--HERPES VIRUSES—
HERPES SIMPLEX VIRUSES VARICELLA-ZOSTER VIRUS
PROPERTIES ~ belong to alphaherpesvirus subfamily
~ genomes HSV-1 & HSV-2 share 50-70% homology
~ share several cross-reactive epitopes w each other
~ some antigenic cross-rxn w VZV
~ man is only natural host for HSV
EPIDEMIOLOGY ~ spread by contact, virus shed in saliva, tears,
genital & other secretion, kiss given to child
~ primary infxn maybe subclinical in most pt,
disease mainly of below 5 yrs.
~ 2 peaks of incidence, 1st at 0-5 yrs and 2nd in late
teens; when sexual activity commences
~ generally, HSV-1- infxn above the belt
HSV-2- elow the belt
~ 40% fr genital sores are HSV-1, 5% fr facial sores
are HSV-2 (d2 oral sexual practice)
~ actual recurrence frequency varies. Mean number
of episodes per year is 1.6
PATHOGENESIS during primary infxn, HSV spread locally and a
short-lived viraemia occur. Spead to sensory
craniospinal ganglia
virus established latency in craniospinal ganglia
~ exact mechanism of latency is unknown
~ reactivation : triggered by physical/psychological
stress, pneumococcal and meningococcal infxn,
fever, irradiation like sunlight and menstruation
~ infect & replicate in mucoepithelial cell--- disease
at siteof infection
CLINICAL ~ acute gingivostomatitis
MANIFESTATION ~ herpes labialis ( clod sore )
~ ocular herpes
~ herpes genitalis
~ other form of cut, herpes
~ meningitis
~ encephalitis
~ neonatal herpes
LAB DX ~ direct detection
– EM of vesicle fluid, rapid result but cant
distinguish btwn HSV-VZV
- imunoflrescence of skin crapping – distinguish
btwn HSV-VZV
~ virus isolation – rapid growth in 1-3 days
~ serology- not that useful bcoz takes 1-2 wks b4 Ab
appear, used to document recent infection
MANAGEMENT ~ Acyclovir- drug choice, available in :
- I.V ( in normal & immunosupprssed pt)
- Oral (tx & long term suppression of mucocut,
herpes & prophylaxis in immunosuppressed
pt)
- Cream ( skin & mucous membrane)
- Ophthalmic ointment
~ famciclovir and valacyclovir- oral only, costly
~ belong to alphaherpesvirus subfamily
~ one antigenic serotype only, although there is some
cross reaction w HSV
~ primary infection is Varicella- endemic, one of
classical papulo-vesicular exanthematous disease of
childhood, prevalence occur in 4-10 yrs old
~ varicella; highly communicable, 90% in close cntct
~most infected b4 adulthood but 10% young adult
remain susceptible
~ herpes zoster, in contrast, occur sporadically, and
evenly throughout the year
~ virus is thought to gain entry via the respi. Tract
and spread shortly after to the regional lymphoid
system and blood causing viraemia
~ after incubation period 14 days, 2ndary viremia the
virus arrives main target organ, the skin.
~ remain latent in cerebral or posterior root ganglia,
in 10-20% pt, single recurrent infection occur after
several decades
~ reactivates in sensory ganglion and track down
sensory nerve to area of skin innervated by
nerve,producingvaricelliform rash in distribution of
dermatome
~ immunity following infection is lifelong (>20)
~ varicella
~rash of chicken pox
~ herpes zoster (shingle)
~congenital VZV infection
~ neonatal varicella
~ virus isolaton- fr ulcer fluid, 1 week for result
~ direct detection- EM of vesicle fluid, rapid result
but cant distinguish btwn HSV-VZV
- imunoflrescence of skin crapping – distinguish
btwn HSV-VZV
- Tzanck Smear – stained ulcer swab / giant cell
~ serology- VZV IgG indicate past infection &
immunity , IgM indicate recent primary infection
~ PCR
~ self-limited, so no specific tx
~ Acyclovir : to immunocompromised pt and normal
ppl w serious complication(pneumonia &
encephalitis
~ ~ famciclovir and valacyclovir
~ passive immunization ( Zoster Ig)
~ live attenuated vaccine is available
 CYTOMEGALOVIRUS
PROPERTIES ~ belong to Betaherpesvirus subfamily
EPIDEMIOLOGY ~ transmission occur in uterus, perinatal or postnatal
~ latency: once infectedm carries for life
~ maybe reactivated fr time to time, during which
virions appear in saliva and urine
~ reinfection may occur, do not differ fr reactivation
~ in dvloped countries w high hygiene, 40-70%
inected
~ in dvlping countries, 90% infected
PATHOGENESIS Once infected, virus remain for life and may
reactivated, esp in immunocompromised person
~ perinatal infection- thru genital secretion, breast
milk, 10 times common than congenital infection
