Infectious Diseases of the Central

Nervous System

Prepared by:
CESAR M. MENDOZA, JR., RMT, M.Bio.Ed.
Nervous System
●
Brain

CNS ●

●
Spinal cord
Meninges

PNS Nerves
●
 Terms related to Nervous System
CSF – Cerebrospinal Fluid found in the surarachnoid
spaces
BBB (Blood Brain Barrier) – supplying nutrients but not
allowing larger particles such as macromolecules
(CHON, antibodies), cells of the immune system, and
microorganisms to pass from the blood into the brain.
NO INDIGENOUS FLORA IN THE NERVOUS
SYSTEM
Microbial access: CNS through fracture/surgery, blood
and lymph to the CSF, along peripheral nerves.
 Infections of the CNS:
ENCEPHALITIS: Inflammation of the BRAIN
ENCEPHALOMYELITIS: Inflammation of the
brain and spinal cord
MENINGITIS: Inflammation of the membranes
of brain and spinal cord
MENINGOENCEPHALITIS: Inflammation of
the brain and meninges
MYELITIS: Inflammation of the spinal cord.
Meningitis
Caused by bacterial, fungal, viral,
pr0tozoan organism
Majority of cases are bacterial:
Streptococcus pneumoniae (elderly)
Haemophilus influenzae (children)
Neisseria meningitidis (adolescents)
Meningitis
Viral meningitis – “aseptic meningitis”; 50%
of viral cases are unidentified
Viruses include: enterovirus – major viral
cause
Others: coxsackievirus, echoviruses,
mumps virus, arbovirus, (arthropod),
poliovirus, adenovirus, measles virus, HSV,
varicella virus
Haemophilus influenzae

Gram negative, has LPS

Common cause of ear, eye, throat infections

Manifestations:
Fever
Vomiting
Nausea
Tiredness
Neisseria meningitidis

Gram negative diplococcus

Causes meningicoccal meningitis, epidemic meningitis
spread by direct contact, usually begins as a throat
infection
can have asymptomatic carriers
Pathogenesis
Transmission:

spread through the exchange of saliva and other

respiratory secretions.
Symptoms:
Septicemia
nausea, vomiting, weakness, low blood pressure
Meningitis
Meningococcal meningitis: N. meningitidis
causes inflammation of the tissue
surrounding the brain and spinal cord (the
meninges)
high fever
headache
stiff neck
Meningococcemia
N. meningitidis

Meningococcemia
(blood):
 fever and rash
purpura
Streptococcus pneumoniae (pneumococcal meningitis)
Gram positive cocci
Spread by droplet infection
Treatment

most broad spectrum antibiotics

vaccine (Pnemoshot) made up of capsular polysaccharide

Listeria monocytogenes – Listeriosis

foodborne primarily unpasteurized dairy products

contaminated with animal feces, can grow in the fridge
are invasive, live in phagocytes, prefers those in the
central nervous system
can be transferred through the placenta resulting in
spontaneous abortion and
still birth
Symptoms: range from asymptomatic to nausea to
septicemis to meningitis,etc.
Other Symptoms
fever and muscle aches
diarrhea
headache
stiff neck
confusion
loss of balance
convulsions
Reservoirs and Mode of Transmission
Reservoirs: Mode of Transmission

Soil Via ingestion of raw or

Water contaminated milk, soft
cheeses, and vegetables
Mud
Infected mammals From mother to fetus in
Infected humans utero or during passage
Soft cheeses through an infected birth
canal
Treatment
ampicillin in the early stages

sulfa drugs in advanced infections

Tetanus and Botulism

Clostridium tetani Clostridium botulinum

produces the tetanus toxin produces the botulinum
which results in toxin which causes
continuous muscle continuous muscle
contraction, can lead to relaxation
systemic organ failure and
death
Clostridium tetani

