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Central Nervous System Diseases
Kaelani, Audrey, Thomas
Rabies, Tetanus and Botulism
- Rabies, Tetanus and Botulism effect the nervous system
- Botulism and Tetanus effect nerve resection
History
Etymology of "Rabies" AKA Lyssa Virus
- Debated as either originating from:
- Sanskrit word "rabhas" = "to do violence"
- Latin word "rabere" = "to rage"
Rabies History
- Today, the virus that causes rabies is classified in the genus Lyssa Virus; named after Lyssa, the Greek goddess of madness, rage, and frenzy.
Timeline
Time
- In 1768, the first documented case of rabies in the United States occurred in Boston after there was an outbreak in dogs.
- In 1804, Georg Gottfried Zinke proved that rabies was transmitted in saliva by injecting animals with saliva from a rabid dog.
- In 1885, Louis Pasteur develops the first attenuated rabies vaccine by growing the virus in rabbits, harvesting it, and then weakening it by drying the infected spinal cord tissue. The same year, 9-year-old Joseph Meister becomes first person to receive PEP post-exposure and survive.
- In 1889, Victor Babes introduced a new method of post exposure prophylaxis by simultaneously administering serum with rabies antibodies along with Pasteur’s vaccine.
- In 1954, the World Health Organization found that the combined use of serum containing rabies antibodies was a more effective post-exposure prophylaxis than the vaccine alone.
Line
- 1967: The rabies human diploid vaccine was developed and is now what is commonly used as both pre/post-exposure treatment
- 1979: A dog vaccine that gives a three-year immunity from rabies was developed and produced
- 2004: Jeanna Giese became the only reported person in history to survive rabies infection following the onset of rabies symptoms without pre- or post-exposure prophylaxis
- 2007: Center of Disease Control and Prevention declared the United States canine rabies free
- 2007: World Rabies Day was first celebrated to raise awareness about rabies and strengthen prevention and control efforts worldwide. It's observed in many countries, including the United States.
Rabies Today
- In the U.S., "Approximately 5,000 animal rabies cases are reported annually to CDC, and more than 90% of those cases occur in wildlife."
- In the U.S., human rabies-related deaths declined - just 1-2 a year since 1960.
Today
- 1960 - 2018: 127 human rabies cases reported in the U.S. 1/4 from dog bites / international travel. 70% caused by rabid bats.
- On a global scale... rabies kills approx. 160 people a day, half being children. Endemic in more than 150 countries. More than 95% of cases reported in Asia and Africa.
- Despite these figures, rabies is 100% preventable with appropriate vaccination and awareness programs.
Tetanus History
Timeline
5th Century BC
1889
*First clinical description
*Japanese bacteriologist and physician isolated tetanus bacteria; it cause disease when injected into animals,
*Proved that tetanus is an anaerobic bacteria.
5th-1889
1884
Birth
* Italian scientist = tetanus infection in animals via puss
* German physician = tetanus in mice via soil
Early 1900's
1970's
*Cases decreasing
*By 1970's an average of 50–100 cases a year
*Pharmaceutical companies began developing anti-serums against tetanus.
*Anti-serums produced in horses, when antibodies developed, the horses blood was harvested and the serum was used for treatment
Early 1900's to the 1970's
1924-1938
Birth
*Military physicians=necessary to use tetanus anti-toxins; even
experiment on soldiers
*Sickness and allergic reactions from tetanus anti-serums
*The tetanus toxoid was developed in 1924 but not commercially available until 1938
Today
*only 1,000 cases a year in USA
*Usually preventable bye vaccination
Today
History of Botulism
Botulism History
- Like all great things, it starts with sausage.
- Latin word for sausage: "Botulus"
- Now used in cosmetic surgery
- Currently considered the most deadly toxin known to man
- 1 gram = 1 million people dead
- Franklin Expedition
Byzantine Empire (10th Century)
Ellezelles, Belgium (1895)
- Emperor Leo VI of Byzantium (866 - 912 A.D.)
- Ban on blood sausages amid cases of food poisoning
- Symptoms were dilated pupils and fatal muscle paralysis
- Multiple cases linked to a smoked ham
- Emile Pierre Van Ermengem (1851 - 1932)
- First to isolate pathogen
- First named Bacillus Botulinus, later renamed Clostridium Botulinum
Timeline
- Sausage poisoning
- First large scale effort to identify a cause
- Similar symptoms
- Justinus Kerner, (1786-1862)
- First to publish a description & postulate therapudic possibility
Württemberg, Germany (1790's)
Cl. Botulinum
O
Today
- Rod shaped, gram positive cocci.
- Lives in soil, produce & animals
- Harmless to consume
- Can produce spores that can lie dormant
- Produces a exotoxin in anaerobic environment that when ingested, causes disease
- Food-borne, infant, wound
Epidemiology & Control
Contact transmission via direct contact.
Modes of transmission: bites, infectious saliva in wounds and aerosols via dogs, cats, bats, skunks, and wolves.
Rabies Epidemiology
Host Factors:
Susceptibility in Human Populations:
Epidemiology
- Rabies lyssavirus can survive outside of a human host via an alternate host.
- Spread from host to host and needs a mammalian host to survive
Rabies Epidemiology
- Both infectious and contagious and shows a propagated pattern of spreading.
- The Bad News: Mortality rate of 99.9% - the highest mortality rate of any disease on earth!
- The Good News: Its high mortality rate decreases its chances of spreading, lowering the risk of an epidemic.
Rabies Control
- Limited mode of transmission and high mortality rate = already low R0 value
Rabies Control
- Lowered further? Yes! Human Intervention.
