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Microbiology, virology, immunology
department
RNA-VIRUSES:
PICORNAVIRUSES
ORTHOMYXOVIRUSES
PARAMYXOVIRUSES
CAUSATIVE AGENTS OF
HEPATITIS VIRUS
Genera of Picornaviruses
Enterovirus
Polio, types 1-3
Coxsackie A ,
1-24
types
Diseases of the human (and other) alimentary
tract (e.g. polio virus)
Coxsackie B, types 1-6
Echo, types 1-34
Other enteroviruses,
types 68-71
Rhinovirus,
types 1-115
Cardiovirus
Aphthovirus
Hepatovirus
Others
Disease of the nasopharyngeal region (e.g.
common cold virus)
Murine encephalomyocarditis, Theiler's murine
encephalomyelitis virus
Foot and mouth disease in cloven footed
animals
Human hepatitis virus A
Drosophila C virus, equine rhinoviruses, cricket
paralysis virus
Pathogenesis of enterovirus infection
Replication in
oropharynx
Rhino,echo,
coxsackie,polio
Primary viremia
Secondary viremia
Target Tissue
Skin
Muscle
Brain
Meninges
Liver
Echo
Echo
Polio
Echo
Echo
Coxsackie
Coxsackie
Coxsackie
Polio
Coxsackie
A
A, B
Coxsackie
Clinical Picornavirus Syndromes
Virus
Polioviruses
(types 1-3)
Diseases (Virus Type)
Undifferentiated febrile illnesses
(types 1-
3)
Aseptic memingitis (types 1-3)
Paralisis and encephalitic
diseases
(types 1-3)
Coxsackievirus
group A
(A1-A, A-24)*
Acute hemorrhagic conjunctivitis (type 24)
Herpangina (types 2-6, 8, 10, 22)
Exanthem (types 4, 5, 6, 9, 16)
Hand-foot-mouth disease (types 5, 10, 16)
Aseptic memingitis (types 1, 2, 4-7, 9, 10, 14,
16, 22)
Paralysis and encephalitic diseases
(occasional types 4, 7, 9, 10)
Hepatitis (types 4, 9)
Virus
Diseases (Virus Type)
Upper and lower respiratory illnesses
Coxsackievirus
9, 10, 16, 21, 24)
group A (A1-A, A- (types
Lymphonodular pharyngitis (10)
24)*
Infantile diarrhea (types 18, 20, 21, 22, 24
variant)
Undifferentiated febrile illnesses
(types 1-
6)
Pleurodinia (types 1-5)
Pericarditis, myocarditis (types 1-5)
Aseptic meningitis types (1-6)
Paralysis and encephalitic diseases
(occasional types 1-5)
Severe systemic infection in infants,
meningoencephalitis and myocarditis
(types 1-5)
Upper and lower respiratory
illnesses
(types 4, 5)
Exanthem, hepatitis, diarrhea (types 5)
Virus
Echoviruses
(1-7, 9, 11,
29-33)*
Diseases (Virus Type)
Aseptic meningitis (many seroypes )
Paralysis and encephalitic diseases
(occasional types 1, 2, 4, 6, 7, 9, 11, 14-16, 18, 22,
30)
Exanthem
(types 1-9, 11, 14, 16, 18, 19, 25, 30,
32)
Hand-foot-mouth disease (19)
Pericarditis, myocarditis (types 1, 6, 9,
19,
22)
Upper and lower respiratory illnesses
(types 4, 9, 11, 20, 22, 25)
Neanatal diarrhea (types 11, 14, 18, 20, 32)
Epidemic mialgia (types 1, 6, 9)
Hepatitis (types 4, 9)
Virus
New
enteroviruses
Diseases (Virus Type)
Pneumonia and bronchiolitis
(types
68, 69)
Acute
hemorrhagic
conjunctivitis
(type 70)
Rhinoviruses
(1-115)
Hepatovirus
(Hepatitis A)
Aseptic meningitis,
meningoencephalitis
Hand-foot-mouth disease (71)
Hepatitis (type 72)
Upper and lower respiratory
illnesses (types 1-115)
Gastroenteritis and hepatitis A
* Reclassification of coxsackievirus A23 as echovirus 9, echovirus 8 as 1, echovirus 10 as
reovirus, echovirus 28 as rhinovirus type 1A, and echovirus 34 as coxsackievirus A24.
Properties of enteroviruses
Property
Enteroviruses
Size (nm)
22-30
Capsid form Icosahedral
Polypeptide VP1, VP2,
VP3, VP4
‘+’, single
RNA type
stain
Stable
Acid
Optimal
temperature for
growth(oC)
37
RNA
Properties
of enteroviruses
This genome RNA serves as an mRNA and
initiates
the
synthesis
of
virus
macromolecules.
The poliomyelitis virus has neither an outer
membrane nor lipids and is therefore not
sensitive to the effect of ether and sodium
desoxycholate.
POLIOMYELITIS
Picornavirus


