Download Macroparasites - School of Public Health

Meet Your
Competition
A Social-Ecological Model
A Social-Ecological Model
Policies, Laws,
Other Cultures
Individual: genotype,
knowledge, beliefs,
experience
Interpersonal:
Family, friends,
social network
Community: Local
Organizational:
School, church, etc.
culture, natural &
built environment
What does it mean to be ‘Alive’?





One or more cells with DNA
Reproduce, grow, develop
Capture & use energy & raw materials
Sense & respond to environment
Evolve over generations
Living Things: 5 Kingdoms
Plants
Animals
Fungi
vertebrates
molds
invertebrates
yeasts
Algae
(plant-like)
Protozoa
(animal-like)
Protista
worms
Eukaryotes
Bacteria
Prokaryotes
Living & Non-living Infectious Agents
Macroparasites
 Animal Kingdom
(worms, arthropods)
 Protista (Protozoa)
Microparasites
 Fungi
Eukaryotes
 Bacteria
Prokaryotes
 Viruses
 Prions
Eukaryotic Cells




Fungi
Plants
Protista
Animals
 DNA in chromosomes in a membrane-bound nucleus.
 Other membrane-bound sub-cellular structures:
• Rough endoplasmic reticulum: for protein synthesis.
• Mitochondria: for metabolism and generation of ATP
(cellular energy).
Bacteria Are Prokaryotes
Prokaryotes are much simpler.
•
•
•
•
They have a circular chromosome (DNA),
but no nuclear membrane.
Most have a cell wall (proteincarbohydrate) outside the cell membrane.
Most reproduce by fission.
They have much simpler structure and
fewer organelles.
Prokaryotes are Simpler than Eukaryotes
Bacterium
Protozoan
Living & Non-living Infectious Agents
Macroparasites
 Animal Kingdom
(worms, arthropods)
 Protista (Protozoa)
Microparasites
Eukaryotes
 Fungi
 Bacteria
 Viruses
 Prions
Prokaryotes
Animal Kingdom (worms, arthropods)
Macroparasites
Flatworms
Roundworms
Vectors
Arthropods
Blood fluke
(Schistosomiasis)
Liver fluke
Pinworm
Ascaris (roundworm)
Trichinosis
Intestinal fluke
Hookworm
Tapeworms
Filariasis
Guinea worm
Mosquitoes
Fleas
Ticks
Lice
Parasite
An organism that spends much of its life living
on or in another organism.
• Macro – large (e.g. tapeworm)
• Micro – small (e.g. intestinal bacteria)
Vector
A non-human animal or microorganism (usually
an insect) that carries and can transmit a
disease agent to humans (by biting).
 Mosquitoes
 Fleas
 Deer tick
 Racoon
malaria
plague
Lyme disease
Rabies
Animal Reservoir
A species that harbors an infectious agent and
provides an ongoing source of future infection
for humans.
A larval cyst is eaten with
poorly cooked infected meat.
Eggs hatch
and form
new cysts.
Larvae pass to small
intestine & attach by
scolex suckers or hooks.
Beef & Pork
Tapeworms
Contaminated vegetation
is eaten by cows or pigs.
Proglottids with eggs
pass out with feces.
Proglottids develop
in 3-4 months.
Heavy infection: discomfort,
vomiting, & diarrhea
Light infection: asymptomatic
Schistosomiasis (Bilharzia)
200+ million people infected worldwide;
mainly Africa, South America, Far East;
FYI
Schistosomiasis
FYI
• Larva (cercariae) from snails penetrate human
skin, causing itching, & get to blood stream,
causing fever & chills.
• Adult male and female schistosomes pair and
live together in human blood vessels. The
females release eggs, some of which are
passed out in the urine (in S. haematobium
infection) or stools (S. mansoni, S. japonicum),
but some eggs are trapped in body tissues.
Immune reactions to eggs lodged in tissues are
the cause of disease.
• Eggs may accumulate in liver, spleen, intestine,
kidney or bladder causing severe damage,
bleeding, weakness, abdominal pain, diarrhea,
and, eventually, even cancer of the bladder.
Schistosome Life Cycle & Transmission
FYI
Eggs in human
feces & urine
egg
Female (arrows) lives in a
groove in the male’s body!
