HERPES SIMPLEX 1 & 2

Causes painful vesicles on the skin at the site of inoculation

HSV1 associated with oro-facial lesions
HSV2 associated with genital lesions
Epidemiology:
HSV1 infection is universal, 100% adults have HSV-1 specific antibodies due to its exposure in
the first few years
HSV2 acquired in adulthood like sexual intercourse, 40% develop antibodies
Transmitted thru shedding of its virus from the lesions or mucus membrane, spreads thru direct
contact through kissing (HSV1), sex (HSV2)

Clinical features:

1) Primary infection: primarily asymptomatic, may have painful blistering rash after 1-3 days post
exposure, localized lesion and may spread to other areas thru auto inoculations

Symptoms are determined by the site of inoculation:

1) Gingivo-stomatitis most common form of primary infection, inoculation through kissing,

painful vesicles inside the mouth, gums, lips and skin around the mouth, vesicles inside the
mouth ulcerates, lesions may occur on the head and neck, self limiting and lesion may heal
within 14 days
2) Eczema herpeticum superinfection of eczematous skin, inoculation into the fingers, an
occupational hazard of medical health workers
3) Conjuctivitis, keratitis lesion on the cornea is called dendritic ulcer because of its branching
appearance, prominent paint & photophobia, edema on the lids, lesion usually heal within 3
weeks
4) Genital herpes due to HSV2, 20-30% due to HSV1, sexually transmitted, vesicles on the genitals
& peri-anal area, maybe confined to the cervix for females, primary eruption last 14-21 days and
maybe associated with specific meningitis

Latency:

Following primary infection, virus enters sensory nerves at the site of inoculation, travels up to
the axon, establish a latent infection in the ganglion supplying the area of the skin, genital area
sacral ganglion, oro facial trigeminal ganglion
Viral genome persists in the plasmid in the nucleus
Periodically, virus reactivates from its latent state: cycle of viral replication in the neuron and
new virus travels down the axon to re-infect the skin
Reactivation may be provoked by stimuli like stress, febrile case, menstruation,
immunosuppression
Clinical features of reactivation:

1) Cold sores (follows gingiva-stomatitis)

2) Vesicles erupt on the muco-cutaneous junctions of the nose & mouth
3) Lesions are more localized than primary infection heals 7-10days
4) Eruption is preceded by paraesthesia of the involved area
5) Recurrent genital herpes
6) Lesions are less extensive, heals more rapidly
7) Recurrence with HSV2 more common than HSV1
8) Rarely, some patients develop aseptic meningitis (Mollarts syndrome) associated with HSV2
infection
9) Keratitis primary infection of the eye, after reactivation the virus reaches cornea via the
ophthalmic trigeminal nerve, dendritic lesion, heals rapidly than primary infection

Clinical syndromes:

1) Acute necrotizing encephalitis infection of the brain, affects neuron of the temporal lobe,
severe & necrotizing infection
Sudden onset of fever, headache, altered personality
High mortality, neurological impairment
May have encephalitis during primary infection or after reactivation
2) Neonatal infection rare, serious infection, poor cell mediated immunity resulting to higher risk
of infection

Exposure may occur:

1) During birth if the mother has genital herpes at the time of delivery, at risk if the mother has
primary infection
2) Post natal period, if the baby is handled by people with herpes lesions
Three forms of disease:
1. Cutaneous
2. Encephalitic
3. Generalized infection disseminated infection, serious case, high fatality includes jaundice,
hepato-splenomegaly, thrombocytopenia, pneumonia, encephalitis, skin lesions
3) Disseminated HSV infection in adults maybe a fulminant case, leads to death before diagnosis
is made, might be fulminant hepatitis, pneumonitis, multi-organ failure or encephalitis
Laboratory diagnosis:

1) Direct detection electron microscopy herpesvirus particles in vesicle fluid

2) Immunofluorescence viral antigen in smears from vesicles
3) Cell culture inoculated into cell monolayers from skin lesions
4) Serology IgG indicates immunity (past exposure)
IgM marker of primary or recurrent infection, but not a reliable marker
5) PCR detects viral genome in clinical materials, HSV PCR on CSF is the test choice for confirming
the diagnosis of HSV encephalitis

Therapy:

Acyclovir drug of choice for treating HSV, interferes viral replication but not active against
latent virus, activity against HSV & VZV & low toxicity

VARICELLA ZOSTER VIRUS

(2) clinical entities:

1) Varicella chicken pox

2) Zoster shingles

Varicella common childhood infection with rare complications, mild febrile illness with
generalized vesicular rash, vesicles erupt in successive crops so that lesions of different ages
are present at the same time after a prodromal period
Lesions progress from macule papule into vesicles pustule scab
For delayed infection until adulthood it maybe severe with complications like pneumonia
At least 21 days incubation period
Transmission thru respiratory droplets or skin lesions direct contact
Primary infection means long lasting immunity

Complications:

1) Post infectious encephalomyelitis self limiting case with good prognosis

2) Pneumonia common among adults
3) Hemorrhagic varicella fulminating infection in immunocompromised patients, high fatality rate
4) Congenital varicella syndrome (vertical transmission) develop among infants born to varicella
infected mothers in the first 20 weeks of pregnancy, infected infants may develop shingles in the
first 18 mos (rare conditions) like limb hypoplasia, muscular atrophy, mental retardation, skin
scarring
Perinatal varicella (post natal transmission)

Infant is infected if mother is infected during perinatal period, mother develops rashes more
than (5) days before delivery, maternal anti-varicella antibodies acquired transplacentally will
protect the neonates, if not then any infant less than (6) months exposed to varicella post
natally receives an VZ hyperimmune globulin as a passive form of infection

Shingles (Zoster)

Reactivation lesions of VZV

Establishes a latent infection in sensory ganglia
Reactivation usually occurs many years after primary infection and is associated with
immunosuppression of the host
After a cycle of infection in the ganglion, virus particles travel to axon to re-infect producing
painful vesicles
Post herpetic neuralgia is a common complication especially in elderly
Rash, new lesions appear for 3-4 days, satellite lesions may appear in remote dermatome
Vesicles evolve like varicella healing complete in 2 weeks
Post herpetic neuralgia common complication, pains in affected dermatome may persist for
months or years after rash has healed, ophthalmic complications, cranial nerve VII, VIII, includes
Bells palsy

Vaccine: live attenuated of varicella zoster released in 2002, highly effective as post exposure
prophylaxis if given 72 hrs of exposure

Laboratory Diagnosis:

1) PCR most sensitive in detecting virus in clinical samples

2) Cell culture
3) Serology IgM antibodies are present both primary infection (varicella) and during reactivation
(zoster)
4) IgM indicates immunity

Treatment: uncomplicated case resolves without treatment; acyclovir especially with complications
Cytomegalovirus

Man is infected in the first few years of life and adulthood 70-90% develop IgG antibodies
Patients may develop an infectious, mononucleosis-like illness associated with fever, sore
throat, lymphadenopathy when primary infection occurs in adulthood
Transmission: virus is shed asymptomatically in the saliva and other body fluids of healthy
carriers, transmitted thru close contact, mother to child in utero or thru breastfeeding, blood
transfusion, organ transplantation

Two clinical situations where infection causes serious disease:

1) Congenital disease infants at risk from infected mother CMV reactivation in pregnancy is
common & result fetal infection
- Clinical features: most infected babies appear normal at birth but later develop deafness
and mental retardation
2) Infection in immunosuppressed patients transplant patients & AIDS patients develops life
threatening disease following primary infection or reactivation, common syndromes like
interstitial pneumonia, retinitis, enteritis, CMV pneumonia (common death in HIV patients)
- Infection in normal host asymptomatic but may result into mononucleosis

