Epidemic Cerebrospinal Meningitis

Department of Infectious Diseases

Luo Hongchun

What is meningitis?

anatomical structure of meninges

Definition
Meningitis is
an inflammation of the membranes lining the brain and spinal
cord
caused most often by infectious agents that cross the body's
blood-brain barrier.
(Infectious agents include bacteria, viruses, fungi and other
organisms such as protozoa, rickettsia.)

Meningococcal meningitis
a form of purulent meningitis
caused by Neisseria meningitidis
The clinical manifestations include hyperpyrexia, severe headache,
frequent vomiting, petechia, ecchymosis, meningeal irritation sign,
etc.
Severe patient usually has septic shock, injury of brain parenchyma.
Meningococcal meningitis can deteriorate to die within 24 hours.

Etiology
u Gram-negative
u aerobic diplococci that are
kidney-shaped,
approximately0.6-0.8 um in
diameter.
u They are difficult to grow on
common culture, but can easily
grow on chocolate or blood or
yolk medium.
Neisseria meningitidis

Etiology
u 13 kinds of serotypes according to specific
capsular polysaccharide antigen
u serotype A,B,C,Y,and W-135 mainly
associated with meningococcal meningitis
u being susceptive to desiccation, damp and hot,
chill, sunlight,ultraviolet ray and general
disinfectant.
u Meningococci autolyze in vitro easily .
diagrammatic model of Neisseria meningitidis

Epidemiology
Source of infection
l
l
l
l

Bacteria-carrier and patient

Higher covert infection rate (up to 40%-50%)
Parasitizing the nasopharynx asymptomatically
Bacteria-carrier has an important significance as source of
infection

Route of transmission
airborne droplets and intimate contacts
(such as kissing, coughing, sharing drinks and food)

Epidemiology
Susceptibility of the crowd
l being commonly susceptible to meningococcus.
l lower Morbidity of infants
l under 5 years of age ,especially at the age of 6 months to 2 years
l obtaining a lasting immunity after infection

Epidemiology
l Risk factors:
complement deficiency
entry into a new environment of crowded condition, such as
university dormitory, military camp
having a history of preceding illness
premature infant
active or passive smoking

Epidemiology
Epidemiologic feature
l A global health problem
l The peak of incidence:in winter or early spring.

Pathogenesis
Virulent factors
A

polysaccharide capsule

pilus

endotoxin

Pathogenesis
Neisseria meningitidis adheres to the
epithelial surface of nasopharynx
N. meningitidis
penetrates the
mucosa and
gains access
to the
bloodstream

N. meningitidis binds to CD46

slip-strand
mispairing
called
asmolecular
switch

N.meningitidis initiates cytoskeletal changes in

epithelial cells

Unencapsulated meningococci enter

epithelial cells to stop capsular biosynthesis

Encapsulated
meningococcal isolates
in bloodstream have
the switch in the on
position

Nasopharyngeal
unencapsulated
carrier isolates have
the switch in the off
position

Pathogenesis
Endotoxins are released
from bacteria
inducing generalized
shwartzman reaction
activating complement system
and raising serum level of
inflammatory mediators
generating circulatory
disturbance and shock
presenting DIC and
secondary fibrinolytic
hyperfunction
leading to multiple
organ failure

Clinical manifestations
Incubation period 1-7 days(usually 2-3days)

Ordinary type

Fulminant type

Mild type

Chronic type

ordinary type
1. Prodromal stage
u liking as upper respiratory
infection
u nonspecific symptoms including
the sudden onset of
fever,drowsiness pharyngalgia,
rhinobyon(nasal obstruction),
losing appetite,nausea, vomiting,
headache, etc
u being neglected easily in this
stage
u easily confusing meningococcal
meningitis with flu

pharyngalgia

2. Septic stage

u getting into this stage rapidly

u presenting hyperpyrexia,headache,
myalgia, decreased ability of
concentration, unconsciousness
u untypical symptoms and signs of
infant
u 70% of cases presents petechiae,
purpura,ecchymosis
u presenting shock, DIC in severe
cases

3.Meningitic stage
u having hyperpyrexia ,
toxic symptoms severe
headache, projectile
vomiting, dysphoria,
stiff neck, positive
Kernigs sign and
Brudzinskis sign, etc
u anterior fontanelle
bulge of infant because
of unclosed anterior
fontanelle
anterior fontanelle bulge

4.Decubation
u The temperature gradually declines to normal scale.
u Consciousness and mental status are ameliorated.
u Petechiae and ecchymoses are absorbed and scab.
u Generally speaking, the patient will be cured within 1-3 weeks.
u Immune complex reactions appear mostly after illness for 714days. They may cause arthritis, pericarditis, conjunctivitis,
urethritis, epiglottitis, but infrequently.

Fulminant type
uan extremely acute onset
udeteriorating rapidly
u dying within 24 hours without effective therapy
ubeing divided into three hypotypes(Shock type,
Meningoencephalitis type, Mixed type)

1.Shock type
u having hyperpyrexia or low temperature,accompanied
with headache, vomiting, petechiae and ecchymoses.
u presenting symptoms and signs of shock in short time.
pale face
perioral cyanosis
acrocyanosis
skin piebaldness
cold limbs
faint pulse

tachypnea,
peripheral circulation failure
blood pressure dropping
urine output decreasing
coma

1.Meningoencephalitis type
u showing the meninge and brain parenchyma injury.
u presenting symptoms and signs of shock in short time.
hyperpyrexia
headache
vomiting
consciousness disorder
coma

intracrinal hypertension
positive meningeal irritation sign
convulsion
cerebral hernia

1.Mixed type
The symptoms in shock type and meningoencephalitis type
occur successively or concurrently

Mild type
u occurring in the late of epidemic of meningococcal
meningitis
uliking as upper respiratory infection(mild fever,
headache, pharyngalgia)
uno change in cerebrospinal fluid
ufinding meningococcus in pharynx swab cultrue

Chronic type
u infrequent occurring
uprolonged the course of illness( extending for several
weeks or months)
uintermittent fever (declining after lasting 12 hours,
but,reoccurring every 1-4 days)
ushowing petechiae, accompanied with arthralgia,
splenomegaly, leukocytosis, positive blood culture

Laboratory examination
1. blood routine examination
u Leukocyte count increases apparently.
u Neutrophils account for 80%-90%.
u Platelets decrease absolutely in patient with DIC.

