1. HERPES VIRUS

2. HERPES VIRUS are capable of causing overt disease
or remaining silent for many years
only to be reactivated, eg shingles.
The name herpes comes from the Latin -herpes which, in turn, comes from the Greek word herpein which means to creep.
This reflects the creeping or spreading nature of the skin lesions caused by many herpes virus types.
There are 25 families in the Herpetoviridae but only eight of them are known to infect man

3. Important human pathogens
Herpes simplex virus Type 1 (HSV1)
Herpes simplex virus Type 2 (HSV2)
Varicella Zoster Virus (VZV)
Epstein Barr virus (EBV)
Cytomegalovirus (CMV)
Herpes lymphotropic virus (HHV6)
Human herpes virus 7(HHV7)
Human herpes virus 8 HHV8)((Kaposi's sarcoma-associate herpes virus)

4. Properties of Herpes virus
All are structurally similar
They are DNA, enveloped virus
They are larger nm in diameter second only to poxvirus
They are the only virus that obtain their envelopes by budding from the nuclear membrane
The virion does not contain polymerase
They are noted for their ability to cause latent infections.

5. STRUCTURE

6. classification of herpes viruses

7. Herpes simplex virus HSV-1 and HSV-2
Lesion caused by HSV-1 are above the waist while those caused HSV- 2 are below the waist
but both types of HSV can infect oral or genital mucosa depending on the regions of contact.

8. Epidemiology HSV 1 and 2 infections are life long
The virus is found in the lesions on the skin and in body fluid
HSV-1 is transmitted primarily in saliva
can spread by kissing
or the use of utensils contaminated with saliva
or by transfer of infectious virus to the hands after which the virus may enter the body via any wound or through eyes

9. Anyone who comes in contact with the fluid containing virus is at risk
Care workers are affected by disease called herpetic whitlow that results in lesions on the fingers
HSV-2 infection is most prevalent in life as number of sexual contact increases
Thus the lowest rates of infection are in children

10. HSV 1 becomes latent in the trigeminal ganglia
Pathogenesis
The virus replicate in the skin or mucous membrane at the initial site of the infection
Then migrate up the neuron and become latent in the sensory ganglion cells
HSV 1 becomes latent in the trigeminal ganglia
HSV-2 becomes latent in the lumber and sacral ganglia
The viruses can be reactivated from the latent by the variety of induces sunlight, hormonal changes, trauma, stress and fever
at which time it migrates down the neuron and replicate in the skin causing lesions

11. Diseases caused by HSV-1 and HSV-2

12. Clinical presentation of HSV-1
1.Gingivostomatitis
occurs in children,
characterized by fever,
irritability and vesicular lesions in the mouth
The lesions heal spontaneously in 2-3 weeks
Many children have asymptomatic primary infections
Herpetic gingivitis 

13. 2.Herpes labialis (Fever blisters or cold sores)
characterised by
crops of vesicles at the mucocutanous junction of the lips or nose
Recurrences frequently reappear at the same site

14. 4.Encephalitis 3.Keratoconjuctivitis
Patients with HSV keratitis may complain of
Pain
Photophobia
Blurred vision
Tearing
Redness
The earliest sign of active viral replication in the corneal epithelium is the development of small, raised, clear vesicles
recurrence can lead to scarring and blindness
4.Encephalitis
Involve the temporal lobe
has high mortality rate
causes severe neurological sequel in those who survive

15. Is a pustule lesion of the skin of the finger or hand
5.herpes whitlow
Is a pustule lesion of the skin of the finger or hand
it is most commonly contracted by dental workers and medical workers exposed to herpes lesions

16. Symptoms of herpetic whitlow
include swelling,
reddening and
tenderness of the skin of infected finger.
This may be accompanied by fever and swollen lymph nodes

17. Disseminated infections such as
esophagitis and pneumonia,
occur in immunocompromised patients
with depressed T cell function

18. HSV-2 presentation 1. Genital herpes
painful vesicular lesions of the male and female genitals and anal area
The lesions are more severe in primary disease than in recurrences
Primary infection is associated with fever and inguinal adenopathy.
Asymptomatic infections occur in both men (in prostate or urethra) and women (in the cervix) it can be the source of infection to other individuals.

