Microbiology and Human Disease Chapter 17:

Infectious Diseases Affecting the Nervous System:

The nervous system has two parts: the central nervous system (CNS), which includes the brain and spinal cord, and the
peripheral nervous system (PNS), which includes nerves and ganglia. The soft tissue of the brain and spinal cord is encased
within the tough casing of three membranes called the meninges. The subarachnoid space is filled with a clear serum-like
fluid called cerebrospinal fluid (CSF). The nervous system is protected by the blood-brain barrier, which limits the passage of
substances from the bloodstream to the brain and spinal cord. At the present time, we believe there is no normal biota in
either the CNS or PNS.

Meningitis is an inflammation of the meninges. The more serious forms are caused by bacteria, often facilitated by
coinfection or previous infection with respiratory viruses.
Here are some examples of microorganisms that cause meningitis:
 Neisseria meningitidis: Gram-negative diplococcus; causes most serious form of acute meningitis.
 Streptococcus pneumoniae: Gram-positive coccus; most frequent cause of community-acquired pneumococcal
meningitis.
 Haemophilus influenzae: Infections have declined sharply because of vaccination.
 Listeria monocytogenes: Most cases are associated with ingesting contaminated dairy products, poultry, and meat.
 Cryptococcus neoformans: Fungus; causes chronic form with more gradual onset of symptoms.
 Coccidioides species: True systemic fungal infection; begins in lungs but can disseminate quickly throughout body;
highest incidence in southwestern United States, Mexico, and parts of Central and South America.
 Viruses: Very common, particularly in children; 90% are caused by enteroviruses.

Neonatal Meningitis: Usually transmitted vertically. Primary causes are Streptococcus agalactiae, Escherichia coli, and
Listeria monocytogenes.

Poliomyelitis is an acute enterovirus infection of the spinal cord. Infection can result in neuromuscular paralysis. Two
effective vaccines against poliovirus exist: Inactivated Salk poliovirus vaccine (IPV) is the only one used now in the United
States; attenuated oral Sabin poliovirus vaccine (OPV) still being used in the developing world.

Meningoencephalitis is caused mainly by two amoebas, Naegleria fowleri and Acanthamoeba. Acute encephalitis is usually
caused by viral infection. Arboviruses carried by arthropods often are responsible. Such examples are Western Equine
Encephalitis (WEE), Eastern Equine Encephalitis (EEE), California Encephalitis, St. Louis Encephalitis (SLE), and West Nile
Encephalitis. Also, Herpes simplex virus type 1 and 2 cause encephalitis in newborns born to HSV-positive mothers.

In subacute encephalitis, symptoms take longer to manifest as compared to acute forms. Toxoplasma gondii, the protozoan,
causes toxoplasmosis, the most common form of subacute encephalitis. This is relatively asymptomatic in the healthy, but
can be severe in immunodeficient people and fetuses.

Prions are proteinaceous infectious particles containing no genetic material. Prions cause transmissible spongiform
encephalopathies (TSEs), neurodegenerative diseases with long incubation periods but rapid progressions once they begin.
Human TSEs are Creutzfeldt-Jakob disease (CJD), Gerstmann-Strussler-Scheinker disease, and fatal familial insomnia.

Rabies is a slow, progressive zoonotic disease characterized by fatal encephalitis. Rabies virus is in the family Rhabdoviridae.
Tetanus is a neuromuscular disease, also called lockjaw; it is caused by Clostridium tetani neurotoxin, tetanospasmin, which
binds target sites on spinal neurons and blocks inhibition of muscle contraction. Botulism is caused by exotoxin of C.
botulinum and associated with eating poorly preserved foods that can also occur as a true infection. Three major forms of
botulism exist: food-borne, infant, and wound.
17.1

Nervous System and Its Defenses:

Component parts of the immune system:
• Central nervous system (CNS): consists of the brain and spinal cord
• Peripheral nervous system (PNS): contains nerves that emanate from the CNS to sense organs and periphery of
the body Three important functions:
• Sensory: fulfilled by sensory receptors at the ends of peripheral nerves that generate nerve impulses that are
transmitted to the CNS
• Integrative: translates sensation into thought
• Motor: receives signals from the CNS in muscles and glands

Brain and Spinal Cord:

Neurons: cells that make up the tissues of the brain and spinal cord; receive and transmit signals to and from the CNS and
PNS
Brain situated inside the skull; spinal cord lies within the spinal column surrounded by vertebrae:
• Soft tissue encased within three meninges
• Dura mater: outermost layer
• Arachnoid mater
• Pia mater
• Subarachnoid space between the arachnoid and pia mater is filled with cerebrospinal fluid