3 types: Poliovirus
1,2,3
30 nm in size
Cultivation. SPE.
The poliomyelitis virus is
cultivated on kidney cells of
green African monkeys and on
diploid human cells devoid of
latent SV40 viruses.
The cytopathic effect is
attended by destruction and the
formation of granules in the
infected cells.
Pathogenesis
Source
of infection: Apparent and
subclinical patients
Incubation: is usually 7-14 days, but it may
range from 3 to 35 days.
Transmission
 Fecal
– oral route: poor hygiene,
dirty diapers (especially in day-care
settings)
 Ingestion via contaminated food
and water
 Contact with infected hands
 Inhalation of infectious aerosols
Pathogenesis
1. The mouth is the portal of entry of the
virus.
2. The virus first multiplies in the tonsils,
the lymph nodes of the neck, Peyer's patches,
and the small intestine.
3. Viremia
4. The central nervous system may then be
invaded by way of the circulating blood.
Poliovirus can spread along axons of peripheral
nerves to the central nervous system , and there
it continues to progress along the fibers of the
lower motor neurons to increasingly involve the
spinal cord or the brain. The anterior horn cells
of the spinal cord are most prominently involved.
Clinical Findings. When an individual
susceptible to infection is exposed to the
virus, one of the following responses may
occur:
 inapparent infection without symptoms
(asymptomatic illness), the minor illness –
90% infected people
 aseptic meningitis – 1%-2% of patients
with poliovirus infections,
 paralytic poliomyelitis, the major illness
0.1% to 2% of persons with poliovirus
Only about 1%
recognized clinically.
of
infections
are
Abortive Poliomyelitis. This is the
commonest form of the disease. The
patient has only the minor illness,
characterized by fever, malaise,
drowsiness, headache, nausea, vomiting,
constipation, and sore throat in various
combinations. The patient recovers in a
few days. The diagnosis of abortive
poliomyelitis can be made only when the
virus
is
isolated
or
antibody
development is measured.
Nonparalytic Poliomyelitis (Aseptic
Meningitis). In addition to the above
symptoms and signs, the patient with
the
nonparalytic
form
presents
stiffness and pain in the back and neck.
The disease lasts 2-10 days, and
recovery is rapid and complete. In a
small percentage of cases, the disease
advances to paralysis.
Paralytic Poliomyelitis. The major
illness usually follows the minor illness
described above, but it may occur
without the antecedent first phase.
The predominating complaint is flaccid
paralysis resulting from lower motor
neuron damage. The maximal recovery
usually occurs within 6 months, with
residual paralysis lasting much longer.
Child with polio sequelae
Lab Diagnosis
Definitive diagnosis is made by osolation of
the virus from stool, CFS, oropharyngeal
secretions
 Cell culture involves fibroblastic MRC-5 cells
CPE is usually evident within 36 hours
 Serotyping is based on neutralization of CPE
by standardized antisera using intersecting
pool followed by specific sera.
 ELISA
 IFA
 neutralizing Test
 CFT

Prevention
Both oral polio vaccine (OPV live,
attenuated， Sabin, 1957) and
inactivated poliovirus vaccine (IPV,
Salk, 1954) are avilable
IPV is used for adult immunization
and Immunocopromised patients
COXSACKIEVIRUSES
The coxsackieviruses comprise a large
subgroup of the enteroviruses. They
produce a variety of illnesses in human
beings, including aseptic meningitis,
herpangina, pleurodynia, hand, foot, and
mouth disease, myo- and pericarditis,
common colds, and possibly diabetes.
Coxsackieviruses have been divided
into 2 groups, A and B, having different
pathogenic potentials for mice.
Group A viruses produce widespread myositis
in the skeletal muscles of newborn mice,
resulting in flaccid paralysis without other
observable lesions.
Group B viruses may produce spasticity effect
in sucking mice, focal myositis, encephalitis,
and, most typically, necrotizing steatitis
involving mainly fetal fat lobules. Some B
strains also produce pancreatitis, myocarditis,
endocarditis, and hepatitis in both suckling and
adult mice.
Normal adult mice tolerate infections with
group B coxsackieviruses.
Herpangina: There is an abrupt onset of fever, sore
throat, anorexia, dysphagia, vomiting, or abdominal pain. The
pharynx is usually hyperaemic, and characteristic discrete
vesicles occur on the anterior pillars of the fauces, the
palate, uvula, tonsils, or tongue. The illness is self-limited
and most frequent in small children.
Exanthems – Rubelliform rashes
Hand, Foot, and Mouth Disease: The syndrome is
characterized by oral and pharyngeal ulcerations and a
vesicular rash of the palms and soles that may spread to the
arms and legs. Vesicles heal without crusting, which clinically
differentiates them from the vesicles of herpes- and poxviruses. The rare deaths are caused by pneumonia.
Hand-foot-and-mouth disease

