Download Common causes of bacterial meningitis in children older than 1

Bacterial Meningitis beyond the Newborn Period
Abd El-Salam Dawood MD
Interventional Pediatric Cardiologist
FIBMS-Ped FIBMS-PedCard
Meningitis is an inflammation of the meninges.
Because death can occur in more than 5% of cases
and morbidity may occur in 30% of survivors, it is still
a feared childhood infection.
Epidemiology:
Common causes of bacterial meningitis in children
older than 1 month of age are Neisseria meningitidis,
Streptococcus pneumoniae and, until recently,
Hemophilus influenzae type b (Hib). While in those <
1 mo, group B streptococcus (GBS) followed by
Listeria monocytogenes are the most common. Most
cases occur in children between 1 month and 5 years
of age, with the highest risk being in infants aged 6 to
12 months.
The incidence of meningococcal meningitis in the
developed countries in those aged 1 to 23 months is
4.5 per 100,000. It is a Gram-negative diplococcus.
Meningococcal disease is more common in males. The
disease generally is acquired from carriers who can
harbor the organism for months. The incidence of
disease peaks in winter. The incubation period is from
1 to 10 days. Host factors, such as terminal
complement
deficiency,
complement-depleting
diseases,
or
properdin
deficiency,
increase
susceptibility to disease.
S. pneumoniae is a gram-positive diplococcus with
tens serotypes. Sepsis and meningitis occur most
frequently with specific serotypes (4, 6B, 9V, 14, 18C,
19F, and 23F).
Hib is a gram-negative coccobacillus. Historically, it
was the leading cause of bacterial meningitis in many
developed countries. In countries where Hib
vaccination is not yet widespread, the disease
continues to be a common occurrence, with a peak
incidence occurring in late autumn or early winter. Host
factors are important because meningitis occurs with
increased frequency in children with diabetes mellitus,
Cushing syndrome, and coma secondary to drug
overdose. Genetic factors also may play a role.
Other bacteria, such as group B streptococcus, Listeria
monocytogenes, Salmonella, and Fusobacterium
necrophorum, can cause meningitis in "normal"
children. Skin flora should be suspected in children
with a dermoid sinus, meningomyelocele, or
hydrocephalus and a cerebrospinal fluid (CSF) shunt.
Cystic fibrosis or burn patients may develop
Staphylococcus aureus or Pseudomonas aeruginosa
meningitis after colonization. In a humidified
atmosphere, P. aeruginosa or Serratia marcescens
infection may occur. Children with sickle cell disease,
and congenital asplenia are especially susceptible to
Salmonella infection, in addition to H. influenzae and S.
pneumoniae. Children who have reticuloendothelial
malignancies, are undergoing chemotherapy, or have
indwelling catheters may develop meningitis from
organisms of low virulence, such as Streptococcus
mitis. In immunocompromised children, Bacteroides
fragilis is a frequent anaerobic cause of meningitis.
Congenital or acquired anatomic defects, such as a
cribiform plate fracture, should be investigated in
cases of recurrent meningitis.
Meningitis with two bacterial types in a CSF culture
may occur in 1% of cases. Meningitis with a bacteria
and a virus or fungus occurs rarely. The clinical course
usually is that of bacterial meningitis.
Pathogenesis:
Initially, upper respiratory tract infection occurs.
Bacteremia
follows,
with
opsonization
and
phagocytosis inhibited by bacterial capsules.
Meningeal seeding occurs. Invasion from a contiguous
infection (e.g., mastoiditis) also can occur.
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Organisms initially are found in the lateral and dorsal
longitudinal (sagittal) sinuses. Central nervous system
(CNS) blood flows may be reduced by 25% to 50%.
Dural inflammation slows the flow from the
subarachnoid space to the sinuses, thereby permitting
spread of infection. A meningeal exudate occurs over
the brain. The spinal cord may be encased in pus.
Purulent material may develop in the ventricles and the
ventricular wall and around the veins and venous
sinuses.
Hypoglycorrhachia and acidosis result in part from
increased glucose use and decreased glucose
transport across the inflamed choroid plexus.
Increased glucose use results in the excess production
of lactate production and the depletion of the highenergy compounds adenosine triphosphate and
phosphocreatine.
