viral infections......................ppt

 Alphaherpesvirinae
 Herpes simplex virus type 1 HSV-1
 Herpes simplex virus type 2 HSV-2
 Varicella-zoster virus VZV
 Betaherpesvirinae
 cytomegalovirus CMV
 Human herpesvirus type 6 HHV-6
 Human herpesvirus type 7 HHV-7
 Gammaherpesvirinae
 Epstein-Barr virus EBV
CLASSIFICATION
(Herpes virus.)

HERPES ZOSTER
Varicella-zoster virus (VZV) is the agent causing chickenpox,
the common childhood infection. Following resolution of
chickenpox, VZV lies dormant in the spinal dorsal root ganglia
until reactivation results in herpes zoster (shingles).
• Shingles" is a syndrome characterized by a painful,
unilateral vesicular rash, usually restricted to a dermatomal
distribution. At times, especially in the immunosuppressed
patient, the infection may spread and produce severe
systemic illness with involvement of multiple visceral
organs and multiple dermatomes (disseminated zoster).

Background Information
 Shingles is a skin rash
caused by the same virus
that causes chickenpox.
 The virus is called the
Varicella zoster virus.
 It occurs most commonly in
people OLDS AND
ADULTS AND CHILDREN.
NHI

 Race
 Blacks are one-fourth as likely as whites to
develop herpes zoster.
 Sex
 Incidence is equal in males and females.
 Age
 Incidence of herpes zoster increases with age.
Approximately 80% of cases occur in persons
older than 20 years. Fewer than 5% of cases are
in those younger than 14 years.


 Pathophysiology
 Exactly why VZV reactives from latency is not fully
understood. However, VZV-specific cell-mediated
immunity has been shown to be a major factor in
determining reactivation of VZV. Cell-mediated VZV-specific
immunity decreases with age and in patients with certain
malignancies. These groups have much higher rates of
herpes zoster. Patients with hypogammaglobulinemia (a
defect of humoral but not cellular immunity) do not have a
higher rate of zoster. This supports the concept of an
important role for cell-mediated immunity in the
pathogenesis of VZV infection.

 Mortality/Morbidity
 A common complication of herpes zoster
is postherpetic neuralgia, pain that persists for
longer than 1 month following resolution of the
vesicular rash. This complication is more
common in patients older than 50 years.
 Postherpetic neuralgia may develop as a
continuation of pain that accompanies acute
zoster, or it may develop following apparent
resolution of the initial zoster reactivation. The
pain of postherpetic neuralgia usually resolves
within 6 months. However, 1% of patients

 Herpes zoster may be associated with a
secondary bacterial infection at the site of the
rash (typically streptococcal or staphylococcal).
 Herpes zoster involving the second branch of the
trigeminal nerve may be associated with
conjunctivitis, keratitis, corneal ulceration,
iridocyclitis, glaucoma, and blindness.
 Complications of the Ramsay Hunt syndrome
(zoster involving cranial nerves V, IX, and X)
may include peripheral facial nerve weakness
and deafness.

 Meningoencephalitis secondary to herpes zoster
is more likely to be seen in immunocompromised
patients than in immunocompetent patients.
Other CNS complications may include myelitis,
cranial nerve palsies, and granulomatous angiitis.
Granulomatous angiitis may result in the
development of a cerebrovascular accident.

Disseminated zoster may be seen in
immunocompromised patients. In such cases,
hematogenous spread may result in the involvement of
multiple dermatomes. Visceral involvement can also
occur. Such systemic involvement can lead to death due
to encephalitis, hepatitis, or pneumonitis

 CLINICAL
 Prodromal pain precedes the rash in approximately 75%
of patients, typically confined to the same dermatomal
distribution. Initially vesicular, the rash gradually
becomes pustular and then crusts over a period of 7-10
days. As with chickenpox, once crusting occurs, the
lesion are no longer infectious. Scarring and
hypopigmentation or hyperpigmentation may persist for
a long period.
 Most patients describe the pain as burning, throbbing, or
stabbing.
 The involved area may be tender to palpation.
 The rash may be pruritic.

 The thoracic dermatomes are the most
commonly involved sites, followed by the
lumbar dermatomes.
 Fewer than 20% of patients have systemic
symptoms, such as headache, fever, malaise,
or fatigue.
 Pain duration is variable but usually less than 1
month.

 Physical
 The primary physical finding is a rash in a unilateral
dermatomal distribution; the rash may be
erythematous, vesicular, pustular, or crusting,
depending on the stage of disease.
 The initial rash is typically "herpetic" in appearance:
small vesicles grouped on an erythematous base. It
has been described as "dew drops on a rose petal."
 Bilateral rash is rare

 Depending on the dermatome involved,
physical examination findings may include the
following:
 Corneal ulcers, conjunctivitis
 Regional lymphadenopathy
 Cranial nerve palsies
 Peripheral facial nerve palsy
 Delirium, confusion, coma (in patients with
meningoencephalitis.

 Lab Studies
 Diagnosis of herpes zoster is based primarily
on clinical findings, specifically the
characteristic location and appearance of the
skin eruption in association with localized pain.
However, in some patients, the presentation of
herpes zoster can be atypical and may require
additional testing. This is particularly true in
immunocompromised patients


Treatment
 The severity of an attack of
shingles can be reduced by
immediate treatment with antiviral
drugs
 Such as acyclovir or valcyclovir
 Antiviral drugs may help the
painful effects of shingles
 Other treatments include
steroids, antidepressants,
anticonvulsants, and topical
agents.
valcyclovir
Acyclovir

 Varicella-zoster virus can be cultured
successfully; this has limited use in the ED due
to the long time required for viral growth.
 If necessary, a definitive diagnosis can be
confirmed by sending swabs to the
laboratory. Lift the top of the lesion and swab the
exposed base. The swab should then be rolled
across a sterile glass side, which is air dried and
sent to the laboratory for staining with
immunofluorescent antibodies. The swab can
also be placed in viral transport medium for
detection of viral DNA by polymerase chain
reaction.

