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Transcript
Microbial Diseases of the
Nervous System
Lesson objectives
– List the anatomical features and the defenses of the nervous
system.
– List the methods of entry of microorganisms into the
nervous system.
– Discuss the important agents of bacterial meningitis; the
symptoms, diagnosis, prevention and treatment.
– Briefly discuss neonatal meningitis.
– Discuss the epidemiology and prevention of tetanus and
botulism.
– List the important viral diseases of the nervous system.
Human Central Nervous system: Brain
and Spinal Cord
Basic layout: Brain and spinal cord are composed of cells
called neurons. The structures are surrounded by three
protective tissues called meninges: From outside to inside:
1) Dura mater: Thick and leathery layer.
2) Subarachnoid space: This is the area bathed by
cerebrospinal fluid (csf). This is the specimen most often
collected to diagnose infections of the nervous system.
3) Pia mater: Thinner layer right next to the brain.
Blood/brain barrier
• Capillaries that feed the central nervous system are
selectively permeable to certain substances. Under
normal circumstances, the meninges (csf) only receive
essential substances from the blood (e.g. O2, water,
sugars, amino acids). Larger materials (e.g. antibodies,
cells, many drugs) do not cross.
• The CNS is “immunologically privileged.” This means,
only certain types of cells carry out immune functions.
There is minimal phagocytosis, and normally, little to
no inflammation.
Why doesn’t the Central Nervous System
mount an aggressive response to non-self?
Normal microbes found in the Central
Nervous System
Any organisms (bacteria, fungi, protozoa, or viruses)
found in nerve tissue or cerebrospinal fluid is
considered a pathological condition.
Meningitis—a life threatening
contagious disease
• -itis: inflammation, so meningitis is an
inflammation of the meninges.
• Meningitis can be immediately life threatening
because it represents increased intracranial
pressure. The function of csf is to cushion the
brain and spinal cord, so edema in the
meninges can damage specific brain functions.
Symptoms of (bacterial) meningitis
•
•
•
•
•
•
Sudden onset
Severe headache
Very stiff neck
High fever
Nausea/vomiting
Disorientation/confusion/seizures
Diagnosis of meningitis
Time is crucial, so the doctor collects a sample of csf.
Bacterial meningitis has certain diagnostic
characteristics that can be detected immediately.
Indicator
Reference value—
normal csf
Bacterial meningitis
Color and appearance
Transparent, colorless
Cloudy, yellow or beige
csf pressure
90-180 mm Hg
Greater than 180 mm
Protein level
20-50 mg/100 ml
Elevated (sometimes
>1000)
Glucose level
40-70 mg/100 ml
decreased
Cells
Few, all monocytes
Abundant neutrophils,
lymphocytes, etc.
Explanations of abnormal findings
• Appearance: cloudiness may be due to increased
cells or organisms.
• Color may be red (intracranial hemorrhage or
traumatic puncture), or yellow (jaundice).
• Protein: elevation due to inflammation, presence
of antibodies, or bacterial products.
• Glucose: decrease due to increased metabolism
or use of glucose reserves by pathogens.
Risk factors for meningitis
• Extreme age: neonates and elderly.
• Immunocompromised persons
(chemotherapy, AIDS)
• Severe alcohol/drug abuse
• Recent cranial surgery
Causative agents for meningitis:
Most common: Neisseria meningitidis: Gram negative
cocci, usually in pairs, intracellular and extracellular.
Forms capsules, which prevent phagocytosis.
In addition to other meningitis symptoms, causes
petechiae: small patches of localized bleeding which
appear as red blotches.
Can be prevented with a vaccine. Recommended for
persons living in close quarters (military, dorm residents)
• Streptococcus pneumoniae: Gram positive
cocci in pairs.
• Mostly seen with elderly or immunocompromised patients.
• Similar symptoms as seen with N. meningitidis
but no petechiae.
• Also avoids host defenses by producing
capsules. Preventable with vaccine
There are many other causes of meningitis. The
more common ones can be classified by population:
Population
Most common pathogens causing meningitis
Newborns (age 0-4 weeks)
E. coli, Streptococcus agalactiae (Group B strep),
Listeria monocytogenes
Small children
Hemophilus influenzae (rare since vaccine developed in
1988). Streptococcus pneumoniae
Children-young adults
Neisseria meningitidis
Over 50 years old
Streptococcus pneumoniae, Listeria monocytogenes
Immunocompromised
All of the above, plus fungi:
Cryptococcus neoformans (yeast), Mycobacterium
species
Recent neurosurgery or head
trauma
Staphylococcus aureus, coagulase negative staph, skin
microbes
How do these populations contract
meningitis?
Population
Newborns (age 0-4 weeks)
Children-young adults
Recent neurosurgery or head
trauma
How did they get infected with agents of meningitis?
Encephalitis—inflammation of the brain
• Usually viral. Includes West Nile Virus.
• Often spread by arthropods (mosquitoes)
• Slower onset than meningitis. Symptoms include flu-like
symptoms, which may resolve on their own.
• Severe symptoms include nausea, confusion, seizures,
personality changes, hallucinations.
• No known treatment. Diagnosed by detecting antibodies
or detecting viral antigens in csf.
• Prevention is aimed at controlling mosquito populations.
Rabies
• Viral brain infection acquired from mammals. Infection
occurs from animal bites. The virus is shed in the
animal’s saliva and enters through the bloodstream.
• Rabies has a 3-12 week incubation period. During this
time, the victim may be infectious, but symptoms have
not appeared.
• Symptoms: flu-like at first, followed by “twitching,”
impaired brain function, extreme thirst compounded
with difficulty swallowing (hydrophobia), and death.
• Vaccines for animals—each year. Humans treated with
gamma globulin (IgG) immediately, followed by four
doses of vaccine given over 2 weeks.
Bacterial neurotoxins
Clostridium tetani tetanus
Clostridium botulinum botulism
Both organisms are Gram positive rods, form
endospores, and are obligate anaerobes.
Tetanus: infection occurs through puncture
wounds containing endospores.
• Risk factors: Anyone exposed to a puncture
wound where animal droppings may be
(farms, horse trails, even if animals have not
been around recently).
• Symptoms: toxin causes rigid paralysis. Death
occurs from suffocation (“lockjaw” prevents
mouth from opening).
• Vaccine—tetanus toxoid. Given every 10 years
and after exposure.
Botulism
• Infection can occur through a wound (like
tetanus). More often, disease occurs through
ingestion of toxin (botulin).
• Causes: improperly canned foods (especially
non-acidic vegetables), infused oils (especially
root vegetables).
• Symptoms: flaccid paralysis: weakness, double
vision, impaired gait, slurred speech.
• Paralysis eventually leads to impaired
breathing (ventilator required).
• Toxin is extremely virulent. Most toxic
substance produced by a living organism (to
humans).
• Prevention: vaccine (for workers), culinary
education on how to prepare/preserve food.