hepatitis viruses (2)

7/30/2019 Hepatitis Viruses (2)

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Dr. N. M. Suryawanshi, MD

Assistant Professor

MIMSR Medical College, Latur


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Infectious hepatitis

children and young adults

contaminated food, water and milk

Pathogenesis:

Ingestion

multiplies in the intestinal epithelium

reaches the liver by hematogenous spread Incubation period- 2-6 weeks


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Clinical disease has two stages

Prodromal or pre-icteric stage

Fever

malaise

Anorexia

nausea

vomiting

liver tenderness

Virus is shed in the feces in the late incubationperiod or prodromal stage

Icteric stage-jaundice

Recovery occurs over a period of 4-6 weeks


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Size 27nm

Envelope non-enveloped

Symmetry icosahedral

Genome single stranded RNA

It belongs to picornavirus family

enterovirus-72

prototype -genus hepatovirus


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resistant :

inactivation by heat at 600C for one hour

ether

pH 3

destroyed by:

autoclaving

boiling for 5 minutes formaldehyde

chlorine


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1. demonstration of virus:

i) immunoelectron microscopy (IEM)

Virus can be visualized by IEM in feces during the

late incubation period and preicteric phase

ii) enzyme linked immunosorbent assay (ELISA)

2. isolation

human and simian cell culture


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3. detection of antibody:

ELISA

specific IgM antibody

recent infection

IgG antibody to HAV At the same time

persists for many years

past infection


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Liver function tests

i) Alanine aminotransferase (ALT) :

Previously designated as SGPT

rise in serum ALT indicate liver damage ii) bilirubin :

Serum bilirubin level rises


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General :

prevention of fecal contamination of food and

water

Passive : Normal pooled human immunoglobulin


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Active :

formalin inactivated alum conjugated HAV grown in human diploid cell culture

It is safe and effective

Dose

two doses

intramuscularly

One attack of the disease gives lastingimmunity


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Size 42nm

double shelled particle

Symmetry icosahedral

Envelope envelopedGenome circular double stranded DNA

Outer surface or envelope- HBsAg

nucleocapsid -inner icosahedral 27 nm,

hepatitis B core antigen (HBcAg)Genome circular double stranded DNA

DNA polymerase


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Other name -Australia antigen

Blumberg and coworkers

Electron microscopy

three types of particles 1. spherical particle-

abundant form

22nm

2-. Tubular particle- 22nm

These two are the surface subunits of HBsAg


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3. double shelled spherical

42nm in diameter

complete hepatitis B virus

Dane particle

Dane and coworkers

hence the name is given as Dane particle


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HBsAg:

surface antigen

HBsAg carries

group- specific antigen a two types of specific antigens,

d or y

w or r 4 antigenic types of HBsAg- adw, adr, ayw and ayr

Type ayw is predominant in India


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HBcAg-

core or nucleocapsid antigen

not detectable in patients blood

HBeAg- appears in serum along with HBsAg

disappears within a few weeks


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genome

Consists of two linear strands of

DNA arranged circularlyplus strand- incomplete

Minus strand-complete

It appears partly double strandedand partially single stranded DNA


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viral DNA polymerase:

associated with the plus

strandfills the gap in the

incomplete strand

make the genome fullydouble stranded


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Genome has four genes coding for different

antigen

HBxAg and its antibody are present in

patients with severe chronic hepatitis


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HBV can not be cultivated in vitro

Virus and its protein

obtained from cell lines transfected with HBV

DNA cloned in yeast and bacteria


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survives

600C for 60 min

ultraviolet irradiation

inactivated: 1000C for 5 min

formaldehyde (1:4000)

glutaraldehyde (2%)


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Parentral route

accidental inoculation of blood, serum, blood

products or other body fluids during medical,

surgical or dental procedures

Perinatal transmission-

from infected mother to newborn

Veneral transmission


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Incubation period- 6 weeks to 6 months

