Meningitis

• Meningitis is the term to denote

inflammation of the meninges. Clinically,
this characteristically results in
the occurrence of meningeal symptoms
(eg, headache, nuchal rigidity,
photophobia) and an increased number of
white blood cells in the cerebrospinal fluid
(CSF; pleocytosis).
• The brain and spinal cord are covered by 3
connective tissue layers collectively called the
meninges which form the blood-brain barrier.
• the pia mater (closest to the
CNS)
• the arachnoid mater
• the dura mater (farthest from
the CNS).
• The meninges contain
cerebrospinal fluid
(CSF).
• Meningitis is an
inflammation of the
meninges, which, if
severe, may become
encephalitis, an
inflammation of the
brain.
 Meningitis:
• inflammation of the pia mater and the arachnoid
mater, with suppuration of the cerebrospinal fluid
 Classification
• Based on duration of symptoms:
– Acute meningitis denotes the evolution of
symptoms within hours to several days.
– Chronic meningitis has an onset and duration
of weeks to months (least 4 weeks).
• In many instances, these syndromes
overlap because they share many
etiologic agents.
• Based on etiology:
• Acute bacterial meningitis denotes a bacterial
cause of this syndrome, Depending on the
specific bacterial cause, eg:
– Streptococcus pneumoniae meningitis,
– meningococcal meningitis,
– Haemophilus influenzae meningitis.
• Fungal and parasitic eg:
– cryptococcal meningitis,
– Histoplasma meningitis,
– Amebic meningoencephalitis.
• acute viral meningitis (eg, enterovirus
meningitis, herpes simplex virus [HSV]
meningitis).
• Non-bacterial meningitis is often
referred to as ‘aseptic meningitis’ – eg.
viral meningitis

• Bacterial meningitis may be referred to

as ‘purulent meningitis’.
 Epidemiology
• Neonates (< 1 Month) • Children (1 month to 15
– Gm (-) bacilli 50-60% years)
– Grp B Strep 20-40% – H. influenzae 40-60%
– Listeria sp. 2-10% • Declining dramatically in
many geographic regions
– H. influenza 0-3%
– N. meningitidis 25-40%
– S. pneumo 0-5%
– S. pneumo 10-20%
• Adults (> 15 years)
– S. pneumo 30-50%
– N. Meningitidis 10-35%
• Major cause in epidemics
– Gm (-) Bacilli 1-10%
• Elderly
– S. aureus 5-15%
– H. influenzae 1-3%
• >60 include Listeria, E. coli, Pseudomonas
 Pathogenesis
• Three major pathways exist by which an infectious agent
(ie, bacteria, virus, fungus, and parasite) gains access to
the central nervous system (CNS) and causes disease:
• The infectious agent colonizes or establishes a localized
infection in the host. From this site, the organism invades
the submucosa by circumventing host defenses and
gains access to the CNS by
– Invasion of the bloodstream (ie, bacteremia, viremia, fungemia,
parasitemia) and subsequent hematogenous seeding of the
CNS, which is the most common mode of spread for most
agents (eg, meningococcal, cryptococcal, syphilitic, and
pneumococcal meningitis);
– A retrograde neuronal (ie, olfactory and peripheral nerves)
pathway (eg, Naegleria fowleri, Gnathostoma spinigerum); or
– direct contiguous spread (ie, sinusitis, otitis media, congenital
malformations, trauma, and direct inoculation during intracranial
manipulation).
 Physiology
• Once inside the CNS, The presence and replication of
infectious agents remain uncontrolled and incite a
cascade of meningeal inflammation due to absence of
host defense.
• Pathophysiology of meningitis include the pivotal role of:
– cytokines (eg, tumor necrosis factor-alpha [TNF-alpha],
interleukin [IL]–1),
– chemokines (IL-8), and
– other proinflammatory molecules in the pathogenesis of
pleocytosis and
– neuronal damage during bacterial meningitis.
• Increased CSF concentrations of TNF-alpha, IL-1, IL-6,
and IL-8 are characteristic findings in patients with
bacterial meningitis.
 Physical
• Signs of cerebral dysfunction are common, including
confusion, irritability, delirium, and coma. These are
usually accompanied by fever and photophobia.
• Signs of meningeal irritation are observed in only
approximately 50% of patients with bacterial meningitis,
and their absence certainly does not rule out meningitis.
– Kernig sign: In a supine patient, flex the hip to 90° while the knee
is flexed at 90°. An attempt to further extend the knee produces
pain in the hamstrings and resistance to further extension.
– Brudzinski sign: Passively flex the neck while the patient is in a
supine position with extremities extended. This maneuver
produces flexion of the hips in patients with meningeal irritation.
– Nuchal rigidity: Resistance to passive flexion of the neck is also
a sign.
– Exacerbation of existing headache by repeated horizontal
movement of the head, at a rate of 2-3 times per second, may
also suggest meningeal irritation.
• Cranial nerve palsies may be observed as a
result of increased ICP or the presence of
exudates encasing the nerve roots.
• Focal neurologic signs may develop as a result
of ischemia from vascular inflammation and
thrombosis.
• Seizures occur in approximately 30% of patients.
• Papilledema and other signs of increased ICP
may be present.
– Coma, increased blood pressure with bradycardia,
and cranial nerve III palsy may be present.
• The presence of papilledema also suggests a
possible alternate diagnosis (eg, brain abscess).
 Papilledema

