Meningitis

Meningitis is an acute inflammation of the protective

membranes covering the brain and spinal cord, known
collectively as the meninges.[1] The most common symp-
toms are fever, headache and neck stiffness. Other symp-
toms include confusion or altered consciousness, vomit-
ing, and an inability to tolerate light or loud noises. Young
children often exhibit only nonspecific symptoms, such
as irritability, drowsiness, or poor feeding.[2] If a rash is
present, it may indicate a particular cause of meningitis;
for instance, meningitis caused by meningococcal bacte-
ria may be accompanied by a characteristic rash.[1][3]
The inflammation may be caused by infection with
viruses, bacteria, or other microorganisms, and less
Neck stiffness, Texas meningitis epidemic of 1911–12.
commonly by certain drugs.[4] Meningitis can be life-
threatening because of the inflammation’s proximity to
the brain and spinal cord; therefore, the condition is clas-
sified as a medical emergency.[1][5] A lumbar puncture
1.1 Clinical features
diagnoses or excludes meningitis.[2] A needle is inserted
into the spinal canal to collect a sample of cerebrospinal In adults, the most common symptom of meningitis is
fluid (CSF), that envelops the brain and spinal cord. The a severe headache, occurring in almost 90% of cases of
CSF is examined in a medical laboratory.[5] bacterial meningitis, followed by nuchal rigidity (the in-
ability to flex the neck forward passively due to increased
Some forms of meningitis are preventable by neck muscle tone and stiffness).[12] The classic triad of
immunization with the meningococcal, mumps, diagnostic signs consists of nuchal rigidity, sudden high
pneumococcal, and Hib vaccines.[1] Giving antibiotics fever, and altered mental status; however, all three fea-
to people with significant exposure to certain types of tures are present in only 44–46% of bacterial meningitis
meningitis may also be useful.[2] The first treatment in cases.[12][13] If none of the three signs are present, acute
acute meningitis consists of promptly giving antibiotics meningitis is extremely unlikely.[13] Other signs com-
and sometimes antiviral drugs.[2][6] Corticosteroids monly associated with meningitis include photophobia
can also be used to prevent complications from exces- (intolerance to bright light) and phonophobia (intolerance
sive inflammation.[3][5] Meningitis can lead to serious to loud noises). Small children often do not exhibit the
long-term consequences such as deafness, epilepsy, aforementioned symptoms, and may only be irritable and
hydrocephalus, or cognitive deficits, especially if not look unwell.[1] The fontanelle (the soft spot on the top of
treated quickly.[1][3] a baby’s head) can bulge in infants aged up to 6 months.
In 2013 meningitis occurred in about 16 million Other features that distinguish meningitis from less severe
people.[7] This resulted in 303,000 deaths globally– down illnesses in young children are leg pain, cold extremities,
from 464,000 deaths in 1990.[8] With appropriate treat- and an abnormal skin color.[14][15]
ment the risk of death in bacterial meningitis is less than Nuchal rigidity occurs in 70% of bacterial meningitis in
15%.[2] Outbreaks of bacterial meningitis occur between adults.[13] Other signs of meningism include the presence
December and June each year in an area of sub-Saharan of positive Kernig’s sign or Brudziński sign. Kernig’s sign
Africa known as the meningitis belt.[9] Smaller outbreaks is assessed with the person lying supine, with the hip and
may also occur in other areas of the world.[9] The word knee flexed to 90 degrees. In a person with a positive
meningitis is from Greek μῆνιγξ méninx, “membrane” Kernig’s sign, pain limits passive extension of the knee.
and the medical suffix -itis, “inflammation”.[10][11] A positive Brudzinski’s sign occurs when flexion of the
neck causes involuntary flexion of the knee and hip. Al-
though Kernig’s sign and Brudzinski’s sign are both com-
monly used to screen for meningitis, the sensitivity of
these tests is limited.[13][16] They do, however, have very
1 Signs and symptoms good specificity for meningitis: the signs rarely occur in
other diseases.[13] Another test, known as the “jolt accen-

1
2 2 CAUSES

tuation maneuver” helps determine whether meningitis is fections may result in hemorrhaging of the adrenal glands,
present in those reporting fever and headache. A person leading to Waterhouse-Friderichsen syndrome, which is
is asked to rapidly rotate the head horizontally; if this does often fatal.[18]
not make the headache worse, meningitis is unlikely.[13] The brain tissue may swell, pressure inside the skull may
Meningitis caused by the bacterium Neisseria menin- increase and the swollen brain may herniate through the
gitidis (known as “meningococcal meningitis”) can be skull base. This may be noticed by a decreasing level
differentiated from meningitis with other causes by a of consciousness, loss of the pupillary light reflex, and
rapidly spreading petechial rash, which may precede abnormal posturing.[3] The inflammation of the brain tis-
other symptoms.[14] The rash consists of numerous small, sue may also obstruct the normal flow of CSF around the
irregular purple or red spots (“petechiae”) on the trunk, brain (hydrocephalus).[3] Seizures may occur for various
lower extremities, mucous membranes, conjuctiva, and reasons; in children, seizures are common in the early
(occasionally) the palms of the hands or soles of the feet. stages of meningitis (in 30% of cases) and do not neces-
The rash is typically non-blanching; the redness does not sarily indicate an underlying cause.[5] Seizures may result
disappear when pressed with a finger or a glass tumbler. from increased pressure and from areas of inflammation
Although this rash is not necessarily present in meningo- in the brain tissue.[3] Focal seizures (seizures that involve
coccal meningitis, it is relatively specific for the disease; one limb or part of the body), persistent seizures, late-
it does, however, occasionally occur in meningitis due to onset seizures and those that are difficult to control with
other bacteria.[1] Other clues on the cause of meningitis medication indicate a poorer long-term outcome.[1]
may be the skin signs of hand, foot and mouth disease and Inflammation of the meninges may lead to abnormali-
genital herpes, both of which are associated with various ties of the cranial nerves, a group of nerves arising from
forms of viral meningitis.[17] the brain stem that supply the head and neck area and
which control, among other functions, eye movement,
1.2 Early complications facial muscles, and hearing.[1][13] Visual symptoms and
hearing loss may persist after an episode of meningitis.[1]
Inflammation of the brain (encephalitis) or its blood ves-
sels (cerebral vasculitis), as well as the formation of blood
clots in the veins (cerebral venous thrombosis), may all
lead to weakness, loss of sensation, or abnormal move-
ment or function of the part of the body supplied by the
affected area of the brain.[1][3]