19. Genital herpes on the penis
© Australian Herpes Management Forum

20. Genital infection IN MALE AND FEMALE

21. HSV proctitis
This is an inflammation of the rectum and the anus

22. 2. Neonatal herpes
Originates from contact with vesicular lesions within the birth canal
can be prevented by performing caesarean section on women with either active lesions or positive viral cultures

23. Both HSV1 and HSV2 can cause severe neonatal infections that are acquired after birth from carriers handling the child
Despite their association with neonatal infections neither HSV1 nor HSV2 cause congenital abnormalities to any significant degree
Aseptic meningitis
Caused by HSV2
is usually mild and self limited disease

24. The present of multinucleated giant cells suggests Herpes infection
Laboratory diagnosis
Isolation of the virus from the lesion by cell culture then detecting virus specific glycoprotein by enzyme-linked immunosorbent assay (ELISA)
Diagnosis from skin lesions can be made by the Tzanck smear in which cells from the base of the vesicle are stained with Giemsa stain.
The present of multinucleated giant cells suggests Herpes infection

25. Encephalitis can be diagnosed by detecting HSV-1 DNA in the spinal fluid using PCR
Neonatal herpes can be diagnosed by use of viral culture or PCR

26. Treatment
Acyclovir the treatment of choice of encephalitis and systemic diseases caused by HSV-1 also in primary and recurrent genital herpes also neonatal infection caused by HSV-2
It shortens the duration of the lesions and reduces the extent of shedding of the virus
Mutant resistant acyclovir have been isolated from patients
famciclovir and valacyclovir can be used in this cases

27. Avoid contact with the vesicular lesion or ulcer
Prevention
Avoid contact with the vesicular lesion or ulcer
Caesarean section is recommended for women at term who have positive viral culture

28. VARICELLA ZOSTER VIRUS
CHICKENPOX AND SHINGLES

29. This virus causes two major diseases, chicken-pox (Varicella), usually in childhood,
and shingles, later in life.
Shingles (Herpes zoster) is a reactivation of an earlier varicella infection.

30. This virus is highly infectious It is spread by respiratory aerosols
Chicken pox
This virus is highly infectious
It is spread by
respiratory aerosols
or direct contact with skin lesions.

31. Pathogenesis The virus infect the mucosa of URT
The virus spread from the URT to lymphocytes
and monocytes and to the reticulo- endothelial system where second viremia occurs
and the virus travels to the skin, mouth, conjunctiva, respiratory tract and to epithelial sites throughout the body forming papule containing multinucleated cells with intracellular inclusions.

32. Incubation period 14-21 days Brief symptoms of fever and malaise occur
Clinical features
Incubation period days
Brief symptoms of fever and malaise occur
Papule vesicular rash then appear in crops on the trunk and spread to the head and extremities.
The rush evolves from papules to vesicles, pustules and finally crust. Itching is marked

34. Complications
Varicella pneumonia and encephalitis are the major rare complications
Reye’s syndrome characterised by encephalitis and liver degeneration esp. in children given aspirin
Its pathogenesis is not known

35. ZOSTER (Shingles)
The occurrence of painful vesicles along the course of a sensory nerve of the head or trunk
Reactivation can lead to chronic burning or itching pain called post-herpetic neuralgia which is seen primarily in the elderly
In immunocompromised patients life threatening disseminated infections such as pneumonia can occur
Diagnosis
Most diagnosis are made clinically
Treatment
No antiviral therapy is necessary for chicken pox or shingles in normal patients
Immunocompromised patients can be treated with acyclovir

36. Prevention
Varicella- zoster immune globulin (VZIG) (effective in preventing varicella but not zoster)
There is a live attenuated vaccine (Varivax) for varicella but is not effective in zoster
and can not be used for immunocompromised patients or pregnant women

37. chickenpox of the new-born
chickenpox of the new-born. The infant contracted chickenpox at birth from her infected mother.

38. chickenpox rash. Some of the sores are red spots and some are blisters

40. Severe atypical episode of shingles affecting the trunk of a person with impaired immunity
Shingles affecting the left side of the trunk

41. Recurrent varicella zoster on the right side of the face
Facial shingles.

42. Presentation of varicella and zoster

43. CYTOMEGALOVIRUS

44. CYTOMEGALOVIRUS Cause
cytomegalic inclusion disease (esp. congenital abnormalities) in the neonates
2.pneumonia in immunocompromised individuals

45. Early in life CMV can be transmitted across the placenta
Transmission
Early in life CMV can be transmitted
across the placenta
within the birth canal
and in breast milk
In young children –Via saliva
Later in life-sexually transmitted
It is present in secretions - saliva, urine, vaginal and semen
The virus can also be spread via blood transfusions and transplants.

