Meningitis Flashcards
define meningism
symptom complex characterised by:
headache, photophobia, vomiting, muscle spams leading to neck rigidity
causes of meningism
meningitis
sub-arachnoid haemorrhage
infection accompanied by bacteraemia
severe influenza
infection spread from the frontal and ethmoid sinuses may produce what?
abscess in the frontal lobe
infection in the middle ear may spread to?
temporal lobe
What feature means that the capillaries of the brain and spinal cord are different to the rest of the vascular system? what does this cause?
no fenestrations and intercellular clefts
less diffusion more active transport
describe the five steps of pathogenesis in most cases of meningitis
- attachment to mucosal epithelial cells
- transgression of the mucosal barrier
- survival in the blood stream
- entry into CSF
- production of overt infection in the meninges with or without brain infection
Common bacterial causes of meningitis (adults)
neisseria meningitis
streptococcus pneumoniae
Common bacterial causes of meningitis (neonates)
e. coli
group B strep
Common viral causes of meningitis
enteroviruses (echovirusees, parechoviruses, coxsackie A and B, polio)
Mumps
HSV
Less common causes of meningitis
Haemophilus influenzae type b listeria monocytogenes mycobacterium tuberculosis leptospirosis borrelia burgdorferi (lyme disease) mycoplasma pneumoniae cryptococcus neoformans (in AIDS) HIV VZV EBV
what organisms may produce a meningo-encephalitis?
enteroviruses
What is aseptic meningitis?
CSF shows excessive # lymphocytes and elevated protein but no organism is cultured
Causes of non-infective meningitis
Tumour cells in CSF drugs chemicals sarcoidosis SLE
meningeal infection should be considered in every patient with?
history of URTI + one of the meningeal symptoms of vomiting, stiff neck, headache, lethargy or clouding of consciousness
neurological signs of meningitis
usually absent or minimal in CN VI, VII, VIII
associated illness
recent skull trauma
alcoholism
DM
CSF microbiology tests
gram stain differential cell count antigen detection test bacterial culture mycobacterial or fungal culture PCR for viruses/bacteria
CSF biochemistry tests
glucose
protien
what will be seen in suspected DIC on blood films?
thrombocytopaenia
abdnormal clotting
increased fibrin degradation products
Appearance of CSF normal
clear
Appearance of CSF bacterial
usually turbid
Appearance of CSF viral
clear to turbid
Appearance of CSF tuberculous meningitis
clear to turbid
CSF cells normal
small numbers <5/mm3
CSF cells bacterial
greatly increased
CSF cells viral
moderately increased
CSF cells tuberculous meningitis
moderate increase
CSF predominant cell type normal
lymphocytes
CSF predominant cell type bacteral
neutrophils
CSF predominant cell type viral
lymphocytes
CSF predominant cell type tuberculous meningitis
lymphocyte or mixed
CSF glucose normal
normal - approx 60% blood level
CSF glucose bacterial
reduced
CSF glucose viral
normal
CSF glucose tuberculous meningitis
reduced
CSF protein normal
normal
CSF protein bacterial
greatly increased
CSF protein viral
moderate increase
CSF protein tuberculous meningitis
greatly increased
what is essential in order to reduce death rate in bacterial meningitis?
early clinical recognition
rapid detection of pathogen
rapid initiation of appropriate bactericidal antimicrobial therapy
early recognition and treatment of sequelae of septicaemia
antibiotic prophylaxis to close contacts
antibiotics in meningitis
benzylpenicillin - meninges must be inflammed, 4hrly high dose
Ceftriaxone
what bacteria causes meningococcal meningitis?
neisseria meningitidis
epidemiology of meningococcal meningitis
children and young adults
sporadic in UK
1/2 causes in 1st 3 months of the year
how can meningococcal meningitis organism be typed?
capsular polysaccharide (serogroup) and outer membrane proteins
what has caused the causes of meningococcal C to decreased?
