herpes virus is common virus which have variety of clinical presentations, like oral herpes lesions or cutaneous lesions ...

1. HERPES VIRUS

2. CONTENTS
INTRODUCTION
SIMPLEX 1
SIMPLEX 2
VARICELLA
EPSTEIN-BARR
CYTOMEGALOVIRUS
HHV-6
HHV-7
KAPOSI’S SARCOMA VIRUS

3. INTRODUCTION
Herpes viruses
•Structure and Composition
oSpherical iscoahedron, 150-200 nm
oDouble-stranded DNA, linear
oMore than 35 proteins
oEnveloped
oReplication from nucleus (budding)

4. •Three subfamilies:
oAlphaherpesviruses - HSV-1, HSV-2, VZV
(Short replicative cycle : 12-18 hours –sensory
(ganglia )
oBetaherpesviruses - CMV, HHV-6, HHV-7
(> 24 hours :salivary glands and other organs )
oGammaherpesviruses - EBV, HHV-8
( narrow host range , lympho blastoid cells )

5. Species
•Simplex 1 (HHV-1) (alpha)
•Simplex 2 (HHV-2) (alpha)
•Varicella (HHV-3) (alpha)
•Epstein-Barr (HHV-4) (gamma)
•Cytomegalovirus (HHV-5) (beta)
•HHV-6 (beta)
•HHV-7 (beta)
•Kaposi’s sarcoma virus (HHV-8) (gamma)

6. Herpes simplex

7. Clinical Manifestations
HSV is involved in a variety of clinical manifestations which
includes ;-
1. Acute gingivostomatitis
2. Herpes Labialis (cold sore)
3. Ocular Herpes
4. Herpes Genitalis
5. Other forms of cutaneous herpes
7. Meningitis
8. Encephalitis
9. Neonatal herpes

8. MUCOSAL
ACUTE GINGIVOSTOMATITIS
•Acute gingivostomatitis is the commonest manifestation
of primary herpetic infection.
•The patient experiences pain and bleeding of the gums.
1 - 8 mm ulcers with necrotic bases are present
•Neck glands are commonly enlarged accompanied by
fever.
•Usually a self limiting disease which lasts around 13
days.

10. MUCOSAL
HERPES LABIALIS (COLD SORE)
•Herpes labialis (cold sore) is a
recurrence of oral HSV.
•45% of orally infected individuals will experience
reactivation. The actual frequency of recurrences
varies widely between individuals.
•Tingling, warmth or itching at the site usually
heralds the recurrence. About 12 hours later,
redness appears followed by papules and then
vesicles.

11. SYMPTOMS
•The symptoms can be mild or severe and may include:
Sores on the inside of the cheeks or gums
Fever
General discomfort, uneasiness, or ill feeling
Very sore mouth with no desire to eat
Halitosis (bad breath Not able to chew or swallow)

12. HSV – Cold Sore

13. OCULAR HERPES
HSV causes corneal blindness.
Diseases caused include the following:-
– Primary HSV keratitis –
– Dendritic ulcers
– Recurrent HSV keratitis
– HSV conjunctivitis
– Acute necrotising retinitis,
chorioretinitis are un common but
serious manifestations

14. KERATOCONJUNCTIVITIS
• Keratoconjunctivitis is inflammation of the cornea and
conjunctiva.
• Primary infection typically presents as swelling of the
conjunctiva and eyelids (blepharo conjunctivitis),
accompanied by small white itchy lesions on the
surface of the cornea.
• The effect of the lesions varies, from minor damage to
the epithelium (superficial punctate keratitis), to
formation of dendritic ulcers.

15. Keratoconjunctivitis

16. HERPES SIMPLEX ENCEPHALITIS
• Herpes Simplex encephalitis is one of the most
serious complications of herpes simplex disease.
There are two forms:
• Neonatal – there is global involvement and the brain
is almost liquefied. The mortality rate approaches
100%.