2 Causes

Meningitis is typically caused by an infection with

microorganisms. Most infections are due to viruses,[13]
Charlotte Cleverley-Bisman developed severe meningococcal
meningitis as a young child; in her case, the petechial rash pro- with bacteria, fungi, and protozoa being the next most
gressed to gangrene and required amputation of all limbs. She common causes.[4] It may also result from various non-
survived the disease and became a poster child for a meningitis infectious causes.[4] The term aseptic meningitis refers to
vaccination campaign in New Zealand. cases of meningitis in which no bacterial infection can be
demonstrated. This type of meningitis is usually caused
Additional problems may occur in the early stage of the by viruses but it may be due to bacterial infection that
illness. These may require specific treatment, and some- has already been partially treated, when bacteria disap-
times indicate severe illness or worse prognosis. The in- pear from the meninges, or pathogens infect a space ad-
fection may trigger sepsis, a systemic inflammatory re- jacent to the meninges (e.g. sinusitis). Endocarditis (an
sponse syndrome of falling blood pressure, fast heart rate, infection of the heart valves which spreads small clusters
high or abnormally low temperature, and rapid breath- of bacteria through the bloodstream) may cause aseptic
ing. Very low blood pressure may occur at an early stage, meningitis. Aseptic meningitis may also result from in-
especially but not exclusively in meningococcal menin- fection with spirochetes, a type of bacteria that includes
gitis; this may lead to insufficient blood supply to other Treponema pallidum (the cause of syphilis) and Borrelia
organs.[1] Disseminated intravascular coagulation, the ex- burgdorferi (known for causing Lyme disease). Menin-
cessive activation of blood clotting, may obstruct blood gitis may be encountered in cerebral malaria (malaria in-
flow to organs and paradoxically increase the bleeding fecting the brain) or amoebic meningitis, meningitis due
risk. Gangrene of limbs can occur in meningococcal to infection with amoebae such as Naegleria fowleri, con-
disease.[1] Severe meningococcal and pneumococcal in- tracted from freshwater sources.[4]
2.2 Viral 3

2.1 Bacterial sinuses and petrous pyramids.[23] Approximately 59% of

recurrent meningitis cases are due to such anatomical ab-
See also: Neonatal infection normalities, 36% are due to immune deficiencies (such as
complement deficiency, which predisposes especially to
recurrent meningococcal meningitis), and 5% are due to
The types of bacteria that cause bacterial meningitis vary
ongoing infections in areas adjacent to the meninges.[23]
according to the infected individual’s age group.

• In premature babies and newborns up to three 2.2 Viral

months old, common causes are group B strepto-
cocci (subtypes III which normally inhabit the vagina Viruses that cause meningitis include enteroviruses,
and are mainly a cause during the first week of life) herpes simplex virus (generally type 2, which produces
and bacteria that normally inhabit the digestive tract most genital sores; less commonly type 1), varicella
such as Escherichia coli (carrying the K1 antigen). zoster virus (known for causing chickenpox and shingles),
Listeria monocytogenes (serotype IVb) is transmitted mumps virus, HIV, and LCMV.[17] Mollaret’s meningi-
by the mother before birth and may cause meningitis tis is a chronic recurrent form of herpes meningitis; it is
in the newborn.[19] thought to be caused by herpes simplex virus type 2.[24]

• Older children are more commonly affected

by Neisseria meningitidis (meningococcus) and 2.3 Fungal
Streptococcus pneumoniae (serotypes 6, 9, 14,
18 and 23) and those under five by Haemophilus There are a number of risk factors for fungal meningitis,
influenzae type B (in countries that do not offer including the use of immunosuppressants (such as after
vaccination).[1][5] organ transplantation), HIV/AIDS,[25] and the loss of im-
munity associated with aging.[26] It is uncommon in those
• In adults, Neisseria meningitidis and Streptococcus with a normal immune system[27] but has occurred with
pneumoniae together cause 80% of bacterial menin- medication contamination.[28] Symptom onset is typically
gitis cases. Risk of infection with Listeria monocyto- more gradual, with headaches and fever being present
genes is increased in persons over 50 years old.[3][5] for at least a couple of weeks before diagnosis.[26] The
The introduction of pneumococcal vaccine has low- most common fungal meningitis is cryptococcal menin-
ered rates of pneumococcal meningitis in both chil- gitis due to Cryptococcus neoformans.[29] In Africa, cryp-
dren and adults.[20] tococcal meningitis is now the most common cause of
meningitis in multiple studies,[30][31] and it accounts for
Recent skull trauma potentially allows nasal cavity bac- 20–25% of AIDS-related deaths in Africa.[32] Other less
teria to enter the meningeal space. Similarly, devices common fungal pathogens which can cause meningitis
in the brain and meninges, such as cerebral shunts, include: Coccidioides immitis, Histoplasma capsulatum,
extraventricular drains or Ommaya reservoirs, carry an Blastomyces dermatitidis, and Candida species.[26]
increased risk of meningitis. In these cases, the per-
sons are more likely to be infected with Staphylococci,
Pseudomonas, and other Gram-negative bacteria.[5] 2.4 Parasitic
These pathogens are also associated with meningitis in
people with an impaired immune system.[1] An infec- A parasitic cause is often assumed when there is a pre-
tion in the head and neck area, such as otitis media or dominance of eosinophils (a type of white blood cell)
in the CSF. The most common parasites implicated are
mastoiditis, can lead to meningitis in a small proportion
of people.[5] Recipients of cochlear implants for hearing
Angiostrongylus cantonensis, Gnathostoma spinigerum,
loss are more at risk for pneumococcal meningitis.[21] Schistosoma, as well as the conditions cysticercosis,
toxocariasis, baylisascariasis, paragonimiasis, and a num-
Tuberculous meningitis, which is meningitis caused by
ber of rarer infections and noninfective conditions.[33]
Mycobacterium tuberculosis, is more common in people
from countries in which tuberculosis is endemic, but is
also encountered in persons with immune problems, such
2.5 Non-infectious
as AIDS.[22]
Recurrent bacterial meningitis may be caused by persist- Meningitis may occur as the result of several non-
ing anatomical defects, either congenital or acquired, or infectious causes: spread of cancer to the meninges
by disorders of the immune system.[23] Anatomical de- (malignant or neoplastic meningitis)[34] and certain
fects allow continuity between the external environment drugs (mainly non-steroidal anti-inflammatory drugs,
and the nervous system. The most common cause of re- antibiotics and intravenous immunoglobulins).[35] It may
current meningitis is a skull fracture,[23] particularly frac- also be caused by several inflammatory conditions, such
tures that affect the base of the skull or extend towards the as sarcoidosis (which is then called neurosarcoidosis),
4 4 DIAGNOSIS

