Download DNA Enveloped virus Herpes virus

HERPES VIRUS
HERPES VIRUS
are capable of causing overt disease
or remaining silent for many years
only to be reactivated, eg shingles.
The name herpes comes from the Latin -herpes
which, in turn, comes from the Greek word herpein
which means to creep.
This reflects the creeping or spreading nature of the
skin lesions caused by many herpes virus types.
 There are 25 families in the Herpetoviridae but only
eight of them are known to infect man
IMPORTANT HUMAN
PATHOGENS
 Herpes
simplex virus Type 1 (HSV1)
 Herpes simplex virus Type 2 (HSV2)
 Varicella Zoster Virus (VZV)
 Epstein Barr virus (EBV)
 Cytomegalovirus (CMV)
 Herpes lymphotropic virus (HHV6)
 Human herpes virus 7(HHV7)
 Human herpes virus 8
HHV8)((Kaposi's sarcoma-associate
herpes virus)
PROPERTIES OF HERPES VIRUS
All are structurally similar
• They are DNA, enveloped virus
• They are larger 120-200nm in diameter second only
to poxvirus
• They are the only virus that obtain their envelopes
by budding from the nuclear membrane
• The virion does not contain polymerase
They are noted for their ability to cause latent
infections.
•
STRUCTURE
CLASSIFICATION OF HERPES VIRUSES
6
HERPES SIMPLEX VIRUS
HSV-1 and HSV-2
Lesion caused by HSV-1 are above
the waist while those caused HSV2 are below the waist
but both types of HSV can infect oral or
genital mucosa depending on the regions
of contact.
EPIDEMIOLOGY
HSV 1 and 2 infections are life long
The virus is found in the lesions on the skin
and in body fluid
HSV-1 is transmitted primarily in saliva
can spread by kissing
or the use of utensils contaminated with
saliva
or by transfer of infectious virus to the
hands after which the virus may enter the
body via any wound or through eyes




Anyone who comes in contact with the fluid
containing virus is at risk
Care workers are affected by disease called herpetic
whitlow that results in lesions on the fingers
HSV-2 infection is most prevalent in life as number
of sexual contact increases
Thus the lowest rates of infection are in children
PATHOGENESIS
 The
virus replicate in the skin or mucous
membrane at the initial site of the infection
 Then migrate up the neuron and become latent
in the sensory ganglion cells
 HSV 1 becomes latent in the trigeminal ganglia
 HSV-2 becomes latent in the lumber and sacral
ganglia
 The viruses can be reactivated from the latent by
the variety of induces sunlight, hormonal
changes, trauma, stress and fever
 at which time it migrates down the neuron and
replicate in the skin causing lesions
Diseases caused by HSV-1 and HSV-2
CLINICAL PRESENTATION OF HSV-1
1.Gingivostomatitis
occurs in children,
• characterized by fever,
irritability and vesicular
lesions in the mouth
• The lesions heal
spontaneously in 2-3 weeks
• Many children have
asymptomatic primary
infections
•
Herpetic
gingivitis
2.HERPES LABIALIS (FEVER BLISTERS OR COLD
SORES)
 characterised
by
 crops of vesicles at
the mucocutanous
junction of the lips
or nose
 Recurrences
frequently reappear
at the same site
•
3.Keratoconjuctivitis
Patients with HSV keratitis
may complain of
• Pain
• Photophobia
• Blurred vision
• Tearing
• Redness
The earliest sign of active viral
replication in the corneal
epithelium is the development
of small, raised, clear vesicles
•
recurrence can lead to
scarring and blindness
4.Encephalitis
•
•
•
Involve the temporal
lobe
has high mortality rate
causes severe
neurological sequel in
those who survive
5.HERPES WHITLOW
•
•
Is a pustule
lesion of the
skin of the
finger or hand
it is most
commonly
contracted by
dental workers
and medical
workers
exposed to
herpes lesions
Symptoms of herpetic
whitlow
• include swelling,
• reddening and
• tenderness of the skin of
infected finger.
• This may be accompanied
by fever and swollen lymph
nodes
Disseminated
infections such as
esophagitis and pneumonia,
 occur in immunocompromised
patients
with depressed T cell function
HSV-2 PRESENTATION
1. Genital herpes
• painful vesicular lesions of the male and
female genitals and anal area
•
The lesions are more severe in primary
disease than in recurrences
•
Primary infection is associated with fever
and inguinal adenopathy.
•
Asymptomatic infections occur in both men
(in prostate or urethra) and women (in
the cervix) it can be the source of infection
to other individuals.
GENITAL HERPES ON THE PENIS
© Australian Herpes Management Forum
GENITAL INFECTION IN MALE AND FEMALE
20
HSV PROCTITIS