46. then local lymphocytes.
Pathogenesis
The virus first infects the upper respiratory tract and
then local lymphocytes.
Circulating lymphocytes then spread the virus to other lymphocytes and monocytes in spleen and lymph nodes.
finally spreads to a variety of epithelial cells including those of salivary glands, kidney tubules, testes and cervix.
Infection is usually asymptomatic (sub-clinical)

47. Congenital disease Abnormalities include
There are two instances in which cytomegalovirus can cause serious disease.
1.During a primary infection of the mother (in utero)
the virus can spread via the placenta to the fetus and congenital abnormalities can occur;
this virus is the most common viral cause of congenital disease.
Abnormalities include
microcephaly,
brain calcification
hepatosplenomegaly
hearing loss,
seizures
and mental retardation can occur

48. If the mother has antibody that will neutralize the virus the foetus will not be infected.
If the foetus is infected during first trimester congenital defects may result
because this is when the organs began to develop

49. 2.Perinatally
Besides infection in utero, infants may be infected perinatal
As noted above, one tissue in which cytomegalovirus can set up a latent infection is the cervical epithelium and immunosuppression associated with pregnancy can lead to reactivation.

50. Also breast epithelium can harbor latent virus that may be similarly reactivated leading to infection of the infant.
Neonates may also receive the virus through infected blood transfusions.
In this case, the amount of virus is much higher and symptoms may occur.
These usually consist of pneumonia and hepatitis.

51. Clinical findings
Approx.20% of infants infective with CMV during gestation show clinically apparent manifestations of cytomegalic inclusion disease such as microcephaly, deafness and jaundice
Hepatosplenomegaly is very common
Cytomegalic inclusion is the leading cause of mental retardation
Infected infant can continue to excrete CMV especially in the urine for several years

52. In immunosupressed adult CMV can cause heterophil-negative mononucleosis which is characterized by
fever
lethargy
and the presence of abnormal lymphocytes in peripheral blood smears

53. Systemic CMV infection especially pneumonitis and hepatitis is high in immunosuppressed patients
eg those with renal and borne marrow transplants
in AIDS patients CMV commonly affects the intestinal tract and cause intractable diarrhoea.
CMV also cause retinitis in AIDS patients which can lead to blindness

54. Lab diagnosis Cell culture Fluorescent antibody
and histologic staining of inclusion bodies in giant cell in urine and in tissue
Treatment
Ganciclovir is effective in treatment of AIDS patients with pneumonia and retinitis
Forscarnet( foscavir) is also effective but cause side effects
CMV is resistant to Acyclovir

55. Prevention
No vaccine
Infants who are shedding viruses in their urine should be kept isolated from other infants
Blood transmission to new born should be CMV antibody negative
if possible only organ from CMV antibody negative donors should be transplanted

56. EPSTEIN BARR VIRUS

57. Epstein-Barr virus is the causative agent of Burkett's lymphoma
Nasal pharyngeal carcinoma
Oral hairy leukoplakia- in lesions in the mouth
and Infectious mononucleosis

58. Transmission and epidemiology
is transmitted primarily by exchange of saliva
e.g. during kissing
Is most common infection worldwide
Infection in the first few years of life is asymptomatic
Is highest in those who are exposed to virus later in life e.g college students

59. Cytotoxic T lymphocytes react against the infected B cells.
Pathogenesis
The infection first occur in oropharynx and then spread to the blood where it affects B lymphocytes
Cytotoxic T lymphocytes react against the infected B cells.
EBV remain latent within B lymphocytes

60. Clinical findings Characterized by fever , sore throat,
lymphadenopathy
and splenomegaly
Anorexia and lethargy are prominent
Hepatitis is frequent
Encephalitis occurs in some patients
Spontaneous recovery usually occur in 2-3 wks.
In immunosupressed patient infection is severe and is often fatal

61. Lab diagnosis
Hematological approach where abnormal lymphocytes are seen on the smear
The EBV-specific antibody test

62. Treatment
No antiviral therapy is necessary for uncomplicated infections mononucleosis
Acyclovir has little activity against EBV but higher doses may be useful in life threatening EBV infections
No EBV vaccine

63. This virus is found worldwide
OTHER HERPES VIRUSES  
Human herpes virus 6
This virus is found worldwide
is found in the saliva of the majority of adults (>90%).
It infects almost all children by the age of two and the infection is life-long.
Again, it replicates in B and T lymphocytes, in the oropharynx.

