Transcript Meningococcal meningitis - Academy of Medicine of Malaysia

Meningococcal
meningitis
Ooi Phaik Yee
Hospital Sungai Buloh
14/9/13
introduction
• Meningitis: clinical syndrome characterized
by inflammation of the meninges
• Meningococcal meningitis
– Caused by Nisseria meningitidis
– first described by Vieusseux during an outbreak
in Geneva, Switzerland in 1805
• Contagious
• High case fatality rate
• Persistent neurological deficits
• disease spectrum:
– occult sepsis with rapid recovery to fulminant
disease
• Fatality rate
– Before1920s: 70%
– overall now: 9 to 12%
– meningococcal sepsis: 40%
• 11 to 19% have sequelae
– hearing loss
– neurological disability
– loss of a limb
Nisseria meningitidis
• Exclusively human, Gram negative,
aerobic diplococci
• 13 serogroups: A,B,C,H,I,K,L,M,X,Y,Z,29E,
W135
• Further classified into 20 serotypes, 10
subtypes & 13 immunotypes
• Most infections caused by serogroup
A,B,C,Y,W135
• Capable of changing the genetic material
& switching from 1 serogroup to another
• Common inhabitant of nasopharynx
• 8-20% of adults are asymptomatic carrier
• Mainly affect young children (<7 months)
• Also in order child & young adults
Meningococcal disease
• 90% is from 3 serogroups: A, B & C
– A & C in Asia & Africa
– B & C Europe & Americas
• All may cause epidemics though the risk
differs.
• Serogroup A
– historically been the main cause of epidemic
– still dominates in Africa during both endemic &
epidemic periods
• Epidemic rate
– Less than 1-3/100,000 in developed nations
– 10-25 per 100,000 in developing countries
• cases among infants < 1 month
– >50% caused by serogroup B
The meningitis belt
• World’s highest disease burden
• sub-Saharan Africa, stretching from Senegal
in the west to Ethiopia in the east
• Epidemics occur in seasonal cycles between
November & June
• Epidemics last 8-15 years
• decline rapidly in rainy season
• mechanisms are thought to be related to
variations in herd immunity
Prevalence of meningococcal
Meningitis
• major epidemics of meningococcal
disease in Asia
– China 1979 & 1980
– Vietnam 1977
– Mongolia 1973-1974 & 1994-1995
– Saudi Arabia 1987
– Yemen 1988
• Europe & the Americas
– lower incidence of epidemics
Transmission & risk factors
• Direct contact or via droplets from respiratory
or throat secretions
• Average incubation period: 4 days (2-10 days)
• household risk if exposed: increase by 400800x
• Transmission highest in 1st week
• Humoral immunity
• Incidence highest in 6-24 months of age
• Some may be carrier for many years before
becoming ill
Risk factors
• Risk factors
– Asplenia
– Deficiency of properdin
– Deficiency of antibody-dependent, complement
mediated immune lysis
– Household crowding
– Active & passive smoking
– Antecedent URTI (mycoplasma pneumonia or virus)
– Chronic underlying illness
• hepatic failure, SLE, multiple myeloma
– HIV
Clinical
menifestations
Clinical manifestations
• 2 forms of meningococcal disease
– Meningitis & meningococcal septicemia
• Invasive meningococcal disease
– Bacteremia without shock (acute mild
meningococcemia)
– Bacteremia with shock but no meningitis
(fulminant meningococcemia)
– Shock & meningitis
– Meningitis alone
– Chronic benign meningococcemia
Meningococcal meningitis
• Hematogenous spread
• 50-55% of pts w meningococcal disease
• Similar to other acute purulent meningitis
Signs & symptoms
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Intense headache
Fever
Stiff neck
Nausea
Vomiting
Photophobia
Lethargy, drowsiness
Rash
Altered mental status ( elderly)
Prolonged course w fever
Young children: signs
• Subacute infection, progresses over several
days
• Irritability
• Projectile vomiting
• Seizures
– usually with a focal onset
– typically during the first few days
• Infants
– may have insidious onset
– stiff neck & other classic signs may be absent
signs
• nuchal rigidity
• lethargy, delirium, coma, convulsions
• only 70% has classic triad of fever, neck stiffness,
& change in mental status.
• petechial or purpuric rash
– 12-18H after onset
– 62% in >30yo, 81% in younger pts
– usually on the trunk, legs, mucous membranes, &
conjunctivae
– Occasionally on the palms & soles
– may progress to purpura fulminans, associated with
multiorgan failure
Nuchal rigidity
• meningococcal septicemia
– Less common
– rapid circulatory collapse & hemorrhagic rash.