Functions of CSF and PNS:

Cerebrospinal fluid (CSF):
• Provides nutrition to the CNS
• Also provides a liquid cushion for the brain and spinal cord
• Microorganisms can be found within the CSF when meningitis occurs
PNS consists of nerves and ganglia:
• Ganglion: swelling in the nerve where cell bodies of neurons aggregate
• Nerves: bundles of axons that receive and transmit nerve signals
• Axons and dendrites of adjacent neurons communicate with each other across a synapse
• Neurotransmitters are released from one cell and act on the next cell in a synapse

Defenses of the Nervous System:

Defenses of the nervous system are mainly structural:
• Bony casings of the brain and spinal cord protect them from traumatic injury
• CSF provides a cushioning function
Blood-brain barrier:
• Vascular interface between the blood vessels serving the brain and the brain itself
• Cells that make up the walls of these blood vessels allow very few molecules to pass through
• Prohibits most microorganisms and most antibiotics from entering the nervous system
CNS is “immunologically privileged”:
• Only able to mount a partial, or different, immune response when exposed to an immunologic challenge
• CNS functions are so vital that even temporary damage that could result from normal immune responses could be
detrimental
Microglia and brain macrophages:
• Have phagocytic capabilities
• Activity is reduced when compared to phagocytic cells in other parts of the body
17.2

Normal Biota of the Nervous System

It is still believed that there is no normal biota in either the CNS or PNS:
• Finding microorganisms of any type in these tissues represents deviation from the healthy state
• Herpesviruses live in a dormant state in the nervous system, but are not considered normal microbiota
• Research suggests that the gut microbiome influences the nervous system in many ways:
• Development of the brain, the blood-brain barrier, and proper construction of peripheral nerves are influenced by
the microbiome in the developing gut

Nervous System Defenses: Bony structures, blood-brain barrier, microglial cells, and macrophages

17.3

Nervous System Diseases (8 microbial agents emphasized)

• Bacterial diseases – Meningitis (1. Neiseria, 2.Haemophilus influenza) – 3.Tetanus – 4.Botulism
• Virus diseases – 5.Zika virus – 6.Poliomyelitis (can also cause meningitis) – 7.Rabies
• Protozoal – 8.Toxoplasmosis

Nervous System Diseases

• Meningitis – meningeal inflammation
• Encephalitis – inflammation of the brain
• Meningoencephalitis – inflammation of both Reasons for inflammation can be infectious or non-infectious

Highlight Disease: Meningitis - bacterial

Inflammation of the meninges:
Anatomical syndrome: many different microorganisms can cause an infection of the meninges and all
produce a similar set of symptoms
More serious forms of acute meningitis are caused by bacteria:
• Entrance to the CNS is facilitated by coinfection or previous infection with respiratory viruses
Meningitis in neonates is most often caused by different microorganisms than those causing disease in children and adults

Diagnosis and treatment:

• Lumbar puncture (spinal tap), Gram stain, and/or culture of CSF are performed when meningitis is suspected
• Treatment with broad-spectrum antibiotics is started immediately
Signs and symptoms:
• Severe headache
• Painful or stiff neck
• Fever
• Nausea and vomiting
• Photophobia (sensitivity to light)
• Skin rashes may be present in specific types of meningitis.
• Increased number of lymphocytes in the CSF

Neisseria meningitidis
• Gram-negative diplococci commonly known as the meningococcus
• Often associated with epidemic forms of meningitis
• Causes the most serious form of acute meningitis and accounts for 15 to 20% of all meningitis cases
• Most cases occur in young children because vaccination is not recommended until age 11
• 12 different capsular strains exist:
• Serotypes B, C, and Y are responsible for most cases of infection -in US-Meningococcal ACWY vaccine available ,
for B serotype, a different vaccine needed
Neisseria meningitidis Pathogenesis and Virulence Factors
• Bacteria enters the body via the upper respiratory tract, moves into the blood, rapidly penetrates the meninges, and
produce symptoms
• Pathogen releases endotoxin into the generalized circulation, which stimulates white blood cells
• Damage to the blood vessels caused by cytokines leads to vascular collapse, hemorrhage, and petechiae on the trunk and
appendages
• In a small number of cases, meningococcemia becomes an overwhelming disease with a high mortality rate
• Bacteria produce IgA protease and a capsule that counters the body’s defenses

Neisseria meningitidis Signs and Symptoms

• Sudden onset of disease
• Fever higher than 40°C or 104°F
• Sore throat
• Chills
• Delirium
• Widespread areas of bleeding under the skin
• Shock
• Coma
• Generalized intravascular clotting
• Cardiac failure
• Damage to the adrenal glands
• Death within a few hours

