Epidemic Cerebrospinal meningitis

Jinfeng Liu,MD,PhD
Department of Infectious
Diseases

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Introduction
Meningococcal meningitis has been
recognized as a serious problem for
almost 200 years. It was first identified
definitely by Vieusseux in Geneva in
1805.

The causative organism, Neisseria
meningitidis, was isolated first in 1887.

Meningococcal disease still is
associated with a high mortality rate
and persistent neurological defects,
particularly among infants and young
children

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Introduction

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Introduction
Meningitis is a general name
for inflammation of the
meninges and the
cerebrospinal fluid.
Meningitis can usually be
caused by infectious agents,
including bacteria, viruses,
fungi, and other organisms.

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Introduction

Knowing whether meningitis is

caused by a virus or bacterium is
important because the severity of
the illness and the treatment is
different.
Viral meningitis is generally less
severe and resolves without
specific treatment, while bacterial
meningitis can be quite severe.
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Meningococc
al meningitis

Etiology

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Etiology

Neisseria meningitidis is a gram-
negative, aerobic, encapsulated
diplococcus which grows best on
enriched media.

The meningococcus has a rapid
autolytic rate.

The bacteria can produce endotoxin
that can activate mono-macrophages
to secret TNF and other cytokines,
Inducing fever, shock, and DIC
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meningococci

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Etiology

Meningococci comprise numerous serogroups
that are based on the composition of their
polysaccharide capsular antigens.

At least 13 serogroups have been described: A,
B, C, D, E, H, I, K, L, W-135, X, Y, and Z.

Serogroups B and C have caused most cases of
meningococcal meningitis in the United States
since the end of World War II; before that,
group A was more prevalent.

serogroup A is still the predominant cause of
meningococcal meningitis in Africa and Asia.

More than 99% of meningococcal infections are
caused by serogroups A, B, C, 29E, or W-135.

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Epidemiology

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Source of infection.
Patients
asymptomatic carriers
Humans are the only natural carrier of
Meningococci

Route of transmission
The modes of infection include direct
contact or respiratory droplets from the
nose and throat of infected people.

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 Susceptible population
Most cases of meningococcal meningitis
occur in children, from infancy to
adolescence. 6M-2Y are the main
susceptible population. (Infants are
protected from meningococcal disease
for the first few months of life by
transferred maternal antibodies and low
rate of meningococcal acquisition. )

In all instances, epidemics occur among

the poorest groups, where crowding and
lack of sanitation are common

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Individuals acquire the infection if they are exposed
to virulent bacteria and have no protective
bactericidal antibodies. Smoking and concurrent
viral infection of the upper respiratory tract
diminish the integrity of the respiratory mucosa and
increase the likelihood of invasive disease.

Crowding living conditions also facilitate disease

spread. since individuals from different areas have
different strains of meningococci, the risk of
invasive disease is higher in the first few days after
exposure to a new strain.

Epidemic season
Incidence is increased in late winter or early
spring

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Frequency:

In the US: Since 1960, the incidence has been

stable, at approximately 0.9-1.5 per 100,000 people
per year.

In the United States, increased frequency of

serogroups B and Y meningococci has been noted
since 1990. The frequency of localized outbreaks
has increased since 1991.

Internationally:

Serogroups A, B, and C are responsible for most

cases of meningococcal disease throughout the
world. In Europe and the America, serogroup B is
the predominant agent . followed in frequency by
serogroup C.

Historically, serogroup A was the main cause of

epidemic meningococcal disease globally, and
serogroup A is still the predominant cause of
meningococcal meningitis in Africa and Asia.
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 In the African "meningitis belt" (a
region of savannah that extends from
Ethiopia in the east to Senegal in the
west), this disease frequently occurs in
epidemics during the hot and dry
weather (December to March).
The recent meningococcal meningitis
pandemic, which began in 1996, has
resulted so far in approximately
300,000 cases being reported to the
World Health Organization (WHO).

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Pathogenesis

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 A number of factors influence the
development of Meningococcal
meningitis, including virulence of the
strain, host defenses, and bacteria-host
interactions. .
local tissue and bloodstream invasion by
bacteria colonized in the nasopharynx
may be a common source. Approximately
5-10% of adults are asymptomatic
nasopharyngeal carriers.

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After adherence to the nasopharyngeal
mucosa, Within 24 hours they can be seen
in the submucosa, close to vessels and local
immune cells.

In most cases, meningococcal colonization

of mucosal surfaces leads to subclinical
infection or mild symptoms.

In approximately 10-20% of cases, N

meningitidis enters the bloodstream. In the
vascular compartment, they may be killed
by bactericidal antibodies, complement, and
phagocytic cells or may multiply, initiating
the bacteremic phase. Organisms replicate
rapidly.
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Meningococci that elaborate a capsule can lead to
invasive disease. The capsule protects them from
desiccation and from host immune mechanisms.
Adhesins and endotoxins also enhance their
pathogenic potential.

