INFECTIOUS DISEASES – NERVOUS SYSTEM
• Microglial cells display phagocytic activity
NERVOUS SYSTEM AND ITS DEFENSES
Two component parts of the NS
• Central nervous system (CNS)
o Brain and spinal cord
• Peripheral nervous system (PNS)
o Nerves emanating from the brain and spinal cord to
sense organs and to the periphery of the body
Important functions of the NS
• Sensory
o Sensory receptors at the ends of peripheral nerves
o Generate nerve impulses transmitted to the CNS
• Integrative
o Translates impulses into sensation or thought
o Drives motor function
• Motor
o Involves muscles and glands
Brain and spinal cord
• Made up of neurons surrounded by bone
o Brain inside the skull
o Spinal cord inside the spinal column
• Brain surrounded by meninges
o Dura mater
o Arachnoid mater
o Pia mater
Cerebrospinal fluid (CSF)
• Cerebrospinal fluid (CSF)
o Fills the subarachnoid space
o Clear, serum-like fluid
o Provides nutrition to the CNS
o Provides a liquid cushion for the brain and spinal cord
• Meningitis: infection of the meninges
Structure of the Peripheral Nervous System
• Ganglia: swelling in the nerve where cell bodies of neurons
congregate
• Nerves: bundles of neuronal axons that receive and
transmit nerve signals
o Axons and dendrites of adjacent neurons
communicate over a synapse
o Neurotransmitters released from one cell on the next
cell in the synapse
The nervous system and its defenses
• Defenses of the NS are mainly structural
o Bony casings of the brain and spinal cord protect them
from traumatic injury
o CSF serves as a cushion against impact
o Blood-brain barrier
Blood-Brain Barrier
• Cells that make up the walls of blood vessels around the
brain allow very few molecules to pass through
o Freer passage of ions, sugars, and other metabolites in
other areas of the body
• Prohibits most microorganisms from passing into the CNS
• Drugs and antibiotics are difficult to introduce into the CNS
when needed
Immune privilege of the CNS
• A different or partial immune response when exposed to
immunologic challenge
• Functions of the CNS are vital for the life of an organism and
temporary damage from a “normal” immune response
could be detrimental
• Cells in the CNS express lower levels of MHC antigens
• Lower quantities of complement proteins
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Specialized immune cells in the CNS
• Brain macrophages exist in the CNS
• Activity of both types of cells is less than that of phagocytic
cells elsewhere in the body
NORMAL BIOTA OF THE NERVOUS SYSTEM
Normal biota of the NS
• It is still believed that the CNS and PNS lack normal biota of
any kind
o Finding microorganisms of any type in these tissues
represents a deviation from a healthy state
o Certain viruses live in a dormant state in the nervous
system between episode of acute disease
– Example: herpes simplex virus
– Not considered normal biota
Human Microbiome Project (HMP)
• Information from the HMP is revealing a potential link
between the gut microbiome and the NS
• Gut microbiota may induce CNS autoimmunity
o Appear to cause changes in the brain chemistry and
behavior
o Phenomenon known as the gut-brain axis
NS DISEASES CAUSED BY MICROORGANISMS
1) Meningitis
• Inflammation of the meninges
• Anatomical syndrome
o Different microbes cause meningitis, and produce a
similar constellation of syndromes
o Noninfectious causes of meningitis exist as well, but are
less common
• Serious forms of acute meningitis are caused by bacteria
• Entrance into the CNS is facilitated by co-infection or
previous infection with respiratory viruses
When meningitis is suspected
• Lumbar puncture to obtain CSF
• Gram stain and/or culture of CSF
• Begin treatment with broad-spectrum antibiotics with a
shift in tx after a diagnosis has been confirmed
Signs and Symptoms of Meningitis
• Meningitis has the following typical symptoms, regardless of
the cause:
o Photophobia
o Headache
o Painful or stiff neck
o Fever
o Increased WBC in CSF
o Certain microorganisms may cause additional
characteristic symptoms
Further details of meningitis