• Waterhouse-Friderichsen syndrome
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widespread petechial hemorrhages
Hemorrhagic adrenalitis
septic shock
disseminated intravascular coagulation (DIC)
• Neurologic sequelae
– sensorineural deafness, mental retardation,
spasticity & seizures
• <1% can present with
– Spiking fever (over days to several weeks)
– Arthralgia
– Arthritis
– Recurrent rash (chronic benign
meningococcemia)
• 20% later developed meningitis
Other infections due to N
meningitidis
• Compartmentalized metastatic infections
• Pericarditis
– Early (first few days): may demonstrate organism
– Late (1-2 weeks): sterile
• Septic arthritis
– late onset, after resolution of meningococcemia
– Isolated, spontaneous
• Others:
– cellulitis, endophthalmitis, conjunctivitis,
pneumonia, siadenitis, pelvic inflammatory
disease
diagnosis
• Gram Stain
– positive in 70-90%
– GRAM NEGATIVE DIPLOCOCCI both inside & outside of
polymorphonuclear cells
• Direct antigen detection w latex agglutination
• Culture from CSF
– Positive in 80%
• PCR
– Not affected by prior initiation of antibiotics
– sensitivity 97% & specificity 99.6%
– available within 2H
• Meningococcemia: skin biopsy
• Meningitis: only CSF generally positive
• Body fluid may be positive in early onset
compartmentalized infections
• Blood culture
– during febrile episodes are not consistently
positive
– Usually negative when afebrile
Antigen testing
• Latex agglutination: detect capsular
antigen of meningococcal serogroups A, B,
C, Y, W135
• Rapid, serogroup specific but not reliable
• Negative GN or Ag detection does not rule
out meningococcal disease
In clinical practice….
• Empirical treatment: based on the most likely
organism
• Institute antibiotics ASAP after LP
• Avoid delays
• Yield increased if specimen is examined
ASAP
– eg CSF should be examined within 1H
• CSF sterilization may occur more rapidly after
initiation of parenteral antibiotics
• complete sterilization within 2H
Lumbar puncture
• Typical CSF abnormalities:
– Increased opening pressure
– Pleocytosis of polymorphonuclear
leukocytosis
• predominantly neutrophils
– Decreased glucose (compare w serum
glucose)
– Increased protein
neuroimaging
• Contrasted computed tomography
– prior to lumbar puncture (? Risk of coning)
– Demonstrates meningeal enhancement
• Magnetic resonance imaging contrasted
– demonstrates meningeal lesions, cerebral
edema, & cerebral ischemia
management
• Potentially fatal, should be treated as a
medical emergency
• Admission is necessary though isolation
may not be necessary
• Important to
– Early recognition
– Prompt initial parenteral antibiotics
– Close monitoring
Empirical management for
suspected meningitis
• Dexamethasone (controversial in adults)
• 3rd generation cephalosporin
– ceftriaxone or cefotaxime
• +/- Vancomycin
• Acyclovir
Adjunctive dexamethasone in
bacterial meningitis
• Decrease cerebral edema & neuronal
injury
• Recommended for all suspected
pneumococcal meningitis
• 0.15 mg/kg q6H x 2-4 days
• 1st dose 10-20 min before or at least
concomitant with the antibiotics
• Significantly reduce unfavorable outcome
& death
• to be continued if confirmed S.
pneumoniae
• Data inadequate to recommend adjunctive
dexa in meningitis caused by other
bacterial pathogens
Definitive management
• Penicillin or Ampicillin
• Ceftriaxone (or cefotaxime)
– if penicillin resistance
• Despite adequate & early treatment, 510% die, typically within 24-48H after
onset
Prevention
chemoprophylaxis
• Prevention of sporadic meningococcal
disease of close contacts of infected
patients
• Eradication of the carrier status
• Mass chemoprophylaxis to control large
outbreaks are not recommended
– multiple sources of exposure & prolonged risk
of exposure
• Ciprofloxacin 500 mg in a single dose
– easiest option in adults.
• Children could receive either
– a single IM injection of ceftriaxone, or
– 4 oral doses of rifampin over 2 days, according to
BW.
• commonly used
– rifampin, ciprofloxacin, ceftriaxone, minocycline,
& spiramycin.
