Download Bacterial Meningitis

Ch 22
Microbial Diseases
of the Nervous
System
Learning Goals
Define central nervous system and blood-brain barrier.
Differentiate meningitis from encephalitis.
Discuss meningitis caused by H. influenzae, S. pneumoniae, N.
meningitidis, and L. monocytogenes.
Explain how bacterial meningitis is diagnosed and treated.
Discuss transmission, etiology, pathogenesis, symptoms,
preventive measures and treatments of tetanus, botulism,
leprosy, poliomyelitis, and rabies.
Compare the Salk and Sabin vaccines.
Discuss the various types of arboviral encephalitis and how they
can be prevented.
Identify the causative agent, vector, symptoms, and treatment for
African trypanosomiasis
Discuss
the Education,
characteristics
of Cummings
diseases caused by prions.
Copyright © 2006 Pearson
Inc., publishing as Benjamin
Anatomy and Physiology Review
How microbes enter the CNS:
 Skull or backbone fractures
 Medical procedures
 Along peripheral nerves
 Blood or lymph
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
The Meninges and Cerebrospinal Fluid
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Fig 22.2
Infectious Diseases of CNS
 Bacteria can grow in CSF in subarachnoid space.
 The BBB prevents passage of some materials
(such as antimicrobial drugs) into CNS.
 Meningitis vs. encephalitis
 Meningitis can be caused by viruses, bacteria,
fungi, and protozoa.
 VIRAL MENINGITIS: Usually mild. Clears up
within a week or two without specific treatment.
Also called aseptic meningitis.
 BACTERIAL MENINGITIS: Much more serious.
Can cause severe disease resulting in brain
damage and death.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Bacterial Diseases of the Nervous
System
Bacterial Meningitis
 Haemophilus influenzae
 S. pneumoniae
 Neisseria meningitidis
 Listeria monocytogenes
Tetanus
Botulism
Leprosy
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Bacterial Meningitis
 The three major causes:
 Haemophilus influenzae
 S. pneumoniae
 Neisseria meningitidis
 Nearly 50 species of opportunistic bacteria can cause
meningitis.
 Symptoms: Fever, headache, stiff neck, followed by
nausea and vomiting
 May progress to convulsions, coma, death
 Diagnosis by Gram stain or latex agglutination of CSF
 Treated with cephalosporins before identification of
the pathogen
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Bacterial Meningitis
Spreads by direct close contact with the discharges from
the nose or throat of an infected person.
None of the bacteria that cause meningitis are very
contagious, and they are not spread by casual contact
or by simply
breathing the air
where a person
with meningitis has
been.
Fig 22.3
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Haemophilus influenzae Meningitis (Hib)
 Gram-negative
aerobic bacteria,
normal throat
microbiota
 Mostly in children
(6 mo to 4 years).
 Capsule antigen type b
 Novel Hib conjugated vaccines coupled the
polysaccharide to a protein  became part of routine
childhood immunizations and dramatically reduced
Hib and Hib meningitis.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Neisseria Meningitis: Meningococcal
Meningitis
 Gram-negative cocci,
capsule
 10% of people are healthy
nasopharyngeal carriers
 Begins as throat infection,
rash, death can occur within
a few hours of onset.
 Continuing threat in daycare centers and schools.
Healthy children and young adults are susceptible.
 Vaccination recommended for college students
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Meningococcal Meningitis cont.
About half the children or adults with meningococcal
meningitis have the same rash – petechiae – as
those with meningococcal septicaemia.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Meningococcal Meningitis cont.
Streptococcus pneumoniae Meningitis:
Pneumococcal Meningitis
 Gram-positive diplococci
 Typically associated with
pneumonia, but may cause
pneumococcal meningitis and
pneumococcal septicemia.
 70% of people are healthy nasopharyngeal
carriers
 Most common in children (1 month to 4 years)
 Mortality: 30% in children, 80% in elderly
 Prevented by conjugated vaccine
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Listeriosis
 Listeria monocytogenes
 Gram-negative
 Reproduce in
phagocytes.
Fig 22.5
 Acquired by ingestion of contaminated food psychrophil!
 May be asymptomatic in healthy adults.
 Causes meningitis in newborns, immunosuppressed,
pregnant women, and cancer patients.