• It can be shown to be acute or chronic:
o Some microorganisms are likely to cause acute
meningitis, others cause chronic meningitis
• In healthy people. It is difficult for microorganisms to reach
the nervous system
o Successful microorganisms are specific. Severity factor
A) Neisseria meningitidis
• Gram-negative diplococci lined-up side by side
• Also known as the meningococcus
• Associated with epidemic forms of meningitis
• Causes the most serious form of acute meningitis
• Responsible for 14% of all meningitis cases
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Dissemination of the Meningococcus from a nasopharyngeal
infection
N. meningitidis Pathogenesis and Virulence Factors
• Meningococcemia: Rare
o High mortality rate
• Endotoxin acts as a potent WBC stimulator
o Damage to blood vessels caused by cytokines
released by WBC leads to vascular collapse,
hemorrhage, and crops of red or purple lesions called
petechiae on the trunk and appendages
N. Meningitidis Oxidase test
B) Streptococcus pneumoniae
• Also referred to as the pneumococcus
• Causes the majority of bacterial pneumonias
• Most frequent cause of community-acquired meningitis
• Does not cause petechiae
• Most likely to occur in patients with underlying susceptibility
• Carriage rates exceed 30% in some populations
• Small, gram-positive, flattened coccus that appears in end-
to-end pairs
• Distinctive appearance in a Gram stain of CSF
• Has a polysaccharide capsule that protects against
phagocytosis
• Produces an alpha-hemolysin and hydrogen peroxide,
both of which have been shown to induce damage in the
CNS
• Two vaccines are available
C) Haemophilus influenzae
• Gram-negative coccobacillus Causes one of the most
severe forms of meningitis in humans
• Often called "Hib" because serotype B is the most common
cause of infection Vaccination has reduced asymptomatic
carriage rates and has virtually eliminated Hib in the United
States
D) Listeria monocytogenes
• Gram-positive, ranges in morphology from coccobacilli to
long filaments in palisade formation
• Does not produce capsules or endospores
• Has 1 to 4 flagella
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• Not fastidious, resistant to cold, heat, salt, pH extremes, and
bile
• Grows inside host cells, moves directly from an infected cell
to an adjacent healthy cell
Listeriosis
• Mild or subclinical in healthy adults
• Causes meningitis and septicemia in the elderly,
immunocompromised, fetuses, and neonates
• Bacterium can cross the placenta and cause premature
abortion and fetal death
• Associated with contaminated dairy products, poultry, and
meat
E) Cryptococcus neoformans
• Fungus that causes chronic meningitis with a gradual onset
of symptoms
• In AIDS patients: fast onset and acute disease
• Widespread in human habitats
• Spherical to ovoid shape with a large capsule
• Transmitted in bird droppings
D) Coccidioides
• "Valley Fever" Fungus with a distinctive morphology:
o 25°C: moist white to brown colony with abundant,
branching, septate hyphae
o 37°C to 40°C: parasitic phase, small spherule
• True systemic fungal infection of high virulence
• Genetic susceptibility gives rise to more serious disease
Coccidioides Transmission and Epidemiology
• Occurs endemically in natural reservoirs
• C. immitis causes disease in California; C. posadasii is found
in northern Mexico, Central and South America, and the
American Southwest, especially Arizona
E) Viral Meningitis
• Four of five meningitis cases are caused by one of a wide
variety of viruses
• Aseptic meningitis: viral meningitis is assumed when a
patient shows symptoms of meningitis but no bacteria or
fungi are found in CSF
• Majority of cases in children
• 90% caused by enteroviruses
• HSV-2 is sometimes known to cause meningitis; other
herpesviruses (HHV-6, HHV-7, and HHV-3) and HIV can
manifest as meningitis as well
• Generally milder than bacterial or fungal meningitis –
usually resolved in 2 weeks; mortality rate is less than 1%
Meningitis Disease Table
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 Neonatal and Infant Meningitis Disease Table

