1





Cause many infections of humans, animals,
plants, and bacteria
Cannot carry out any metabolic pathway
Neither grow nor respond to the environment
Cannot reproduce independently
Obligate intracellular parasites
2




Cause most diseases that plague
industrialized world
Virus – miniscule, acellular, infectious agent
having one or several pieces of either DNA or
RNA
No cytoplasmic membrane, cytosol, or
organelles
Have extracellular and intracellular state
3

Extracellular state
◦
◦
◦
◦
◦
Called virion
Protein coat (capsid) surrounding nucleic acid
Nucleic acid and capsid also called nucleocapsid
Some have phospholipid envelope
Outermost layer provides protection and
recognition sites for host cells
4

Intracellular state
◦ Capsid removed
◦ Virus exists as nucleic acid
5






Type of genetic material they contain
Kinds of cells they attack
Size of virus
Nature of capsid coat
Shape of virus
Presence or absence of envelope
6
Figure 13.4
7





Show more variety in nature of their genomes
than do cells
May be DNA or RNA; never both
Primary way scientists categorize and classify
viruses
Can be double stranded (ds) or single stranded
(ss) so they are called dsDNA, ssDNA, dsRNA,
or ssRNA
Much smaller than even a gene of a host cell!
8

Most are very host-specific: Most only infect
particular kinds of host cells
◦ Due to affinity of viral surface proteins for
complementary proteins on host cell surface

A few are generalists – infect many kinds of
cells in many different hosts
9



Capsids – protein coats that provide
protection for viral nucleic acid and means of
attachment to host’s cells
Capsid composed of proteinaceous subunits
called capsomeres
Some capsids composed of single type of
capsomere; other composed of multiple types
10



Acquired from host cell during viral replication
or release; envelope is portion of membrane
system of host
Composed of phospholipid bilayer and
proteins; some proteins are virally-coded
glycoproteins (spikes)
Envelope’s proteins and glycoproteins often
play role in host recognition
11



Dependent on host’s organelles and enzymes
to produce new virions
Replication cycle may or may not result in death
of host cell
Stages of lytic replication cycle
◦
◦
◦
◦
◦
Attachment
Entry
Synthesis
Assembly
Release
12



Chemical attraction
Animal viruses do not have tails or tail fibers
Have glycoprotein spikes or other attachment
molecules that mediate attachment
13
14
15
Entry/Penetration
16


Each type of animal virus requires different
strategy depending on its nucleic acid
Must consider
◦ How mRNA is synthesized?
◦ What serves as template for nucleic acid replication?
17
18
Figure 13.13





Most DNA viruses assemble in and are
released from nucleus into cytosol
Most RNA viruses develop solely in cytoplasm
Number of viruses produced and released
depends on type of virus and size and initial
health of host cell
Enveloped viruses cause persistent infections
Naked viruses released by exocytosis or may
cause lysis and death of host cell
19
Enveloped and Naked
 Lysis
 Exocytosis
20
◦ Enveloped
 Budding
21




When animal viruses remain dormant in host
cells
May be prolonged for years with no viral
activity, signs, or symptoms
Some latent viruses do not become
incorporated into host chromosome
When provirus is incorporated into host DNA,
condition is permanent; becomes permanent
physical part of host’s chromosome
22




Normally, animal’s genes dictate that some
cells can no longer divide and those that can
divide are prevented from unlimited division
Genes for cell division “turned off” or genes that
inhibit division “turned on”
Neoplasia – uncontrolled cell division in
multicellular animal; mass of neoplastic cells is
tumor
Benign vs. malignant tumors
◦ Metastasis
◦ Cancers
23




Some carry copies of oncogenes as part of
their genomes
Some stimulate oncogenes already present in
host
Some interfere with tumor repression when
they insert into host’s repressor gene
Several DNA and RNA viruses are known to
cause ~15% of human cancers
◦
◦
◦
◦
Burkitt’s lymphoma
Hodgkin’s disease
Kaposi’s sarcoma
Cervical cancer
24
Figure 13.15
25

In Whole Organisms
◦ Bacteria
◦ Plants and Animals
 Embryonated Chicken Eggs

In Cell (Tissue Culture)
26
Figure 13.17
27
Figure 13.18
28




A prion is an infectious agent composed of
protein in a misfolded form.
This is in contrast to all other known infectious
agents (virus/bacteria/fungus/parasite) which
must contain nucleic acids (either DNA, RNA, or
both).
All known prion diseases affect the structure of
the brain or other neural tissue and all are
currently untreatable and universally fatal.
Prions are responsible for "mad cow disease" in
cattle and Creutzfeldt–Jakob disease (CJD) in
humans.
29
Tertiary Structures of Prion proteins
30
Figure 13.21


Prion Diseases
◦ Mad Cow Disease
◦ Creutzfeldt–Jakob disease
◦ Kuru
DNA Viruses
◦ Poxviridae: Smallpox
◦ Herpesviridae: Cold sores,
chicken pox,
mononucleosis
◦ Hepadnoviridae: Hepatitis B
◦ Papillomaviridae: Warts
◦ Adenoviridae: Common
cold, pink eye

RNA Viruses
◦ Picornaviridae: Polio, Hepatitis
A, common cold
◦ Coronaviridae: Common cold
◦ Calicivirus: Stomach flu
◦ Flaviviridae: Hepatitis C; West
Nile, Zika
◦ Retroviridae: AIDS
◦ Togaviridae: German Measles
◦ Paramyxovirus: Measles,
mumps
◦ Orthomyxovirus: Influenza
◦ Rhabdoviridae: Rabies
◦ Filoviridae: Hemorrhagic Fever
◦ Reoviridae: Stomach flu
31

Cattle
◦ Bovine spongiform encephalopathy (BSE; Mad Cow
Disease)

Humans
◦ Creutzfeldt–Jakob disease (CJD)
◦ Degenerative brain disease, incurable and fatal
◦ Can get it from use of contaminated brain products
such as Human Growth Hormone obtained from the
pituitary glands of persons who died from
Creutzfeldt–Jakob Disease

Kuru
◦ From cannibalism. Called Laughing Sickness; tremors
are also classic symptoms
32




All involve fatal neurological
degeneration, deposition of
fibrils in brain, and loss of
brain matter
Large vacuoles form in brain;
characteristic spongy
appearance
Spongiform encephalopathies
(causes holes in the brain)
Only destroyed by
incineration; not cooking or
sterilization
33




Kuru is an incurable degenerative neurological
disorder caused by a prion found in humans.
The term "kuru" derives from the Fore word
"kuria/guria" ("to shake"), a reference to the body
tremors that are a classic symptom of the disease
It is now widely accepted that Kuru was transmitted
among members of the Fore tribe of Papua New
Guinea via cannibalism.
It is also known among the Fore as the laughing
sickness due to the pathologic bursts of laughter
people would display when afflicted with the disease.
34
35
– Classified based on the type of DNA they contain, the
presence or absence of an envelope, size, and the
host cells they attack
•
•
Contain either double-stranded DNA (dsDNA)
or single-stranded DNA (ssDNA) for their
genome
Double-stranded DNA viruses
– Poxviridae, Herpesviridae, Hepadnoviridae,
Papillomaviridae, and Adenoviridae
36


There are currently 21 families of viruses known
to cause disease in humans.
There are six ds DNA families:
 Three are enveloped
 Poxviridae, Herpesviridae, and Hepadnaviridae



Three are non-enveloped
Papillomaviridae, Adenoviridae, Polyomaviridae

(the latter is not covered here)
There is one ss DNA family that infects humans:
◦ They are non-enveloped
 Parvoviridae (not covered here)
37


Prion Diseases
◦ Mad Cow Disease
◦ Creutzfeldt–Jakob disease
◦ Kuru
DNA Viruses
◦ Poxviridae: Smallpox
◦ Herpesviridae: Cold sores,
chicken pox,
mononucleosis
◦ Hepadnoviridae: Hepatitis B
◦ Papillomaviridae: Warts
◦ Adenoviridae: Common
cold, pink eye

RNA Viruses
◦ Picornaviridae: Polio, Hepatitis
A, common cold
◦ Coronaviridae: Common cold
◦ Calicivirus: Stomach flu
◦ Flaviviridae: Hepatitis C; West
Nile, Zika
◦ Retroviridae:AIDS
◦ Togaviridae: German Measles
◦ Paramyxovirus: Measles,
mumps
◦ Orthomyxovirus: Influenza
◦ Rhabdoviridae: Rabies
◦ Filoviridae: Hemorrhagic Fever
◦ Reoviridae: Stomach flu
38

Poxviridae
◦ Smallpox

Herpesviridae
◦ Cold sores, chicken pox, mononucleosis

Hepadnoviridae
◦ Hepatitis B

Papillomaviridae
◦ Warts

Adenoviridae
◦ Common cold, pink eye
39





Double-stranded DNA viruses
Have complex capsids and envelopes
Largest viruses
Infect many mammals
Most animal poxviruses are species specific
◦ Unable to infect humans because they cannot attach
to human cells


Infection occurs primarily through the
inhalation of viruses
Close contact is necessary for infection by
poxviruses
40



Smallpox and molluscum contagiosum are the
two main poxvirus diseases of humans
Some diseases of animals can be transmitted to
humans
All poxviruses produce lesions that progress
through a series of stages
41
Figure 24.2
42