1 cm
Living Things: 5 Kingdoms
Plants
Animals
Fungi
vertebrates
molds
invertebrates
yeasts
Algae
(plant-like)
Protozoa
(animal-like)
Protista
worms
Eukaryotes
Bacteria
Prokaryotes
Living & Non-living Infectious Agents
Macroparasites
 Animal Kingdom
(worms, arthropods)
 Protista (Protozoa)
Microparasites
 Fungi
Eukaryotes
 Bacteria
Prokaryotes
 Viruses
 Prions
Algae
(plant-like)
Protozoa
(animal-like)
“Red Tide” Protista
Algal Bloom ("Red Tide”): a dense patch of certain dinoflagellates in water.
They’re not really “tidal,” and they’re not always red and don’t always cause
water discoloration. The blooms that occur in Florida and New England are
from different dinoflagellates. They produce neurotoxins (nerve toxins) that
can kill fish, birds, marine mammals and contaminate shellfish.
Protozoa
Single-celled, animal-like protista. They ingest food by
phagocytosis. They can move via pseudopods (amoeba)
or whip-like flagella. Some cause human disease.
Leishmaniasis
Trypanosomiasis
(sleeping sickness)
Trichomoniasis
Giardia
Malaria
Toxoplasmosis
Cryptosporidiosis
(Be able to give examples.)
Giardia lamblia
• A one-celled, microscopic intestinal parasite
that is a common cause of waterborne disease
worldwide.
• Incubation: 1-2 wks; duration 2-6 weeks.
• Symptoms: diarrhea, stomach cramps, weight
loss, dehydration.
• Spread:
 by swallowing feces-contaminated water
Includes recreational water (swimming pools, hot
tubs, fountains, lakes, ponds, or streams)
contaminated with sewage or feces from humans
or animals.
 by eating uncooked contaminated food.
Toxoplasmosis
Odero Kibati: A Kenyan Boy With Malaria
Odero’s blood sample
FYI
A chemical signal causes
simultaneous rupture of
thousands of red blood
cells (RBC), releasing
parasites & toxins.
Cycle repeats every
48 hours (tertian malaria).
Skin
Causes intense cold, shivers.
Then fever, headache,
delirium. Finally, a quiet
period, when merozoites
enter new red cells.
Relevance of Biology
to Public Health?
Pork/Beef
Tapeworm
Fish
Tapeworm
Schistosomiasis
Living & Non-living Infectious Agents
Macroparasites
 Animal Kingdom
(worms, arthropods)
 Protista (Protozoa)
Microparasites
Eukaryotes
 Fungi
 Bacteria
 Viruses
 Prions
Prokaryotes
Fungi
Important in breaking down dead organic material &
recycling nutrients through ecosystems. They supply
nutrients to the roots of many plants. Provide a source of
antibiotics. They provide food (mushrooms, truffles), make
bread rise, and enable fermentation of sugar to alcohol.
Potato blight
Candidiasis
Fungi also cause a number of plant
Aspergillosis
and animal diseases: in humans,
ringworm, athlete's foot, and
several more serious diseases are
caused by fungi. Because fungi are
Tinea capitis
more chemically and genetically
(ringworm of the head)
similar to animals than other
organisms, this makes fungal
diseases very difficult to treat.
Tinea pedis
Cryptococcosis
(Be able to give examples.)
(athlete’s foot)
Fungi


Plant-like, but fungi lack chlorophyll.
Fungi grow into a substrate & absorb nutrients from it.
– Saprophytes decompose dead organic matter.
– Parasitic fungi feed on living organisms without killing them
(e.g. ringworm & athletes foot).
– Mutualistic, living with other species, e.g. lichens (algae +
fungus) grow in a symbiotic relationship on rocks & trees.
Hyphae & Mycelia
Branching hyphae.
Fungi are generally composed of branching
filaments (“hyphae”) that sometimes form a large
interlacing mass called a “mycelium”, a term that
applies to the whole body of any fungus. The
hyphae have cross walls, but they are perforated
allowing free passage of nuclei and cytoplasm.
So, they are not truly multi-cellular (plants are).
Types Of Fungi
• Molds: form mycelia
(e.g. Penicillium chrysogenum)
•
Mushrooms: Large, organized
hyphal structures.