17. •Focal disease – the temporal lobe is most commonly
affected. This form of the disease appears in children and
adults. It is possible that many of these cases arise from
reactivation of virus. The mortality rate is high (70%)
without treatment.
•It is of most importance to make a diagnosis of HSE early.
It is general practice that IV acyclovir is given in all cases
of suspected HSE before laboratory results are available.

18. Herpes Simplex Encephalitis
CT Scan Autopsy

19. MENINGITIS
• Most commonly associated with primary HSV-2
infection; less likely with recurrences of genital
herpes
• Benign, self-limited (contrast with encephalitis)
• Usually affects sexually active young adults
• No neurologic sequelae; not clear if acyclovir
treatment alters course of mild meningitis

20. GENITAL HERPES
• Genital lesions may be primary, recurrent or initial.
• Many sites can be involved which includes the penis,
vagina, cervix, anus, vulva, bladder, the sacral
nerve routes, the spinal and the meninges.
• The lesions of genital herpes are particularly prone
to secondary bacterial infection eg. S.aureus,
Streptococcus, Trichomonas and Candida Albicans.

21. GENITAL HERPES
•Dysuria is a common complaint, in severe cases, there
may be urinary retention.
•60% of patients with genital herpes will experience
recurrences. Recurrent lesions in the perianal area
tend to be more numerous and persists longer than
their oral HSV-1 counterparts.

22. HSV – CONGENITAL/PERINATAL
• Perinatal infection:
• 75% are due to HSV 2; acquired during delivery
• Post natal infection
• HSV-1 acquired from maternal genital, oral or breast
lesions or nosocomial infection from other infected
babies

24. HERPETIC WHITLOW
• A herpetic whitlow is a lesion (whitlow) on a finger or
thumb caused by the herpes simplex virus.
• Herpes whitlow can be caused by infection by HSV-1 or
HSV-2.
• HSV-1 whitlow is often contracted by health care
workers that come in contact with the virus; it is most
commonly contracted by dental workers and medical
workers exposed to oral secretions.

26. Laboratory Diagnosis
• Direct Detection
 Electron microscopy of vesicle fluid - rapid
result but cannot distinguish between HSV and
VZV
 Immunofluorescence of skin scrappings - can
distinguish between HSV and VZV
 PCR - now used routinely for
the diagnosis of herpes simple
encephalitis

27. Cytopathic Effect of HSV
in cell culture: Note the
ballooning of cells.
Positive immunofluorescence
test for HSV antigen in
epithelial cell.

28. Laboratory Diagnosis
Virus Isolation
• Viral culture (gold standard)
• Preferred test if genital ulcers or other
mucocutaneous lesions are present
• Highly specific (>99%)
• Sensitivity depends on stage of lesion; declines
rapidly as lesions begin to heal
• Positive more often in primary infection (80%–
90%) than with recurrences (30%)

29. Laboratory Diagnosis
Polymerase Chain Reaction (PCR)
• More sensitive than viral culture; has been used instead
of culture in some settings; however PCR tests are not
widely available
• Preferred test for detecting HSV in spinal fluid

30. TYPE-SPECIFIC SEROLOGIC TESTS
• Type-specific and nonspecific antibodies to HSV
develop during the first several weeks to few months
following infection and persist indefinitely
• Presence of HSV-2 antibody indicates anogenital
infection
• Presence of HSV-1 does not distinguish anogenital
from orolabial infection
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31. HERPES B VIRUS
•Formerly known as Herpes simiae
•Officially known as cercopithecine herpesvirus 1
•Almost always fatal in humans
oHas high propensity for central nervous system
and causes substantial damage
oSurvivors usually have neurological disorders
•No effective treatment

32. MANAGEMENT
• There is no method to eradicate herpes virus from the
body, but antiviral medications can reduce the
frequency, duration, and severity of outbreaks.
• Analgesics such as ibuprofen and acetaminophen can
reduce pain and fever.
• Topical anesthetic treatments such as prilocaine,
lidocaine, benzocaine or tetracaine can also relieve
itching and pain

33. ANTIVIRAL
There are several antivirals that are effective for treating
herpes including:
• Aciclovir (acyclovir),
• Valaciclovir (valacyclovir),
• Famciclovir,
• Penciclovir.