64. Human herpes virus-6 has two forms,
HHV-6A and HHV-6B. 
The latter causes exanthem subitum.
symptoms include fever and sometimes upper respiratory tract infection and lymphadenopathy.
The symptoms last a few days after an incubation period of around 14 days.

65. exanthem subitum macropapular rash

66. The fever subsides leaving a macropapular rash on the trunk and neck that last a few days longer.
This virus may co-infect HIV-infected T4 lymphocytes exacerbating the replication of HIV.

67. Patients with HIV have a higher infection rate than the normal population.  
HHV-6 has  been associated with a number of neurological disorders, including encephalitis and seizures.
It has been postulated to play a role in  multiple sclerosis and chronic fatigue immunodeficiency syndrome. 

68. Human herpes virus 7
This virus binds to the CD4 and replicates in T (CD4+) cells and is found in the saliva of the majority of the adult population (>75%).
Most people acquire the infection as children and it remains with them for the rest of their lives.
It is similar to HHV-6 and may be responsible for some cases of exanthem subitum

70. It infects peripheral blood lymphocytes.
Human herpes virus 8
This is known as Kaposi's sarcoma associated herpes virus and is found in the saliva of many AIDS patients.
It infects peripheral blood lymphocytes.

71. Sexually transmitted through semen.
transmission
Sexually transmitted through semen.
Transmitted through mother to child
Organ transplant

72. This is a simian virus found in old world monkeys
Herpes B
This is a simian virus found in old world monkeys
but it can be a human pathogen in people who handle monkeys (monkey bites are the route of transmission).
In humans, the disease is much more problematic than it is in its natural host.

73. about 75% of human cases result in death with serious neurological problems (encephalitis) in many survivors.
There is also evidence that the disease can be passed from a monkey-infected human to another human.
In vitro the virus is sensitive to both Acyclovir and Ganciclovir and these are recommended for therapy. Their efficacy is unknown. 

74. Papillomavirus

75. Papillomavirus (HPV) - Properties
Non enveloped, DNA virus
small 60nm diameter
These viruses are very difficult to study
as they do not grow in cell cultures and experimental animals.

76. About 70 different types of papilloma virus can infect humans
They account for more than 80% of cervical cancers
Cause papillomas (benign tumors of squamous cells) e.g. warts on the skin
Penile, vulvar and rectal cancers are also associated with HPV.

77. Highly adopted to human skin and mucosa
At least 25 types including HPV 6,11,16 and 18 can infect the genital area and are sexually transmitted.
HPV 1 and 4 causes plantar warts
HPV 2,3 and 10 causes warts on the knees and fingers.
Subtypes 6 and 11 account for 90% of genital warts

78. Warts Warts can be Filiform with finger-like projection Flat topped,
Flat as they grow inwards due to external pressure (planter warts)
A cauliflower-like protuberance (e.g. genital warts)
A flat area of dysplasia on the cervix
Epidermal dysplasia verruciformis

79. Genital warts are among the most common sexually transmitted diseases
Transmission
By skin to skin contact
Genital warts are among the most common sexually transmitted diseases
Skin warts are more common in children and young adults and tend to regress in older adults
Warts viruses can survive on inanimate objects such as; wrestling mats, towels and shower floors

80. The cells grow abnormally and produce warts.
Pathogenesis
PV infect squamous epithelial cells induce within those cells a characteristic cytoplasmic vacuoles.
These vacuolated cells called koilocytes are the hallmark of infection by these virus.
The cells grow abnormally and produce warts.
Most warts are benign( and do not progress to malignancy

81. Penile warts

82. Vagina warts

83. Treatment - warts
Like other tumors, warts can be treated by killing or removing all abnormal cells.
To accomplish this;
- Wart cells can be destructed by application of karyolitic agents (i.e. salicylic acid)
- Freezing with dry ice (solid CO2) or liquid nitrogen.
- By burning the tissue with an electrically heated needle
- Or by surgical removal

84. Most HPV infections resolve spontaneously
For those infected with the high risk subtypes, roughly 5-10% will develop persistent HPV infection
It is estimated that 40% of young women are infected with HPV within 3 years of starting sexual activity.
Up to 80% of women acquire the HPV infection at least once during their lives.