•
Yeasts (Candida): single-celled forms
(Candida albicans)
Candida albicans
Branching hyphae.
Unicellular yeast.
Oral thrush in a patient
receiving chemotherapy.
Candida species are common fungi that are normal flora on our
skin and in our respiratory, genital, and digestive tracts. Normal
flora usually keep it in check. However, they can cause
infections, which can be mild (diaper rash and vulvar rash) or
severe (oral thrush, esophagitis, and rapidly fatal systemic
diseases in immunocompromised people). Candida is usually a
yeast, but can form hyphae.
Tinea (Ringworm)
• Cause: a fungus that grows on skin.
• Spreads in rings. The center clears & a
•
•
•
•
new ring of infection develops at the edge.
Ringworm of scalp is spread by sharing of
hats, combs, or brushes.
Ringworm of the body can be spread on
towels, clothing, or sports equipment.
Dogs & cats can be infected and can pass
it to people through direct contact.
Personal hygiene is important in
preventing spread.
Cryptococcus
(Not to be confused with cryptosporidiosis,
a protozoan that causes diarrhea.)
• A yeast found in soil and bird droppings worldwide.
• Can cause pneumonia or meningitis in
immunocompromised people.
Aflatoxins
A kernel of corn infected
with Aspergillus flavus.
• Substances produced by certain species of Aspergillus mold
(a mold that grows on peanuts, corn, grain).
• Metabolites of the toxins have high affinity for DNA and
produce multiple abnormalities in gene expression. As a
result they interfere with many cellular processes.
• Aflatoxins are carcinogenic in rats, ducks, mice, trout &
subhuman primates. Trout are the most susceptible, & only
1ppb of aflatoxin B1 will cause liver cancer in trout.
• Some studies indicate that aflatoxins increase the risk of
liver cancer in humans who are hepatitis B carriers.
Penicillin
Mycelium (mold)
Bacteria
• Originally from a mold; now many synthetics.
• Microorganisms synthesize molecules that enable them to
defend against or compete with other microorganisms.
Ergotism
The poisonous part is the sclerotium
(ergot body), a grain-shaped fungal
mass. Federal law prohibits use of
cereal grains containing more than
0.3% sclerotia by weight.
• Caused by a mold of rye grass, wheat,
and barley.
• Two syndromes are produced by ingestion:
1) “Gangrenous” (Vascular constriction)
Ingestion of small amounts daily can cause constriction of
blood vessels, which in turn causes decreased blood flow
with coldness, numbness, loss of function, and dry
gangrene. In humans gastrointestinal distress and
headache may be present.
2) “Convulsive (Neurological changes)
Ingestion of larger quantities causes constrictive symptoms
plus hyperexcitability, paranoia, rapid pulse, and
belligerence, spasms & delirium.
St. Anthony’s Fire
Salem Witch Trials
Living & Non-living Infectious Agents
Macroparasites
 Animal Kingdom
(worms, arthropods)
 Protista (Protozoa)
Eukaryotes
Microparasites
 Fungi
 Bacteria
 Viruses
 Prions
Prokaryotes
Defining Characteristics of Bacteria
1. Prokaryotes: a chromosome with circular
DNA, but no nuclear membrane.
2. Most have a cell wall (proteincarbohydrate) outside the cell membrane.
3. Most reproduce by fission.
• The most abundant organisms. Billions in a handful of soil. The bacteria
in your gut & on your skin outnumber the cells in your body.
• Live in deserts, hot springs, oceans, glaciers.
FYI
3. Bacteria Are Living Organisms
That Grow & Reproduce By Fission
Video: Bacterial Growth and Division
Bacteria (Prokaryotic)
(Be able to give
examples.)