1. Up-to-date rabies vaccination in pet cats, ferrets, and dogs
2. Establishing animal control protocols for sick wildlife
3. Prevention vaccination in humans when traveling to high-risk areas or if potentially exposed to the virus
*The mode of transmission cannot be changed but risking such transmission can be avoided by limiting contact with wildlife (both you and your pets!)
Tetanus Epidemiology And Control
Tetanus Epidemiology
Where Is It?
-Soil and intestine of humans and animals,
Transmission
- Contaminated wounds
When And Where Is It Common?
-Peaks in summer
-Tropical climate = Year round
Communicability
-Not contagious
Tetanus
Vaccination and Prevention
Vaccination and prevention
- Toxoid
- Children = recommended to have 5 doses
- Additional dose every 10 years to stay immune
- Booster shoot = given 48 hr for people who immunization = out of date
- High risk of falling + not fully immunized = tetanus antitoxin
Tetanus in USA
Cl. Botulinum Epidemiology
O
Botulism Epidemiology
- Botulism has NO R-zero potential
- Horizontal & vertical transmission does not occur
- Common source. Incidence relies on outbreaks from a single source
- Food-borne vs. Infant
- No latent period
- Incubation period (2hrs-8days)
Control
O
Botulism Control
- Everyone is susceptible
- Canning practices both commercial and home methods have improved
- Medical equipment is kept sterile
Vaccination
O
Botulism Vaccination
- No Vaccine, Potential toxoid
- Antitoxin can be administered (limited)
- excessive botox usage can result in diminished effects
Pathogenesis
Incubation Period:
Time between exposure to the virus and the first appearance of symptoms (30 - 90 days on average but depends on circumstances)
Prodromal Period:
Rabies Pathogenesis
When the virus first enters the CNS and begins to cause damage (2 - 10 days on average)
Acute Neurologic Period:
Depends on Severity!
Acute Neurologic Period:
- Usually lasts 2-10 days and most inevitably results in death
- Symptoms vary depending on severity of exposure:
- Furious rabies: most common type people experience (violent physical and neurological symptoms)
- Paralytic rabies: affects <20% of people (starting at site of entry, muscles gradually weaken, followed by total paralysis and death)
- Most common symptoms: Hyperactivity, excessive salivation, hydrophobia, paranoia, aggression, hallucinations, seizures
- The rabies infection causes massive brain inflammation and symptoms will soon lead to a coma followed by death.
How It Works:
- Viral infection transmitted by animals - causes inflammation of the brain and spinal cord (encephalomyelitis). Once at spinal cord and brain, rabies is almost ALWAYS fatal.
- Major site of infection is point of entry
- Has the capacity to evade immune response = virulent!!!!
Rabies Pathogenesis
RABV proteins ESSENTIAL in evasion of immune response
-allow efficient replication in muscle tissues
-evasion dependent on the RABV phosphoprotein/nucleoprotein/G protein
-Phosphoprotein targets interferon-beta, myxovirus resistance protein, Oas1 genes = decreased expression of these genes
-Efficient replication in muscle tissues is essential for neuroinvasion & RABV depends on evading specific immune responses to move through body
Causation of Symptoms
Clinical Diagnosis:
Causation of Symptoms:
In Animals:
- The symptoms of rabies = virus reaced the brain or spinal cord.
- Animal must be euthanized to proceed with the test
- Requires tissue from 2 parts of brain - pref. brain stem/cerebellum
In Humans:
- Once it reaches the brain, it affects the area in charge of swallowing, speaking, and breathing...
- Several tests necessary, no single one
- Samples: saliva, serum, spinal fluid, and skin biopsies of hair follicles at the nape of the neck
- Causing uncontrollable muscle spasms in throat/larynx --> hydrophobia!
- Saliva = virus isolation or reverse transcription followed by polymerase chain reaction (RT-PCR)
- Serum and spinal fluid = tested for antibodies to rabies virus
- Skin biopsy specimens = examined for rabies antigen in the cutaneous nerves at the base of hair follicles
Core Classifications:
Characteristics
- Species: Rabies Lyssavirus
- Linear, single-stranded RNA (ssRNA) core
- Enveloped helical capsid
- Capsid = "bullet shaped"
- Rhabdoviradae family
How Dose Tetnus Cause it's Symtomtoms
Characteristics
- Characterized by spastic paralysis
- Gram + bacteria
- Spore former
Characteristics
Tetanus Pathogenesis
Tetanus Pathogenesis
- Anaerobic conditions = spores germinate
- Produces very potent toxins
- Interferes with reels of neurotransmitters + blocks inhibitor impulses
- Neonatal tetanus occurs, because of umbilical stump infection
Tetanus Side Effects
-Muscle contractions in the jaw and neck (lock jaw)
-Chills, fever, skin rash
- Irritability, pain, itching
Tetanus Side Effects
Exotoxin formation & entry
O
Exotoxin Formation
- Exotoxin is produced by bacteria
- Food-borne, Infant & wound
- 7 types exist (A-G)
- Gut/wound -> Blood
- Toxin binds to muscle neurons
- blocks the release of acetylcholine
- leads to descending symetrical paralysis
Pathogenicity
O
Pathogenicity
- High pathogenicity
- Virulence:
- infectous dose - 30-100 ng
- lethal dose
- ingestion - 1000 ng
- inhalation - 10-13 ng
- Intravenous - 1.3-2.1 ng
- Paralysis begins at cranial nerves
- Drooping eyelids
- If left untreated, disease can cause cardiac and respiratory failure
Treatment
O
Treatment
- Treatment is very limited
- No rapid tests available
- Passive administration of equine-derived antibodies
- can cause hypersensitivity
- Antitoxin also exists, can halt progression of paralysis
- Mechanical ventilation
- Differential diognosis
- ELISA and PCR-based assay
- Serum can be injected into mice who are then tested