Optic disc swelling that is caused by increased intracranial pressure

• Systemic findings upon physical examination
may provide clues to the etiology.
– Morbilliform rash with pharyngitis and adenopathy
may suggest a viral etiology (eg, Epstein-Barr virus
[EBV], cytomegalovirus [CMV], adenovirus, HIV).
– Macules and petechiae that rapidly evolve into
purpura suggest meningococcemia (with or without
meningitis).
– Vesicular lesions in a dermatomal distribution suggest
varicella-zoster virus.
– Genital vesicles suggest HSV-2 meningitis.
– Sinusitis or otitis suggests direct extension into the
meninges, usually with S pneumoniae and H
influenzae.
– Rhinorrhea or otorrhea suggests a CSF leak from a
basilar skull fracture, with meningitis most commonly
caused by S pneumoniae.
 – Hepatosplenomegaly and lymphadenopathy suggest
a systemic disease, including viral (eg,
mononucleosis like syndrome in EBV, CMV, and HIV)
and fungal (eg, disseminated histoplasmosis)
disease.
– The presence of a murmur suggests infective
endocarditis with secondary bacterial seeding of the
meninges.
– Evidence of parotitis is observed in some cases of
mumps meningitis.
– The presence of a ventriculoperitoneal shunt or a
cochlear implant may suggest a bacterial cause of
meningitis.
•
In contrast to bacterial meningitis, patients with
aseptic meningitis syndrome usually appear
clinically nontoxic with no vascular instability.
 Causes

Acute bacterial meningitis

The Most Common Bacterial Pathogens Based on
Age and Predisposing Risks
Risk and/or Predisposing
Bacterial Pathogen
Factor
S agalactiae (group B
streptococci)
Age 0-4 weeks
E coli K1
L monocytogenes
S agalactiae
E coli
Age 4-12 weeks H influenzae
S pneumoniae
N meningitidis
N meningitidis
Age 3 months to 18 years S pneumoniae
H influenzae
S pneumoniae
Age 18-50 years N meningitidis
H influenzae
 S pneumoniae
N meningitidis
Age older than 50 years
L monocytogenes
Aerobic gram-negative bacilli
S pneumoniae
N meningitidis
Immunocompromised state
L monocytogenes
Aerobic gram-negative bacilli
Staphylococcus aureus
Coagulase-negative staphylococci
Intracranial manipulation, including
Aerobic gram-negative bacilli,
neurosurgery
including
Pseudomonas aeruginosa
S pneumoniae
Basilar skull fracture H influenzae
Group A streptococci
Coagulase-negative staphylococci
S aureus
CSF shunts
Aerobic gram-negative bacilli
Propionibacterium acnes
 S pneumoniae
• S pneumoniae, is a common colonizer of the human
nasopharynx (5-10% of healthy adults and 20-40% of healthy
children).

• It causes meningitis by escaping the local host defenses and

phagocytic mechanisms, either through choroid plexus seeding
from bacteremia or through direct extension from sinusitis or
otitis media.