Increased CSF protein is caused partly by the flow of
albumin-rich fluid into the subdural space secondary to
inflammation and increased vascular permeability.
Cerebral cortex damage produces the neurologic
sequelae of meningitis.
Clinical manifestations and complications:
Nerve inflammation leads to meningeal symptoms and
signs. Early pressure on peripheral nerves may lead to
motor or sensory deficits.
Meningitis can develop slowly over the course of
several days, or it can be fulminant, with onset
occurring within hours. The clinical presentation
depends on the age of presentation:
Cerebral edema results from vasogenic, interstitial,
and cytotoxic processes. Vasogenic edema results
from increased permeability of the blood brain barrier.
Interstitial edema occurs with decreased CSF
resorption as proteins, leukocytes, and debris interfere
with the function of the arachnoid villi. Cytotoxic edema
results from host and bacterial toxic factors, which
increase intracellular water and sodium and loss of
intracellular potassium.
Increased ICP often exceeds 300 mm H2O.
Hypoxemia and ischemia from decreased perfusion
may result. Papilledema is a rare occurrence because
of the brief duration of increased pressure.
Hydrocephalus rarely occurs beyond the neonatal
period. Communicating hydrocephalus may result from
adhesive arachnoid thickening about the basal cisterns.
Obstructive hydrocephalus may result from fibrosis
and reactive gliosis obliterating the aqueduct of Sylvius
or the foramina of Magendie and Luschka. In some
cases, meningitis is associated with the syndrome of
inappropriate antidiuretic hormone release (SIADH),
causing water retention and a relative sodium loss by
the kidney. SIADH increases the risk of developing
electrolyte abnormalities, increased ICP, and seizures.
Dehydration also can occur from increased insensible
losses and decreased intake.
In infants: fever or hypothermia, lethargy, respiratory
distress, jaundice, vomiting, diarrhea, poor feeding,
restlessness, irritability, decreased muscle tone, full
fontanelle, seizures.
In children: fever, chills, photophobia, anorexia,
confusion, altered consciousness, coma, cranial nerve
palsies, upper respiratory symptoms, petechial or
purpuric rash, myalgia, arthralgia, nuchal rigidity,
headache, nausea, vomiting, malaise, restlessness,
lethargy, ataxia, hyperesthesia, back pain, seizures,
kernig sign, brudzinski sign.
Fever and meningeal inflammation symptoms occur in
85% of patients. Nuchal rigidity may appear late,
especially in a young child. Seizures occur in 30% of
cases at some time before or during the course of
illness. Infants may have a bulging fontanelle, but such
appears late and in only approximately 30% of infants
(13% of children without meningitis). Papilledema is a
rare development; if present, a search for other
processes (e.g., brain abscess, venous sinus
occlusion, subdural empyema) should be performed.
Transient or permanent cranial nerve damage may
cause deafness, vestibular disturbance, ataxia, and
extraocular or facial nerve paralysis. Optic-nerve
arachnoiditis may lead to optic atrophy and blindness.
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Focal neurologic deficits may exist on admission in
15% of children and in 30% of children with
pneumococcal meningitis. When focal signs are
present without seizures, cortical necrosis, occlusive
vasculitis, or thrombosis of cortical veins probably has
occurred. Infants may have only restlessness,
irritability, poor feeding, or unstable temperature.
Adolescents
may
present
with
behavioral
abnormalities that may be confused with drug abuse or
psychiatric disorders.
Kernig sign (while supine with the leg flexed at the hip
to 90 degrees and the knee flexed, pain occurs on leg
extension beyond 135 degrees) and Brudzinski sign
(while supine, leg flexion occurs when the neck is
flexed) may be absent in 50% of cases, especially if
antibiotics have been given.
Subdural effusions may occur in 50% of cases.
Although usually asymptomatic, they may cause
increasing
head
circumference,
abnormal
transillumination, vomiting, seizures, full fontanelle,
focal neurologic signs, or persistent fever. They usually
resolve spontaneously.
Meningomyelitis or spinal cord infarction may lead
to spastic paraparesis, with or without sensory loss.
Early arthritis may be caused by invasions of the
organism itself, whereas late arthritis more likely is
immunologically induced. Arthralgia and myalgia also
may occur.
Pericardial effusions usually resolve with the
administration of antibiotic therapy. However,
pericardial effusion with persistent fever may require
drainage.
