Herpes viridae HSV 1,2 and VZV

Herpesviridae HSV 1,2 and VZV :

Herpesviridae HSV 1,2 and VZV Dr.T.V.Rao MD Dr.T.V.Rao MD 1

Herpesviridae:

Herpesviridae The Herpesviridae are a large family of DNA viruses that cause diseases in animals, including humans The family name is derived from the Greek word herpein ("to creep"), referring to the latent , re-occurring infections typical of this group of viruses. Herpesviridae can cause latent or lytic infections. Dr.T.V.Rao MD 2

Herpes Viruses DNA group :

Herpes Viruses DNA group Most important Human Pathogens Wide Host cell range Life Long Infection –Periodic reactivation Immunocompromised Large number of genes, Some viruses susceptible to treatment. Dr.T.V.Rao MD 3

CLASSIFICATION (Human pathogens):

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) Dr.T.V.Rao MD 4

Infecting Humans.:

Infecting Humans. Herpes Simplex virus 1 and 2 Varicella Zoster Viruses Cytomegalovirus virus Epstein Barr virus Human Herpes viruses 6, 7. Kaposi's Sarcoma associated Viruses Dr.T.V.Rao MD 5

Properties of Herpes Viruses.:

Properties of Herpes Viruses. Spherical in Shape Icosahedral 150 to 200 nm in size Genome – Double stranded DNA Linear Envelope contains Glycoprotein's Dr.T.V.Rao MD 6

Out Standing Characteristics:

Out Standing Characteristics Encode many enzymes. Cause Latent Infections. Indefinite persistence. Relation in Immunocompromised. Relation to Cancers. Dr.T.V.Rao MD 7

Herpes Virus Replication:

Herpes Virus Replication Replicates in Host Cell Nucleus Form Cow dry A Type inclusion bodies. More than 50 different types proteins in infected cell. Large number of enzymes in DNA synthesis Dr.T.V.Rao MD 8

Herpes Simplex 1 and 2 :

Herpes Simplex 1 and 2 Dr.T.V.Rao MD 9

Herpesviridae:

Herpesviridae Group:Group I Family: Herpesviridae Subfamily: Alphaherpesvirinae Genus: Simplexvirus Species Herpes simplex virus 1 (HWJ-1) Herpes simplex virus 2 (HWJ-2) Dr.T.V.Rao MD 10

Herpes Simplex Virus:

Herpes Simplex Virus HSV are spherical in shape Ds DNA 35 protein s Dr.T.V.Rao MD 11

Human Herpes Virus 1 and 2:

Human Herpes Virus 1 and 2 They are also called Human Herpes Virus 1 and 2 ( HHV-1 and HHV-2 ) and are neurotropic and neuroinvasive viruses; they enter and hide in the human nervous system, accounting for their durability in the human body. HSV-1 is commonly associated with herpes outbreaks of the face known as cold sores or fever blisters, whereas HSV-2 is more often associated with genital herpes. Dr.T.V.Rao MD 12

Pathogenesis of HSV 1 &2:

Pathogenesis of HSV 1 &2 Initial infection site Migration through Neuron replication Sensory ganglia latency reactivation Reactivation is through stress stimuli such as UV light, fever, hormonal changes, surgical trauma to the neuron HSV-1: trigeminal ganglia HSV-2: sacral ganglia Antibodies do not prevent reactivation Dr.T.V.Rao MD 13

Infections in Humans.( Herpes Simplex 1 and 2 )‏:

Infections in Humans.( Herpes Simplex 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. Dr.T.V.Rao MD 14

HERPES SIMPLEX VIRUS (HSV):

HERPES SIMPLEX VIRUS (HSV ) HSV 1 infect the upper part of the body - 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 the infections Dr.T.V.Rao MD 15

Properties of Herpes Simplex Viruses Type 1 and 2:

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. Dr.T.V.Rao MD 16

Out characters of Herpes group of viruses:

Out characters of Herpes group 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. Dr.T.V.Rao MD 17

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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 Dr.T.V.Rao MD 18

Virus Grows in the following.:

Virus Grows in the following . 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

Sources of infection:

Sources of infection - Saliva - Skin lesions Oropharyngeal lesions - Carriers Dr.T.V.Rao MD 20

Transmission:

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. Dr.T.V.Rao MD 21

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Pathogenesis.:

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 Dr.T.V.Rao MD 23

Pathogenesis :

Pathogenesis Entry by skin or mucous membranes viral multiplication sensory nerve lysis of cells root ganglia vesicles latency ulcers REACTIVATION COLD FEVER SURGERY UNKNOWN Dr.T.V.Rao MD 24

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Predisposition of Latent Infection in:

Predisposition of Latent Infection in Ganglion Trigeminal HSV 1 Sacral HSV 2 Immunity. Cell Mediated ( CMI ) ‏ Predisposing Factors Axonal Injury Physical and Emotional stress U V light 80% Adults harbour Antibodies to HSV Dr.T.V.Rao MD 26

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Clinical Manifestations:

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. Dr.T.V.Rao MD 31

Recurrent Blisters in Herpes simplex 1:

Recurrent Blisters in Herpes simplex 1 Dr.T.V.Rao MD 32

Herpes lesions in the oral cavity:

Herpes lesions in the oral cavity Dr.T.V.Rao MD 33

Eye Infections and Genital Infections.:

Eye Infections and Genital Infections . Corneal ulcerations pacifications Blindness Vesiculo ulcerative Lesions penis, Cervix, Vulva and Vagina. Manifest with Painful lesions. Dr.T.V.Rao MD 34

Herpes simplex 1 infecting eye:

Herpes simplex 1 infecting eye Dr.T.V.Rao MD 35

Herpes 2 producing Genital Lesions:

Herpes 2 producing Genital Lesions Dr.T.V.Rao MD 36

Skin Infections :

Skin Infections Infect abrasions Dentists, ( Herpetic Whitlow) Health care workers, Eczema , Burns Dr.T.V.Rao MD 37

Neonatal Herpes.:

Neonatal Herpes. In Uterus At Birth After Birth. Delivery By Caesarean Section Reduces the Infection Dr.T.V.Rao MD 38

Neonatal Infection – Normal delivery:

Neonatal Infection – Normal delivery Dr.T.V.Rao MD 39

Other Manifestations.:

Other Manifestations. Meningitis, Encephalitis Multi organ Involvement Increased incidence in Immune compromised AIDS, Haematological Malignancies. Dr.T.V.Rao MD 40

Recurrent infections in HSV 1 and 2:

Recurrent infections in HSV 1 and 2 Dr.T.V.Rao MD 41

Immunity:

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 in immunity Dr.T.V.Rao MD 42

Laboratory Diagnosis:

Laboratory Diagnosis Microscopy, Antigen Detection DNA detection PCR. Viral Isolation. Serology Dr.T.V.Rao MD 43

Laboratory Diagnosis:

Laboratory Diagnosis Specimen: Vesicular fluid- Corneal scrapping 1- Direct Virus Demonstration: a) L/M: Tzanck smear – from the base of vesicles, 1% aq. soln. of toluidine blue ‘O’ shows multinucleated giant cells with faceted nuclei & homogenously stained ‘ground glass’ chromatin (Tzanck cells) Giemsa stained smear – intranuclear Cowdry type A inclusion bodies Dr.T.V.Rao MD 44

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B) Direct Immunofluorescence: Cell scrapings from lesions are stained with monoclonal antibodies conjugated with a fluorescence dye. Viral inclusion bodies appear in UV microscope as a bright green Intranuclear particles C) PCR: for detection of viral DNA in CSF Dr.T.V.Rao MD 45

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2- Viral Isolation: tissue culture: human diploid fibroblasts, human amnion, human embryonic kidney: CPC (syncytium formation) seen in 24-48 hrs. 3) Serology : useful in the diagnosis of primary infection, Ab (IgM) detection by ELISA, NT or CFT. Dr.T.V.Rao MD 46

Laboratory diagnosis:

Childhood infections common Second peak at onset of sexual activity Viral shedding persons with recurrences infected but asymptomatic persons Mucocutaneous lesions can be diagnosed clinically Laboratory diagnosis Dr.T.V.Rao MD 47

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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 Dr.T.V.Rao MD 48

Microscopy,:

Microscopy, Tzanck Smear Intranuclear Type A Inclusion Bodies Electron Microscopy Fluorescent Antibody Dr.T.V.Rao MD 49

Specimens for Diagnosis.:

Specimens for Diagnosis. Saliva. CSF Vesicle fluid. Dr.T.V.Rao MD 50

Viral Isolation in:

Viral Isolation in Chick embryo In Tissue Cultures Primary Embryonic Kidney Human Amnion Dr.T.V.Rao MD 51

Serology,:

Serology, ELISA Test Neutralization Tests Complement Fixation Tests Dr.T.V.Rao MD 52

Chemotherapy:

Chemotherapy Idoxuridine used topically in eye and skin infections – first successful antiviral agent. Acyclovir and vidarabine helps in systemic infections Other Drugs – Valaciclovir, Famiciclovir, Orally effective Foscarnet. Dr.T.V.Rao MD 53

Epidemiology.:

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 Dr.T.V.Rao MD 54

Varicella Zoster:

Varicella Zoster Dr.T.V.Rao MD 55

History of Chickenpox:

History of Chickenpox The name chicken pox because the blisters that appeared seemed like the skin that has been pecked by the chicken.. Dr.T.V.Rao MD 56

Herpes Virus:

Herpes Virus Dr.T.V.Rao MD 57

Properties of Virus.:

Properties of Virus. Like Herpes Virus Icosahedrons shape ds DNA Dr.T.V.Rao MD 58

Varicella Zoster ( Herpes Virus) DNA Virus :

Varicella Zoster ( Herpes Virus) DNA Virus Varicella -Chicken pox. Contagious Disease Mainly Children Generalized Vesicular eruptions on Skin and Mucous membranes Severe manifestations in Adults and Immune compromised. Dr.T.V.Rao MD 59

HERPES VARICELLA ZOSTER HVZ:

HERPES VARICELLA ZOSTER 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 Dr.T.V.Rao MD 60

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Varicella (Chicken Pox):

Varicella (Chicken Pox) Mild, highly contagious disease chiefly affecting children Mode of transmission: - airborne droplets and direct contact from varicella patients - Vesicular fluid of Zoster patients can be the source of Varicella in susceptible children Dr.T.V.Rao MD 62

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Shingles (Herpes Zoster ) ‏ Rash Limited to Distribution of Single Sensory Ganglion In Adults and immune compromised Sporadic Dr.T.V.Rao MD 63

Varicella –Zoster Virus (VZV):

Varicella –Zoster Virus (VZV) Causes 2 major diseases Varicella (chicken pox): primary infection usually in childhood Zoster ( shingles): reactivation of an earlier varicella Dr.T.V.Rao MD 64

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HERPES VARICELLA ZOSTER HVZ:

HERPES VARICELLA ZOSTER 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-infectious encephalitis generalized varicella (in immunocompromised patients) congenital and neonatal varicella Dr.T.V.Rao MD 66

Herpes Zoster:

Herpes Zoster Primary Contact - Chicken Pox Reactivation - Zoster (Partially Immune ) ‏ Dr.T.V.Rao MD 67

Culturing virus:

Culturing virus Grows in Human embryonic Tissue Produce inclusion bodies No difference in virus In Chicken pox and zoster infection Dr.T.V.Rao MD 68

Pathogenesis and Pathology:

Pathogenesis and Pathology Varicella virus enter through URT/Conjunctiva. Lymph nodes Viremia Liver and spleen Secondary viremia Infects Mononuclear Cells Rash Vesicle formation Dr.T.V.Rao MD 69

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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 life Dr.T.V.Rao MD 70

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Clinical Picture: Incubation period: 10-21 days Symptoms: mild fever & rash Rash: first appears on the trunk, then face and limbs Flat macules become papules then vesicles Followed by crust formation The crust is often shed off and heals without 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 Dr.T.V.Rao MD 71

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Herpes Zoster:

Herpes Zoster Skin Lesions Inflammation of Sensory Nerves and Ganglia Single Ganglion Dorsal root Ganglion Dr.T.V.Rao MD 73

Entry of Varicella Zoster virus:

Entry of Varicella Zoster virus Dr.T.V.Rao MD 74

Skin lesions showing different stages:

Skin lesions showing different stages Dr.T.V.Rao MD 75

Clinical Findings.:

Clinical Findings. Varicella, Incubation 10-20 days Fever, Malaise Rash Trunk –Face –Limbs – Buccal and Pharyngeal mucosa Lesions at all stages Macules, Papules, Vesicles, Crusts, May last 5 days, Hundreds of eruptions. Dr.T.V.Rao MD 76

Skin lesions of chickenpox:

Skin lesions of chickenpox Dr.T.V.Rao MD 77

Chicken pox lesions in the buccal cavity:

Chicken pox lesions in the buccal cavity Dr.T.V.Rao MD 78

Herpes Zoster involving a Nerve segment:

Herpes Zoster involving a Nerve segment Dr.T.V.Rao MD 79

Complications:

Complications 1- pneumonia especially in adults, may be fatal 2- rarely: fulminant encephalitis, which may be a manifestation of Reye’s syndrome that occurs as a consequence of salicylates intake during infection Dr.T.V.Rao MD 80

Congenital Varicella Syndrome & Neonatal Varicella:

Congenital Varicella Syndrome & Neonatal Varicella Primary maternal infection during the 1 st trimester may lead to congenital varicella syndrome ( serious & fatal): skin lesions, hypoplasia of limbs, chorioretinitis & CNS defects Primary maternal infection near the time of birth can lead to widely disseminated infection in the new born with mortality rate of 35% If rash began a week or more before delivery , maternal Abs transferred via placenta – baby gets the infection but escapes clinical disease Dr.T.V.Rao MD 81

Immune compromised :

I mmune compromised HIV / AIDS Malignancies. Organ transplantations Corticosteroid usage Leukaemia's . Dr.T.V.Rao MD 82

HERPES VARICELLA ZOSTER HVZ:

HERPES VARICELLA ZOSTER 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-infectious encephalitis generalized varicella (in immunocompromised patients) congenital and neonatal varicella Dr.T.V.Rao MD 83

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Pain and hyperaesthesia Dr.T.V.Rao MD 84

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Pain and hyperaesthesia Dr.T.V.Rao MD 85

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Pain and hyperaesthesia Dr.T.V.Rao MD 86

HERPES ZOSTER:

HERPES ZOSTER 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 CLINICAL EM of vesicle fluid SEROLOGY IgM detection Dr.T.V.Rao MD 87

Zoster.:

Zoster. Associated with Immune compromised. Manifest with severe pain Vesicles on trunk , head, neck Trigeminal Neuralgia Dr.T.V.Rao MD 88

Zoster (shingles):

Zoster (shingles) Sporadic disease in adults or immunocompromised patients Results from reactivation of latent VZV Rash similar to varicella but limited to a nerve distribution to the skin innervated by a dorsal root ganglion (dermatom) Dr.T.V.Rao MD 89

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Pain and hyperaesthesia Dr.T.V.Rao MD 90

Other Complications.:

Other Complications. Encephalitis, Mother to Child transmission Varicella Pneumonia. Fatal Complications . Dr.T.V.Rao MD 91

Laboratory Diagnosis.:

Laboratory Diagnosis. Smears --Scrapings from Lesions Demonstration of Multi nucleated giant cells Tzanck smears DNA Demonstration Cell cultures, Fluorescent –antibody ELISA PCR Dr.T.V.Rao MD 92

Epidemiology :

Epidemiology Communicable Disease World wide prevalence Common in < 10 year olds. Zoster in Adults Droplet spread Dr.T.V.Rao MD 93

Treatment :

Treatment Specific treatment is indicated mainly in Immunodeficient and elderly subjects and also in complicated with Varicella pneumonia,encephalitis,and disseminated zoster Acyclovir and Famiciclovir. Dr.T.V.Rao MD 94

Prevention of Chickenpox:

Prevention of Chickenpox Susceptible population children adults living in close proximity Do nothing Immunize live attenuated vaccine Protect if contact with patient with chickenpox and at risk of severe disease Zoster Immune Globulin (ZIG) Dr.T.V.Rao MD 95

Vaccine available:

Vaccine available A live modified Varicella virus lyophilised vaccine which can be stored at low temp is available for 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 Immunocompromised children. But not useful for treatment Dr.T.V.Rao MD 96

Programme created by Dr.T.V.Rao MD for Medical and Paramedical Students in the Developing World :

Programme created by Dr.T.V.Rao MD for Medical and Paramedical Students in the Developing World Email doctortvrao@gmail.com Dr.T.V.Rao MD 97