 TREATMENT
 Symptomatic treatment
patients with herpes zoster usually experience pain.
Antiviral and steroid therapy provides relatively
minor relief of pain, and analgesics are often
needed.
 Initial therapy may include nonsteroidal anti-
inflammatory drugs (NSAIDs).
 In many cases, narcotic analgesia is necessary.
 Wet to dry dressings with tap water or 5%
aluminum acetate (Burow solution). Apply to the
affected skin for 30-60 minutes 4-6 times per day.
 Bland lotions (ie, Calamine) may help relieve
discomfort

 Antiviral therapy for uncomplicated herpes
zoster
The goals of antiviral therapy are to
decrease pain, to promote healing of skin
lesions, and to prevent or reduce
the severity of postherpetic neuralgia.
Acyclovir and the newer antivirals
valacyclovir and famciclovir have been
shown to be effective if given within 48-72
hours of the appearance of the rash.

 The duration of antiviral treatment in studies
has varied from 7-21 days. Based on current
literature, for immunocompetent patients,
acyclovir for 7-10 days or a 7-day course of the
newer agents is appropriate. Longer courses
may be needed in immunocompromised
patients Combined antiviral and
corticosteroid therapy for uncomplicated
herpes zoster

 The addition of corticosteroids has been
evaluated in patients treated with acyclovir.
The benefit of steroids included accelerated
healing of lesions and more rapid resolution of
acute pain. Though statistically significant, the
benefits were small.
 Treatment of complicated herpes zoster.
 Treat all immunosuppressed patients with
antivirals, even when the onset of symptoms is
more than 72 hours

 Valacyclovir should be used if oral therapy is
selected.
 Consider treatment with intravenous acyclovir for
the following patients:
 Drug NameAcyclovir (Zovirax
 Adult DoseImmunocompromised adults: 800
mg PO q4h (5 times/d) for 7-10 d; alternatively,
10 mg/kg/dose or 500 mg/m2/dose IV q8h
 Pediatric DoseImmunocompromised children: 250-600
mg/m2/dose PO 4-5 times/d for 7-10 d; alternatively, 10
mg/kg/dose or 500 mg/m2/dose IV q8h


 Acetaminophen (Tylenol, Aspirin-Free Anacin)
:
 Adult Dose325-650 mg PO q6h, or 1000 mg
tid/qid; not to exceed 4 god.
 Pediatric Dose<12 years: 10-15 mg/kg/dose PO
q4-6h prn; not to exceed 2.6 g/d
>12 years: 650 mg q4h; not to exceed 5 doses in
24 h.

 Complications:
 Ocular involvement with facial zoster
 Meningoencephalitis
 Cutaneous dissemination
 Superinfection of skin lesions
 Hepatitis/pneumonitis
 Peripheral motor weakness/segmental
myelitis
 Cranial nerve syndromes, particularly
ophthalmic and facial (Ramsay Hunt
syndrome)
 Corneal ulceration

 Prognosis
 Rash usually resolves within 14-21 days.
 Postherpetic neuralgia is defined as pain
persisting at least 1 month after the rash has
healed. Its incidence increases dramatically
with age (ie, 4% in those aged 30-50 years,
50% in those older than 80 years.

HERPES
INFECTIONS
GENITAL HERPES

HERPES SIMLEX
Tow subtypes :HSV type -1
and HSV type -2

HERPES SIMLEX
HSV type I is usually around the mouth, and type
II is usually around genitals, but BOTH types
can infect either site due to oral sex or finger
spread.
The herpes virus remains in the body FOR LIFE.
There is not cure, only treatment to ease
symptoms.
HSV can be spread to others WITHOUT ANY
visible blisters or sores.

HSV type 1
Spread by direct contact
and droplet infection .

Clinical features
 Primary infection in form of fever with
either clusters of painful blisters on
the face or a painful gingivostomatits
with buccal ulceration and
lymphadenopathy
 Once infected, cell-mediated immunity
develops.

HSV type 2
 Mainly after puberty and usually affects
the genital area .
 Transmitted sexually .

Clinical features
 Vulvovaginitis : burning irritation,
dysuria and L.N. enlargement .
 Vesiculation ,weeping & crusting .
 Systemic : fever ,headache &
meningeal irritation .

Symptoms of herpes
Occur 2-20 days after contact with infected partner
Blisters or rash: small, painful, fluid-filled blisters can appear anywhere –
penis, vulva, thighs, buttocks,inside vagina, throat, mouth, eyes, fingers, etc.
Flu-like symptoms: fever, headache, nausea, swollen glands, aching muscles
Painful urination: pain and swelling may be severe, may be unable to urinate

SYMPTOMS of HERPES
 Occur 2-20 days after contact with infected
partner
 Blisters or rash: small, painful, fluid-filled
blisters can appear anywhere – penis, vulva,
thighs, buttocks, inside vagina, throat, mouth,
eyes, fingers, etc.
 Flu-like symptoms: fever, headache, nausea,
swollen glands, aching muscles
 Painful urination: pain and swelling may be
severe, may be unable to urinate

HERPES OUTBREAKS
PRIMARY EXPOSURE
First-time outbreaks are the most severe and
most painful, and it takes form 1 to 3 weeks for
the sores to heal over.
Blisters rupture, causing open sores that can
sometimes run together to make large sores.
Scarring can occur.
SECONDARY (RECURRENT) EPISODES
Secondary or “recurrent” outbreaks are less painful than the
first episode, but they are still painful and troublesome.
The average number is about 4 to 7 flare-ups per year, but
some women have them monthly along with their periods.
Other factors that seem, to cause flare-ups are: tight clothes,
sun exposure, stress, fatigue, illness. Diet, sexual activity.