In the genus Orthopoxvirus
Commonly known as variola
Exists in two forms
◦ Variola major causes severe
disease that can result in
death
◦ Variola minor causes a less
severe disease with a much
lower mortality rate
Both forms infect internal
organs and then move to the
skin where they produce pox
Scars result on the skin,
especially on the face
43

There are a number of factors that allowed
eradication of smallpox
◦ Inexpensive, stable, and effective vaccine
◦ No animal reservoirs
◦ Obvious symptoms allow for quick diagnosis and
quarantine
◦ Lack of asymptomatic cases
◦ Virus is only spread via close contact
44






can be produced in large quantities
stable for storage and transport
stable in aerosolized form (up to 2 days)
high mortality
highly infectious (person-to-person spread)
most of the world has little to no immunity
45

Vaccination
◦ vaccination stopped in 1979 (1972 in U.S.)
 last case in U.S. 1949
 2 million deaths Worldwide in 1967
◦ Vaccinia virus
 leaves scar

Supportive therapy – no effective antiviral
once infected
46






Caused by Molluscipoxvirus
Spread by contact among infected children
Sexually active adults can sometimes contract a
genital form of the disease
Skin disease characterized by smooth, waxy, tumorlike nodules on the face, trunk, and limbs
Virus produces a weak immune response
Causes neighboring cells to divide rapidly thus acting
like a tumor-causing virus
47





Poxvirus infections also occur in animals
Transmission of these poxviruses to humans
require close contact with infected animals
Infections of humans are usually mild
Can result in pox and scars but usually little
other damage
Cowpox was used by Edward Jenner to
immunize individuals against smallpox
48

A teenager in the Netherlands who rescued a
drowning kitten from a ditch developed a large,
blackened open wound on her wrist, which took
multiple doctors several weeks to find its rare cause.
49

The kitten that the girl rescued was sick and died the
following day, and the 17-year-old developed a red
wound on her wrist that blistered before turning
black. She also developed painful red bumps on her
arm, spanning from the wound on her wrist up to
her armpit.
50


The doctors got in touch with a virologist
whose lab was equipped to run tests for
cowpox. A few days later, lab results proved
the cowpox virus was, indeed, the culprit.
The girl had been treated by different doctors
for about 13 days by then.
51

Poxviridae
◦ Smallpox

Herpesviridae
◦ Cold sores, chicken pox, mononucleosis

Hepadnoviridae
◦ Hepatitis B

Papillomaviridae
◦ Warts

Adenoviridae
◦ Common cold, pink eye
52


Viruses attach to a host cell’s receptor and
enter the cell through the fusion of its envelope
with the cell membrane
Herpesviruses can have latency
◦ They may remain inactive inside infected cells
◦ Viruses may reactivate causing a recurrence of
manifestations of the disease
53

Herpesviruses include various genera
◦ Simplexvirus, Varicellovirus, Lymphocryptovirus,
Cytomegalovirus, Roseolovirus

Herpesviruses are also designated by “HHV” (for
“human herpesvirus”) and a number indicating
the order in which they were discovered
54








HHV1
HHV2
HHV3
HHV4
HHV5
HHV6
HHV7
HHV8
=
=
=
=
=
=
=
=
HSV1 (Herpes simplex 1; cold sores)
HSV2 (Herpes simplex 2; STD)
VZV (varicella-zoster; chicken pox)
EBV (Epstein-Barr virus)
CMV (cytomegalovirus)
roseola infantum (major cause)
roseola infantum (minor cause)
KS (Kaposi’s sarcoma)
55



Often result in slowly spreading skin lesions
Viruses of this genus are commonly known as
herpes simplex virus or HSV
2 species of herpes simplex
◦ Herpes simplex virus type 1 (HSV-1)
◦ Herpes simplex virus type 2 (HSV-2)
56
Herpes simplex virus type 1 (HSV-1)
57
Herpes simplex virus type 2
58
Epidemiology and Pathogenesis of HSV
Infections
• Active lesions are the usual source of infection
• Aysmptomatic carriers can shed HSV-2 genitally
• Transmission of the viruses occurs through close bodily
contact
• Viruses enter the body through cracks or cuts in
mucous membranes
• Skin lesions result from inflammation and cell death at
the site of infection
• Herpes virions can spread from cell to cell through the
formation of syncytia
59




HSV-1 infections typically occur via casual
contact in children
HSV-2 infections are acquired between the ages
of 15 and 29 from sexual activity
Herpes infections often result in the recurrence
of lesions
Up to two-thirds of patients experience
recurrences due to activation of the latent virus
60
Figure 24.561

Diagnosis
◦ Characteristic lesions, especially in the genital region
and on the lips, is often diagnostic
62
◦ HSV infections are among the few viral diseases that
can be controlled with chemotherapeutic agents
◦ Topical applications of the drugs limit the duration of
the lesions and reduce viral shedding
◦ The drugs don’t cure the diseases or free nerve cells
of latent viral infections
63


Commonly referred to as VZV
Causes two diseases
◦ Varicella
 Often called chicken pox
 Typically occurs in children
◦ Herpes zoster
 Also called shingles
 Usually occurs in adults
64




Chicken pox is a highly infectious disease
seen most often in children
Viruses enter the skin through the respiratory
tract and the eyes
Virus replicate at the site of infection then
travel via the blood throughout the body
Chickenpox in adults is typically more severe
than the childhood illness
65

Chicken pox is a
common illness that
causes an itchy rash
and red spots or
blisters (pox) all over
the body. The blisters
are small and sit on an
area of red skin that
can be anywhere from
the size of a pencil
eraser to the size of a
dime.




Chickenpox is caused by a
virus called varicella zoster.
(VZV) is a type of herpes
virus that causes two types
of diseases, chickenpox and
shingles.
It’s an airborne virus that
can spread easily . You can
get it from an infected
person who sneezes,
coughs, or by sharing food
or drinks. You can also get
it if you touch the fluid
from a chickenpox blister.
The infected person is
highly contagious for 1-2
days before the rash
appears and continue to be
contagious through the first
4-5 days or until all the
blisters have crusted over.
Late winter and early spring
is the most common time
that the virus spreads.




It usually takes 14 to 16 days to get the symptoms of chickenpox after
you have been around someone with the virus. This is called the
incubation period.
The first symptoms of chickenpox are often fever, headache, and sore
throat.
Other symptoms include:
 Being Tired
 Loss of appetite
 Flu like symptoms
 Rash (First appears on the face and trunk, and then spreads
throughout the body)
 Itchy blistering (There are typically 250-500 itchy blisters).
More Severe/Unusual Symptoms
 Skin around spots/blisters become painful and red
 Breathing difficulties
 Chest pain
 Scars
 Pneumonia
 Brain damage
 Death

The illness is highly contagious and can be spread by
direct contact or through the air by sneezing or
coughing. Also, someone can get it by coming in
contact with fluid from chickenpox blisters. For that
reason, children with chickenpox need to be kept out
of school or day care for about a week or more until
all blisters have dried and crusted over. The illness
causes an itchy rash that usually forms between 200
and 500 blisters over the entire body, headaches,
coughing, and fussiness. So even if the illness is mild,
it still means five to 10 days of being uncomfortable.
70




Common illness among
kids in the United States,
particularly those under age
12.
You are at risk for
chickenpox if you have
never had the illness and
have not had the
chickenpox vaccine.
Living with someone who
has chickenpox.
It is usually a mild disease,
however it can be serious,
especially in young infants
and adults.





A doctor may prescribe or advice
on how to reduce symptoms of
itchiness and discomfort, and
also on how to prevent the
infection from spreading to
other people.
Treatment depend on a person’s
age, heath, and severity.
Home remedies:
◦ Tylenol or Ibuprofen to reduce
fever and discomfort.
◦ Over the counter
antihistamines may help
reduce itching. Oatmeal baths
and soothing lotions
(calamine, or aveeno).
Antiviral medicines sometimes
are given to shorten the length
of the illness.
Healthy teens and adults with
varicella usually have more
severe symptoms than children
and are at a higher risk for
complications, still most home
remedies should work.





Risk complications are greater with pregnant women and
newborns up to 4 weeks of age, as well as those with
weakened immune systems (cancer patients undergoing
chemotherapy, or have a chronic condition such as lupus or
rheumatoid arthritis).
In rare cases the blisters become infected with bacteria. If the
skin around the spots and blisters become red and tender,
most likely they have become infected.
According to the NHS (National Health Service) between 5% to
14% of all adults with chickenpox develop respiratory
complications, such as pneumonia. The risk is significantly
greater for adults smokers.
Some other complications from chickenpox may include
meningitis, and blood poisoning.
Even though complications are possible, most patients who
have them make a full recovery.


