Communicable disease

Topic: Human HERpes virus (HHV)

Lecturer: yapendon md

HUMAN HERPES VIRUS (HHV)

Herpes Simplex virus
Human Herpes Infection - Is a nucleus replicating, icosaahedral, enveloped
- Lifetime – latent inside cells DNA virus
- Not a lifetime disease but a lifetime infection - The envelope contains at least 8 glycoproteins
- The matrix or tegument which contacts both the
HHV envelope and the capsid contains at least 15-20
- Greek “herpein” = to creep proteins
- latency and recurrent infection
- DNA virus HSV GENOMES ENCODES FOR
- 8 commonly described human herpes virus - 11 surface glycoproteins:
- HHV 1- HHV 8  For attachment & fusion of the viral
 HHV 1 and HHV 2: Herpes Simplex 1 & membrane and that of the target cell-
2 gB, gC, gD and gH
 HHV 3: Varicella Zoster  Immune escape – gC, gE and gL
 HHV 4: EBV
 HHV 5: CMV HSV2
 HHV 6 and HHV 7: Roseola - more associated with genital herpes
 HHV 8: Kaposi’s sarcoma (AIDS)
HSV1
HH Name Target cell Latency in Transmissi - More associated with the face
V type on - Common in children
1 HSV-1 Mucoepithelia Neuron Close - Vesicular lesions in mouth
contact - However, both HSV 1 and 2 can occur either in
2 HSV-2 Mucoepithelia Neuron Close
mouth or in genital
contact
Usually
sexual TRANSMISSION
Contact or  Close contact with an infected person
VSV Mucoepithelia Neuron respiratory - Shedding of virus occurs in skin lesion, saliva,
route secretions from genital area

3
 Contaminated hands may infect via abraided
4 EBV B lymphocyte B Saliva
epithelia lymphocyte skin or through mucosa and conjunctiva
5 CMV Epithelia Monocyte Contact, BT,  HSV 1 is usually spread mouth to mouth
monocyte, and transplantati (kissing or the use of utensils contaminated
lymphocyte lymphocyte oncongenita by saliva)
l  Vertical transmission
6 Herpes Contact or - Pre-natal
lymphotr respiratory
- Perinatal
opic T route
T lymphocyte lymphocyte - Can Cause herpes simplex
and others and others encephalitis in newborn
7 HHV-7 T lymphocyte T Unknown PATHOPHYSIOLOGY
and others lymphocyte
and others INFECTION OF MUCOEPITHELIAL CELLS AND
8 HHV-8 Endothelial Unknown Exchange of REPLICATION
/Kaposi’s cells body fluids
↓
Sarcoma
Neuronal axonal retrograde transports to the ganglion
From the oral mucosa goes to the trigeminal ganglia
CHILDHOOD SKIN RASHES
th
- 6 disease- Roseola, HHV6
 From the genital mucosa the virus enter the sacral  gE and gL binds the Fc portion of the IgG
ganglia S2-S5 coating the virus with immunoglobulin and
↓ hides it from the immune system
Goes into LATENCY PERIOD
Latent in the nerve cell bodies in sensory an autonomic Clinical characteristics of HSV infection
ganglia for years  Benign but can also cause severe disease
↓  Persistent resulting to latency
Antegrade transport to the original site of infection and - First outbreak after exposure is commonly more
contiguous area via sensory nerves leads to recurrence severe and has a 1% risk of developing aseptic
of lesions meningitis
↓
Viremia can occur causing spread to the other body LESIONS
parts - Skin and mucous membrane of the mouth, lips,
↓ and genitalia
RETURN OF LESIONS - May recur periodically as outbreaks of sores/
skin lesion near the site of original infection
IMMUNE RESPONSE HSV - Clear vesicle with erythematous base –
- Cellular and Humoral “DEWDROP ON A ROSE PETAL”
- INF and NK cells limits the infection - May encrust and ulcerate
- Cytotoxic T cells and macrophages may identify - Some are asymptomatic but with viral
and kill the infected T cells shedding
- Antibodies against surface glycoproteins may o A normal finding of the genital area is
leads to neutralization not a guarantee that you are free from
Herpes Simplex
MECHANISM OF LATENCY IN NEURAL GANGLIA:
LAT-RNA HERPES SIMPLEX HERPES SIMPLEX
VIRUS 1 VIRUS 2
Latency Associated Transcript (LAT-RNA) expressed Encephalitis Meningitis
by HSV Conjunctivitis Gingivostomatitis,
- Regulate the host genome and interferes natural tonsillitis, labialis
cell death mechanism Gingivostomatitis, Pharyngitis
 By maintaining the infected host cell , Tonsillitis, labialis
LAT preserves a reservoir of HSV for Pharyngitis, Esophagitis Perianal herpes
latent recurrence Herpes Gladiatorum Genital herpes
Tracheobronchitis Herpes Whitlow
HSV EVADE THE IMMUNE SYSTEM THROUGH:
Genital herpes
- Interference with MHC Class I presentation of
antigen on the cell surface of infected cells Herpes whitlow
 Thru blockade of the TAP transporter
induced by the secretion of ICP 47 ORAL HERPES
 TAP maintains the integrity of the MHC - Cause by either HSV 1 or HSV 2
Class I molecule before it is transported - Infections in children are usually the result of
via the golgi apparatus for recognition HSV-1
by CD8 and CTLs on the cell surface
- Direct cell to cell transfer without entering the - Trigeminal nerve is the most commonly
extracellular space and avoid contact with infected
humoral antibodies o Extension to the superior and inferior
- Immune escape ganglia occur