Facial cellulitis, pneumonia, epiglottitis, and
endophthalmitis also can be presenting signs of
meningitis.
In one-half or more cases of meningococcal disease,
the patient may have purpura or petechiae (a
nonblanching rash) during the course.
Shock with profound hypotension may occur in 5%
of meningococcal and Hib meningitis cases.
Disseminated intra-vascular coagulation (DIC) may
occur.
Death can occur within hours,
administration of adequate therapy.
despite
the
Diagnosis:
No single symptom or sign is pathognomonic for
meningitis because any, none, or all of the clinical
manifestations described may be present.
Definitive diagnosis is established through a positive
identification of the organism in the CSF.
Lumbar Puncture: A lumbar puncture (LP) must be
performed if meningitis is suspected. Increased
numbers of neutrophils and increased protein and
decreased glucose concentrations suggest the
presence of bacterial infection (see table 1).
Contraindications to performing an LP are
cardiopulmonary compromise, signs of possible
increased ICP (e.g., papilledema, altered respiratory
efforts, focal neurologic signs), and skin infection over
the LP site. "Herniation rarely may occur with
increased ICP". Papilledema is a late sign of increased
ICP, so a careful neurologic examination should be
done. In children with suspected increased ICP or
altered mental status, antibiotics should be given
immediately after taking blood cultures and an
emergency computed tomographic (CT) scan should
be done before the LP is performed. A reliance on
blood cultures and clinical signs is inadequate because
both may be misleading, particularly if prehospital
antibiotics have been given. If an LP cannot be
performed, meningitic doses of antibiotics should be
administered until the procedure can be performed.
When an LP is performed, CSF pressure should be
measured. CSF color should be recorded.
Microscopy should include a total leukocyte count and
differential. Most (95%) healthy children older than 3
months of age have no CSF neutrophils, which are the
initial leukocytes in the CSF. A later change to
monocytes and lymphocytes occurs during recovery. If
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the LP is traumatic, a safe approach is to wait for
culture results.
A Gram stain should be performed. Most results will be
positive. Prehospital administration of antibiotics may
reduce Gram-stain yields to 40% to 60%. Normal CSF
may be found (10%), therefore, cultures should be
performed regardless of fluid appearance or cell count.
Blood cultures may be positive in as many as 90% of
cases if antibiotics have not been given. Routine
prehospital antibiotics generally do not have a
significant effect on CSF cell counts, but they may
reduce culture yields to less than 50% from a normal
yield of up to 85%.
A Gram stain from purpuric or petechial skin lesions
may reveal the organism.
A urine culture should be obtained in a child younger
than 1 year of age before giving antibiotics, if possible.
Throat or nasopharyngeal cultures are not helpful
(colonization by one organism can occur with infection
by another).
TABLE 1: CSF FINDINGS IN DIFFERENT CONDITIONS.
WBC (/mm3)
Protein
(mg/dl)
Glucose
(mg/dl)
< 5; 75%
lymphocytes
100-10,000 or more;
Polymorphonuclear
cells (PMNs)
predominate
5-10,000; PMNs
usual
20 – 45
>50 (75% of
blood level)
Decreased,
usually <40
(<50% serum
glucose)
Normal or
decreased
Normal or
slightly
elevated (80150)
Rarely >1,000 cells.
PMNs early but
mononuclear cells
predominate
through most of the
course
Usually 50200
Generally
normal;
(decreased
in mumps 1520% of cases)
Usually
elevated
10-500; PMNs early,
but lymphocytes
predominate
through most of the
course
100-3,000;
may be
higher in
presence
of block
<50 in most
cases;
decreases
with time if
treatment is
not provided
Condition
Pressure
(mm H2O)
Normal child
50-80
Acute bacterial
meningitis
Usually
elevated (100300)
Partially treated
bacterial meningitis
Normal or
elevated
Viral meningitis or
meningoencephalitis
Tuberculous
meningitis
Rapid Diagnostic Tests:
Because countercurrent immunoelectrophoresis and
latex particle agglutination tests provide results rapidly,
these tests are used most commonly, but both have
limitations. Enzyme-linked immunosorbent assays
Usually
100-500
Usually
100-500
Comments
Organisms usually seen on
Gram stain and recovered
by culture
Organisms may be seen on
Gram stain
Pretreatment may render
CSF sterile. Antigen may be
detected by agglutination
test
Herpes Simplex (HSV)
encephalitis is suggested by
focal seizures or by focal
findings on CT or MRI scans
or EEG. Enteroviruses and
HSV infrequently recovered
from CSF. HSV and
enteroviruses may be
detected by PCR of CSF
Acid-fast organisms almost
never seen on smear.