Latent virus can reactivate later in life,
producing a rash known as shingles
The rash is characteristic for its localization
along a dermatome - dorsal roots from the
spine
74
75
Figure 24.10
Shingles
• Also known as Herpes Zoster
• Painful blistering skin rash



Caused by the Varicella- Zoster virus also
known as the virus that causes chicken pox
After you get chicken pox the virus remains
dormant.
Reasons it may become active again are a low
immune system, older in age 60 and above,
or if you got chicken pox before the age of 1.
Shingles
•
•
•
•
Red Patches on the skin followed by small
blisters
The blisters break, forming small sores that
begin to dry and form crusts. The crusts fall
off in 2 to 3 weeks.
The rash usually involves a narrow area from
the spine around to the front of the belly area
or chest.
The rash may involve the face, eyes, mouth,
and ears.
•
•
•
•
•
•
•
Abdominal pain
Fever and chills
General sick feeling
Genital sores
Headache
Joint pain
Swollen glands (lymph
nodes)


Physician may prescribe an antiviral drug such as
Acyclovir, Famciclovir, and Valacyclovir.
Strong anti-inflammatory medicines called
corticosteroids, such as prednisone, may be used
to reduce swelling and pain
Vaccination
• CDC recommends two doses of chickenpox vaccine for
children, adolescents, and adults. Two doses of the
vaccine are about 98% effective at preventing
chickenpox.
• Children should receive two doses of the vaccine—the
first dose at 12 through 15 months old and a second
dose at 4 through 6 years old.
• When you get vaccinated, you protect yourself and
others in your community. This is especially important
for people who cannot get vaccinated, such as those
with weakened immune systems or pregnant women.
• Some people who are vaccinated against chickenpox
may still get the disease. However, it is usually milder
with fewer blisters and little or no fever.
83
Are Children Required to Get a
Chickenpox Vaccination?
• Most states require that children entering
child care, school and even colleges and
universities, show evidence of immunity to
chickenpox either by having had the illness or
evidence of receiving the chickenpox vaccine.
84
Monitoring the Impact of Varicella Vaccination
•
•
•
•
•
•
•
•
Chickenpox used to be very common in the United States. In the early 1990s, an average of 4
million people got varicella, 10,500 to 13,000 were hospitalized (range, 8,000 to 18,000), and 100
to 150 died each year. In the 1990s, the highest rate of varicella was reported in preschool-aged
children.
Chickenpox vaccine became available in the United States in 1995. In 2010, 90% of children 19 to
35 months old in the United States had received one dose of varicella vaccine, varying from 72% to
97% by state and city. Among adolescents 13 to 17 years of age without a prior history of disease,
90% had received 1 dose of varicella vaccine, and 58% had received 2 doses of the vaccine.
Each year, more than 3.5 million cases of varicella, 9,000 hospitalizations, and 100 deaths are
prevented by varicella vaccination in the United States.
Varicella incidence in 26 states, which had adequate and consistent reporting to the National
Notifiable Disease Surveillance System (NNDSS), declined by 45% from 2000 to 2005 with an
additional 77% decline from 2006 to 2010 after the second dose of varicella vaccine was
recommended. Overall, varicella declined 82% from 2000 to 2010.
National hospitalization rates for varicella declined overall by 71% during 2000 to 2006 compared
with rates from 1988 to 1995. In people younger than 20 years of age, hospitalization rates declined
by approximately 95%.
Varicella deaths declined by 98.5% in children and adolescents less than 20 years of age during
2008 to 2009 compared with 1990 to 1994. Deaths declined by 96% in adults less than 50 years of
age and by 49% in adults 50 years of age or older.
Varicella incidence among HIV-infected children declined 63% during 2000-2007 compared to
1989-1999.
Varicella vaccination provides indirect benefits to people who are not eligible for vaccination.
Varicella incidence among infants, a group not eligible for varicella vaccination, declined by 90%
from 1995 to 2008.
85
People at High Risk for Complications
•
•
Immunocompromised Persons
Immunocompromised persons who get varicella are at risk of developing visceral
dissemination (VZV infection of internal organs) leading to pneumonia, hepatitis,
encephalitis, and disseminated intravascular coagulopathy. They can have an atypical varicella
rash with more lesions, and they can be sick longer than immunocompetent persons who get
varicella. The lesions may continue to erupt for as long as 10 days, may appear on the palms
and soles, and may be hemorrhagic.
•
•
People with HIV or AIDS
Children with HIV infection tend to have atypical rash with new crops of lesions presenting
for weeks or months. HIV-infected children may develop chronic infection in which new
lesions appear for more than one month. The lesions may initially be typical maculopapular
vesicular lesions but can later develop into non-healing ulcers that become necrotic, crusted,
and hyperkeratotic. This is more likely to occur in HIV-infected children with low CD4 counts.
Some studies have found that VZV dissemination to the visceral organs is less common in
children with HIV than in other immunocompromised patients with VZV infection. The rate of
complications may also be lower in HIV-infected children on antiretroviral therapy or HIVinfected persons with higher CD4 counts at the time of varicella infection. Retinitis can occur
among HIV-infected children and adolescents.
Most adults, including those who are HIV-positive have already had varicella disease and are
86
VZV seropositive. As a result, varicella is relatively uncommon among HIV-infected adults.
•
•
People at High Risk for Complications
• Pregnant Women
• Pregnant women who get varicella are at risk for serious
complications; they are at increased risk for developing pneumonia,
and in some cases, may die as a result of varicella.
• If a pregnant woman gets varicella in her 1st or early 2nd trimester,
her baby has a small risk (0.4 – 2.0 percent) of being born with
congenital varicella syndrome. The baby may have scarring on the
skin, abnormalities in limbs, brain, and eyes, and low birth weight.
• If a woman develops varicella rash from 5 days before to 2 days
after delivery, the newborn will be at risk for neonatal varicella. In
the absence of treatment, up to 30% of these newborns may
develop severe neonatal varicella infection.
87
Possible Side Effects of Chickenpox
Vaccine
• Getting chickenpox vaccine is much safer than
getting the disease. Most people who get the
vaccine do not have any problems with it. But,
as with any vaccine, there is a very small
chance of having a side effect. Serious side
effects to the chickenpox vaccine are very
rare. They are usually more likely to occur
after the first dose than after the second one.
88
Possible Side Effects of Chickenpox
Vaccine
•
•
•
•
Possible reactions include:
Soreness, redness, or swelling where the shot was given
Fever
Mild rash or several small bumps after vaccination. If you get
chickenpox rash after vaccination, you can spread the disease to
others. But, this is very rare. If you have chickenpox rash, you
should stay away from people with weakened immune systems.
• Seizure (jerking and staring spell) that may be caused by fever.
Seizures after chickenpox vaccination may or may not be related to
chickenpox vaccine.
• Serious side effects from chickenpox vaccine are extremely rare.
They may include severe brain reactions and low blood count.
These side effects happen so rarely that experts cannot tell whether
they are caused by chickenpox vaccine or not.
89
Possible Side Effects of Chickenpox
Vaccine
• Possible reactions after ProQuad® (or MMRV)
vaccination
• Children who get the first dose of ProQuad®
vaccine at 12 to 23 months old may have a higher
chance of a seizure caused by fever. This is in
comparison to children who get the measles,
mumps, and rubella vaccine and the chickenpox
vaccine separately during a doctor visit. But,
these seizures are not common. They may be
scary for parents, but they are not harmful to
children.
90
Epstein-Barr Virus Infections
• Also referred to as EBV or HHV-4
• Can cause a number of different diseases
91



Transmission of EBV usually occurs via saliva
Virions initially infect the epithelial cells of the
pharynx and parotid salivary glands
The virus then enters the bloodstream where it
invades the B lymphocytes
92


The viruses become latent in B cells and
immortalize them by suppressing apoptosis
Symptoms of infectious mononucleosis arise
from the immune response
◦ Cytotoxic T cells kill virus infected B
lymphocytes
93


Cancer development appears to depend in part
on various cofactors
Extreme diseases arise in individuals with T cell
deficiency
◦ Such individuals are susceptible because infected cells
are not removed by cytotoxic T cells allowing the virus
to proliferate
94



Also referred to as CMV
Cells infected with this virus become enlarged
CMV infections is one of the more common
infections of humans
95

Transmission occurs through bodily secretions
◦ Requires close contact and a large exchange of
secretion
◦ Usually occurs via sexual intercourse
◦ Also transmitted by in utero exposure, vaginal birth,
blood transfusions, and organ transplants


Most CMV infections are asymptomatic
CMV causes infectious mononucleosis (second
to EBV)
96

Fetuses, newborns, and immunodeficient
patients can develop complications
◦ CMV can cause birth defects and may result in death
◦ AIDS patients or other immunocompromised adults
may develop pneumonia, blindness, or
cytomegalovirus mononucleosis, which is similar to
infectious mononucleosis
97

Human herpesvirus 6 (HHV-6)
◦ In the genus Roseolovirus
◦ Causes roseola which is characterized by a pink rash
on the face, neck, trunk, and thighs
◦ Linked to multiple sclerosis by some researchers
◦ Can cause mononucleosis-like symptoms
◦ Infection with HHV-6 may make individuals more
susceptible to AIDS
98

Human herpesvirus 8 (HHV-8)
◦ Causes Kaposi’s sarcoma, a cancer seen in AIDS
patients
◦ The virus is not found in cancer-free patients or in
normal tissues of victims
99

Poxviridae
◦ Smallpox

Herpesviridae
◦ Cold sores, chicken pox, mononucleosis

Hepadnoviridae
◦ Hepatitis B

Papillomaviridae
◦ Warts

Adenoviridae
◦ Common cold, pink eye
10
0



Hepatitis B
Symptoms include loss of appetite, nausea,
vomiting, body aches, mild fever, dark urine,
jaundice.
Can also cause cancer in people with cirrhosis
of the liver.
◦ Therefore, it is an oncovirus. There are seven
human oncoviruses.
10
1
10
2