• Oily chloramphenicol
– in areas with limited health facilities
Vaccination
Meningococcal vaccine: 3 types
• Polysaccharide vaccines
– Available >30 yrs ago
– bivalent (groups A & C), trivalent (groups A, C &
W), or tetravalent (groups A, C, Y & W135)
• outer membrane proteins (OMP) for
serogroup B
– No polysaccharide vaccines for serogroup B
– Used in Cuba, New Zealand & Norway
• Meningococcal conjugate vaccine
– against group C: since 1999
– Tetravalent A, C, Y & W135 conjugate vaccines:
used since 2005 in Canada, USA & Europe.
Conjugate vs polysaccharide
• advantages of conjugate vaccine
– higher & more sustainable immune response
against group A meningococcus
– reduces the carriage & transmission of the
bacteria in the throat
– expected to confer long-term protection
– cheaper
– particularly effective in protecting children <
2yo, who do not respond to conventional
polysaccharide vaccines.
Immunization
• Primary vaccination: for older than 2 yrs (2-55yo)
• recommended for adults & children at high risk
• 3 months to 2 yrs under special circumstances
(approved by FDA in August 2013)
• High-risk persons
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military recruits
contacts to index cases
travellers to areas of high incidence or outbreaks
patients with asplenia
adolescents with HIV infection
persons with terminal complement disorders
Malaysian scenario
• Vaccines available
– Meningococcal A & C
– Menomune A , C, Y, W-135
– Mencevax A, C, Y, W-135
• not routinely recommended
• compulsory for the Hajj pilgrims & Umrah following the
1987 serogroup A meningococcal disease outbreak.
• Since 1988, Malaysian Hajj pilgrims had received the
bivalent A & C vaccine
• Beginning 2002 Hajj, Saudi health officials require
certification of quadrivalent meninggococcal
vaccination covering serogroups A, C, Y, & W-135 for
all entering pilgrims.
conclusion
• Meningococcal meningitis has high mortality
& morbidity rate.
• All meningitides including the meningococcal
meningitis should always be treated as
medical emergency.
• Early recognition & treatment are mandatory
to prevent complications
• chemoprophylaxis & mass vaccination to
prevent further transmission, in susceptible
individuals
Thank you
Meningococcal polysaccharide
vaccine
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Quadrivalent: A,C, Y, W-135
Bivalent: A & C
Primary vaccination: for older than 2 yrs (2-55yo)
3 months to 2 yrs under special circumstances
(approved by FDA in August 2013)
• Children: 2 doses 3 months apart
• Ab response is serogroup specific & independent
• Protective levels of ab are usually achieved within
7 days of vaccination
vaccination
• Serogroup A polysaccharide: induce ab as
early as 3 months of age
• Adult: 4-5 yrs
• Serogp C: poorly immunogenic in children
• Both serogp A &C: good immunogenicity,
clinical efficacy≥ 85%
• Ab level & clinical efficacy reduced markedly
during the first 3 yrs of vaccination
• Detectable up to 10yrs of vaccination
• Multiple doses of serogroup A or C poly
saccharide may cause tolerance
• Adverse effects mild
– Pain & redness (4-56%)
– Transient fever (4%)
• Severe reaction: rare
• Drawback: absence of activity against
serogroup B meningococci
• Use of group B capsule in a vaccine risks
the induction of autoimmunity
• Ab response to group B is limited after
natural infection hence group B capsular
polysaccharide is poor candidate for
vaccine replacement.
Conjugated polysaccharide
vaccine
• Quadrivalent
• Induces T cell dependent response
• Improve immune response, priming
immunologic memory & leading to a
booster response to subsequent doses
• Long lasting immunity
• Induces Herd immunity
• 70% expected to be preventable
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Safe
Immunogenic
Reduces the nasopharyngeal carriage rate
Contraindicated in known allergy to any
component of vaccine including the diphtheria
toxoid
• Routine childhood vaccination not recommended
• Relative ineffectiveness in age <2yo ( highest risk
of sporadic disease & realtively short duration of
protection)
• Routine vaccination recommended for certain
gp w high risk
– Autonomic or functional asplenia
– Lab personnel & healthcare worker w are
routinely exposed to N meningitidis
• WHO: mass vaccinate every district in
epidemic & alert phase
• Single dose of polysaccharide for travelers>
18 months of age to epidemic or high rate of
endemic meningococcal disease
revaccination
• Persons high risk for infection, particularly
children who were first vaccinated < 4 yo
• To consider revaccination after 2-3 yrs if
risk still high