Plague
E. coli
Cholera
Clostridium
Staphylococcus
Streptococcus
Salmonella
Chlamydia
Rickettsias
Gonorrhea
Syphilis
Tuberculosis
Lyme Disease
Rickettsia
• Rocky Mountain spotted fever
• Typhus (jail fever)
FYI
Borrelia burgdorferi
(Lyme Disease)
10-26 mm
•Lyme Disease
FYI
FYI
Lyme Disease
http://www.nature.com/nrmicro/journal/v10
/n2/fig_tab/nrmicro2714_F1.html
Vibrio cholera
2 mm
FYI
Cholera
Treponema
pallidum
10 mm
Syphilis
FYI
Salmonella
2-5 mm
Salmonellosis
FYI
Escherichia coli
2-6 mm

Most are normal flora of intestine
 Some strains cause diarrhea
 Some strains make toxins
 Urinary tract infection
FYI
E. Coli O157:H7
NPR
Transmission: ( the main source is cattle)
– Undercooked hamburgers
– Salami
– Alfalfa sprouts, spinach
– Lettuce
– Unpasteurized milk, apple juice/cider
– Feces contaminated water (wells, pools, public
drinking water.
Clinical: 2-5 days after ingestion: nausea, cramps, bloody
diarrhea, fatigue, occasionally vomiting.
• Lasts 5-10 days. Antibiotics & anti-diarrhea medications
are not recommended.
• Occasionally causes hemolytic uremic syndrome
(destruction of platelets and renal failure).
Clostridium
1 mm



FYI
Botulism
Tetanus
Gas gangrene
Some bacteria form spores under adverse environmental
conditions. Each bacterium forms a single “endospore”, which
transforms into an active bacterium when conditions are
favorable. Spore formation allows Anthrax and Clostridia to
survive in soil under conditions unfavorable to growth.
Staphylococcus
1 mm

Abscesses
 Boils
 Pneumonia
 Toxic shock syndrome
 Methicillin-resistant S. aureus (MRSA)
FYI
Streptococcus
< 0.2 mm



Impetigo
Pneumonia
“Flesh-eating bacteria”
FYI
Yersinia pestis
2 mm

Plague
FYI
Neisseria


Gonorrhea (Neisseria gonorrhea)
Meningitis (Neisseria meningitidis)
FYI
Chlamydia
1 mm


STD (symptomatic or asymptomatic); PID
Newborns: conjunctivitis; pneumonia
FYI
Normal Flora
• Healthy internal tissues (e.g. blood, brain,
muscle, etc.) are free of microorganisms, but
skin & mucous membranes in contact with
environmental organisms become colonized by
some. (Organisms regularly found at a given
site are the “normal flora.”
• The normal flora of humans is consists of >200
species of bacteria. Their makeup depends on
age, sex, stress, nutrition, etc.
Examples of Normal Flora
FYI
BACTERIUM
Skin
Eyes
Nose
Pharynx
Mouth
Colon
Lower
urethra
Vagina
Staphylococcus
epidermidis
++
+
++
++
++
+
++
++
Staphylococcus
aureus*
+
+/-
+
+
+
++
+/-
+
Streptococcus
salivarius
++
++
Enterococcus
faecalis*
+/-
+
++
+
+
+
+
+
+
+
++
+
Streptococcus
pneumoniae*
Streptococcus
pyogenes*
+/+/-
+/-
+/-
Neisseria
meningitidis*
+/+/-
+/+
Escherichia coli*
+/-
+/-
+/-
+
++
+
+
Proteus sp.
+/-
+
+
+
+
+
+
+/-
+/-
+
+/-
+
+
+
++
++
+/-
++
Pseudomonas
aeruginosa*
Haemophilus
influenzae*
Lactobacillus sp.
Clostridium sp.*
+/-
+
++
Benefits of Normal Flora
1. Prevent colonization by pathogens by competing for
attachment & nutrients.
2. Synthesize vitamins that are absorbed as nutrients by the
host (e.g. K & B12).
3. Produce substances that inhibit pathogenic species.
4. Stimulate the development of certain tissues, e.g. colon and
lymphatic tissues in gastrointestinal tract.
5. Stimulate production of cross-reactive antibodies. Since the
normal flora behave as antigens in an animal, they induce
low levels of antibodies that cross react with similar
antigens on pathogens, preventing infection or invasion.
Living & Non-living Infectious Agents
Macroparasites
 Animal Kingdom
(worms, arthropods)
 Protista (Protozoa)
Eukaryotes
Microparasites
 Fungi
 Bacteria
 Viruses
 Prions
Prokaryotes
Viruses Are Non-Living
Assemblies of Organic Molecules
Polio virus
A virus is a non-cellular
infectious agent .
Tobacco
mosaic
virus
Bacteriophage T4
Anatomy of Influenza Virus
A virus consists of a protein coat
wrapped around a nucleic acid core.