connective tissue disorders such as systemic lupus ery- the meninges and leading to “interstitial” edema (swelling
thematosus, and certain forms of vasculitis (inflammatory due to fluid between the cells). In addition, the walls
conditions of the blood vessel wall), such as Behçet’s dis- of the blood vessels themselves become inflamed (cere-
ease.[4] Epidermoid cysts and dermoid cysts may cause bral vasculitis), which leads to decreased blood flow and a
meningitis by releasing irritant matter into the subarach- third type of edema, “cytotoxic” edema. The three forms
noid space.[4][23] Rarely, migraine may cause meningitis, of cerebral edema all lead to increased intracranial pres-
but this diagnosis is usually only made when other causes sure; together with the lowered blood pressure often en-
have been eliminated.[4] countered in acute infection, this means that it is harder
for blood to enter the brain, consequently brain cells are
deprived of oxygen and undergo apoptosis (programmed
3 Mechanism cell death).[1]
It is recognized that administration of antibiotics may
The meninges comprise three membranes that, together initially worsen the process outlined above, by increas-
with the cerebrospinal fluid, enclose and protect the brain ing the amount of bacterial cell membrane products
and spinal cord (the central nervous system). The pia released through the destruction of bacteria. Particu-
mater is a very delicate impermeable membrane that lar treatments, such as the use of corticosteroids, are
firmly adheres to the surface of the brain, following all the aimed at dampening the immune system’s response to this
minor contours. The arachnoid mater (so named because phenomenon.[1][3]
of its spider-web-like appearance) is a loosely fitting sac
on top of the pia mater. The subarachnoid space separates
the arachnoid and pia mater membranes and is filled with 4 Diagnosis
cerebrospinal fluid. The outermost membrane, the dura
mater, is a thick durable membrane, which is attached to 4.1 Blood tests and imaging
both the arachnoid membrane and the skull.
In bacterial meningitis, bacteria reach the meninges by In someone suspected of having meningitis, blood tests
one of two main routes: through the bloodstream or are performed for markers of inflammation (e.g. C-
through direct contact between the meninges and either reactive protein, complete blood count), as well as blood
the nasal cavity or the skin. In most cases, meningitis fol- cultures.[5][37]
lows invasion of the bloodstream by organisms that live The most important test in identifying or ruling out
upon mucous surfaces such as the nasal cavity. This is meningitis is analysis of the cerebrospinal fluid through
often in turn preceded by viral infections, which break lumbar puncture (LP, spinal tap).[38] However, lumbar
down the normal barrier provided by the mucous sur- puncture is contraindicated if there is a mass in the brain
faces. Once bacteria have entered the bloodstream, they (tumor or abscess) or the intracranial pressure (ICP) is
enter the subarachnoid space in places where the blood– elevated, as it may lead to brain herniation. If someone
brain barrier is vulnerable—such as the choroid plexus. is at risk for either a mass or raised ICP (recent head in-
Meningitis occurs in 25% of newborns with bloodstream jury, a known immune system problem, localizing neu-
infections due to group B streptococci; this phenomenon rological signs, or evidence on examination of a raised
is less common in adults.[1] Direct contamination of the ICP), a CT or MRI scan is recommended prior to the
cerebrospinal fluid may arise from indwelling devices, lumbar puncture.[5][37][39] This applies in 45% of all adult
skull fractures, or infections of the nasopharynx or the cases.[3] If a CT or MRI is required before LP, or if
nasal sinuses that have formed a tract with the subarach- LP proves difficult, professional guidelines suggest that
noid space (see above); occasionally, congenital defects antibiotics should be administered first to prevent delay
of the dura mater can be identified.[1] in treatment,[5] especially if this may be longer than 30
[37][39]
The large-scale inflammation that occurs in the subarach- minutes. Often, CT or MRI scans are performed at
[1]
noid space during meningitis is not a direct result of bac- a later stage to assess for complications of meningitis.
terial infection but can rather largely be attributed to the In severe forms of meningitis, monitoring of blood elec-
response of the immune system to the entry of bacteria trolytes may be important; for example, hyponatremia is
into the central nervous system. When components of common in bacterial meningitis, due to a combination of
the bacterial cell membrane are identified by the immune factors, including dehydration, the inappropriate secre-
cells of the brain (astrocytes and microglia), they respond tion of the antidiuretic hormone (SIADH), or overly ag-
by releasing large amounts of cytokines, hormone-like gressive intravenous fluid administration.[3][40]
mediators that recruit other immune cells and stimulate
other tissues to participate in an immune response. The
blood–brain barrier becomes more permeable, leading to 4.2 Lumbar puncture
“vasogenic” cerebral edema (swelling of the brain due
to fluid leakage from blood vessels). Large numbers of A lumbar puncture is done by positioning the per-
white blood cells enter the CSF, causing inflammation of son, usually lying on the side, applying local anes-
4.3 Postmortem 5

otics then this may rule out bacterial meningitis.[42]