This is an
inflammation of the
rectum and the anus
2. Neonatal herpes
• Originates from contact with vesicular
lesions within the birth canal
• can be prevented by performing
caesarean section on women with either
active lesions or positive viral cultures
 Both
HSV1 and HSV2 can cause severe
neonatal infections that are acquired after
birth from carriers handling the child
 Despite their association with neonatal
infections neither HSV1 nor HSV2 cause
congenital abnormalities to any
significant degree
 Aseptic meningitis
 Caused by HSV2
 is usually mild and self limited disease
LABORATORY DIAGNOSIS
•
Isolation of the virus from the lesion by cell
culture then detecting virus specific
glycoprotein by enzyme-linked immunosorbent
assay (ELISA)
Diagnosis from skin lesions can be made by the
Tzanck smear in which cells from the base of
the vesicle are stained with Giemsa stain.
• The present of multinucleated giant cells
suggests Herpes infection
•
•
Encephalitis can be diagnosed
by detecting HSV-1 DNA in
the spinal fluid using PCR
Neonatal herpes can be
diagnosed by use of viral
culture or PCR
TREATMENT
 Acyclovir the treatment of choice of
encephalitis and systemic diseases
caused by HSV-1 also in primary and
recurrent genital herpes also neonatal
infection caused by HSV-2
 It shortens the duration of the lesions and
reduces the extent of shedding of the virus
 Mutant resistant acyclovir have been
isolated from patients
 famciclovir and valacyclovir can be
used in this cases
PREVENTION
Avoid
contact with the vesicular
lesion or ulcer
Caesarean section is
recommended for women at term
who have positive viral culture
VARICELLA ZOSTER VIRUS
CHICKENPOX AND SHINGLES
This
virus causes two major
diseases, chicken-pox (Varicella),
usually in childhood,
and shingles, later in life.
Shingles (Herpes zoster) is a
reactivation of an earlier varicella
infection.
CHICKEN POX
This
virus is highly infectious
It is spread by
respiratory aerosols
or direct contact with skin
lesions.
PATHOGENESIS
The virus infect the mucosa of URT
The virus spread from the URT to lymphocytes
and monocytes and to the reticuloendothelial system where second viremia
occurs
and the virus travels to the skin, mouth,
conjunctiva, respiratory tract and to
epithelial sites throughout the body forming
papule containing multinucleated cells with
intracellular inclusions.
CLINICAL FEATURES
 Incubation
period 14-21 days
 Brief symptoms of fever and malaise
occur
 Papule vesicular rash then appear in
crops on the trunk and spread to the
head and extremities.
 The rush evolves from papules to
vesicles, pustules and finally crust.
Itching is marked
Complications
Varicella pneumonia and
encephalitis are the major rare
complications
Reye’s syndrome characterised by
encephalitis and liver degeneration
esp. in children given aspirin
Its pathogenesis is not known
ZOSTER (SHINGLES)
•
•
The occurrence of painful vesicles along the
course of a sensory nerve of the head or trunk
Reactivation can lead to chronic burning or
itching pain called post-herpetic neuralgia
which is seen primarily in the elderly
In immunocompromised patients life threatening
disseminated infections such as pneumonia
can occur
Diagnosis
• Most diagnosis are made clinically
Treatment
•
•
•
No antiviral therapy is necessary for chicken
pox or shingles in normal patients
Immunocompromised patients can be treated
with acyclovir
PREVENTION
•
•
•
Varicella- zoster immune
globulin (VZIG) (effective in
preventing varicella but not
zoster)
There is a live attenuated
vaccine (Varivax) for varicella
but is not effective in zoster
and can not be used for
immunocompromised patients or
pregnant women
chickenpox of the
new-born. The
infant contracted
chickenpox at
birth from her
infected mother.
CHICKEN POX
chickenpox rash.
Some of the sores
are red spots and
some are blisters
Severe atypical episode of
shingles affecting the trunk
of a person with impaired
immunity