 Can cross placenta and cause spontaneous abortion
and stillbirth
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Tetanus (Lockjaw)
 Clostridium tetani
 Gram-positive, endospore-forming, obligate
anaerobe
 Grows in deep wounds.
 Tetanospasmin (exotoxin / neurotoxin) released
from dead cells blocks relaxation pathway in
muscles. Tetanospasmin action.
 Prevention by vaccination with tetanus toxoid
(DTaP) and booster (dT).
 Treatment with tetanus immune globulin.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Tetanospasmin Action
Blockage of
inhibitory NT release
in CNS (glycine and
GABA – gammaanimobutyric acid)
Result ?
Reminiscent of ?
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Why characteristic
backward arc?
Characteristic
condition:
Opistothonos
Neonatal tetanus with severe muscle
contractions.
-courtesy of CDC-
Botulism
 Clostridium botulinum
 Gram-positive, endospore-forming, obligate anaerobe,
ubiquitous in soil and H2O
 Intoxication (ingestion of botulinum toxin): 7 different
Neurotoxins (exotoxins, A, B and E cause most human
illness)
 Type A
 60-70% fatality
 Found in CA, WA, CO, OR, NM.
 Type B
 25% fatality
 Europe and eastern United States
 Type E
 Found in marine and lake sediments
Copyright
© 2006 Pearson
Education, Inc., publishing
as Benjamin Cummings
 Pacific
Northwest,
Alaska,
Great Lakes area
Botulinum Toxin: Most Potent Toxin on Earth
 Mechanism of action: Irreversible inhibition
of ACh release from motor neuron 
________
 Treatment: ?
 Prevention
 Proper canning
 Nitrites prevent endospore germination in
sausages
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
3 Forms of Botulism
1. Foodborne botulism: Intoxication not
infection! Endospores survive improper
canning procedures.
2. Wound botulism: ~ symptoms as above,
start ~ 4 days after wound infection
3. Infant botulism: due to ingestion
of endospores  C. botulinum
growing in intestines.
In animals: limberneck
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Botulinum Toxin: Killer and Healer
Botox (Botulinum toxin type A)
Medical uses: blephrospasms,
strabismus, torticollis . . . . . etc.
Under investigation: migraine
headaches, hyperhidrosis
Cosmetic purposes
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Spastic
torticollis:
neck in a
twisted or
bent position
Blepharospasm is a focal
dystonia characterized by
increased blinking and
involuntary closing of the eyes.
Leprosy or Hansen’s Disease
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Mycobacterium leprae (acid-fast rod)

Grows best at 30°C  cooler body regions (peripheral
nerves and skin cells)

Transmission requires prolonged contact with an
infected person. Mostly via nasal secretions of
lepromatous leprosy patients
Incubation time: Months to 10 years
Two forms depending on immune response
1. Tuberculoid (neural) form: Loss of sensation in skin
areas; positive lepromin test
2. Lepromatous (progressive) form: in case of cell
mediated IS failure) Disfiguring nodules over body;
negative lepromin test
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Tuberculoid leprosy in a 24-year-old Samoan woman with sevenmonth history of expanding plaque on cheek. Note the thickened
accessory nerve coursing over the sternomastoid muscle.
Patient with active,
neglected nodulous
lepromatous
leprosy. With
treatment, all
nodules could be
reversed.
©WHO/TDR/McDou
gall
Azadegan Clinic,
Teheran: The foot of
a woman that has
been grossly
disfigured through
leprosy infection. ©
World Health
Organization/TDR/C
rump
Deformity due to nerve damage with its consequent ulcers and
resorption of bone. Such deformities can be worsened by careless
use of the hands. © WHO/TDR
Viral Diseases of the Nervous System
Poliomyelitis
Rabies
Viral encephalitis
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Poliomyelitis – Infantile Paralysis
 Poliovirus (Enteroviruses of picornaviridae)
 Transmitted by ingestion. 3 strains of polio virus
(1, 2, and 3)
 90% of cases asymptomatic
 Initial symptoms: Sore throat and nausea
 Viremia may occur; if persistent, virus can enter
the CNS; Selective destruction of motor neurons
and paralysis occurs in <1% of cases.