RNA
Some have DNA; some have RNA.
Viruses Are Non-Living
• They are non-cellular.
• They reproduce only when their genetic material & a few
enzymes enter a host cell & use its biosynthetic machinery.
• They cannot sense & respond.
• They cannot capture and use energy & raw materials.

One or more cells with DNA
 Reproduce, grow, develop
 Capture & use energy & raw materials
 Sense & respond to environment
 Evolve over generations
Criteria
For Life
Replication of Influenza Virus
1. Viral coat glycoproteins,
hemagglutinen, bind to cell
surface receptors with
neuraminic acid
2. Viral genome (8 RNA strands)
replicates itself and viral
proteins
3. Progeny virus self-assemble at
surface & bud off from host cell
Virus Infecting A Cell
A Comparison of
Bacteria
&
Viruses
Bacteria
Viruses
Complete simple (prokaryotic) cells
Non-cellular
0.5 – 5 m m in diameter
.02 – .2 m m
Genes on a DNA chromosome ring
Genes in short strand of DNA or RNA
Surrounded by cell membrane & cell wall
(& sometimes a sticky capsule)
Surrounded by protein capsid
Spherical, rod-shaped, or spiral
Usually simple geometric shape
Can reproduce independently
Hijack other cells to replicate
Energy from sun, nutrients, chemicals
Energy for replication always from host
Most free-living or symbiotic;
only about 5% pathogenic
All parasitic, almost all pathogenic
Diseases caused by destruction of cells , toxins
released by bacteria, inflammation (host’s
immune response)
Diseases caused by interactions of viruses with
genes, destruction of cells during replication,
inflammatory response
Recognize and attach to host cells through
matching proteins
Recognize and attach to host cells through
matching proteins
Most respond to certain antibiotics
Unresponsive to antibiotics
Some survive hard times as living endospores
Many are fragile, but some survive long periods
Relative Sizes
A Rogue’s Gallery
of Viruses
Bacteriophage T4
Tobacco mosaic virus
Chickenpox
Human papilloma virus
Smallpox
Polio
Herpes
SARS
Mumps
HIV
Influenza
Ebola
(Be able to give examples.)
Bacteriophage T4
FYI
• A virus that infects bacteria.
• Useful for genetically engineering bacteria.
• sheaths
• tail fibers
DNA
core
Smallpox
FYI
Influenza
FYI
Patterns of Viral Infection
production
Acute : virus rapidly kills cells; rapid, self-limiting
or fatal disease. e.g. Influenza, smallpox, SARS
Chronic : No immediate cell death.
e.g. hepatitis B & C
Virus
LatentTime
infection: dormant infection with
episodic reactivation. e.g. shingles
Slow : initial infection cleared; intermittent increases
in “viral load” ultimately defeat the host. e.g. HIV
Varicella
(Chickenpox)
Chickenpox: Relatively mild in childhood, more
severe in adults, & extremely severe in
immunocompromised people.
With the initial infection there may be a latent
infection in nerve cells (dorsal root or cranial
nerve). See the next slide for an example.
Herpes Zoster (Shingles)
“Shingles” or Herpes zoster is a reactivation of the
chickenpox virus that can occur in older adults or people
with impaired immune function. Painful lesions appear
along a dermatome & may persist for months. Zoster
lesions contain live virus and may cause chickenpox in
susceptible people.
Shingles along trigeminal
(5th cranial) nerve
Shingles along a rib
Type I Herpes Simplex –
Latent Infection
• Nearly everyone has this virus in ganglia in face (clusters of
•
nerve cell bodies).
Stress (e.g. sunburn) reactivates virus, which move down
neuron to their tips near the skin and infect epithelial cells
causing sores.
Living & Non-living Infectious Agents
Macroparasites
 Animal Kingdom
(worms, arthropods)
 Protista (Protozoa)
Eukaryotes
Microparasites
 Fungi
 Bacteria
 Viruses
 Prions
Prokaryotes
"If an evil force could devise an agent capable
of damaging the human race, he would make it
indestructible, distribute it as widely as possible
in animal feed so that it would pass to man, and
program it to cause disease slowly so that
everyone would have been exposed to it before
there was any awareness of its presence."
