VIRAL DISEASES OF THE
Dr. Mengistu Hiletework
• Structural components of a viral particle
( virion); nucleic acid, capsid, and in
certain groups of viruses only, an
outermost membrane or envelope
• DNA and RNA virus groups
• DNA virus types are parvovirus,
papovirus, adenovirus, herpesvirus, and
• RNA viruses are picornavirus,
• Double-stranded DNA
• Viruses in this group are varicella-zoster
virus, herpes simplex virus-1 and-2,
cytomegalovirus, Epstein-Barr virus,
• HSV-1 and HSV-2 infections
• Can be asymptomatic; latent infection
• “First episode” or “Recurrent”
• Most patients have no lesions or findings
when they are initially infected with an
HSV.The first clinical lesion is already a
D/Dg of HS
• Herpes zoster
• Syphilitic chancre
• In herpetic gingivostomatitis,
diptheria,coxsackie virus infections, and
oral erythema multiforme
Histopathology of Herpes simplex
• The vesicles are intraepidermal
• The affected epidermis and adjacent inflamed
dermis are infiltrated with leukocytes.
• Ballooning degeneration of the epidermal cells
to produce acantholysis.
• The most characteristic feature is the presence
of multinucleated giant cells.
Genital Herpes( GH)
• Usually due to HSV-2
• Clinical presentation has a broad clinical
spectrum from totally asymptomatic to
severe genital ulcer disease.
Other clinical manifestations of HS
• Herpetic sycosis
• Herpes Gladiatorium
• Herpetic Whitflow
• Herpetic keratoconjunctivitis
• Eczema Herpeticum( Kaposi varicelliform
• Intrauterine and Neonatal Herpes simplex
Intrauterine(IH) and Neonatal
Herpes( NH) Simplex
• 85% occur at the time of delivery, 5% occur in utero
with intact membranes, and 10% to 15% from
nonmaternal sources after delivery.
• Inutero infection may result in fetal anomalies like limb
hypoplasia, intracerebral calcifications,. including skin
lesions and scar.
• The risk of infection for an infant delivered vaginally
when the mother has active recurrent genital herpes
infection is b/n 2-5%, where as it is 26% to 56% if the
maternal infection at delivery is a first episode.
Treatment of Orolabial Herpes
• Topical Acyclovir cream( not ointment)
• Oral therapy: acyclovir, valacyclovir,
• In frequent orolabial recurrences, chronic
acyclovir suppressive therapy in a dose of
400 mg. twice a day can reduce the
number of outbreaks by 50%.
Management of GH
• Initial clinical episode with oral acyclovir, 200
mg, 5xa day or 400 mg 3xa day, famciclovir,250
mg, 3x a day, or valacyclovir 1000mg twice a
day, all for 7-10 days.
• For recurrent genital herpes, acyclovir 200 mg.
5x a day or 800 mg. twice a day or famciclovir
125 mg. twice a day , both for 5 days.
Valacyclovir may be used as a dose of 500 mg
twice a day for 3 days.
Management of GH Cont…
• For patients with more than 6-12 frequent
recurrences per year, suppressive therapy of
acyclovir 400 mg. twice a day, 200 mg 3x a day,
or 800 mg. once a day will suppress 85%
recurrence. It can be stopped after 10 years.
• Chronic suppressive therapy reduces
asymptomatic shedding by almost 95%.
• Chronic suppressive therapy is safe and lab.
Monitoring not required.
Management Of NH
• Iv acyclovir
• Vacuum- assisted delivery increases the
relative risk of neonatal varicella by
• Cesarean section in the setting of active
genital lesions or prodromal symptoms.
• Commonly known as chickenpox
• The primary infection with VZV
• Incubation period is 10 t0 21 days( usually
14 to 15 days)
• Transmisson is by direct contact with the
lesions and by the respiratory route, with
the initial viral replication in the
nasopharynx and conjunctiva
• An initial viremia between 4 and 6 days seeding
the liver, spleen, lungs, and perhaps other
• A secondary viremia occurs at days 11 to 20,
resulting in infection of the epidermis and
appearance of characteristic skin lesions.