Shingles affecting
the left side of the
trunk
Recurrent varicella
zoster on the right
side of the face
Facial shingles.
PRESENTATION OF VARICELLA AND ZOSTER
CYTOMEGALOVIRUS
CYTOMEGALOVIRUS
Cause
1. cytomegalic inclusion disease
(esp. congenital abnormalities) in
the neonates
•
2.pneumonia in
immunocompromised individuals
TRANSMISSION
Early in life CMV can be transmitted
• across the placenta
• within the birth canal
• and in breast milk
In young children –Via saliva
Later in life-sexually transmitted
It is present in secretions - saliva, urine,
vaginal and semen
The virus can also be spread via blood
transfusions and transplants.
PATHOGENESIS
The virus first infects the upper
respiratory tract and
then local lymphocytes.
Circulating lymphocytes then
spread the virus to other
lymphocytes and monocytes in
spleen and lymph nodes.
finally spreads to a variety of
epithelial cells including those of
salivary glands, kidney tubules,
testes and cervix.
Infection is usually asymptomatic
(sub-clinical)
CONGENITAL DISEASE
There are two instances in which cytomegalovirus
can cause serious disease.
1.During a primary infection of the mother (in utero)
the virus can spread via the placenta to the fetus
and congenital abnormalities can occur;
this virus is the most common viral cause of
congenital disease.
Abnormalities include






microcephaly,
brain calcification
hepatosplenomegaly
hearing loss,
seizures
and mental retardation can occur
•
•
•
If the mother has antibody that will
neutralize the virus the foetus will
not be infected.
If the foetus is infected during first
trimester congenital defects may
result
because this is when the organs
began to develop
2.Perinatally
Besides infection in utero, infants
may be infected perinatal
As noted above, one tissue in which
cytomegalovirus can set up a latent
infection is the cervical epithelium
and immunosuppression associated
with pregnancy can lead to
reactivation.
 Also
breast epithelium can harbor latent
virus that may be similarly reactivated
leading to infection of the infant.
 Neonates may also receive the virus
through infected blood transfusions.
 In this case, the amount of virus is much
higher and symptoms may occur.
 These usually consist of pneumonia and
hepatitis.
CLINICAL FINDINGS
 Approx.20%
of infants infective with CMV
during gestation show clinically apparent
manifestations of cytomegalic inclusion
disease such as microcephaly, deafness and
jaundice
 Hepatosplenomegaly is very common
 Cytomegalic inclusion is the leading cause of
mental retardation
 Infected infant can continue to excrete CMV
especially in the urine for several years
In
immunosupressed adult CMV
can cause heterophil-negative
mononucleosis which is
characterized by
 fever
 lethargy
and the presence of abnormal
lymphocytes in peripheral blood
smears
 Systemic
CMV infection especially
pneumonitis and hepatitis is high in
immunosuppressed patients
 eg those with renal and borne marrow
transplants

in AIDS patients CMV commonly affects
the intestinal tract and cause
intractable diarrhoea.
 CMV
also cause retinitis in AIDS
patients which can lead to blindness
LAB DIAGNOSIS
 Cell
culture
Fluorescent antibody
and histologic staining of inclusion bodies in
giant cell in urine and in tissue
 Treatment

Ganciclovir is effective in treatment of AIDS patients
with pneumonia and retinitis

Forscarnet( foscavir) is also effective but cause side
effects

CMV is resistant to Acyclovir
PREVENTION
No vaccine
 Infants who are shedding viruses in their urine
should be kept isolated from other infants
 Blood transmission to new born should be CMV
antibody negative
 if possible only organ from CMV antibody
negative donors should be transplanted

EPSTEIN BARR VIRUS
EPSTEIN BARR VIRUS
Epstein-Barr
virus is the causative
agent of
 Burkett's lymphoma
 Nasal pharyngeal carcinoma
 Oral hairy leukoplakiain lesions in the mouth
and Infectious mononucleosis
TRANSMISSION AND EPIDEMIOLOGY
is
transmitted primarily by
exchange of saliva
e.g. during kissing
Is most common infection worldwide
Infection in the first few years of
life is asymptomatic
Is highest in those who are exposed
to virus later in life e.g college
students
PATHOGENESIS
The
infection first occur in
oropharynx and then spread to
the blood where it affects B
lymphocytes
Cytotoxic T lymphocytes react
against the infected B cells.
EBV remain latent within B
lymphocytes
CLINICAL FINDINGS
 Characterized
by
fever ,
 sore throat,
 lymphadenopathy
 and splenomegaly
 Anorexia and lethargy are prominent
 Hepatitis is frequent
 Encephalitis occurs in some patients
 Spontaneous recovery usually occur in 2-3 wks.
 In immunosupressed patient infection is severe
and is often fatal

LAB DIAGNOSIS
Hematological approach where abnormal
lymphocytes are seen on the smear
The EBV-specific antibody test

TREATMENT
No antiviral therapy is necessary for
uncomplicated infections mononucleosis
 Acyclovir has little activity against EBV but
higher doses may be useful in life threatening
EBV infections
 No EBV vaccine

