26 Nervous System Infections

rare

Nervous system has no microbiome and their infections are very lethal

» threatens ability to move, feel, or even think

» bacterial infections of nervous system can be fatal, even with antibiotics

Thankfully, these infections are very [__] due to the presence of the blood-brain barrier in the CNS

Meningitis

Central Nervous System (CNS) » brain and spinal cord surrounded by meninges

Infections that occur here lead to inflammation:

• Encephalitis: inflammation of the brain

• [__]: inflammation of meninges

• Meningoencephalitis: infection of both brain and membranes

Peripheral Nervous System (PNS) » network of nerves throughout body

» motor neurons carry messages from CNS to body

» sensory neurons transmit sensations to the CNS

routes of invasion

Pathways that pathogens can travel through

in the CNS:

» blood (primary route) → eg. Poliovirus

» peripheral nerves → Rabies, Herpes-simplex virus (HSV), Varicella-zoster virus (VSV)

» location invasion through trauma

Typical [__] for bacteria is through infecting the meninges of the CNS

Bacterial meningitis

[__] » less common but more severe than viral meningitis

» common cold, followed by throbbing headache, fever, pain, and stiffness of neck and back

» nausea and vomiting

» deafness, confusion, loss of consciousness; coma may develop

» death may occur within hours

Spread: respiratory droplets ← highly contagious

» respiratory droplets travel in the bloodstream to the meninges

» high risk in military barracks. dormitories

Causative agent: Streptococcus pneumoniae » Gram-positive streptococci

Haemophilus influenzae* » Gram-negative rod

Neisseria meningitidis » Gram-negative diplococci

(*) » now new primary causative agent is S. pneumonia as H. influenzae has a vaccine now

Confirmed/Diagnosed: Lumbar puncture → inserting thin needing into lower back to collect cerebrospinal fluid

→ normal should have clear CSF; positive has cloudy CSF that can be Gram-stained for causative agent

Prevention: vaccine against [__]

» those exposed to [__] get treated Prophylactic antimicrobial medications upon exposure

» avoidance of crowds and increased handwashing

Treatment: broad-spectrum antibiotics given immediately while determining cause (Gram-negative or Gram-positive bacteria)

» case-fatality rate of untreated approaches 100%

» with treatment, fatality is 10-20%

Pneumococcal meningitis

[__] caused by Streptococcus pneumoniae » gram-positive diplococci that also causes otitis, sinusitis and pneumonia)

Progresses to [__] when S. pneumoniae enters bloodstream to travel to the meninges

» 10% case-fatality rate in adults, higher in infants, elderly, and immunocompromised

Treatment and prevention: Pneumococcal vaccine

→ conjugate vaccine (PCV13) against 13 serotypes

→ intended for children under 2, adults over 65 and those with certain health problems

» Capsular polysaccharide vaccine (PPsV23) effective against 23 serotypes for others

Meningococcal Meningitis

[__] is meningitis that is frequent in young adults (outbreaks in many crowded places)

» similar symptoms to Pneumococcal meningitis, except it has petechiae: presence of purplish spots on skin

» endotoxic shock can occur (due to its agent) and can lead to death in under 24 hours

Causative agent: Neisseria meningitidis » Gram-negative encapsulated diplococci

Treatment: antibiotics are effective → <10% mortality in treated populations; 70-90% in untreated

» Prophylactic/preventive antibiotics (rifampin) given to exposed individuals to prevent epidemics

Prevention: Meningococcal vaccine » recommended for ages 11-18 and those at increased risk ages 2-55

→ typically more frequent (again) in younger age so not a routine vaccine for everyone

Haemophilus meningitis

[__]: once caused meningitis in 1/200 children under 5 years; vaccine reduced incidence by 99%

» begins with mild cold symptoms; progresses to severe headache, fever, vomiting

» older children = stiff neck ; infants = bulging “soft spot” on their heads

» may rapidly progress to coma and death

» untreated fatality rate = 90% (5% with treatment)

» survivors have 10-30% lasting neurological damage → hearing loss, delayed language development, mental retardation, etc.

Causative agent: Haemophilus influenza type b » encapsulated, Gram-negative rod

Prevention: Hib vaccine (Haemophilus influenza type b vaccine) » routinely given to children

Treatment: antibiotics → cefotaxime, ceftriaxone, prophylactic rifampin for those exposed

Listeriosis

[__]: disease wherein elderly and immunocompromised (like pregnant women, as it can cross placenta) are more susceptible

Causative agent: Listeria monocytogenes » motile, Gram-positive rod.