Various other specialized tests may be used to dis-
tinguish between different types of meningitis. A
latex agglutination test may be positive in meningitis
caused by Streptococcus pneumoniae, Neisseria meningi-
tidis, Haemophilus influenzae, Escherichia coli and group
B streptococci; its routine use is not encouraged as it rarely
leads to changes in treatment, but it may be used if other
tests are not diagnostic. Similarly, the limulus lysate test
may be positive in meningitis caused by Gram-negative
bacteria, but it is of limited use unless other tests have
been unhelpful.[5] Polymerase chain reaction (PCR) is a
Gram stain of meningococci from a culture showing Gram neg- technique used to amplify small traces of bacterial DNA
ative (pink) bacteria, often in pairs in order to detect the presence of bacterial or viral DNA
in cerebrospinal fluid; it is a highly sensitive and spe-
cific test since only trace amounts of the infecting agent’s
thetic, and inserting a needle into the dural sac (a sac DNA is required. It may identify bacteria in bacterial
around the spinal cord) to collect cerebrospinal fluid meningitis and may assist in distinguishing the various
(CSF). When this has been achieved, the “opening causes of viral meningitis (enterovirus, herpes simplex
pressure” of the CSF is measured using a manometer. virus 2 and mumps in those not vaccinated for this).[17]
The pressure is normally between 6 and 18 cm water Serology (identification of antibodies to viruses) may be
(cmH2 O);[38] in bacterial meningitis the pressure is usu- useful in viral meningitis.[17] If tuberculous meningitis
ally elevated.[5][37] In cryptococcal meningitis, intracra- is suspected, the sample is processed for Ziehl-Neelsen
nial pressure is markedly elevated.[41] The initial appear- stain, which has a low sensitivity, and tuberculosis cul-
ance of the fluid may prove an indication of the nature ture, which takes a long time to process; PCR is being
of the infection: cloudy CSF indicates higher levels of used increasingly.[22] Diagnosis of cryptococcal menin-
protein, white and red blood cells and/or bacteria, and gitis can be made at low cost using an India ink stain
therefore may suggest bacterial meningitis.[5] of the CSF; however, testing for cryptococcal antigen in
blood or CSF is more sensitive, particularly in people
The CSF sample is examined for presence and types of with AIDS.[43][44]
white blood cells, red blood cells, protein content and
glucose level.[5] Gram staining of the sample may demon- A diagnostic and therapeutic difficulty is “partially treated
strate bacteria in bacterial meningitis, but absence of bac- meningitis”, where there are meningitis symptoms after
teria does not exclude bacterial meningitis as they are receiving antibiotics (such as for presumptive sinusitis).
only seen in 60% of cases; this figure is reduced by a When this happens, CSF findings may resemble those of
further 20% if antibiotics were administered before the viral meningitis, but antibiotic treatment may need to be
sample was taken. Gram staining is also less reliable in continued until there is definitive positive evidence of a
particular infections such as listeriosis. Microbiological viral cause (e.g. a positive enterovirus PCR).[17]
culture of the sample is more sensitive (it identifies the
organism in 70–85% of cases) but results can take up to
48 hours to become available.[5] The type of white blood 4.3 Postmortem
cell predominantly present (see table) indicates whether
meningitis is bacterial (usually neutrophil-predominant) Meningitis can be diagnosed after death has occurred.
or viral (usually lymphocyte-predominant),[5] although at The findings from a post mortem are usually a widespread
the beginning of the disease this is not always a reliable inflammation of the pia mater and arachnoid layers of
indicator. Less commonly, eosinophils predominate, sug- the meninges. Neutrophil granulocytes tend to have mi-
gesting parasitic or fungal etiology, among others.[33] grated to the cerebrospinal fluid and the base of the brain,
The concentration of glucose in CSF is normally above along with cranial nerves and the spinal cord, may be sur-
[45]
40% of that in blood. In bacterial meningitis it is typi- rounded with pus — as may the meningeal vessels.
cally lower; the CSF glucose level is therefore divided by
the blood glucose (CSF glucose to serum glucose ratio).
A ratio ≤0.4 is indicative of bacterial meningitis;[38] in
the newborn, glucose levels in CSF are normally higher, 5 Prevention
and a ratio below 0.6 (60%) is therefore considered
abnormal.[5] High levels of lactate in CSF indicate a For some causes of meningitis, protection can be pro-
higher likelihood of bacterial meningitis, as does a higher vided in the long term through vaccination, or in the short
white blood cell count.[38] If lactate levels are less than 35 term with antibiotics. Some behavioral measures may
mg/dl and the person has not previously received antibi- also be effective.
6 6 MANAGEMENT

Still, some countries (New Zealand, Cuba, Norway and

Chile) have developed vaccines against local strains of
group B meningococci; some have shown good re-
sults and are used in local immunization schedules.[49]
Two new vaccines, both approved in 2014, are effec-
tive against a wider range of group B meningococci
strains.[50][51] In Africa, until recently, the approach
for prevention and control of meningococcal epidemics
was based on early detection of the disease and emer-
gency reactive mass vaccination of the at-risk population
with bivalent A/C or trivalent A/C/W135 polysaccha-
ride vaccines,[53] though the introduction of MenAfriVac
(meningococcus group A vaccine) has demonstrated ef-
fectiveness in young people and has been described as a
Histopathology of bacterial meningitis: autopsy case of a per- model for product development partnerships in resource-
son with pneumococcal meningitis showing inflammatory infil- limited settings.[54][55]
trates of the pia mater consisting of neutrophil granulocytes (in-
set, higher magnification).
Routine vaccination against Streptococcus pneumoniae
with the pneumococcal conjugate vaccine (PCV), which
is active against seven common serotypes of this
5.1 Behavioral pathogen, significantly reduces the incidence of pneu-
mococcal meningitis.[47][56] The pneumococcal polysac-
Bacterial and viral meningitis are contagious; however, charide vaccine, which covers 23 strains, is only admin-
neither is as contagious as the common cold or flu.[46] istered to certain groups (e.g. those who have had a
Both can be transmitted through droplets of respiratory splenectomy, the surgical removal of the spleen); it does
secretions during close contact such as kissing, sneez- not elicit a significant immune response in all recipi-
ing or coughing on someone, but cannot be spread by ents, e.g. small children.[56] Childhood vaccination with
only breathing the air where a person with meningi- Bacillus Calmette-Guérin has been reported to signifi-
tis has been.[46] Viral meningitis is typically caused by cantly reduce the rate of tuberculous meningitis, but its
enteroviruses, and is most commonly spread through fecal waning effectiveness in adulthood has prompted a search
contamination.[46] The risk of infection can be decreased for a better vaccine.[47]
by changing the behavior that led to transmission.