Neisseria meningitidis Transmission and Epidemiology

• Bacteria do not survive long in the environment:
• Usually acquired through close contact with secretions or droplets
• Sporadic or epidemic incidence in late winter or early spring
• Reservoir of infection is humans harboring the pathogen in the nasopharynx
• Carriers living in close quarters with susceptible individuals more readily transmit the disease: families, day cares,
college dorms, military barracks:
• Highest risk groups are young children, older children, and young adults

Neisseria meningitidis Culture and Diagnosis

Suspicion of bacterial meningitis constitutes a medical emergency:
• Differential diagnosis must be done with haste and accuracy
• Meningococcal meningitis must be confirmed or ruled out because it can be rapidly fatal
• Treatment is begun with this organism in mind until it is ruled out Cerebrospinal fluid, blood, or nasopharyngeal
samples: • Stained and observed for characteristic diplococci
• Specific rapid tests are available for detecting capsular polysaccharide or cells directly from specimens without
culturing.
• Modified Thayer-Martin or chocolate agar are used for cultures, incubated in a high CO2 atmosphere.
• Presumptive identification of the genus obtained through Gram stain and oxidase testing
•Lumbar puncture (spinal tap), Gram stain, and/or culture of CSF are performed when meningitis is suspected
•Treatment with broadspectrum antibiotics is started immediately - treatment is shifted if necessary after a
diagnosis is confirmed

Neisseria meningitidis Prevention and Treatment

1. Infection rate in most populations is 1%, indicating a well developed natural immunity
2. Treated meningococcemial disease has a mortality rate of 15%:
1. Vital that antibiotic therapy begin as soon as possible
2. High doses of penicillin G given intravenously
3. Treatment for shock and intravascular clotting may also be required
3. Individuals in close contact with infected patients should receive preventive therapy with rifampin or tetracycline
4. Vaccination recommended for pre teen up to 12 then booster at 16 in US - Meningococcal ACWY vaccine available, for B
serotype, a different vaccine needed
Meningitis: Haemophilus influenzae
• Causes severe form of meningitis
• U.S. cases are mostly caused by serotype B strains
• Much less common in the U.S. since vaccine was introduced in 1988: Hib vaccine (at 2 months and 5 yrs of age)
• If people fail to get vaccinated, herd immunity will be compromised
• Globally still common and an important cause of the disease in children under 5
• Gram negative cocobacilli

Meningitis: Viruses
Aseptic meningitis: no bacteria or fungi are found in the CSF:
• Viruses cause 4 of 5 cases of meningitis.
• May have noninfectious causes
Majority of cases occur in children:
• 90% caused by enteroviruses
• Common cause of viral meningitis is initial infection with HSV-2, concurrent with a genital infection
• Occasionally, other viruses gain access to the nervous system
Generally milder than bacterial or fungal meningitis:
• Usually resolved within 2 weeks
• Mortality rate less than 1%
Diagnosis begins with the failure to find bacteria, fungi, or protozoa in the CSF:
• Confirmed by viral culture or specific antigen tests In most cases, no treatment is needed

Highlight Disease: Zika Virus Disease

Microcephaly: babies born with abnormally small heads
Causative agent: Zika virus in the Flaviviridae family
• Related to dengue fever, West Nile fever, and yellow fever
Signs and symptoms:
• Adults: range from none to skin rash, conjunctivitis, and muscle and joint pain:
• Also triggers Guillain-Barré syndrome in some adults
• Babies who acquire it during gestation: congenital Zika virus syndrome:
• Small head, vision problems, involuntary movements, seizures, and irritability
• Symptoms of brain stem dysfunction such as swallowing problems are also common

Transmission and epidemiology:

• Transmitted by the bite of the Aedes mosquito, via sexual intercourse with infected individuals, and vertically in utero
• Rapid spread throughout Americas:
• 175 cases in U.S. as of mid-2017: 174 in travelers returning from affected areas, 1 acquired through sexual transmission
Prevention and treatment:
• No vaccine currently available
• Provide supportive measures:
• Patients experiencing Guillain-Barré syndrome should receive intensive physical therapy and may require
mechanical ventilation
• Testing strategies to impair mosquito reproduction • Prevent mosquito bites