Men C vaccine
group A strains of meningococcal meningitis are commonly responsible for outbreaks where?
indian sub-continent
middle east
sub-saharan Africa
why are polysaccharides not generally highly immunogenic?
similar or identical repeating sugar residues linked together and do not contain a wide variety of epitopes, as proteins usually do
for what strains of meningococcal are their vaccines?
A + C vaccine = some protection
C = very effective
B = not yet part of UK schedule
what type of organism are meningococcal meningitis?
gram negative diploccoi
where can n. meningitidis be isolated from?
blood
petechiae or purpuric skin lesions (occasionally)
clinical syndromes in meningococcal infection
meningitis
fulminant meningococcal septicaemia
what is fulminant meningococcal septicaemia?
characterised by startling suddenness of symptoms causing with rapid deterioration in consciousness, fever, septicaemic shock with renal failure, and disseminated intravascular coagulation (DIC). CSF is sterile with little or no increase in white blood cells (i.e. this syndrome is technically not meningitis), but the outcome is generally worse. FIFTY PERCENT OF THESE PATIENTS DIE WITHIN
THE FIRST 24 HOURS OF ILLNESS. For this reason, antibiotics should be given by the GP prior to hospitalisation. A purpuric rash is characteristic. This is the Waterhouse- Friedrichsen syndrome, where autopsy reveals bilateral adrenal haemorrhages with
adrenal ablation/hypoadrenalism.
why are oly 50% of children with meningococcal disease sent to hospital after the first consultation?
non-specific symptoms in first 4-6 hrs
classic feature of meningococcal disease?
purpuric rash
describe a purpuric rash
does not blanche on pressure
describe chronic meningococcaemia
uncommon illness that may last weeks or even months with a rash (recurring every 48-72 hours), joint pains, malaise and fever, sometimes complicated by endocarditis.
what may be related to chronic meningococcaemi
serum complement deficiency
treatment of meningococcal meningitis or sepsis
early antipoints
GP - parenteral penicillin 3-4 MU
hospital - high dose ceftriaxone prior to LP but after blood cultures
supportive therapy
at time of discharge a meningococcal meningitis patient should be given what and why?
rifampicin or ciprofloxacin (adults only) to eradicate carriage of N. meningitidis from the nasopharynx
poor clinical prognostic factors in meningococcal septicaemia
delay in instigation of antibiotic therapy
extremes of age
purpuric lesions
shock with absence of signs of meningitis and hyperpyrexia (rectal temperature > 40)
poor laboratory prognostic factors in meningococcal septicaemia
presence of DIC
metabolic acidosis
absence of polymorph leucocytosis
notification and prophylaxis of meningococcal meningitis
all cases notified
all close contacts and the index case before discharge from hospital should recieve chemoprohylaxis with rifampicin or ciprofloxacin
what organism causes pneumococcal meningitis?
streptococcus pneumoniae
what is the most frequent cause of bacterial meningitis in adults?
streptococcus pneumoniae
what are common predisposing factors for the development of pneumococcal meningitis?
pneumonia sinusitis endocarditis head trauma alcoholism splenectomy
what type of organism as pneumococci?
gram +ve diplococci
alpha haemolytic
what is an important virulence factor on pneumocci? why?
capsular serotype
antiphagocytic
what is the treatment of choice for pneumococci?
benzylpenicillin
where are penicillin resistant strains of pneumococci developing?