Complications
 Corneal ulceration.
 Acute encephalitis.
 Eczema herpeticum.
 Erythema multiforme.

Complications :
 Autoinoculation: self-spread to eyes or other parts of
body, can lead to scarring or blindness.
 Higher risk of cervical cancer, need more frequent
Pap smears and doctor’s visits to detect it
 Newborn Infections: sever skin rash, brain damage,
blindness, or possibly death (up to 50%)

HERPES AND PREGNANCY
Babies can be infected at birth,
especially during a primary outbreak in
the mother.
Mother has primary
outbreak at
delivery/birth
50% of babies become infected
60% die of the infection
50% of survivors have severe
brain damage
A Cesarean delivery can be performed to avoid infection of the baby.

TREATMENT
Acyclovir topically.
Oral acyclovir 200 mg five
times for 6 days.

HERPES ZOSTER
Caused by varicella zoster virus
(VZV).
Results from a reactivation of vzv
dormant in one of sensory ganglia.

CLINICAL FEATURES
May be a prodromal phase of
tingling or pain which is then
followed by a painful and tender
blistering eruption in a dermatomal
distribution & it is unilaterally.

The blisters are arranged in
groups & may become
pustular with crust formation.
The rash usually takes 2-4
weeks.

COMPLICATIONS
Post-herpetic neuralgia:
severe persistent pain.
Ocular if ophthalmic nerve is
involved.

TREATMENT
Analgesics .
Antibiotics for secondary
bacterial infection .
Acyclovir 800 mg 5 times a
day for 7 days .

Mumps is an acute self-limited infection,
once commonplace but now unusual in
developed countries because of
widespread use of vaccination. It is
characterized by fever, bilateral or
unilateral parotid swelling and tenderness,
and the frequent occurrence of
meningoencephalitis and orchitis.

ETIOLOGY.
Mumps virus is in the family
Paramyxoviridae and the genus
Rubulavirus. It is a single-stranded
pleomorphic RNA virus encapsulated in a
lipoprotein envelope and possessing 7
structural proteins

EPIDEMIOLOGY.
In the prevaccine era, mumps occurred
primarily in young children between the
ages of 5 and 9 and in epidemics about
every 4 years. Mumps infection occurred
more often in the winter and spring months

Mumps is spread from person to person by
respiratory droplets. Virus appears in the
saliva from up to 7 days before to as long
as 7 days after onset of parotid swelling.
The period of maximum infectiousness is
1–2 days before to 5 days after parotid
swelling. Viral shedding before onset of
symptoms and in asymptomatic infected
individuals impairs efforts to contain the
infection in susceptible populations.

PATHOLOGY AND PATHOGENESIS.
Mumps virus targets the salivary glands,
central nervous system (CNS), pancreas,
testes, and, to a lesser extent, thyroid,
ovaries, heart, kidneys, liver, and joint
synovia
Following infection, initial viral replication
occurs in the epithelium of the upper
respiratory tract. Infection spreads to the
adjacent lymph nodes by the lymphatic
drainage, and viremia ensues, spreading

Salivary gland ducts are lined with necrotic
epithelium, and the interstitium is infiltrated
with lymphocytes. Swelling of tissue within
the testes may result in focal ischemic
infarcts. The cerebrospinal fluid (CSF)
frequently contains mononuclear
pleocytosis, even in individuals without
clinical signs of meningitis.

CLINICAL MANIFESTATIONS.
The incubation period for mumps ranges
from 12 to 25 days, but is usually 16 to 18
days. Mumps virus infection may result in
clinical presentation ranging from
asymptomatic or nonspecific symptoms to
typical illness associated with parotitis with
or without complications involving several
body systems.

 The typical case presents with a prodrome
lasting 1–2 days consisting of fever,
headache, vomiting, and malaise. Within 24
hours, patients report an ear pain localized
near the lobe of the ear and aggravated by a
chewing movement of the jaw.
 Parotitis then appears and may be
unilateral initially but becomes bilateral in
about 70% of cases .
 The parotid gland is tender, and parotitis
may be preceded or accompanied by ear

The opening of the Stensen duct may be red
and edematous. The parotid swelling peaks
in approximately 3 days then gradually
subsides over 7 days. Fever resolves in 3
to 5 days along with the other systemic
symptoms.
A morbilliform rash is rarely seen.
Submandibular salivary glands may also
be involved or may be enlarged without
parotid swelling.