Richard Lacey, British microbiologist
Darren Jones
• A farm worker in England.
• He died from Creutzfeldt-Jakob disease, a
•
progressive neurodegenerative disorder
caused by abnormal prions.
CJD is the human form of Mad Cow Disease.
1920: Hans Creutzfeldt describes a progressive neurological &
mental disturbance in a 23 y.o. woman. Alfons Jakob describes
3 more in 1921 & the term 'Creutzfeldt-Jakob disease' (CJD) is
coined.
CJD: deposition of abnormal
proteins causes loss of motor
control, progressive
dementia, paralysis and
wasting. Terminally, the
patient is usually mute, rigid
& unresponsive.
1950s: “kuru” in Papua New Guinea turns out to be due
ingesting brain tissue of dead relatives for religious reasons.
Similar Diseases in Animals
 Scrapie: a disease in sheep and goats; probably existed
for 200 years before jumping to cattle, when rendered
(cooked) meat meal from sheep was fed to cattle as a
protein supplement.
 Bovine Spongiform Encephalopathy (BSE): a
progressive degeneration of the nervous system causing
nervousness, aggression, incoordination, abnormal gait,
heightened sensory perception, itching, excessive licking, &
death. The label "Mad Cow Disease" is related to abnormal
motor nerve control & aggressiveness.
 Feline Spongiform Encephalopathy has been transmitted
in zoos to many animals (cheetah, puma, ocelot, ostrich).
The brain becomes vacuolated (full of holes like a "sponge").
Neurons contain vacuoles containing abnormally folded prion
proteins that cannot be broken down by normal cellular
degradation processes. Accumulation of these proteins leads
to degeneration & death of nerve cells in the brain.
What Is Prion Disease?
Prusiner's hypothesis:
A mutant prion is an abnormally folded prion protein (PrPSc)
that is resistant to heat & sterilization, and does not evoke an
immune response. The protein is chemically the same, but
folds differently. The abnormal protein contacts normal proteins
in neural tissue and induces them to refold into an abnormal
conformation as well. Refolded molecules induce the same
change in still more proteins. The abnormal proteins resist
degradation and accumulate in neural tissue causing damage.
Alpha helices
Beta sheet
• The normal protein has alpha helices, regions twisted into a
spiral. The abnormal prion has beta sections (straight)
where spirals should be. The straight beta sections can selfassociate to form beta-sheets.
• When an abnormal (infectious) PrPSc form contacts a
normal PrP, the normal form can switch from alpha-helical
to beta-sheet form. This starts a chain reaction in which
newly converted PrPSc change the shape of normal PrP.
The Origins of BSE In The UK
• BSE in Britain was caused by feeding cattle rendered
protein produced from the carcasses of scrapie-infected
sheep.
 The use of meat and bone meal in cattle rations as
a source of protein has been common for several
decades. In the early 1980's they eliminated a
solvent-extraction process and steam-heat
treatment & this may have allowed transmission
of the infective agent to cattle. The feeding of
animal protein derived from ruminants ceased in
Britain in July 1988.
• In cases of BSE in cattle, the agent has been found only
in brain tissue, spinal cord and retina. It has not been
found in meat or milk.
BSE Epidemic in England
Time course of epidemic BSE in the UK, 1986-2000,
with dates of major precautionary interventions.
SBO= specified bovine offals (brain, spinal cord, thymus, tonsil, spleen &
intestines) from cattle > 6 months old;
MBM= meat & bone meal (protein residue produced from rendering.
Prion Diseases In Man
• Classical CJD: sporadic; 1 per million, generally in older patients.
Actual incidence may be higher: One study found that 6/46 cases
clinically diagnosed as Alzheimer's were CJD at autopsy. Can be
inherited.
• In New Guinea, a variant called Kuru causes periodic outbreaks
through cannibalistic practices. Pathologically similar to CJD and
scrapie.
•
Iatrogenic forms: (accidentally caused during therapy)
 51 of 968 children treated in France with Human Growth Hormone
became infected with CJD.
 Via corneal graft transplants.
 Via cerebral cortex electrodes & surgical instruments, despite
repeated cleanings and sterilizations.
• Variant CJD (vCJD): from eating of cattle with BSE
Scrapie, BSE, kuru, CJD, etc. are caused by different prions.