34. Varicella zoster

35. VARICELLA
• Primary infection results in varicella (chickenpox)
• Incubation period of 14-21 days
• Presents fever, lymphadadenopathy. a widespread
vesicular rash.
• The features are so characteristic that a diagnosis can
usually be made on clinical grounds alone.

36. •Complications are rare but occurs more frequently and with
greater severity in adults and immunocompromised patients.
•Most common complication is secondary bacterial infection of
the vesicles.
•Severe complications which may be life threatening include
viral pneumonia, encephalititis, and haemorrhagic chickenpox.

38. NEONATAL VARICELLA
• VZV can cross the placenta in the late stages of
pregnancy to infect the fetus congenitally.
• Neonatal varicella may vary from a mild disease to
a fatal disseminated infection.
• If rash in mother occurs more than 1 week before
delivery, then sufficient immunity would have been
transferred to the fetus.

39. NEONATAL VARICELLA
•Zoster immunoglobulin should be given to susceptible
pregnant women who had contact with suspected cases of
varicella.
•Zoster immunoglobulin should also be given to infants
whose mothers develop varicella during the last 7 days of
pregnancy or the first 14 days after delivery.

40. LABORATORY DIAGNOSIS
The clinical presentations of varicella or zoster are so
characteristic that laboratory confirmation is rarely
required.
Laboratory diagnosis is required only for atypical
presentations, particularly in the immunocompromised.
– Virus Isolation - rarely carried out as it requires 2-3
weeks for a results.

41. LABORATORY DIAGNOSIS
Direct detection - electron microscopy may be used for
vesicle fluids but cannot distinguish between HSV and VZV.
Immunofluorescense on skin scrappings can distinguish
between the two.
Serology - the presence of VZV IgG is indicative of past
infection and immunity. The presence of IgM is indicative
of recent primary infection.

42. PROPHYLAXIS
• V – Z immunoglobulins.
• Live attenuated varicella vaccine.
•Preventive measures should be considered for individuals at
risk of contracting severe varicella infection e.g. leukaemic
children, neonates, and pregnant women
•Where urgent protection is needed, passive immunization
should be given. Zoster immunoglobulin (ZIG) is the
preparation of choice but it is very expensive. Where ZIG is
not available, HNIG should be given instead.

43. HERPES ZOSTER
 Zoster is the manifestation of recurrent infection
following a primary attack of chicken pox.
 Both chicken pox and herpes zoster (shingles) are
caused by varicella.
 Unlike herpes labialis, repeated recurrences of zoster
are very rare.
 Infection typically affect adult of middle age or over.

44.  Pain precedes the rash (vesicles).
 Shingles causes severe pain, and commonly occurs on
the trunk on one side.
 The trigeminal nerve is affected in about 15% of cases
of shingles.

45. •Lesions localized to one side, within the distribution of any
of the divisions of the trigeminal nerve and in the mouth up
to the midline.
•Malaise can be severe.
•Regional lymph node are enlarged and can be life-threatening
in HIV disease.

46. TREATMENT
 in severe case : oral acyclovir 800 mg five times daily
for 7-10 days should be given at the earliest possible
moment, together with analgesic.

47. RAMSAY HUNT SYNDROME
• Involvement of facial nerve with VZV
• Facial nerve palsy
• Vesicles in external auditory meatus
• Vesicles on palate
• Symptoms :dizziness, loss of taste.
• In most cases, this is self limiting condition but rarely
in some patients there may be permanent facial
weakness.