85. Persistent HPV infection
Persistent HPV infection disrupts the normal cell turnover at the transformation zone
With the cells multiplying perpetually, pre-cancerous cells form.
The pre-cancerous cells could, in the long run, invade underlying tissue: Invasive cancer
The process from HPV infection to cancer is very slow taking many years, even decades.

86. Physical symptoms of cervical cancer may include
Signs and symptoms
The most common finding in patients with cervical cancer is an abnormal Papanicolaou (Pap) test result.
Physical symptoms of cervical cancer may include
Abnormal vaginal bleeding
Vaginal discomfort
Malodorous discharge
Dysuria

87. Because many women are screened routinely, the most common finding is an abnormal Papanicolaou (Pap) test result. Typically, these patients are asymptomatic.
Clinically, the first symptom of cervical cancer is
abnormal vaginal bleeding, usually postcoital.
vaginal discomfort,
malodorous discharge,
and dysuria

88. The tumor grows by extending
along the epithelial surfaces,
both squamous and glandular,
upward to the endometrial cavity,
throughout the vaginal epithelium,
and laterally to the pelvic wall.

89. It can invade the bladder and rectum directly,
leading to constipation,
hematuria,
fistula,
and ureteral obstruction, with or without hydroureter or hydronephrosis.
The triad of leg edema, pain, and hydronephrosis suggests pelvic wall involvement.
The common sites for distant metastasis include extra pelvic lymph nodes,
liver, lung, and bone.

90. Early age of becoming sexually active Multiple sex partners
risk factors
Early age of becoming sexually active
Multiple sex partners
Unprotected sexual intercourse: condoms estimated to give around 70% protection against HPV.
Concomitant STIs

91. Penile cancer

92. Anal Cancer

93. Oropharyngeal cancer

94. prevention Achieved through regular screening
Treatment of pre-cancerous lesions
The vast majority of cervical cancer deaths are in developing countries largely because of lack of screening programmes
Limited resources (supplies, trained personnel, equipment, quality control, health care infrastructure, and effective follow-up procedures)
? Political will

95. Screening:
LIQUID BASED CYTOLOGY (LBC) /PAP SMEAR
Sample collected using a brush with a detachable head
The head with the sample is detached into the specimen pot with the preservative.
In the laboratory, the fluid with the sample is spun to separate and remove contaminants e.g. Pus, inflammatory cells and mucus.
The remaining cervical cells are then made into a thin layer on a slide and read under a microscope as normal
Adoption of this method has reduced the recall rate from 1 in 10 to 1 in 100.

96. Brush for LBC
Traditional Pap Smear

97. Visual inspection with acetic acid (VIA)
Also called ‘direct visual inspection’ or cervicoscopy
An alternative to cytologic examination in low-resource settings.
Involves applying 3-5% Acetic acid (vinegar) to the cervix using a spray or cotton swab.
Observe the cervix with a naked eye after 1 minute
Obvious acetowhite areas would be regarded as positive for at least pre-cancerous cells.
VIA does not require a laboratory or intensive staff training and results are immediately available.

98. Acetowhite
Normal cervix

99. Visual Inspection with Lugol’s Iodine: VILI
VILI stands for Lugol’s iodine is applied to the cervix and this is inspected for non- staining areas.
Results of VILI are immediately available, offering the advantage of treatment or follow-up care without delay.

100. Other Screening Methods HPV DNA testing
Detects DNA from 13 high risk genotypes
A sample of cells collected from the vagina or cervix using a swab or brush
Laboratory processed
Very good in identifying those who already have cervical disease and those at high risk of developing it
Remains quite expensive

101. ..The Fast HPV Test detect DNA from 14 high-risk types of HPV.
Results available in hours
The test equipment is portable, with the option of battery power.

102. Primary Prevention: Vaccination
Vaccination against the high risk HPV subtypes now available
Gardasil® protecting against infection by subtypes 16 and 18 as well as 6 and 11
Cervarix™ protects against subtypes 16 and 18.
Both are administered in the form of injections.
Three injections given in intervals over a course of six months.

103. HPV vaccination
Aim is to get girls vaccinated before they become sexually active and exposed to the virus.
The vaccines have been shown to be almost 100% effective in preventing dysplasia and subsequent cervical cancer
In addition, effective in preventing, the related albeit less common vulvar and vaginal cancers.