 The classic illness of mumps consists of
swelling of the parotid gland (ie, parotitis,
parotiditis). However, mumps is no longer the
most common cause of parotitis. Systemic
symptoms include low-grade fever, headache,
malaise, anorexia, and abdominal pain. Acid-
containing foods may aggravate discomfort of
the parotid gland. Ordinarily, the parotid gland
is not palpable, but in patients with mumps, it
rapidly progresses to maximum swelling over
several days. Unilateral swelling usually

 Orchitis: Approximately one third of
postpubertal male patients develop unilateral
orchitis. It usually follows parotitis but may
precede parotitis or occur in the absence of
parotitis. Usually, it appears in the first week of
parotitis, but it can occur in the second or third
week. Bilateral orchitis occurs much less
frequently, and although gonadal atrophy may
follow orchitis, sterility is rare even with
bilateral involvement. Prepubertal boys may
develop orchitis, but it is uncommon in those

 Meningoencephalitis
 CNS involvement with mumps is not uncommon,
and it occurs more often as meningitis rather than
true encephalitis. It may precede parotitis or
appear in the absence of parotitis but usually
occurs in the first week after parotitis. Headache,
fever, nausea, vomiting, and meningismus are
common. Marked changes in sensorium and
convulsions are not usual

In clinically diagnosed meningoencephalitis, a CSF
mononuclear pleocytosis occurs, as does normal
glucose, although hypoglycorrhachia has been reported.
The mumps virus may be isolated from CSF early in the
illness. Mumps meningoencephalitis carries a good
prognosis and is usually associated with an uneventful
recovery. Other clinical manifestations of mumps include
pancreatitis accompanied by severe abdominal pain,
chills, fever, and persistent vomiting. Thyroiditis,
oophoritis, and mastitis occasionally occur.

Deafness: Neuritis of the auditory nerve may result in
deafness. Sudden onset of tinnitus, ataxia, and vomiting
is followed by permanent deafness. Other neurologic
complications include facial nerve neuritis and myelitis.
Other complications: Less common complications
include arthritis, myocarditis, and hematologic
complications.

DIAGNOSIS.
When mumps was highly prevalent, the diagnosis
could be made based on history of exposure to
mumps infection, an appropriate incubation period,
and development of typical clinical findings.
Confirmation of the presence of parotiditis could
be made with demonstration of an elevated
amylase level.

Leukopenia with a relative lymphocytosis was a
common finding. Today, in patients with parotiditis
of >2 days of unknown cause, a specific diagnosis
of mumps should be confirmed or ruled out by
virologic or serologic means. This may be
accomplished by isolation of the virus in cell
culture, detection of viral antigen by direct
immunofluorescence, or identification of nucleic
acid by reverse transcriptase polymerase chain
reaction. Virus can be isolated from upper
respiratory tract secretions, CSF, or urine during
the acute illness.

Serologic testing is usually a more convenient and
available mode of diagnosis. A significant increase
in serum mumps immunoglobulin G (IgG) antibody
between acute and convalescent serum specimens
by complement fixation, neutralization
hemagglutination, or enzyme immunoassay (EIA)
tests establish the diagnosis. However, IgG
antibody tests may cross react with antibodies to
parainfluenza virus. More commonly, an EIA for
mumps IgM antibody is used to identify recent
infection. Skin testing for mumps is neither
sensitive nor specific and should not be used.

DIFFERENTIAL DIAGNOSIS.
Parotid swelling may be caused by many other
infections and noninfectious conditions. Viruses
that have been shown to cause parotitis include
parainfluenza 1 and 3, influenza A,
cytomegalovirus, Epstein-Barr virus,
enteroviruses, lymphocytic choriomeningitis virus,
and HIV.

Purulent parotitis, usually caused by
Staphylococcus aureus, is unilateral, extremely
tender, and associated with an elevated white blood
cell count, and may have purulent drainage from the
Stensen duct. Submandibular or anterior cervical
adenitis due to a variety of pathogens may also be
confused with parotitis. Other noninfectious causes
of parotid swelling include obstruction of the
Stensen duct, collagen vascular diseases such as
Sjögren syndrome, systemic lupus erythematosis,
and tumor.

TREATMENT.
No specific antiviral therapy is available for
mumps. Management should be aimed at reducing
the pain associated with meningitis or orchitis and
maintenance of adequate hydration. Antipyretics
may be given for fever

VIRAL HEPATITIS
Dr.Bouni-Tima-ade University_ infectious disease

A
“Infectious”
“Serum”
Viral hepatitis
Enterically
transmitted
Parenterall
y
transmitted
F, G, TTV
? other
E
NANB
B D C
Viral Hepatitis - Historical Perspectives

Source of
virus
feces blood/
blood-derived
body fluids
blood/
blood-derived
body fluids
blood/
blood-derived
body fluids
feces
Route of
transmission
fecal-oral percutaneous
permucosal
percutaneous
permucosal
percutaneous
permucosal
fecal-oral
Chronic
infection
no yes yes yes no
Prevention pre/post-
exposure
immunization
pre/post-
exposure
immunization
blood donor
screening;
risk behavior
modification
pre/post-
exposure
immunization;
risk behavior
modification
ensure safe
drinking
water
Type of Hepatitis
A B C D E

Hepatitis A Virus

Hepatitis A virus
 HAV is a single stranded RNA picornavirus.
 One stable serotype only.
 Difficult to grow in cell culture.
 Viral antigen is found in serum, stool and liver
only during acute infection.
 IgM antibody appear early in the disease but
diminishes within several weeks, followed by
the development of protective IgG antibody,
which persist usually for life.

Epidemiology
 Hepatitis A is the most common type of viral
hepatitis occurring world wide, often in
epidemics.
 The disease is commonly seen in autumn
and affects children and young adults.
 Overcrowding and poor sanitation facilitate
spread.
 There is no carrier state.

Transmission
 Spread of infection is mainly by the faecal-oral
route and arises from the ingestion of
contaminated water or food.
 Infected persons excrete viruses in the faeces
for about 2-3 weeks before the onset of the
illness and for up to 2 weeks thereafter.