Poliomyelitis
 Acute enteroviral infection of the spinal cord that can cause neuromuscular paralysis; also known as infantile
paralysis
 Efforts of a WHO campaign have greatly reduced the incidence of polio, but no civilization or culture has escaped its
devastation:
• Bill Gates has contributed $700 million to help eradicate polio
• In 2014, India was declared polio-free
• Also in 2014, the WHO declared a public health emergency because polio had spread to eight countries in Africa and the
Middle East
Poliomyelitis Signs and Symptoms
Short-term, mild viremia
Mild, nonspecific symptoms of fever, headache, nausea, sore throat, and myalgia (muscle pain) If viremia persists:
• Viruses carried to the CNS through the blood supply
• Spreads along specific pathways in the spinal cord and brain
• Neurotropic: infiltrates motor neurons of the anterior horn of the spinal cord
• Can also attack spinal ganglia, cranial nerves, and motor nuclei
Paralytic disease:
• Invasion of motor neurons causes flaccid paralysis
• Paralysis of the muscles of the legs, abdomen, back, intercostals, diaphragm, pectoral girdle, and bladder can
result
Bulbar poliomyelitis:
• Brain stem, medulla, or cranial nerves are affected
• Loss of control of cardiorespiratory regulatory centers; requires use of mechanical respirators
• Unused muscles begin to atrophy, growth is slowed, and severe deformities of the trunk and limbs develop:
• Crippled limbs are often very painful

Poliomyelitis Causative Agent

Poliovirus in the family Picornaviridae, genus Enterovirus:
• Named for its small size (pico)
• Nonenveloped, nonsegmented RNA virus
• Naked capsid confers chemical stability and resistance to acid, bile, and detergents:
• Survives the gastric environment and other harsh conditions

Poliomyelitis Pathogenesis and Virulence Factors

After ingestion, polioviruses adsorb to receptors of mucosal cells in the oropharynx and intestine:
• They multiply in mucosal epithelia and lymphoid tissue; large numbers of viruses are shed in the throat, in
feces, and some leak into the blood
Depending on the number of viruses in the blood and the duration of their stay, individuals may develop:
• No symptoms
• Mild, nonspecific symptoms such as fever and short-term muscle pain
• Devastating paralysis

Poliomyelitis Transmission and Epidemiology

Virus is spread through food, water, hands, objects contaminated with feces, and mechanical vectors
The 20th century saw a very large rise in paralytic polio cases:
• Also the century in which effective vaccines were developed Infection was eliminated from the Western
Hemisphere in the late 20th century:
• Difficult to eradicate from the developing world

Poliomyelitis Treatment
• Alleviation of pain and suffering
• Acute phase: muscle spasm, headache, and associated discomfort alleviated by pain relieving drugs
• Respiratory failure may require artificial ventilation maintenance
• Prompt physical therapy to diminish crippling deformities and retrain muscles is recommended after the acute
phase subsides

Poliomyelitis Prevention
• Vaccination as early in life as possible, usually in 4 doses, starting at 2 months of age
• Adult candidates for immunization are travelers and members of the armed forces
Two forms of the vaccine:
• Inactivated poliovirus vaccine (IPV) developed by Jonas Salk in 1954
• Oral poliovirus vaccine (OPV) developed by Sabin in the 1960s:
• Contains an attenuated virus that can (rarely) revert to a neurovirulent strain that can cause disease
Subacute Encephalitis
Symptoms take longer to show up and are less striking than acute encephalitis
Causes of subacute encephalitis: (extra credit)
• Toxoplasma gondii
• Persistent measles virus 7 to 15 years after initial infection
• Prions can cause spongiform encephalopathy.
• Variety of infections with primary symptoms elsewhere in the body

Toxoplasma gondii
• Infection in the fetus and in immunodeficient people is severe and often fatal
• Recent data show that infection in otherwise healthy people can have profound effects on the brain:
• People with a history of Toxoplasma infection are more likely to display thrill-seeking behaviors and slower
reaction times

Toxoplasma gondii Signs and Symptoms

Most cases are asymptomatic or have mild symptoms such as sore throat, lymph node enlargement, and low-grade fever
Patients with immune suppression due to infection, cancer, or drugs have a grim outlook:
• Chronic or subacute encephalitis
• Extensive brain lesions and fatal disruptions of the heart and lungs
Pregnant women have a 33% chance of transmitting the infection to the fetus
Congenital infection in the first or second trimester is associated with:
• Stillbirth
• Liver and spleen enlargement
• Liver failure
• Hydrocephalus
• Convulsions
• Damage to the retina, resulting in blindness

Pathogenesis and virulence factors:

• Obligate intracellular parasite with the ability to invade host cells
Transmission and epidemiology:
• Parasite undergoes a sexual phase in the intestine of cats and is released in the feces:
• Becomes an infective oocyst that survives in moist soil for several months
• Pseudocyst: asexual cyst state in tissues
• Oocysts are spread to intermediate hosts such as rodents and birds.
• Cycle continues when cats eat infected prey
• Stanford University scientists discovered that the protozoan crowds into the part of the rat brain that directs the rat to
avoid cat urine:
• When Toxoplasma infects rats, they lose their fear of cats.
• Cats eat the fearless rats, ensuring continuation of the Toxoplasma life cycle