Hand-foot-and-mouth
disease: mostly
coxackie A

fever, malaise, sore
throat, vesicles on
bucсal mucosa,
tongue, hands, feet,
buttocks

highly infectious

resolution – 1w
ECHOVIRUSES
(enteric cytopathogenic human orphan
viruses)
Not produce diseases in sucking mice,
rabbits, or monkeys. Monkey kidney and
human embryonated kidney cell culture
Aseptic meningitis, febrile illnesses with or
without rash, common colds, and acute
hemorrhagic conjunctivitis are among the
diseases caused by echoviruses.
Boston exanthem disease. Rashes are commonest
in young children.
RHINOVIRUSES
Rhinoviruses
are
isolated
commonly
from the nose and
throat
but
very
rarely from feces.
These viruses cause
upper
respiratory
tract
infections,
including
the
"common cold."
Orthomyxovirus Family
The name myxovirus was originally applied
to influenza viruses. It meant virus with an
affinity for mucins.
A model of the influenza virion
Types: A, B, C
Influenza A:
In Birds
16 H variants
9 N variants
In Humans
3 H variants
(H1, H2, and H3)
2 N variants
(N1 and N2)
Subtypes: H1N1, H2N2,H2N3
Influenza Viruses:
Antigenic Shift
Avian
Reservoir
Human
virus
Avian
virus
Other
mammals?
Swine
New
Reassorted
virus
Influenza Viruses:
Antigenic Drift

Gradual accumulation of mutations
that allow the hemagglutinin to escape
neutralizing antibodies (Point mutation
in HA gene)

Epidemic strains thought to have
changes in three or more antigenic
sites
Pathogenesis and Pathology
The virus enters the respiratory tract in airborne
droplets. Viremia is rare. Virus is present in the
nasopharynx from 1-2 days before to 1-2 days after
onset of symptoms.
Inflammation of the upper respiratory tract
causes necrosis of the ciliated and goblet cells of the
tracheal and bronchial mucosa but does not affect
the basal layer of epithelium.
Interstitial pneumonia may occur with necrosis of
bronchiolar epithelium and may be fatal. The
pneumonia is often associated with secondary
bacterial invaders: staphylococci, pneumococci,
streptococci, and Haemophilus influenzae.
Clinical Findings
The incubation period is 1 or 2 days.
Chills, malaise, fever, muscular aches,
prostration, and respiratory symptoms may
occur. The fever persists for about 3 days;
complications are not common, but
pneumonia, myocarditis, pericarditis, and
central nervous system complications occur
rarely. The latter include encephalomyelitis,
polyneuritis, Guillain-Barre syndrome, and
Reye's syndrome (see below).
Influenza Vaccines




Whole virus vaccine: inactivated virus
vaccine grown in embryonated eggs; 7090% effective in healthy persons <65 years
of age, 30-70% in persons ≥65 years
Split virus vaccine: previously associated
with fewer systemic reactions among the
elderly and children <12 years
Subunit vaccine: composed of H and N
Live, attenutated influenza virus vaccines
under development
Influenza: Chemoprophylaxis
Amantadine and rimantadine: effective
against type A, but not type B, influenza
viruses; block the M2 ion channel
 70-90% effective in preventing illness
 Administered to individuals at high risk of
complications who are vaccinated after
outbreak of infection, persons with
immune defficiency

Influenza: Chemotherapy
Amantadine (adults and children ≥ 1 year)
and rimantadine (adults)
 Zanamivir and oseltamivir:
neuraminidase inhibitors active against
both type A and B influenza viruses
 Reduce duration of illness by ~1 day when
administered within 2 days of the onset of
illness (uncomplicated influenza)

