1. بسم الله الرحمن الرحيم

2. Herpesviridae HSV1,2,VZV,CMV&EBV
By: Dr.Malak El-Hazmi
Assistant Professor & Consultant Virologist College of Medicine & KKUH

3. Herpesviridae 1- Herpes simplex virus type -1 HSV-1
3- Varicella –Zoster virus VZV
4- Epstein- Barr virus EBV
5- Cytomegalovirus CMV
6- Human herpes virus type HHV-6
7- Human herpes virus type HHV-7
8- Human herpes virus type HHV-8

4. dsDNA, Enveloped, Icosahedral Virus
HERPESVIRVS
dsDNA, Enveloped, Icosahedral Virus

5. Features of herpesviruses
Herpesviridae
Features of herpesviruses
All herpesviruses are structurally identical
Replicate in nucleus
Intranuclear inclusions
Envelope from nuclear mb
Latent infection
Cause high morbidity and mortality in immuno ed patients
Some herpesviruses
Associated with cancers e.g. EBV & HHV8

6. Sub family Virus Target cell Latency
Alpha HHV1 HHV2 HHV3
HSV1 HSV2 VZV
Neuron
Mucoepithelial
Monocyte Lymphocyte&Epithelial cells
Beta
Mono & lymphocyte
CMV
HHV5
Gamma
B lymphocyte, Epithelial cells
HHV4
EBV
B lymphocyte

7. HERPES SIMPLEX VIRUS HSV
Location of lesions

8. Immunity Not Completed
Pathogenesis
HSV-1 becomes latent in trigeminal g
HSV-2 becomes latent in lumber & sacral g
Typical Lesion
Immunity Not Completed

9. Epidemiology
HSV1
HSV2
Transmission Direct contact with lesions & Contaminated secretions
Saliva Sexual contact during birth [perinatal]
Age Children Adolescent& adults
Source Herpetic lesions
Asymptomatic shedding

10. HSV-1 Infections Asymptomatic Diseases of HSV-1 Oral infections
1ْGingivostomatitis / herpetic stomatitis
Pharyngitis / tonsillitis
Herpes labialis (cold sores) – R

11. Diseases of HSV-1 Keratoconjunctivitis: Herpetic whitlow: 1o & R
Keratitis R
dendritic ulcer
may cause blindness
Herpetic whitlow: 1o & R
Toddlers
Nurses & dentists

12. Diseases of HSV -1 Oral infections Herpetic whitlow : 1o & R
Gingivostomatitis / herpetic stomatitis
Pharyngitis / tonsillitis
Herpes labialis (cold sores} – R
Herpetic whitlow : 1o & R
Nurses & dentists
Toddlers
Keratoconjunctivitis:
Keratitis dendritic ulcer may cause blindness
Encephalitis
Disseminated disease
Immuno ed patients
1o or R R R

13. Diseases of HSV2 Neonatal herpes Aseptic meningitis
Genital herpes: STD
1o or R
Neonatal herpes
Aseptic meningitis

14. Comparison of Diseases Caused by HSV-1 and HSV-2
Site
Disease Caused By HSV-1
Disease Caused by HSV-2
Skin
Vesicular lesions above the waist
Vesicular lesions below the waist (especially genitals)
Mouth
Gingivostomatitis
Rare
Eye
Keratoconjunctivitis
Central nervous system
Encephalitis (temporal lobe)
Meningitis
Neonate
Skin lesions and disseminated infection
Dissemination to viscera in immunocompromised patients
Yes

15. Diagnosis Clinically Lab Dx. Direct ex: Serological test:
HSV
Clinically
Lab Dx.
Direct ex:
Vesicular fluid for E/M & virus isolation
Cells scraping from the base of vesicles ImmunoFluorescent test (Ag)** Tzanck smear (Giemsa stain)
CSF for DNA-HSV by PCR in HE
Serological test:
IgM AB*
≥ 4 fold increase in AB titers b/t acute & convalescent sera.

16. Treatment Prevention Acyclovir Foscarnet
HSV
Acyclovir
Severe diseases
Systemic diseases
Immuno ed patients
Foscarnet
Acyclovir resistant strains of HSV
Prevention
Avoid contact with herpetic lesions & its secretions
Gloves & hand washing
C/S for pregnant lady with infected birth canal
Sex education
No vaccine

17. Varicella - Zoster Virus VZV
Varicella : Chickenpox:
1o illness
Generalized vesicular rash
Zoster: Shingles:
Recurrent form
Localized VR

18. Varicella Zoster Adults & immuno ed host Children
VZV
Varicella
Children
Late winter & early spring
highly infectious disease (communicable)
Epidemic
Respiratory droplets
Direct & Indirect contact
Transplacental
Zoster
Adults & immuno ed host
No seasonal distribution
Sporadic
Age
Incidence
Transmission
Rarely
May give V in s-host

19. Pathogenesis Immunity : to Varicella, not to zoster
VZV
Pathogenesis
VZV remains latent in trigeminal ganglia,
or in dorsal root ganglia.
Immunity : to Varicella, not to zoster

20. Varicella Complications IP = 2 -3 wks Vesicular rash
VZV
IP = 2 -3 wks
Vesicular rash
Starts on trunk , spread to face & limbs
Appears in successive waves
Healing without scarring
Mild in children, Severe in adults & immuno ed patients
Complications
Secondary bacterial infection of skin lesions
Reye’s syndrome
Pneumonia
Encephalitis

21. Varicella in Pregnancy
VZV
Varicella in Pregnancy
Severe disease in pregnant women e.g. pneumonia
Intrauterine infections
Congenital varicella syndrome
Neonatal varicella
< 7 days of delivery severe disease
> 7 days before delivery mild disease