OTHER HERPES VIRUSES
Human herpes virus 6
 This virus is found worldwide
 is found in the saliva of the majority of
adults (>90%).
 It infects almost all children by the age of
two and the infection is life-long.
 Again, it replicates in B and T
lymphocytes, in the oropharynx.
Human
herpes virus-6 has two
forms,
HHV-6A and HHV-6B.
The latter causes exanthem
subitum.
symptoms include fever and
sometimes upper respiratory tract
infection and lymphadenopathy.
The symptoms last a few days
after an incubation period of
around 14 days.
EXANTHEM SUBITUM MACROPAPULAR
RASH
The
fever subsides leaving a
macropapular rash on the trunk and
neck that last a few days longer.
This virus may co-infect HIV-infected
T4 lymphocytes exacerbating the
replication of HIV.

 Patients
with HIV have a higher
infection rate than the normal
population.
 HHV-6 has been associated with a
number of neurological disorders,
including encephalitis and seizures.
 It has been postulated to play a role
in multiple sclerosis and chronic
fatigue immunodeficiency syndrome.
HUMAN
HERPES VIRUS
7
This virus binds to the CD4 and replicates
in T (CD4+) cells and is found in the saliva of
the majority of the adult population (>75%).
 Most people acquire the infection as children
and it remains with them for the rest of their
lives.
 It is similar to HHV-6 and may be
responsible for some cases of exanthem
subitum

HUMAN HERPES VIRUS 8
 This
is known as Kaposi's sarcoma
associated herpes virus and is found in
the saliva of many AIDS patients.
 It infects peripheral blood lymphocytes.
TRANSMISSION
 Sexually
transmitted through semen.
 Transmitted through mother to child
 Organ transplant
HERPES B
This
is a simian virus found in
old world monkeys
 but it can be a human pathogen
in people who handle monkeys
(monkey bites are the route of
transmission).
In humans, the disease is much
more problematic than it is in its
natural host.
about 75% of human cases result in
death with serious neurological problems
(encephalitis) in many survivors.
 There is also evidence that the disease
can be passed from a monkey-infected
human to another human.
 In vitro the virus is sensitive to both
Acyclovir and Ganciclovir and these are
recommended for therapy. Their efficacy
is unknown.

PAPILLOMAVIRUS
PAPILLOMAVIRUS (HPV) - PROPERTIES
 Non
enveloped, DNA virus
 small 60nm diameter
 These viruses are very difficult to study
 as they do not grow in cell cultures and
experimental animals.
About
70 different types of papilloma
virus can infect humans
They account for more than 80% of
cervical cancers
Cause papillomas (benign tumors of
squamous cells) e.g. warts on the skin
Penile, vulvar and rectal cancers
are also associated with HPV.
 Highly
adopted to human skin and mucosa
 At least 25 types including HPV 6,11,16
and 18 can infect the genital area and are
sexually transmitted.
 HPV 1 and 4 causes plantar warts
 HPV 2,3 and 10 causes warts on the
knees and fingers.
 Subtypes 6 and 11 account for 90% of
genital warts
WARTS
 Warts
-
-
can be
Filiform with finger-like projection
Flat topped,
Flat as they grow inwards due to external
pressure (planter warts)
A cauliflower-like protuberance (e.g.
genital warts)
A flat area of dysplasia on the cervix
Epidermal dysplasia verruciformis
TRANSMISSION
By
skin to skin contact
Genital warts are among the most
common sexually transmitted diseases
Skin warts are more common in
children and young adults and tend to
regress in older adults
Warts viruses can survive on
inanimate objects such as; wrestling
mats, towels and shower floors
PATHOGENESIS
PV
infect squamous
epithelial cells induce within
those cells a characteristic
cytoplasmic vacuoles.
These vacuolated cells called
koilocytes are the hallmark of
infection by these virus.
The cells grow abnormally
and produce warts.
Most warts are benign( and do
not progress to malignancy
PENILE
WARTS
VAGINA WARTS
TREATMENT - WARTS
•
•
Like other tumors, warts can be treated by killing or
removing all abnormal cells.
To accomplish this;
- Wart cells can be destructed by application of
karyolitic agents (i.e. salicylic acid)
- Freezing with dry ice (solid CO2) or liquid
nitrogen.
- By burning the tissue with an electrically heated
needle
- Or by surgical removal




