On surface prevent activation of
complement and allow microbe to escape phagocytosis

How Microobes Enter the Nervous System

• Skull or spinal fractures
• Medical procedures
• Along peripheral nerves
• Blood or lymph

Microbial Diseases of the Nervous System

• Bacteria can grow in the cerebrospinal fluid in thesubarachnoid space of the CNS. 
• The blood brain barrier (capillaries) prevents passage of some materials (such as antimicrobialdrugs) into the CNS. 
• This fluid may be sampled using a rocedure called a
lumbar puncture (spinal tap). 

Bacterial Diseases of the NS

• The following group of diseases are all caused by bacteria.
• If treatable, antibiotics may be effective.

Meningitis

Inflammation of meninges.

Encephalitis

Inflammation of the brain.

Bacterial Meningitis

• Fever, headache, and stiff neck
• Followed by nausea and vomiting
• May progress to convulsions and coma
• Diagnosis by Gram stain or agglutination test of CSF
• Meningitis is a medical emergency and can be highly contagious.

Bacterial Meningitis Treatment

Treatment with antibiotics can be effective; which

drug depends on the organism involved.

Haemophilus influenzae

• Occurs mostly in children (6 months to 4 years).
• Gram-negative aerobic bacteria, normal throat microbiota
• Caused most often by one strain, identified as capsule antigen type b, Haemophilus influenzae type b or Hib
• Prevented by Hib vaccine

• N. meningitidis, common name meningococcus
• Gram-negative aerobic cocci, capsule
• 10% of people are healthy nasopharyngeal carriers
• Begins as throat infection, often accompanied by a petechial rash
• The only meningitis with a rash
• Vaccination recommended for college students.

Petechial rash of meningococcal disease

A petechial rash is caused by hemorrhages under the skin.

Streptococcus pneumoniae

• Streptococcus pneumoniae (common name pneumococcus), a Gram-positive encapsulated  diplococcus
• 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 vaccination, now recommended for infants as well as the elderly

*Listeriosis

• Listeria monocytogenes
• Gram-positive aerobic rod
• Usually causes mild flu-like disease in adults but can enter the CNS and cause meningitis, with a mortality rate as high as 50%
• Usually foodborne; it can be transmitted to fetus where it may cause abortion, stillbirth, or meningitis in the infant.

• An important factor in the virulence of Listeria is that it can reproduce in phagocytes.

*Tetanus

• Clostridium tetani
• Gram-positive, endospore-forming, obligate anaerobe
• Grows in deep wounds.
• Tetanospasmin (a toxin) blocks relaxation pathway in muscles, causing constant muscle contraction. 

• Infants in developing countries often get tetanus through an infected umbilicus.

Tetanus Treatment

• Prevention by vaccination with tetanus toxoid (DTP) and booster (dT).
• Treatment with tetanus immune globulin.

*Botulism

• Clostridium botulinum
• Gram-positive, endospore-forming, obligate anaerobe
• Intoxication comes from ingesting botulinal toxin.
• Botulinal toxin blocks release of neurotransmitter causing flaccid paralysis.
• Botox is a form of botulism toxin that is used cosmetically; it also has some applications in controlling neurological disorders such as cerebral palsy.

• Wound botulism results from growth of C. botulinum in wounds.

• Infant botulism results from C. botulinum growing in intestines.

*Botulism Source of Infection

• Sources of infection occur most often in canned foods that have been inadequately heated during processing.
• Home-canned foods are frequently to blame.

Botulism Prevention

• Proper canning
• Chemicals can prevent endospore germination in sausages.

• Treatment: Supportive care and antitoxin.

Botulism in infants

• Infant botulism is characterized by constipation and muscle weakness;
• Occurs through ingestion of spores which germinate and produce toxin in the gut.
• Honey has been implicated in infant botulism.

Leprosy (Hansen’s Disease)

Mycobacterium leprae

• Acid-fast rod that grows best at 30°C.
• Grows in peripheral nerves and skin cells.
• Transmission requires prolonged contact with an infected person.

• One of the first signs of leprosy is loss of pigment in the skin, along with numbness.

Leprosy (Hansen’s Disease)

• Tuberculoid (neural) form: Loss of sensation in skin areas; positive lepromin test
• Lepromatous (progressive) form: Disfiguring nodules over body; negative lepromin test

• Poliomyelitis
• Salk Polio Vaccine
• Rabies
• Arboviral Encephalitis

 

Poliovirus

• Transmitted by ingestion
• Initial symptoms: Sore throat and nausea
• Viremia may occur; if persistent, virus can enter the CNS; destruction of motor cells and paralysis occurs in <1% of cases.
• Prevention is by vaccination (enhancedinactivated polio vaccine).