Hepatitis A Virus Transmission
 Close personal contact
(e.g., household contact, sex contact, child day care
centers)
 Contaminated food, water
(e.g., infected food handlers, raw shellfish)
 Blood exposure (rare)
(e.g., injecting drug use, transfusion)

Endemicity
Diseas
e Rate
Peak Age
of Infection Transmission Patterns
High Low to
High
Early
childhood
Person to person;
outbreaks uncommon
Moderate High Late
childhood/
young adults
Person to person;
food and waterborne
outbreaks
Low Low Young adults Person to person;
food and waterborne
outbreaks
Very low Very low Adults Travelers; outbreaks
uncommon
Hepatitis A Virus Transmission

Hepatitis A - Clinical Features
 Non-specific symptoms:
Nausea.
Anorexia.
 Jaundice after 1 or 2 weeks.
 Urine become dark.
 Stool become pale.
 The liver is moderately enlarged.

 Spleen is palpable in about 10% of patients.
 Occasionally , tender lymphadenopathy is
seen.
 Transient rash in some cases.

 Incubation period: Average 30 days
Range 15-50 days
 Jaundice by <6 yrs, <10%
age group: 6-14 yrs, 40%-50%
>14 yrs, 70%-80%
 Complications: Fulminant hepatitis
Cholestatic hepatitis
Relapsing hepatitis
 Chronic sequelae: None

Complications
 Fulminant hepatitis with liver coma and death.
 Extra hepatic complications include:
 Arthritis.
 Vasculitis.
 Myocarditis.
 Renal failure.

Fecal
HAV
Symptoms
0 1 2 3 4 5 6 1
2
2
4
Hepatitis A Infection
Total anti-
HAV
Titre ALT
IgM anti-HAV
Months after exposure
Typical Serological Course

Laboratory Diagnosis
 Acute infection is diagnosed by the detection of HAV-IgM
in serum.
 Past Infection i.e. immunity is determined by the detection
of HAV-IgG.
 Cell culture – difficult and take up to 4 weeks, not
routinely performed
 Direct Detection – PCR of faeces. Can detect illness
earlier than serology but rarely performed.

 Many cases occur in community-wide outbreaks
 no risk factor identified for most cases
 highest attack rates in 5-14 year olds
 children serve as reservoir of infection
 Persons at increased risk of infection
 travelers
 homosexual men
 injecting drug users
Hepatitis A Vaccination.

 Pre-exposure
 Travelers to intermediate and high
HAV-endemic regions
 Post-exposure (within 14 days)
Routine
 household and other intimate contacts
Selected situations
 institutions (e.g., day care centers)
 common source exposure (e.g., food prepared by
infected food handler)
Hepatitis A Prevention - Immune
Globulin

Hepatitis B Virus

HEPATITIS B VIRUS -
VIROLOGY
Hepatitis B virus (HBV) is a member of
theHepadnavirus family-”hepatotropic DNA viruses”
• large DNA virus with a circular chromosome
with an RNA stage in the host cell during its
replicative cycle
• Replicative RNA subsequently produces viral
DNA that leads to synthesis of the viral proteins.
(retrovirus-like reverse transcription)

Hepatitis B Virus - Virology
• The major proteins involved in HBV infection
are the surface antigen (HBsAg), core
antigen (HBcAg) and the e antigen (HBeAg).
– HBsAg is an element of the outer surface of the
virus
– HBcAg and HBeAg are different forms of the same
polyprotein
– HBcAg is made up of subunit proteins to form the
genomic core of the full virus
– HBeAg is a truncated form thought to play a role in
signaling for viral replication

Hepatitis B Virus - Virology
 Double stranded DNA virus,the + strand not complete
 Replication involves a reverse transcriptase.
 Complete Dane particle 42 nm, 28 nm electron dense core,
containing HBcAg and HBeAg. The coat and the 22 nm
free particles contain HBsAg
 At least 4 phenotypes of HBsAg are recognized.
 The HBcAg is of a single serotype
 Hepatitis B virus (HBV) has been classified into 8
genotypes (A-H).
 It has not yet been possible to propagate the virus
in cell culture.

Epidemiology.
• HBV is a worldwide public health concern
– It is estimated that 350 million people are
carriers of the virus
– prevalence rates in Africa and Asia of greater
than 8%
– In developing nations, the major route of
acquisition of HBV is vertical transmission
– in the Western Hemisphere, most acquire HBV in
adolescence and adulthood via sexual or
parenteral routes

Epidemiology.
 2 billion with positive serology
 300 million HBV carriers
 500,000 deaths globally
 High Prevalence= SE Asia, China, Africa
 USA = 1.2 million chronic Hep B patients

 Sexual - sex workers and homosexuals are
particular at risk.
 Parenteral - IVDA, Health Workers are at
increased risk.
 Perinatal - Mothers who are HBeAg positive are
much more likely to transmit to their offspring
than those who are not. Perinatal transmission is
the main means of transmission in high
prevalence populations.
Hepatitis B Virus
Modes of Transmission

MODES OF TRANSMISSION
 Perinatal infection
 Blood Transfusion
 Horizontal transmission
 Sexual transmission
 Intravenous drug use / percutaneous
inoculation.
 Nosocomial
 Organ transplantation-Anti-HBc screening

HBV Clinical features
 Incubation of HBV after exposure averages 60-
90 days Range 45-180 days before the onset of
symptoms.
• Acute HBV infection is subtle in most cases
– may be symptomatic in about 30% of patients.