This is the viral hepatitis that is primarily spread by
sexual contact (it is PRIMARILY a sexually
transmitted disease) or sharing needles by drug
users.
Only about 50% of infected persons have flu-like
symptoms, including fatigue, fever, headache,
nausea, vomiting, muscle aches, and dull pain in
the upper right of the abdomen.
Jaundice, a yellowish cast to the skin, can also be
present. Some persons have an acute infection that
lasts only three to four weeks.
Others have a chronic form of the disease that
leads to liver failure and a need for a liver
transplant.
10
3


Since there is no treatment for an HBV
infection, prevention is imperative by a
vaccine, which is safe and does not have any
major side effects.
This vaccine is now on the list of
recommended immunizations for children.
10
4

Poxviridae
◦ Smallpox

Herpesviridae
◦ Cold sores, chicken pox, mononucleosis

Hepadnoviridae
◦ Hepatitis B

Papillomaviridae
◦ Warts

Adenoviridae
◦ Common cold, pink eye
10
5

Causes papillomas, commonly known as warts
◦ Benign growths of the epithelium of the skin or
mucous membranes






Papillomas form on many body surfaces
Often painful and unsightly
HPV Type 1 (feet)
HPV Type 2 (hands)
HPV Type 16 and 18 (cervical cancer)
HPV Type 6 and 11 (genital warts)
10
6




Types 1 and 2 (hands and
feet) enter through a tiny
break in the skin
Genital warts are transmitted
via direct contact
All types spread by
autoinoculation
Genital warts are a common
sexually transmitted disease
and are associated with an
increased risk of cancer
10
7

Diagnosis
◦ Usually based on observation of the papillomas and
pin-point bleeding upon debridement of callous on
top. The warts are angiotrophic, so they pull little
blood vessels into the epidermis to feed them.
◦ Diagnosis of cancers results from inspection of the
genitalia and by a PAP smear in women

Treatment
◦ Some warts can be removed through various methods
(laser is best since it cauterizes the wound so viruses
cannot escape and migrate to a new area). However,
they frequently come back.
◦ Treatment of cancers involves radiation and chemical
therapy
10
8
Pinpoint bleeding on debridement
10
9

Prevention
◦ Prevention of common skin warts is difficult
 Wear gloves when doing jobs that might nick the skin
 Wear shoes so tiny cuts don’t occur
◦ Genital warts can be prevented by abstinence and
perhaps safe sex
11
0

2006 - Advisory committee on immunization
practices (ACIP) recommended the HPV vaccine
◦ recommended for girls/women 9-26 yrs old
 before sexual contact
 recommended at 11-12 years of age
◦ vaccine (Gardasil) protects against strains HPV 6, 11,
16, and 18
11
1

Poxviridae
◦ Smallpox

Herpesviridae
◦ Cold sores, chicken pox, mononucleosis

Hepadnoviridae
◦ Hepatitis B

Papillomaviridae
◦ Warts

Adenoviridae
◦ Common cold, pink eye
11
2



One of the causative agents of the common
cold
Spread via respiratory droplets
Respiratory infections
◦ Viruses are taken into cells lining the respiratory tract
via endocytosis
◦ Symptoms include sneezing, sore throat, cough,
headache, and malaise
11
3
11
4


Infection of the intestinal tract can produce
mild diarrhea
Infection of the conjunctiva can result in
pinkeye
11
5


diarrhea in children
respiratory infection in children and adults
◦ military recruits




close contact
physical activities (deep inhalation of virus into lungs)
stress
after infection, see immunity
11
6




RNA viruses are either double stranded or single
stranded.
The single stranded RNA viruses are subclassified
according to the sense or polarity of their RNA: they
are called positive-sense RNA viruses or negativesense RNA viruses.
Positive-sense viral RNA is similar to mRNA and thus
can be immediately translated by the host cell.
Negative-sense viral RNA is complementary to mRNA
and thus must be converted to positive-sense RNA by
an RNA polymerase before translation.
11
7

There are seven positive ss RNA families:
◦ Three are non enveloped
 Picornaviridae, Caliciviridae, and Astroviridae (latter one not
covered)
◦ Four are enveloped
 Coronoviridae, Flaviviridae, Retroviridae, and Togaviridae

There are six negative ss RNA families:
◦ All are enveloped
 Paramyxoviridae, Orthomyxoviridae, Rhabdoviridae, Filoviridae,
Arenaviridae, and Bunyaviridae (latter two not covered)

There is one ds RNA family
 Reoviridae
11
8


Prion Diseases
◦ Mad Cow Disease
◦ Creutzfeldt–Jakob disease
◦ Kuru
DNA Viruses
◦ Poxviridae: Smallpox
◦ Herpesviridae: Cold sores,
chicken pox,
mononucleosis
◦ Hepadnoviridae: Hepatitis B
◦ Papillomaviridae: Warts
◦ Adenoviridae: Common
cold, pink eye

RNA Viruses
◦ Picornaviridae: Polio, Hepatitis
A, common cold
◦ Calicivirus: Stomach flu
◦ Coronaviridae: Common cold
◦ Flaviviridae: Hepatitis C; West
Nile, Zika
◦ Retroviridae: AIDS
◦ Togaviridae: German Measles
◦ Paramyxovirus: Measles,
mumps
◦ Orthomyxovirus: Influenza
◦ Rhabdoviridae: Rabies
◦ Filoviridae: Hemorrhagic Fever
◦ Reoviridae: Stomach flu
11
9


Picornaviridae
◦ Polio, Hepatitis A,
common cold
Calicivirus
◦ Stomach flu

Coronaviridae

Flaviviridae


◦ Common cold
◦ West Nile
◦ Hepatitis C
◦ Zika
Retroviridae
◦ AIDS
Togaviridae

Paramyxovirus
◦ Measles, mumps

Orthomyxovirus


Influenza
Rhabdoviridae
◦ Rabies

Filoviridae
◦ Hemorrhagic Fever

Reoviridae
◦ Stomach flu
◦ German Measles
12
0



Positive RNA acts like mRNA and can be used
by a ribosome to translate protein
Negative RNA must first be transcribed as
mRNA to be processed by a ribosome
RNA viruses are categorized by their genomic
structure, the presence of an envelope, and the
size and shape of their capsid
12
1

Yosemite officials say 1,700 visitors risk rare
rodent disease
http://fxn.ws/TpFPp2
12
2

Enteroviruses
◦ Polio
◦ Hepatitis A
◦ Rhinovirus
12
3

Found
◦ in respiratory secretions
◦ stool of an infected person
◦ Parents, teachers, and child care center workers
may also become infected by contamination of the
hands with stool from an infected infant or toddler
during diaper changes.
12
4




First described by Michael Underwood in 1789
First outbreak described in U.S. in 1843
21,000 paralytic cases reported in the U. S. in 1952
Global eradication in near future
12
5





Enterovirus (RNA)
Three serotypes: 1, 2, 3
Minimal immunity between serotypes
Rapidly inactivated by heat, formaldehyde,
chlorine, ultraviolet light
Most poliovirus infections are asymptomatic
12
6





Fecal oral entry
Replication in pharynx, GI tract,
local lymphatics
Hematologic spread to lymphatics and central
nervous system
Viral spread along nerve fibers
Destruction of motor neurons
12
7
Poliomyelitis—United States, 1950-2007
25000
Inactivated vaccine
Cases
20000
15000
10000
Live oral vaccine
5000
0
1950
Last indigenous case
1960
1970
1980
1990
2000
12
8
Table 25.2
12
9


Exclusive use of IPV recommended in 2000
OPV no longer routinely available in the
United States
13
0



Only IPV is available in the
United States
Schedule begun with OPV should be
completed with IPV
Any combination of 4 doses of IPV and
OPV by 5 years constitutes a complete
series
13
1



Rare local reactions (IPV)
No serious reactions to IPV have been
documented
Paralytic poliomyelitis (OPV)
13
2




Epidemic jaundice described by Hippocrates
Differentiated from hepatitis B in 1940s
Serologic tests developed in 1970s
Vaccines licensed in 1995 and 1996
13
3




Picornavirus (RNA)
Humans are only natural host
Stable at low pH
Inactivated by high temperature (185°F or
higher), formalin, chlorine
13
4
13
5


This is a virus you get when you or a food
worker doesn’t wash the hands after going to
the bathroom, and then you eat.
It CAN also be sexually transmitted through
oral/anal contact, but it is not primarily
considered as a STD.
13
6




Fecal oral entry
Viral replication in the liver
Virus present in blood and feces 10-12 days
after infection
Virus excretion may continue for up to 3
weeks after onset of symptoms
13
7
Hepatitis A - United States, 1966-2007
70000
Vaccine
Licensed
60000
Cases
50000
40000
30000
20000
10000
0
1966
1970
1975
1980
1985
1990
1995
2000
2005
Year
13
8


Inactivated whole virus vaccines
Pediatric and adult formulations
◦ Pediatric formulations vaccines approved for
persons 12 months through 18 years
◦ Adult formulations approved for persons 19 years
and older
13
9

For healthy persons 12 months through 40
years of age:
◦ single-antigen hepatitis A vaccine should be
administered as soon as possible after exposure

For persons older than 40 years:
◦ immune globulin is preferred
◦ vaccine can be used if IG cannot be obtained
MMWR 2007;56(No.41):1080-4
14
0




Cause most cases of the common cold
Infections are limited to the upper respiratory
tract
A single virus is often sufficient to cause a cold
The virus can be spread through aerosols, via
fomites, or via hand-to-hand contact
Cough and
sneeze into
your elbow.
Wash hands
often.
14
1


Direct person-to-person contact is the most
common means of transmission
Individuals can acquire some immunity against
serotypes that have infected them in the past
◦ As a result, the number of infections tends to
decrease with age
14
2


Picornaviridae
◦ Polio, Hepatitis A,
common cold
Calicivirus
◦ Stomach flu

Coronaviridae

Flaviviridae


◦ Common cold
◦ West Nile
◦ Hepatitis C
◦ Zika
Retroviridae
◦ AIDS
Togaviridae

Paramyxovirus
◦ Measles, mumps

Orthomyxovirus


Influenza
Rhabdoviridae
◦ Rabies

Filoviridae
◦ Hemorrhagic Fever

Reoviridae
◦ Stomach flu
◦ German Measles
14
3



Norwalk – genus name for
original Norwalk virus and
other Norwalk-like viruses.
Family Calicivirus.
Calicivirae found worldwide,
infecting humans, primates,
and cattle, among others.
Increasingly being
recognized as leading cause
of food borne illness.
14
4
Virus first identified in Norwalk, Ohio, 1973.
 Noted to commonly be a problem on cruise
ships.
 Associated with contaminated food or water
supplies.

14
5
Noroviruses found in stool and vomit of
infected.
 Very contagious – infection via eating
contaminated food, contact with sick
individual or contaminated surfaces.

14
6
Acute gastroenteritis.
 Illness begins suddenly, from 12-48 hours
after ingestion. Brief illness period.
 Very young, elderly, and those with weakened
immune systems may experience more severe
symptoms.
 Infectiousness may last up to 2 weeks, no
evidence of long-term carriers.

New 'vomiting virus' strain
behind recent US
outbreaks, http://fxn.ws/Ts7oEv
14
7


Picornaviridae
◦ Polio, Hepatitis A,
common cold
Calicivirus
◦ Stomach flu

Coronaviridae

Flaviviridae


◦ Common cold
◦ West Nile
◦ Hepatitis C
◦ Zika
Retroviridae
◦ AIDS
Togaviridae

Paramyxovirus
◦ Measles, mumps

Orthomyxovirus


Influenza
Rhabdoviridae
◦ Rabies

Filoviridae
◦ Hemorrhagic Fever

Reoviridae
◦ Stomach flu
◦ German Measles
14
8






Named due to the corona-like halo formed by
their envelopes
Transmitted via large droplets from the upper
respiratory tract
Second most common cause of colds
Can cause gastroenteritis in children
Diseases are mild
No treatment or vaccine is available
14
9
0
Diarrhea
Nausea &
Vomiting
Running
nose
Sore throat
Sputum
Dizziness
Headache
Cough
Myalgia
Chills & Rigor
Fever
% of patients
100
90
80
70
60
50
40
30
20
10


Picornaviridae
◦ Polio, Hepatitis A,
common cold
Calicivirus
◦ Stomach flu

Coronaviridae

Flaviviridae


◦ Common cold
◦ West Nile
◦ Hepatitis C
◦ Zika Virus
Retroviridae
◦ AIDS
Togaviridae

Paramyxovirus
◦ Measles, mumps

Orthomyxovirus


Influenza
Rhabdoviridae
◦ Rabies

Filoviridae
◦ Hemorrhagic Fever

Reoviridae
◦ Stomach flu
◦ German Measles
15
1


West Nile Virus
Hepacivirus
◦ Hepatitis C

Zika Virus
15
2




Mosquito-borne virus first identified in the West Nile
area of the East African nation of Uganda in 1937.
Birds are the most common animal infected.
Approximately 80% of West Nile virus infections in
humans are subclinical, which cause no symptoms.
In the cases where symptoms do occur —termed West
Nile fever in cases without neurological disease—the
time from infection to the appearance of symptoms
(incubation period) is typically between 2 and 15
days. Symptoms may include fever, headaches,
fatigue, muscle pain.
15
3

Less than 1% of the cases are severe and
result in neurological disease when
the central nervous system is affected by
encephalitis (brain infection).
15
4



A dead gray tree squirrel found July 9, 2013
at Big Bear Lake has tested positive for West
Nile virus.
Most people get infected with the virus by the
bite of an infected mosquito that fed on an
infected bird.
About 1 in 5 people develop a symptom such
as a fever.
15
5
15
6



This is the form you get PRIMARILY from
infected blood.
It is very serious and can lead to chronic
hepatitis, liver cancer, and death.
It CAN be transmitted sexually, but it is not
PRIMARILY known as a STD.
15
7



A jury awarded $41.7 million to a woman who sued her
prestigious boarding school after contracting a Tick-borne
encephalitis virus on a school trip to China that left her unable to
speak and brain damaged.
Munn, of New York City, was a ninth-grader when she joined a
school-supervised trip to China during the summer of 2007,
according to her lawsuit. The then-15-year-old suffered insect
bites that led to tick-borne encephalitis, her attorneys said.
The school failed to ensure that the students take any
precautions against ticks and allowed them to walk through a
densely wooded area known to be a risk area for tick-borne
encephalitis and other tick- and insect-transmitted illnesses, her
attorneys said.
15
8


Zika virus is spread to people through mosquito bites.
The most common symptoms of Zika virus disease
are fever, rash, joint pain, and conjunctivitis (red eyes).
The illness is usually mild with symptoms lasting from
several days to a week. Severe disease requiring
hospitalization is uncommon.
In May 2015, the Pan American Health Organization
(PAHO) issued an alert regarding the first confirmed
Zika virus infection in Brazil. The outbreak in Brazil led
to reports of Guillain-Barré syndrome and pregnant
women giving birth to babies with birth defects and
poor pregnancy outcomes.
15
9





US States
Travel-associated Zika virus disease cases reported:
52
US Territories
Local mosquito-borne transmission of Zika virus has
been reported in the Commonwealth of Puerto Rico,
the US Virgin Islands, and America Samoa.
On February 1, 2016, the World Health Organization
declared a Public Health Emergency of International
Concern(PHEIC) because of clusters of microcephaly
and other neurological disorders in some areas
affected by Zika. On February 8, 2016, CDC elevated
its EOC activation to a Level 1, the highest level.
16
0
16
1




Prior to 2015, Zika virus outbreaks occurred in
areas of Africa, Southeast Asia, and the Pacific
Islands.
In May 2015, the Pan American Health
Organization (PAHO) issued an alert regarding
the first confirmed Zika virus infections in Brazil.
Currently, outbreaks are occurring in many
countries.
Zika virus will continue to spread and it will be
difficult to determine how and where the virus
will spread over time.
16
2





About 1 in 5 people infected with Zika virus become
ill (i.e., develop Zika).
The most common symptoms of Zika are fever, rash,
joint pain, or conjunctivitis (red eyes). Other common
symptoms include muscle pain and headache. The
incubation period (the time from exposure to
symptoms) for Zika virus disease is not known, but is
likely to be a few days to a week.
The illness is usually mild with symptoms lasting for
several days to a week.
People usually don’t get sick enough to go to the
hospital, and they very rarely die of Zika.
Zika virus usually remains in the blood of an infected
person for about a week but it can be found longer in
some people.
16
3




The symptoms of Zika are similar to those
of dengue, diseases spread through the same
mosquitoes that transmit Zika.
See your healthcare provider if you develop the
symptoms described above and have visited an
area where Zika is found.
If you have recently traveled, tell your healthcare
provider when and where you traveled.
Your healthcare provider may order specialized
blood tests to look for Zika or other similar
viruses like dengue.
16
4



There is no vaccine to prevent or specific medicine to treat
Zika infections.
Treat the symptoms:
◦ Get plenty of rest.
◦ Drink fluids to prevent dehydration.
◦ Take medicine such as acetaminophen (Tylenol®) to relieve fever
and pain.
◦ Do not take aspirin and other non-steroidal anti-inflammatory
drugs.
◦ If you are taking medicine for another medical condition, talk to
your healthcare provider before taking additional medication.
If you have Zika, prevent mosquito bites for the first week
of your illness.
◦ During the first week of infection, Zika virus can be found in the
blood and passed from an infected person to a mosquito through
mosquito bites.
◦ An infected mosquito can then spread the virus to other people.
16
5

Microcephaly is a condition where a baby’s
head is much smaller than expected. During
pregnancy, a baby’s head grows because the
baby’s brain grows. Microcephaly can occur
because a baby’s brain has not developed
properly during pregnancy or has stopped
growing after birth, which results in a smaller
head size. Microcephaly can be an isolated
condition, meaning that it can occur with no
other major birth defects, or it can occur in
combination with other major birth defects.
16
6







Seizures
Developmental delay, such as
problems with speech or
other developmental
milestones (like sitting,
standing, and walking)
Intellectual disability
(decreased ability to learn and
function in daily life)
Problems with movement and
balance
Feeding problems, such as
difficulty swallowing
Hearing loss
Vision problems
16
7


Picornaviridae
◦ Polio, Hepatitis A,
common cold
Calicivirus
◦ Stomach flu

Coronaviridae

Flaviviridae


◦ Common cold
◦ West Nile
◦ Hepatitis C
◦ Zika
Retroviridae
◦ AIDS
Togaviridae

Paramyxovirus
◦ Measles, mumps

Orthomyxovirus


Influenza
Rhabdoviridae
◦ Rabies

Filoviridae
◦ Hemorrhagic Fever

Reoviridae
◦ Stomach flu
◦ German Measles
16
8




A retrovirus only has mRNA therefore is an obligate
intracellular parasite.
Once inside the host cell cytoplasm the virus uses its own
reverse transcriptase enzyme to produce DNA from its
mRNA. This is the reverse of the usual replication pattern,
so it is named a retro (backwards) virus.
The host cell then treats the viral DNA as part of its own
genome, translating and transcribing the viral genes along
with the cell's own genes, producing the proteins required
to assemble new copies of the virus.
It is difficult to detect the virus until it has infected the
host.
16
9




Human Immunodeficiency Virus (HIV)
Causes acquired immunodeficiency syndrome
(AIDS).
The HIV virus infects Helper T-Cells, and the
AIDS disease causes progressive failure of the
immune system, which allows lifethreatening opportunistic infections and
cancers to thrive.
Infection with HIV occurs by the transfer of
blood, semen, vaginal fluid, pre-ejaculate, or
breast milk.
17
0



During the initial infection, a person may
experience a brief period of influenza-like
illness.
This is typically followed by a prolonged
period without symptoms.
As the illness progresses, it interferes more
and more with the immune system, making
the person much more likely to get
infections, including opportunistic infections
and tumors that do not usually affect people
who have working immune systems.
17
1





HIV is transmitted primarily via unprotected sexual intercourse
(including anal and even oral sex), contaminated blood
transfusions, hypodermic needles, and from mother to child
during pregnancy, delivery, or breastfeeding.
Some bodily fluids, such as saliva and tears, do not transmit HIV.
Prevention of HIV infection, primarily through safe sex and
needle-exchange programs, is a key strategy to control the
spread of the disease.
There is no cure or vaccine; however, antiretroviral treatment can
slow the course of the disease and may lead to a near-normal
life expectancy.
While antiretroviral treatment reduces the risk of death and
complications from the disease, these medications are expensive
and may be associated with side effects.
17
2




If you have a positive AIDS test, you are
considered to be HIV positive.
Then you get a blood test. If your helper TCell count (CD4) is below 200 mm3, the
diagnosis is AIDS.
If the cell count is higher, you do not have
AIDS yet, but you are still HIV positive. You
need to have blood tests periodically.
It takes up to six months for an HIV test to
show positive after exposure.
17
3





Genetic research indicates that HIV originated in westcentral Africa during the early twentieth century.
AIDS was first recognized by the Centers for Disease
Control and Prevention (CDC) in 1981 and its cause—HIV
infection—was identified in the early part of the decade.
Since its discovery, AIDS has caused an estimated 36
million deaths (as of 2012).
As of 2012, approximately 35.3 million people are living
with HIV globally.
AIDS is considered a pandemic—a disease outbreak which
is present over a large area and is actively spreading.
17
4

http://americablog.com/2013/06/hiv-beingused-to-cure-cancer-leukemia.html
17
5


Picornaviridae
◦ Polio, Hepatitis A,
common cold
Calicivirus
◦ Stomach flu

Coronaviridae

Flaviviridae


◦ Common cold
◦ West Nile
◦ Hepatitis C
◦ Zika
Retroviridae
◦ AIDS
Togaviridae

Paramyxovirus
◦ Measles, mumps

Orthomyxovirus


Influenza
Rhabdoviridae
◦ Rabies

Filoviridae
◦ Hemorrhagic Fever

Reoviridae
◦ Stomach flu
◦ German Measles
17
6

Togaviridae
◦ Rubivirus (rubella)
◦ Designated arboviruses because they are
often transmitted by arthropods
17
7








Togaviridae
“German measles’
Rubella virus is the causative agent
One of the five childhood diseases that
produces skin lesions
Infection begins in the respiratory system but
spreads throughout the body
Characterized by a rash of flat, pink to red
spots
Infections in children are usually not serious
Adults can develop arthritis or encephalitis
17
8


Rubella infections of pregnant women can
result in congenital defects or death of the child
Vaccination has been effective at reducing the
incidence of rubella
17
9



From Latin meaning "little red"
Discovered in 18th century - thought to be
variant of measles
Congenital rubella syndrome (CRS) described
by Gregg in 1941
18
0




Respiratory transmission of virus
Replication in nasopharynx and regional
lymph nodes
Viremia 5-7 days after exposure with spread
to tissues
Placenta and fetus infected during viremia
18
1
Incubation period 14 days
(range 12-23 days)
 Prodrome of low-grade fever
 Maculopapular rash 14-17 days after
exposure
 Lymphadenopathy in second week

18
2





12.5 million rubella cases
2,000 encephalitis cases
11,250 abortions (surgical/spontaneous)
2,100 neonatal deaths
20,000 CRS cases
◦ deaf - 11,600
◦ blind - 3,580
◦ mentally retarded - 1,800
18
3




Infection may affect all organs
May lead to fetal death or premature delivery
Severity of damage to fetus depends on
gestational age
Up to 85% of infants affected if infected
during first trimester
18
4







Deafness
Cataracts
Heart defects
Microcephaly
Mental retardation
Bone alterations
Liver and spleen damage
18
5



Isolation of rubella virus from clinical
specimen (e.g., nasopharynx, urine)
Positive serologic test for rubella IgM
antibody
Significant rise in rubella IgG by any standard
serologic assay (e.g., enzyme immunoassay)
18
6


Most reported rubella in the U.S. since the
mid-1990s has occurred among foreign-born
Hispanic adult
Majority of CRS since 1997 occurred in
children of unvaccinated women born to
Hispanic women, most born in Latin America
18
7
Rubella - United States, 1980-2007
4500
4000
3500
3000
2500
2000
1500
1000
500
0
1980
CRS
40
35
30
25
20
15
CRS Cases
Rubella Cases
Rubella
10
5
0
1985
1990
1995
Year
2000
2005
18
8



Acute onset of generalized maculopapular rash,
and
Temperature of >99°F (37.2 °C), if measured,
and
Arthralgia or arthritis, lymphadenopathy, or
conjunctivitis
18
9


Picornaviridae
◦ Polio, Hepatitis A,
common cold
Calicivirus
◦ Stomach flu

Coronaviridae

Flaviviridae


◦ Common cold
◦ West Nile
◦ Hepatitis C
◦ Zika
Retroviridae
◦ AIDS
Togaviridae

Paramyxovirus
◦ Measles, mumps

Orthomyxovirus


Influenza
Rhabdoviridae
◦ Rabies

Filoviridae
◦ Hemorrhagic Fever

Reoviridae
◦ Stomach flu
◦ German Measles
19
0

Includes the Paramyxoviridae, Orthomyxovirus,
Rhabdoviridae, and Filoviridae families
19
1


Measles and Mumps
Influenza

Rabies

Ebola virus
19
2


Picornaviridae
◦ Polio, Hepatitis A,
common cold
Calicivirus
◦ Stomach flu

Coronaviridae

Flaviviridae


◦ Common cold
◦ West Nile
◦ Hepatitis C
◦ Zika
Retroviridae
◦ AIDS
Togaviridae

Paramyxovirus
◦ Measles, mumps

Orthomyxovirus


Influenza
Rhabdoviridae
◦ Rabies

Filoviridae
◦ Hemorrhagic Fever

Reoviridae
◦ Stomach flu
◦ German Measles
19
3




One of five classical childhood diseases
Spread in the air via respiratory droplets
Viral spread requires large, dense populations
of people
Viruses infect the respiratory tract and then
spread throughout the body
19
4


Characteristic lesions called Koplik’s spots
appear on the mucous membrane of the mouth
Lesions then appear on the head and spread
over the body
19
5




Highly contagious viral illness
First described in 7th century
Near universal infection of childhood in
prevaccination era
Common and often fatal in developing areas
19
6




Paramyxovirus (RNA)
Hemagglutinin important surface antigen
One antigenic type
Rapidly inactivated by heat and light
19
7




Respiratory transmission of virus
Replication in nasopharynx and regional
lymph nodes
Primary viremia 2-3 days after exposure
Secondary viremia 5-7 days after exposure
with spread to tissues
19
8


Incubation period 10-12 days
Prodrome
◦ Stepwise increase in fever to
103°F or higher
◦ Cough, coryza (head cold), conjunctivitis
◦ Koplik spots (rash on mucous membranes)
Coryza = Head cold
19
9

Rash
◦
◦
◦
◦
◦
2-4 days after prodrome, 14 days after exposure
Maculopapular, becomes confluent
Begins on face and head
Persists 5-6 days
Fades in order of appearance
20
0
Measles Complications
Condition
Diarrhea
Otitis media
Pneumonia
Encephalitis
Hospitalization
Death
Percent reported
8
7
6
0.1
18
0.2
Based on 1985-1992 surveillance data
201
Measles
• As many as one in 20 children with measles
gets pneumonia and about one in 1,000
develop encephalitis.
• For every 1,000 children who get measles, one
or two will die, according to the U.S. Centers
for Disease Control and Prevention.
• The measles virus is easily spread when an
infected person coughs or sneezes.
202



Isolation of measles virus from a clinical
specimen (e.g., nasopharynx, urine)
Significant rise in measles IgG by any
standard serologic assay (e.g., EIA, HA)
Positive serologic test for measles IgM
antibody
20
3
Measles - United States, 1950-2007
Cases (thousands)
900
800
700
600
Vaccine Licensed
500
400
300
200
100
0
1950
1960
1970
1980
1990
2000
20
4



12 months is the recommended and
minimum age
MMR given before 12 months should not be
counted as a valid dose
Revaccinate at 12 months of age or older
20
5



College students
International travelers
Healthcare personnel
◦ All persons who work in medical facilities
should be immune to measles
20
6
Acute viral illness
 Parotitis and orchitis described by
Hippocrates in 5th century BCE
 Viral etiology described by Johnson and
Goodpasture in 1934
 Frequent cause of outbreaks among
military personnel in prevaccine era

20
7




Paramyxovirus
RNA virus
One antigenic type
Rapidly inactivated by chemical agents, heat,
and ultraviolet light
20
8




Respiratory transmission of virus
Replication in nasopharynx and regional lymph nodes
Viremia 12-25 days after exposure with spread to tissues
Multiple tissues infected during viremia, especially parotid
salivary glands
20
9
CNS involvement
15% of clinical cases
Orchitis
20%-50% in post- pubertal
males
Pancreatitis
2%-5%
Deafness
1/20,000
Death
Average 1 per year
(1980 – 1999)
Mumps—United States, 1980-2007
14000
12000
Cases
10000
8000
6000
4000
2000
0
1980
1985
1990
Year
1995
2000
2005
21
1

Acute onset of unilateral or bilateral tender,
self-limited swelling of the parotid or other
salivary gland lasting more than 2 days
without other apparent cause
21
2



Respiratory Syncytial Virus (RSV) may be responsible for up to
90% of bronchiolitis cases in young children
Bronchiolitis is acute inflammation of the airways,
characterised by wheeze.
A syncytium is a multinucleate cell which can result from
multiple cell fusions
21
3



Diagnosis is based on the signs of respiratory
distress verified by immunoassay
Treatment is supportive
Ribavirin is used to treat extreme cases
21
4


Picornaviridae
◦ Polio, Hepatitis A,
common cold
Calicivirus
◦ Stomach flu

Coronaviridae

Flaviviridae


◦ Common cold
◦ West Nile
◦ Hepatitis C
◦ Zika
Retroviridae
◦ AIDS
Togaviridae

Paramyxovirus
◦ Measles, mumps

Orthomyxovirus


Influenza
Rhabdoviridae
◦ Rabies

Filoviridae
◦ Hemorrhagic Fever

Reoviridae
◦ Stomach flu
◦ German Measles
21
5



Caused by two species of orthomyxovirus,
designated types A and B
Infection occurs primarily through inhalation
of airborne viruses
Rarely attack cells outside the lungs
21
6
21
7


Death of the epithelial cells infected with influenza viruses
eliminate the lungs first line of defense against infections, the
epithelial lining
Flu patients become more susceptible to secondary bacterial
infections
21
8

AEROSOL
◦ 100,000 TO
1,000,000 VIRIONS
PER DROPLET


18-72 HR
INCUBATION
SHEDDING
219






FEVER
HEADACHE
MYALGIA
COUGH
RHINITIS
OCULAR SYMPTOMS
22
0

SEVERITY
◦ VERY YOUNG
◦ ELDERLY
◦ IMMUNOCOMPROMISED
◦ HEART OR LUNG
DISEASE
22
1



CROUP (YOUNG CHILDREN)
PRIMARY INFLUENZA VIRUS PNEUMONIA
SECONDARY BACTERIAL INFECTION
◦ Streptococcus pneumoniae
◦ Staphlyococcus aureus
◦ Hemophilus influenzae
22
2





Usually caused by excess aspirin
consumption in children, especially during
viral infections.
liver - fatty deposits
brain - edema
vomiting, lethargy, coma
risk factors
◦ youth
◦ certain viral infections (influenza, chicken pox)
◦ aspirin
22
3



cardiac complications
encephalopathy
liver and CNS
◦ Reye’s syndrome

peripheral nervous system
◦ Guillian-Barré syndrome
22
4

1976/77 swine flu vaccine
◦ 35,000,000 doses
 354 cases of GBS
 28 GBS-associated deaths
 recent vaccines much lower risk
22
5

MAJOR CAUSES OF INFLUENZA VIRUSASSOCIATED DEATH
◦ BACTERIAL PNEUMONIA
◦ CARDIAC FAILURE

90% OF DEATHS IN THOSE OVER 65 YEARS OF
AGE
22
6

HA and NA accumulate mutations
◦ RNA virus

immune response no longer protects fully

sporadic outbreaks, limited epidemics
22
7
Figure 25.39
22
8
•
“new” HA or NA proteins
•
pre-existing antibodies do not protect
•
may get pandemics
22
9
Figure 25.39
23
0
Influenza epidemiology
• Influenza A has wide host range
– Birds (natural), sea mammals, horses, pigs, humans
• Strains are described by antigenicity of HA and NA, which are
designated by numbers
• Currently 15 HA (1-15) and 9 NA (1-9) described
–
–
–
–
–
1918 “Spanish flu” pandemic – H1N1
1957 “Asian flu” epidemic – H2N2
1968 “Hong Kong flu” pandemic – H1N2
1977 “swine flu” epidemic – H1N1
1999 – current threat is H5N1, similar to 1918 strain
• Epidemiology involves close contact of humans, farm animals,
and birds –especially in Asia
• Kills >20,000 per year in the US normally
231
Swine Flu
232

‘BEST GUESS’ OF MAIN ANTIGENIC TYPES
◦ CURRENTLY




type A - H1N1
type A - H3N2
type B
each year choose which variant of each subtype is the
best to use for optimal protection
23
3

inactivated
egg grown
sub-unit vaccine for children

reassortant live vaccine approved 2003


◦ for healthy persons (those not at risk for
complications from influenza infection) ages 5-49
years
23
4


REST, LIQUIDS, ANTI-FEBRILE AGENTS (NO
ASPIRIN FOR AGES 6MTHS-18YRS)
BE AWARE OF COMPLICATIONS AND TREAT
APPROPRIATELY
23
5


Picornaviridae
◦ Polio, Hepatitis A,
common cold
Calicivirus
◦ Stomach flu

Coronaviridae

Flaviviridae


◦ Common cold
◦ West Nile
◦ Hepatitis C
◦ Zika
Retroviridae
◦ AIDS
Togaviridae

Paramyxovirus
◦ Measles, mumps

Orthomyxovirus


Influenza
Rhabdoviridae
◦ Rabies

Filoviridae
◦ Hemorrhagic Fever

Reoviridae
◦ Stomach flu
◦ German Measles
23
6

Rhabdoviridae
◦ Include a variety of plant and animal pathogens
◦ Rabies is the most significant pathogen

Filoviridae
◦ Cause a number of emerging diseases
◦ Include Ebola and Marburg hemorrhagic fevers
23
7




Rabies virus is the causative agent
Classical zoonotic disease of mammals
97% of cases of human rabies is from the bite
of an infected dog. That is why the government
passed a law to mandate that all pet dogs have
a rabies vaccination.
Most human deaths from rabies is from the bite
of a bat, which goes unnoticed and therefore is
untreated.
23
8



Any warm blooded animal can get rabies
if bitten by an infected animal.
All rabies-infected animals will die
within 30 days of being bitten.
The only exception are the few animals
that are asymptomatic carriers of rabies:
◦
◦
◦
◦
Bats
Skunks
Raccoons
Foxes
23
9


Patient with rabies, 1959

It usually takes about 30 days
for symptoms to show after a
bite from an infected animal
(the virus slowly travels
towards the brain), but
sometimes symptoms begin
as early as 4 days.
Treatment must begin within
10 days after exposure.
Once symptoms occur,
treatment does not work and
the disease is always fatal in
2-10 days.
24
0



Early-stage symptoms of rabies are malaise,
headache and fever, progressing to acute pain,
violent movements, uncontrolled excitement,
depression, and hydrophobia.
Finally, the patient may experience periods of mania
and lethargy, eventually leading to coma.
The primary cause of death is usually respiratory
insufficiency.
Frothing at the mouth is
caused by paralysis of the
tracheal muscles, making it
hard to swallow.
24
1

Diagnosis

Treatment
◦ Neurological symptoms of rabies are unique and
usually sufficient
◦ By the time symptoms and antibodies occur it is too
late to intervene
◦ Treatment of the site of infection
◦ Injection of human rabies immune globulin
◦ Vaccination with human diploid cell vaccine (HDCV)
 Viral replication and movement to the brain is slow
enough to allow effective immunity to develop before
disease develops
24
2



All human cases of rabies were fatal until a
vaccine was developed in 1885 by Louis Pasteur
and Émile Roux.
Their original vaccine was harvested from
infected rabbits, from which the virus in the
nerve tissue was weakened by allowing it to dry
for five to ten days.
They injected the vaccine into 50 dogs in June,
and 10 days later injected the dogs with blood
from a rabid dog. They then had to wait 30 days
to make sure the vaccine worked.
24
3



However, on July 6, a poor peasant woman spent
her life savings on a train ticket to transport her
9 year old son 200 miles to Paris to see Dr.
Pasteur. He had been bitten by a rabid dog and
she had heard of Pasteur’s work on the smallpox
vaccine.
Since Pasteur was a chemist and not a medical
doctor, he had to convince the medical doctor to
administer the vaccine.
Pasteur told him he had tested the vaccine on 50
dogs, but he did not tell him the 30 day period
had not elapsed yet.
24
4