• Individuals are infectious for at least 4 days
before and 5 days after the appearance of the
Varicella, Clinical Manifestation
• Severity of the disease is age dependent,
with adults having more severe disease
and a greater risk of visceral disease
• Lifelong immunity
• Second episode of “varicella” indicates
either immunosuppression or another viral
infection such as coxsackievirus
Pregnant Women and Neonates
• Maternal infection with the VZV during the
first 20 weeks of gestation may result in a
syndrome of congenital varicella
syndrome (CVS) as well as severe illness
in the mother.
• CVS is characterized by anomalies like
hypoplastic limbs,cutaneous scars, and
ocular and CNS disease.
• Varicella can be extremely severe and even fatal
in immunosuppressed patients, especially in
individuals with impaired cell-mediated
• Prior varicella does not always protect the
immunosuppressed host from multiple episode.
• Immunosuppression , especially hematologic
malignancy and HIV infection increase the risk
Pregnant Women and Neonates,
• In some cases increased preterm labor.
• The risk of zoster occurring postnatally is
greatest in foetus infection of 25 to 36 weeks of
• If the mother develops 5 days before and 2 days
after delivery, neonatal varicella can occur and
be severe, as transplacental delivery of
antivaricella antibody has been inadequate.
Diagnosis of Varicella
• Tzanck smear, characteristic
multinucleate giant cells
• If needed, DFA test, which is rapid, and
will both confirm the infection and type of
• VZV grows poorly and slowly, so culture is
Complications of Varicella
• Secondary bacterial infection with
staphylococcus aureus or a streptococcal
• Rarely osteomyelitis, other deep-seated
infections or septicemia
• Pneumonia uncommon in normal children,
but seen more in adults.
• Cerebellar ataxia and encephalitis
• Asymptomatic myocarditis and hepatitis
Varicella Complications, Cont…
• Reye syndrome, a syndrome of hepatitis and acute
encephalopathy, is associated with the use of aspirin to
treat the symptoms of varicella.
• Aspirin is absolutely contraindicated in patients with
varicella.In any child with varicella and severe vomiting,
Reye syndrome should be excluded.
• Symptomatic thrombocytopenia is a rare manifestation,
which occurs either with the exanthem or several weeks
• Purpura fulminans, a form of disseminated intravascular
coagulation with low levels of protein C and S.
• Acyclovir therapy to be started early within
24 h of the appearance of the eruption
• Aspirin is contraindicated
• Topical antipruritic lotions
• Dressing the patient in light, cool clothing,
and keeping the environment cool
• Severe fulminant cutaneous disease and
visceral complications are treated with IV
acyclovir, 10 mg/kg every 8 hour.
• A single live attenuated viral vaccine for children
aged 1 to 12, and persons aged 13 and older,
two vaccinations , 4 t0 8 weeks apart.
• In healthy children,97% of efficacy during the
first year and 84 % efficacy for the next 8 years.
• Immunized children may develop varicella of
reduced severity on exposure to natural
Zoster ( Shingles, Herpes Zoster)
• Zoster is caused by reactivation of VZV.
• VZV remains latent in the dorsal root ganglion cells.
• Replication of the virus some later time, traveling down
the sensory nerve into the skin.
• Immunosuppression, especially haematologic
malignancy and HIV infection increase the risk for zoster.
Classical presentation of zoster
• Dermatomes mostly affected are thoracic
(55%), cranial(20%), the trigeminal nerve
being the most common single nerve
involved. Lumbar (15%), and sacral(5%)
• A correlation with the pain severity and
extent of the skin lesions
• Elderly persons tend to have more severe
Herpes Zoster, Cont…
• Lesions may become hemorrhagic, necrotic, or
• Rarely the patient may have pain, but no skin
lesions (Zoster sine herpete)
• Lesions may develop on the mucous membrane
within the mouth in zoster of the maxillary or
mandibular division of the facial nerve or in the
vagina in the S2 or S3 dermatomes.