Toxoplasma gondii Transmission and Epidemiology

Humans are constantly exposed to Toxoplasma:
• Serological testing shows 90% of the population has had prior exposure
Sources of infection:
• Raw or undercooked meat
• Unhygienic handling of cat feces
• Inhalation of dusts contaminated with infected cat droppings
• Tachyzoites cross the placenta to the fetus
Hygiene is of paramount importance in control of Toxoplasma:
• Adequate cooking or freezing below -20°C
• Hand washing after handling cats or cat feces
Rabies
Slow, progressive zoonotic disease:
• Characterized by fatal encephalitis
• Distinct pathogenesis and symptoms
• Distributed nearly worldwide except for perhaps two dozen countries with rigorous animal control
Signs and symptoms:
• Incubation period is 1 to 2 months or more, depending on the wound site, severity, and inoculation dose
• Shorter incubation period in facial, scalp, or neck wounds because of the closer proximity to the brain
• Prodromal phase begins with fever, nausea, vomiting, headache, fatigue, and other nonspecific symptoms
• Until recently, humans were never known to survive rabies
• A handful of patients have recovered in recent years after long-term treatment

Rabies Pathogenesis and Virulence Factors

• Infection begins when an infected animal’s saliva enters a puncture site
• Virus is occasionally inhaled or inoculated through membranes of the eye
• Virus remains up to a week at the trauma site, where it multiplies
• Virus then gradually enters nerve endings and advances toward the ganglia, spinal cord, and brain
• After viral multiplication in the brain, the virus travels to the eye, heart, skin, and oral cavity
• Cycle is completed when the virus replicates in the salivary gland and is shed in the saliva
Clinical rabies proceeds through several distinct stages and ends almost inevitably in death unless post-exposure vaccination
is performed before symptoms begin
• Virulence is associated with an envelope glycoprotein that gives the virus the ability to spread in the CNS and
invade certain types of neural cells

Pathology of Rabies Infection:

If bitten in hands and face (areas rich in nerve fibers), it can be especially dangerous and shorten incubation time
1. Virus enters tissue from saliva of biting animal
2. Virus replicates in muscles near bite
3. Virus moves up peripheral nervous system to CNS
4. Virus ascends spinal cord
5. Virus reaches brain and causes fatal encephalitis
6. Virus enters salivary glands and other organs of victim

Rabies Transmission and Epidemiology

• Primary reservoirs of the virus are wild mammals such as canines, skunks, raccoons, badgers, cats, and bats
• Both wild and domestic mammals can spread the disease through bites, scratches, and inhalation of droplets
• Annual worldwide total for human rabies is estimated at about 35,000 to 50,000 cases, but only a tiny number of
these occur in the U.S.:
• Majority are transmitted to humans from bats
• Most U.S. cases of rabies occur in wild animals, while dog rabies has declined

Epidemiology of animal rabies in the U.S. varies:

• Most common wild animal reservoir hosts are raccoons, bats, and skunks
Regional differences in the dominant reservoir also occur:
• California: skunks
• East: raccoons
• Texas: foxes
Diagnosis requires multiple tests:
• Reverse transcription PCR is used with saliva samples.
• Must be accompanied by detection of antibodies to the virus in serum or spinal fluid
• Skin biopsies are also used. (Usually brain tissue post mortem)
Rabies Prevention and Treatment
 Bite from a wild or stray animal demands assessment of the animal, meticulous care of the wound, and a specific
treatment regimen
A combination of passive and active post-exposure immunization is indicated:
• Post exposure: Wound is infused with human rabies immune globulin (HRIG) to impede spread of the virus
• Globulin is also injected intramuscularly to provide immediate systemic protection
• A full course of vaccination is started
• High-risk groups such as veterinarians, animal handlers, laboratory personnel, and travelers should receive three
doses to protect against exposure
• DNA vaccine for rabies is in development
• No effective treatment available once symptoms appear.

