Presented by:Group C

PCL II

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1. HAKIZIMANA NIYOYITA ADOLPHE UG121136812. HAKORIMANA FIDELE UG121135293. HATEGEKIMANA INNOCENT UG121138234. HAVUGARUREMA LEONARD UG121131635. IGIRANEZA BRAVE UG121134496. IMFURANKUNDA HABIMANA HONORIN UG121129867. INGABIRE DIANE UG12115269 8. INGABIRE PROSPER UG121131839. ISHIMWE ELICIEN UG1211297310. ISHIMWE EPIPHANIE UG1211361011. ISHIMWE MARIE CONSOLATRICE SAGE UG 1211422612. NSANZIMANA Jean de Dieu UG12113945

GROUP MEMBERS

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 .

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Hepatitis A Virus

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Source ofvirus

feces blood/blood-derived

body fluids

blood/blood-derived

body fluids

blood/blood-derived

body fluids

feces

Route oftransmission

fecal-oral percutaneouspermucosal

percutaneouspermucosal

percutaneouspermucosal

fecal-oral

Chronicinfection

no yes yes yes no

Prevention pre/post-exposure

immunization

pre/post-exposure

immunization

blood donorscreening;

risk behaviormodification

pre/post-exposure

immunization;risk behaviormodification

ensure safedrinking

water

Introduction cont’d

A B C D E

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

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

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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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Transmission-Epidemiology

EndemicityDisease

RatePeak Age

of InfectionTransmission 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 adultsPerson to person;food and waterborne outbreaks

Very low Very low Adults Travelers; outbreaks uncommon

Global Patterns of Hepatitis A Virus

Transmission

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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

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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- antigen on the liver Ⅰcells, CTL(cytotoxic T lympocyte)may kill the target cell infected with 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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REPLICATION CYCLE OF HAV

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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

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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: 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: None04/10/23 GROUP C;PCL II 21

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.

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FecalHAV

Symptoms

0 1 2 3 4 5 6 12

24

Hepatitis A Infection

Total anti-HAV

Titre

ALT

IgM anti-HAV

Months after exposure

Typical Serological Course

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prevention

Control of source of infection Cut off the route of transmission Protection of susceptible population

Active immunityPassive immunity

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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 infectiontravelershomosexual meninjecting drug users

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Hepatitis A Vaccination Strategies

Epidemiologic Considerations

Pre-exposuretravelers to intermediate and high

HAV-endemic regions

Post-exposure (within 14 days)Routinehousehold and other intimate contactsSelected situationsinstitutions (e.g., day care centers)common source exposure (e.g., food prepared by

infected food handler)

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Prevention - Immune Globulin

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 0, 6–12

VAQTA¶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:

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Clinical microbiology made ridiculously simple www.pubmed.com

GOD BLESS YOU ALL!!!!!!!!!!!!!

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