48. CYTOMEGALO VIRUS
• Belong to the beta herpesvirus subfamily of
herpesviruses
• Double stranded DNA enveloped virus
• Nucleocapsid 105nm in diameter, 162 capsomers

49. CLINICAL FEACTURES
Cytomegalic Inclusion disease of Newborn(10%)
characterised by varied type of clinical manifestations.
•Hepatospleenomegaly
•Jaundice
•Thrombocytopenic purpura
•Haemolytic anaemia
•Microcephaly
•Cerebral calcifications.
•Mental retardation.
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50. Primary infection-
Usually asymptomatic.
In a minority of cases, the syndrome of infectious
mononucleosis may develop which consists of fever,
lymphadenopathy, and splenomegaly.

51. Immunocompromised patients such as transplant
recipients and AIDS patients are prone to severe CMV
disease such as pneumonitis, retinitis, colitis, and
encephalopathy.
Reactivation or reinfection with CMV is usually
asymptomatic except in immunocompromised patients.

52. Labotary Diagnosis
Adults: Urine, Saliva, Semen & Cervical
secretions.
Neonate: Urine
1. Microscopy:
Centrifuged deposits of secretions.
Giemsa stain: Cytomegalic cells
52

53. PREVENTION
• No vaccine is available.
• Live attenuated vaccine known as the Towne 125, AD
169 stains , and purified CMV polypeptide vaccine )
• Prevention of CMV disease in transplant recipients
o Screening and matching the CMV status of the
donor and recipient
o Use of CMV negative blood for transfusions
o Administration of CMV immunoglobulin to
seronegative recipients prior to transplant
o Give antiviral agents such as acyclovir and
ganciclovir prophylactically.

54. EPSTEIN – BARR (EB) VIRUS
•Burkitt's lymphoma in 1964 .
•Affinity for B – lymphocytes (CD 21 receptors.)
•80 – 90% of children by three years of age.
•Asymptomatic.
•Not highly contagious.
•Droplets are not infectious.
Source : Saliva, Oropharyngeal secretions
54

55. INFECTIOUS MONONUCLEOSIS
Incubation period : 4 – 8weeks
(Glandular disease, Kissing disease)
•Acute self limiting illness.
•Fever, sore throat.
•Lymphadenopathy.
•Sub clinical Hepatitis,
• Tender spleenomegaly
55

56. Sore throat
Cervical lymphadenopathy Hepatosplenomegaly

57. BURKITT’S LYMPHOMA
• Burkitt's lymphoma (BL) occurs endemically in parts
of Africa (where it is the commonest childhood
tumour) and Papua New Guinea.
• It usually occurs in children aged 3-14 years. It
respond favorably to chemotherapy.

58. NASOPHARYNGEAL CARCINOMA
• Nasopharyngeal carcinoma (NPC) is a malignant
tumour of the squamous epithelium of the nasopharynx.
• It is very prevalent in S. China, where it is the
commonest tumour in men and the second commonest
in women.
• NPC usually presents late and thus the prognosis is
poor.

59. LAB DIAGNOSIS
1.Blood smear examination :Atypical Lymphocytosis.
2.Paul - Bunnel test:
Heterophile antibody detection test.
Inactivated serum + 1% sheep RBC
suspension  370C  4 hrs 
Agglutination (>100)
3. EBV Specific antibodies:
EBNA Ab EBNA
Ig M VCA, Ig G VCA
4. PCR: More sensitive.
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60. HHV – 6 & HHV -7
Isolated in 1986
Transmission through Oral secretions.
It is thought that HHV-6 and HHV-7 are related to each other
in a similar manner to HSV-1 and HSV-2.
Roseola infantum (Exanthema subitum)
•High fever with generalized rash.
•Chronic fatigue syndrome.
60

61. HUMAN HERPES VIRUS 8
• Originally isolated from cells of Kaposi’s sarcoma (KS)
• Firmly associated with Kaposi’s sarcoma
• Most patients with KS have antibodies against HHV-8