Laboratory examination
2. cerebrospinal fluid examination
u Having little change in CSF in initial stage or shock type
u Increasing intracranial pressure in classic meningitic stage
u Presenting purulent CSF
total leukocytes
glucose and chloride

polymorphanuclear leukocytes
protein concentration

Laboratory examination
3. bacteriologic examination
u Collecting spicemen before using antibiotics
u Culturing CSF, blood, or tissue fluid in petechia

Laboratory examination
4. other tests
u Serologic test
u Polymerase-chain-reaction (PCR) analysis

Complication
1.neurogenic deafness
2.epilepsy
3.hydrocephalus
4.diffuse brain damage
5.other complications : persistent headache, otitis media, purulent
arthritis, endocarditis, pericarditis, neurasthenia, irritability, altered
sleep pattern, difficulty in concentration ,gangrene of extremities,
adrenal insufficiency, renal failure, pulmonary fibrosis, reduced
pulmonary function

Diagnosis
epidemic history

clinical manifestations

laboratory examinations

Diagnosis
1. suspected case
u having epidemiological history of meningococcal meningitis
u clinical manifestations and CSF examination coincide with
purulent meningitis

Diagnosis
2. clinical diagnosed case
u having epidemiological history of meningococcal meningitis
u having clinical manifestations and purulent CSF , accompanied
with petechiae and ecchymoses

Diagnosis
3. confirmed case
positive bacteria culture or immunological detecting based on
clinical diagnosed case

Differential diagnosis
1. purulent meningitis caused by other bacteria
l

no obviously seasonal characteristics

no petechiae , no ecchymoses in skin

bacteriological examination

Differential diagnosis
2. tuberculous meningitis
l

having a history of tuberculosis or a close contact with

tuberculosis cases

mild fever, night sweat, emaciation

no petechiae ,no ecchymoses

SCF examination: increasing monocytes and protein

concentration; decreasing glucose and chloride

Prognosis
1. favorable prognosis
the patients with effective treatment in common type

2. poor prognosis
the patients in fulminant type
infants under the age of one year
old people

Treatment
1. antibiotic therapy
u giving the appropriate antibiotics within 30 minutes
u diminishing the probability of positive CSF culture due to
antibiotic therapy
u the first choice of the drug for the patient with bacterial
meningitis prior to susceptibility result:Third-generation
cephalosporins

Treatment
u Third-generation cephalosporins:
ceftriaxone: 2g,iv,q12h in adults; 50-100mg/kg/day,iv,q12h in
children
cefotaxime: 2g,iv,q4h in adults; 50mg/kg/day, iv,q4h in children
u Meropenem: 1g,iv,q8h in adults; 40mg, iv,q8h in children
u Penicillin:

being administered intravenously (IV) or intramuscularly

never being administered intrathecally

4 million units, iv,q4h in adults(an upper limit of 24 million units/day)

200000-400000units/kg/day, iv ,q8h in children

Treatment
u Chloramphenicol :
75-100 mg/kg/day,iv, q6h(a maximum dose of 4 g/day)
u Duration of antibiotics therapy:

basing upon the severity of initial illness and the response of the
patient

treatment for seven days

Treatment
2. treatment of shock
ureceiving a therapy in a tertiary care medical facility whenever
possible
uneeding fluid infusion based on antibiotic therapy
ucrystalloid in combination with colloid

Treatment
u in the first hour: 1000ml of liquids to the adults
10-20ml/kg liquids to the children
u in the first 24 hours: 2000-3000ml of infusion volumes to the adults
50-80ml/kg infusion volumes to the childern.
u vasoactive drug: Dopamine, dobutamine, noradrenaline, and
adrenaline

Treatment
3. treatment of DIC
u using heparin as soon as possible (low molecular heparin)
u coagulation time: 2.5-3 times of normal value
u infusing fresh plasma, platelet after correcting hypercoagulability

Treatment
4. usage of Glucocorticoid
u 10-20mg of dexamethesone per day to adults
0.2-0.5mg/kg per day to children
u the duration of usage : usually no more than 3 days

Treatment
4. dehydration therapy
u 125ml of 20% mannitol , iv, q4-6h
u diuretic, glucocorticoid with mild dehydration effect

Prophylaxis
1. administrating the source of infection
u diagnosing as soon as possible
u quarantine time:
until the symptoms disappear for 3 days
no less than 7days after illness
being observed at least 7days for the people contacting with
patients

Prophylaxis
2. cutting off the route of transmission
u .Ameliorating sanitation
u .Keeping indoor ventilation
u .Enhancing hygiene education
u .Avoiding a big party
u .Wearing mask outdoors

Prophylaxis
3. protecting the susceptible population
u the main objects of vaccination:
the children under the age of 15 years old
the recruits in military camp
the people with immunodeficiency
u a quadrivalent vaccine: containing serogroups A,C,W-135 and Y

Prophylaxis
4. Chemoprophylaxis
u

applying to the following population:

household
daycare
kissing contact
medical personnel experiencing intensive contact with oral
secretions