3) Rabies
• Slow, progressive zoonotic disease characterized by fatal
encephalitis
• Furious rabies
o Agitation, disorientation, seizures, twitching
o Hydrophobia
• Dumb rabies
o Patient is paralyzed, disoriented, stuporous
• Both forms progress to a coma phase:
o Death results from cardiac or respiratory arrest

Structure of the Rabies Virus

2. Neonatal and Infant Meningitis

• Usually the result of an infection transmitted by the mother
in utero or during passage through the birth canal
• As more premature babies survive, rates of neonatal
meningitis increase
• Morbidity has increased but mortality rates have
significantly declined
• Two most common causes are Streptococcus agalactiae
and Escherichia coli
• Listeria monocytogenes is also found frequently in neonates
Rabies Transmission and Epidemiology
A) Streptococcus agalactiae • Reservoirs: wild mammals such as canines, skunks,
• Lancefield group B streptococci raccoons, badgers, cats, and bats
• Colonizes 10 to 30% of female genital tracts o Spread to domestic animals and humans through
• Most frequent cause of neonatal meningitis bites, scratches, and inhalation of droplets
• Treated with IV penicillin G, sometimes supplemented with • Estimated 35,000 to 50,000 human cases per year
an aminoglycoside worldwide
o United States: 6000 to 7000 animal cases per year
B) Escherichia coli o 2004: transmission of rabies through donated organs
• K1 strain is second most common cause of neonatal and tissues
meningitis o Transmission through cornea implants
• Most common in premature babies
• Prognosis is poor: Rabies Prevention and Treatment
o 20% mortality rate • Imperative that treatment begins after exposure and
o Brain damage among those who survive before symptoms develop
• Usually transmitted by the mother's birth canal • Passive and active postexposure immunization
• Vaccination of domestic animals, veterinarians, animal
C) Cronobacter sakazakii handlers, laboratory personnel, and travelers
• Found mainly in the environment and can survive very dry • Vaccine incorporated into bait to treat wild animals
conditions
• Implicated in outbreaks of neonatal and infant meningitis
through contaminated powdered infant formula
• Cases of Cronobacter meningitis are rare Mortality rates
can reach 40%

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Rabies Disease Table Stages of Infection and Pathogenesis of Poliomyelitis

4) Poliomyelitis
• Acute enteroviral infection of the spinal cord
o Can cause neuromuscular paralysis
• Signs and symptoms:
o Fever, headache, nausea, sore throat, myalgia
o Neurotropic: infiltrates the motor neurons of the
anterior horn of the spinal cord
o Also attacks the spinal ganglia, cranial nerves, and
motor nuclei
• Paralytic disease Polio Prevention
o Various degrees of flaccid paralysis of the muscles of • Humans are the only known reservoir
the legs, abdomen, back, intercostals, diaphragm, • Vaccination as early in life as possible with 4 doses, starting
pectoral girdle, and bladder at 2 months of age
• Bulbar poliomyelitis o IPV: developed by Salk in 1954, used in the United
o Brain stem, medulla, and cranial nerves are affected States
o Loss of control of cardiorespiratory regulatory centers o OPV: developed by Sabin in the 1960s
• Post-polio syndrome
o Progressive muscle deterioration in 25% to 50% of Poliomyelitis Disease Table
patients decades after the initial infection

Typical Structure of a Picornavirus

5) Tetanus
• Clostridium tetani:
o Common resident of soil and Gl tracts of animals
o Gram-positive, endospore-forming rod
o Endospores are only produced under anaerobic
conditions

Neonatal Tetanus
• Kills approximately 35,000 newborns each year
• Majority of infections are a direct result of unhygienic
practices during childbirth in developing countries

Tetanospasmin
• Neurotoxin
• Binds to target sites on peripheral motor neurons on the
spinal cord, brain, and sympathetic nervous system
• Blocks inhibition of muscle contraction, causing muscles to
contract uncontrollably, resulting in spastic paralysis
• Death results from paralysis of respiratory muscles and
respiratory arrest

Tetanus Prevention
• One of the world's most preventable diseases
• Vaccination with the tetanus toxoid, usually in combination
with diphtheria and pertussis toxoids
• Vaccinations given to children under 7 years

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 • Td booster should be given every 10 years thereafter
• Toxoid should also be given to injured persons who have
never been immunized, have not completed the series, or
whose last booster was received more than 10 years
previously
• Vaccine can also be given with passive TIG

Tetanus Disease Table

6) Botulism
• Intoxication: caused by an exotoxin
• Associated with eating poorly preserved foods
• Three major forms:
o Food-borne botulism
o Infant botulism
o Wound botulisms

Botulinum Toxin
• Toxin travels from the bloodstream to the neuromuscular
junctions of skeletal muscles
• Prevents the release of acetylcholine, resulting in flaccid
paralysis
• Utilized by doctors to treat uncontrolled muscle spasms,
migraine headaches, and other conditions
o Also used cosmetically

Botulism Disease Table

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