causative agent of tetanus

organism is found in soil, especially heavily-manured

soils, and in the intestinal tracts and feces of various
animals.
Tetanus
from a potent neurotoxin (tetanus toxin or
tetanospasmin)

highly fatal disease

Mortality rates reported vary from 40% to 78%

http://en.wikipedia.org/wiki/Tetanus
 Pathogenesis
result from small puncture wounds or lacerations which
become contaminated with C. tetani spores that germinate
and produce toxin

toxin produced during cell growth, sporulation and lysis

migrates along neural paths from a local wound to sites of

action in the CNS
Neonatal tetanus
follows infection of the umbilical stump in infants
born to nonimmune mothers (therefore, the infant
has not acquired passive immunity)

usually results from a failure of aseptic technique

during the birthing
 Toxin Action
Tetanospasmin initially binds to peripheral nerve terminals
transported within the axon and across synaptic junctions
until it reaches the CNS
becomes rapidly fixed to gangliosides at the presynaptic
inhibitory motor nerve endings, and is taken up into the
axon by endocytosis
Effect of the toxin:block the release of inhibitory
neurotransmitters (glycine and gamma-amino butyric
acid) across the synaptic cleft, which is required to check
the nervous impulse
If nervous impulses cannot be checked by normal
inhibitory mechanisms, it produces the
generalized muscular spasms characteristic of
tetanus.

Tetanospasmin act by selective cleavage of a

protein component of synaptic vesicles,
synaptobrevin II, and this prevents the release of
neurotransmitters by the cells
Clinical pattern of generalized tetanus
severe painful spasms and rigidity of the
voluntary muscles

 "lockjaw“

progressive rigidity and violent spasms of the

trunk and limb muscles

spasms of the pharyngeal muscles cause difficulty

in swallowing
Treatment

Tetanus – part of DPT vaccine, given pre-made antitoxin

antibodies which will bind and neutralize toxin (passive
immunization) plus a booster shot of the DT vaccine
Clostridium botulinum
large anaerobic bacillus that forms subterminal
endospores

widely distributed in soil, sediments of lakes and
ponds, and decaying vegetation, intestinal tracts of
birds, mammals and fish
 Pathogenesis of Botulism
Food-borne Botulism
Infant Botulism
botulinum toxin is ingested
with food disease occurs in
infants 5 - 20 weeks of
absorbed by the upper part of age that have been
the GI tract, passes into the exposed to solid foods
blood stream by which it
reaches the peripheral
neuromuscular synapses  characterized by
constipation and weak
binds to the presynaptic sucking ability and
stimulatory terminals and
blocks the release of the generalized weakness
neurotransmitter
acetylcholine
Botulinum Toxin

Botulinum neurotoxins predominantly affect

the peripheral nervous system reflecting a
preference of the toxin for stimulatory motor
neurons at a neuromuscular junction

The toxin binds to the neuron and prevents the

release of acetylcholine across the synaptic
cleft

 Primary symptom is weakness or flaccid

paralysis
Clinical symptoms of botulism
begin 18-36 hours after toxin ingestion with
weakness, dizziness and dryness of the mouth

 Nausea and vomiting may occur

 Neurologic features soon develop: blurred

vision, inability to swallow, difficulty in speech,
descending weakness of skeletal muscles and
respiratory paralysis
Prevention
Proper food handling and preparation

The spores of C. botulinum can survive boiling

(100 degrees at 1 atm) for more than one hour
although they are killed by autoclaving