Low grade Fever , jaundice

Three phases

1.Preicteric phase- anorexia, nausea,weakness, myalgia, nausea and vomiting

2. Icteric phase- patient develops jaundice,

pale stools and dark urine

3. Convalescent phase- malaise and fatigue


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Two types

1. super carriers:

Have Hbe Ag in blood

Highly infectious Blood contains high titre of HBs Ag and DNA

polymerase

HBV present in blood

Very minute amount of serum or blood

transmit infection


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Simple carriers:

No Hbe Ag in blood

Low level of HBs Ag

HBV and DNA polymerase are absent Transmit the infection only when large

volume of blood or serum are transferred(

blood transfusion)


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Serological methods:

Detection of antigen and antibodies

ELISA

RIA


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i) HBsAg-

First marker to appear in blood after infection

Disappear with recovery from clinical disease

Persist for years in carriers Ii)antiHBsAg-

Appears within week after disappearance of

HBsAg

Persist for long periods


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Iii) HBeAg-

Appear in the serum along with HBsAg

Disappears within a few weeks

Sera containing HBeAg is highly infectious It is an indicator of active intrahepatic viral

replication

Iv) antiHBe Ag-

Appears after disappearance of HBeAg


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V) HBcAg-

Not detected in serum

Detected in liver cells by immunofluorescence

Vi)antiHBcAg- Appear in a week or two after appearance of HBsAg

Earliest antibody to appear in blood remains lifelong

Initially it is IgM type but later on it is IgG type

Viral DNA polymerase-

Appear in serum during preicteric phase


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PCR:

HBV DNA level detected in serum by PCR

Biochemical tests:

Serum bilirubin- indicates the degree of jaundice

SGOT and SGPT


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General measures-

Screening of HBsAg and HBeAg in blood donors

Use of unsterile needles and syringes must be

avoided to prevent infection


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Passive immunisation:

Hepatitis B imunoglobulin (HBIG)

Prepared from donors with donors with high

titres of anti-HBs

Doses-

300-500IU

intramuscularly

Administered as early as possible afterexposure


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i) plasma derived vaccine-

Ii) Recombinant hepatitis B vaccine-

Produced by recombinant DNA In yeasts in which

a plasmid containing the gene of HBsAg has been

incorporated

Three doses

at 0, 1 and 6 months

Route- intramuscularly into deltoid muscles


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No specific antiviral treatment

Interferon-

Combination with antiviral agents

(lamivudine and famcyclovir)


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Family-flaviviridae

Genus- hepacivirus

Species Hep.C virus

Size- 50-60nm single stranded RNA


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ELISA:

Detection of anti-HCV antibody

Immunoblot assay-

Used for confirmation PCR-

Viral genome (HCV RNA)


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Interferon alpha

Ribavirin


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Morphology :

Defective virus as it is dependent on helper

function of HBV for replication

Spherical 36-38nm

Ss RNA

Enveloped


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Mode of entry-

Repeated blood transfusion

Clinical features:

I P- 2-12 week HDV results in hepatitis

Severity is more than HBV


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Detection of delta antigen in the nuclie of

hepatocytes

immunofluorescence test

Indirect immunoperoxidase stainDetection of nucliec acid (HDV RNA)

radiolabelled probes

Ab detection

ELISA RIA


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Properties:

Small-27-38nm

Shape-spherical

Capsid- icosahedral Envelope absent

Genome- S S RNA


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Mode of transmission-

Ingestion of contaminated water

Clinical features:

IP- 2-8 weeks Fever, anorexia, nausea, vomiting, liver

tenderness

Does not lead to chronic hepatitis, cirrhosis,

cancer


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Direct demonstration of virus particle

Detection of HEV RNA

Specimen- stool

EMDetection of antibodies-

IgM or IgG to HEV

ELISA

Western blot test


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RNA virus

Route of entry-

parenteral,

blood transfusion Pathogenicity:

Acute hepatitis

Chronic hepatitis

Fulminant hepatitis

hepatitis viruses (2)

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