• Common bacterial cause of meningitis, accounting for 47% &

mortality rates among the bacterial agents that cause
meningitis (19-26%).
• It is the most common bacterial agent in meningitis associated
with basilar skull fracture and CSF leak.

• It may be associated with other foci of infection, such as

pneumonia, sinusitis, or endocarditis (ie, Austrian syndrome).

• Patients with hyposplenism, hypogammaglobulinemia, multiple

myeloma, glucocorticoid treatment, defective complement (C1-
C4), diabetes mellitus, renal insufficiency, alcoholism,
malnutrition, and chronic liver disease are at increased risk.
 N meningitidis
• N meningitis is a gram-negative diplococcus that
is carried in the nasopharynx of otherwise healthy
individuals. It initiates invasion by penetrating the
airway epithelial surface.

• Most sporadic cases (95-97%) are caused by

serogroups B, C, and Y, while the A and C strains
are observed in epidemics (<3% of cases).

• Presently, it is the leading cause of bacterial

meningitis in children and young adults,
accounting for 59% of cases.
 Risk factors
• (1) deficiencies in terminal complement
components (eg, membrane attack complex,
C5-C9), which increases attack rates but is
associated with surprisingly lower mortality
rates;
• (2) properdin defects that increase the risk of
invasive disease;
• (3) antecedent viral infection, household
crowding, chronic medical illness, corticosteroid
use, and active or passive smoking; and
• (4) overcrowding places.
 Meningococcal meningitis:
Clinical signs in children and adults

Not all of these

symptoms are
necessarily
present at the
same time
 Severe Outcome of
Meningococcemia

Petichial Rash

Severe Late-Stage Meningococcal Infection in a 15-Year-Old Boy

 Types of vaccine
• Purified capsular polysaccharide vaccines
– bivalent vaccine against serogroups A and C
– quadrivalent vaccine for serogroups A,C, Y
and W135
• Protein-polysaccharide conjugate
vaccines.
– Three monovalent meningococcal C
conjugate vaccines
– Pending approval - quadrivalent conjugate
vaccine (ACYW135)
 H influenzae
• H influenzae is a small, pleomorphic, gram-negative
coccobacilli that is frequently found as part of the normal
flora in the upper respiratory tract of humans.
• Since the implementation of the HIB vaccine, the
carriage rates for the encapsulated type B strain have
decreased from 2-4% to less than 1%.
• It can spread from one individual to another by airborne
droplets or direct contact with secretions.
• It primarily affects infants younger than 2 years.
• Its isolation in adults suggests the presence of an
underlying medical disorder, including paranasal
sinusitis, otitis media, alcoholism, CSF leak following
head trauma, functional or anatomic asplenia, and
hypogammaglobulinemia.
 L monocytogenes
• L monocytogenes is a small gram-positive bacillus that
causes 8% of bacterial meningitis cases and is
associated with one of the highest mortality rates (22%).
• Most human cases appear food-borne. It is a common
food contaminant, with a recovery rate of up to 70% from
raw meat, vegetables, and meats.
• Outbreaks have been associated with consumption of
contaminated coleslaw, milk, cheese, and alfalfa tablets.
• Persons at risk include pregnant women, infants and
children, elderly individuals (>60 y), patients with
alcoholism, adults who are immunosuppressed (eg,
steroid use, transplant recipients, patients with AIDS),
individuals with chronic liver and renal disease,
individuals with diabetes, and those with conditions of
iron overload (eg, hemochromatosis or transfusion-
induced iron overload).
 S agalactiae
• S agalactiae (group B streptococci) is a gram-
positive coccus that is isolated from the lower
gastrointestinal tract.
• It also colonizes the female genital tract at a rate
of 5-40%, which explains why it is the most
common (70%) agent of neonatal meningitis.
• It has also been reported in adults, primarily
affecting individuals older than 60 years. The
overall case-fatality rate in adults is 34%.
• Predisposing risks in adults include diabetes
mellitus, pregnancy, alcoholism, hepatic failure,
renal failure, and corticosteroid treatment.
 Aerobic gram-negative bacilli
(eg, E coli, Klebsiella pneumoniae, Serratia
marcescens, P aeruginosa, Salmonella species)
• The gram-negative bacilli can cause meningitis
in certain groups of patients. E coli is a common
agent of meningitis among neonates.
• Other predisposing risk factors include
– (1) neurosurgical procedures or intracranial
manipulation;
– (2) old age;
– (3) immunosuppression;
– (4) high-grade gram-negative bacillary bacteremia;
and
– (5) disseminated strongyloidiasis, which has been
reported as a classic cause of gram-negative bacillary
bacteremia (as a result of the translocation of gut
microflora with the Strongyloides stercoralis larva
during hyperinfection syndrome).
 Staphylococcus species
(S aureus and coagulase-negative staphylococci)
• Staphylococci species are gram-positive cocci
that are part of the normal skin flora.
• Meningitis caused by staphylococci is
associated with the following risk factors:
– (1) status postneurosurgery and posttrauma,
– (2) presence of CSF shunts, and
– (3) infective endocarditis and paraspinal infection.
• Staphylococcus epidermidis is the most
common cause of meningitis in patients with
CNS (ie, ventriculoperitoneal) shunts.
 Aseptic meningitis syndrome
• Aseptic meningitis is the most common
infectious syndrome affecting the CNS.
• Most episodes are caused by a viral
pathogen, but they can also be caused by
bacteria, fungi, or parasites .
• Importantly, partially treated bacterial
meningitis accounts for a large number of
meningitis cases with a negative
microbiologic workup.
 Infectious Agents Causing Aseptic
Meningitis Syndrome
Category Agent
Partially-treated bacterial meningitis, L
monocytogenes, Brucella species, Rickettsia
rickettsii , Ehrlichia species, Mycoplasma
Bacteria
pneumoniae, B burgdorferi , Treponema
pallidum, Leptospira species
Mycobacterium tuberculosis, Nocardia species
 Naegleria fowleri, Acanthamoeba species,
Balamuthia species, Angiostrongylus
Parasites cantonensis, G spinigerum,
Baylisascaris procyonis
S stercoralis, Taenia solium (cysticercosis)

