Herpes Viridae HSV 1 and 2 VZV

8/6/2019 Herpes Viridae HSV 1 and 2 VZV

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Herpesviridae HSV 1,2 and VZV

Dr.T.V.Rao MD

Dr.T.V.Rao MD 1


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Herpesviridae The Herpesviridae are a large family

of DNA viruses that cause diseases in

animals, including humans The familyname is derived from the Greek wordherpein ("to creep"), referring to thelatent , re-occurring infections typicalof this group of viruses.Herpesviridae can cause latent or lyticinfections.

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http://en.wikipedia.org/wiki/Lytic_cyclehttp://en.wikipedia.org/wiki/Lytic_cycle


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Herpes Viruses DNA group Most important

Human Pathogens Wide Host cell range Life Long Infection

Periodic reactivation Immunocompromised

Large number ofgenes,

Some virusessusceptible totreatment. Dr.T.V.Rao MD 3


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Alphaherpesvirinae Herpes simplex virus type 1 HSV-1 Herpes simplex virus type 2 HSV-2

Varicella-zoster virus VZV Betaherpesvirinae

cytomegalovirus CMV

Human herpesvirus type 6 HHV-6 Human herpesvirus type 7 HHV-7

Gammaherpesvirinae

Epstein-Barr virus EBV

CLASSIFICATION(Human pathogens)

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Infecting Humans.Herpes Simplex virus 1 and 2Varicella Zoster VirusesCytomegalovirus virusEpstein Barr virusHuman Herpes viruses 6, 7.Kaposi's Sarcoma associated

Viruses Dr.T.V.Rao MD 5


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Properties of HerpesViruses.

Spherical in Shape Icosahedral 150

to 200 nm in size Genome Double

stranded DNALinear

Envelope containsGlycoprotein's

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Out Standing Characteristics

Encode many enzymes. Cause Latent Infections. Indefinite persistence. Relation in

Immunocompromised. Relation to Cancers.

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Herpes Virus ReplicationReplicates in Host Cell NucleusForm Cow dry A Type inclusionbodies.More than 50 different types proteins

in infected cell.Large number of enzymes in DNAsynthesis

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Herpes Simplex1 and 2

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Herpesviridae Group:Group I

Family: Herpesviridae Subfamily: Alphaherpesvirinae Genus: Simplexvirus

Species Herpes simplex

virus 1 (HWJ-1)Herpes simplex virus 2 (HWJ-2)

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http://en.wikipedia.org/wiki/Herpesviridaehttp://en.wikipedia.org/wiki/Herpesviridaehttp://en.wikipedia.org/wiki/Alphaherpesvirinaehttp://en.wikipedia.org/wiki/Alphaherpesvirinaehttp://en.wikipedia.org/wiki/Alphaherpesvirinaehttp://en.wikipedia.org/wiki/Alphaherpesvirinaehttp://en.wikipedia.org/wiki/Herpesviridaehttp://en.wikipedia.org/wiki/Herpesviridae


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Herpes Simplex Virus

HSV arespherical inshape

Ds DNA 35 protein s

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Human Herpes Virus 1 and 2

They are also called Human Herpes Virus 1 and 2 (HHV-1 and HHV-2 ) and areneurotropic and neuroinvasive viruses;

they enter and hide in the human nervoussystem, accounting for their durability inthe human body. HSV-1 is commonlyassociated with herpes outbreaks of theface known as cold sores or fever blisters,whereas HSV-2 is more often associatedwith genital herpes.

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Pathogenesis of HSV 1 &2

Initialinfection

siteMigration through Neuron

replication Sensory ganglia

latency

Reactivation is t hrough stress stimulisuch as UV light, fever,

hormonal changes,surgical trauma to the neuron

HSV-1: trigeminal gangliaHSV-2: sacral ganglia

Antibodies do not prevent reactivation

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Infections in Humans.( HerpesSimplex 1 and 2 )

Wide spread in Humans Broad Host Ranges. Replicate in Many types of Cells. Produce cytolytic effects Most Common Diseases. Gingival stomatitis, Kerato conjunctivitis Encephalitis Genital diseases, New Born Infections, Latent Infections in Nerve

Cells, Recurrence.