5.3 Antibiotics
5.2 Vaccination
Short-term antibiotic prophylaxis is another method of
prevention, particularly of meningococcal meningitis. In
Since the 1980s, many countries have included
cases of meningococcal meningitis, preventative treat-
immunization against Haemophilus influenzae type
ment in close contacts with antibiotics (e.g. rifampicin,
B in their routine childhood vaccination schemes. This
ciprofloxacin or ceftriaxone) can reduce their risk of con-
has practically eliminated this pathogen as a cause of
tracting the condition, but does not protect against fu-
meningitis in young children in those countries. In the
ture infections.[37][57] Resistance to rifampicin has been
countries in which the disease burden is highest, how-
noted to increase after use, which has caused some to
ever, the vaccine is still too expensive.[47][48] Similarly,
recommend considering other agents.[57] While antibi-
immunization against mumps has led to a sharp fall in the
otics are frequently used in an attempt to prevent menin-
number of cases of mumps meningitis, which prior to
gitis in those with a basilar skull fracture there is not
vaccination occurred in 15% of all cases of mumps.[17]
enough evidence to determine whether this is beneficial
Meningococcus vaccines exist against groups A, B, C, or harmful.[58] This applies to those with or without a CSF
W135 and Y.[49][50][51] In countries where the vaccine for leak.[58]
meningococcus group C was introduced, cases caused by
this pathogen have decreased substantially.[47] A quadri-
valent vaccine now exists, which combines all four vac-
cines. Immunization with the ACW135Y vaccine against 6 Management
four strains is now a visa requirement for taking part
in Hajj.[52] Development of a vaccine against group B Meningitis is potentially life-threatening and has a high
meningococci has proved much more difficult, as its sur- mortality rate if untreated;[5] delay in treatment has been
face proteins (which would normally be used to make a associated with a poorer outcome.[3] Thus, treatment with
vaccine) only elicit a weak response from the immune sys- wide-spectrum antibiotics should not be delayed while
tem, or cross-react with normal human proteins.[47][49] confirmatory tests are being conducted.[39] If meningo-
6.1 Bacterial meningitis 7

coccal disease is suspected in primary care, guidelines a head injury, whether the person has undergone re-
recommend that benzylpenicillin be administered before cent neurosurgery and whether or not a cerebral shunt is
transfer to hospital.[14] Intravenous fluids should be ad- present.[5] In young children and those over 50 years of
ministered if hypotension (low blood pressure) or shock age, as well as those who are immunocompromised, the
are present.[39] In children routine intravenous fluids for addition of ampicillin is recommended to cover Listeria
two days may improve outcomes in those who arrive at monocytogenes.[5][37] Once the Gram stain results become
hospital after being sick for some time.[59] Given that available, and the broad type of bacterial cause is known,
meningitis can cause a number of early severe complica- it may be possible to change the antibiotics to those likely
tions, regular medical review is recommended to identify to deal with the presumed group of pathogens.[5] The re-
these complications early[39] and to admit the person to sults of the CSF culture generally take longer to become
an intensive care unit if deemed necessary.[3] available (24–48 hours). Once they do, empiric therapy
Mechanical ventilation may be needed if the level of may be switched to specific antibiotic therapy targeted
to the specific causative organism and its sensitivities to
consciousness is very low, or if there is evidence of
respiratory failure. If there are signs of raised in- antibiotics.[5] For an antibiotic to be effective in menin-
tracranial pressure, measures to monitor the pressure gitis it must not only be active against the pathogenic
may be taken; this would allow the optimization of the bacterium but also reach the meninges in adequate quan-
cerebral perfusion pressure and various treatments to de- tities; some antibiotics have inadequate penetrance and
crease the intracranial pressure with medication (e.g. therefore have little use in meningitis. Most of the an-
mannitol).[3] Seizures are treated with anticonvulsants.[3] tibiotics used in meningitis have not been tested directly
Hydrocephalus (obstructed flow of CSF) may require in- on people with meningitis in clinical trials. Rather, the
sertion of a temporary or long-term drainage device, such relevant knowledge has mostly derived from laboratory
as a cerebral shunt.[3] studies in rabbits.[5] Tuberculous meningitis requires pro-
longed treatment with antibiotics. While tuberculosis of
the lungs is typically treated for six months, those with
tuberculous meningitis are typically treated for a year or
6.1 Bacterial meningitis longer.[22]
6.1.1 Antibiotics
6.1.2 Steroids