Bacterial cell wall components initiate a cascade of

complement- and cytokine-mediated events that
result in at least 3 critical events: increased
permeability of the blood-brain barrier, cerebral
edema, and presence of toxic mediators in the CSF.

The bacteria can produce endotoxin that can

activate mono-macrophages to secret TNF and
other cytokines, Inducing fever, shock, and DIC

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Clinical
manifestation

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 The clinical manifestations of
meningococcal disease can be
quite varied and can range from
transient fever and bacteremia to
fulminant disease with death
ensuing within hours of onset of
clinical symptoms

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Incubation period

1 7 days general 2 3days

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 Clinical types

ordinary type

Fulminant type

Mild type

Chronic Meningococcemia
Persistent meningococcal
bacteremia associated with low-grade
fever, rash , and arthritis has been
reported

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 Classic symptoms
Fever A high fever and chills
Headache
acute onset of intense headache
a very bad headache that won't
go away

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Severe malaise (feeling very
unwell)
lassitude, anorexia (Lack of
interest in drinking and
eating) body aches Sensitivity to
light (photophobia) Nausea and
vomiting

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Mental status changes:
confusion and
sleepiness feeling
very sleepy or unable
to fully wake up .

dysphoric
phrenitis coma
(Stupor or coma is less
common. If coma is
present, the prognosis
is poor. )

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 Seizures 30-40%in children, 20-30% in adults
The majority of seizures have a focal onset.

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Skin rash

Skin rash is a characteristic sign of
this disease Patients older than 30 years
were noted to have petechiae (62%) less
frequently than younger patients (81%).
Appearance

the rash is hemorrhagic . it doesnt blanch
with pressure. ( Petechia, purpuric rash)

Petechia is manifested as discrete lesions 1
to 2 mm in diameter .

in some patients, Petechia can be confluent
and it have putrescence in the central of
rash. The color turns black

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Distribution
A petechial or purpuric rash usually is
found on the trunk, legs, mucous
membranes, and conjunctivae. especially
on the hip. Occasionally, it is on the palms
and soles.
The number of petechia sometimes
correlate with the severity of disease
The rash may progress to purpura
fulminant, when it usually is associated
with multiorgan failure (ie, Waterhouse-
Friderichsen syndrome).
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Signs of meningeal irritation

neck stiffness/ back stiffness

Nuchal rigidity generally not
present in children <1 y or in
patients with altered mental status

Kernig sign: Passive knee extension
in supine patient elicits neck pain
and hamstring resistance.

Brudzinski sign: Passive neck or
single hip flexion is accompanied by
involuntary flexion of both hips.
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Brudzinski sign

Kernig sign

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-Bulging fontanelle (the soft spots on an infant's head

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A more severe but less common form
of meningococcal disease is
meningococcal septicemia, which is
characterized by rapid circulatory
collapse and a hemorrhagic rash.

The Waterhouse-Friderichsen
syndrome may develop in 10-20% of
children with meningococcal infection.
This syndrome is characterized by
large petechial hemorrhages in the
skin and mucous membranes, fever,
septic shock, and DIC.

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Complicati
on

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 Brain damage, cranial nerve
dysfunction
myocarditis (inflammation of the
heart)
hydrocephalus (blockage of spinal
fluid in brain)
Deafness
blindness

Paralysis of various muscles

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Laboratory
Findings

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(1) Routine detection of blood
WBC: 15 30109/L ,neutrocyte
increase mainly about 80

(2)Detection of CSF

A lumbar puncture (LP) is a procedure in

the cerebrospinal fluid (CSF), is removed
and examined. This test is sometimes
also called a spinal tap

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 First, the child is positioned so
that the spaces between the
vertebrae (bones of the spine)
are as wide as possible. Infants
and small children lie on their
sides curled up with their knees
under their chin, like the letter C.
The skin is cleaned with an
antibacterial solution and alcohol.

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 Next, a small, hollow
needle is inserted
through the skin and
then forward through
the space between
the vertebrae in the
lower back until it
enters the space that
contains the spinal
fluid

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The spinal fluid drips out through the
needle into a sequence of collection
tubes and is sent to the lab

Take tube #1 to chemistry lab for glucose
, electrolytes and protein.

Take tube #2 to hematology lab for cell
count.