Tetanus
Neuromuscular disease also known as “lockjaw”
Caused by Clostridium tetani:
• Common resident of cultivated soil and the gastrointestinal tracts of animals
• Gram-positive, endospore-forming bacillus
• Endospores often swell in the vegetative cell
• Spores only produced under anaerobic conditions

Tetanus Signs and Symptoms

Tetanospasmin:
• Powerful neurotoxin released by C. tetani
• Binds to target sites on peripheral motor neurons, spinal cord and brain, and in the sympathetic nervous system
• Toxin acts by blocking the inhibition of muscle contraction, causing muscles to contract uncontrollably
• First symptoms are clenching of the jaw, followed by arching of the back, flexion of arms, and extension of legs
Risus sardonicus:
• The “sardonic grin” conferred by lockjaw looks eerily as though the person is smiling
• Death most often occurs due to paralysis of the respiratory muscles and respiratory arrest

Neonatal tetanus can occur due to application of mud, dung, or ashes to the umbilical stump.

Tetanus Pathogenesis and Virulence Factors

Mere presence of endospores in a wound is not sufficient to initiate infection:
• Bacterium is unable to invade damaged tissues readily
• Organism is anaerobic, and endospores cannot become established unless tissues are necrotic and poorly supplied
with blood
As vegetative cells grow, tetanospasmin is released into the infection site:
• Toxin spreads to nearby motor nerve endings in the injured tissue, binds to them, and travels via axons to the
ventral horns of the spinal cord
• Toxin blocks release of neurotransmitters
• Only a small amount of toxin is required to initiate symptoms

Tetanus Transmission and Epidemiology

• Endospores enter the body through:
• Accidental puncture wounds
• Burns
• Umbilical stumps
• Frostbite
• Crushed body parts
• Incidence is low in North America
• Most cases occur among geriatric patients and IV drug abusers
Historically, the worldwide incidence of maternal and neonatal tetanus has been high, causing 60,000 deaths each year:
• The World Health Organization has made dramatic global progress in reducing mortality through the promotion of
more hygienic delivery practices and vaccination

Tetanus Prevention and Treatment

A patient with a clinical appearance suggestive of tetanus should immediately receive antitoxin therapy with human tetanus
immune globulin (TIG) and Penicillin G Recommended vaccination series:
• 1- to 3-month-old babies consists of three injections given 2months apart, followed by boosters at 1 and 4 years
• Protection lasts 10 years
• Pregnant women should be vaccinated
• Toxoid with TIG should be given to injured persons who have never been immunized, or whose last booster was received
more than 10 years previously

Botulism
Intoxication:
• Caused by an exotoxin
• Associated with eating poorly preserved foods
• Can also occur as a true infection
Until recently it was relatively common and frequently fatal:
• Modern techniques of food preservation and medical treatment have reduced its incidence and fatality rate
Three forms of botulism are distinguished by their means of transmission and the population they affect
1) Infant Botulism 70% to 75%
2) Foodborne Botulism 20% to 30%
3) Wound Botulism <3%

Infant Botulism:
This is currently the most common type of botulism in the United States, with approximately 75 cases reported annually.
The exact food source is not always known, although raw honey has been implicated in some cases, and the endospores are
common in dust and soil. Apparently, the immature state of the neonatal intestine and microbial biota allows the
endospores to gain a foothold, germinate, and give off neurotoxin. As in adults, babies exhibit flaccid paralysis, usually
manifested as a weak sucking response, generalized loss of tone (the “floppy-baby syndrome”), and respiratory
complications. Although adults can also ingest botulinum endospores in contaminated vegetables and other foods, the adult
intestinal tract normally inhibits this sort of infection. Finding the toxin or the organism in the feces confirms the diagnosis.

Foodborne Botulism:
Many botulism outbreaks occur in home-processed foods, including canned vegetables, smoked meats, and cheese spreads.
Several factors in food processing can lead to botulism. Endospores can be present on the vegetables or meat at the time of
gathering and are difficult to remove completely. When contaminated food is put in jars and steamed in a pressure cooker
that does not reach reliable pressure and temperature, some endospores survive (botulinum endospores are highly heat
resistant). At the same time, the pressure is sufficient to evacuate the air and create anaerobic conditions. Storage of the
jars at room temperature favors endospore germination and vegetative growth, and one of the products of the cell’s
metabolism is botulinum, the most potent microbial toxin known. Bacterial growth may not be evident in the appearance of
the jar or can or in the food’s taste or texture, and only minute amounts of toxin may be present. Botulism is never
transmitted from person to person. Some laboratories attempt to identify the toxin in the offending food. Alternatively, if
multiple patients present with the same symptoms after ingesting the same food, a presumptive diagnosis can be made. The
cultivation of C. botulinumin feces is considered confirmation of the diagnosis since the carrier rate is very low.

Wound Botulism:
Perhaps three or four cases of wound botulism occur each year in the United States. In this form of the disease, endospores
enter a wound or puncture, much as in tetanus, but the symptoms are similar to those of foodborne botulism. Increased
cases of this form of botulism are being reported in intravenous drug users as a result of needle puncture. The toxin should
be demonstrated in the serum, or the organism should be grown from the wound.

