Chapter 19
Infectious Diseases Affecting the Nervous System
Structure of the nervous system
Divided into two parts:
• Central nervous system (CNS)
– Brain and Spinal Cord
• Peripheral nervous system (PNS)
– Nerves that transfer commands between the CNS and muscles and glands
– Sensory nerves-carry signals towards the CNS
– Motor nerves - carry signals away from the CNS
– Mixed nerves-carry signals both toward and away from the CNS
• Brain and spinal cord are covered with three membranes – meninges
– Dura mater – outermost membrane
– Arachnoid – middle membrane
– Pia mater innermost membrane
– Between arachnoid and pia mater there is a space that is filled with a fluid – cerebrospinal fluid in which bacteria can multiply.
Portals of Infection of the Central Nervous System
• CNS is an axenic environment
– It has no normal microbiota
– Restricted permeability of blood vessels (no microbes can pass into the CNS)
• Pathogens may access the CNS:
– Breaks in the bones and meninges
– Medical Procedures
– Traveling through peripheral neurons to the CNS
Meningitis
• An infection of the membranes – meningitis
• Can be caused by
– Bacteria
• Streptococcus pneumoniae
• Haemophylus influenzae
• Neisseria meningitidis
• 50 other species of bacteria
– Viruses
– Fungi
– Protozoa
An infection of the brain – encephalitis
• Bacteria cause disease in two ways
– Infect cells of the nervous system
• Meningitis
• Leprosy
– Bacteria growing elsewhere release toxins that affect neurons
• Botulism
• Tetanus
Bacterial meningitis
• Signs and Symptoms
– Sudden high fever and severe meningeal inflammation
• Inflamed cranial meninges: severe headache, vomiting,
• Inflamed spinal meninges: stiff neck, altered muscle control
– Infection of the brain, or encephalitis, can result in behavioral changes, coma, and death
– Signs and symptoms may develop rapidly
Hemophilus influenza
• Gr negative bacteria, normal throat microflora.
• Causes meningitis in children (6 month to 4 years old)
• Of all bacterial meningitises H. influenzae accounts for most often cases
• Existing vaccine
Neisseria meningitides
• Gr- cocci (meningococcus)
• The cells are surrounded by thick capsules that protect them from phagocytosis
• Normal microbiota in the nose and throat
• Begins as a throat infection
• Virulence factor: endotoxin -stimulates white blood cells - cytokines released – blood vessels affected – hemorrhage. Death in few hours
• Vaccine available – not for all serotypes
• Treatment: Intravenous injection of antibiotic (Penicillin G) - as soon as possible
Streptococcus pneumonia
• Gr+ diplococcus
• Causes pneumococcal meningitis in children (1 month to 4 years old).
• It is a common flora of the mouth and throat. It also causes pneumonia and ear infections
• Mortality rate high (30% in children and 80% in the elderly)
• Vaccine available, recommended for infants under the age of 2
Listeriariosis
• Causative agent:Listeria monocytogenes (gr+ rods)
• Infects animals and humans
• Source of infection: ingestion of contaminated food (dairy products, meat..)
• Affects:
– Adults with compromised immune system
– Pregnant women are especially susceptible
• Fetus infected through placenta
– abortions, and stillbirths
• Newborns infected through the birth canal
• Grows in central nervous system and placenta
• Treatment: penicillin G
Fungal Meningitis
• Fungi rarely infect the CNS
• Cryptococcosis - fungal meningitis
• Caused by Cryptococcus neoformans – a yeast
• Found in soil and pigeon droppings
• Infection via inhalation
• Mycoses may spread from the lungs to the CNS via the blood
• Symptoms: headaches, stiff neck
• Affects especially AIDS patients
Naegleria meningoencephalitis
• Caused by Naegleria fowleri – amaeba
• The victims are children who swim in ponds and streams.
• The pathogen infects the nasal mucous membrane and then the brain.
• The disease is fatal (100%).
Arboviral Encephalitis
• Arboviruses are arthropod-borne viruses
• The virus is transmitted by mosquito to humans and horses.
• Proliferation of the disease occurs during summer months.
• Symptoms: Chills, fever, headache, and even death.