Organisms may be
recovered in culture of large
volumes of CSF.
Mycobacterium tuberculosis
may be detected by PCR of
CSF
(ELISA), polymerase chain reaction assay (PCR), and
others are helpful in some cases.
Countercurrent immunoelectrophoresis in 1 hour
identifies Hib, S. pneumoniae, N. meningitidis, group B
streptococcus, and other bacteria. A negative
countercurrent immunoelectrophoresis result does not
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exclude bacteremia or meningitis caused by these
organisms.
A PCR analysis of CSF has been used to detect
microbial DNA in patients with bacterial meningitis.
Primers are available for detection of S. pneumoniae,
N. meningitidis, and Hib simultaneously. No falsepositive results were noted.
Rapid detection tests are not necessary for all patients.
They may be helpful in situations such as a traumatic
LP or in a patient who has been pretreated with
antibiotics.
Differential Diagnosis:
Many other processes produce signs and symptoms
that mimic meningitis. High on the list should be
infection with mycobacteria, fungi, viruses, or protozoa.
Other noninfectious processes include a CNS abscess,
bacterial endocarditis with embolism, subdural
empyema, and brain tumor.
Treatment:
Because of increasing penicillin resistance in S.
pneumoniae, most centers use cefotaxime (225 to
300 mg/kg/day in three to four divided doses) or
ceftriaxone (100 mg/kg/day in two divided doses) for
children older than 3 months of age. In children aged 1
to 3 months, ampicillin (400 mg/kg/day in four divided
doses) should be added because of the possible
presence of L. monocytogenes or enterococcal
infection. Because of the high frequency of S.
pneumoniae resistant to penicillin and to thirdgeneration
cephalosporins,
vancomycin
(60
mg/kg/day in four divided doses) should be given with
cefotaxime or ceftriaxone until an organism is identified
and its sensitivities determined. If an organism other
than S. pneumoniae is suspected, such as when a
Gram stain shows gram-negative organisms in a
meningococcal outbreak, alternative therapy can be
considered. N. meningitidis penicillin resistance also is
widely variable.
Vancomycin combined with ceftriaxone or cefotaxime
appears to be synergistic. It should not be used as
monotherapy. When cephalosporin resistance is
demonstrated
or
patients
are
allergic
to
cephalosporins, vancomycin can be combined with
rifampin.
Meropenem (a carbapenem) either alone (120
mg/kg/day every 8 hours) or in combination with other
drugs, may be effective for treating patients who
cannot tolerate vancomycin.
The duration of antibiotic therapy depends on the
causative agent and the clinical response. Minimal
duration for Hib and S. pneumoniae is 10 days. A
minimum of 7 days is required for meningococcal
meningitis. The patient should be afebrile for 5 days
before halting therapy. Although outpatient therapy is
less costly than is hospitalization and it returns patients
to their normal environment sooner, it currently is not
recommended. Gram-negative meningitis should be
treated for a minimum of 3 weeks.
If clinical improvement is slow, if dexamethasone is
used, or if a resistant strain is identified on the initial
culture, a repeat LP is indicated after 24 to 48 hours of
therapy. Cell counts, protein, and glucose levels may
be abnormal, but a repeat LP must have a negative
Gram stain and sterile culture results. If S. pneumoniae
is present in the repeat culture, rifampin (20
mg/kg/day in two divided doses) should be added.
Another LP should be performed 24 to 48 hours after
starting rifampin.
Adjunctive Therapy:
Because the effect of bacterial meningitis is affected
greatly by the host response, corticosteroids have
been suggested as adjunctive therapy. In experimental
meningitis,
corticosteroids
reduce
meningeal
inflammation, thereby reducing ICP and significantly
increasing cerebral perfusion.