Botulism Signs and Symptoms

Action of the botulinum toxin:
 • Travels to its principal site of action, the neuromuscular junctions of skeletal muscles
• Prevents the release of acetylcholine, the neurotransmitter that initiates the signal for muscle contraction
• The result is flaccid paralysis, the opposite effect of tetanus
• Usual time before onset of symptoms is 12 to 72 hours, depending on the size of the dose
Early symptoms:
• Double vision
• Difficulty swallowing
• Dizziness
• No sensory or mental lapse
Later symptoms:
• Descending muscular paralysis
• Respiratory compromise; death results from respiratory arrest
• Mechanical respirators have reduced fatality to 10%

Botulism Causative Agent

Clostridium botulinum:1800: botulus- latin word for sausage- blood sausage encourage growth of endospore by providing
anaerobic environment. Store at room temp. after short heating that did not kill heat resistant endospores)
• Endospore-forming anaerobe
• Does damage through the release of an exotoxin
• Inhabits the soil and water and occasionally the intestinal tract of animals
• Distributed worldwide, but occurs most often in the Northern Hemisphere
• Species has seven types that vary in distribution among animals, regions of the world, and types of exotoxin:
• Human disease is usually associated with types A, B, E, and F
• Animal disease is usually associated with types A, B, C, D, and E Botulinum, the C. botulinum neurotoxin, results in
flaccid paralysis, a loss of ability to contract the muscles

Botulinal Types- facts

• Type A toxin (the most heat resistant)
– 60–70% fatality if untreated
– Found in CA, WA, CO, OR, NM (Oregon family died (12) after eating home canned string beans)
• Type B toxin
– 25% fatality without treatment
– Europe and eastern United States
• Type E toxin
– usually destroyed by boiling. Alaskan native s have highest rate of botulism because they avoid use of heat for
cooking. (traditional food: Muktuk: sliced flippers of seal or whales stored anaerobically for weeks until they
approach putrefaction)
– 25% fatality
– Found in marine and lake sediments
– Pacific Northwest, Alaska, Great Lakes area

Botulism Causative Agent

Culture and diagnosis:
• Diagnostic standards are different for the three presentations of botulism
• A suspected case of botulism should trigger a phone call to the state health department or the CDC before
proceeding with diagnosis or treatment
Prevention and treatment:
• The CDC maintains a supply of antitoxin that, when administered soon after diagnosis, can prevent the worst
outcomes of the disease
• Patients are managed with respiratory and cardiac support systems
• Hospitalization is required in all cases and recovery takes weeks, with a 5% mortality rate
• Add nitrites to sausage, proper canning procedures

Appendix of Image Long Descriptions:

Neisseria meningitidis Culture and Diagnosis - Appendix
A drop of oxidase reagent is placed on a suspected Neisseria or Branhamella colony. If the colony reacts with the chemical to
produce a purple to black color, it is oxidase-positive; those that remain white to tan are oxidase-negative. Because several
species of gram-negative rods are also oxidase positive, this test is presumptive for these two genera only if a Gram stain has
verified the presence of gram-negative cocci.

Events in Tetanus - Appendix

(a) After traumatic injury, bacteria infecting the local tissues secrete tetanospasmin, which is absorbed by the peripheral
axons and is carried to the target neurons in the spinal column. (b) In the spinal cord, the toxin attaches to the junctions of
regulatory neurons that inhibit inappropriate contraction. Released from inhibition, the muscles, even opposing members of
a muscle group, receive constant stimuli and contract uncontrollably. (c) Muscles contract spasmodically, without regard to
regulatory mechanisms or conscious control.

Infectious Diseases Affecting the Nervous System - Appendix

Encephalitis is caused by Arboviruses, Herpes simplex virus 1 or 2, and JC virus. Subacute Encephalitis is caused by
Toxoplasma gondii and Prions. Rabies is caused by the Rabies virus. Tetanus is caused by Clostridium tetani. Creutzfeldt-
Jakob Disease is caused by a Prion. Meningoencephalitis is caused by Naegleria fowleri and Acanthamoeba. Meningitis has
many possible causes including Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenza, Listeria
monocytogenes, Cryptococcus neoformans, Coccidioides, and Various viruses. Neonatal Meningitis is caused by
Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes, Cronobacter sakazakii. Zika virus disease is caused by
Zika virus. Polio is caused by Poliovirus. And Botulism is caused by Clostridium botulinum.

