.
• Smears are stained with gram. When present in large
numbers in specimens, the organism can be directly
detected by immunofluorescence or by PCR.
• Direct detection of H. influenzae polysaccharide in CSF by
latex agglutination commercial kits.
• Culture on chocolate agar at 37°C in 5% CO2. Colonies are
identified by; their morphology, inability to grow in absence
of X-V growth factors, serologically with specific antisera or
by DNA probes.
Treatment
Cefotaxime given intravenously or
ceftriaxone are the drugs of choice for
Hib meningitis.
Prevention
Haemophilus b conjugated (Hib) vaccines containing the
capsular polysaccharide conjugated to a carrier protein is
recommended for children at 2, 4, 6 months and at 12-15
months. The vaccine may be given in combination with DTP
i.e. DTPH.
Chemoprophylaxis:
Rifampin is giving to non immune children in close contact
with meningitis patients.
Streptococcus agalactiae
These belong to Lancefield group B and are β-haemolytic
but bacitracin resistant. They hydrolyze hippurate and are
CAMP factor positive.
They inhabit about 25% of the normal adult vagina. They are
acquired by the infant from the birth canal during labour and
cause neonatal septicaemia, meningitis and pneumonia.
The main predisposing factor is delayed delivery after rupture
of membranes-longer than 18 hours. Premature babies are at
higher risk. Women identified as carriers should receive
intravenous ampicillin at least 4 hours prior to delivery.
CAMP test
Str. agalactiae characterized
by the production of a
protein that causes
enhanced hemolysis on
sheep blood agar when
combined with β-hemolysin
of S. aureus.
Cryptococcus neoformans
C. neoformans are yeast cells with a
gelatinous capsule. It is found in soil
contaminated with the excreta of birds specially
pigeons' faeces.
It is an opportunistic pathogen affecting mainly
immunosuppressed individuals specially AIDS
patients.
Infection occurs by inhalation where it causes
subclinical lung affection or pneumonia. It may
spread systemically to the CNS causing
meningoencephalitis.
Laboratory diagnosis
1- Direct microscopic examination of sputum and
CSF after staining with India ink, reveals large
gelatinous capsule around budding yeast cells.
2- Cultures done on SDA without actidione, at 20-
37°C show mucoid colonies which are identified by
India ink staining, biochemical reactions (urease
positive) and DNA probes.
3- Capsular antigens are detected in CSF, serum or
urine by using latex agglutination test or ELISA.
4- Antibodies are detected in patients' sera.
Cryptococcus neoformans , India ink stained
film showing the capsule around budding yeast
cells