Food containers that bulge may contain gas

produced by C. botulinum and should not be
opened or tasted

 Other foods that appear to be spoiled should

not be tasted
Treatment

Botulism – no vaccine, given antitoxin antibodies

Mycobacterium leprae (Leprosy)
relative of Mycobacterium tuberculosis
lives in peripheral nerves and skin cells, intracellular
pathogen
grows best at 30C so prefers extremities such as
fingers, toes, nose
produces enzymes that degrade the nerve cells
loose sensation, tissue damage
spread by prolonged direct contact with nasal
secretions carrying M. leprae
 not at all highly contagious
http://www.google.com.ph/#hl=en&safe=active&q=Mycobacterium+leprae+%28Leprosy%29%0B&meta=&fp=a4738ba4588c5dff
Treatment

rifampin
dapsone (a sulfa drug)
 vaccine trials with live, attenuated M. leprae to target cell
mediated response because this is an intracellular
pathogen and you need to kill both the bacterium and the
infected host cell
Viral Diseases of the Nervous System
Poliomyelitis, Polio, Infantile Paralysis

an acute viral infectious disease spread from person to person,

primarily via the fecal-oral route

Symptoms: inflammation of the CNS, especially the anterior horn cells

of the spinal cord and the brainstem (the portion of the brain between
the cerebral hemispheres and spinal cord)

80-90% of clinical infections, chiefly in young children, does not

involve the CNS

Symptoms:slight fever, malaise, headache, sore throat, vomiting 3-5

days after exposure. Recovery occurs in 24-72 hours (abortive type of
polio)
Polio Virus
virus lives in motor neurons

Reservoir: Infected humans

MOT:
direct contact by ingestion of fecal contaminated food
or water

enters via the gastro-intestinal tract then penetrates to

surrounding neurons
Treatment

OPV (oral polio vaccine) produces IgA

new vaccine – killed virus, given as an injection, targets

the nervous system directly, produces IgG
Rabies
a viral neuroinvasive disease that causes acute
encephalitis (inflammation of the brain) in warm-
blooded animals

With mental depression, restlessness, headache,

fever, malaise, paralysis, salivation, spams of throat
muscles induced vby a slight breeze or drinking
water, convulsions, death due to respiratory failure

 It is zoonotic (i.e. transmitted by animals)

Rabies Virus
transmitted by bite from infected host or aerosol from
host, not contagious

virus shed in saliva

 infection begins in the peripheral nerves and travels

to the brain

long incubation period: 5-8 weeks before symptoms

seen
Treatment
1.passive immunization with pre-made anti-rabies abs that
will neutralize any free virus

2. active immunization by injection of live attenuated

virus, stimulates cell mediated response, works well due
to the very long incubation period
 Arboviral Encephalitis
arbo = arthropod borne
by arthropod (insect) bite – insect is unharmed but
carries the virus
virus enters blood and peripheral nerves, travels to the
brain and causes encephalitis

- e.g. Manitoba has Western Equine Encephalitis

(WEE) Virus
birds and horses are reservoirs
spread by mosquitoes
Symptoms
Treatment

none, 100% mortality, rare occurrence

horses given vaccine of attenuated virus

mosquito control is the best prevention

 Lymphocytic Choriomeningitis
A rodentborne viral disease that presents as aseptic
memingitis, encephalitis, or meningoencephalitis

Maybe asymptomatic or symptomatic

Fever, malaise, lack of appetite, headache, nausea,

vomiting, sore throat, coughing, joint pain, chest
pain, salivary gland pain
Etiologic Agent: Reservoir:

Lymphocytic Infected rodents,

Choriomemningitis primarily common
Virus (LCMV) house mouse
Mode of Transmission
Exposure to mouse urine, droppings, saliva or
nesting materials

Virus can enter broken skin, the nose, the eyes, or

the mouth

Via bite of an infected rodent

Organ transplantation
 Disease Pathogen Reservoirs Vectors
Eastern Equine EEE virus(RNA Birds, Horses Aedes, Coquilletida,
Encephalitis virus,Family Culex, Culiseta
(EEE) Togaviridae) mosquitoes
California CEV (RNA Rodents, Rabbits Aedes and Cules
Encephalitis virus,Family mosquitoes
Bunyaviridae)
LaCrosse LaCrosse encephalitis Chipmunks, Aedes mosquitoes
Encephalitis virus (RNA Squirrels
virus,Family
Bunyaviridae)