Additional treatment with corticosteroids (usually

dexamethasone) has shown some benefits, such as a
reduction of hearing loss, and better short term neu-
rological outcomes[61] in adolescents and adults from
high-income countries with low rates of HIV.[62] Some
research has found reduced rates of death[62] while other
research has not.[61] They also appear to be beneficial in
those with tuberculosis meningitis, at least in those who
are HIV negative.[63]
Structural formula of ceftriaxone, one of the third-generation ce- Professional guidelines therefore recommend the com-
falosporin antibiotics recommended for the initial treatment of mencement of dexamethasone or a similar corticosteroid
bacterial meningitis. just before the first dose of antibiotics is given, and con-
tinued for four days.[37][39] Given that most of the benefit
Empiric antibiotics (treatment without exact diagnosis) of the treatment is confined to those with pneumococ-
should be started immediately, even before the results cal meningitis, some guidelines suggest that dexametha-
of the lumbar puncture and CSF analysis are known. sone be discontinued if another cause for meningitis is
The choice of initial treatment depends largely on the identified.[5][37] The likely mechanism is suppression of
kind of bacteria that cause meningitis in a particular overactive inflammation.[64]
place and population. For instance, in the United King-
Additional treatment with corticosteroids have a differ-
dom empirical treatment consists of a third-generation
ent role in children than in adults. Though the bene-
cefalosporin such as cefotaxime or ceftriaxone.[37][39] In
fit of corticosteroids has been demonstrated in adults as
the USA, where resistance to cefalosporins is increasingly
well as in children from high-income countries, their use
found in streptococci, addition of vancomycin to the ini-
in children from low-income countries is not supported
tial treatment is recommended.[3][5][37] Chloramphenicol,
by the evidence; the reason for this discrepancy is not
either alone or in combination with ampicillin, however,
clear.[61] Even in high-income countries, the benefit of
appears to work equally well.[60] corticosteroids is only seen when they are given prior to
Empirical therapy may be chosen on the basis of the the first dose of antibiotics, and is greatest in cases of
person’s age, whether the infection was preceded by H. influenzae meningitis,[5][65] the incidence of which has
8 8 EPIDEMIOLOGY

decreased dramatically since the introduction of the Hib fluid,[1] the severity of the generalized illness, a decreased
vaccine. Thus, corticosteroids are recommended in the level of consciousness or an abnormally low count of
treatment of pediatric meningitis if the cause is H. in- white blood cells in the CSF.[3] Meningitis caused by
fluenzae, and only if given prior to the first dose of an- H. influenzae and meningococci has a better prognosis
tibiotics; other uses are controversial.[5] than cases caused by group B streptococci, coliforms and
S. pneumonia.[1] In adults, too, meningococcal menin-
gitis has a lower mortality (3–7%) than pneumococcal
6.2 Viral meningitis disease.[3]
In children there are several potential disabilities which
Viral meningitis typically only requires supportive ther-
may result from damage to the nervous system, includ-
apy; most viruses responsible for causing meningitis are
ing sensorineural hearing loss, epilepsy, learning and be-
not amenable to specific treatment. Viral meningitis
havioral difficulties, as well as decreased intelligence.[1]
tends to run a more benign course than bacterial menin-
These occur in about 15% of survivors.[1] Some of the
gitis. Herpes simplex virus and varicella zoster virus
hearing loss may be reversible.[69] In adults, 66% of all
may respond to treatment with antiviral drugs such as
cases emerge without disability. The main problems are
aciclovir, but there are no clinical trials that have specif-
deafness (in 14%) and cognitive impairment (in 10%).[3]
ically addressed whether this treatment is effective.[17]
Mild cases of viral meningitis can be treated at home Tuberculous meningitis in children continues to be as-
with conservative measures such as fluid, bedrest, and sociated with a significant risk of death even with treat-
analgesics.[66] ment (19%), and a significant proportion of the surviving
children have ongoing neurological problems. Just over a
third of all cases survives with no problems.[70]
6.3 Fungal meningitis

Fungal meningitis, such as cryptococcal meningitis, is 8 Epidemiology

treated with long courses of high dose antifungals, such as
amphotericin B and flucytosine.[43][67] Raised intracranial
pressure is common in fungal meningitis, and frequent
(ideally daily) lumbar punctures to relieve the pressure
are recommended,[43] or alternatively a lumbar drain.[41]

7 Prognosis

Demography of meningococcal meningitis.

meningitis belt
epidemic zones
sporadic cases only

Although meningitis is a notifiable disease in many coun-

tries, the exact incidence rate is unknown.[17] In 2013
Disability-adjusted life year for meningitis per 100,000 inhabi- meningitis resulted in 303,000 deaths – down from
tants in 2004.[68] 464,000 deaths in 1990.[8] In 2010 it was estimated
that meningitis resulted in 420,000 deaths,[71] excluding
[72]
Untreated, bacterial meningitis is almost always fatal. Vi- cryptococcal meningitis.
ral meningitis, in contrast, tends to resolve spontaneously Bacterial meningitis occurs in about 3 people per 100,000
and is rarely fatal. With treatment, mortality (risk of annually in Western countries. Population-wide studies
death) from bacterial meningitis depends on the age of have shown that viral meningitis is more common, at 10.9
the person and the underlying cause. Of newborns, 20– per 100,000, and occurs more often in the summer. In
30% may die from an episode of bacterial meningitis. Brazil, the rate of bacterial meningitis is higher, at 45.8
This risk is much lower in older children, whose mor- per 100,000 annually.[13] Sub-Saharan Africa has been
tality is about 2%, but rises again to about 19–37% in plagued by large epidemics of meningococcal menin-
adults.[1][3] Risk of death is predicted by various factors gitis for over a century,[73] leading to it being labeled
apart from age, such as the pathogen and the time it takes the “meningitis belt”. Epidemics typically occur in the
for the pathogen to be cleared from the cerebrospinal dry season (December to June), and an epidemic wave
 9

can last two to three years, dying out during the inter- Simon Flexner and markedly decreased mortality from
vening rainy seasons.[74] Attack rates of 100–800 cases meningococcal disease.[82][83] In 1944, penicillin was first
per 100,000 are encountered in this area,[75] which is reported to be effective in meningitis.[84] The introduc-
poorly served by medical care. These cases are predomi- tion in the late 20th century of Haemophilus vaccines led
nantly caused by meningococci.[13] The largest epidemic to a marked fall in cases of meningitis associated with this
ever recorded in history swept across the entire region pathogen,[48] and in 2002, evidence emerged that treat-
in 1996–1997, causing over 250,000 cases and 25,000 ment with steroids could improve the prognosis of bacte-
deaths.[76] rial meningitis.[61][64][83]
Meningococcal disease occurs in epidemics in areas
where many people live together for the first time, such as
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[83] Swartz MN (October 2004). “Bacterial meningitis—