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HERPES SIMPLEX VIRUS (HSV )

HSV 1 infect the upper part of thebody

- mouth and the face HSV 2 infect the lower part of the

body- genital infections

There is little cross protection

Therefore, one can get both theinfections Dr.T.V.Rao MD 15


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Properties of Herpes Simplex Viruses

Type 1 and 2

Similar in Organization Restriction Enzyme Differentiates H S V 1 contact with Saliva. H S V 2 Sexual Maternal infection ( Genital Infection

spreads to New Born ) Replicates in 8-16 hours.

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Out characters of Herpesgroup of viruses

Out standing characters 1 Encode many enzymes Latent infections are common Persist indefinitely in infected hosts. Frequent reactivation in infected hosts Some care cancer causing.

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About 75% of the adults show +ve for HSV 1 infection HSV 1 infections include

-i. Oropharyngeal

. Children - very painful. due to kissing of elders

. acute gingivostomatitis

. problem of feeding

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Virus Grows in thefollowing .

Primary and Continues Cell lines. Monkey and Rabbit Kidney, Human Amnion Syncytial formation and Giant cell

formations Multiplies in Chorio Allontoic membrane Monoclonal Antibodies differentiates

Type 1 and 2 types.Dr.T.V.Rao MD 19


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Sources of infection

- Saliva- Skin lesions

Oropharyngeallesions

- Carriers

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Transmission Close contact Skin and epithelial contact, Defects in Mucosal membrane Multiples Locally, Enters through cutaneous nerve fibers Intraaxonally to Ganglion

Centrifugal Migration Recurrent manifestation in Skin and Mucosa.

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Pathogenesis. Most Common Human Viral Infection Causes cytolytic effect causes the

necrosis of cells. Infects Skin and Mucous membrane Cowdry type A inclusions are produced Multinucleated Giant cells are

demonstrated

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Pathogenesis

Entry by skin or mucous membranes

viral multiplication sensory nerve

lysis of cells root ganglia

vesicles latency

ulcersREACTIVATION

COLDFEVER

SURGERYUNKNOWN

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Predisposition of LatentInfection in

Ganglion Trigeminal HSV 1 Sacral HSV 2 Immunity. Cell Mediated ( CMI ) Predisposing Factors

Axonal InjuryPhysical and Emotional stress

U V light80% Adults harbour Antibodies to HSV

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Clinical Manifestations Oropharyngeal Disease Buccal Gingival

Mucosa Incubation 3 to 5 days

May last for 2-3 weeks Gingvo stomatitis Sub mandibular

lymphadenopathy

Present with painful ulcers.

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Recurrent Blisters in Herpes simplex 1

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Herpes lesions in the oral

cavity

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Herpes simplex 1 infecting eye

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H 2 d i


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Herpes 2 producingGenital Lesions

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Skin Infections Infect abrasions

Dentists, ( HerpeticWhitlow) Health careworkers,

Eczema , Burns

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Neonatal Herpes.

In Uterus At Birth After Birth. Delivery By Caesarean

SectionReduces the Infection

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Neonatal Infection Normaldelivery

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Other Manifestations. Meningitis, Encephalitis Multi organ Involvement Increased incidence in Immune

compromised AIDS, Haematological Malignancies.

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R t i f ti i HSV


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Recurrent infections in HSV1 and 2

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Immunity

Mothers Ig G protects for 6 months. Primarily Ig M Later Ig g produced.

Main Participants in Immunity.C M I and Killer Cells and

Interferon play major role inimmunity

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Laboratory Diagnosis

Microscopy, Antigen Detection DNA detection PCR. Viral Isolation. Serology

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Laboratory Diagnosis Specimen: Vesicular fluid- Corneal scrapping1- Direct Virus Demonstration:a) L/M:

1. Tzanck smear from the base of vesicles,1% aq. soln. of toluidine blue O shows multinucleated giant cells with faceted

nuclei & homogenously stained ground glasschromatin (Tzanck cells)

2. Giemsa stained smear intranuclear Cowdry typeA inclusion bodies

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B) Direct Immunofluorescence: Cell scrapings from lesions are stained

with monoclonal antibodies conjugatedwith a fluorescence dye. Viralinclusion bodies appear in UVmicroscope as a bright greenIntranuclear particles

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2- Viral Isolation: tissue culture: humandiploid fibroblasts, human amnion, humanembryonic kidney: CPC (syncytiumformation) seen in 24-48 hrs.