South Africa
Spain
in what way are pneumococci developing resistance?
chromosomal change coding fro different penicillin binding proteins
onset of symptoms in pneumococcal meningitis
The onset of symptoms is usually acute with
meningitis developing in 1-2 days. Patients
are more likely to have altered conscious
level or focal neurological signs than
those with haemophilus or meningococcal
meningitis. Petechiae can occur although
this is uncommon. Always look for concurrent
infection in the sinuses and ear or the
presence of skull defects, notably fractures.
treatment of pneumococcal meningitis
high dose ceftriaxone
complications of pneumococcal meningitis
death - 30-50% loss of hearing cranial nerve defects hemiparesis hydrocephalus seizures
what drug may reduce the complications of pneumococcal meningitis?
dexamethasone
prevention of pneumococcal meningitis
pneumococcal vaccine - 23 common polysaccharide capsular serotypes
recommended > 65 yrs
<65 - splenectomy, DM, chronic renal disease, Cardio-resp disease, HIV
<2yrs conjugate vaccine - Prevenar, 7 common polysaccharide
what is a common presentation of haemophilus influenzae meningitis?
young child
URTI followed by rapid deterioration
signs of haemophilus influenzae meningitis
Antecedent symptoms of upper respiratory
tract infection and an associated otitis
media/pharyngitis are common. There are
often few signs of meningitis, with fever and
lethargy/drowsiness being more common.
Petechial spots are rare. Nuchal rigidity is
often absent. In late disease, seizures and
coma may occur. Rapid fulminant disease or a
syndrome characterised by an insidious onset
(similar to TB meningitis) may occur.
what type of organism is haemophilus influenzae?
pleomorphic
mixture of gram -ve cocci and bacilli
haemophilus influenzae with a polysaccharide capsule is often associated with what infection?
meningitis
epiglottitis
arthritis
haemophilus influenzae without a polysaccharide capsule is often associated with what infection?
oro-pharyngeal commensals
exacerbations of COPD in adults
why is blind therapy with amoxycillin or ampicillin no longer recommended for haemophilus influenzae?
10-15% produce b-lactamase
dexamethasone has been shown to cause what in haemophilus influenzae meningitis infected patients?
improve survival
reduce long-term neurological sequelae
what prophylaxis should be given to close contacts of haemophilus influenzae meningitis patients?
rifampicin
describe the haemophilus influenzae b vaccine
The type b polysaccharide capsule is not very
immunogenic in young children unless linked
(conjugated) to a carrier protein. A variety
of suitable carrier proteins (eg, diphtheria
or tetanus toxoids, group B meningococcal
outer membrane proteins) may be used. The
conjugate Hib vaccine was introduced in 1993
in the UK and is recommended for all infants
from two months of age. Three doses should
be given, with an interval of one month
between doses.
what type of organism is listeria monocytogenes?
gram +ve bacillis
what age group are especially vulnerable to listeria monocytogenes meningitis?
neonates
to cover listeria, the initial management of meningitis in adults over the age of 55 should include what?
IV ampicillin
who is most likely to have tuberculous meningitis in the UK?
elderly men or alcoholics
describe the clinical features of tuberculous meningitis
Meningitis follows rupture of a subependymal
tubercle into the subarachnoid space. In
childhood, it is usually an early post-primary
event associated with either miliary TB or
pleural effusion. In adults, at least threequarters
will have clinical evidence of
extrameningeal tuberculosis. TBM should be
considered in any patient with meningism
and low grade fever who has active extrameningeal
tuberculosis. It usually presents
subacutely with lethargy, chronic headache
and change in mentation. It may present
occasionally with an acute and severe
meningitis with unconsciousness.
describe the investigations in tuberculous meningits
The CSF white cell response is mixed or
lymphocytic in nature. Only 30-40% of initial
CSF examinations are positive for acid and
alcohol fast bacilli (AAFB) on Ziehl-Neelsen
stain, but many more cases are subsequently
proven on culture. Note, that in general,
culture is a much more sensitive technique
than microscopy. The importance of repeated
lumbar punctures cannot be over-emphasised
in achieving better microbiological diagnosis.
TBM should always be considered as a
possible diagnosis if the CSF glucose is
reduced and Gram stain and conventional
culture are negative, especially in the
absence of any previous antibiotic therapy.