Sensorineural hearing loss is an important sequela of
bacterial meningitis. In children with Hib meningitis,
numerous studies have shown that dexamethasone
(0.15 mg/kg per dose every 6 hours for 2 days) given
rapidly just before or with administration of antibiotics
significantly reduces hearing loss. Studies of
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corticosteroids in pneumococcal meningitis are more
limited. Some have shown a benefit, but others have
not. A meta-analysis found that dexamethasone given
before the first dose of antibiotics in pneumococcal
meningitis resulted in improved outcome for severe
hearing loss. In meningococcal meningitis, the use of
corticosteroids has not been studied adequately.
The benefit of administering corticosteroids for other
neurologic sequelae also is controversial.
The use of corticosteroids is not benign. They may
delay CSF sterilization, especially in pneumococcal
meningitis. Corticosteroids should not be used for
more than 2 days because studies have shown no
improvement with a longer course. The risk of
gastrointestinal bleeding occurring is not significantly
increased in a 2-day course. Dexamethasone also can
suppress clinical signs, leading to a false sense of
clinical improvement.
It should not be used in children with partially treated
bacterial meningitis, nonbacterial meningitis, or CNS
abnormalities.
Supportive Care:
The first 3 days of treatment for bacterial meningitis are
the most critical. Vital signs should be taken every 30
minutes until the patient is stable, then hourly for 48
hours, with rectal temperatures measured every 4
hours. The patient's body weight, urine specific gravity,
serum electrolytes (sodium, potassium, chloride, and
bicarbonate), and osmolality of serum and urine should
be measured on admission and every 12 hours for the
first 36 hours. A complete blood count with differential
and platelets should be performed on admission and
repeated as indicated. Coagulation factors should be
checked if petechiae, purpura, or abnormal bleeding is
present.
A complete neurologic evaluation should be performed
on admission, followed by brief neurologic checks
every 4 hours for the first several days. Complete
neurologic evaluation should be performed daily. In
children younger than 18 months, daily head
circumference measurements and transillumination
should be done. These procedures may permit the
detection of subdural effusion or hydrocephalus.
To prevent vomiting and aspiration, and to allow better
assessment of fluid intake, the patient should receive
nothing by mouth initially. A careful intake and output
record is required. All patients should be assessed
carefully for hydration status and development of
syndrome of inappropriate ADH secretion (SIADH).
The best indicators of SIADH are absence of signs of
dehydration, increased body weight, decreased serum
osmolality, and continued sodium excretion despite
hyponatremia. If SIADH is demonstrated, fluids should
be given at 1,000 mL/m2/day. Fluids can be liberalized
to maintenance requirements (1,600 mL/m2/day) as
the serum sodium level normalizes, usually within 1
day. Restriction of fluids should not occur in all patients.
If dehydration is present, maintenance fluids plus
sodium and water deficit replacement over the course
of 24 to 48 hours can be given.
In patients with septic shock, fluid must be provided to
maintain circulation and blood pressure. Central
venous pressure monitoring helps to avoid fluid
overload. Plasma or albuminized saline and dopamine
and dobutamine may improve blood pressure while
minimizing fluid intake.
When signs of increased ICP such as a bulging
anterior fontanelle or progressive lethargy occur,
elevation of the head to 30 degrees may help.
Increased ICP with deterioration of mental status or
signs of cerebral herniation may be treated with
intravenous mannitol (0.5 g/kg over 30 minutes,
repeated as necessary) and, if necessary, placement
of an ICP monitoring device. ICP should be kept at less
than 20 mm Hg. Hyperventilation may compromise
cerebral blood flow and increase the risk of infarction.
In the absence of focal neurologic signs, a CT scan is
not needed to identify effusions because they are part
of the normal pathophysiology of the disease. Other
indications for obtaining a CT scan include focal
neurologic signs, prolonged obtundation, focal
seizures, rapidly increasing head circumference,
persistently increased CSF protein, persistent CSF
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granulocytosis, or chronically recurring meningitis.
Radioisotope imaging may be helpful in some patients
to show collections of purulent material.
Seizures must be controlled with emergency
management and anticonvulsants as needed. If the
seizures no longer are apparent by the third or fourth
hospital day, anticonvulsants can be discontinued. An
electroencephalogram may be indicated when (a) focal
seizures are noted, (b) seizures persist beyond the
third hospital day, or (c) prolonged alteration of
consciousness occurs.
