Transcript HAV GRP C.PCL II

Presented by:Group C
PCL II
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GROUP MEMBERS
1. HAKIZIMANA NIYOYITA ADOLPHE
2. HAKORIMANA FIDELE
3. HATEGEKIMANA INNOCENT
4. HAVUGARUREMA LEONARD
5. IGIRANEZA BRAVE
6. IMFURANKUNDA HABIMANA HONORIN
7. INGABIRE DIANE
8. INGABIRE PROSPER
9. ISHIMWE ELICIEN
10. ISHIMWE EPIPHANIE
11. ISHIMWE MARIE CONSOLATRICE SAGE
12. NSANZIMANA Jean de Dieu
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UG12113681
UG12113529
UG12113823
UG12113163
UG12113449
UG12112986
UG12115269
UG12113183
UG12112973
UG12113610
UG 12114226
UG12113945
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Hepatitis A Virus Introduction
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Naked RNA virus
Related to enteroviruses, formerly known as
enterovirus
72,
now
put
in
its
actual
family:picornavirus
One stable serotype only
Difficult to grow in cell culture: primary marmoset cell
culture and also in vivo in chimpanzees and
marmosets .
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Hepatitis A Virus
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Introduction cont’d
A
Source of
virus
Route of
transmission
Chronic
infection
Prevention
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B
C
D
E
feces
blood/
blood/
blood/
blood-derived blood-derived blood-derived
body fluids
body fluids
body fluids
feces
fecal-oral
percutaneous percutaneous percutaneous
permucosal
permucosal
permucosal
fecal-oral
no
yes
pre/postexposure
immunization
pre/postexposure
immunization
yes
yes
blood donor
pre/postscreening;
exposure
risk behavior immunization;
modification risk behavior
modification
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ensure safe
drinking
water
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HAV biology
HAV is one kind of picornavirus and used to be classified as
enterovirus type72, but recently, it is considered to be
classified as heparnavirus
Hepatitis A virion is a naked spherical particle, diameter 27nm
Consists of a genome of linear, single-stranded RNA, 7.5kb.
The genome may be divided into 3 coding region: P1 region
(encoding structural protein), P2 and P3 regions (encoding
non-structure protein)
During acute stage of infection, HAV can be found in blood and
feces of infected human and primates
Marmoset and chimpanzee are susceptible animals
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HAV STRUCTURE
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HAV
on EM
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HAV biology
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HAV can not cause cytopathy, replicate within cytoplasma of
hepatocytes and via bile are discharged with feces
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7 genotypes, 1, 2, 3, 7 types from human body
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Only one antigen-antibody system. Anti-HAV IgM is diagnostic
evidence of recent infection, IgG is protective antibody.
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Resistance of HAV: 56°C, 30 min, usually temperature 1
week, dry feces at 25°C 30 days, fresh water, sea
water ,shellfish or soil for several months. 70% alcohol at
25°C , 3 min, 100°C, 5 min and ultraviolet, 1 min
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Transmission-Epidemiology
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Close personal contact
(e.g., household contact, sex contact, child
day care centers)
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Contaminated food, water
(e.g., infected food handlers, raw shellfish)
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Blood exposure (rare)
(e.g., injecting drug use, transfusion)
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Global Patterns of
Hepatitis A Virus Transmission
Disease Peak Age
Endemicity Rate of Infection Transmission Patterns
High
Low to
High
Moderate
High
Low
Low
Very low
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Early
childhood
Person to person;
outbreaks uncommon
Late
Person to person;
childhood/ food and waterborne
young adults outbreaks
Young adults Person to person;
food and waterborne
outbreaks
Very low Adults
Travelers; outbreaks
uncommon
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pathogenesis
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HAV invade into human body by mouth and
cause viremia.
 After one week,the HAV reach liver cells
replicate within.
 Then enter intestine with bile and appear in
feces.
 It’s believed that damage of liver cells maybe
caused by immune response.
 HAV does not cause cytopathy
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 After HAV replicating and discharging, liver
cells damage begin
 Animal experiment proved that immune
complex may attend the pathogenesis of HA:
 activated T cell secrete γ-INF that promote
the representation of HLA-Ⅰantigen on the
liver cells, CTL(cytotoxic T lympocyte)may kill
the target cell infected with HAV
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REPLICATION CYCLE OF HAV
Step 1:
HAV attaches to the basilar surface of the hepatocyte. (HAV
demonstrates hepatotropism)
The virion binds with its specific glycoprotein receptor.
The capsule is internalized through the host cell membrane
via clathrin-mediated endocytosis.
Step 2:The viral genomic RNA is released into the host cell.
Step 4: Reverse transcription of the ssRNA strand occurs.
Steps 3,5: The reverse transcribed dsRNA is translated into
viral proteins. The proteins are then assembled and
packaged into vesicles.
Step 6:The vesicles are released at the apical surface of
hepatocyte
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Clinical presentation
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Prodrome(EARLY STAGE)
patients may have mild flulike symptoms
of anorexia, nausea and vomiting,
fatigue, malaise, low-grade fever
(usually < 39.5°C), myalgia, and mild
headache
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Icteric phase
In the icteric phase, dark urine appears
first (bilirubinuria).
 Pale stool soon follows, although this is
not universal.
 Jaundice occurs in most (70-85%) adults
with acute HAV infection;
 The degree of icterus also increases with
age.
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Relapsing hepatitis A
 Relapsing hepatitis A is an uncommon
sequela of acute infection, is more
common in elderly persons
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Incubation period:
Jaundice by
age group:
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Complications:
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Chronic sequelae:
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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
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Laboratory Diagnosis
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Acute infection is diagnosed by the detection of HAV-IgM
in serum by EIA.
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Past Infection i.e. immunity is determined by the detection
of HAV-IgG by EIA.
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Cell culture – difficult and take up to 4 weeks, not
routinely performed
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Direct Detection – EM, PCR technique. It can detect
illness earlier than serology but rarely performed.
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Hepatitis A Infection
Typical Serological Course
Total antiHAV
Symptoms
Titr
e
ALT
Fecal
HAV
0
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1
IgM anti-HAV
2
3
4
5
MonthsGROUP
after
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prevention
Control of source of infection
 Cut off the route of transmission
 Protection of susceptible population
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 Active immunity
 Passive immunity
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Hepatitis A Vaccination Strategies
Epidemiologic Considerations
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Many cases occur in community-wide outbreaks
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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
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Prevention - Immune Globulin
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Pre-exposure
 travelers
to
intermediate
HAV-endemic regions
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and
high
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)
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Vaccine
HAVRIX§
VAQTA¶
Age(years)
Dose*
Volume(mL)
Two-does
schedule(mos)†
1-18
720 (EL.U.)
0.5
0, 6–12
>18
1,440 (EL.U.)
1.0
0, 6–12
1-18
25 (U)
0.5
0, 6–18
>18
50 (U)
1.0
0, 6–18
* EL.U. = enzyme-linked immunosorbent assay (ELISA) units. U = units.
† 0 months represents the timing of the initial dose; subsequent numbers represent the months after the initial
dose.
§ Hepatitis A vaccine, inactivated, GlaxoSmithKline Biologicals. This vaccine also is licensed for a 3-dose series
in children aged 1–18 years, with 360 EL.U., 0.5-mL doses at 0, 1, and 6–12 months.
r
¶ Hepatitis A vaccine, inactivated, Merck & Co., Inc
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REFERENCES:
Clinical microbiology made ridiculously simple
www.pubmed.com
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GOD BLESS YOU ALL!!!!!!!!!!!!!
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