1. Ch 17
Infectious Diseases Affecting the Nervous System

2. 17.1/2 The Nervous System and Its Defenses
BBB advantages and disadvantages?
CNS vs. PNS
Skull or backbone fractures
Medical procedures
Along peripheral nerves
Blood or lymph
The BBB prevents passage of some materials (such as antimicrobial drugs) into CNS.
Phagocytic glia cell?
How do microbes enter the CNS ?
Normal Microbiota?
Compare to Fig 17.1 2

3. The inflammation of the brain is called
Meningitis
Neuritis
Encephalitis
Hydrocephalus
Answer: c

4. Highlight Disease: Meningitis
Meningitis can be caused by viruses, bacteria, fungi, and protozoa.
BACTERIAL MENINGITIS: Rarer but much more serious than viral meningitis. Can cause severe disease resulting in brain damage and death. Mortality rate  10%
Bacteria can grow in CSF in subarachnoid space.
Meningitis vs. encephalitis
Entrance to CNS facilitated by coinfection or previous infection with respiratory viruses
Viral meningitis much more common but milder. Usually resolves in 2 weeks. Mortality rate < 1%
an infection of the fluid around the spinal cord and the fluid that surrounds the brain. It often affects children and young adults, although persons of any age can become infected. 4

5. Spinal Tap (Lumbar Puncture) whenever suspicion of meningitis

6. Signs and Symptoms Headache Painful or stiff neck Fever
Nausea and vomiting
Photophobia = sensitivity to __________
Skin rashes may be present in specific types of meningitis.
Increased number of lymphocytes in CSF

7. Neisseria meningitidis: Meningococcal Meningitis
Gram-neg cocci, capsule
3-30 % of people are healthy naso-pharyngeal carriers
Threat in day-care centers and schools.
Mostly in children < 6 – 36 months; Sporadic outbreaks among young adults!
Vaccination recommended for college students
Begins as throat infection, typical rash  death may occur within a few hours of onset.

8. Meningococcal Rash
About half the children or adults with meningococcal meningitis have rash that does not fade
Exotoxins damage blood vessel walls  blood leaks into skin
Glass test (pressure test): Septicemic rash usually does not fade under pressure. (Not 100% reliable.) 8

9. Pneumococcal Meningitis: S. pneumoniae
Gram-positive diplococci, capsule
Typically associated with pneumonia, but may cause pneumococcal meningitis and septicemia.
70% of people are healthy nasopharyngeal carriers
Most common in children (1 month to 4 years)
Mortality: 30% in children, 80% in elderly
Increasing antibiotic resistance!

10. Haemophilus influenzae Meningitis (Hib)
Gram-negative, pleomorphic coccobacilli, capsule
Common part of normal throat microbiota
Vaccination!
Slide 1. Haemophilus influenzae These small, pleomorphic gram-negative bacteria range in shape from round (cocci) to short, thin rods (bacilli); hence the bacteria are called “coccobacilli.” In specimens from patients with pneumonia caused by Haemophilus influenzae, both neutrophils and bacteria are usually plentiful. However, if examination of the slide is not thorough, the coccobacilli may be inconspicuous in the background of pink-staining mucus. Other organisms, such as Eikenella corrodans or Bacteroides species, are also pleomorphic gram-negative coccobacilli; but they rarely cause pneumonia.
Fastidious  needs factors in blood (genus name!). Species name is misnomer.
Mostly in children under age 4 (especially around 6 month of age. Why?)
Also causes pneumonia, otitis media, epiglottitis 10

11. Listeriosis – Listeria monocytogenes
Gram-positive
Reproduce inside phagocytes.
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
Primary reservoir: Soil and water

12. Worker in day-care center became ill with fever, rash, headache, and abdominal pain. Patient had precipitous clinical decline and died on 1st day of hospitalization. Diagnosis confirmed by Gram staining of CSF (see image on the left)
Can you identify infections that could cause these symptoms?
Listeriosis
Haemophilus influenza Meningitis
Meningococcal Meningitis
Pneumococcal Meningitis

13. Bacterial Meningitis: Review
Three major causes:
Haemophilus influenzae
Neisseria meningitidis
S. pneumoniae
 50 opportunistic bacterial species can cause meningitis (L. monocytogenes, S. pyogenes, S. aureus)
Symptoms: Fever, headache, stiff neck, followed by nausea and vomiting  convulsions, coma, shock, and death
Immediate Antibiotics then diagnosis by Gram stain or latex agglutination of CSF
Not very contagious  spreads by direct close contact with discharge from nose/throat of infected person.
Bacterial meningitis is usually more severe than the viral meningitis. Bacterial meningitis can have serious after-effects, such as brain damage, hearing loss, limb amputation, or learning disabilities. The leading causes of this type of meningitis are the bacteria:
Streptococcus pneumoniae and
Neisseria meningitidis (usually referred to as "meningococcus" and the disease it causes as meningococcal disease) 13

14. Cryptococcosis: Cryptococcus neoformans
Fungal Meningitis
Cryptococcosis: Cryptococcus neoformans
Valley fever  meningitis
Soil fungus associated with pigeon and chicken. Aerosolization of dried up contaminated droppings.
Transmission: Respiratory route; spreads through blood to the CNS
Mortality up to 30% – Primarily affects AIDS patients
Diagnosis: Serology to detect cryptococcal antigens in serum or CSF

15. Cryptococcus neoformans
Figure 1. The C. neoformans infectious cycle. C. neoformans resides in the environment and has been found associated primarily with pigeon droppings and Eucalyptus trees. It is thought that infection of humans generally occurs when basidiospores produced by C. neoformans in nature are inhaled into the lungs. Inhaled spores are deposited into the alveoli and germinate to establish a dormant infection or disseminate to the central nervous system. Once dissemination has occurred, viable cells can be cultured from the cerebrospinal fluid of affected individuals.