The treatment of subdural effusions usually is not
necessary unless the effusions are suspected as being
the cause of focal seizures or increased ICP, or the
source of prolonged fever. Subdural empyema should
be drained and treated with antibiotics.
Intravenous heparin (1 mg/kg every 4 hours) may be
beneficial in disseminated intravascular coagulation,
although no controlled studies have documented the
benefit of this course of action.
Fever lasts for 5 days in most children. If fever lasts
longer than 8 days, a thorough search for brain
abscess, subdural or pleural empyema, septic arthritis,
thrombophlebitis, or pericarditis should be done.
Nosocomial infections and drugs may prolong the
duration of fever. Persistent fever also may arise from
poor therapeutic response associated with the
presence of organisms resistant to the antibiotics
chosen for therapy.
Although serum CRP is not sensitive enough to
distinguish bacterial from aseptic meningitis on
admission, an admission CRP determination can be
drawn and compared with subsequent CRP levels. A
secondary increase in CRP or a slow decline may
indicate complications not yet clinically evident.
Performing a predischarge LP normally is not
necessary.
Prognosis:
Poor prognosis occurs with young age, delays before
appropriate antibiotics are started, and the presence of
disorders that compromise the host response to
infection. Patients whose CSF cultures grow more than
107 organisms frequently have more seizures,
subdural effusions, bacteremia, speech disturbance,
hearing loss, and prolonged fevers. Elevated CNS IL1ß and TNF have been associated with a higher risk of
developing neurologic sequelae, as has very low CSF
white blood cell count. Complications such as focal
neurologic findings at admission, focal deficits,
seizures during the infection, SIADH, purpura, shock,
hypothermia, or a low white or red blood cell count at
admission all have been associated with poor
prognosis.
Death rates vary widely. Rates up to 55% have been
reported in developing countries.
Meningitis sequelae include hearing loss, mental
retardation, seizures, spasticity and paresis,
hydrocephalus, blindness, behavior disorders, and
neuropsychological or auditory dysfunctions that
adversely affect academic performance.
Prevention:
Prophylaxis can prevent the spread of N. meningitidis
and H. influenzae. Pneumococcal prophylaxis is not
recommended because contacts are not at
significantly increased risk of developing infection.
Anyone who develops fever after exposure to patients
with any form of bacterial meningitis should get prompt
medical attention.
N. meningitidis prophylaxis with rifampin (10 mg/kg,
with a 600 mg maximum, every 12 hours) for 2 days
should be given within 24 hours of case recognition.
Household, day-care, and close contacts of the patient
during the previous 7 days should receive rifampin.
Medical personnel exposed to the patient's secretions
in the first 24 hours after the start of antibiotics should
receive prophylaxis. Ciprofloxacin (500 mg orally) in
one dose can be used for contacts older than 18 years
of age. Ceftriaxone (125 mg intramuscularly in those
younger than 12 years of age and 250 mg for those
older than 12 years) is an effective alternative to
rifampin and can be used. The index patient should
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receive prophylaxis on discharge unless treated with
ceftriaxone or cefotaxime.
Hib prophylaxis with rifampin (20 mg/kg, with a 600 mg
maximum, once daily) for 4 days eliminates most
nasopharyngeal carriage of Hib. Rifampin should be
given to day-care or nursery school contacts if two or
more cases occur within 60 days. Children who have
received Hib vaccine should receive prophylaxis.
Vaccines:
Hib conjugate vaccine (0.5 mL per dose) has two
dosing schedules. The child may receive the vaccine
at 2, 4, and 6 months and requires a 12 to 15-month
booster.
Hib conjugate vaccine is recommended routinely for
children to prevent invasive Hib disease.
S. pneumoniae vaccine (Pneumovax 23, 0.5 mL per
dose) is recommended for use after 2 years of age for
high-risk children, such as those with sickle cell
disease, functional or anatomic asplenia, nephrotic
syndrome, or immunocompromised, or when the effect
of infection could be severe, as in children with certain
congenital heart diseases. This vaccine is
recommended for all children younger than 24 months
of age and generally is given at 2, 4, 6, and 12 months
of age (four doses).