Chest x-ray (showing miliary TB) or CT head
scan (showing tuberculoma) may be helpful in
the diagnosis. PCR can now be used to detect
mycobacterial DNA in CSF and is available in
certain reference laboratories. Liquid culture
systems allow M.tuberculosis to grow in
10-14 days.
treatment for tuberculous meningitis
as for pulmonary TB
prognosis of tuberculous meningitis
Extremes of age, duration of symptoms (illness greater than 2 months) and the presence of a neurological deficit are poor prognostic markers in TBM. Resistant organisms lead to a poor response and increasing the drug dosage may not be effective.
leptospirosis and lyme disease are caused by what?
spirochaetes
leptospirosis and lyme disease may cauase?
apparent aseptic meningitis
what is leptospirosis caused by and how is it transmitted?
leptospira interrogans
animal urine
leptospirosis is associated with what occupations?
farmers
abattoir workers
watersports
exposure to rats, dogs or cattle
leptospirosis presents with?
septicaemic illness with fever, rigors, myalgia, vomiting, conjunctival effusion and meningism
followed by rash and hepato-renal damage
how is diagnosis of leptospirosis made?
serology
what cases lyme disease and how is it spread?
borrelia burgdorferi
ticks - ixodes species from an animal reservoir e.g. rodents or deer
clinical presentation of lyme disease
erythema chronicum migrans
some may later develop neurological symptoms incl meningitis and peripheral or cranial (esp VII) neuropathes
how is diagnosis of lyme disease made?
serology
when in the year is viral meningitis most common?
late summer
early autum
most common causes of viral meningitis
enterovirus esp echovirus and coxsackie
in immunocompromised patients persistent infection with enterovirus may cause what?
chronic enteroviral meningitis
meningoencephalitis
important causes of viral meingitis
mumps polio HSV2 VZV during reactivation with or without rash EBV - seroconversion illness HIV
clinical presentation of viral meningitis
Most patients have a non-specific prodromal
illness, followed by rapid onset of headache,
photophobia, low grade fever and a stiff
neck. Patients are usually lucid and alert. If
encephalitis is also present, then lethargy,
confusion, seizures and focal neurological
signs occur. With enteroviral meningitis, a
rash may be present which, if petechial, may
resemble menincococcaemia. With mumps
meningitis, 50% do not have detectable
parotitis
investigations in viral meningitis
PCR of CSF for enteroviruses, herpes
simplex, mumps and other viruses is now the
investigation of choice because it is much
more sensitive and rapid than culture. The
CSF in viral meningitis shows a lymphocytosis
with normal CSF glucose. Enteroviruses can
also be detected in throat swabs (in viral
transport medium) and from faeces, and
although their presence here does not prove
causation, testing by PCR is appropriate.
Testing for HIV should be considered,
remembering that the initial screening test
may be negative if the symptoms are part of
a seroconversion illness.
treatment of viral meningitis
enterovirus + parechoviruses - usualy recover in 72 hrs
chronic infection - IV IG
HSV - aciclovir, initially IV
prognosis of viral meningitis
most make complete recovery with no long-term sequelae
mumps - deafness, orchitis, testicular atrophy
prevention of viral meningitis
MMR
Hand hygiene
cause of fungal meningitis
cryptococal meningitis
what yeast is the most important cause of meningitis in patients with HIV?
cryptococcus neoformans
other than HIV, crytococcus neoformans may rarely cause fungal meningitis in patients with?
diabetes
lymphoma
those receiving immunosuppressive drugs
where is cryptococcus neoformans found?
bird droppings esp pigeons
microbiology of cryptococcus neoformans
The organism is a yeast which has a
polysaccharide capsule, the capsule being
visualised as a clear zone around the yeast
cell on staining with India ink. Investigation
by Gram stain shows yeast cells which are
indistinguishable from Candida sp. CSF
examination with Indian ink may demonstrate
the capsule (not present in Candida sp.), but
artefacts are easily mis-identified as capsular
yeasts, and this test should not be relied
upon in the absence of a Gram stain showing
typical yeast cells. Measurement of CSF and
serum cryptococcal polysaccharide antigen
is an important means of diagnosis, but C
neoformans grows readily on culture.