Homework:

1. T or F: Botulism is different from tetanus in that botulism causes muscles to relax while tetanus causes muscles to
contract. true
2. Poliomyelitis is an acute enteroviral infection of the spinal cord that causes neuromuscular paralysis.
3. In the past, this disease often affected small children and was called infantile paralysis
4. Because of this, vaccination is a mainstay of polio prevention today, and is started in infants at about 2 months of
age
5. There are two forms of vaccine utilized today.
6. Inactivated poliovirus vaccine was developed by Salk in 1954 and is now the form used for all childhood vaccinations
due to its low risk to individuals being vaccinated.
7. In contrast, oral polio vaccine (OPV), developed by Sabin in the 1960s, contains an attenuated virus and can be
easily administered by mouth making it useful still in polio eradication programs in developing countries today.
8. It poses many risks, however, such as the attenuated virus can multiply in vaccinated people and spread to others or
it can revert to a neurovirulent strain causing disease, making the OPV virtually unusable in the United States today.
9. Select all of the statements that describe the IPV. It contains three serotypes of the polio virus, It is prepared from
animal cell culture, It is the form of polio vaccine currently used in the United States, It contains inactivated virus.
10. Choose the statement that best describes the normal microbiota of the nervous system. there is no normal biota
present
11. Match the statement to the disease that it most accurately describes:
Rabies - Slow, progressive zoonotic viral disease characterized by fatal encephalitis and with hydrophobia as a
symptom
Poliomyelitis - Acute enteroviral infection of the spinal cord that can cause neuromuscular paralysis
Tetanus - A neuromuscular disease caused by a spore-forming bacterium that produces a powerful neurotoxin that
leads to spastic paralysis
Botulism - An intoxication, associated with eating poorly preserved foods, which results in flaccid paralysis
12. T or F: The nervous system lacks normal biota, and the presence of any microorganism indicates a deviation from
the healthy state. True
13. T or F: The CNS is an "immunologically privileged" site, which means that the immune response in these sites is
enhanced. False
14. Tetanus and botulism are similar in that both diseases: are caused by Clostridium species, are intoxications
(symptoms of disease due to toxins produced by bacteria), can be transmitted by dirty needles (wound)
15. Order the following choices from the outermost structure to the innermost structure to test your knowledge of the
anatomical features surrounding the brain. 1. Skull 2. dura matter 3. arachnoid mater 4. subarachnoid space
5. pia mater
16. Select all of the statements that describe the OPV. It is easily administered by mouth, it is prepared from animal cell
cultures, it contains attenuated virus
17. T or F: The neurotoxin produced by Clostridium tetani blocks the inhibition of muscle contractions resulting in
spastic paralysis. True (C. tetani releases a powerful neurotoxin, tetanospasmin, that binds to target sites on
peripheral motor neurons, spinal cord and brain, and in the sympathetic nervous system. The toxin acts by blocking
the inhibition of muscle contraction. Without inhibition of contraction, the muscles contract uncontrollably,
resulting in spastic paralysis.)
18. Mosquito eradication could change the epidemiology of zika virus
19. Bite from a raccoon: Which of the following diseases is the greatest risk to the patient, considering the mechanisms
of injury? Rabies
20. The RN advises the patient to seek medical attention immediately
21. If the patient is diagnosed with this infectious disease, the RN anticipates that treatment of the patient will include
which of the following? Wound care with immune globulin, intramuscular injection of immune globulin, human
diploid cell vaccine course, all of these would be treatments.
22. The RN advises the patient that without treatment, he is at risk of which of the following? Fatal encephalitis
23. Toxoplasmosis prevention includes hygienic precautions
24. What are the symptoms of Zika? Skin rash, Guillain-Barre syndrome, conjunctivitis
25. T of F: Most cases of Toxoplasmis are asymptomatic. True
26. Two diseases that are very dangerous for pregnant mothers due to congenital birth defects they can cause are: zika
and toxoplasmosis
27. Cerebrospinal fluid is found in the subarachnoid space
28. Meningococcemia is best treated with ceftriaxone, penicillin or chloramphenicol, associated with high fever,
vascular collapse, hemorrhage, and petechiae, started from a nasopharyngeal infection, caused by a gram-negative
diplococcus, all of the choices are correct
29. Neisseria meningitides is transmitted by close contact
30. Which organism is the definitive host for Toxoplasma gondii? Cat
31. Treatment of an animal bite for possible rabies includes debridement, washing the bite with soap and detergent,
infusing the wound with human rabies immune globulin (HRIG), postexposure vaccination with inactive vaccine, all
are correct
32. What are the features that H. influenza posses that can distinguish it from Neisseria meningitidis? H. influenzae does
not cause a skin rash and it’s prevented by Hib vaccine