Symptoms of Hep B
 Early symptoms include:
-general discomfort, fatigue, lack of appetite,
skin rash, nausea, vomit, flu-like symptoms
 Relatively few cases : JAUNDICE follows
with yellow skin and dark urine
 Jaundice and other symptoms usually
resolve in 3-4 weeks

HBV CLINICAL FEATURES
 Symptoms include:
– Fever
– Jaundice
– Malaise
– abdominal pain
– clinical course identical to HAV.
• Symptoms appear after the peak period of
Hepatitis B surface antigen (HBsAg) levels
have peaked in the bloodstream

• 90% of patients with acute HBV infection will
resolve their illness spontaneously
• very small percentage of patients develop
fulminant hepatic failure
• 2-6% of older children and adults develop a
chronic carrier state where the virus remains
active at a low level-30% of 1-5 yr olds

• HBV carriers are at high risk for end stage
liver disease and ultimately hepatocellular
carcinoma-25% mortality in children who
acquire chronic infection at birth
• Patients with chronic HBV infection may also
present with glomerulonephritis secondary to
immune complex deposition.
• In addition to their own morbidity and
mortality, HBV carriers represent the
largest reservoir for transmission of HBV

EXTRAHEPATIC
MANIFESTAIONS
10-20% of patients
 Arthritis-dermatitis
 CNS: Seizures, Guillain-Barre' syndrome,
peripheral neuropathy
 CVS: Pericarditis, myocarditis Polyarteritis
nodosa
 GI: Pancreatitis
 RENAL:. Membranous glomerulonephritis
 HEME: aplastic anemia Cryoglobulinemia

 Incubation period: Average 60-90 days
Range 45-180 days
 Clinical illness (jaundice): <5 yrs, <10%
5 yrs, 30%-50%
 Acute case-fatality rate: 0.5%-1%
 Chronic infection: <5 yrs, 30%-90%
5 yrs, 2%-10%
Hepatitis B - Clinical Features

Spectrum of Chronic Hepatitis B Diseases
1Chronic Persistent Hepatitis – (asymptomatic)
2. Chronic Active Hepatitis - (symptomatic
exacerbations of hepatitis)
3. Cirrhosis of Liver
4. Hepatocellular Carcinoma

HEPATITIS B-PREGNANCY
HBV can infect pregnant women but does not
cause more severe disease than seen in the
general population
•Chronic carriers should have uncomplicated
pregnancies unless liver failure is present.
Significance of HBV infection during pregnancy
lies in risk of transmission to the infant-90%
of infants develop chronic HBV

Symptoms
HBeAg anti-HBe
Total anti-HBc
IgM anti-HBc anti-HBs
HBsAg
0 4 8 12 16 20 24 28 32 36 52 100
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Weeks after Exposure
Titre

IgM anti-HBc
Total anti-HBc
HBsAg
Acute
(6 months)
HBeAg
Chronic
(Years)
anti-HBe
0 4 8 12 16 20 24 28 32 36 52 Years
Titre
Progression to Chronic Hepatitis B Virus Infection

Symptomatic Infection
Chronic Infection
Age at Infection
Chronic Infection (%)
Symptomatic
Infection
(%)
Birth 1-6 months 7-12 months 1-4 years Older Children
and Adults
0
20
40
60
80
100
100
80
60
40
20
0
Outcome of Hepatitis B Virus Infection
by Age at Infection
Chronic
Infection
(%)

Chronic Hepatitis B Virus Infection
 Chronic viremia
 Responsible for most mortality
 Overall risk 5%
 Higher risk with early infection

 High (>8%):
 lifetime risk of infection >60%
 early childhood infections common
 Intermediate (2%-7%):
 lifetime risk of infection 20%-60%
 infections occur in all age groups
 Low (<2%):
 lifetime risk of infection <20%
 most infections occur in adult risk groups
Global Patterns of Chronic HBV
Infection

High Moderate
Low/Not
Detectable
blood semen urine
serum vaginal fluid feces
wound exudates saliva sweat
tears
breastmilk
Concentration of Hepatitis B
Virus in Various Body Fluids

Hepatitis B Complications
 Fulminant hepatitis
 Hospitalization
 Cirrhosis
 Hepatocellular carcinoma
 Death

Diagnosis
 A battery of serological tests are used for the diagnosis of acute and
chronic hepatitis B infection.
 HBsAg - used as a general marker of infection.
 HBsAb - used to document recovery and/or immunity to HBV
infection.
 anti-HBc IgM - marker of acute infection.
 anti-HBcIgG - past or chronic infection.
 HBeAg - indicates active replication of virus and therefore
infectiveness.
 Anti-Hbe - virus no longer replicating. However, the patient can still
be positive for HBsAg which is made by integrated HBV.
 HBV-DNA - indicates active replication of virus, more accurate than
HBeAg especially in cases of escape mutants. Used mainly for
monitoring response to therapy.

LABORATORY DIAGNOSIS
• Detection of HBV infection involves detecting
the presence of: – Viral
genetic material. – Viral
proteins (antigens). – Antibody
response to viral antigens.

HEPATITIS B-TREATMENT
 No need to treat acute HBV infection
 Chronic HBV can be treated because of high risk
of progression to:
– Cirrhosis
– Hepatocellular carcinoma

• Options are 4:
– Interferon-α-response rate of around 30%
after 4-6 months of therapy, most durable of
available therapies because lower relapse rate.
– Lamivudine(3TC)-arrests viral replication
temporarily, however mutation renders virus
resistant, viral load rises again but lower

 Adefovir- former HIV agent that is active against HBV
at lower concentrations. Active against lamivudine
resistant virus as well with no new resistance mutations
detected after 1 year.
Tenofovir- HIV agent that has activity against HBV,
good for treating dual infected patients, less experience
overall.