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11 External links
• Meningitis at DMOZ
• Meningitis Centers for Disease Control and Preven-
tion (CDC)
14 12 TEXT AND IMAGE SOURCES, CONTRIBUTORS, AND LICENSES

12 Text and image sources, contributors, and licenses

12.1 Text
• Meningitis Source: https://en.wikipedia.org/wiki/Meningitis?oldid=712145348 Contributors: Malcolm Farmer, Alex.tan, Rsabbatini, Ed-
ward, Gabbe, Pandora, Ixfd64, Mac, Theresa knott, Angela, Jebba, Randomned, Rob Hooft, Bemoeial, Tpbradbury, Saltine, Raul654,
Robbot, Gak, Altenmann, Kowey, Naddy, Caknuck, Hadal, Psb777, Richy, Nunh-huh, Ævar Arnfjörð Bjarmason, Zigger, Michael De-
vore, Gamaliel, LLarson, Jfdwolff, Guanaco, Gadfium, Andycjp, DocSigma, Antandrus, BozMo, Seannyob, Vogon77, TonyW, Neutrality,
Joyous!, Adashiel, Discospinster, Rich Farmbrough, Paul August, Bender235, JoeSmack, CanisRufus, Remember, Art LaPella, Peter
Greenwell, Bobo192, Smalljim, Davidruben, Arcadian, TheProject, MPerel, Sam Korn, WMMartin, Nsaa, Jumbuck, Alansohn, Oliver-
lewis, Falsifian, Babajobu, Wouterstomp, Axl, Bart133, Carioca, LFaraone, Scott Gall, Alai, Oystertoadfish, 2004-12-29T22:45Z, LOL,
The Wordsmith, Kmg90, Bbatsell, John Hill, MarcoTolo, Dysepsion, Mandarax, Siqbal, Graham87, Jclemens, Mendaliv, Edison, Sjö, So-
lace098, Sjakkalle, Rjwilmsi, XP1, Mdanciu, Remurmur, Yamamoto Ichiro, Titoxd, FlaBot, RobertG, Wknight8111, Itinerant1, RexNL,
Gurch, Karelj, Stevenfruitsmaak, King of Hearts, Chobot, DVdm, Cuahl, YurikBot, Wavelength, Borgx, Rxnd, Gaius Cornelius, Cam-
bridgeBayWeather, Eleassar, Polarlys, Rsrikanth05, Wimt, NawlinWiki, EgbertW, Wiki alf, Mccready, Nephron, Rmky87, Starryboy,
Mgcsinc, Tony1, Mysid, Bota47, Andrewr47, DRosenbach, Rcinda1, Supalognon, User27091, Encephalon, Cbogart2, Colin, ZoFreX,
JoanneB, Kungfuadam, Paul Erik, Jkpjkp, DVD R W, Steven Pounders, AndrewWTaylor, Isoxyl, Mathiasm~enwiki, A bit iffy, Smack-
Bot, Espresso Addict, Federalist51, KnowledgeOfSelf, Unyoyega, Jagged 85, Jfurr1981, DTM, Delldot, Dlodge, Jwestbrook, Gilliam,
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pus, Ryulong, Hu12, Nehrams2020, Iridescent, Wjejskenewr, StephenBuxton, GDallimore, Igoldste, Wwallacee, DavidOaks, Chovain,
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Jesse Viviano, WeggeBot, Richard Keatinge, AndrewHowse, Neonlife, Cydebot, Vanished user 45po45lr87gj, Khatru2, Anthonyhcole,
Corpx, Quibik, DumbBOT, Chrislk02, Garik, UberScienceNerd, Thijs!bot, Epbr123, Supermood00d, Mojo Hand, Woody, Jimmymags,
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oladitis, A12n, VoABot II, MastCell, JamesBWatson, WhatamIdoing, Animum, Loonymonkey, Allstarecho, P.B. Pilhet, DerHexer, Glud-
wiczak, Inclusivedisjunction, Patstuart, Tuffcunz, Whitewolf926, S3000, Leaderofearth, Yobol, MartinBot, Kamaki, CliffC, Gandydancer,
Rettetast, Gmchambless, Lilac Soul, Jargon777, Iarescientists, AnonHat, J.delanoy, DrKay, Xris0, Cocoaguy, Darth Mike, Century0, Nitro-
gen660, Jeyradan, Dispenser, Katalaveno, Kangie, McSly, Mikael Häggström, Devouring-One, Fateddy, SJP, Danaidae, Hanacy, Gambole,
Cdhaptomos, DorganBot, Terence1122, Useight, Lalvers, Lights, Decemberween, ABF, KJSatz, Encyclopedia Angel, RingtailedFox, Al-
noktaBOT, Soliloquial, Barneca, Umalee, Philip Trueman, Geoffshaw50, TXiKiBoT, Oshwah, GimmeBot, Cosmic Latte, Tricky Victoria,
Katoa, Briony192, Garrondo, Tony Schwarz, Melsaran, KieferAdair, Jackfork, Monkeynoze, PaladinWhite, Desh101, Madhero88, Jon
salisbury, Bkhuey, Another account, Burntsauce, Ceranthor, Countincr, Doc James, Davodavy, Praefectorian, Seungfire24, Cdizzle23, Pe-
dianon, SieBot, Zenlax, Calliopejen1, Graham Beards, Winchelsea, Triwbe, Yintan, Vanished user 82345ijgeke4tg, Keilana, The Unknown
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Stephen Shaw, AbeerZaki, Mygerardromance, Nn123645, Asd28, Agamgik, Senorerik, Denisarona, Tatterfly, Troy 07, Ytraere, Wikipedi-
anMarlith, Atif.t2, Elassint, ClueBot, Meningitis5590, LAX, Jackollie, James Lednik, Kennvido, Fyyer, The Thing That Should Not Be,
Zoncept, Tanglewood4, Taroaldo, Drmies, Anghel Stefan Andrei, DanielDeibler, CounterVandalismBot, Ottawahitech, Piledhigherand-
deeper, Wawot1, Mspraveen, Phileasson, Excirial, Zaharous, Sanjpatel1, Peter.C, 4-409r-0, Morel, Revotfel, Navicular, Jesuseats, Thingg,
Aitias, Savolya, SoxBot III, Pirags, MasterOfHisOwnDomain, DumZiBoT, RexxS, XLinkBot, Wnb0518, Jan D. Berends, Stickee, Ost316,
Southlynbrook, TFOWR, Thatguyflint, Cunard, Addbot, Xp54321, Mortense, DOI bot, MartinezMD, Orinoco-w, Looie496, Download,
Tunning, LaaknorBot, DFS454, Bassbonerocks, FiriBot, Favonian, LinkFA-Bot, West.andrew.g, Numbo3-bot, Tide rolls, Bartledan,
Woodfinden1, Frehley, Luckas-bot, Yobot, EchetusXe, Ptbotgourou, Fraggle81, TaBOT-zerem, THEN WHO WAS PHONE?, Anakn-
gAraw, Andreas Werle, Tempodivalse, AnomieBOT, Judo112, Floquenbeam, Ajutla, Qizix, Galoubet, Kingpin13, Bluerasberry, Citation
bot, Daniel Benfield, Fmilley, GB fan, Xqbot, Zad68, 4twenty42o, Champlax, Mlenoirh, Peter grotzinger, Omnipaedista, AshleyLaFleche,
GenOrl, Sabrebd, HxCMoShWiTmE, Medicinedecoded, Babyseal82, Sesu Prime, Izvora, Marvin 101, FrescoBot, Shipnerd62962, DOC-
traind, Jdsaxyman, KSWarrior8, Whoosit, Dxccc, Giliganislanderererer, Richarddc, Neonasigoreng, JaredFTW, Milf 6969, OpticalDream,
Yowahsup888, Wireless Keyboard, Citation bot 1, Pinethicket, I dream of horses, HRoestBot, 10metreh, Jonesey95, Pelmeen10, Make-
upnliesx3, 1230abcz, RedBot, Midnight Comet, Niri.M, FoxBot, Trappist the monk, Afr77, Vrenator, LawBot, Caranordberg, Suffusion
of Yellow, Romanlopez2011, Tbhotch, DARTH SIDIOUS 2, Mean as custard, RjwilmsiBot, TjBot, Lightnem, Whywhenwhohow, Emaus-
Bot, Orphan Wiki, WikitanvirBot, Candicell, Immunize, Richie-Zhang, Benhoganpivot, IncognitoErgoSum, Rybody, Erpert, ZéroBot, Fæ,
Meningvax, Allforrous, Wieralee, Szalakóta, ZoelAllen3, Hazard-SJ, Lldenke, Chattanoogadoc, Coasterlover1994, L Kensington, Don-
ner60, Frankblaze, ChuispastonBot, Caroline Going, Teaktl17, ClueBot NG, Jack Greenmaven, Movses-bot, O.Koslowski, Liljoe4195,
Helpful Pixie Bot, Schmoozin, Drsandybrook, MKar, Scorpian ad, MusikAnimal, Vaizdu, Mark Arsten, Je.rrt, Rachel.truger, Drboulware,
Ginger Maine Coon, Animalloveraudra, Abidparakkal, Akmscott, BattyBot, David.moreno72, Mdann52, Pinkie Pie, ChrisGualtieri, Jig-
garman, Jon206, Dexbot, SantoshBot, Ildiko Santana, SoledadKabocha, Cebderby, Viewmont Viking, Palma Marton Chatonnet, Kfh123,
TaraLatimer, Paum89, BurritoBazooka, Themaninwhiteandblack, Shirin-Rose King, Chickenkfc, Asangaw, Babitaarora, Dradilramzan,
Seppi333, Falmajed, NottNott, Immunizeca, Dominick0207, Andrue 12345, Dodi 8238, A3BDFAD9EC0B, Monkbot, Zıpırdak, TheQ
Editor, Qwertyxp2000, Meningitiscentre, Poiuytrewqvtaatv123321, Spartan - 117, SamFernEspin, Boonoa23456782345678, Appendices,
Ares.Zachariades, KasparBot, 3 of Diamonds, Oluwa2Chainz, Toby1285, Kfcjdjrbccsblv ndb, Barbara (WVS), We Them Boys, Assassi-
nanup, Msilvestro63 and Anonymous: 977