 Post-polio syndrome 30 y later: Crippling
deterioration of originally affected muscles due
to aging process of “replacement neurons”.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Poliomyelitis
Fig 22.11
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Prevention and Treatment
FDR, President from
1932 to 1945
 1955: Salk vaccine
(Inactivated – IPV)
 1961: Sabine vaccine (Live,
attenuated, oral – OPV).
Advantages ?
 OPV has caused all the
polio cases in the US
between 1980 and 1999
 2000: CDC recommends
new IPV (E_IPV) for routine
immunization
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Rabies Virus (of Rhabdoviridae)
 Zoonosis – Transmission from saliva of rabid animal
 Virus multiplies in skeletal muscles, then retrograde axonal
transport to CNS (encephalitis), then back out to periphery
(salivary glands etc.)
 Initial symptoms may include muscle spasms of the mouth
and pharynx and hydrophobia.
 Furious rabies: Animals
restless then highly
excitable.
 Paralytic rabies: Animals
unaware of surroundings.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Treatment and Prevention
 Highly fatal – only handful of people survived
 Preexposure prophylaxis: Human diploid
cells vaccine (HDCV) applied i.m.
 Postexposure treatment: Vaccine plus
immune globulin (HDCV applied i.m. on days
0, 3, 7, 14, and 28)
 Rodents and rabbits seldom get rabies. Dogs,
cats, cattle, skunks, racoons, etc. do 
Vaccination of pets! If necessary vaccination
of wild populations
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
ORV
genetically
engineered, vacciniarabies glycoprotein
(V-RG) virus has
proven to be orally
effective in raccoons.
CDC rabies prevention
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Arboviral Encephalitis
Fig 22.14
 Arboviruses are
arthropod-borne viruses
that belong to several
families.
 Prevention is by
controlling mosquitoes.
 The incidence of arboviral encephalitis increases in
the summer months, when mosquitoes are most
numerous.
 Diagnosis is based on serological tests.
 Control of mosquito vector is most effective way to
control encephalitis.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Notifiable Arboviral Encephalitis Infections
Encephalitis Reservoir
Mosquito
vector
Western
equine
Birds,
horses
Culex
Eastern
equine
Birds,
horses
Aedes,
Culiseta
St. Louis
Birds
Culex
California
West Nile
Small
mammals
Birds,
mammals
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Aedes
Culex,
Aedes
U.S.
distribution
Fungal and Protozoan NS Infections
Fungal:
Cryptococcosis or Cryptococcus neoformans
meningitis (airborne) – Primarily affects AIDS
patients ( .4%)
Soil fungus associated with pigeon and chicken
droppings.
Protozoan:
Trypanosomiasis: African sleeping sickness
Amebic Meningoencephalitis
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
African Sleeping Sickness or African
Trypanosomiasis
Caused by Trypanosoma brucei; vector: tsetse fly (daybiting)
 T.b. gambiense infection is chronic (2 to 4 years).
 T.b. rhodesiense infection is more acute (few months).
Antigenic variation allows for persistent evasion of the
immune system  Cyclic parasitemia (7-10 days)
Symptoms: chancre - intermittent fever – CNS invasion.
Without treatment: death
Treatment: Eflornithine
blocks an enzyme
necessary for the parasite
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Antigenic Variation in African Trypanosomiasis
Fig 22.16
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
T.b. gambiense
T.b. rhodesiense
Transmissible Spongiform Encephalopathies
Caused by prions – infectious proteins
Prions convert normal proteins into abnormal proteins
Post mortem sponge-like appearance of brain tissue
(large vacuoles in the cortex and cerebellum) due to
loss of nerve cells
Transmitted by ingestion or transplant or inherited.
Chronic and fatal
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Prions
Human Prion Diseases
 Creutzfeldt-Jakob Disease (CJD)
 Variant Creutzfeldt-Jakob Disease (vCJD)
 Gerstmann-Straussler-Scheinker Syndrome
 Fatal Familial Insomnia
 Kuru (of Fore, New Guinea)
Animal Prion Diseases
 Bovine Spongiform Encephalopathy (BSE)
 Chronic Wasting Disease (CWD)
 Scrapie
 Transmissible mink encephalopathy
 Feline spongiform encephalopathy
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings