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7/30/2019 Herpes Viruses - 2013 (FN)
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HERPES VIRUSES
Dr F Noordeen
Department of Microbiology
Faculty of Medicine
Peradeniya
April 2013
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Mechanisms by which herpes viruses cause
disease in humans
Host defenses against viruses
Main clinical features of viral infections/disease
Principles of diagnosis treatment and prevention
viral infections/disease in humans
Learning outcomes
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EM of a Herpes Virus
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CLASSIFICATION
Genome - DNA Viruses
Morphology - Icosahedral
- Large baggy envelope
Enzymes - DNA polymerase
- HSV & VZV thymidine kinase
Reproduction - Nucleus of host cell
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CLASSIFICATION
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
Human Herpesvirus type 8 HHV- 8
Gammaherpesvirinae
Epstein-Barr virus EBV
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HERPES SIMPLEX VIRUS
Primary infection - Contact with HSV
Latent infection - Virus persists in root ganglia
Reactivation - Production of infective virus
by latently infected cell
Recurrence - Clinical disease produced
by reactivation
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Pathogenesis
Entry by skin or mucous membranes
viral multiplication sensory nerve
lysis of cells root ganglia
vesicles latency
ulcersREACTIVATION
ColdFever
Surgery
Unknown
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Stomatitis with secondary skin lesions
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Primary infection of the skin
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Recurrent
infection
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Herpetic infection of the eye
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Herpetic whitlowHerpetic whitlow
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Vulvovaginitis in child
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Genital herpes inan adult male
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Genital herpes inan adult female
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Genital herpes in
adult female(Herpetic cervicitis)
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Epidemiology
Childhood infections common
Second peak at onset of sexual activity
Viral shedding/reservoirs
persons with recurrences infected but asymptomatic persons
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Laboratory diagnosis
Useful
Genital & eye infections
HVZ & HSV in immunocompromised
Herpes encephalitis
Specimens
Aspirate from vesicle
Scraping from base of ulcer
Serum/CSF for antibody
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Laboratory diagnosis
1. Microscopy
- Light - giant cells & inclusions
- Electron microscopy
2. Antigen detection - ELISA and IFT
3. Virus culture & identification
4. DNA detection - PCR (Encephalitis)
5. Antibody detection - ELISA and IFT
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Treatment for HSV infections
1. Acyclovir : Topical and oral formulations
2. Idoxyuridine
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HERPES VARICELLA ZOSTER - HVZ
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
Generalised varicella (in immunocompromised patients)
Congenital and neonatal varicella
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Varicella rash in child
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Varicella vesicleson palate
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Varicella vesicles
on conjunctiva
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HERPES ZOSTER
Reactivation of VZV
Dermatomal distribution and may recur
Can disseminate in immunocompromised
patients
Complications
Post herpetic pain
Ophthalmic zoster - corneal scarring and loss of vision
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Diagnosis of Zoster
Clinical features and lesion distribution
EM/IFA of vesicle fluid
Serology - IgM detection
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Skin supplied by cervical roots 4 & 5 are affected
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Thoracic segments are affected
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Prevention of chicken pox
Children & adults living in close proximity
Do nothing Immunise with
live attenuated
vaccine
Protect contact
with patient with
chickenpox and
at risk of severe
disease
Zoster Immuno
Globulin (ZIG)
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EPSTEIN-BARR VIRUS - EBV
Discovered in 1964 by Epstein and Barr
Definite association with malignancy
Is able to transform cells resulting inimmortalisation of cells
2 types of virus A & B which may co-exist
in a same person
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Infectious mononucleosis
Affects adolescents and young adults
Worldwide distribution
Called kissing disease
IP - one month
Presents with fever,
sore throat, rash and swollen lymph nodes
DIAGNOSIS
Raised WBC with >20% lymphocytes
Paul-Bunnell test (heterophil antibodies) or mono spot
DIAGNOSIS
Raised WBC with >20% lymphocytes
Paul-Bunnell test (heterophil antibodies) or mono spot
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Blood film with abnormal
mononuclear cells
1st week - normal/raised
neutropenia
2nd week - leukoctosis with
(lymphoctosis)
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EnanthumEnanthum -- Rashes on the palateRashes on the palate
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Inflamed throat
without exudate
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Follicular
exudate
Patches of
white exudate
Patch of
white exudate
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Syndromes caused by EBV
Burkitts lymphoma Children 4-12 years
Subsaharan Africa and New Guinea
Nasopharyngeal carcinoma Adults 20-50 years old
Southern China
B cell lymphoma
Children and adults
Primary immunodeficiency
Patients with AIDS
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BURKITTS LYMPHOMA
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NASOPHARYNGEAL CARCINOMA
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Cytomegalovirus infections
Ubiquitous virus
Most populations - infections in early childhood
Often asymtomatic
Latency
Clinical disease increasing due to increasing
number of immunocompromised patients
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Cytomegalovirus infections
Foetal infection Transmission from mother via placenta
Clinically normal 80%
Causes congenital CMV
Death 1%
Cytomegalic inclusion disease 4%
Late onset hearing defect/mental retardation 15%
Infantile infections
Transmission during birth or breast feeding
Usually asymptomatic
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Cytomegalovirus infections
Young children Transmission from other children
Usually asymptomatic
Adolescent/adult Transmission during kissing, sexual intercourse or blood
transfusion
Occasionally IM like syndrome
Immunocompromised Exogenous PRIMARY INFECTION
Endogenous REACTIVATION
Pneumonitis, GI infection
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Cytomegalovirus infections
Diagnosis - Difficult Presence of virus or antibody to CMV does not indicate
a current CMV infection/disease
Different strategies used in different clinical situations
Isolation of virus from urine
within 30 days of birth
Antigen detection in
buffy coat - indicates
viraemia
* CMV specific IgG positive indicates past infection
Congenital CMV
Immunocompromised
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Treatment and prevention
Congenital CMV Prevention not possible
CMV in transplant recipients Prevention
Treatment
Test IgG before transplant
Use only seronegative donors
Early diagnosis
Reduce immunosuppression
Ganciclovir
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OTHER HUMAN HERPES VIRUSES
Human Herpes Virus 6 (HHV6) Discovered in 1988
Worldwide
Virus replicates in T and B cells
Infection occurs in first 3 years of life
Clinical disease - Exanthem subitum (Roseola infantum)
Mild acute febrile illness
Incubation period of 2 weeks
Fever lasts several days
Macular papular rash appears within 2 days of fever
85% of adults carry virus in saliva
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Exanthem subitum
(Roseola infantum)
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OTHER HUMAN HERPES VIRUSES
HHV7 Isolated from CD4 positive cells
Virus present in saliva of >75% of adults
Role in disease is unclear Evidence of infection present (seroconversion)
HHV8
Detected in epithelial cells of Kaposi sarcoma
Also present in semen
Postulated as cause of Kaposi sarcoma
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1.1 Name three (5) herpes viruses that causedisease in humans
(25 Marks)
1.2 How can you make an aetiological diagnosisof 3 diseases you have named in 1.1?
(75 Marks)
SAQ September 2011