IMMUNE ESCAPE - Gingivostomatitis and pharyngitis

- HSV glycoprotein: gC, gE, and gL o are the most common clinical
 gC binds complement C3 protein causing manifestation of first episode HSV 1
depletion of C3 from the serum and inhibits infection
complement-mediated reaction

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 - Herpes labialis/cold sore
o the most common presentation of
reactivation of latent HSV 1 infection
PRIMARY HERPETIC GINGIVOSTOMATITIS
- Clear vesicular lesions followed by ulcers that
have a white appearance
- Initially on the lips then spread to the mouth and
pharynx
- Herpes pharyngitis is often associated with other
viral infections of respiratory
WHAT TRIGGER RECURRENCE/REACTIVATION
 Other illnesses such as cold and influenza,
eczema
 Emotional and physical stress
 Exposure to bright sunlight
 Gastric upset
 Fatigue or injury
 Menstruation
HERPES SIMPLEX KERATITIS (DENDRITIC)
- Primarily caused by HSV-1
- Affects the ophthalmic br. of trigeminal nerve
- Can be recurrent, may lead to blindness
HERPETIC WHITLOW
- Cause by either HSV 1 or HSV 2
- Due to manual contact with herpes-infected
body secretions
- Enter small wounds
Reactivation from the trigeminal ganglia can result to
recurrence and known as cold sores
CLOSE BODY CONTACT
HERPES GLADIATORUM
- Contracted by wrestlers
- Head and neck region (which are frequently
sites of contact in wrestling holds)
HERPES RUGBEIORUM (SCRUM POX)
- Contracted by rugby players
ECZEMA HERPETICUM
- Seen in children with active eczema,
preexisting atopic dermatitis, and can spread
over the skin at the site of eczema lesions
- Can spread to other organs such as the liver
and adrenals
GENITAL HSV INFECTION
- Usually due to HSV-2 with about 105 due to
HSV-1
- Primary infection is often asymptomatic
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 But can have fever, myalgia, glandular
inguinal adenitis, pain, itching, dysuria,
vaginal and urethral discharge.
- Secondary episodes of genital herpes, are due
to reactivation of virus in the sacral ganglion
 Less severe and shorter duration than
the first episode
- Painful lesions can develop on the glans or shaft
of the penis of men
- In both sexes the urethra can be involved
- Painful lesion can develop on the vulva, cervix
and perianal region of women
- Infection may be accompanied by vaginal
discharge
HSV 2 AND HIV 1
- HSV-2 infection is an independent risk factor in
the acquisition and transmission of infection with
HIV-1
- HIV-1 virions can be shed from herpetic lesions
to genital HSV-2
- Reactivation is associated with a localized
persistent inflammatory response consisting of
high concentration of CCr5-enriched CD8+ T
cells as well as inflammatory dendritic cells in
the submucosa of the genital
- Patient with herpes have a 2-3x risk of acquiring
the disease
- More reactivation of HSV-2 in HIV patient with
low CD4 and heavy viral load
HSV DIAGNOSIS
ISOLATION OF HSV IN CELL CULTURE
- Preferred virologic test but with low
sensitivity
PCR assays for HSV DNA
- More sensitive and have been used instead of
viral culture
- Lack of HSV detected (i.e. culture or PCR)
does not indicate a lack of HSV infection, as
viral shedding is intermittent and the number of
virus declines as the lesions heals
TZANK SMEAR
- Smear of the base of the lesion show
multinucleated giant cells and Cowdry type A
inclusion bodies (insensitive)
- Biopsy (specimen use for tissue culture)
- Forms characteristic cytopathic effects (plaque)
including multinucleated cell
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HSV Serologic Test
- Both type-specific and nontype-specific o Suppressive therapy, if >6x per year
antibodies to HSV develop during the first - For HIV (+)
several weeks after infection and persist - For HIV (-)
indefinitely
- Type specific serologic test is based on HSV TREATMENT FIRST CLINICAL EPISODE X 7 TO 10
specific glycoprotein G1 (HSV1) and DAYS
glycoprotein G2(HSV2)  Acyclovir 400 mg PO TID x 5-10 days OR
- Can be used to diagnose primary infection  Famcyclovir 500 mg PO BID x 5-10 days OR
- Recurrence is not usually accompanied by a rise  Valacyclovir 1g PO BID x 5-10 days
in antibody levels
EPISODIC THERAPY FOR RECURRENT GENITAL
WHEN IS ANTIBODY TO HSV USEFUL HERPES