Laboratory Diagnosis
Throat washings or garglings are obtained
within 3 days after onset and should be tested at
once or stored frozen. Penicillin and streptomycin
are added to limit bacterial contamination.
For rapid detection of influenza virus in clinical
specimens, positive smears from nasal swabs may
be demonstrated by specific staining with
fluorescein-labeled antibody.
Paired sera are used to detect rises in HI, CF,
or Nt antibodies.
Family Paramyxoviridae
Genes:
Morbillivirus – measles virus,
Respirovirus – parainfluenza virus
(serotypes 1 and 3)
Rubulavirus - mumps virus,
parainfluenza virus
2, 4а, 4b),
Pneumovirus – RS-virus
(serotypes
PARAMYXOVIRUSES
pleomorphic
HN/H/G glycoprotein
SPIKES
F glycoprotein
SPIKES
helical nucleocapsid (RNA minus
NP protein)
lipid bilayer membrane
polymerase complex
M protein
STRUCTURE-PARAMYXOVIRUSES
Cell fusion. In the course of infection, paramyxo-
viruses cause cell fusion, long recognized as giant cell
formation.
MUMPS (Epidemic Parotitis)
Mumps is an acute contagious disease
characterized
by
a
nonsuppurative
enlargement of one or both of the parotid
glands, although other organs may also be
involved.
Properties of the Virus: The mumps virus
particle has the typical paramyxovirus
morphology. Typical also are the biologic
properties of hemagglutination, neuraminidase,
and hemolysin.
Epidemiology
The disease reaches its highest incidence in
children age 5-15 years, but epidemics occur
in army camps.
Humans are the only known reservoir of
virus.
The virus is transmitted by direct contact,
airborne droplets, or fomites contaminated
with saliva and, perhaps, urine. The period of
communicability is from about 4 days before
to about a week after the onset of symptoms.
Pathogenesis and Pathology
The virus travels from the mouth to the
parotid gland, where it undergoes primary
multiplication. This is followed by a generalized
viremia and localization in testes. ovaries,
pancreas, thyroid, or brain.
The ducts of the parotid glands show
desquamation
of
the
epithelium,
and
polymorphonuclear cells are present in the
lumens. There are interstitial edema and
lymphocytic infiltration.
Orchitis
PARAINFLUENZA VIRUS
The
parainfluenza
viruses
are
paramyxoviruses with morphologic and biologic
properties typical of the genus.
They grow welt in primary monkey or human
epithelial cell culture but poorly or not at all in
the embryonated egg. They produce a minimal
cytopathic effect in cell culture but are
recognized by the hemadsorption method.
Laboratory diagnosis may be made by the HI,
CF, and Nt tests.
PIV STRUCTURE
MEASLES (Rubeola)
Measles is an acute, highly infectious
disease
characterized
by
a
maculopapular
rash,
fever,
and
respiratory symptoms.
Properties of the Virus: Measles
virus is a typical paramyxovirus. It
lacks neuraminidase activity.
Measles virus
Pathogenesis and Pathology
Infection is contracted by inhalation of droplets
expelled in sneezing or coughing. Measles is spread
during the catarrhal prodromal period; they are
infectious from 1-2 days prior to the onset of symptoms
until a few days after the rash has appeared
The virus enters the respiratory tract, enters cells,
and multiplies there. During the prodrome, the virus is
present in the blood, throughout the respiratory tract,
and
in
nasopharyngeal,
tracheobronchial,
and
conjunctival secretions. It persists in the blood and
nasopharyngeal secretions for 2 days after the
appearance of the rash. Transplacental transmission of
the virus can occur.
Pathogenesis and Pathology
Koplik's spots are vesicles in the mouth formed
by focal exudations of serum and endothelial
cells, followed by focal necrosis. In the skin the
superficial capillaries of the corium are first
involved, and it is here that the rash makes its
appearance.
Generalized
lymphoid
tissue
hyperplasia occurs. Multinucleate giant cells are
found in lymph nodes, tonsils, adenoids, spleen,
appendix, and skin. In encephalomyelitis, there
are
petechial
hemorrhages,
lymphocytic
infiltration, and later, patchy demyelination in the
brain and spinal cord.
Koplik's spots
RESPIRATORY SYNCYTIAL (RS)
VIRUS
This labile paramyxovirus produces a
characteristic syncytial effect, the
fusion of cells in human cell culture. It is
the single most serious cause of
bronchiolitis and pneumonitis in infants.
Properties of the Virus: RS virus does
not hemagglutinate.
RSV- Structure
immunofluoresent stain
RSV- syncytium formation
Pathogenesis and Pathology
This disease is transmitted by coughing,
sneezing, sharing wash cloths towels and
other things with someone with RSV.
This disease is
extremely serious
when it comes to
children and infants
under the age of 3 and
elders.
This disease can result
in death.
Symptoms for this disease are: sneezing, runny
nose, sore throat, low fever, common cold
symptoms just more severe.
Treatment:
Supportive
Fluids, oxygen,
respiratory support,
bronchodilators
Antiviral Agents
Ribavirin (Virazole), a
synthetic guanosine
analogue, given as an
aerosol
RSV Bronchiolitis- clinical features
Prophylaxis
 Combination
live
virus
(measles-mumps-rubella)
vaccines
 Live attenuated measles virus vaccine
effectively prevents measles.
Hepatitis is an inflammation of the liver.
Human hepatitis is caused by at least six
genetically and structurally distinct viruses.
The diseases caused by each of these
viruses are distinguished in part by the
length of their incubation periods and the