12.2 Images
• File:Ceftriaxone_structure.png Source: https://upload.wikimedia.org/wikipedia/commons/0/0c/Ceftriaxone_structure.png License:
Public domain Contributors: Own work Original artist: Edgar181
12.3 Content license 15

• File:Charlotte_Cleverley-Bisman_Meningicoccal_Disease.jpg Source: https://upload.wikimedia.org/wikipedia/commons/2/29/

Charlotte_Cleverley-Bisman_Meningicoccal_Disease.jpg License: CC-BY-SA-3.0 Contributors: http://www.babycharlotte.co.nz/
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• File:Meningitis-Epidemics-World-Map.png Source: https://upload.wikimedia.org/wikipedia/commons/b/b1/
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• File:Meningitis_Histopathology.jpg Source: https://upload.wikimedia.org/wikipedia/commons/f/f9/Meningitis_Histopathology.jpg
License: CC BY-SA 3.0 Contributors: Own work Original artist: Marvin 101
• File:Meningitis_world_map_-_DALY_-_WHO2004.svg Source: https://upload.wikimedia.org/wikipedia/commons/c/ca/Meningitis_
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• Vector map from BlankMap-World6, compact.svg by Canuckguy et al. Original artist: Lokal_Profil
• File:Neck_stiffness.jpg Source: https://upload.wikimedia.org/wikipedia/commons/5/54/Neck_stiffness.jpg License: Public domain
Contributors: Sophian, Abraham: Epidemic cerebrospinal meningitis (1913), St. Louis, C.V Mosby (Scan from archive.org). Original
artist: L.A. Marty, M.D, Kansas City
• File:Neisseria_meningitidis.jpg Source: https://upload.wikimedia.org/wikipedia/commons/7/75/Neisseria_meningitidis.jpg License:
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