N. meningitidis vaccine is recommended for individuals
at high risk for the acquisition of disease. The
American Academy of Pediatrics has recommended
that conjugate mcv4 vaccine should be given to
adolescents, to adolescents at high school entry and
to college freshman living in dormitories. Immunization
with meningococcal polysaccharide quadrivalent
vaccine (mpsv4) recommended for children 2 years of
age and older in high-risk groups, including those with
asplenia, and those with terminal deficiencies of the
complement system or with properdin deficiency. It
also is recommended for individuals travelling to
hyperendemic areas or in an epidemic due to a
meningococcal type contained in the vaccine.
Meningitis in the newborn:
Any newborn with bacterial sepsis is also at risk for
meningitis. The incidence is low in infants with earlyonset (first 7 days) sepsis but much higher in infants
with late-onset (>7 days) infection. The workup for any
newborn with signs of infection should include a spinal
tap. Diagnosis is suggested by a CSF protein greater
than 150 mg/dL, glucose less than 30 mg/dL, more
than 25 leukocytes/mL, and a positive Gram stain. The
diagnosis is confirmed by culture. The most common
organisms are GBS and gram-negative enteric
bacteria. Although sepsis can be treated with
antibiotics for 10–14 days, meningitis should be
treated for 21 days. The mortality rate of neonatal
meningitis is approximately 25%, with significant
neurologic morbidity present in one third of the
survivors. Use of dexamethasone has not been
studied in neonates.
Viral Meningoencephalitis:
Viral meningoencephalitis is an acute inflammatory
process involving the meninges and, to a variable
degree, brain tissue. These infections are relatively
common and may be caused by a number of different
agents. In most instances, the infections are selflimited.
Etiology:
Enteroviruses are the most common cause of viral
meningoencephalitis. The severity of infection caused
by enteroviruses ranges from mild, self-limited illness
to severe encephalitis resulting in death or significant
sequelae.
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Arboviruses are arthropod-borne agents, responsible
for some cases of meningoencephalitis during summer
months. Mosquitoes and ticks are the most common
vectors after biting infected birds or small animals.
The cerebral cortex, especially the temporal lobe, is
often severely affected by HSV; the arboviruses tend
to affect the entire brain; rabies has a predilection for
the basal structures.
Several members of the herpes family of viruses can
cause meningoencephalitis. Herpes simplex virus
type 1 (HSV-1) is an important cause of severe,
sporadic encephalitis in children and adults. Brain
involvement usually is focal; progression to coma and
death occurs in 70% of cases without antiviral therapy.
Severe encephalitis with diffuse brain involvement is
caused by herpes simplex virus type 2 (HSV-2) in
neonates who usually contract the virus from their
mothers at delivery. Varicella-zoster virus (VZV) may
cause CNS infection in close temporal relationship with
chickenpox. Cytomegalovirus (CMV) infection of the
CNS may be part of congenital infection or
disseminated disease in immunocompromised hosts.
Epstein-Barr virus (EBV) has been associated with
myriad CNS syndromes. Human herpes virus 6 (HHV6) can cause encephalitis, especially among
immunocompromised hosts.
Clinical Manifestations:
Mumps is a common pathogen in regions where
mumps vaccine is not widely used. Mumps
meningoencephalitis is mild, but deafness may be a
sequela. Meningoencephalitis is caused occasionally
by respiratory viruses (adenovirus, influenza virus,
parainfluenza virus), rubeola, rubella, or rabies; it may
follow live virus vaccinations against polio, measles,
mumps, or rubella.
Epidemiology and pathogenesis:
Infection with enteroviruses is spread directly from
person to person, with a usual incubation period of 4-6
days. Most cases in temperate climates occur in the
summer and fall.
Neurologic damage is caused by direct invasion and
destruction of neural tissues by actively multiplying
viruses or by a host reaction to viral antigens. A
marked degree of demyelination with preservation of
neurons and their axons is considered to represent
predominantly “postinfectious” or “allergic” encephalitis.
The progression and severity of disease are
determined by the relative degree of meningeal and
parenchymal involvement, which is determined by the
specific etiology. Some children may appear to be
mildly affected initially, only to lapse into coma and die
suddenly. In others, the illness may be ushered in by
high fever, violent convulsions interspersed with
bizarre movements, and hallucinations alternating with
brief periods of clarity, followed by complete recovery.
The onset of illness is generally acute. The presenting
manifestations in older children are headache and
hyperesthesia, and in infants, irritability and lethargy.