22. zoster A localized unilateral VR & pain Post-herpetic neuralgia
VZV
A localized unilateral VR & pain
Thoracic zoster
R dorsal root g
Ophthalmic zoster
R trigeminal g
Ramsay-Hunt syndrome rare
Post-herpetic neuralgia
Dissemination of zoster in immuno ed patients

23. Diagnosis Clinically Lab Dx. Direct ex: Serological test:
VZV
Diagnosis
Clinically
Lab Dx.
Direct ex:
Vesicular fluid for E/M & virus isolation
Cells scraping from the base of vesicles ImmunoFluorescent test (Ag)** Tzanck smear (Giemsa stain)
CSF for DNA-VZV by PCR in encephalitis
Serological test:
IgM AB*
≥ 4 fold increase in AB titers b/t acute & convalescent sera.

24. Treatment: Indications Antiviral drugs:
VZV
Treatment:
Indications
Neonates
Immuno ed patients
Adults with moderate to severe disease
Patients with complications
Ophthalmic zoster
Antiviral drugs:
Acyclovir
Valacyclovir
Famicilovir
A acyclovir resistant strains of VZV Foscarnet

25. Prevention Infection control practice
VZV
Prevention
Infection control practice
Live -attenuated Varicella vaccine
Two doses
Immunocompetent children & Adults
VZIG
Immuno ed patient & non-immune pregnant& neonate born to mother who acquired varicella around delivery
<4 days after exposure

26. Epstein – Barr Virus EBV
HHV-4 , gammaherpesvirinae
Special features
It is lymphotropic
It has oncogenic properties
Its antigenic composition

27. Epidemiology Distribution :worldwide Transmission: Age:
EBV
Epidemiology
Distribution :worldwide
Transmission:
Saliva [kissing disease]
Blood [rarely]
Age:
Socio-economic status: SE
Low SE class early childhood
High SE class adolescence

28. Clinical Features: Immunocompetent host Chronic EBV infection
Asymptomatic
Infectious mononucleosis [glandular fever]
Mainly in teenagers & young adults
IP = 4-7 weeks
Fever, pharyngitis, malaise, LAP, hepatosplenomegaly & abnormal LFT
Rash may follow ampicillin
Last 2- 3 weeks
Complications
( acute air way obstruction, splenic rupture, CNS inf)
Chronic EBV infection

29. Immunocompromised host
EBV
Clinical Features :
Immunocompromised host
Lymphoproliferative disease ( LD)
Patients with decrease CMI
Transplant recipients PTLD
Oral hairy leukoplakia (OHL)
Non-malignant lesion
HIV-infectedpatients immuno ed patients

30. EBV – Associated Malignancies
Burkitt’s lymphoma
A tumor of lymphoid tissue
African children
Malaria can act as a cofactor
Nasopharyngeal carcinoma
A tumor of epithelial origin
Adults
China

31. EBV
Diagnosis:
Hematology:
WBC lymphocytosis Atypical lymphocytes

32. Diagnosis: Serology: EBV Ags & EBV-DNA in lymphoid & other tissues
Non-specific AB test
Heterophile Abs +ve
Paul-Bunnell or mono-spot test
EBV-specific AB test:
IgM Abs to EBVirus capsid antigen
Serology is not reliable in immuno ed patients
EBV Ags & EBV-DNA
in lymphoid & other tissues

33. EBV

34. Prevention: Management: Treatment:
EBV
Management:
Treatment:
Antiviral drug is not effective in IMN
Acyclovir is used in treating OHL
Prevention:
No vaccine

35. Cytomegalovirus CMV Betaherpesvirinae – HHV-5 Special features
Its replication cycle is longer
Infected cell enlarged with multinucleated [cyto=cell, megalo=big]
Resistant to acyclovir
Latent in monocyte & lymphocyte & other

36. Epidemiology Distribution: worldwide Transmission Early in life:
CMV
Epidemiology
Distribution: worldwide
Transmission
Early in life:
Transplacenta
Birth canal
Breast milk
Young children: saliva
Later in life: sexual contact
Blood transfusion & organ transplant

37. Acquired Infection Immunocompetent host Immunocompromised host
CMV
Acquired Infection
Immunocompetent host
Asymptomatic
Self-limited illness
Hepatitis
Infectious mononucleosis like syndrome
[Heterophile AB is –ve]
Immunocompromised host
1o or R
Pneumonia, Hepatitis, Encephalitis
Retinitis, Esophagitis, Colitis

38. Congenital Infections:
CMV
Congenital Infections:
Clinically normal
15% Hearing defect mental retardation
4% Cytomegalic inclusion disease
1% death

39. Lab. Diagnosis [Owl’s –eye] CMV
Histology: Intranuclear inclusion bodies
[Owl’s –eye]

40. Lab. Diagnosis Culture: In human fibroblast 1-4 wks CPE
CMV
Lab. Diagnosis
Culture:
In human fibroblast
1-4 wks CPE
Shell Vial Assay days
Serology:
AB IgM: 1 or R inf IgG: previous exposure
Ag CMV pp65 Ag by IFA
PCR

41. Treatment Ganciclovir Foscarnet: the 2nd drug of choice
CMV
Treatment
Ganciclovir
is effective in the Rx of severe CMV inf.
e.g. CMV retinitis, pneumonia
Foscarnet: the 2nd drug of choice

42. Prevention: Screening Leukocyte-depleted blood
CMV
Prevention:
Screening
organ donors
Organ recipients
Blood donors
Leukocyte-depleted blood
Chemoprophylaxis: Ganciclovir
Immunoprophylaxis: CMVIG
No vaccine

43. Thank you