1. Presented by:Group C PCL II
HEPATITIS A VIRUS
3/25/2017
GROUP C;PCL II

2. 1. HAKIZIMANA NIYOYITA ADOLPHE UG12113681
GROUP MEMBERS
1. HAKIZIMANA NIYOYITA ADOLPHE UG
2. HAKORIMANA FIDELE UG
3. HATEGEKIMANA INNOCENT UG
4. HAVUGARUREMA LEONARD UG
5. IGIRANEZA BRAVE UG
6. IMFURANKUNDA HABIMANA HONORIN UG
7. INGABIRE DIANE UG
8. INGABIRE PROSPER UG
9. ISHIMWE ELICIEN UG
10. ISHIMWE EPIPHANIE UG
11. ISHIMWE MARIE CONSOLATRICE SAGE UG
12. NSANZIMANA Jean de Dieu UG
3/25/2017
GROUP C;PCL II

3. Hepatitis A Virus Introduction
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 .
3/25/2017
GROUP C;PCL II

4. Hepatitis A Virus
3/25/2017
GROUP C;PCL II 6

5. Introduction cont’d A B C D E Source of feces blood/ blood/ blood/
virus
blood-derived
blood-derived
blood-derived
body fluids
body fluids
body fluids
Route of
fecal-oral
percutaneous
percutaneous
percutaneous
fecal-oral
transmission
permucosal
permucosal
permucosal
Chronic no
yes
yes
yes no
infection
Prevention
pre/post-
pre/post-
blood donor
pre/post-
ensure safe
exposure
exposure
screening;
exposure
drinking
immunization
immunization
risk behavior
immunization;
water
modification
risk behavior
modification
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GROUP C;PCL II 3

6. 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
3/25/2017
GROUP C;PCL II

7. HAV STRUCTURE
3/25/2017
GROUP C;PCL II

8. HAV on EM
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GROUP C;PCL II

9. HAV biology
HAV can not cause cytopathy, replicate within cytoplasma of hepatocytes and via bile are discharged with feces
7 genotypes, 1, 2, 3, 7 types from human body
Only one antigen-antibody system. Anti-HAV IgM is diagnostic evidence of recent infection, IgG is protective antibody.
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
3/25/2017
GROUP C;PCL II

10. Transmission-Epidemiology
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)
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GROUP C;PCL II 11

11. Global Patterns of Hepatitis A Virus Transmission
Disease
Peak Age
Endemicity
Rate
of Infection
Transmission Patterns
High
Low to
Early
Person to person;
High
childhood
outbreaks uncommon
Moderate
High
Late
Person to person;
childhood/
food and waterborne
young adults
outbreaks
Low
Low
Young adults
Person to person;
food and waterborne
outbreaks
Very low
Very low
Adults
Travelers; outbreaks
uncommon
3/25/2017
GROUP C;PCL II 15

12. 3/25/2017
GROUP C;PCL II

13. 3/25/2017
GROUP C;PCL II

14. pathogenesis 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
3/25/2017
GROUP C;PCL II

15. 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
3/25/2017
GROUP C;PCL II

16. 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
3/25/2017
GROUP C;PCL II

17. 3/25/2017
GROUP C;PCL II

18. Clinical presentation
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
3/25/2017
GROUP C;PCL II

19. 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.
3/25/2017
GROUP C;PCL II

20. Relapsing hepatitis A
Relapsing hepatitis A is an uncommon sequela of acute infection, is more common in elderly persons
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GROUP C;PCL II

21. Incubation period: Average 30 days Range 15-50 days
Jaundice by <6 yrs, <10% age group: yrs, 40%-50% >14 yrs, 70%-80%
Complications: Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis
Chronic sequelae: None
3/25/2017
GROUP C;PCL II 7

22. Laboratory Diagnosis
Acute infection is diagnosed by the detection of HAV-IgM in serum by EIA.
Past Infection i.e. immunity is determined by the detection of HAV-IgG by EIA.
Cell culture – difficult and take up to 4 weeks, not routinely performed
Direct Detection – EM, PCR technique. It can detect illness earlier than serology but rarely performed.
3/25/2017
GROUP C;PCL II

23. Hepatitis A Infection Typical Serological Course Total anti-HAV Titre
Symptoms
Titre
ALT
Fecal
HAV
IgM anti-HAV 1 2 3 4 5 6 12 24
Months after exposure
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GROUP C;PCL II 9

24. prevention Control of source of infection
Cut off the route of transmission
Protection of susceptible population
Active immunity
Passive immunity
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GROUP C;PCL II

25. Hepatitis A Vaccination Strategies
Epidemiologic Considerations
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
3/25/2017
GROUP C;PCL II 18

26. Prevention - Immune Globulin
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)
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GROUP C;PCL II 27

27. Two-does schedule(mos)†
Vaccine
Age(years)
Dose*
Volume(mL)
Two-does schedule(mos)†
HAVRIX§
1-18
720 (EL.U.)
0.5
0, 6–12
>18
1,440 (EL.U.)
1.0
VAQTA¶
25 (U)
0, 6–18
50 (U)
* 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
3/25/2017
GROUP C;PCL II

28. REFERENCES: Clinical microbiology made ridiculously simple
3/25/2017
GROUP C;PCL II

29. THANK YOU FOR YOUR KIND ATTENTION
GOD BLESS YOU ALL!!!!!!!!!!!!!
3/25/2017
GROUP C;PCL II