• Different forms of encephalitis: Western equine encephalitis, Eastern equine encephalitis, St. Luis encephalitis, California encephalitis, Japans B encephalitis
West Nile Virus
• A new arbovirus disease
• Infects birds and humans
• Symptoms:
– Body aches, headache, Polio-like paralysis and fatal encephalitis (especially in elderly)
• Treatment: alleviate symptoms
• Prevention involves limiting contact with mosquitoes
– Use netting and insect repellants
– Reduce mosquito numbers by eliminating stagnant water
Diseases caused by prions
• Prions are infectious proteins
• They cause spongiform degeneration of the brain – transmissible spongiform encephalitis
• Abnormally folded prion proteins – transform the normal protein
• Unclear why the initial prion misfolds
• Prion disease include Sheep scrapie, mad cow disease, and variant Creutzfeldt-Jakob disease
Creuzfeldt-Jacob disease
• Brain tissue has spongioform lesions (caused by accumulation of PrP
• Symptoms: altered behavior, dementia, memory loss, senility
• Not communicable disease
• Some transmission is possible
– Transplants
– Contaminated surgical instruments
– Injection of growth hormones from infected pituitary glands
Sheep scrapie
• Symptoms: The infected animal scrapes itself against the wall. Loss of motor control – death
• Mad cow disease – the animals must be destroyed
Viral diseases of nervous system
Rabies
• Caused by rabies virus (rhabdovirus)
• Acquired by the bite of an infected animal (also transmitted by aerosol)
• After infection the virus multiplies in skeletal muscles (up to few months)
• Then the virus enters the peripheral nerves through which it travels to central nervous system.
• Symptoms: spasm of muscles, hydrophobia, biting behavior, excitability, increased salivation, difficulties in swallowing. Damage to nervous system – death.
• Diagnosis: immunofluorescent detection of viral antigens in saliva or brain tissue (dead animal)
• Reservoir of infection: dog, cat, skunk, bat, fox, raccoon
• Treatment: 5-6 injection of vaccine + rabies immune globulin
• Prevention: Vaccination of dogs and cats
Poliomyelitis (Polyo)
• Caused by polyovirus.
• The infection is initiated with ingestion of the virus (contaminated water)
• Disease starts with the mild symptoms (fever, sore throat, nausea)
• Primary area of infection is throat and small intestine. Next, tonsils, lymph nodes, blood and central nervous system
• Virus multiplies in the motor nerve cells – cell dies
• Severe symptoms: 1% of infected will suffer from paralysis
Polio vaccines
Two types of vaccines available:
• Salk vaccine - used in Europe
– Viruses inactivated with formalin
– Must be injected
– Booster required
• Sabin vaccine – was more popular in the US
– Oral vaccine
– Living attenuated viruses
– Disadvantage – may cause disease
– Lifelong immunity
– No longer available in the USA
Bacterial diseases
Tetanus
• Caused by Clostridium tetani - anaerobic, endospore forming gr+ rod
• Contracted by infection of the wound with rusty nails. Clostridium is found in the soil contaminated with animal feces.
• Signs/Symptoms: Tightening of the jaw and neck muscles, followed by fever and muscle spasms
• Incubation period: Five days to fifteen weeks
• Clostridium spores enter a host through a wound on the skin and then it replicates
• Produce tetanospasmin toxin blocks the release of neurotransmitters
• Toxin is:
• taken up into the nerve axon and transported to the central nervous system
• fixed to the inhibitory motor nerve endings – blocking the inhibitory impulses
• Treatment: Human tetanus immunoglobulin, penicillin
• Prevention: Vaccination with tetanus toxoid (DTP)
Botulism
• Caused by Clostridium botulinim
• Not transmitted from person to person
• Source of infection: home processed foods, vegetables, fruits, meat, fish
• Spores can survive at high temperatures
• Clostridium produces exotoxin (botulinum toxin) - the most poisonous naturally occurring substance – the lethal dose is 1ng/kg
• Latin – Botulus: sausage
• Treatment: antitoxin therapy
• The toxin blocks the release of acetylcholin – neuro transmitter
• Therefore the muscle remains relaxed – flacid paralisis
Infant Botulism
• Infants do not have established normal microflora – infant botulism
• Cases reported with honey
– should not be given to infants under 1 year of age
Protozoan diseases of the nervous system
African trypanosomiasis - sleeping sickness
• Caused by Trypanosoma brucei gambiense.
• It is transmitted by the bite of tsetse fly
• In early stage the protozoa is found in low numbers in the blood (2-4 years).
• In later stage the pathogen moves to central nervous system
• Symptoms: decrease in physical activity and mental acuity, coma, and death.
• Difficulty in developing a vaccine – the parasite changes the protein coat
• Prevention: eliminating tse-tse flies
• Treatment:
– At early stage: suramin
– Late stage (brain infected): arsenic-based drug