Most HPV infections resolve spontaneously
For those infected with the high risk subtypes,
roughly 5-10% will develop persistent HPV
infection
It is estimated that 40% of young women are
infected with HPV within 3 years of starting
sexual activity.
Up to 80% of women acquire the HPV infection at
least once during their lives.
PERSISTENT HPV INFECTION
 Persistent
HPV infection disrupts the
normal cell turnover at the
transformation zone
 With the cells multiplying perpetually,
pre-cancerous cells form.
 The pre-cancerous cells could, in the long
run, invade underlying tissue: Invasive
cancer
 The process from HPV infection to cancer
is very slow taking many years, even
decades.
SIGNS AND SYMPTOMS
•
The most common finding in patients
with cervical cancer is an abnormal
Papanicolaou (Pap) test result.
86
•
Physical symptoms of cervical cancer
may include
 Abnormal
vaginal bleeding
 Vaginal discomfort
 Malodorous discharge
 Dysuria
Because many women are screened
routinely, the most common finding is an
abnormal Papanicolaou (Pap) test result.
Typically, these patients are asymptomatic.
• Clinically, the first symptom of cervical
cancer is
 abnormal vaginal bleeding, usually
postcoital.
 vaginal discomfort,
 malodorous discharge,
87
 and dysuria
•
The tumor grows by extending
• along the epithelial surfaces,
• both squamous and glandular,
• upward to the endometrial
cavity,
• throughout the vaginal
epithelium,
• and laterally to the pelvic wall.
•
88
•
•
•
•
•
•
•
•
It can invade the bladder and rectum directly,
leading to constipation,
hematuria,
fistula,
and ureteral obstruction, with or without
hydroureter or hydronephrosis.
The triad of leg edema, pain, and
hydronephrosis suggests pelvic wall
involvement.
The common sites for distant metastasis include
extra pelvic lymph nodes,
liver, lung, and bone.
RISK FACTORS
Early
age of becoming sexually
active
Multiple sex partners
Unprotected sexual intercourse:
condoms estimated to give around
70% protection against HPV.
Concomitant STIs
PENILE
CANCER
ANAL
CANCER
OROPHARYNG
EAL CANCER
PREVENTION
 Achieved
through regular screening
 Treatment of pre-cancerous lesions
 The vast majority of cervical cancer deaths are in
developing countries largely because of lack of
screening programmes
 Limited resources (supplies, trained personnel,
equipment, quality control, health care
infrastructure, and effective follow-up procedures)
 ? Political will
SCREENING:
LIQUID BASED CYTOLOGY (LBC) /PAP SMEAR
 Sample collected using a brush with a detachable
head
 The head with the sample is detached into the
specimen pot with the preservative.
 In the laboratory, the fluid with the sample is spun to
separate and remove contaminants e.g. Pus,
inflammatory cells and mucus.
 The remaining cervical cells are then made into a thin
layer on a slide and read under a microscope as
normal

Adoption of this method has reduced the recall
rate from 1 in 10 to 1 in 100.
Traditional Pap Smear
Brush for LBC
VISUAL INSPECTION WITH ACETIC ACID (VIA)






Also called ‘direct visual inspection’ or cervicoscopy
An alternative to cytologic examination in low-resource
settings.
Involves applying 3-5% Acetic acid (vinegar) to the
cervix using a spray or cotton swab.
Observe the cervix with a naked eye after 1 minute
Obvious acetowhite areas would be regarded as
positive for at least pre-cancerous cells.
VIA does not require a laboratory or intensive staff
training and results are immediately available.
Acetowhite
Normal cervix
VISUAL INSPECTION WITH LUGOL’S IODINE: VILI


VILI stands for Lugol’s iodine is applied to
the cervix and this is inspected for nonstaining areas.
Results of VILI are immediately available,
offering the advantage of treatment or
follow-up care without delay.
OTHER SCREENING METHODS
HPV DNA TESTING
 Detects
DNA from 13 high risk genotypes
 A sample of cells collected from the vagina or
cervix using a swab or brush
 Laboratory processed
 Very good in identifying those who already
have cervical disease and those at high risk
of developing it
 Remains quite expensive
..THE FAST HPV TEST
detect DNA from 14 high-risk types of HPV.
 Results available in 2 - 3 hours
 The test equipment is portable, with the
option of battery power.

PRIMARY PREVENTION: VACCINATION

Vaccination against the high risk HPV subtypes now
available
Gardasil® protecting against infection by subtypes
16 and 18 as well as 6 and 11
Cervarix™ protects against subtypes 16 and 18.

Both are administered in the form of injections.



Three injections given in intervals over a course of six
months.
HPV VACCINATION
Aim is to get girls vaccinated before they
become sexually active and exposed to
the virus.
 The vaccines have been shown to be
almost 100% effective in preventing
dysplasia and subsequent cervical cancer
 In addition, effective in preventing, the
related albeit less common vulvar and
vaginal cancers.