~ 2-10% infants infected at 6 months worldwide
~ postnatal infection- thru saliva, sexual tansmission
may occur as well as blood & transplanted organs
CLINICAL ~ congenital infection-
MANIFESTATION - 2nd most cause of mental retard, 40% chance
follow primary infection
- Maybe transmitted to fetus in all stages
- No evidence of teratogenicity, damage of fetus
result fr destruction of target cell once ther are
formed
cytomegalic inclusion disease:
- CNS abnormalities( microcephaly, retardation,
spastic, epilepsy)
- Eye- optic atrophy & choroidoretinitis
- Ear – sensorineural deafness
- Liver- hepatosplenomegaly, jaundice
- Lung(pneumonia), heart(myocarditis)
- Late sequela- sensorineural deafness & low IQ
~ perinatal infection- asymptomatic
~ postnatal infection- asymptomatic
~ immunocopromised : retinitis, colitis, encephalpthy
~ reactivation or reinfection is asymptomatic except
in immunocompromised pt
LAB DX ~ direct detection
-pp65 CMV antigaenaemia test for rapid dx
-biopsy specimen for CMV inclusion Abs
~ virus isolation-4 weeks for result. DEAFF test give
result in 24-48 hours
~ serology: IgG (past infection) IgM (primary infxn)
~ PCR assays
MANAGEMENT Tx :
~ congenital infection : choice of abortion
~ peri and postnatal infection: no need to treat
~ immuncompromised : antiviral therapy,
ganciclovir, foscarnet, cidofovir
Prevention:
~no vaccine available, a candidate live-attenuated
vaccine, recombinant vaccine also being developed
~ prevention in transplant recipient is complicated. It
needs measure :
- screen & match CMV status, use CMV –ve
blood transfusion, administer CMV Ig to sero-
ve recipient, give antiviral agent eg ganciclovir
EPSTEIN-BARR VIRUS
~ belong to Gammaherpesvirus subfamily
~ in dvloped cntries:
- 2 peaks infection; 1st- 1-6 yrs old, 2nd: 14-20 yrs
old
~ in dvlping cntries:
- occur much earlier at 2 yrs old, 90% kids
sero+ve
~ virus transmitted thru saliva, in kissing
~ once infected, a lifelong carrier state dvlop low
grade infection, kept in check by immune defenses
~ low grade replication & shedding in epi. Cell of
pharynx of all sero+ve person
~EBV can immortalize B-lymphocyte in vitro&vivo
~assoc w several diff diseases act directly or one of
several cofactors
~ infectious mononucleosis
~ Burkitts lymphoma
~ nasopharyngeal carcinoma
~ lymphoproliferative disease & lymphoma
~ X-linked lymphoproliferative syndrome
~ chronic infectious mononucleosis
~ oral leukoplakia in AIDS pt
~ chronic interstitial pneumonitis in AIDS
~ acute EBV usually made by heterophil Ab test
and/or detection of anti-EBV VCA IgM
~ cases of Burkitts Lymphoma diagnosed by hstology
The tumor can be stained w AB to lambda light chains
which reveal monoclonal tumor of B-cell
~caes of NPC diagnosed by Histology. Determination
of titre of anti-EBV VCA IgA is screening for lesion
Vaccination :
- vaccine that prevent primary EBV infection
should be able to control both BL & NPC
- given in early life. Useful in sero-ve transplant
recipient and those w severe IM, eg male
offspring of Xlinked proliferative syndrome
carrier
- not preferably be a subunit vaccine since there
is a danger that live vaccine still tumoregenic
- Ag chosen is the MA Ag gp 340/220
- Still try in Africa
 HUMAN HERPESVIRUS 6 AND 7 HUMAN HERPESVIRUS 8
PROPERTIES ~belong to Betaherpesvirus subfamily ~ belong to Gammaherpesvirus subfamily
~dsDNA genome of 170 kb ~ originally isolated fr Kaposi’s Sarcoma (KS)
~ main target cell is T-lymphocyte, B-lymphocyte too ~ to be firmly assoc. w KS
~ HHV-6 & 7 share limited nucleotide homology and
antigenic cross-reactivity
~ both related to each other in similar manner HSV-1
and HSV-2
EPIDEMIOLOGY ~ both ubiquitous and found worldwide
~ both infection are requied rapidly after age 4 month
when the effect of maternal AB wears off
~ by the time adulthood, 90-99% infected by both
PATHOGENESIS ~ transmitted thru contact w saliva & breastfeeding
~ remain latent in body after primary infection and
reactivate time to time
CLINICAL ~ primary HHV-6 : Roseala Infantum (in child)
MANIFESTATION ~most cases occur in infant btwn 4m-2 yrs old
~ spiking fever dvlop over period 2 days followed by
mild rash. Fever high enough to cause febrile
convulsion
~ if primary infction is delayed to adult, there is small
chance an infectious mononucleosis-like disease.