Cryptococcus neoformans, C immitis,

Fungi B dermatitidis, H capsulatum
Candida species,Aspergillus species
 Viruses
•Enterovirus
–Poliovirus, Echovirus, Coxsackievirus A,
Coxsackievirus B, Enterovirus 68-71

•Herpesvirus
–HSV-1 and HSV-2, Varicella-zoster virus,
EBV, CMV, HHV*-6, HHV-7

•Paramyxovirus
–Mumps virus, Measles virus
 Viruses

•Togavirus
–Rubella virus
•Flavivirus
–Japanese encephalitis virus, St. Louis
encephalitis virus
•Bunyavirus
–California encephalitis virus, La Crosse
encephalitis virus
•Alphavirus
–Eastern equine encephalitis virus,
Western equine encephalitis virus,
Venezuelan encephalitis virus
 Viruses

•Reovirus
–Colorado tick fever virus
•Arenavirus
–LCM virus
•Rhabdovirus
–Rabies virus
•Retrovirus
–HIV
 Acute viral meningitis:
Viral meningitis comprises most aseptic meningitis
syndromes.
• Enterovirus
– Enterovirus belongs to the family Picornaviridae. It is classified further to
include polioviruses (3 serotypes), coxsackievirus A (23 serotypes),
coxsackievirus B (6 serotypes), echovirus (31 serotypes), and the newly
recognized enterovirus serotypes 68-71.
– They are distributed worldwide, and the infection rates vary depending
on the season of the year and the age and socioeconomic status of the
population.
– The virus is usually spread by fecal-oral or respiratory routes and occurs
during summer and fall in temperate climates and year-round in tropical
regions.
– Most of the infections occur in individuals who are younger than 15
years, with the highest attack rates in children who are younger than 1
year.
– The nonpolio enteroviruses (NPEV) account for approximately 90% of
cases of viral meningitis in which a specific pathogen can be identified.
– In patients with deficient humoral immunity (eg, agammaglobulinemia),
enterovirus meningitis may have a fatal outcome.
• Herpesvirus
– The Herpesviridae family consists of large DNA-containing
enveloped viruses. Eight members are known to cause human
infections, and all have been implicated in meningitis
syndromes, with the exception of HHV-8 or Kaposi sarcoma–
associated virus.
– HSV-1 is a cause of encephalitis, while HSV-2 more commonly
causes meningitis. Although more commonly associated with
HSV-2, both viruses have been implicated to cause Mollaret
syndrome, a recurrent but benign aseptic meningitis syndrome.
– EBV, or HHV-4, and CMV, or HHV-5, may manifest as
meningitis during the mononucleosis syndrome.
– Varicella zoster virus (VZV), or HHV-3, and CMV are causes of
meningitis in immunocompromised hosts, especially patients
with AIDS and transplant recipients.
– HHV-6 and HHV-7 have been reported to cause meningitis in
transplant recipients.
• Arthropod-borne viruses
– The most common arthropod-borne viruses are St.
Louis encephalitis virus (a flavivirus), Colorado tick
fever, and California encephalitis virus (bunyavirus
group, including La Crosse encephalitis virus).
– St. Louis encephalitis virus is a mosquito-borne
flavivirus that may cause a febrile syndrome, aseptic
meningitis syndrome, and encephalitis. The infection
usually occurs during the summer and early fall, with
symptoms typical of acute aseptic meningitis.
– Other members of the flavivirus group that may cause
aseptic meningitis include tick-borne encephalitis
virus and Japanese encephalitis virus.
– California encephalitis is a common childhood
disease of the CNS that is caused by a virus in the
genus Bunyavirus. Most of the cases of California
encephalitis are probably caused by mosquito-borne
La Crosse virus. The infection with symptoms typical
of acute aseptic meningitis.
• Lymphocytic choriomeningitis virus
– LCM virus is a member of the arenaviruses, a family
of single-stranded RNA-containing viruses with
rodents as the animal reservoir.
– The infection occurs worldwide, and most human
cases occur among young adults during autumn.
– The modes of transmission include aerosols and
direct contact with rodents.
– Following exposure, an incubation period of
approximately 5-10 days ensues, followed by a
nonspecific febrile illness and an acute onset of
aseptic meningitis. This may be associated with
orchitis, arthritis, myocarditis, and alopecia.
• Human immunodeficiency virus
– Aseptic meningitis syndrome may be the presenting symptom in
a patient with acute HIV infection. This usually is part of the
mononucleosis like acute sero-conversion phenomenon.
– Always suspect HIV as a cause of aseptic meningitis in a patient
with risk factors such as intravenous drug use and in individuals
who practice high-risk sexual behaviors.