» Psychrotroph bacterium that infects GI tract, then enters bloodstream

Spread: contaminated refrigerated foods → unpasteurized milk, meat, coleslaw, cantaloupe, chicken, soft cheese, and cream

Prevention: cook and reheat food well

» pregnant women and people at risk should avoid soft cheeses (unfermented cheese), refrigerated meat spreads, raw or smoked seafood

» bacteriophage mixture » lyses L. monocytogenes. spread on meats during production → increased safety 80-90%

Hansen’s Disease

[__]: “leprosy.”

» gradual pigmentation changes, numbness or tingling in hands and feet

» loss of hair, ability to sweat (affects glands), and sensation in the extremities

» muscle wasting and ulceration → loss of fingers and toes due to unnoticed or untreated injury

» severe cases: thickening of nose and ears, deep wrinkling of facial skin, collapse of supporting structure in nose

cell mediated response of patients causes variations of disease

» Tuberculoid leprosy → found in patients with strong response; limits spread

» Lepromatous leprosy → found in patients with weaker response, bacterial multiply and spread; more contagious form of leprosy

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Spread: direct contact, nasal secretions, from wild armadillos

→ armadillos are known harborers of agent; agents for study are grown inside armadillos

Prevention and Treatment: no proven vaccine or cure

» Treat with multi-drug regimen which only slow down disease and control their resistance

→ those with tuberculoid leprosy will take dapsone + rifampin for 6 months

→ those with lepromatous leprosy will also add clofazimine for 2 years

Mycobacterium leprae

Leprosy

Causative agent: [__] aerobic, acid-fast Gram-positive rod

» genome is fully sequenced and known to have many missing genes → why it’s pathogenic and relies on a host to multiply

» cannot be grown on artificial media; only on live cells

» generation time of ~12 days

» preferentially attacks and damages peripheral nerves and grows within macrophages

Clostridial diseases

Not a nervous system infection, but does cause paralysis

[__] caused by effects of powerful neurotoxins of pathogens

• Tetanus (lock jaw) » Clostridium tetani

  • due to neurotoxin tetanospasmin → spasmic paralysis

• Botulism » Clostridium botulinum

Botulism

[__] results in flaccid paralysis of muscles

Death comes from paralysis of respiratory muscles

Types based on their spread/mode of acquisition:

• Food-borne [__]: consumption of non-acidic home-canned foods

• Infant [__]: most common in US, infants being fed by honey which has endospores

→ babies’ stomachs are not as acidic as ours, in which our acidity can kill the endospore

• Wound [__]: due to abuse of injected drugs; contract [__] from contaminated needles

• Iatrogenic [__]: results when too much botox is injected; botox = botulinum toxin A

Treatment and prevention: intravenous antitoxin → neutralizes toxin

» babies placed on respirators with feeding support

» avoid feeding honey to babies under 1 year of age

Clostridium botulinum

Botulism

Causative agent [__]: anaerobic, Gram-negative, spore-forming rod

» causes all types of Botulism

» produces botulinum toxin: one of the most powerful poisons known (1g said to kill ~1million people)

→ toxin passes into bloodstream

→ blocks release of neurotransmitter at intramuscular junction; causes flaccid paralysis (muscle can’t contract)

Causes death in the paralysis of respiratory muscles

Viral meningitis

[__]: much milder than bacterial meningitis

» similar symptoms but less severe; causes little lasting damage

» CSF is clear

Causative agents: Coxsackle virus, Echovirus

Spread: fecal-oral route or respiratory drops → spread to bloodstream

Treatment: none available

Prevention: hand-washing, avoiding crowded swimming pools

» no vaccines

Viral Encephalitis

[__]: inflammation of the brain by viruses

» onset and abrupt fever, headache, and vomiting

» swelling of brain → Nervous system abnormalities and brain damage

→ results in disorientation, localized paralysis, seizures, and coma in patients

» 2-50% mortality rate, depending on infecting agent

Causative agent: Arboviruses (arthropod-borne viruses)

eg. West Nile Virus → West Nile DIsease

» can cross blood-brain barrier to cause inflammation of our brain there

Treatment and Prevention: no proven antiviral therapy or vaccine for humans

» vector control

Poliomyelitis

[__] results in paralysis that shrink our muscles and cause bones to not form properly

» respiratory muscles become paralyzed as well

Causative agent: Poliovirus

Spread: fecal-oral route (contaminated food or water)

» infects throat and intestinal tract and head to the bloodstream

» enters nervous system and attacks our motor nerves

Treatment and Prevention: no treatment

» supportive care, ventilator if required (back then had “iron lungs”)

» Vaccines

→ Salk (IPV) and Sabin (OPV) = super successful it completely eradicated [__] from US

→ gl