St. Louise St. Louise Encephalitis Birds Culex mosquitoes

Encephalitis virus(RNA virus,
Family Flaviviridae)
West Nile Virus West Nile virus(RNA Birds, Pehaps Horses Culex mosquitoes
Encephalitis virus, Family
Flaviviridae)
Western Equine WEE virus (RNA virus, Birds, Horses Aedes and Culex
Encephalitis Family Togaviridae) mosquitoes
(WEE)
Protozoan Diseases of the Nervous System
African Trypanosome – Sleeping Sickness
MOT: TseTse fly bite

Trypanosome enters the blood then travels to the

central nervous system, then brain causing meningitis
or encephalitis
Symptoms
Main symptom: coma (sleeping sickness)

Others: headache, stiff neck, sleep disturbance,

depression, followed by progressive mental
deterioration, focal seizures, tremors, and
palsiesprogresses to coma and the ultimate
death of the patient often secondary to
pneumonia or sepsis.   Without treatment,
African trypanosomiasis is a universally fatal
illness
Two forms
Trypanosoma brucei Trypanosoma brucei
gambiense rhodesiense

found in west and found in eastern and

central Africa southern Africa
causes a chronic causes an acute infection
infection
Treatment
none, no vaccine as the trypanosome keeps changing

 prevention is best: using mosquito netting and

insecticides
American Trypanosomiasis
known as Chagas’ disease
Causative agent: Trypanosoma cruzi

Triatomine bug
Signs & Symptoms

Acute •Romaña’s sign, or swelling of the eye on one side of the face,
usually at the bite wound or where feces were rubbed into the eye
fatigue, fever, enlarged liver or spleen, and swollen lymph glands.
Sometimes, a rash, loss of appetite, diarrhea, and vomiting occur
•last for 4-8 weeks

Indeterminate •Eight to 10 weeks after infection, the indeterminate stage begins.

• During this stage, people do not have symptoms.

Chronic •Ten to 20 years after infection

•Cardiac problems, including an enlarged heart, altered heart rate
or rhythm, heart failure, or cardiac arrest are symptoms of chronic
disease, enlargement of parts of the digestive tract, which result in
severe constipation or problems with swallowing
Leishmaniasis

disease transmitted by the bite of the phlebotomine

sandfly,
transmits the Amastigotes leishmania parasite
Signs and symptoms

skin sores which erupt weeks to months after the

person affected is bitten by sand flies

 Other consequences: manifest anywhere from a few

months to years after infection - fever, damage to the
spleen and liver, and anaemia.
 Forms of Leishmaniasis
Visceral leishmaniasis – (kala-azar, black fever, and Dumdum
fever) the most serious form and potentially fatal if untreated.

Cutaneous leishmaniasis – the most common form which causes

a sore at the bite site, which heal in a few months to a year,
leaving an unpleasant looking scar. This form can progress to any
of the other three forms.

Diffuse cutaneous leishmaniasis – this form produces widespread

skin lesions which resemble leprosy and is particularly difficult to
treat.

Mucocutaneous leishmaniasis –( Espundia," and "Leishmaniasis

americana) commences with skin ulcers which spread causing
tissue damage to (particularly) nose and mouth
Naegleria fowleri
free-living amoeba typically found in warm fresh water,
from 25–35 °C (77–95 °F) in an amoeboid or temporary
flagellate stage

can invade and attack the human nervous system via

the nose
Causes primary amoebic meningoencephalitis
Signs and Symptoms
Fever
Headache
Stiff neck
Lethargy
Confusion
Altered level of consciousness
Seizures
Brain tissue with Naegleria fowleri
Acanthamoeba
one of the most common protozoa in soil, and also
frequently found in fresh water and other habitat
Acanthamoeba granulomatous encephalitis

altered mental status

Headaches
Fever
 neck stiffness
 seizures
 focal neurological signs such as cranial nerve palsies
and coma all leading to death within one week to
several months