• Other viruses causing meningitis

– Patients with meningitis caused by the mumps virus usually
present with the triad of fever, vomiting, and headache. It follows
the onset of parotitis (salivary gland enlargement occurs in 50%
of patients), which clinically resolves in 7-10 days.
– Adenovirus (serotypes 1, 6, 7, and 12) has been associated with
cases of meningoencephalitis. Chronic meningoencephalitis has
been reported with serotypes 7, 12, and 32. The infection is
usually acquired through a respiratory route.
 Chronic meningitis
• Chronic meningitis is a constellation of signs and
symptoms of meningeal irritation associated with CSF
pleocytosis that persists for longer than 4 weeks. The
agents responsible for chronic meningitis are:
Category Agent
M tuberculosis , B burgdorferi, T pallidum , Brucella
Bacteria species, Francisella tularensis,Nocardia species
Actinomyces species
C neoformans , C immitis , B dermatitidis , H
capsulatum
Fungi
Candida albicans, Aspergillus species,Sporothrix
schenckii
Acanthamoeba species, N fowleri , Angiostrongylus
Parasites cantonensis, G spinigerum, B procyonis, Schistosoma
species,S stercoralis, Echinococcus granulosus
• Chronic bacterial meningitis
– Brucella species are small gram-negative coccobacilli
that cause zoonoses as a result of infection with
Brucella abortus, Brucella melitensis, Brucella suis,
and Brucella canis.
– Transmission to humans occurs following direct or
indirect exposure to infected animals (eg, sheep,
goat, cattle).
– Direct infection of the CNS occurs in fewer than 5% of
cases, with most patients presenting with acute or
chronic meningitis.
– Persons at risk include individuals who had contact
with infected animals (eg, sheep, goat, cattle) or their
products (eg, intake of unpasteurized milk products).
Veterinarians, abattoir workers, and laboratory
workers dealing with these animals are also at risk.
• Tuberculous meningitis
– M tuberculosis is an acid-fast bacillus that causes a broad range of
clinical illnesses that can affect virtually any organ of the body.
– It is worldwide in distribution, and humans are its only reservoir.
– It is spread through airborne droplet nuclei.
– Always consider tuberculous meningitis in the differential diagnoses of
patients with aseptic meningitis or chronic meningitis syndromes.
– Involvement of the CNS with tuberculous meningitis is usually caused
by rupture of a tubercle into the subarachnoid space.
– The presentation may be acute, but the classic presentation is
subacute and spans weeks. Patients generally have a prodrome of
fever of varying degrees, malaise, and intermittent headaches. Patients
often develop central nerve palsies (III, IV, V, VI, and VII), suggesting
basilar meningeal involvement.
– Clinical staging of meningeal tuberculosis is based on neurologic
status. Stage 1 shows no change in mental function with no deficits and
no hydrocephalus. Stage 2 refers to a patient with confusion and
evidence of neurologic deficit. Stage 3 refers to an individual with
stupor and lethargy.
 Spirochetal meningitis
• T pallidum
– T pallidum is a slender tightly coiled spirochete that is usually acquired
by sexual contact. Other modes of transmission include direct contact
with an active lesion, passage through the placenta, and blood
transfusion (rare). The median incubation period before the appearance
of symptoms is 21 days (range 3-90 d), during which time spirochetemia
develops.
– Three stages of disease are described, and involvement of the CNS can
occur during any of these stages.
– Syphilitic meningitis usually occurs during the primary or secondary
stage, complicating 0.3-2.4% of primary infections during the first 2
years. Its presentation is similar to other agents of aseptic meningitis,
with headache, nausea, vomiting, and meningismus.
– Other CNS syphilitic syndromes include meningovascular syphilis,
parenchymatous neurosyphilis, and gummatous neurosyphilis, all of
which are manifestations of late symptomatic neurosyphilis.
Meningovascular syphilis occurs later in the course of untreated syphilis,
and the symptoms are dominated by focal syphilitic arteritis (ie, focal
neurologic symptoms associated with signs of meningeal irritation) that
spans weeks to months and results in stroke and irreversible damage if
left untreated. Patients with HIV have an increased risk of accelerated
progression.
• B burgdorferi
– B burgdorferi is the agent of Lyme disease, the most
common vector-borne disease in the United States. It
is a tick-borne spirochete.
– Lyme disease is characterized by 3 stages. Although