3) Serology : useful in the diagnosis ofprimary infection, Ab (IgM) detection byELISA, NT or CFT.

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Childhood infectionscommon

Second peak at onset ofsexual activity

Viral shedding persons with recurrences infected but asymptomatic

persons

Laboratory diagnosis

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Useful genital & eye infections HVZ & HSV in immunocompromised

patients

herpes encephalitis Specimens

aspirate from vesicle

scraping from base of ulcer serum / CSF for antibody

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Microscopy, Tzanck Smear Intranuclear

Type A InclusionBodies Electron

Microscopy Fluorescent

AntibodyDr.T.V.Rao MD 49


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Specimens for Diagnosis.

Saliva. CSF Vesiclefluid.

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Viral Isolation in Chick embryo In Tissue

CulturesPrimary

Embryonic

KidneyHuman

AmnionDr.T.V.Rao MD 51


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Serology, ELISA Test Neutralization

Tests Complement

FixationTests

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Chemotherapy Idoxuridine used topically in eye and skin

infections first successful antiviralagent.

Acyclovir and vidarabine helps insystemic infections

Other Drugs Valaciclovir, Famiciclovir, Orally effective Foscarnet.

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Epidemiology. World Wide Distribution HSV 1 early in life 6 months to 3 years. 70% to 90% Adults have Antibodies Poor Living Conditions HSV 2 Sexually transmitted. Risk to mother and fetus Abortions < 20 weeks gestation HSV 2 increases predisposition to HIV infection

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Varicella Zoster

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History of Chickenpox

The namechicken poxbecause theblisters thatappeared

seemed like theskin that hasbeen pecked by the chicken..

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Herpes Virus

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Properties of Virus.

Like Herpes

Virus Icosahedrons

shape dsDNA

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Varicella Zoster ( Herpes Virus)DNA Virus

Varicella -Chickenpox.

Contagious Disease

Mainly ChildrenGeneralized Vesicular

eruptionson Skin and Mucous

membranesSevere manifestations in

Adults and Immunecompromised. Dr.T.V.Rao MD 59

HERPES VARICELLA ZOSTER


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HVZ Causes chicken pox -fever + characteristic rash variable incubation period 14-21 days usually mild in children and more severe in adults complications

secondary infection - uncommon varicella pneumonia secondary bacterial pneumonia S aureus &

pneumococci post-infetious encephalitis generalised varicella (in immunocompromised patients) congenital and neonatal varicella

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Varicella (Chicken Pox) Mild, highly contagious

disease chieflyaffecting children

Mode of transmission:

- airborne droplets anddirect contact fromvaricella patients

- Vesicular fluid ofZoster patients can bethe source of Varicellain susceptible children

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Shingles (Herpes Zoster )

Rash Limited to Distribution of SingleSensory GanglionIn Adults and immune compromised

Sporadic

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Varicella Zoster Virus (VZV)

Causes 2 majordiseases

Varicella (chickenpox): primaryinfection usually inchildhood

Zoster ( shingles):reactivation of anearlier varicella

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pneumococci post-infectious encephalitis generalized varicella (in immunocompromised patients) congenital and neonatal varicella

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Herpes Zoster Primary

Contact -

Chicken Pox Reactivation

- Zoster(PartiallyImmune )

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Culturing virus Grows in

Human embryonic TissueProduce inclusion bodiesNo difference in virusIn Chicken pox and

zoster infectionDr.T.V.Rao MD 68


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Pathogenesis and Pathology Varicella virus enter through

URT/Conjunctiva.