epidemiology of the infection.
Characteristics of Human Hepatitis Viruses
Virus
Family/ Genus
Size/
Genome
Length
Transmi
of
ssion of
Incuba
Infection
tion
Vaccine
HAV
Picornaviridae
(enterovirus
72)
27-30
nm,
ss RNA
15-40
days
Mostly
oralfecal
No
HBV
Hepadnaviridae
(hepadnavirus)
142 nm,
circular
ds DNA
50180
days
Parenteral
Recombi
nant
subunit
vaccine
HCV
Flaviviridae
30-50
nm
ssd RNA
14-28
days
Parenteral
No
Characteristics of Human Hepatitis Viruses
Size/
Genome
Length
of
Incubation
Transmis Vaccine
sion of
Infection
Virus
Family/ Genus
HDV
Unclassified
35-40
nm
ss RNA
50-180
days*
Parenteral
No
HEV
Caliciviridae
27-34
nm
sst RNA
6
weeks
Oralfecal
No
Hepatitis A virus
Electron microscopy of fecal extracts
Hepatitis A virus
Family
Genus
Virion
Envelope
Genome
Stability
Transmission
Prevalence
Fulminant disease
Chronic disease
Oncogenic
Picornaviridae
Hepatovirus
27 nm icosahedral
No
ssRNA
Heat- and acid-stable
Fecal-oral
High
Rare
Never
No
Global Prevalence of Hepatitis A
Infection
HAV Prevalence
High
Intermediate
Low
Very Low
Hepatitis A Transmission
Fecal-oral contamination of food or water
Food handlers
Raw shellfish
Travel to endemic areas
Close personal contact
Household or sexual contact
Daycare centers
Natural infection with HAV is seen only in
human.
Hepatitis A - Clinical Features
• Incubation period:
• Jaundice by
age group:
• Complications:
• Chronic sequelae:
Average 30 days
Range 15-50 days
<6 yrs,
<10%
6-14 yrs, 40%-50%
>14 yrs, 70%-80%
Fulminant hepatitis
Cholestatic hepatitis
Relapsing hepatitis
None
Clinical Variants
of Hepatitis A Infection
Asymptomatic (anicteric) disease
Children under 6 years of age, > 90%
Children from 6-14 years old, 40-50%
Symptomatic (icteric) disease
Adults and children over 14, 70-80%
Pathogenesis
of Hepatitis A virus infections
During an asymptomatic incubation period, the
liver is infected and large amounts of virus can be
shed in the feces.
Symptoms usually begin abruptly with fever,
nausea, and vomiting. The major area of cell
necrosis occurs in the liver, and the resulting
enlargement of the liver frequently causes
blockage of the biliary excretions, resulting in
jaundice, dark urine, and clay colored stool. A
fulminant form of hepatitis A occurs in only 1% to
4% of patients. Complete recovery can require 8
to 12 weeks, especially in adults.
Concentration of Hepatitis A Virus
in Various Body Fluids
Body fluid
Feces
Serum
Saliva
Urine
100
102
104
Infection Doses per ml
106
108
1010
During convalescence, patients frequently
remain
weak
and
occasionally
mentally
depressed.
In humans, the severity of the disease varies
considerably with age, most cases occurring in
young children are mild and undiagnosed,
resolving without sequelae. In contrast to HBV,
HAV infections result in no extrahepatic
manifestations of acute infection and no long term
carrier state, and they are not associated with
either cirrhosis or primary hepatocellular
carcinoma.
Diagnosis
of Hepatitis A virus infections.
The diagnosis of individual cases of hepatitis A
usually is not possible without supporting
laboratory findings. Virus particles frequently can
be detected in fecal extracts by use of IFT.
Standard RIA also can be used to detect the
presence of HAV antigens in fecal extracts. An
ELISA using anti-HAV linked to either horseradish
peroxidase or alkaline phosphatase also is used to
detect fecal HAV.
In addition, a specific diagnosis of hepatitis A
can be made by demonstrating at least a four fold
rise in anti-HAV antibody levels in serum.
Typical Serologic Course of Acute
Hepatitis A Virus Infection
Symptoms
ALT
Total anti-HAV
Fecal
HAV
0
1
IgM anti-HAV
2
3
4
5
6
Months after exposure
12
24
Control
of Hepatitis A virus infections.
Proper
sanitation
to
prevent
fecal
contamination of water and food is the most
effective way to interrupt the fecal-oral
transmission of hepatitis A.
Pooled immune serum globulin from a large
number of individuals can be used to treat
potentially
exposed
poisons,
and
its
effectiveness has been well established.
Control
of Hepatitis A virus infections.
Formalin inactivated HAV vaccines have
been developed and some have been
licensed.
Additional approaches using recombinant
DNA techniques also are being used to
generate
subunit vaccines or novel
recombinant vaccine strains.
Structure
of the Hepatitis B virion
HBe
FIGURE. Fraction of the blood serum from a patient with a
severe ease of hepatitis. The larger spherical particles, or Dane
particles, are 42 nm in diameter and are the complete hepatitis B
virus. Also evident are filaments of capsid protein (HBsAg).
Hepatitis B virus
Family
Genus
Envelope
Genome
Stability
Transmission
Prevalence
Fulminant disease
Chronic disease
Oncogenic
Hepadnaviridae
Orthohepadnavirus
Yes (HBsAg)
dsDNA
Acid-sensitive
Parenteral
High
Rare
Often
Yes
HBV - Epidemiology
About 300 million people world-wide are
thought to be carriers of HBV, and many carriers
eventually die of resultant liver disease.
Many HBV infections are asymptomatic
(especially in children). However, many infections
become persistent, leading to a chronic carrier
state. This can lead to chronic active hepatitis and
cirrhosis later in life. The HBV carrier state also is
strongly associated with one of the most common
visceral
malignancies
world-wide,
primary
hepatocellular carcinoma.
Epidemiology
of Hepatitis B virus infections.
For years, it was believed that a person could
