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

1. HAKIZIMANA NIYOYITA ADOLPHE UG12113681 GROUP MEMBERS 1. HAKIZIMANA NIYOYITA ADOLPHE UG12113681 2. HAKORIMANA FIDELE UG12113529 3. HATEGEKIMANA INNOCENT UG12113823 4. HAVUGARUREMA LEONARD UG12113163 5. IGIRANEZA BRAVE UG12113449 6. IMFURANKUNDA HABIMANA HONORIN UG12112986 7. INGABIRE DIANE UG12115269 8. INGABIRE PROSPER UG12113183 9. ISHIMWE ELICIEN UG12112973 10. ISHIMWE EPIPHANIE UG12113610 11. ISHIMWE MARIE CONSOLATRICE SAGE UG 12114226 12. NSANZIMANA Jean de Dieu UG12113945 3/25/2017 GROUP C;PCL II

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

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

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 3/25/2017 GROUP C;PCL II 3

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

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

HAV on EM 3/25/2017 GROUP C;PCL II

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

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) 3/25/2017 GROUP C;PCL II 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

3/25/2017 GROUP C;PCL II

3/25/2017 GROUP C;PCL II

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

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

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

3/25/2017 GROUP C;PCL II

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

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

Relapsing hepatitis A Relapsing hepatitis A is an uncommon sequela of acute infection, is more common in elderly persons 3/25/2017 GROUP C;PCL II

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 3/25/2017 GROUP C;PCL II 7

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

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 3/25/2017 GROUP C;PCL II 9

prevention Control of source of infection Cut off the route of transmission Protection of susceptible population Active immunity Passive immunity 3/25/2017 GROUP C;PCL II

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

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) 3/25/2017 GROUP C;PCL II 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

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

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