Variant CJD (vCJD)
BSE in Europe correlated with vCJD
occurrence, which predominantly affects
younger persons (median age at death:
29 years) and has atypical clinical
features (prominent psychiatric or
sensory symptoms, delayed onset of
neurologic abnormalities, duration of
illness of at least 6 months, and a
diffusely abnormal non-diagnostic EEG).
The BSE agent is found in brain, spinal cord, retina, dorsal root
ganglia (nervous tissue along the backbone), distal ileum, and
the bone marrow of cattle experimentally infected with this
agent by the oral route.
Bovine Spongiform Encephalopathy in the United
States — An Epidemiologist’s View
Christl A. Donnelly, Sc.D. N Engl J Med 350;6 February 5, 2004
“Thus, the available evidence suggests that if the current
control measures are well enforced, then the risk, if any,
from U.S. cattle, is very low, although further regulation to
limit exposure to material from cervids infected with chronic
wasting disease would further reduce the potential risk of
cervid-to-cattle transmission. Consumers need not be overly
anxious about the risks they may have incurred by
consuming beef, but they should press authorities to test
more cattle, to strengthen the regulations on feed
production, and to extend the ban on brain and spinal cord
in food for human consumption to include cattle younger
than 30 months of age.”
How Did Abnormal Prions Originate?
A mutation that changes a single DNA base pair can change
one or more amino acids in the protein gene product, and
the protein’s properties may be altered.
DNA:
TAC-TTC-GGC-TCA-ATT-CTA
mRNA: AUG-AAG-CCG-AGU-GAU-UAA
Amino acid
sequence in
protein:
Methionine-Lysine-Proline-Serine-Aspara….
DNA:
TAC-TTC-GGT-TCA-ATT-CTA
mRNA: AUG-AAG-CCA-AGU-GAU-UAA
Amino acid
sequence in
protein:
Methionine-Lysine-Leucine-Serine-Aspara….
In PrP changing only one base pair out of 750 causes the
amino acid leucine to be substituted for proline in the PrP
protein, making it more susceptible to flipping from the normal
a-helix form into the infectious b-sheet form. Thus, prion
diseases can be inherited as well as transmissible.
Sickle Cell Anemia
Sickle Cell Anemia
Also results from a mutation due to
replacement of a single base in DNA.
FYI
Diagnosis of BSE
• Confirmation of disease is only possible by postmortem examination of brain tissue. Because the
prion protein is an incorrectly folded normal protein,
no inflammatory or immune response is generated.
• No test currently exists to detect BSE in a live
animal. The diagnosis must be made at necropsy
by examining brain tissue histologically and
biochemically.
The Good News …
• CJD death rate in the US has remained stable
at about one case per million population per
year.
• In addition, CJD deaths in persons aged <30
years in the US remain extremely rare (<1 case
per 100 million per year).
The News On
Prion Diseases
Bad news:
• Long incubation period (10 years).
• Mortality 100%.
• Prions persist in the environment.
More bad news:
• Like influenza, this disease can jump species
barriers. No current treatment or ante-mortem
diagnostic test exists.
Even more bad news:
• Development of a vaccine is unlikely.
Routes of Transmission
• Highest concentrations of PrPSc are in central nervous
system (brain and spinal cord). Also likely in spleen,
thymus, lymph nodes, lung.
 Not spread by droplet or airborne transmission
 No documented spread via contact with blood or
body fluids, but spread by these means is a
possibility.
• If working with prion-contaminated material, avoid
contact with punctured skin.
 If caring for someone with prion disease
universal precautions are adequate.
Inactivation of Prions
• Prions are extremely resistant to conventional
inactivation procedures including irradiation,
boiling, dry heat, and chemicals (formalin,
betapropiolactone, alcohols).
• Prions are inactivated by
 1N sodium hydroxide,
 4.0 M guanidinium hydrochloride or
isocyanate,
 sodium hypochlorite (2% free chlorine)
 steam autoclaving at 132C for 4.5 hours.
FYI
FYI
Prevention of vCJD
• Enhanced BSE surveillance & culling of sick
•
•
animals.
Ban of “specified risk materials” from animal feed
& human food chain.
Banning of the use of mechanically recovered
meat from the vertebral column of cattle, sheep,
and goats for human food.