Take tube #3 to microbiology and
immunology lab for Gram stain, bacterial
culture, acid-fast bacillus (AFB) stain and
tuberculosis (TB) cultures, India ink stain
and fungal cultures,

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a cloudy
spinal
fluid

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 Increased opening pressure (>180
mm H2O)
Pleocytosis of polymorphonuclear
leukocytes ( WBC counts between 10
and 10,000 cells/mm3, predominantly
neutrophils)
Decreased glucose concentration
(<45 mg/dL)
Increased protein concentration (>45
mg/dL)

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Isolating the organism
Gram stain and culture of CSF identify
the etiological organism, N meningitides.
1 Gram stain
Gram stain is positive in 70-90% of untreated
cases, centrifuged CSF deposit Petechiae

2 bacteria culture
culture results are positive in as many as 80%
of cases.
CSF and Blood culture provide the main
diagnostic yield. are needed for identification of
N meningitidis and the serogroup of
meningococci, as well as for determining its
susceptibility to antibiotics.
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 Polymerase chain reaction (PCR) may
be used to complement standard
laboratory procedures for the
diagnosis of meningococcal
meningitis.
The IS-1106 PCR is a rapid and
sensitive test for confirmation of the
diagnosis; its sensitivity is not
affected by prior antibiotic treatment.
PCR of the nspA gene was also
reported to be a fast diagnostic test.

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 Imaging Studies
CT X-RAY is usually normal

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Diagnosis

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Early detection and treatment may lower the
fatality rate by 15%

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 The diagnosis is usually made by
epidemiological data; clinic
manifestation and Laboratory tests
.
Isolating the organism is gold
standard of diagnosis

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Differential
diagnosis

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Encephalitis: should be
considered as the primary
diagnosis in patients in whom focal
signs, convulsions or disturbance
of consciousness are prominent in
the clinical picture

Aseptic meningitis: connective

tissue disease, drug induced, viral
or fungal meningitis

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Prognosis

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Prognosis depends on the
pathogen, patient's age
and condition, and
severity of acute illness.

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Treatment

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Pathogen treatment (antibiotic therapy)
Meningococcal disease is potentially fatal and
always should be viewed as a medical
emergency. Admission to a hospital is
necessary. To prevent serious neurological
morbidity and death, prompt institution of
antibiotic therapy is essential when the
diagnosis of bacterial meningitis is suspected.
Obtain CSF promptly, before any neuroimaging
studies, unless the patient is in a coma or has
papilledema, focal neurological deficits, or
seizures.
Institute antimicrobial therapy as soon as
possible after the lumbar puncture is
performed.
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Causal treatment (antibiotic therapy)

Once meningitis is
diagnosed, an
infected person will
be treated with
several antibiotics

Antibiotics must
permeate through the
blood-brain barrier.

it must be sensitive to
the agents .

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The first successful treatment of
meningitis with intravenous penicillin
was reported in 1944,

the first clinical trials using high doses

of intravenous penicillin as monotherapy
for the treatment of meningitis were
reported in 1950.

Since then, penicillin has remained the

drug of choice for the treatment of
meningococcal meningitis

It is safe and effective.

Adult Dose 20, 0000u/kg/d iv q6h

Pediatric Dose 50,000 U/kg/d iv q6h

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Unresponsiveness to penicillin has not
been observed in the United States.
Routine testing for susceptibility of
meningococcal isolates is not
necessary, unless the patient does not
exhibit appropriate clinical response.

Therapy should be changed to

ceftriaxone (or cefotaxime) if the
isolate is resistant to penicillin.

Third-generation cephalosporins have

been used successfully in the
treatment of pediatric cases of
meningococcal meningitis

cefotaxime, ceftriaxone
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Sulfonamides
now have a very limited role in the
treament of meningococcal infection
Chloramphenicol
Most strains are susceptible to it
,it is still the drug of choice. but the
side-effects (granulocytopenia,
aplastic anemia, thrombocytopenia)
shoud be pay attention to.

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Rifampin, quinolones, and
ceftriaxone are the
antimicrobials used to
eradicate meningococci from
the nasopharynx.

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10 to 14 days
of therapy is
usually
sufficient.

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General treatment

isolating the patient

strict bed rest
nursing and diet
*closely observe the changes of the
temperature , pulse and blood
pressure
* keep the clear of skin , mouth and
eyes
* provide a liberal calorie, nutritious

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symptomatic treatment

High fever
physical cooling
Salicylates and antipyretics shoud be used

severe toxemia
Steroids
may been adiministed at the same
time of using effective antibiotics
Dexamethasone may interrupt the
cytokine-mediated neurotoxic effects
of bacteriolysis, which are at
maximum in the first days of
antibiotic use.
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 shock
Evaluate and treat patient for shock or
hypotension. Infuse crystalloid, blood
plasma, albumin et.al.
Cerebral edema
diuresis (ie, furosemide 20 mg IV,
mannitol 1 g/kg IV q6h-q8h)
DIC
The problem of DIC is ominous. Heparin
treatment is needed in the early stage
of disease development

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Prevention

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 Control the source of infection

for patients for

carriers

Block the route of transmission

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Protect susceptible population
vaccination for susceptible individual

Two vaccine preparations derived from

the capsular polysaccharide of groups
A and C meningocicci are
recommended. Many studies have
demonstrated its high efficacy
Simpler prevention may be practiced
by good habits such as washing hands
often and avoiding sharing food and
drinks with others
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thank you

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