Lymph nodes ViremiaLiver and spleen

Secondary viremiaInfects Mononuclear CellsRash Vesicle formationDr.T.V.Rao MD 69

Pathogenesis :


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Pathogenesis : VZV infects the mucosa of the upper

respiratory tract Multiplies in the regional LNs Primary viremia and spread to liver and

spleen Secondary viremia follows with viral

spread to the skin

Typical rash occurs VZV remains latent in the dorsal root

ganglia for lifeDr.T.V.Rao MD 70

Clinical Picture:


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Clinical Picture: Incubation period: 10-21 days Symptoms: mild fever & rash Rash: first appears on the trunk, then faceand limbs Flat macules become papules then vesicles Followed by crust formation

The crust is often shed off and healswithout scarring Cropping is a characteristic feature of

varicella rash: fresh vesicles appear in crops,

so that all stages of macules, papules,vesicles & crusts are seen at the same time More severe in adults

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Herpes Zoster Skin Lesions Inflammation of

Sensory Nervesand Ganglia Single Ganglion Dorsal root

Ganglion

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Entry of Varicella Zoster


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Entry of Varicella Zostervirus

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Skin lesions showing different


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Skin lesions showing differentstages

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Clinical Findings. Varicella, Incubation 10-20 days Fever, Malaise

Rash Trunk

Face

Limbs

Buccal andPharyngeal mucosa Lesions at all stages

Macules, Papules, Vesicles, Crusts,May last 5 days, Hundreds of eruptions.

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Skin lesions of chickenpox

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Chicken pox lesions in the


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Chicken pox lesions in thebuccal cavity

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Herpes Zoster involving a


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Herpes Zoster involving aNerve segment

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Congenital Varicella Syndrome & Neonatal


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Congenital Varicella Syndrome & NeonatalVaricella

Primary maternal infection during the 1 st trimester may lead to congenitalvaricella syndrome ( serious & fatal): skinlesions, hypoplasia of limbs, chorioretinitis &

CNS defects Primary maternal infection near the timeof birth can lead to widely disseminatedinfection in the new born with mortalityrate of 35%

If rash began a week or more before delivery,maternal Abs transferred via placenta baby getsthe infection but escapes clinical disease

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Immune compromised HIV / AIDS Malignancies.

Organtransplantations Corticosteroid

usage Leukaemia's .

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pneumococci post-infectious encephalitis generalized varicella (in immunocompromised patients) congenital and neonatal varicella

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Pain and hyperaesthesia

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HERPES ZOSTER


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Reactivation of HVZ

dermatomal distribution may recur can disseminate in immunocompromised patients complications

post herpetic pain ophthalmic zoster -corneal scarring and loss of vision

DIAGNOSIS

CLINICALEM of vesicle fluid

SEROLOGY

IgM detectionDr.T.V.Rao MD 87


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Zoster.

Associated with Immunecompromised.

Manifest with severe pain Vesicles on trunk , head, neck

Trigeminal Neuralgia

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( hi l )


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Zoster (shingles)

Sporadic disease inadults orimmunocompromisedpatients

Results fromreactivation of latentVZV

Rash similar tovaricella but limited to

a nerve distribution tothe skin innervated bya dorsal root ganglion(dermatom)

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Other Complications.

Encephalitis, Mother to Child

transmission Varicella Pneumonia. Fatal Complications .

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Laboratory Diagnosis. Smears --Scrapings from Lesions

Demonstration of Multi nucleated giant cellsTzanck smears

DNA DemonstrationCell cultures,Fluorescent antibodyELISA PCR

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Epidemiology


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Communicable Disease World wide prevalence

Common in < 10 year olds. Zoster in Adults

Droplet spread

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Treatment Specific treatment is indicated mainly

in Immunodeficient and elderlysubjects and also in complicated withVaricella pneumonia,encephalitis,anddisseminated zoster

Acyclovir and Famiciclovir.

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Prevention of Chickenpox


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Susceptible populationchildren

adults living in close proximity

Do nothing

Immunizelive attenuated

vaccine

Protect if contact with patient with chickenpoxand at risk of severe diseaseZoster Immune Globulin (ZIG)Dr.T.V.Rao MD 95


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Vaccine available A live modified Varicella virus

lyophilised vaccine which can bestored at low temp is availablefor protection

Children 1 -12 years given single

dose. >12 years 2 doses 2 -6 weeks

apart High titre serum from

convalescing from herpes zoster

protect Immunocompromisedchildren.

But not useful for treatment

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Developing World

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Herpes Viridae HSV 1 and 2 VZV