become infected only by the injection of blood or
serum from an infected person or by the use of
contaminated needles or syringes. As a result,
the older name for this disease was serum
hepatitis.
It has now been shown that this supposition is
not true.
Epidemiology
of Hepatitis B virus infections.
Using serologic techniques, HBsAg has been
found in feces, urine, saliva, vaginal secretions,
semen, and breast milk. Undoubtedly, the
mechanical transmission of infected blood or
blood products is one of the most efficient
methods of viral transmission, and infections
have been traced to tattooing, ear piercing,
acupuncture, and drug abuse. Neonatal
transmission also appears to occur during
childbirth. Virus can be sexually transmitted.
Hepatitis B Transmission
1. HBV spread mainly by parenteral route
2. direct percutaneous inoculation of infected serum
or plasma
3. indirectly through cuts or abrasions
4. absorption through mucosal surfaces
5. absorption of other infectious secretions (saliva or
semen during sex)
6. possible transfer via inanimate environmental
surfaces
7. vertical transmission soon after childbirth
(transplacental transfer rare)
8. close, intimate contact with an infected person
Who is at greatest risk
for HBV infection?
drug abusers
 blood product recipients
 accounts for 5-10% postransfusion hepatitis
 hemodialysis patients
 people from southeast asian countries
(70-80%)
Who is at greatest risk
for HBV infection?
 lab personnel working with blood products
 sexually active homosexuals
 persons with multiple and frequent sex
contacts
 medical/dental personnel
In hospitals, HBV infections are a risk for both
hospital personnel and patients because of
constant exposure to blood and blood products.
Pathogenesis
of hepatitis B virus infections.
Acute hepatitis caused by HBV
cannot be clinically distinguished
from hepatitis caused by HAV.
HBV
infections
are
characterized by a long incubation
period, ranging from 50 to 180
days.
Symptoms such as fever, rash,
and arthritis begin insidiously, and
the severity of the infection varies
widely. Mild cases that do not result
in jaundice are termed anicteric.
In more severe cases,
characterized by
headache, mild fever,
nausea, and loss of
appetite, icterus
(jaundice) occurs 3 to 5
days after the initial
symptoms.
The duration and severity of the disease vary from
clinically inapparent to fatal fulminating hepatitis. The
overall fatality rate is estimated to be 1% to 2%, with
most deaths occurring in adults older than 30 years of
age.
Differential Characteristics
of Hepatitis A and Hepatitis B
Characteristic
Hepatitis A
Hepatitis B
Length of incubation
period
15-40 days
50-180 days
Host range
Humans and possibly
nonhuman primates
Humans and some
nonhuman primates
Seasonal occurrence
Higher in fall and winter Year round
Age incidence
Much higher in children All ages
Occurrence of
jaundice
Much higher in adults
Higher in adults
Virus in blood
2-3 weeks before
illness to 1-2 weeks
after recovery
Several weeks before
illness to months or
years after recovery
Differential Characteristics
of Hepatitis A and Hepatitis B
Characteristic
Hepatitis A
Hepatitis B
Virus in feces
2-3 weeks before
illness to 1-2
weeks after
recovery
Rarely present, or
present in very
small amounts
Size of virus
27-32 nm
42 nm
Diagnosis based
on
Liver function
tests,
clinical symptoms,
and history
Liver function
tests, clinical
symptoms, history,
and presence of
HBsAg in blood
Effective vaccine
No
Yes
Chronic Hepatitis B Virus Infections.
Between 6% and 10% of clinically
diagnosed patients with hepatitis B
become chronically infected and continue
to have HBsAg in their blood for at least 6
months, and sometimes for life.
Chronic infections can be subdivided
into two general categories:
1. chronic persistent hepatitis
2. and chronic active hepatitis.
Chronic Hepatitis B Virus Infections.
The latter is the most severe and often
eventually leads to cirrhosis or the development
of primary hepatocellular carcinoma.
The prevalence of chronic carriers varies
widely in different parts of the world, from 0.1%
to 0.5% in the United States to up to 20% in
China, Southeast Asia, and some African
countries.
Diagnosis
of Hepatitis B virus infections.
As in all cases of viral hepatitis, abnormal liver
function is indicated by increased levels of liver
enzymes such as serum glutamic oxaloacetic
transaminase and alanine aminotransferase (ALT).
The presence of HBsAg confirms a diagnosis of
hepatitis B, and its serologic detection is routinely
carried out in diagnostic laboratories and blood
banks using radioimmunoassays or enzyme-linked
immunosorbent assay's.
Diagnosis
of Hepatitis B virus infections.
HBV core protein presence in serum
is believed to reflect active replication
of HBV and is a marker for active
disease. The appearance of anti-HBc
antibodies generally correlates with a
good prognosis and a decline in virus
replication.
Diagnosis
of Hepatitis B virus infections.
All carriers have antibodies to HBcAg, and
some have antibodies to HBeAg. Those who do
not possess antiHBe may have circulating
HBeAg. Carriers with high concentrations of
Dane particles and circulating HBeAg appear to
be more likely to suffer liver damage than those
in whom only HBsAg can be detected. However,
such persons are much more likely to be
transmitters of the disease than are those who
have solely HBsAg in their blood.
PRACTICE
HBsAg
 HBcAB (TOTAL)
 HBsAB
 HAV-IGM
 HCV

N.
N.
N.
N.
N.
NO evidence of viral hepatitis viruses.
PRACTICE
HBsAG
 HBcAB (TOTAL)
 HBsAB
 HAV-IGM
 HCV

PAST INFECTION.
N.
P.
P.
N.
N.
PRACTICE
HBsAg
 HBcAB (total)
 HBsAB
 HAV-IGM
 HCV

IMMUNIZATION.
N.
N.
P.
N.
N.
PRACTICE
HBsAg
 HBcAB (Total)
 HBsAB
 HAV-IGM
 HCV

P.
P.
N.
N.
N.
MAY BE ACUTE OR CHRONIC.
Order Hep. B Core IgM to clarify.
The IgM will be positive , If Acute.
PRACTICE
HBsAg
 HBcAB (TOTAL)
 HBsAB
 HAV-IGM
 HCV

P.
P.
N.
P.
P.
Co-infection with HBV, HAV, and HCV
PRACTICE





HBsAG
HBcAB (total)
HBsAB
HAV-IGM
HCV
P.
P.
P.
N.
N.
Past infection with recovery, and
then re-infection that has become
chronic, this is very rare but does
happen.
CONTROL
OF HEPATITIS B VIRUS INFECTIONS.
 The examination of all donor blood for the
presence of HBsAg.
 Passive immunization with hepatitis B immune
globulin (HBIG). One important and effective use
for HBIG, however, is the prevention of active
hepatitis B infections in neonates born to
mothers who are chronic carriers of HBsAg.
HBIG also can be given to nonimmune
individuals known to have been exposed to HBV.
 Active immunization with HBsAg promises to
provide a vehicle for the control of hepatitis B.
Hepatitis C virus.
HCV is RNA virus. Sequence analysis has revealed
that HCV is organized in a manner similar to the
flaviviruses and that it shares biologic characteristics with
this family.
Structural model of the Hepatitis C virus.
Model of Human Hepatitis C Virus
Lipid Envelope
Capsid Protein
Nucleic Acid
Envelope Glycoprotein E2
Envelope Glycoprotein E1
Hepatitis C viruses
Family
Genus
Virion
Envelope
Flaviviridae
Hepacivirus
60 nm spherical
Yes
Genome
Stability
Transmission
ssRNA
Ether-sensitive, acid-sensitive
Parenteral
Prevalence
Fulminant disease
Chronic disease
Oncogenic
Moderate
Rare
Often
Yes
Hepatitis C: A Global Health Problem
170-200 Million (M) Carriers Worldwide
United
States
3-4 M
Americas
12-15 M
Western
Europe
5M
Eastern
Europe
10 M
Far East Asia
60 M
Southeast Asia
30-35 M
Africa
30-40 M
Australia
0.2 M
HCV
accounts for 90-95% of post transfusion
hepatitis
 risk of sexual transmission lower than for HBV
 risk through casual contact low
 vertical transmission possible
 risk increased if mother is positive for HCV
RNA
 risk increased if mother is HIV positive
 overall prevalence estimated
at 1.4%