 Recurrent genital symptoms or atypical  Acyclovir 400 mg PO TID x 5 days OR
symptoms with negative HSV culture  Acyclovir 800mg PO BID x 5 days OR
 A clinical diagnosis of genital herpes without  Acyclovir 800mg PO TID x 2 days OR
laboratory confirmation  Famcyclovir 125mg PO BID x 5 days OR
 A partner with genital herpes  Famcyclovir 1000mg PO BID x 1 day OR
 Valacyclovir 500mg PO BID x 3 days OR
PREVENTION OF GENITAL HERPES  Valacyclovir 1g PO OD x 5 days
 Counseling regarding the natural history of o Should start within 1 day of lesion onset
genital herpes, sexual and perinatal or during prodrome
transmission, and methods to reduce
transmission RECOMMENDED REGIMENS FOR DAILY
o Sexual transmission of HSV can occur SUPPRESSIVE THERAPY IN PERSONS INFECTED
WITH HIV
during the asymptomatic period
 Acyclovir 400-800 mg po BID or TID OR
o Asymptomatic viral shedding is more
 Famciclovir 500 mg po BID OR
frequent in genital HSV 2 infection
 Valacyclovir 500 mg po BID
than genital HSV 1 infection and is
most frequent 12 months after
SUPPRESSSIVE THERAPY FOR RECURRENT
acquiring HSV2
GENITAL HERPES
 Acyclovir 400mg PO BID OR
 Abstinent from sexual activity with uninfected
 Famcyclovir 250mg PO BID OR
partners when lesions or prodromal symptoms
 Valacyclovir 500mg PO OD OR
are present.
 Valacyclovir 1g PO OD
 Encouraged to inform their current sex partners.
 Reduces the frequency of recurrence by 70-80%
 Risk for neonatal HSV infection should be
in patients who have frequent recurrence ie >/=
explained.
6 yr
 Safety for acyclovir is up to 6 years, 1 year for
TREATMENT HSV
valcyclo and famciclo
 Goal of Antiviral treatment
 Outbreaks diminished over time in many
o Reduce the viral load (unable to
patients
completely eliminate the virus)
 Quality of life frequently improved
o Reduce the physical severity of
 Decreased transmission to partner
outbreak associated lesion
o Reduce the amount of infected cells
TREATMENT FOR SEVERE DISEASE
shed thus lowering the chance of
 Disseminated infection, pneumonitis, or hepatitis
transmission to others
 CNS complications (e.g meningitis or
 Acyclovir, Famacylclovir, Valacyclovir
encephalitis)
 Treatment of first episode
o Acyclovir 5-10 mg/kg/body weight IV
 Treatment of recurrent genital herpes
fr 8 hours for 2-7 days or until clinical
o Episodic therapy
improvement is observed, followed by
- For HIV (+)
oral antiviral therapy to complete at
- For HIV (-)
least 10 days of total therapy
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 EEG:
HSV ENCEPHALITIS
- Usually due to HSV 1 except in newborn (HSV
2)
- Most common sporadic viral encephalitis
- Mortality rate in untreated patients is 70%
o 19% among treated patients
- More than 50% of survivors are left with
moderate or severe neurologic deficits
- In an acute or subacute illness
- Cause both general and focal signs of cerebral
dysfunction
o Neurons are quickly overwhelmed by a
lyttic and hemorrhagic process
distributed in an asymmetric fashion
throughout medial temporal and inferior
frontal lobe
- 84% sensitive to abnormal PATTERNS IN HSE
but lacks specificity (32%)
- Spike and slow- or periodic sharp wave patterns
over the involved temporal lobes.
HSV ENCEPHALITIS TREATMENT
- EMPIRIC TREATMENT WITH ACYCLOVIR
o Recommended pending confirmation of
the diagnosis because the drug of
choice, is relatively nontoxic and
because the prognosis for untreated
HSE is poor.
2
o 10 mg.kg (or 500 mg/m ) IV every 8
hours for 14-21 days, dose infused over
an hour.

HSV ENCEPHALITIS MANIFESTATIONS

- Fever (90%)
- Headache (81%)
- Psychiatric problems (71%)
- Seixures (67%)
- Vomiting (46%)
- Focal weakness (33%)
- Memory loss (24%)
- Alteration consciousness (97%)
- Dysphasia (76%)
- Ataxia (38%)
- Hemiparesis (38%)
- Cranial nerve defects (32%)
- Visual field loss (14%)
- Papilledema (14%)

HSV ENCEPHALITIS WORKUP

CSF ANALYSIS
- Mononuclear pleocytosis of 10-500 WBC
- Elevated RBC 10-500/ul
- Elevated protein 60-700mg/dl
- normal or mildly decreased glucose 30-40 mg/dl

PCR: Confirmatory test

- 94-98% sensitive, 98-100% specific, (+) within
24 hrs of illness and remain positive for at least
5-7 days after start of antiviral

IMAGING STUDIES
- MRI is preferred than CT
- Localized temporal abnormalities are suggestive
HSE

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