Treatment
 Interferon - for HBeAg +ve carriers with chronic active hepatitis. Response
rate is 30 to 40%.
 alpha-interferon 2b (original)
 alpha-interferon 2a (newer, claims to be more efficacious and efficient)
 Lamivudine - a nucleoside analogue reverse transcriptase inhibitor. Well
tolerated, most patients will respond favorably. However, tendency to relapse
on cessation of treatment. Another problem is the rapid emergence of drug
resistance.
 Adefovir – less likely to develop resistance than Lamivudine and may be used
to treat Lamivudine resistance HBV. However more expensive and toxic
 Entecavir – most powerful antiviral known, similar to Adefovir
 Successful response to treatment will result in the disappearance of HBsAg,
HBV-DNA, and seroconversion to HBeAg.

HEPATITIS B-PREVENTION
• Pillars of prevention are:
– Recombinant vaccine
– Hepatitis B Immune Globulin

• Vaccine:
– Recombinant protein (HBsAg) purified and
combined with adjuvant
– 3 doses given routinely to infants OR to
adolescents and high risk adults as catch
up program
– Prevents 90-95% protection that is durable

VACCINATION
 > 90% efficacy
 Indications:
 All neonates
 Household contacts
 High risk behavior
 Health care workers
 Chronic dialysis
 Repeated transfusion

Hepatitis B Vaccine
 Composition Recombinant HBsAg
 Efficacy 95% (Range, 80%-100%)
 Duration of
Immunity 20 years or more
 Schedule 3 Doses
 Booster doses not routinely recommended

Recommended Dose of Hepatitis
B Vaccine
Infants and children
<11 years of age
Adolescents 11-19
years
Adults >20 years
Recombivax HB
Dose (mcg)
0.5 mL (5)
0.5 mL (5)
1.0 mL (10)
Engerix-B
Dose (mcg)
0.5 mL (10)
0.5 mL (10)
1.0 mL (20)

• HBIG:
– Concentrated IVIG with high anti-HBV titer
– Used primarily for high risk post-exposure
prophylaxis
• Needle stick exposure
• Infant born to mother with known chronic infection or
unknown status-dose in first 12 hours if known HBsAg+
mom, up to 7th day if mom is determined later to be
HBsAg+ >>90-95% efficacy in preventing transmission
• Household contact with blood exposure
• Sexual contact with person with chronic HBV

Prevention
 Vaccination - highly effective recombinant vaccines are now
available. Vaccine can be given to those who are at increased
risk of HBV infection such as health care workers. It is also
given routinely to neonates as universal vaccination in many
countries.
 Hepatitis B Immunoglobulin - HBIG may be used to protect
persons who are exposed to hepatitis B. It is particular
efficacious within 48 hours of the incident. It may also be given
to neonates who are at increased risk of contracting hepatitis B
i.e. whose mothers are HBsAg and HBeAg positive.
 Other measures - screening of blood donors, blood and body
fluid precautions.

hypervariable
region
capsid envelop
e
protein
protease/helica
se
RNA-
dependent
RNA polymerase
c22
5’
cor
e
E1 E2 NS
2
NS
3
33c
NS
4
c-100
NS
5
3’
Hepatitis C Virus

Hepatitis C Virus
Genome resembled that of a flavivirus
positive stranded RNA genome of around 10,000 bases
1 single reading frame, structural genes at the 5' end, the non-
structural genes at the 3' end.
enveloped virus, virion thought to 30-60nm in diameter
 morphological structure remains unknown
HCV has been classified into a total of six genotypes
(type 1 to 6) on the basis of phylogenetic analysis
Genotype 1 and 4 has a poorer prognosis and response
to interferon therapy,

Hepatitis C Virus
• First discovered in 1989 to be the major
cause of transfusion related “non-A, non-B”
hepatitis
• Currently, there is no established cell culture
system for HCV
• chimpanzees are the only available
laboratory animal model, so little is still known
about the mechanisms of infection

Hepatitis C- The Burden
• Epidemiology-
– Approximately 2% of US is HCV antibody
positive- 4 million people
– 350 million people worldwide
– 0.2 to 0.4% of children are HCV antibody
positive
– Leading indication for adult liver transplant
in US

Hepatitis C-Transmission
• HCV is transmitted by contact with
contaminated blood or blood containing body
fluids:
– intravenous drug use
– blood transfusion or transplantation prior to
1992
– Vertical transmission

Hepatitis C-Transmission
• HCV is possibly transmitted by other routes, but
substantial proof is lacking:
– Breastfeeding-not likely and not contraindicated by
CDC
– Sexual transmission-not likely, but if so, VERY
inefficient means of transmission
– Sharing razors and toothbrushes-more likely than
others, actually contraindicated by CDC in guidelines
– Tattooing-unlikely and not an indication for testing
according to CDC

 Transfusion or transplant from infected donor
 Injecting drug use
 Hemodialysis (yrs on treatment)
 Accidental injuries with needles/sharps
 Sexual/household exposure to anti-HCV-positive
contact
 Multiple sex partners
 Birth to HCV-infected mother
Risk Factors Associated with
Transmission of HCV

Incubation period: Average 6-7 wks
Range 2-26 wks
Clinical illness (jaundice): 30-40% (20-30%)
Chronic hepatitis: 70%
Persistent infection: 85-100%
Immunity: No protective
antibody
response identified
Hepatitis C - Clinical Features

Clinical features
• Clinical manifestations:
– Acute subclinical hepatitis is most common after
blood borne exposure
– chronic hepatitis is also relatively asymptomatic.
– Symptoms are indolent when they do occur,
sometimes months to years later and include:
• Fever
• Fatigue
• jaundice.
– Patients may only present with signs of end stage
liver disease.