rare during stage I, CNS involvement (with meningitis)
may occur and is characterized by the concurrent
appearance of erythema migrans at the site of tick
bite. More commonly, aseptic meningitis syndrome
occurs 2-10 weeks following the erythema migrans
rash. This represents stage 2 of Lyme disease, or the
borrelial hematogenous dissemination stage. Chronic
neuroborreliosis is a hallmark of the third stage of
Lyme disease and is characterized by subacute
encephalopathy manifested by disturbance in mood,
memory, language, or sleep.
 Fungal meningitis
• C neoformans
– C neoformans is an encapsulated yeastlike fungus that is
ubiquitous and has a worldwide distribution. It has been found in
high concentrations in aged pigeon droppings and pigeon
nesting places.
– The 4 serotypes are designated A through D, with the A
serotype causing most human infections. Serotypes B and C
have been restricted mostly to tropical and subtropical regions,
and serotype B has been isolated from eucalyptus trees.
– The infection is characterized by the gradual onset of symptoms,
the most common of which is headache.
– The onset may be acute, especially among patients with AIDS. A
large number of cases occur in healthy hosts (eg, with no known
T-cell defect); however, approximately 50-80% of cases occur in
immunocompromised hosts. At particular risk are individuals with
defects of T-cell–mediated immunity (eg, those who use
steroids, cyclosporine, and other immunosuppressants).
– Most cases have occurred among individuals with AIDS and
among organ transplant recipients. It has also been reported in
patients with idiopathic CD-4 lymphopenia, Hodgkin disease,
and sarcoidosis.
• C immitis
– C immitis is a dimorphic fungus that exists in mycelial and yeast
(spherule) forms. It is a soil-based fungus with a distribution
limited to the endemic regions of the Western Hemisphere,
within the north and south 40° latitudes (ie, parts of the
southwest United States, Mexico, and Central and South
America).
– The infection follows inhalation of the Arthroconidia.
Extrapulmonary dissemination to the skin (most common), joints,
and bones occurs in predisposed individuals.
– Coccidioidal meningitis is the most serious form of
dissemination, and it usually is fatal if left untreated. These
patients may present with headache, vomiting, and altered
mental function associated with pleocytosis, elevated protein
levels, and decreased glucose levels. Eosinophils may be a
prominent finding in the CSF.
– Persons at risk include individuals exposed to the endemic
regions (eg, tourists and local populations) and those with
immune deficiency (ie, AIDS, organ transplantation).
• B dermatitidis
– B dermatitidis is a dimorphic fungus that has been
reported to be endemic in North America (eg,
Mississippi and Ohio River basins). It has also been
isolated from parts of Central America, South
America, the Middle East, and India.
– The natural habitat of this fungus is not well defined.
Soil that is rich in decaying matter and environments
around riverbanks and waterways have been
demonstrated to harbor the fungus during outbreaks
and are thought to be risk factors for acquiring the
infection.
– Inhalation of the conidia establishes a pulmonary
infection. Dissemination may occur in certain
individuals (including patients with AIDS) and may
involve the skin, bones and joints, genitourinary tract,
and the CNS. Involvement of the CNS occurs in fewer
than 5% of cases, and patients may present with an
abscess or fulminant meningitis.
• H capsulatum
– H capsulatum is one of the dimorphic fungi that exist
in mycelial and yeast forms. It is usually found in soil.
– It has been reported from many areas of the world,
with the Mississippi and Ohio River valleys being the
most endemic regions in North America.
– Primary infection follows inhalation exposure.
Dissemination occurs in individuals with underlying
immune deficiency (eg, from HIV or pharmaceutical
agents) and extremes of age.
– Involvement of the CNS is rare but may occur as part
of disseminated histoplasmosis and manifests most
frequently as chronic meningitis.
– Patients may present with headache, cranial nerve
deficits, or changes in mental status months prior to
diagnosis.
• Candida species
– Candidal species are ubiquitous in nature. They are
normal commensals in humans and are found in the
skin, the gastrointestinal tract, and the female genital
tract.
– The most common species is C albicans, but the
incidence of non-albicans candidal infections (eg,
Candida tropicalis) is increasing, including species with