WHO IS AT GREATEST RISK
FOR HCV INFECTION?
drug abusers
 blood product recipients (anti-HCV screening
has greatly reduced risk)
 hemodialysis patients
 lab personnel working with blood products
 sexually active homosexuals
 persons with multiple and frequent sexual
contacts
 medical/dental personnel (3-10% via
needlestick from infected patient)

HCV - Diagnosis
Diagnostic Tests
Hepatitis C antibody tests
Qualitative HCV RNA tests
Quantitative HCV RNA tests
Genotyping
Hepatitis Delta virus.
Vírus da Hepatite Delta (HDV)
Vírus da Hepatite B
Vírus da Hepatite Delta
Envelope
AgHBs
Envelope
AgHBs
DNA
polimerase
RNA
42 nm
DNA
Core (27 nm)
AgHBc
AgHBe
Vírus Delta
Core (27 nm)
Virus Delta
Characteristics of hepatitis D viruses
Family
Genus
Envelope
Genome
Stability
Transmission
Prevalence
Fulminant
disease
Chronic disease
Oncogenic
Unclassified
Deltavirus
Yes (HBsAg)
ssRNA
Acid-sensitive
Parenteral
Low, regional
Frequent
Often
?
Two principal models of HDV infection have
been described
1. coinfection (the simultaneous introduction
of both HBV and HDV into a susceptible host),
2. superinfection (the infection of an HBV
carrier with HDV).
HDV INFECTION PATTERNS
Coinfection
acute simultaneous infection with HBV and HDV
often results in fulminant infection


(70% cirrhosis)
survivors rarely develop chronic infection

Superinfection



(< 5%)
results in HDV superinfection in an HBsAg
carrier (chronic HBV)
can occur anytime during chronic disease
usually results in rapidly progressive subacute
or chronic hepatitis
HDV


Transmission
Percutaneous
Sexual
- Common
- Yes, rare
Incubation period
- 21 - 45 (days)
Clinical illness at presentation jaundice 10%, higher with superinfection
Fulminant
- 2 – 7.5%
Case-fatality rate
- 1 – 2%
Chronic infection
Superinfection – 80%
Coinfection < 5%
HDV
Diagnostic tests
Acute infection
Chronic infection
IgM anti-HDV
IgG anti-HDV, HBsAg +
Immunity
Not applicable
Hepatitis E virus.
HEV is a small, nonenveloped RNA virus.
Recent
information
about
the
genomic
organization and other properties of the virus
strongly suggests that it is a calicivirus.
Hepatitis E virus
Family
Genus
Virion
Envelope
Caliciviridae
Unnamed
30-32 nm, icosahedral
No
Genome
Stability
Transmission
ssRNA
Heat-stable
Fecal-oral
Prevalence
Fulminant disease
Chronic disease
Regional
In pregnancy
Never
Oncogenic
No
Hepatitis E virus.
Epidemiology
Many cases of acute viral hepatitis in Asia,
Middle East and North Africa are caused by HEV.
Mainly young adults
Can infect primates, swine, sheep, rats
It is transmitted through the fecal-oral route
(human to human) but is unrelated to HAV. The
disease usually is caused by the ingestion of
fecally contaminated water.
Maternal-infant transmission occurs and is often
fatal.
HEV Clinical Characteristics
Similar to hepatitis A
Incubation period 15 – 60 (days)
Clinical Illness at presentation - 70 – 80% in
adults
Can cause severe acute hepatitis
Subclinical infection is common
Jaundice
Common
Fulminant
<1%, in pregnancy up to 30%
Case-fatality rate 0.5 – 4%
1.5 – 21% in pregnant women
Chronic infection None
HEV
Diagnostic tests
Acute infection IgG anti-HEV (sero-conversion)
Chronic infection Not applicable
Immunity
Not applicable
Hepatitis E
Prevention
Passive (Immune serum globulin)
Does not prevent infection
May ameliorate hepatitis
Active (Vaccine)
Anti-ORF2 prevents infection in chimps and
humans
Clinical trials in progress