16. Highlight Disease: Polio
aka: Poliomyelitis or Infantile Paralysis
Causative agent: Poliovirus (Enteroviruses of Picornaviridae)
Transmitted by ingestion. 3 strains of polio virus
90% of cases asymptomatic
Initial symptoms: Sore throat and nausea
Viremia may occur; if persistent, virus can enter CNS  = “neurotropic”

17. Selective destruction of motor neurons and paralysis occurs in <1% of cases.
Rare bulbar poliomyelitis affects brain stem (resp. regulatory center etc.)

18. Post-polio syndrome (PPS) 30 y later in 25% to 50% of affected people: Crippling deterioration of originally affected muscles due to aging process of “replacement neurons”.

19. Prevention and Treatment
1955: Salk vaccine – IPV ______________
1961: Sabine vaccine – OPV ______________ Advantages ?
OPV has caused all the polio cases in the US between and 1999
2000: CDC recommends new IPV (eIPV) for routine immunization
FDR, President from 1932 to 1945
US Annual Incidence
Advantages: cheaper, no injection, better local immunity and can spread from person to person.
Franklin D. Roosevelt was the 32nd President of the United States. Not only did he serve an unprecedented four terms in office, but he was also the first president with a significant physical disability. FDR was diagnosed with infantile paralysis, better known as polio, in 1921, at the age of 39. Although dealing with this crippling disease was difficult, many believe that his personal struggles helped shape FDR, both as a man and as a president.
eIPV — Poliovirus Vaccine Inactivated Enhanced Potency 19

20. Acute Encephalitis
Almost always viral, e.g. Arboviruses: _______________ viruses that belong to several families.
Symptoms: Brain symptoms with acute fever and rash
Prevention by mosquito control.
Sentinel animals, e.g.: caged chickens
Diagnosis based on serological tests
Symptoms from subclinical to coma and death
Sentinel animal: An animal deliberately placed in a particular environment to detect the presence of an infectious agent, such as a virus.

21. Notifiable Arboviral Encephalitis Infections
Reservoir
Mosquito vector
U.S. distribution
Western equine
Birds, horses
Culex
Eastern equine
Aedes, Culiseta
St. Louis
Birds
California
Small mammals
Aedes
West Nile
Birds, mammals
Culex, Aedes

22. Transmissible Spongiform Encephalopathies: TSEs
Nervous System Diseases Caused by Prions
Transmissible Spongiform Encephalopathies: TSEs
Prions convert normal proteins into abnormal proteins
Post mortem sponge-like appearance of brain tissue large vacuoles in cortex and cerebellum due to loss of neurons
Chronic and fatal
Transmitted by ingestion or transplant or inherited. 22

23. Prions Typical diseases Sheep scrapie Creutzfeldt-Jakob disease Kuru
Typical diseases
Sheep scrapie
Creutzfeldt-Jakob disease
Kuru
Bovine spongiform encephalopathy 23

24. Preventing Prion Diseases
Surgical instruments sterilized by
NaOH
Extended autoclaving at 134C

25. Rabies Virus (of Rhabdoviridae)
Zoonosis – Transmission from saliva of rabid animal
Virus multiplies in skeletal muscles retrograde axonal transport to CNS (encephalitis)  back out to periphery, salivary glands etc.
Initial symptoms may include muscle spasms of the mouth and pharynx and hydrophobia.
Furious rabies: restless then highly excitable.
Paralytic rabies: unaware of surroundings.

26. Prevention and Treatment
Highly fatal – only handful of people survived
Preexposure prophylaxis: Human diploid cells vaccine (HDCV) applied i.m.
Postexposure prophylaxis (PEP):
Vaccine (HDCV, applied i.m. on days 0, 3, 7, 14, and 28)
Human rabies immune globulin (RIG)
HDCV = Human Diploid Cell Vaccine
2011: Jeanna Giese graduates from college

27. Rodents and rabbits seldom get rabies
Rodents and rabbits seldom get rabies. Dogs, cats, cattle, skunks, raccoons, bats, etc. do  Vaccination of pets! If necessary vaccination of wild populations
ORV
The vaccinia - rabies glycoprotein (VRG) recombinant virus vaccine (Raboral®) This vaccine consists of a partially attenuated recombinant vaccinia virus (Copenhagen strain) with a gene encoding for rabies virus glycoprotein (2).
Long Island raccoons help themselves to rabies vaccine at a Cornell bait station.
The oral rabies vaccine, manufactured by Merial Inc.,
consists of a sachet or plastic packet containing the
Raboral V-RG® rabies vaccine. The vaccine sachets
are either coated in fishmeal crumbs or encased inside
fishmeal polymer baits about the size of a matchbox.
When a raccoon bites into a bait, the sachet
ruptures, allowing the vaccine to make contact in the
animal’s mouth and throat. Animals that have contact
with an adequate dose of the vaccine develop an
immunity to rabies. As the number of vaccinated animals
in the population increases, the ability to transmit
the disease in the raccoon population decreases,
creating a barrier to stop the spread of the raccoon
variant.
rabies prevention: bait station 27

28. Reported Cases of Rabies in Animals