antifungal resistance (eg, Candida krusei, Candida
glabrata).
– Involvement of the CNS usually follows hematogenous
dissemination. The most important predisposing risk
for acquiring disseminated candidal infection appears
to be iatrogenic in nature (eg, use of broad-spectrum
antibiotics and indwelling devices such as urinary and
vascular catheters). AIDS is also considered a
predisposing risk factor. Infection may also follow
neurosurgical procedures, such as placement of
ventricular shunts.
• S schenckii
– S schenckii is an endemic dimorphic fungus
that is often isolated from soil, plants, and
plant products. It has been reported
worldwide, with most cases coming from the
tropical regions of the Americas.
– Extracutaneous manifestations may occur,
with meningeal sporotrichosis (a rare
complication) being the worst complication of
S schenckii infections. AIDS is a reported
underlying risk factor in many described
cases. It is associated with a poor outcome.
 Parasitic meningitis
• Free-living amoebas (ie, Acanthamoeba, Balamuthia, Naegleria)
– Infection with free-living amoebas is an infrequent but often life-
threatening human illness, even in immunocompetent individuals.
– N fowleri is the only recognized human pathogenic species of Naegleria,
and it is the agent of primary amebic meningoencephalitis (PAM). The
parasite has been isolated in lakes, pools, ponds, rivers, tap water, and
soil. Infection occurs when swimming or playing in the contaminated
water sources (eg, inadequately chlorinated water and sources
associated with poor decontamination techniques). The N fowleri
amoebas invade the CNS through the nasal mucosa and cribriform
plate.
– PAM occurs in 2 forms. The first form is an acute onset of high fever,
photophobia, headache, and change in mental status, similar to
bacterial meningitis, occurring within a week following exposure.
Because it is acquired through the nasal area, involvement of the
olfactory nerves may manifest as abnormal smell sensation. Death
occurs in 3 days in patients who are not treated. The second form, the
subacute or chronic form, is an insidious onset of low-grade fever,
headache, and focal neurologic signs. Duration of illness is weeks to few
months.
– Acanthamoeba and Balamuthia cause granulomatous amebic
encephalitis, which is a subacute opportunistic infection that spreads
hematogenously from the primary site of infection (skin or lungs) to the
CNS and causes an encephalitis syndrome.
Histopathology of amoebic
meningoencephalitis.
 Helminthic eosinophilic meningitis
• A cantonensis, the rat lungworm, can cause eosinophilic meningitis
(pleocytosis with >10% eosinophils) in humans. Humans acquire the
infection by ingesting raw mollusks. Following ingestion, most
patients with symptomatic disease present with nonspecific and self-
limited abdominal pain caused by larval migration into the bowel
wall. On rare occasions, the larva can migrate into the CNS and
cause eosinophilic meningitis.
• G spinigerum, a gastrointestinal parasite of wild and domestic dogs
and cats, may cause eosinophilic meningoencephalitis. This is
common in Southeast Asia, China, and Japan but has been
reported sporadically worldwide. Humans acquire the infection
following ingestion of undercooked infected fish and poultry.
• B procyonis is an ascarid parasite that is prevalent in the raccoon
populations in the United States and rarely causes human
eosinophilic meningoencephalitis. Human infections occur following
accidental ingestion of food products contaminated with raccoon
feces.
 Lab Studies
• The cornerstone in
the diagnosis of
meningitis is
examination of the
CSF.
– In general, whenever
the diagnosis of
meningitis is strongly
considered, promptly A spinal needle is inserted,
perform a lumbar usually between the 3rd
and 4th lumbar vertebrae
puncture. in the lower spine.
– Measure the opening pressure and send the fluid for
cell count (and differential count), chemistry (ie, CSF
glucose and protein), and microbiology (ie, Gram
stain and cultures).
– CT scan of the brain may be performed prior to
lumbar puncture in some patient groups with a higher
risk of herniation. These groups include those with
newly onset seizures, an immunocompromised state,
signs suspicious for space-occupying lesions (such as
papilledema and focal neurologic signs), and
moderate-to-severe impairment in consciousness.
– Special studies, such as serology and nucleic acid
amplification, may also be performed depending on
clinical suspicion.
 Opening WBC count per
Agent Glucose (mg/dL) Protein (mg/dL) Microbiology
Pressure µL