Clinical features
Clinical manifestations:
– 60-70% of adults progress to chronic
infection, men>women
– Only about 50% of children, increases with
age
– Acute Fulminant hepatic failure with HCV is
exceedingly rare

Chronic Hepatitis C Infection
 The spectrum of chronic hepatitis C infection is
essentially the same as chronic hepatitis B
infection.
 All the manifestations of chronic hepatitis B
infection may be seen, albeit with a lower
frequency i.e. chronic persistent hepatitis, chronic
active hepatitis, cirrhosis, and hepatocellular
carcinoma.

Symptoms
anti-
HCV
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4
Hepatitis C Virus Infection
Titre
Month
s
Years
Time after
Exposure

Hepatitis C-Pregnancy
• Acute HCV infection can and does occur
during pregnancy
• more common to see a pregnant patient who
either has known chronic HCV infection or has
chronic infection diagnosed during her prenatal
evaluation
• HCV infection has not been shown to be more
severe during pregnancy
• HCV has not been shown to more rapidly
progress during pregnancy

Hepatitis C-Pregnancy
• HCV is vertically transmitted
– 5-10% overall transmission, but only 3-5%
go on to chronic infection
– Jumps to 20-25% in setting of HIV- HCV
co-infection (pre-HAART era)

Laboratory Diagnosis
 HCV antibody - generally used to diagnose hepatitis C
infection. Not useful in the acute phase as it takes at least 4
weeks after infection before antibody appears.
 HCV-RNA - various techniques are available e.g. PCR and
branched DNA. May be used to diagnose HCV infection in
the acute phase. However, its main use is in monitoring the
response to antiviral therapy.
 HCV-antigen - an EIA for HCV antigen is available. It is
used in the same capacity as HCV-RNA tests but is much
easier to carry out.

Prognostic Tests
 Genotyping – genotype 1 and 4 have a worse prognosis overall and
respond poorly to interferon therapy. A number of commercial and in-
house assays are available.
 Genotypic methods – DNA sequencing, PCR-hybridization e.g. INNO-
LIPA.
 Serotyping – particularly useful when the patient does not have detectable
RNA.
 Viral Load – patients with high viral load are thought to have a poorer
prognosis. Viral load is also used for monitoring response to IFN
therapy. A number of commercial and in-house tests are available.

Treatment
 Interferon - may be considered for patients with
chronic active hepatitis. The response rate is
around 50% but 50% of responders will relapse
upon withdrawal of treatment.
 Ribavirin - there is less experience with ribavirin
than interferon. However, recent studies suggest
that a combination of interferon and ribavirin is
more effective than interferon alone.

 Screening of blood, organ, tissue donors
 High-risk behavior modification
 Blood and body fluid precautions
Prevention of Hepatitis C

HBsAg
RNA
 antigen
Hepatitis D (Delta) Virus

Hepatitis D Virus
 The delta agent is a defective virus which shows
similarities with the viroids in plants.
 The agent consists of a particle 35 nm in diameter
consisting of the delta antigen surrounded by an
outer coat of HBsAg.
 The genome of the virus is very small and consists
of a single-stranded RNA

 Coinfection
– severe acute disease.
– low risk of chronic infection.
 Superinfection
– usually develop chronic HDV infection.
– high risk of severe chronic liver disease.
– may present as an acute hepatitis.
Hepatitis D - Clinical Features

 Percutanous exposures
injecting drug use
 Permucosal exposures
sex contact
Hepatitis D Virus Modes
of Transmission

anti-HBs
Symptoms
ALT Elevated
Total anti-HDV
IgM anti-HDV
HDV RNA
HBsAg
HBV - HDV Coinfection
Time after Exposure
Titre

Jaundice
Symptoms
ALT
Total anti-HDV
IgM anti-HDV
HDV RNA
HBsAg
HBV - HDV Superinfection
Time after
Titre

 HBV-HDV Coinfection
Pre or postexposure prophylaxis to prevent
HBV infection.
 HBV-HDV Superinfection
Education to reduce risk behaviors among
persons with chronic HBV infection.
Hepatitis D - Prevention

Hepatitis E Virus

Hepatitis E Virus
 Calicivirus-like viruses
 unenveloped RNA virus, 32-34nm in diameter
 +ve stranded RNA genome, 7.6 kb in size.
 very labile and sensitive
 Can only be cultured recently

 Incubation period: Average 40 days
Range 15-60 days
 Case-fatality rate: Overall, 1%-3%
Pregnant women,
15%-25%
 Illness severity: Increased with age
 Chronic sequelae: None identified
Hepatitis E - Clinical Features

Symptoms
ALT IgG anti-HEV
IgM anti-HEV
Virus in stool
0 1 2 3 4 5 6 7 8 9 1
0
1
1
1
2
1
3
Hepatitis E Virus Infection
Typical Serologic
Course
Titer

 Most outbreaks associated with faecally contaminated drinking
water.
 Several other large epidemics have occurred since in the Indian
subcontinent and the USSR, China, Africa and Mexico.
 In the United States and other nonendemic areas, where
outbreaks of hepatitis E have not been documented to occur, a
low prevalence of anti-HEV (<2%) has been found in healthy
populations. The source of infection for these persons is
unknown.
 Minimal person-to-person transmission.
Hepatitis E -
Epidemiologic Features

 Avoid drinking water (and beverages with ice) of
unknown purity, uncooked shellfish, and uncooked
fruit/vegetables not peeled or prepared by traveler.
 IG prepared from donors in Western countries
does not prevent infection.
 Unknown efficacy of IG prepared from donors in
endemic areas.
 Vaccine?
Prevention and Control Measures for
Travelers to HEV-Endemic Regions

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