• Zoster may appear in recent surgical scars.
Complications of Herpes zoster
• Disseminated Herpes Zoster
• Opthalmic zoster
* If external division of the nasociliary
branch affected ( Hutchinson’s sign)
* If vesicles on the lid margin
• Ocular involvement is most commonly uveitis
and keratitis. Less common ones are glaucoma,
optic neuritis, encephalitis,hemiplegia, and acute
Complications of Zoster, Cont..
• Ramsay Hunt syndrome , resulted from
involvement of the facial and auditory
nerves,caused by herpetic inflammation of the
• Delayed contralateral hemiparesis, a rare but
serious complication that occurs by affecting the
first branch of the trigeminal nerve by direct
extension on the nerve , gaining access to the
CNS and infecting the cranial arteries.
Complications of Zoster, Cont…
• Motor neuropathy in about 3% of patients
• If S3 or less often S2 or S4 are involved,
urinary hesitancy or acute urinary
• Pseudo-obstruction, colonic spasm,
dilatation, obstipation, constipation and
reduced anal sphincter tone in T6 to T12,
lumbar, or sacral zoster
Pain( Postherpetic Neuralgia)
• Preceding, within and after the eruption
• Oral analgesia, nonsteroidal
antiinflammatory drugs, and opiate
• Capsaicin topically every few hours, but
the application itself may cause burning
• Local anaesthtics such as 10% lidocaine
in gel form
Postherpetic Neuralgia, Cont…
• Sublesional anaesthesia, epidural blocks,
and sympathetic blocks with and without
• Systemic corticosteroids are controversial
• Tricyclics such as antitriptyline/or
nortriptyline, and despiramine started at
25 mg/night or 10 mg. over the age of 65-
70. Dose gradually increased upto 100
Zoster in immunosuppressed
• Increased rate in immunosuppressed
individuals by organ transplantation,
connective tissue disease, or by agents to
treat these conditions (corticosteroids,
sirolimus, and tacrolimus)
• Zoster is 30x more common in HIV-
Zoster in immunosuppressed
• Murmatomal, more ulcerative and
necrotic,severe scar and disseminated zoster
• Disseminated zoster may be associated with the
syndrome of inappropriate antidireutic hormone
secretion (SIADH)and present with
hyponatemia, abdominal pain and ileus. Here
the skin lesions may be small and resemble
“papules” rather than vesicles
Herpes zoster in
• Often have recurrence of zoster upto 25%
of patients with AIDS
• Two atypical presentations of zoster in
Ecchtymatic lesions, which are punched
out ulcerations with a central crust, and
Diagnosis of Zoster
The same techniques used for the
diagnosis of varicella
Histopathology of Zoster
• As in HS, the vesicles in zoster are
• Acidophilic inclusion bodies similar to those
seen in herpes simplex are present in the nuclei
of the cells of the epithelium
• Multinucleated keratinocytes, nuclear moulding,
and perpheral condensation of the nucleoplasm
are characteristic and confirmatory of an
infection with either HSV or VZV.
D/ Dg of HZ
Herpes simplex if the HS lesions are linear
(zosteriform) or the zoster lesions are
small and localized to one side, not
involving the whole dermatome.
• Following zoster, within a month and
rarely larger than 3 months after zoster
inflammatory skin lesions may rarely occur
within the affected dermatome.
• Clinically, flat-topped or annular papule in
• Histologically granulomatous inflammation
Treatment of HZ
• Middle-aged and elderly patients, restrict
physical activity or even stay home in bed
• Local applications of heat, as with an
electric heating pad or a hot-water bottle
• Simple local application of gentle pressure
with the hand or with an abdominal binder
Treatment of HZ, Cont…
• Antiviral therapy:
The main benefit is in reduction of the
duration of the zoster-associated pain and
more rapid resolution of skin lesions.
Valacyclovir ( 100o mg.), famciclovir( 500
mg.),3x a day are as effective or superior
to acyclovir ( 800 mg.,5x a day) probably
because of better absorption.