Treatment: nucleoside analogue ganciclovir used to treat severe life threatening infections
immunocompromised patients with toxic effects

Laboratory diagnosis: seropositive individuals harboring the virus in their tissues & may reactive and
shed regularly through life without causing disease

1) Direct detection detected thru immunofluorescence (pp65), a positive pp65 means significant
disease
2) Cell culture
3) Serology IgG indicates previous exposure, harbors latent virus, IgM indicates recent primary
infection or reactivation
4) PCR most reliable method
Epstein-Barr Virus

Most infected by the time they reach adulthood

Succeeding primary infection the virus persist in a latent form in B lymphocytes of the host
Sporadic reactivation is associated in shedding in saliva
Transmission: close contact or kissing
Clinical syndrome:
1) Infectious mononucleosis (primary infection)
2) Lympho-proliferative disorder in immunocompromised
3) Burkitts lymphoma
4) Tumors eg. Form of Hodgkins disease
5) Oral hairy leuoko-plakia

Infectious Mononucleosis (IM) illness from primary infection, 4-7 days incubation period, close
contact or kissing excreted thru saliva, self limiting but some cases of prolonged convalescence
Laboratory diagnosis:
1) Heterophile antibody Paul Bunnel test (Monospot): screening test for acute IM;
70-80% develop IgM antibodies that agglutinate sheep RBC
2) Specific serologic test antibody to the viral capsid and nuclear antigens are useful for
confirming acute IM
IgG and IgM to viral capsid antigen (VCA) detected early during acute phase VCA IgM
IgG to EBV nuclear antigen (EBNA) detected in late convalescence (>6 months post
infection)

B cell and latency EBV infects B cells & forms latent infection, six viral genes, EBNA1-6 are
expressed during latent stage, transform B cell into an immortal, continuously dividing cell
Lymphoproliferative disorders immunosuppressed patients especially organ transplant
patients develop polyclonal proliferation of their own EBV transformed B cells due to impaired
ability to eliminated EBV infected cells, occasionally proliferating cells may undergo malignant
transformation resulting to mono-clonal malignant tumor, this nonHodgkins lymphoma are
highly aggressive and atypical locations like CNS in AIDS patients
Burkitts lymphoma (BL) high grade B cell lymphoma, 100% aggressive BL tumors are
associated with EBV causing malignancy due to DNA damaging events

Nasopharyngeal carcinoma malignant tumor of the squamous epithelium of the nasopharynx,

undifferentiated forms are associated with EBV

Hodgkins disease mixed cellularity & lymphocyte depleted forms, history of adult infectious
mononucleosis associated with threefold increase incidence

Oral hairy leukoplakia proliferation of oral squamous epithelium caused by EBV, painless
lesions white plaques on the tongue, common among HIV patients
Human Herpesvirus 6 (HHV6)

Primary infection is usually acquired early in life

Launches a latent infection
Clinical features: mostly asymptomatic, diseases usually includes:
1) Roseda infantum primary lesions in babies, a febrile illness with rash which occurs in
the first few months of life
2) Infectious mononucleosis like illness in adults experiencing primary infection
3) Interstitial pneumonitis & encephalitis in immunocompromised patients
Primary infection in infants are usually asymptomatic, 20% cases may develop high fever with
eruption of maculopapular rash as fever subsides, later establish latency
Epidemiology: virus is shed thru saliva & other body fluids as carriers, transmitted from mother
to child or between siblings

Herpes Virus
HUMAN HERPES VIRUS 7 (HHV7)
Closely related with HHV6
Isolated from the peripheral blood mononuclear cells
Not known to cause any disease
Human herpesvirus 8 (HHV8)
Was identified in the tissues of a Kaposi sarcoma patient
Low prevalence having .2 10% adults develop antibodies
Develops a persistent latent infection on the host
Not pathogenic among healthy people yet essential in the malignant process of Kaposi sarcoma,
(primary effusion lymphoma in AIDS patients, multicentric Castlemans disease