General Properties: NA

 DNA
 Single or Double stranded
 Glycosylated and/or Methylated
• Cytosine, Uracil, Thymine
 Circular
or Linear
 Unique purine and/or pyrimidine
bases
 Bound protein molecules
 General Properties: Capsid
 Protomers -> Capsomeres -> Capsid
 Protein Coat
 Organization gives the virus form
 Icosahedral
• Triangular face with hexon
• 12 corners with penton
 Helical
• Protomers not grouped in capsomeres
• Bound together to form a ribbon which folds
 Complex
 General Properties:
Envelope
 Lies outside the capsid
 Made up of lipids, proteins, CH20
 Contains antigens from host & virus
 Enveloped or Nonenveloped (naked)
 +/- Spikes
 Glycoprotein projections of envelope
 Functions
• Enzymatic
• Adsorption
• Hemagglutin
 Viral Replication Cycle
 Adsorption (Attachment): viral protein + host cell receptor
 Penetration
 Uncoating: cytoplasm of host using proteolytic enzymes
 Replication of NA (DNA)
 Early Transcription (ds DNA is needed, ss-> ds)
 Early Translation (mRNA-> enzymes for viral DNA)
 Late Transcription (ds DNA used)
 Late Translation (mRNA-> proteins for capsid)
 Assembly: NA + capsid
 Maturation
 Enveloped: cell membrane
 Non-enveloped: naked, accumulated in cell -> inclusions
 Complex: multilayered membrane
 Release: via cell lysis
 Viral Pathogenicity
 Contributing Factors
 Ability to enter cell
 Ability to grow in cell
 Ability to combat host defenses
 Ability to produce damage
• Cell Lysis via hypersensitivity reactions (II, IV)
• Production of toxic substances
• Cell transformation
• Metabolism and cellular products: Turn “on” genes
• Structural: Nuclear or Cytoplasmic inclusions
 DNA VIRUS
Name of Virus With Shape of Capsid Strand
Envelope

Papovaviridae Papillomavirus Icosahedral

(circular NC)
Polyomavirus
Adenoviridae
NO Linear
DS

Poxviridae Linear

Parvoviridae B19 icosahedral SS

Herpes simplex 1 Icosad eltahedral
Herpes simplex 2

Varicella-Zoster virus
Epstein-Barr virus

Herpesviridae Cytomegalovirus YES DS

Herpes T Lymphotropic virus

Herpes Virus 7

Kaposi’s Sarcoma related Virus

Hepadnaviridae HBV Circular with RT Partially DS

 Therefore…

 All DNA viruses are double stranded except

Parvoviridae
 All DNA viruses are non-enveloped except
Herpesviridae and Hepadnaviridae
 All Herpesviruses are
icosadeltahedrals/icosahedral
 Important Things to
Remember…
 Largest DNA virus-
 Smallest DNA virus-

 ssDNA virus-

 Cytoplasmic Replication-
NAME OF VIRUS DISEASE

Papovaviridae a. Papilloma virus Warts, Cervical carcinoma

b. Polyoma virus Renal Disease, PML
Adenoviridae Respiratory Infection
Parvoviridae a. Parvovirus B19 Aplastic Crisis, fifth disease,
hydrops fetalis, Slapped Cheek
Syndrome
Poxviridae a. Vaccinia ---vaccine
b. Variola Smallpox
Herpesviridae a. HSV 1 Facial Herpes
b. HSV 2 Genital Herpes
c. Varicella Zoster Virus Chickenpox
d. Epstein Barr virus Burkitt’s Lymhoma, IM
e. Cytomegalovirus Neonatal deafness and mental
retardation
f. Herpes T-Lymphotropic Virus Roseola exanthema
g. HHV 7
h. Kaposi’s sarcoma virus AIDS Related Herpes
Hepadnaviridae a. Hepatitis B virus Hepatitis, Cirrhosis, Primary
Hepatocarcinoma
 Naked- with fibers at
verices
 Linear and DS viral core
genome- encodes protein
for both mRNA and DNA
synthesis
 With Serotypes- due to
difference of penton bases
in the fiber
 STRUCTURE
Size: 70-90nm
Non-enveloped
icosahedral virus
Capsid comprised of
3 surface coat proteins
 Fibers
 Pentons
 Hexons
Adenovirus Serotype
Diseases
 Acute Respiratory
Distress (ARD)
 Common cold
 Hemorrhagic
Cystitis
 Pink-eye
 Gastroenteritis
 Hepatitis
 Disease Serotype
Endemic Respiratory Disease 1,2,5
Acute respiratory disease of military 3,4,7,14,21
recruits
Adenoviral pneumonia 3,4,7b,14,21
Epidemic Keratoconjunctivitis 8,19
Pharygoconjunctival fever 3,7
Pertussis syndrome 1,2,3,5
Acute hemorrhagic cystitis 1,4,7,11,21
Hepatic disorders 3,7
Gastroenteritis 9,12,13,18,25-29,40-42
Intussusception 1,2,5
Musculoskeletal disorders 7
Genital infections 19
Skin infections 2,4,7,21
Infections in immunocompromised hosts 32,34,35,36
Mode of Transmission
 Who are at Risk?
Day-Care
Center

PEOPLE

Military
Swimming Training
Pool Clubs Camps
…Don’t worry, adenoviruses are
not transmitted through contact
with pigs!
Secondary Infection

Virus spreads to fingers

 In contact to
eyes
 Adenovirus
conjunctivitis
 What does the virus targets?
Respiratory
Tract

Conjunctiva Mucoepithelial Gastrointestinal

Cells Tract

Cornea
Respiratory Tract Infection
 Common cold symptoms
 Sore Throat
 Severe cough
 Swollen lymph nodes
 Headache
 Non-productive “croupy” cough
 Intestinal Tract Infection
 Abrupt onset of water diarrhea
 Fever
 Abdominal Tenderness
 Vomiting

• Notice: Both cases have very similar symptoms to

common cold and influenza

• Respiratory secretion culture

• Stool culture
• Chest x-ray
• Blood work
Geography/Season

The virus is found worldwide

No seasonal incidence
Modes of Control
VACCINATION

 Live vaccines for

serotype 4 and 7
is available for
military use
 Summary of Adenoviridae

 Posseses long fiber for attachment to the

host cell
 Causes _______________________ in
children
 Severe diarrheal disease in newborns and
immunocompromised
 Associted with respiratory infections, UTI, GI
infections, and Eye infections
 Structure and Composition
 Spherical icosahedron, 150-200 nm
 Double-stranded DNA, linear
 More than 35 proteins
 Enveloped
 Latency occurs in the neurons
 Replication from nucleus (budding)
 Features
• Encode many enzymes
• Establish latent infections
• Lifelong persistence
• Significant cause of death in
immunocompromised hosts
• Some can cause cancers
 Why Enveloped but causes lysis?

 DNA replication and Assembly occurs ALL

in the “nucleus”
 Virus gets its envelope from the nuclear
membrane as it buds to the cytoplasm
 Virus is released by exocytosis and lysis
Human Herpesvirus 1 & 2
HSV1,2 or Herpes Simplex
 HSV1: Associated with
oro-facial lesions
 HSV2: Associated with
genital lesions
 Direct contact
 Subclinical
 Vessicles
 Latency
 DX: Culture, EM
 Reactivation: stress,
UV, fever
• Classification (human viruses)
• Subfamilies
• Alpha
• Beta
• Gamma
• Species
• Simplex 1 (HHV-1) (alpha)
• Simplex 2 (HHV-2) (alpha)
• Varicella (HHV-3) (alpha)
• Epstein-Barr (HHV-4) (gamma)
• Cytomegalovirus (HHV-5) (beta)
• HHV-6 (beta)
• HHV-7 (beta)
• Kaposi’s sarcoma virus (HHV-8) (gamma)
 HSV 1 and 2

• Herpes Simplex viruses

• Two species
• HSV-1: oropharyngeal sores
(children)
• HSV-2: genitalia (young adults)
• Global
• HSV-1 and 2 infections are life-long.
• HSV-1
• Most commonly acquired by children
• Most adults are seropositive
• Only a small proportion have recrudescence
• HSV-2
• Most commonly acquired by young adults
• Sexually-transmitted disease
• About 1 in 6 Americans has HSV-2
• Fetal/newborn transmission
• Increased risk for HIV infection
 Disease caused by
Herpes Simplex Viruses
 Oral Herpes - Cold sores
 Herpetic gingiovostomatitis, the infection, often
initially on the lips spreads to all parts of the mouth
and pharynx.
 Eczema Herpeticum
 This is found in children with active
eczema.
 The virus can spread to other organs
such as the liver and adrenals.
 Disease caused by Herpes
Simplex Viruses
 Genital Herpes
 Is usually the result of HSV-2.
 Primary infection is often asymptomatic but many
painful lesions can be developed on the shaft of the
penis and vulva, vagina, cervix and perianal region of
women.
 • Children- oral herpes
• Sexually active people

• Nurses
• RMT
• Physicians
Herpetic
Whitlow
 APPROACH TEST/COMMENT

Direct microscopic examination of cells Tzanck smear shows multinucleated

from base of lesion giant cells and Cowdry type A
inclusion bodies
Cell culture HSV replicates and causes identifiable
CPE in most cell cultures

Assay of tissue biopsy, smear, or Enzyme immunoassay,

vesicular fluid for HSV antigen immunofluorescent stain, and in situ
DNA probe analysis are used
HSV type distinction Type-specific antibody, DNA maps of
(HSV-1 vs. HSV-2 restriction enzymes, SDS gel protein
patterns, and DNA probe analysis are
used
Serology Serology is not useful except for
epidemiology
Diagnosis of HSV
Infections
• Acyclovir drug of choice
• No vaccine is available
• Health care workers must
always wear gloves
• With active genital lesion
-
 Varicella Zoster Virus (HHV
3)
 Transmitted through the
respiratory route/fluid from
lesions
 Lesions first appear on the
scalp and trunk
 Lesions appear as a vesicle
with clear fluid resembling DX: EM, culture, serology for IgM

TX: Acyclovir, nucleoside analog

__________________________ of Guanosine. Binds to
DNA polymerase after it is
 Remains latent in the incorporated into host DNA.

_____________________________
 Varicella-Zoster virus
 Clinical spectrum
• Almost always apparent
• 10-21 day incubation
• Malaise, fever, rash for about 5 days
• Complications are rare
• Primary infection as an adult is usually more
serious
• Immunocompromised patients
 Zoster
• Usually occurs in aged or immunodeficient persons
• Often starts as lesions on the lower back
• Painful
• Usually resolves without complications
 Varicella-Zoster virus
 Varicella (“chickenpox”)
 Zoster (“shingles”)

Disease mechanism of VZV

• Initial replication occurs in the respiratory
tract
• Targets epithelial cells and fibroblasts
V
I
R
E
M
I
A
 Epidemiology of VZV
infection
 Virus is transmitted mainly by respiratory droplet
 Who are at Risks?
 Children (age 5-9): mild class disease
 Teens and adults: more severe disease with potential
pneumonia
 Immunocompromised people and newborns: at risk for
life threatening pneumonia, encephalitis, and
progressive-disseminated varicella
 Elderly and immunocompromised people: at risk for
recurrent disease (Zoster(Shingle))
Varicella

 After an incubation period of

approximately 14-16 days the disease
begins with low grade fever, malaise
and the appearance of a chracteristic
generalized pruritic vesicular eruption
(“dewdrop on a rose petal”)
 Modes of Control
 Antiviral drugs are available
 Immunity is lifelong

 Varicella-zoster immunoglobulin is available

for immunocompromised people and staff
exposed to virus as well as newborns of
mothers showing symptoms within 5 days of
birth.
 Live vaccine (Oka strain) is available.
 Difference of Chickenpox and Smallpox
CHICKENPOX SMALLPOX

Distribution Relative density is Relative density is

centripetal centrifugal
Predominance on flexor Predominance on extensor
surfaces and flexures surfaces and prominences
Mode of Evolution Lesions appear in crops Lesions progress from
stage to stage
synchronously

Time of Evolution Rapid Relatively slow

Lesions Superficial Deep set

Oval or totally irregular Tend to be circular and
Unilocular regular
Scarring is slight and Vesicles multilocular
superficial Scarring is severe and
deep
Causes ____________________________
Shed in the saliva through oral contact
Most common signs include:

_____________________________________
Differential WBC count shows lymphocytosis
with atypical cells: _________________
 __________________-
lymphoma of the jaw and face ;
endemic in children in Africa

 _________________________-
common in Southern China and
Southeast Asia
Transmission

 Salivary exchange
 Kissing Disease
 Close oral contact
 Sharing of items such as
toothbrushes, cup, spoon and fork
Who are at Risk?

 Children
 Teenagers
 Immunocompromised patients
 Formerly known as ________________________
 Transmitted through: direct contact with saliva,
blood transfusions, organ transplants
 Asymptomatic or mild infection in healthy
individuals
 May remain latent in white blood cels, endothelial
cells, and other organs
 Most common congenital viral pathogen
 May manifest as pneumonia 1 month
after transplant
_________________________
o Direct examination: large cells with large
intranuclear, basophils staining
inclusions
______________________
 Modes of Transmission

 Occurs via blood, organ transplant, and

secretions, including urine, salive, semen,
cervical secretions, breast milk, and tears
 Transmitted orally and sexually, in blood
transfusion, in tissue transplant, in utero, at
birth and by nursing
 Who are at Risk?

 Babies of mother who seroconvert during term:

at high risk for congenital defects
 Sexually active people
 Blood and organ recipients
 Burn patients
 Immunocompromised people, who may have
symptoms and recurrent disease
Modes of Control

 Antiviral drug are available for

patients with AIDS
 Screening for potential blood organ
donors for CMV reduces
trnasmission of the virus
 CMV Syndrome
TISSUE CHILDREN/ADULTS IMMUNOCOMPROMISED
PATIENTS
Predominant nature of Inapparent infection Disseminated disease,
disease severe disease
Eyes - Chorioretinitis
Lungs - Pneumonia

Gastrointestinal Tract - Esophagitis, colitis

Nervous System Polyneuritis, myelitis Meningitis and
encephalitis, myelitis
Lymphoid System Mononucleosis Leukopenia,
syndrome, lumphocytosis
posttransfusion
syndrome
Major Organs Carditis, hepatitis Hepatitis
Neonates Deafness, mental -
retardation
 Laboratory Tests for Diagnosis of CMV
infection
TEST FINDING
Cytology and Histology “OWL’S EYE” inclusion
bodies
Antigen detection
In situ DNA probe
hybridization
Cell culture Cytological effect in human
diploid fibroblasts

Serology Immunofluorescence
detection of early antigens
Primary infection
 Herpes Virus 6

 Human B Lymphotrophic virus (HV-6)

 Roseola infantum or exanthem
subitum
• Is a common exanthema of childhood
caused by infection with HHV 6. It is
characterized by a febrile illness with mild
constitutional symptoms lasting 3-5 days.
After rapid defervescence, a pink macular
or maculopapular rash appears primarily
on the trunk and lasting hours to days.
Herpesvirus 7 and 8

 HHV 7
 Cryptic Infection of Helper T cells
 Fatal encephalitis

o HHV 8
 Karposi’s Sarcoma
 Cancer found in AIDS patients
 Also causes Primary Effusion Lymphoma
VIRUS DISEASE
Papillomavirus warts
Polyomavirus
BK Virus Renal Disease
JC Virus Progressive Multifocal
Leukoencephalopathy
(PML)
 Unique Properties of Papovaviruses

 There is a small icosahedral capsid virion

 Double stranded circular DNA genome is
replicated and assembled in the nucleus
 There are two major genera:
 _________________: HPV types 1 to 58+ ( as
determined by genotype; types defined by DNA
homology, tissue tropism, and association with
oncogenesis)
 _________________: SV-40, JC virus, BK virus
 Human Papillomavirus
(commonly called Genital Warts)
 Human Papillomavirus (HPV) is a virus that can
cause various disease states including “genital”
or “venereal” warts

 Papillomaviruses are a complex group of DNA

tumor viruses. They can cause benign growths
(papillomas), cancers, or more commonly,
transient infections

 HPV infection is causally associated with

cervical cancer ; other genital cancers including
anal, penile, vulvar, and vaginal cancers may
have HPV as co-factor
 Epidemiology of HPV and
Cervical Cancer
 Over 99% of cervical cancers have HPV DNA
detected within the tumor
 70% of cervical cancer is caused by one of two
types of HPV, 16 or 18
 The quadrivalent HPV vaccine protects against
Types 6, 11, 16 and 18
 Risk Factors for Acquiring a
Genital HPV Infection

 Young age (less than 25 years)

 Multiple sex partners
 Early age at first intercourse (16 years or
younger)
 Male partner has (or has had) multiple sex
partners
HPV Transmission

 Direct skin-to-skin contact

 Usually, but not always sexual contact
 Infected birth canal
 Fomites (very rare)
What about oral sex?

 It can occur in the mouth, throat or

respiratory tract
 It is relatively uncommon
 It appears to be an inefficient mode
for transmission
HPV Incubation

 Average incubation is 3 weeks to 1

year

 Possibly years before appearance of

warts or cervical abnormalities

 Some will be transient and may never

be detected
 Clinical Syndrome Associated with Papillomaviruses
HPV TYPES
SYNDROME COMMON UNCOMMON
SKIN WARTS
Plantar Warts 1 2,4
Common Warts 2,4 1,7,26,29
Flat warts 3,10 27,28,41
Epidermodysplasia 5,8,17,20,36 9,12,14,15,19,21-25,38,46
verrruciformis
BENIGN HEAD AND NECK TUMORS
Laryngeal papilloma 6,11 -
Oral papilloma 6,11 2,16
Conjunctival papilloma 11 -
ANOGENITAL WART
Condyloma acuminate 6,11 1,2,10,16,30,44,45
Cervical intraepithelial 16,18 11,31,33,35,42-44
neoplasia, Cancer
 Different Types of Warts

 _________________- Common warts, typically

single or multiple, flesh colored, dome-shaped
papules with a rough, verrucous surface
 Thrombosed vessels (black dot) on the surface

o ______________________- Plantar Warts; occur on

weight bearing areas of the feet and commonly
exhibit overlying hyperkeratosis
o Dark brown dots
 __________________- Flat Warts; occur
primarily on the face and extremities
 Small, flesh or brown-colored, broad based papules
varying in number
 Autoinoculation from trauma, such as shaving is a
common means of viral spread

 _____________________________- characterized by
soft, flesh-colored polypoid or acuminate warts that
occur in the anogenital region
• Can be extensive and cause pain, itching and bleeding
 Common Symptoms of Genital
Warts in Males & Females
 The symptoms may include single or multiple
fleshy growths around the penis, scrotum,
groin, vulva, vagina, anus, and/or urethra

 They may also include: itching, bleeding, or

burning, and pain

 The symptoms may recur from time to time

Genital Warts in a Male
HPV Penile Warts
Pearly Penile Papules
Intra-meatal Wart of the Penis
(and Gonorrhea)
 Circumcision and HPV

• Risk for penile cancer

• May influence the risk of HPV acquisition,
transmission and cervical cancer
Female Genital Warts
HPV Warts on the Thigh
Perianal Warts
Complications of Genital Warts
(if untreated)
 It may destroy body tissue around the
genitals and anus
 For pregnant women
 Delivery complications or need for C-
section
 Juvenile Onset Recurrent Respiratory
Papillomatosis (JO-RRP)
 Testing & Treatment for
Genital Warts
 Can be detected in a clinical exam;

 Can be treated by removing the warts;

 The virus cannot be removed, so the

warts may grow back.
HPV Diagnostic Techniques

 History
 Visual exam
 Pap smears
 DNA testing
Papillomavirus
Treatment

 Primary goal for treatment of visible

warts is the removal of symptomatic
warts
 Therapy may reduce but probably does
not eradicate infectivity
 Difficult
to determine if treatment
reduces transmission
No laboratory marker of infectivity
Variable results utilizing viral DNA
HPV Treatment Options
 Chemical agents
 Cryotherapy
 Electrosurgery
 Surgical excision
 Laser surgery
 Imiquimod
(Aldara)
 Defer treatment
 Natural therapies
 Surgical removal

 Patient-applied
Podofilox (Condylox) 0.5% solution or gel
Apply 2x/day for 3 days, followed by 4 days of no therapy.
Repeat as needed, up to 4x
or
Imiquimod (Aldara) 5% cream
Apply 1x/day @ bedtime 3x/week for up to 16 weeks

 Provider-administered
Cryotherapy (liquid nitrogen) *repeat every 1-2 weeks
or
Podophyllin resin 10-25% *thoroughly wash off in 1-4 hrs
or
Trichloroacetic or
Bichloroacetic acid 80-90%
*can be repeated weekly
 Therapy choice needs to be guided by
preference of patient, experience of provider,
and patient resources (time and/or money)
 No evidence exists to indicate that any one
regimen is superior
 An acceptable alternative may be to do
nothing but watch and wait; possible
regression/uncertain transmission
 Case Study

Amy was diagnosed with genital warts and

successfully treated with liquid nitrogen therapy
three years ago. The genital warts have never
returned after therapy.
Amy has met someone new and she wants
to begin a sexual relationship. She wants to know
if she needs to disclose her prior infection to her
new partner.

What would you tell Amy?

 HPV
is
INCURABLE
Warts can and often do recur after
treatment.

Virus can remain in surrounding tissue

after warts have been destroyed.
Perinatal complications
HPV and Pregnancy

 No link with premature labor,

miscarriage, or other complications
 Low rate of transmission to baby
 Range is generally from 0.4 to 1.1
cases/100,000 births
 C-section is not recommended in most
instances
Treatment Regimens
 Papillomavirus
Treatment in Pregnancy
 Imiquimod, podophyllin, and podofilox should not
be used in pregnancy
 Many specialists advocate wart removal due to
possible proliferation and friability
 HPV types 6 and 11 can cause respiratory
papillomatosis in infants and children
 Preventative value of cesarean section is
unknown; may be indicated for pelvic outlet
obstruction or if vaginal delivery would result in
excessive bleeding
HPV in Neonates

 Those who develop warts will usually

do so within several weeks
 First-born child
 Juvenile onset recurrent respiratory
papillomatosis (JO-RRP)
 rare -- 1 per 100,000 births
 types 6 and 11
 occurs up to age four
 HPV DNA Classification
 Low Risk HPV Types: 6,11,40,42,43,44, 54, 61,
72, 73, 81
 types 6 and 11 responsible for 95% of visible warts

 High-Risk HPV Types: 31,33,35,39,45, 51, 52,

56, 58, 59, 68,82
High cancer risk: 16
 Most common-50% of cervical cancer
High cancer risk: 18
 10-12% of cervical cancer

*Risk not well established yet: 26, 53, 66, 73

 Can a person be
re-infected with HPV?
 There appears to be humoral and probably
cellular immunity that develops to a specific type
of HPV after a person has been infected with it
and “has cleared” it.
 The risk for re-infection with that specific type of
HPV appears to be rare.
 However, a person can be infected with more
than one type of HPV
 HPV and Cervical Cancer
 Infection is generally indicated by the detection of
HPV DNA
 Routine Pap smear screening ensures early
detection (and treatment) of pre-cancerous
lesions
 Only a small percentage of women infected with
genital HPV develop persistent infections
 Only women who develop persistent infections are at
risk for developing high-grade pre-cancerous
changes / cervical cancer
 Most women with persistent HPV infection do NOT
develop precancerous changes/cervical cancer
 The most critical factor for developing cervical cancer is
not having routine pap smears
 Cofactors for Cervical Cancer
 Active/passive  Weakened immune
Cigarette Smoking system
 Chronic inflammation  Multiple sex partners
associated with other  Sex at an early age
STDs  Nutritional
 Long term use of deficiencies
oral contraceptives  Mother who took
 High number of live DES
births*  Lack of
circumcision of
male partner(s)

LACK OF SCREENING IS THE MOST IMPORTANT FACTOR

 What is the difference between the Pap
test, a biopsy and an HPV test?

 Pap test finds abnormal cell changes on the

cervix
 Biopsy is when a cluster of cells is removed
from the cervix to confirm earlier Pap smear
results and rule out cancer
 HPV test looks for genetic material (DNA) of
HPV within cells.
 HPV Vaccine

 Approved in June 2006

 Produced by Merck and Co.
 First vaccine to prevent cervical cancer
 Recombinant vaccine
 Approved for use in females aged 9-26
 Ideally, before becoming sexually active
 Protects against infection with Types
6, 11, 16, 18
 Women aren’t protected if they have already been
infected with the HPV type(s) that are covered by the
vaccine prior to vaccination
 Will Gardasil help a female who
already has a vaccine type HPV?
 Gardasil only works to prevent four HPV types
 It is not a treatment for one or more of the HPV
types
 However, females already infected with one or
more of the four types of HPV can still receive
protection from the vaccine HPV type(s) she has
not acquired
 Can males use Gardasil?

 Gardasil has not been approved for use in

males, but the manufacturer currently has a
study underway to see if it is safe and effective
for men.
 Once the study is complete, the FDA will review
the data and make recommendations
 How is Gardasil administered?

 Three injections given over a six-month period

 Initial dose
 Second dose is given 2 months later
 Third and last dose is given 4 months after the
second dose or six months after the initial dose
 It is administered in the upper arm or thigh
(intramuscularly)
 Potential adverse reactions
 Mild/moderate pain or tenderness at the
injection site
 Females who are allergic to yeast or any
component of the vaccine should not receive
Gardasil.
 It is not a live vaccine, so it cannot cause an
infection with HPV.
 The vaccine is not recommended for pregnant
women.
 Lactating women can receive the HPV vaccine.
 Immunocompromised women can receive this
vaccine.
 How long does the vaccine
protection last?
 Vaccine protection is usually not known when a
vaccine is first introduced
 Studies that have followed women for 5 years
indicate they are still fully protected
 More research is being done to see if a booster
will be needed years later
 It is not yet known how much protection would
be given with only one or two vaccines (of the
three)
HPV Prevention

 Abstinence
 Monogamy
 Condoms
 Removal of warts
 Vaccine (Females aged 9-26)

50% to 70% of sex partners of

people with genital warts already
have or do develop warts.
 Mode of transmission:
______________________________________
 Infections are asymptomatic
 Virus establishes persistent and latent infection in
organs such as the kidneys and lungs
 JC Virus:_______________
 BK Virus:_______________
 In immunocompromised people, JC virus is
activated then spreads to the brain, and
causes PML, a convetional slow virus disease
 In PML, JC virus partially transforms
astrocytes and kills oligodendrocytes,
causing charactersitic lesions and sites of
demyelination
 BK virus is ubiquitous but is not associated
with serious disease
 Laboratory Diagnosis

 Cell Cuture
 Virus isolation-BK: ______________________________

 Virus isolation-JC:_______________________________
 ss DNA (+ or -)
 Icosahedron
 Nonenveloped
 Smallest DNA
virus
 Mode of
Transmission:
Respiratory
Droplet
 Only ____________________ is known to cause
human infection
 Causative agent of:
____________________________
 Characterized by:
_________________________________
o Virus has affinity for RBC trigger cells
o May develop
___________________________________
 Largest of all
viruses
 Oval to brick-
shaped and
complex
morphology
• “dumbbell” core
(contains nucleic
acid)
• Lateral bodies
(unknown function)
 POXVIRUSES

 In eighteenth-century England, smallpox

accounted the deaths of one third of children.

 The development of the first live vaccine in

1796 and the later worldwide distribution of this
vaccine led to the eradication of smallpox by
1980.

 Reference stocks of smallpox virus in two

World Health Organization (WHO) laboratories
were destroyed in 1996.
 Unfortunately stocks of the virus still exist in
the United States and in Russia.

 Smallpox is considered a category A agent

by the Centers for Disease Control and
Prevention (CDC), with anthrax, plague,
botulism, tularemia because of their great
potential as bioterrorism-biowarfare agents.
The largest viruses, almost visible on light
microscopy (300 nm) and are ovoid to brick shaped
with a complex morphology.
 Structure and Replication
 The replication of poxviruses is unique among
the DNA-containing viruses, in that the entire
multiplication cycle takes place within the host
cell cytoplasm.

 Viral DNA then replicates in electron-dense

cytoplasmic inclusions (Guarnieri's
inclusion bodies), referred to as factories.
 Pathogenesis and
Immunity
 After being inhaled, smallpox virus replicates in
the upper respiratory tract.
 Dissemination occurs via lymphatic and cell-
associated viremic spread.
 Internal and dermal tissues are inoculated after a
second viremia, causing the simultaneous eruption
of the characteristic "pocks.“

 Molluscum contagiosum and the other poxviruses,

however, are acquired through direct contact with
lesions.
 Epidemiology
 Smallpox and molluscum contagiosum are strictly
human viruses.

 In contrast, the natural hosts for the other

poxviruses important to humans are vertebrates
other than humans (e.g., cow, sheep, goats).
 The viruses infect humans only through accidental
or occupational exposure (zoonosis).
 Epidemiology

 Smallpox (variola) was very contagious and was

spread primarily by the respiratory route. It was
also spread less efficiently through close contact
with dried virus on clothes or other materials.

 Despite the severity of the disease and its

tendency to spread, several factors contributed to
its elimination.
 Properties of Natural Smallpox
That Led to Its Eradication
 Viral Characteristics
 Exclusive human host range (no animal reservoirs or vectors)
 Single serotype (immunization protected against all infections)
 Disease Characteristics
 Consistent disease presentation with visible pustules
(identification of sources of contagion allowed quarantine and
vaccination of contacts)
 Vaccine
 Immunization with animal poxviruses protects against
smallpox
 Stable, inexpensive, and easy-to-administer vaccine
 Presence of scar indicating successful vaccination
 Public Health Service
 Successful worldwide WHO program combining vaccination
and quarantine
 Clinical Syndromes
 SMALLPOX
 The two variants of smallpox were variola major,
which was associated with a mortality of 15% to
40%, and variola minor, which was associated with
a mortality of 1%.

 Smallpox was usually initiated by infection of the

respiratory tract with subsequent involvement of
local lymph glands, which in turn led to viremia.
 Smallpox
 After a 5- to 17-day incubation period, the infected
person experienced high fever, fatigue, severe
headache, and malaise, followed by the vesicular
rash in the mouth and on the body.

 Vomiting, diarrhea, and excessive bleeding

 The simultaneous outbreak of the vesicular rash
distinguishes smallpox from the vesicles of varicella-
zoster, which erupt in successive crops.
Smallpox
 Smallpox
 Was the first disease to be controlled by
immunization, and its eradication is one of the
greatest triumphs of medical epidemiology.
 Eradication resulted from a massive WHO campaign
to vaccinate all susceptible people,
 The campaign began in 1967 and succeeded.
 The last case of naturally acquired infection was
reported in 1977, and eradication of the disease was
acknowledged in 1980.
 Variolation
 An early approach to immunization, involved the
inoculation of susceptible people with the virulent
smallpox pus. It was first performed in the Far East
and later in England.

 Variolation was associated with a fatality rate of

approximately 1%, a better risk than that associated
with smallpox itself.

 In 1796, Jenner developed and then popularized a

vaccine using the less virulent cowpox virus, which
shares antigenic determinants with smallpox.
 VACCINIA
 Vaccinia, a form of cowpox, was used for the
smallpox vaccine.

 The vaccination procedure consisted of scratching

live virus into the patient's skin and then observing
for the development of vesicles and pustules.

 Encephalitis and progressive infection (vaccinia

necrosum), the latter occurring occasionally in
immunocompromised patients.
 ORF, COWPOX, AND MONKEYPOX

 Human infection with the orf (poxvirus of sheep

and goat) or cowpox (vaccinia) virus is usually an
occupational hazard resulting from direct contact
with the lesions on the animal.

 A single nodular lesion usually forms on the point

of contact, such as the fingers, hand and is
hemorrhagic or granulomatous.

 Then regress in 25 to 35 days, generally without

scar formation. The lesions may be mistaken for
anthrax.
 Monkeypox causes a milder version of smallpox
disease.
Orf
 MOLLUSCUM
CONTAGIOSUM
 The lesions differ significantly from pox lesions in
being nodular to wartlike.
 Begin as papules and then become pearl-like,
umbilicated nodules that have a central caseous
plug.
 The incubation period for molluscum contagiosum
is 2 to 8 weeks, and the disease is spread by direct
contact (e.g., sexual contact, wrestling) or fomites
(e.g., towels).
 MOLLUSCUM
CONTAGIOSUM
 They are most common on
the trunk, genitalia, and
proximal extremities and
usually occur in a cluster
of five to 20 nodules.

 The disease is more

common in children than
adults, but its incidence is
increasing in sexually
active individuals.
Vaccine

 Stable, inexpensive, easy to

administer vaccine
 Presence of scar indicating
successful vaccination
VIRUS DISEASE SOURCE LOCATION

Variola Smallpox (now Humans Extinct

extinct)
Vaccinia Used for smallpox Laboratory product -
vaccination
Orf Localized lesion Zoonosis-sheep, Worldwide
goats
Cowpox Localized lesion Rodents, cats, Europe
cows
Pseudocowpox Milker’s nodule Dairy cows Worldwide

Monkeypox Generalized Monkeys, squirrels Africa

disease
Bovine papular Localized lesions Calves, beef cattle Worldwide
stomatitis virus
Tanapox Localized lesions Monkeys Africa

Yabapox Localized lesions Monkeys, baboons Africa

Molluscum Many skin lesions Humans Worldwide

contagiosum
 HEPADNAVIRIDAE
 _____________________- the double-
shelled form, recognized as the whole
virus particle
 Originally referred to as
_______________________
 Associated with Primary Hepatocellular
Carcinoma
 About _________ progress to chronic form
Hepatitis B Virus
Virus Hepatitis B
Family Hepadnaviridae
Genus Orthohepadnavirus
Virion 42 nm, spherical
Envelope Yes (HBsAg)
Genome dsDNA
Genome size 3,2kb
Stability Acid-sensitive
Transmission Parenteral
Prevalence High
Fulminant disease Rare
Chronic disease Often
Oncogenic Yes
Markers:
First serological marker to appear, persistence
for more than 6 months may indicate chronic
infection
Marker of infectivity

Persists for life, indicates recovery or immunity

after immunization

Indicator of recent acute infection, useful in

detecting infection during the window period

Lifelong marker for hepatitis B

Usually associated with favorable outcome,

recovery, and reduced infectivity; first serological
evidence of convalescent phase

Demonstrates the presence of virus particles in

the specimen, indicator of infectivity
 HOW THE VIRUS REPRODUCES ??

 1. First the virus attached to

a liver cell membrane. 2. The virus is then
transported into the liver
cell
 4. Once within the cell nucleus
the hepatitis B DNA causes
the liver cell to produce, via
messenger RNA; HBs
protein, HBc protein, DNA
 3. The core particle then polymerase, the HBe
releases it’s contents of protein, and other
DNA and DNA undetected protein and
polymerase into the liver enzymes.
cell nucleus  DNA polymerase causes
the liver cell to make copies
of hepatitis B DNA from
messenger RNA.
5. The cell then assembles ’live’ copies of virus.
 6. However because of 7. The copies of the virus and
the excess numbers of excess surface antigen are
surface proteins produced released from the liver cell
many of these stick membrane into blood stream
together to form small and from there can infect
spheres and chains. other liver cells.
These can give a
characteristic “ ground
glass” appearance to
blood samples seen
under a microscope.
 ANTIGEN OF HEPATITIS B VIRUS:

 HBsAg = surface (coat) protein ( 4 phenotypes : adw, adr, ayw and

ayr)
 HBcAg = inner core protein (a single serotype)
 HBeAg = secreted protein; function unknown
 WHO IS AT GREATEST
RISK FOR HBV INFECTION?
DRUG ABUSERS  LAB PERSONNEL
 BLOOD PRODUCT
RECIPIENTS WORKING WITH
 ACCOUNTS FOR 5-10% BLOOD PRODUCTS
POSTRANSFUSION HEPATITIS
 SEXUALLY ACTIVE
 HEMODIALYSIS HOMOSEXUALS
PATIENTS
 PEOPLE FROM  PERSONS WITH
SOUTHEAST ASIAN MULTIPLE AND
COUNTRIES (70-80%) FREQUENT SEX
CONTACTS
 MEDICAL/DENTAL
PERSONNEL