Not all people bitten by a rabid animal will
get rabies, so no one could be sure that the
boy even had the virus.
The vaccination regimen was to give 2 shots a
day, starting with a very weakened virus, and
increasing the virulence of the organism each
day. By the 10th day, the shots would contain
the fully virulent live rabies organism. If the
person did not have rabies, they will now!
24
5


They then injected the vaccine into a boy with
rabies. They gave one injection on each side
of the abdomen, into the peritoneal cavity.
These injections were repeated daily for 10
days, and on the last day, they gave him the
live rabies virus.
It was the first time a human ever survived
rabies. Therefore, they continued this painful
treatment until the 1990’s since they did not
know what else to do!
24
6


Nine year old
Joseph Meister had
been bitten by a
dog that had
rabies.
The boy recovered
after receiving the
vaccine from
Pasteur. When he
grew up he
became a
caretaker at the
Pasteur Institute.
24
7



Modern treatment is just one injection of human
rabies immunoglobulin (HRIG) into the deltoid
muscle. This is 100% effective if given early.
Awakening to find a bat in the room, or finding a
bat in the room of a previously unattended child
or mentally disabled or intoxicated person, is
regarded as an indication for this post-exposure
prophylaxis.
Prevention
◦ Vaccination of domestic dogs and cats can help control
rabies
◦ Little can be done to eliminate rabies in wild animals
24
8
24
9
Source: Centers for Disease Control and Prevention, November 2010


Picornaviridae
◦ Polio, Hepatitis A,
common cold
Calicivirus
◦ Stomach flu

Coronaviridae

Flaviviridae


◦ Common cold
◦ West Nile
◦ Hepatitis C
◦ Zika
Retroviridae
◦ AIDS
Togaviridae

Paramyxovirus
◦ Measles, mumps

Orthomyxovirus


Influenza
Rhabdoviridae
◦ Rabies

Filoviridae
◦ Hemorrhagic Fever

Reoviridae
◦ Stomach flu
◦ German Measles
25
0





Marburg virus and Ebola virus are the causative
agents
The natural reservoir and mode of transmission
to humans are unknown
Spread from person to person via contaminated
bodily fluids, primarily blood, and
contaminated syringes
The virions attack many cells of the body,
especially macrophages and liver cells
Infections results in uncontrolled bleeding
under the skin and from every body opening
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1


The only treatment involves fluid replacement
Up to 90% of human victims die
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2



It is a member of the Filoviridae
family (the only other member is
Marburgvirus).
ss, negative sense RNA
Has a distinct characteristic “6”
shape.
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3
First
found in a province in Sudan and its
neighboring country, Zaire (1976). The Zaire outbreak
280/318 cases resulted in death. The Sudan strain
caused death in 397/602 cases.
1989: Ebola made its way to the United States. A lab
worker was infected by the monkeys he was working
with (Maccaca fascicularis). Workers developed
antibodies to Ebola, but did not get sick.
1994: Cote d’ Ivory- only one case here: a scientist
conducted an autopsy on a wild chimpanzee. He fell
ill, but did not die.
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4
In total, there are 4 known, documented
strains of Ebola:
◦
◦
◦
◦
Ebola
Ebola
Ebola
Ebola
Zaire (EBO-Z): a 90% death rate
Sudan (EBO-Z): lower death rate
Reston
Cote d’ Ivory
All strains of Ebola are classified as Biosafety Level 4,
meaning Hazmat suits, multiple airlocks, ultraviolet
light rooms. Workers must be cleared to handle
BSL4.
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5
25
6
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7



One of the easiest methods of transmission in
Ebola is through bodily fluids (blood,
secretions).
Handling infected animals can also lead to
infection with Ebola.
While monkeys were able to transfer Ebola
between themselves via airborne particles,
this type of aerosol transfer has not been
demonstrated setting in a laboratory setting.
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8
Incubation
periods can be anywhere from 2-21 days.
Common symptoms include: sudden onset of fever,
headaches, sore throat, muscle pains, and intense
weakness.
More intense symptoms include: maculopapular
rash, kidney/liver disfunction.
Possible internal/external bleeding.
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9
Internal
bleeding is caused by Ebola’s
coagulpathy ability. This describes a
dysfunction in the host blood clotting system.
When infected, host macrophages begin to
express Tissue Factor (TF). TF attracts clotting
molecules from the blood, leaving the rest of
the body susceptible.
Small holes in the capillaries are then cut by
Ebola. Without clotting factors, the host
bleeds continuously, dying of what some have
called “a million cuts.”
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0
Unfortunately,
no reservoirs have been
identified for Ebola. Several times, scientists
have brought in rodents, bats, primates,
plants, and arthropods to test for Ebola.
 Ebola could not be detected or isolated from
any of these reservoirs.
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1



As there is no known cure for Ebola,
treatment options are very limited for
patients.
Typically, supportive therapy is used
(balancing patient’s fluids, electrolytes,
maintaining oxygen status and blood
pressure).
While there are no cures yet, that does not
mean several groups are not working to
create one.
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2




Barrier Nursing Techniques are employed to
prevent further infection. Screens are placed
around the patient’s bed.
Anyone treating the patient must wear gowns,
masks, and gloves.
Any items used to treat the patient are
immediately put into a sterilizing solution
afterwards.
Changing sheets must also be done with care, to
minimize the possibility of launching airborne
particles or droplets of contagious material.
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3
264
Cures/Vaccines
• 1999: BBC researchers, led by Dr. Maurice Iwu, investigated
the garcinia kola plant, typically eaten in Western Africa.
Medicine men in those areas had long been using it and
introduced it to the researchers. In a lab setting, the plant
has been shown to inhibit Ebola multiplication.
• 2001: Mice injected subcutaneously with Ebola did not
become sick, but mounted an immune response. Serum
from these mice were used to treat new mice before or
after Ebola injection. All of the mice treated with serum
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survived.


Picornaviridae
◦ Polio, Hepatitis A,
common cold
Calicivirus
◦ Stomach flu

Coronaviridae

Flaviviridae


◦ Common cold
◦ West Nile
◦ Hepatitis C
◦ Zika
Retroviridae
◦ AIDS
Togaviridae

Paramyxovirus
◦ Measles, mumps

Orthomyxovirus


Influenza
Rhabdoviridae
◦ Rabies

Filoviridae
◦ Hemorrhagic Fever

Reoviridae
◦ Stomach flu
◦ German Measles
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6






Cause infantile gastroenteritis
Account for approximately 50% of all cases of
diarrhea in children requiring hospitalization
Transmitted via the fecal-oral route
usually self-limited
replacement of water and electrolytes
A vaccine is available that provides some
protection but has been linked to a rare bowel
blockage condition in some children
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7




First identified as cause of diarrhea in 1973
Most common cause of severe diarrhea in
infants and children
Nearly universal infection by 5 years of age
Responsible for up to 500,000 diarrheal
deaths each year worldwide
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8



There is an oral vaccine called "Rotarix“.
It is given to babies at 2 months of age and
the second at 4 months of age.
If the infant has not completed the
vaccination by 5 months of age, it is
ineffective.
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9
270
Randy Travis in critical condition with
viral cardiomyopathy
• July 9, 2013
• the singer's health deteriorated rapidly over the past
several days after he developed what he thought was
a cold.
• The Mayo Clinic website describes cardiomyopathy
as a disease that weakens and enlarges the heart
muscle, making it harder for the heart to pump
blood and carry it to the rest of the body. It can lead
to heart failure. Treatments range from medications
and surgically implanted devices to heart transplants.
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Viral cardiomyopathy
• Viral cardiomyopathy occurs when viral infections
cause myocarditis with a resulting thickening of the
myocardium and dilation of the ventricules.
• These viruses include Coxsackie B and adenovirus,
echoviruses, influenza H1Ni, Epstein-Barr virus,
rubella (German measles virus), varicella
(chickenpox virus), mumps, measles, parvoviruses,
yellow fever, dengue fever, polio, rabies and the
viruses that cause hepatitis A and C.
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

Prion Diseases
◦ Mad Cow Disease
◦ Creutzfeldt–Jakob disease
◦ Kuru
DNA Viruses
◦ Poxviridae: Smallpox
◦ Herpesviridae: Cold sores,
chicken pox,
mononucleosis
◦ Hepadnoviridae: Hepatitis B
◦ Papillomaviridae: Warts
◦ Adenoviridae: Common
cold, pink eye

RNA Viruses
◦ Picornaviridae: Polio, Hepatitis
A, common cold
◦ Coronaviridae: Common cold
◦ Calicivirus: Stomach flu
◦ Flaviviridae: Hepatitis C; West
Nile, Zika
◦ Retroviridae: AIDS
◦ Togaviridae: German Measles
◦ Paramyxovirus: Measles,
mumps
◦ Orthomyxovirus: Influenza
◦ Rhabdoviridae: Rabies
◦ Filoviridae: Hemorrhagic Fever
◦ Reoviridae: Stomach flu
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3
Love Story
I will seek and find you.
I shall take you to bed and have my way with you.
I will make you ache, shake & sweat until you moan & groan.
I will make you beg for mercy, beg for me to stop.
I will exhaust you to the point that you will be relieved when I'm finished
with you.
And, when I am finished, you will be weak for days.
All my love,
The Flu
Now get your mind out of the gutter and go get your
Flu shot!
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