VIRAL DISEASES of the Nervous System:

Salk Polio Vaccine

• In 1954, the Salk vaccine was tested nationwide, with mass inoculations of school children.
• A million children participated in the tests, making it the largest clinical test of a drug or vaccine in medical history.

Polio Vaccines

• The Sabin vaccine (attenuated virus) is administered orally, which enhances its use in areas where trained medical personnel may not be available to give inoculations.
• However, there is a small risk of paralytic polio resulting from the oral vaccine, so it is no longer recommended for routine use in the U.S.

Rabies

• Transmitted by animal bite.
• Virus multiplies in skeletal muscles, then in brain cells, causing encephalitis.
• Initial symptoms may include muscle spasms of the mouth and pharynx, and hydrophobia.
• Rabies is notifiable in both humans and animals.

Furious rabies

Animals are restless then highly excitable.

Paralytic rabies

Animals seem unaware of surroundings

Preexposure prophylaxis

Injection of human cell vaccine.

Postexposure treatment

Vaccine plus immune globulin.

Control of Rabies

• Rabies is controlled largely through licensing (requiring vaccination) of domestic pets, both cats and dogs.
• Distribution of oral vaccine in baits helps control rabies in wild animals.

Arboviral Encephalitis

• Viruses that are transmitted by arthropods are called arboviruses, where “arbo-” stands for “arthropod-borne”.
• Arboviruses are arthropod-borne viruses that belong to several families.
• Prevention is by controlling mosquitoes
• Usually characterized by fever, headache, and
• altered mental status ranging from confusion to coma.
• In areas where arboviruses are endemic, many people are immune as the result of subclinical or symptomatic disease.
• Birds are the most common reservoir, but other nimals may also harbor arboviruses.

 

 

FUNGAL DISEASES of the Nervous System

There is one fungal disease of the nervous

system, although it is possible for other fungal

pathogens to gain access to nervous tissue and

cause disease.

Cryptococcus neoformans

• Soil fungus associated with pigeon and chicken droppings.
• Transmitted by the respiratory route; spreads through blood to the CNS.
• Mortality up to 30%.
• Treatment: Amphotericin B and flucytosine.

• Pigeon droppings provide ideal conditions for growth of Cryptococcus

•  

  Cryptococcus maydisseminate and cause skin lesions prior to invading the CNS.

PROTOZOAL DISEASES of the Nervous System

• African Trypanosomiasis (“sleeping sickness”)
• Amebic Meningoencephalitis

 

African Trypanosomiasis (“sleeping sickness”)

• Trypanosoma brucei gambiense infection is chronic (2 to 4 years).
• T. b. rhodesiense infection is more acute (few months).
• Transmitted from animals to humans by tsetse fly.
• Prevention: Elimination of the vector.
• Parasite evades the antibodies through antigenic variation (see next slide).

Amebic Meningoencephalitis

• Naegleria fowleri infects the nasal mucosa (typically during swimming) and then penetrates the brain.
• The fatality rate is nearly 100%, death occurring soon after the appearance of symptoms.
• Acanthameba causes a granulomatous encephalitis, which is chronic and slowly progressive.

PRION DISEASES of the Nervous System

• Prions are proteins that are found in all cells of the body; they are especially abundant in brain tissue.

• Diseases occur when prions change shape. It is not known what causes this to occur, but there is some evidence that earlier viral infections may precipitate the change from ormal prions to abnormal ones that cause disease.

Prions

• Infectious proteins
• Inherited and transmissible by ingestion, transplant, and surgical instruments
• Extremely resistant to heat; even autoclaving cannot halt infectivity

Replication of Prions

• Prions normally occur on all cells of the body, and are especially abundant on nerve tissue (brain)
• PrPC: Normal cellular prion protein, on cell surface
• PrPSc: Scrapie protein; accumulates in brain cells forming plaques and vacuoles (holes in the brain tissue, giving it a spongy appearance.

Inherited Prion Diseases

• Creutzfeldt-Jakob disease (CJD)
• Can be misdiagnosed as dementia or Alzheimer’s disease
• Fatal familial insomnia
• Very rare

Transmissible Spongiform Encephalopathies

• Caused by prions
• Sheep scrapie
• Bovine spongiform encephalopathy (BSE, “mad cow disease”)
• Variant Creutzfeldt-Jakob disease (vCJD; transmissible)
• Kuru
• Transmitted by ingestion or transplant
• All prion diseases are chronic and fatal

Kuru