clinical features of cryptococcal meningitis
Most commonly, there is a subacute onset of
symptoms with low grade fever, headache,
nausea, lethargy, confusion and abdominal
pain. Meningism is less common, although
it can develop quickly as the condition
progresses.
treatment of cryptococcal meningitis
parenteral amphotericin
sometimes combination with flucytosine
prevention of cryptococcal meningitis
Long term chemoprophylaxis with fluconazole is now given to patients with HIV infection following an episode of cryptococcal meningitis (secondary prophylaxis).
how does neonatal meningitis differ from adult?
1. The symptoms and signs are usually nonspecific or not well localised. 2. The bacteria commonly involved are group B streptococci, E. coli and L. monocytogenes as well as enteroviruses and parechoviruses. Predisposing conditions include low birth weight, prolonged rupture of membranes and maternal diabetes mellitus.
incidence of neonatal meningitis in UK
1/2,500 births
most common causes of neonatal meningitis
group b strep
e. coli
listeria monocytogenes
group b strep are commensals where?
female genital tract
what type of organism are e. coli?
lactose fermenting gram -ve baccili
where is e coli found?
GIT
what strains of e. coli are commonly responsible for neonatal meningitis?
capsulate K1
e. coli is usually sensitive to what antibiotic?
cefotaxime
group b strep are commonly sensitive to what antibiotics?
benzylpenicillin
amoxycillin
in pregnant women what does listeria monocytogenes cause?
febrile flu-like bacteraemic illness
in pregnancy what may listeria monocytogenes cause?
abortion
neonatal sepsis
what is the treatment of choice for listeria monocytogenes?
ampicillin and gentamicin for 3 weeks or longer
clinical features of early onset neonatal meningitis
within 3 days of birth and associated with prematurity or a difficult or prolonged birth. Marked respiratory distress, bacteraemia and a high mortality (50%) are typical. The organism has usually been acquired at birth from the mother’s genital tract.
clinical features of late onset neonatal meningitis
more than one week after birth. The infection is typified by bacteraemia and meningitis but pulmonary involvement is rare. Mortality is 10-20%. The organism may have been spread by cross-infection from other mothers, babies or healthcare workers.
diagnosis of bacterial neonatal meningitis
Neonatal CSF and blood cultures are central to making the diagnosis. Maternal blood cultures and cultures of specimens from the genital tract may also be helpful.
diagnosis of viral neonatal meningitis
CSF, EDTA blood, faeces and nasopharyngeal secretions
treatment of neonatal meningitis
Parenteral ampicillin (to cover group B streptococci and Listeria) and gentamicin or cefotaxime (to cover the gram negative bacilli) are used in combination, until the causative organism is identified. IVIG may be appropriate for enteroviruses or parechoviruses.
prognosis of neonatal meningitis
Neonatal meningitis is associated with a high mortality (up to 50%) and neurological and developmental sequelae (in about 33% of the patients). Early and appropriate treatment is therefore essential.
prevention of neonatal meningitis
Chemoprophylaxis to prevent neonatal Group B strep infection is given to high risk mothers during labour - usually amoxicillin or co-amoxiclav. Significant risk factors for Group B neonatal infection include preterm delivery (<37wks), a prolonged interval between membrane rupture and delivery (>18hrs), a previous infant with Group B streptococcal disease, and intrapartum fever. Screening for Group B Strep in pregnancy is recommended in the USA, but the disease is more common there and in the UK, intrapartum prophylaxis of high risk deliveries is considered sufficient.
Source isolation of neonates with enterovirus or parechovirus, if necessary by cohorting during an outbreak, and strict attention to hand hygiene are essential to prevent spread. IVIG may be appropriate for neonatal contacts.