Specific
pathogen
Bacterial 100-5000; demonstrated in
200-300 <40 >100
meningitis >80% PMNs* 60% of Gram
stains and 80%
of cultures

Normal,
Normal but
10-300; reduced in Viral isolation,
Viral meningitis 90-200 may be slightly
lymphocytes LCM and PCR† assays
elevated
mumps

Tuberculous 100-500; Acid-fast

180-300 Reduced, <40 Elevated, >100 bacillus stain,
meningitis lymphocytes culture, PCR

Cryptococcal 10-200; India ink,

180-300 Reduced 50-200 cryptococcal
meningitis lymphocytes antigen, culture

Normal but Negative

Aseptic 10-300;
90-200 Normal may be slightly findings on
meningitis lymphocytes workup
elevated

0-5; Negative
Normal values 80-200 50-75 15-40 findings on
lymphocytes workup
 • Vaccination
– The use of the HIB vaccination is strongly recommended in
susceptible individuals.
– Vaccination against S pneumoniae is strongly encouraged in
susceptible individuals, including individuals older than 65 years
and those with chronic cardiopulmonary illnesses.
– Vaccinations against encapsulated bacterial organisms (eg, S
pneumoniae, N meningitidis) are encouraged for those with
functional or structural asplenia. Always administer vaccinations
expediently to individuals who undergo splenectomy.
– Offer vaccination with quadrivalent meningococcal
polysaccharide vaccine to all high-risk populations, including
those with underlying immune deficiencies, those who travel to
hyperendemic areas and epidemic areas, and those involved
with laboratory work that deals with routine exposure to N
meningitidis. College students who live in dormitories or
residence halls are at modest risk; inform them about the risk
and offer vaccination.
– Vaccination against N meningitidis is recommended for all
adolescents aged 11-18 years.
– Vaccination against measles and mumps effectively eliminates
aseptic meningitis syndrome caused by these pathogens.