~ no firm evidence linking HHV-6 to lymphoma or
lymphoproliferative disease
~ no firm disease assoc. w HHV-7 at present
LAB DX ~ Roseala Infantum: diagnosed on clinical grounds ~ HHV-8 DNA is found in almost 100% of KS
~serology: IgM and IgG detected ~ most pt w KS have Ab against HHV-8
~ seroprevalence of HHV-8 is low among the general
population but high in person susceptible to KS, such
as homosexual
MANAGEMENT ~ no specific antiviral tx for HHV-6 infection
 HERPES GENITALIS
HERPES GENITALIS DISSEMINATED HERPES SIMPLEX
~ genital lesion maybe primary, recurrent, initial
~ genital lesion maybe primary, recurrent, initial ~ in immunocompromised person, widespread vesicular like
~site: penis, vagina, cervix, anu, vulva, bladder, sacral
~site: penis, vagina, cervix, anu, vulva, bladder, sacral chickenpox, involve lung, liver, spleen, CNS
nerve route, spinal & meninges.
nerve route, spinal & meninges.
~ dysuria, severe cases : urinary retention ~ encephalitis is severe, brain is liquefied
~ dysuria, severe cases : urinary retention
~mild meningitis can present OTHER CUTANEOUS MANIFESTATION :
~mild meningitis can present
~ 60% will have recurrence, in perianal area tend to be ~ Eczema herpaticum
~ 60% will have recurrence, in perianal area tend to be
more numerous & longer than oral HSV-1 ~ herpetic whitlow = arise fr implantation of virus into skin &
more numerous & longer than oral HSV-1
typically affect the finger

ORAL-FACIAL HERPES HERPES SIMPLEX ENCEPHALITIS

ORAL-FACIAL HERPES HERPES SIMPLEX ENCEPHALITIS
Acute Gingivostomatitis ~ most serious complication of herpes simplex disease.
Acute Gingivostomatitis ~ most serious complication of herpes simplex disease.
~ commonest on primary infection, neonatal- globally & brain is liquefied.mortality 100%
~ commonest on primary infection,
~ pain and gum bleeding, 1-8 mm ulcer,
~ pain and gum bleeding, 1-8 mm ulcer, CLINICAL
CLINICAL
neonatal- globally & brain is liquefied.mortality 100%
focal disease- common affect temporal lobe.appear in chilfren
focal disease- common affect temporal lobe.appear in chilfren
With necrotic bases, cervical lymp gland enlarged & adult.possible that it arises fr reactivation. Mortality 70%
With necrotic bases, cervical lymp gland enlarged
~ self-limiting, last around 13 days
~ self-limiting, last around 13 days
MANIFESTATI
MANIFESTATI & adult.possible that it arises fr reactivation. Mortality 70%
without tx
Herpes Labialis without tx
Herpes Labialis
Recurrence of oral HSV, prodrome og tingling, warmt, ON
ONOF
OFHERPES
HERPES
~important to dx HSE early,IV acyclovir given to all suspected
~important to dx HSE early,IV acyclovir given to all suspected
HSE before lab result available
Recurrence of oral HSV, prodrome og tingling, warmt, HSE before lab result available
itching at site
itching at site
12 hrs later, redness—papule--vesicles
SIMPLEX
SIMPLEX
12 hrs later, redness—papule--vesicles
VIRUSES
VIRUSES

NEONATAL
NEONATAL HERPES
HERPES SIMPLEX
SIMPLEX (1)(1)
~ babyusually infected primarily during passage thru birth canal
~ babyusually infected primarily during passage thru birth canal
~ premature membrane rupturing is risk factor
~ premature membrane rupturing is risk factor
~risk of perintl transmision high if florid primary infection in mom
~risk of perintl transmision high if florid primary infection in mom
~ smaller risk fr recurrent maternal lesion bcoz lower viral load and presence of specific Abs.
~ smaller risk fr recurrent maternal lesion bcoz lower viral load and presence of specific Abs.
~ baby can be infected fr other sources like oral lesion fr mother or hepatic whillow in nurse
~ baby can be infected fr other sources like oral lesion fr mother or hepatic whillow in nurse
~ spectrum of neonatal HSV varies fr mild disease localized to skin to fatal disseminated infection
~ spectrum of neonatal HSV varies fr mild disease localized to skin to fatal disseminated infection
~ when
~ whenbrain is involved, prognosis is poor. If survived, they have residual disabilities
brain is involved, prognosis is poor. If survived, they have residual disabilities
~ give acyclovir and prevent by caeserian section
~ give acyclovir and prevent by caeserian section

CLINICAL MANIFESTATION OF VARICELLA ZOSTER VIRUS