1. VIROLOGICAL ASPECT OF HERPES

2. VIROLOGICAL ASPECT OF HERPES
History
Celsus describe an actual herpetic lesion.
Galen's describe lesions similar caused by HSV
John Astruc, describe herpes genitalis
Unna in 1883 describe recurrences of genital lesions
Fournier, in 1896, wrote about the diagnosis and treatment of genital herpes

3. CHARACTERISTIC Enveloped double stranded DNA viruses.
genome of around 150 kb
Set up latent infection following primary infection.
Reactivation are more likely to take place during periods of immunosuppression.
Both primary infection and reactivation are likely to be more serious in immunocompromised patients.

4. CHARACTERISTIC
Genome consisits of long and short fragments, giving a total of 4 isomers.
Three subfamilies:
Alphaherpesviruses - HSV-1, HSV-2, VZV
Betaherpesviruses - CMV, HHV-6, HHV-7
Gammaherpesviruses - EBV, HHV-8
Reactivation are more likely to take place during periods of immunosuppression

5. PATHOPHYSIOLOGY
HSV is spread by contact, as the virus is shed in saliva, tears, genital and other secretions.
Primary infection, HSV spreads locally,
Latency in trigeminal nerve ganglion
The exact mechanism of latency is not known

6. Herpes Simplex Virus-1
Latency in trigeminal nerve ganglion 6

7. PATHOPHYSIOLOGY True latency is no viral replication
Persistence is a low level of viral replication.
Reactivation many triggers:
physical or psychological stress,
infection (pneumococcal and meningococcal) fever
radiation
menstruation.

8. CLINICAL MANIFESTATIONS
1. Acute gingivostomatitis
2. Herpes Labialis (cold sore)
3. Ocular Herpes
4. Herpes Genitalis
5. Other forms of cutaneous herpes
6. Meningitis
7. Encephalitis
8. Neonatal herpes

9. 2. Indirect Examination (Virus Isolation)
LABORATORY TEST
1. Direct Examination
2. Indirect Examination (Virus Isolation)
3. Serology

10. DIRECT EXAMINATION 1. Antigen Detection immunofluorescence, ELISA etc.
2. Electron Microscopy morphology of virus particles
immune electron microscopy
3. Light Microscopy histological appearance
inclusion bodies
4. Viral Genome Detection
hybridization with specific nucleic acid probes polymerase chain reaction (PCR)

11. INDIRECT EXAMINATION 1.Cell Culture cytopathic effect (CPE)
haemabsorption
immunofluorescence
2. Eggs haemagglutination
inclusion bodies
3. Animals disease or death

12. CYTOPATHIC EFFECT (1)
Cytopathic effect of enterovirus 71 and HSV in cell culture: note the ballooning of cells. (Virology Laboratory, Yale-New Haven Hospital, Linda Stannard, University of Cape Town)

13. CYTOPATHIC EFFECT (2)
Syncytium formation in cell culture caused by RSV (top), and measles virus (bottom).
(courtesy of Linda Stannard, University of Cape Town, S.A.)

14. HAEMADSORPTION
Syncytial formation caused by mumps virus and haemadsorption of erythrocytes onto the surface of the cell sheet.
(courtesy of Linda Stannard, University of Cape Town, S.A.)

15. Viruses Isolated by Cell Culture

16. PROBLEMS WITH CELL CULTURE
Long period (up to 4 weeks) required for result.
Often very poor sensitivity, sensitivity depends on a large extent on the condition of the specimen.
Susceptible to bacterial contamination.
Susceptible to toxic substances which may be present in the specimen.
Many viruses will not grow in cell culture e.g. Hepatitis B, Diarrhoeal viruses, parvovirus, papillomavirus.

17. ELECTRON MICROSCOPY
106 virus particles per ml required for visualization, 50, ,000 magnification normally used. Viruses may be detected in the following specimens.
Faeces Rotavirus, Adenovirus
Norwalk like viruses
Astrovirus, Calicivirus
Vesicle Fluid HSV
VZV
Skin scrapings papillomavirus, orf
molluscum contagiosum

18. ELECTRON MICROGRAPHS Adenovirus Rotavirus
(courtesy of Linda Stannard, University of Cape Town, S.A.)

19. PROBLEMS WITH ELECTRON MICROSCOPY
Expensive equipment
Expensive maintenance
Require experienced observer
Sensitivity often low

20. SEROLOGY Classical techniques Newer techniques
Complement fixation tests
Haemaglutination inhibition tests
Immunofluorescence techniques
Neutralization tests
Counter immunoelectrophoresis
Newer techniques
Radioimmunoassay
ELISA
Particle aglutination
Western blot

21. EPIDEMIOLOGY
HSV is spread by contact, saliva, tears, genital and other secretions.
Infection results a kiss given to a child or adult from a person shedding the virus.
Primary infection is usually subclinical to very young children below 5 years.
There are 2 peaks of incidence, the first at years and the second in the late teens.
About 10% of the population acquires HSV infection through the genital route

22. TREATMENT
Acyclovir is the drug of choice regardless of infection status (oral and IV formulations available)
Treat neonatal HSV with 20 mg/kg/dose intravenously 3 times daily for 21 days
For skin, eye, mouth disease, treat for 14 days

23. antiviral chemotherapy
PREVENTION
antiviral chemotherapy
Education
Condoms
vaccines.

24. TERIMA KASIH

25. Herpes Simplex viruses
HSV-1- lesions on the oropharynx, cold sores, fever blisters
occurs in early childhood
HSV-2 lesions on the genitalia
can be spread without visible lesions
humans only reservoir
treatment: acyclovir, famciclovir, valacyclovir 25

26. Herpes Simplex Virus-1
Latency in trigeminal nerve ganglion 26

27. Herpes Virus 27

28. The Lytic Cycle

29. The Lysogenic Cycle