Headache is most often frontal or generalized;
adolescents frequently complain of retrobulbar pain.
Fever, nausea and vomiting, photophobia, and pain in
the neck, back, and legs are common. As body
temperature increases, there may be mental dullness,
progressing to stupor in combination with bizarre
movements and convulsions. Focal neurologic signs
may be stationary, progressive, or fluctuating.
Exanthems often precede or accompany the CNS
signs, especially with echoviruses, coxsackieviruses,
VZV, measles and rubella. Examination often reveals
nuchal rigidity without significant localizing neurologic
changes.
Specific forms or complicating manifestations of CNS
viral infection include Guillain-Barre syndrome,
transverse myelitis, hemiplegia, and cerebellar ataxia.
Diagnosis:
The diagnosis of viral encephalitis is usually made on
the basis of the clinical presentation of nonspecific
prodrome followed by progressive CNS symptoms.
The diagnosis is supported by examination of the CSF
(see table 1). The CSF should be cultured for viruses,
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bacteria, fungi, and mycobacteria; in some instances,
special examinations are indicated for protozoa,
mycoplasma, and other pathogens. Other tests of
potential value in the evaluation of patients with
suspected viral meningoencephalitis include an
electroencephalogram (EEG) and neuroimaging
studies. The EEG typically shows diffuse slow-wave
activity, usually without focal changes. Neuroimaging
studies (CT or MRI) may show swelling of the brain
parenchyma. Focal seizures or focal findings on EEG,
CT, or MRI, especially involving the temporal lobes,
suggest HSV encephalitis.
Detection of viral antigen by polymerase chain reaction
may be useful in the diagnosis of CNS infection caused
by HSV and enteroviruses.
A serum specimen should be obtained early in the
course of illness and, if viral cultures are not diagnostic,
again 2-3 wk later for serologic studies.
Treatment:
With the exception of the use of acyclovir for HSV
encephalitis, treatment of viral meningoencephalitis
is supportive. Treatment of mild disease may require
only symptomatic relief. Headache and hyperesthesia
are treated with rest, non–aspirin-containing
analgesics, and a reduction in room light, noise, and
visitors. Acetaminophen is recommended for fever.
Codeine, morphine, and medications to reduce nausea
may be useful. Intravenous fluids are occasionally
necessary because of poor oral intake. More severe
disease may require hospitalization and intensive care.
It is important to monitor patients with severe
encephalitis closely for convulsions, cerebral edema,
inadequate respiratory exchange, disturbed fluid and
electrolyte balance, aspiration and asphyxia, and
cardiac or respiratory arrest of central origin. In
patients with evidence of increased ICP, placement of
a pressure transducer in the epidural space may be
indicated. The risks of cardiac and respiratory failure
or arrest are high with severe disease. All fluids,
electrolytes, and medications are initially given
parenterally. In prolonged states of coma, parenteral
alimentation is indicated. SIADH is common in acute
CNS disorders; monitoring of serum sodium
concentrations is required for early detection. Normal
blood levels of glucose, magnesium, and calcium must
be maintained to minimize the likelihood of convulsions.
If cerebral edema or seizures become evident,
vigorous treatment should be instituted.
Prognosis:
Motor incoordination, convulsive disorders, total or
partial deafness, and behavioral disturbances may
follow viral CNS infections. Visual disturbances due to
chorioretinopathy and perceptual amblyopia may also
occur.
Neurodevelopmental
and
audiologic
evaluations should be part of the routine follow-up of
children
who
have
recovered
from
viral
meningoencephalitis.
Most children completely recover from viral infections
of the CNS. If the clinical illness is severe and
substantial parenchymal involvement is evident, the
prognosis is poor, with potential deficits being
intellectual, motor, psychiatric, epileptic, visual, or
auditory in nature. Severe sequelae should also be
anticipated in those with infection caused by HSV.
Approximately 10% of children younger than 2 yr with
enteroviral CNS infections suffer an acute complication
such as seizures, increased ICP, or coma. Almost all
have favorable long-term neurologic outcomes.
Prevention:
Widespread use of effective viral vaccines for polio,
measles, mumps, rubella, and varicella has almost
eliminated CNS complications from these diseases.
Control of encephalitis due to arboviruses has been
less successful because specific vaccines for the
arboviral diseases are not available.
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